This patent application describes extracts and compounds from the aerial roots of Ficus benghalensis that promote hair growth and reduce hair loss. It discloses a method of producing extracts from the aerial roots through a series of solvent extractions, and fractionating the extracts to isolate active compounds. Some fractions and compounds, such as the ethyl acetate fraction, showed ability to increase viability of hair follicles and hair growth. The application suggests these natural products may offer treatments for hair loss with fewer side effects than current drugs.
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Report Link- https://www.cognitivemarketresearch.com/Choke-Valve-Market-Report Cognitive Market Research provides detailed analysis of Choke Valve in our recently published report titled, "Choke Valve 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Choke Valve market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Choke Valve market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #ChokeValveReport #ChokeValveMarket #ChokeValveMarketForecast #ChokeValveMarketStatus #ChokeValveMarket2021
Sample Global Cell Roller Bottles Market Report 2022 - Cognitive Market Resea...Cognitive Market Research
Global Cell Roller Bottles Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Cell-Roller-Bottles-Market-Report
Cognitive Market Research provides detailed analysis of Global Cell Roller Bottles in our recently published report titled, "Global Cell Roller Bottles 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Global Cell Roller Bottles market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Global Cell Roller Bottles market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #GlobalCellRollerBottlesReport #GlobalCellRollerBottlesMarket #GlobalCellRollerBottlesMarketForecast #GlobalCellRollerBottlesMarketStatus #GlobalCellRollerBottlesMarket2022
Report Link- https://www.cognitivemarketresearch.com/Flushable-Wet-Wipes-Market-Report
Cognitive Market Research provides detailed analysis of Flushable Wet Wipes in our recently published report titled, "Flushable Wet Wipes 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Flushable Wet Wipes market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Flushable Wet Wipes market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #FlushableWetWipesReport #FlushableWetWipesMarket #FlushableWetWipesMarketForecast #FlushableWetWipesMarketStatus #FlushableWetWipesMarket2021
Sample Global Hair Removel Market Report 2021 - Cognitive Market Research.docxCognitive Market Research
Hair Removel Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Hair-Removel-Market-Report
Cognitive Market Research provides detailed analysis of Hair Removel in our recently published report titled, "Hair Removel 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Hair Removel market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Hair Removel market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #HairRemovelReport #HairRemovelMarket #HairRemovelMarketForecast #HairRemovelMarketStatus #HairRemovelMarket2022
Cognitive Market Research provides detailed analysis of Hydroalcoholic Gel Market in our recently published report titled, "Hydroalcoholic Gel Market 2020" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Hydroalcoholic Gel market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Hydroalcoholic Gel market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Cognitive Market Research provides detailed analysis of Air Negative Ion Generator in our recently published report titled, "Air Negative Ion Generator 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Air Negative Ion Generator market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Air Negative Ion Generator market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.#AirNegativeIonGeneratorReport #AirNegativeIonGeneratorMarketForecast #AirNegativeIonGeneratorMarketStatus #AirNegativeIonGeneratorMarket2021
https://www.cognitivemarketresearch.com/consumer-goods/air-negative-ion-generator-market-report
Report Link- https://www.cognitivemarketresearch.com/Flea-and-Tick-Collar-Market-Report
Cognitive Market Research provides detailed analysis of Flea and Tick Collar in our recently published report titled, "Flea and Tick Collar 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Flea and Tick Collar market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Flea and Tick Collar market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #FleaandTickCollarReport #FleaandTickCollarMarket #FleaandTickCollarMarketForecast #FleaandTickCollarMarketStatus #FleaandTickCollarMarket2021
This patent invention presents the apparatus, methods, and systems for automated liquid droplet manipulation include an open droplet supporting surface. An actuator can translate the surface in space with at least one degree freedom of movement to influence movement of one or more droplets on the surface. In one embodiment, the surface is patterned with areas that attract the droplets and interstitial areas that repel the droplets to enhance transport of droplets. For example, for water-based droplets the attracting areas can be hydrophilic and the repelling hydrophobic. In one embodiment, the repelling areas are superhydrophobic. Electromechanical movement of the surface avoids expensive and complex microfluidic fabrication and components, and avoids electrowetting requirements.
Apparatus, methods, and systems for automated liquid droplet manipulation include an open droplet supporting surface. An actuator can translate the surface in space with at least one degree freedom of movement to influence movement of one or more droplets on the surface. In one embodiment, the surface is patterned with areas that attract the droplets and interstitial areas that repel the droplets to enhance transport of droplets. For example, for water-based droplets the attracting areas can be hydrophilic and the repelling hydrophobic. In one embodiment, the repelling areas are superhydrophobic. Electromechanical movement of the surface avoids expensive and complex microfluidic fabrication and components, and avoids electrowetting requirements.
Report Link- https://www.cognitivemarketresearch.com/Fish-Tanks-Market-Report
Cognitive Market Research provides detailed analysis of Fish Tanks in our recently published report titled, "Fish Tanks 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Fish Tanks market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Fish Tanks market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
#FishTanksReport #FishTanksMarket #FishTanksMarketForecast #FishTanksMarketStatus #FishTanksMarket2021
Global Acrolein Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Acrolein-Market-Report
Cognitive Market Research provides detailed analysis of Global Acrolein in our recently published report titled, "Global Acrolein 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Global Acrolein market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Global Acrolein market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #GlobalAcroleinReport #GlobalAcroleinMarket #GlobalAcroleinMarketForecast #GlobalAcroleinMarketStatus #GlobalAcroleinMarket2022
Dowload the free PDF file of Report Sample Pages. Cognitive Market Research has recently published report titled, "Nitrile Medical Gloves Market 2020" which provides detailed analysis of Nitrile Medical Gloves Market. The market study focuses on understanding industry dynamics along with driving factors to provide the key elements fueling the current market growth. The report also identifies restraints for Nitrile Medical Gloves market, to understand factors which will restrict the growth of Nitrile Medical Gloves market. Key industrial factors such as macroeconomic and microeconomic factors are studied in depth with the help of PESTEL analysis in order to have a holistic view of factors impacting Nitrile Medical Gloves market growth in various regions across the globe. Market forecast takes place with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Lens Cleaning Solution Market Report 2020 Dowload the free PDF file of Report Sample Pages. Cognitive Market Research has recently published report titled, "Lens Cleaning Solution Market 2020" which provides detailed analysis of Lens Cleaning Solution Market. The market study focuses on understanding industry dynamics along with driving factors to provide the key elements fueling the current market growth. The report also identifies restraints for Lens Cleaning Solution market, to understand factors which will restrict the growth of Lens Cleaning Solution market. Key industrial factors such as macroeconomic and microeconomic factors are studied in depth with the help of PESTEL analysis in order to have a holistic view of factors impacting Lens Cleaning Solution market growth in various regions across the globe. Market forecast takes place with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Sample Global Cell Roller Bottles Market Report 2022 - Cognitive Market Resea...Cognitive Market Research
Global Cell Roller Bottles Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Cell-Roller-Bottles-Market-Report
Cognitive Market Research provides detailed analysis of Global Cell Roller Bottles in our recently published report titled, "Global Cell Roller Bottles 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Global Cell Roller Bottles market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Global Cell Roller Bottles market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #GlobalCellRollerBottlesReport #GlobalCellRollerBottlesMarket #GlobalCellRollerBottlesMarketForecast #GlobalCellRollerBottlesMarketStatus #GlobalCellRollerBottlesMarket2022
Report Link- https://www.cognitivemarketresearch.com/Flushable-Wet-Wipes-Market-Report
Cognitive Market Research provides detailed analysis of Flushable Wet Wipes in our recently published report titled, "Flushable Wet Wipes 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Flushable Wet Wipes market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Flushable Wet Wipes market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #FlushableWetWipesReport #FlushableWetWipesMarket #FlushableWetWipesMarketForecast #FlushableWetWipesMarketStatus #FlushableWetWipesMarket2021
Sample Global Hair Removel Market Report 2021 - Cognitive Market Research.docxCognitive Market Research
Hair Removel Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Hair-Removel-Market-Report
Cognitive Market Research provides detailed analysis of Hair Removel in our recently published report titled, "Hair Removel 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Hair Removel market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Hair Removel market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #HairRemovelReport #HairRemovelMarket #HairRemovelMarketForecast #HairRemovelMarketStatus #HairRemovelMarket2022
Cognitive Market Research provides detailed analysis of Hydroalcoholic Gel Market in our recently published report titled, "Hydroalcoholic Gel Market 2020" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Hydroalcoholic Gel market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Hydroalcoholic Gel market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Cognitive Market Research provides detailed analysis of Air Negative Ion Generator in our recently published report titled, "Air Negative Ion Generator 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Air Negative Ion Generator market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Air Negative Ion Generator market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.#AirNegativeIonGeneratorReport #AirNegativeIonGeneratorMarketForecast #AirNegativeIonGeneratorMarketStatus #AirNegativeIonGeneratorMarket2021
https://www.cognitivemarketresearch.com/consumer-goods/air-negative-ion-generator-market-report
Report Link- https://www.cognitivemarketresearch.com/Flea-and-Tick-Collar-Market-Report
Cognitive Market Research provides detailed analysis of Flea and Tick Collar in our recently published report titled, "Flea and Tick Collar 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Flea and Tick Collar market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Flea and Tick Collar market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #FleaandTickCollarReport #FleaandTickCollarMarket #FleaandTickCollarMarketForecast #FleaandTickCollarMarketStatus #FleaandTickCollarMarket2021
This patent invention presents the apparatus, methods, and systems for automated liquid droplet manipulation include an open droplet supporting surface. An actuator can translate the surface in space with at least one degree freedom of movement to influence movement of one or more droplets on the surface. In one embodiment, the surface is patterned with areas that attract the droplets and interstitial areas that repel the droplets to enhance transport of droplets. For example, for water-based droplets the attracting areas can be hydrophilic and the repelling hydrophobic. In one embodiment, the repelling areas are superhydrophobic. Electromechanical movement of the surface avoids expensive and complex microfluidic fabrication and components, and avoids electrowetting requirements.
Apparatus, methods, and systems for automated liquid droplet manipulation include an open droplet supporting surface. An actuator can translate the surface in space with at least one degree freedom of movement to influence movement of one or more droplets on the surface. In one embodiment, the surface is patterned with areas that attract the droplets and interstitial areas that repel the droplets to enhance transport of droplets. For example, for water-based droplets the attracting areas can be hydrophilic and the repelling hydrophobic. In one embodiment, the repelling areas are superhydrophobic. Electromechanical movement of the surface avoids expensive and complex microfluidic fabrication and components, and avoids electrowetting requirements.
Report Link- https://www.cognitivemarketresearch.com/Fish-Tanks-Market-Report
Cognitive Market Research provides detailed analysis of Fish Tanks in our recently published report titled, "Fish Tanks 2021" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Fish Tanks market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Fish Tanks market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
#FishTanksReport #FishTanksMarket #FishTanksMarketForecast #FishTanksMarketStatus #FishTanksMarket2021
Global Acrolein Market Report 2022
Report Link- https://www.cognitivemarketresearch.com/Acrolein-Market-Report
Cognitive Market Research provides detailed analysis of Global Acrolein in our recently published report titled, "Global Acrolein 2022" The market study focuses on industry dynamics including driving factors to provide the key elements fueling the current market growth. The report also identifies restraints and opportunities to identify high growth segments involved in the Global Acrolein market. Key industrial factors such as macroeconomic and microeconomic factors are studied in detail with help of PESTEL analysis in order to have a holistic view of factors impacting Global Acrolein market growth across the globe. Market growth is forecasted with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc. #GlobalAcroleinReport #GlobalAcroleinMarket #GlobalAcroleinMarketForecast #GlobalAcroleinMarketStatus #GlobalAcroleinMarket2022
Dowload the free PDF file of Report Sample Pages. Cognitive Market Research has recently published report titled, "Nitrile Medical Gloves Market 2020" which provides detailed analysis of Nitrile Medical Gloves Market. The market study focuses on understanding industry dynamics along with driving factors to provide the key elements fueling the current market growth. The report also identifies restraints for Nitrile Medical Gloves market, to understand factors which will restrict the growth of Nitrile Medical Gloves market. Key industrial factors such as macroeconomic and microeconomic factors are studied in depth with the help of PESTEL analysis in order to have a holistic view of factors impacting Nitrile Medical Gloves market growth in various regions across the globe. Market forecast takes place with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Lens Cleaning Solution Market Report 2020 Dowload the free PDF file of Report Sample Pages. Cognitive Market Research has recently published report titled, "Lens Cleaning Solution Market 2020" which provides detailed analysis of Lens Cleaning Solution Market. The market study focuses on understanding industry dynamics along with driving factors to provide the key elements fueling the current market growth. The report also identifies restraints for Lens Cleaning Solution market, to understand factors which will restrict the growth of Lens Cleaning Solution market. Key industrial factors such as macroeconomic and microeconomic factors are studied in depth with the help of PESTEL analysis in order to have a holistic view of factors impacting Lens Cleaning Solution market growth in various regions across the globe. Market forecast takes place with the help of complex algorithms such as regression analysis, sentiment analysis of end-users, etc.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
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Thyroid Gland- Gross Anatomy by Dr. Rabia Inam Gandapore.pptx
Us published appln no 20120128796 a1
1. Ill l Ill l l I Ill l Il l Ill l Ill l Il l Ill l Ill l Ill l Il l Ill l Ill l Il l l Ill Il l Ill
US 20120128796A1
(19) nited States
(12) Patent Application Publication (lO) Pub. No.: S 2012/0128796 A1
Armani et al. (43) Pub. Date: May 24, 2012
(54) EXTRACTS AND COMPOUNDS FROM FICUS Publication Classification
BENGHALENSIS FOR INCREASING HAIR
(51) Int. CI.
GROWTH AND DECREASING HAIR LOSS
A61K 36/60 (2006.01)
A61K 31/7016 (2006.01)
(76) Inventors: Antonio Armani, Richmond Hill
A61K 31/7028 (2006.01)
(CA); Sara Armani, Richmond Hill
A 61P 17/14 (2006.01)
(CA); Charitha Seneviratne,
Mississanga (CA); Reza Nazari, U.S. Cl ............................... 424/725; 514/53; 514/23
(52)
Richmond Hill (CA)
Appl. No.: 13/051,543 (57) ABSTRACT
(21)
This application discloses natural product extracts and com-
(22) Filed: Mar. 18, 2011 pounds from an aerial root of a Ficus plant, such as Ficus
benghalensis. The application also discloses the use of natu-
Related U.S. Application Data
ral product extracts and compounds from Ficus plants for
(60) Provisional application No. 61/315,729, filed on Mar. increasing hair growth and decreasing hair loss. Methods of
19, 2010, provisional application No. 61/379,915, producing the extracts and isolating the compounds are fur-
filed on Sep. 3, 2010. ther disclosed.
2. Patent Application Publication May 24, 2012 Sheet 1 of 20 US 2012/0128796 A1
HF-explant growth assay
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g
iiGURE "t
iHF recipient growth ass
FliGUR.E 2
22. US 2012/0128796 A1 May 24, 2012
EXTRACTS AND COMPOUNDS FROM FICUS [0008] In addition, since the length and size of the hair
BENGHALENSIS FOR INCREASING HAIR depends on the length of the anagen phase and size of the hair
GROWTH AND DECREASING HAIR LOSS follicle respectively, another way to promote hair growth is to
use compounds that prolong the length of the anagen phase
and increase hair follicle size.
CROSS REFERENCE TO RELATED
APPLICATIONS SUMMARY OF THE DISCLOSURE
[0001] This non-provisional application claims priority [0009] The invention relates to a method of producing an
from U.S. provisional application No. 61/315,729 filed on extract, its fractions, sub-fractions and compounds from an
Mar. 19, 2010 and U.S. provisional application No. 61/379, aerial root portion ofa Ficus plant, optionally Ficus bengha-
915 filed on Sep. 3, 2010, both of which are incorporated lens&, where the extract and its fractions, sub-fractions and
herein by reference in their entirety. compounds are useful as hair growth-increasing agents and/
or hair loss-decreasing agents. The aerial root portion option-
ally comprises an aerial root tip. The method typically
FIELD involves preparing a crude extract of an aerial root portion of
a Ficus plant, optionally the aerial root tip, and fractionating
[0002] This application discloses natural product extracts the crude extract with at least one solvent to obtain various
and compounds from an aerial root of a Ficus plant, such as fractions.
Ficus benghalensis, that are useful for increasing hair growth [0010] The invention also relates to a method where the
and decreasing hair loss in mammals. Methods of producing solvent is selected from the group consisting of n-hexane,
the extracts and isolating the compounds are also disclosed. dichioromethane, ethyl acetate, methanol and water.
[0011] The invention further relates to a method where a
series of fractions are obtained by:
BACKGROUND
[0012] (a) performing a n-hexane extraction on the crude
extract to obtain a n-hexane fraction and a first residue,
Hair Loss [0013] (b) performing a dichloromethane extraction on
the first residue to obtain a dichloromethane fraction and
[0003] Genetic pattern hair loss affects approximately one-
a second residue,
half of the world’s male population and more than one-quarter
[0014] (c) performing an ethyl acetate extraction on the
of the female population. Current treatments for hair loss
second residue to obtain an ethyl acetate fraction and a
include surgical hair restoration and pharmaceutical interven-
third residue,
tions.
[0015] (d) performing a methanol extraction on the third
[0004] Small organic compounds are currently sold for residue to obtain a methanol fraction and a fourth resi-
treating hair loss. These compounds have shown limited due, and
results. For example, the oral medication finasteride is used to [0016] (e) performing a water extraction on the fourth
treat balding. However, as finasteride affects serum DHT residue to obtain a water fraction.
levels, it can lead to numerous side effects. The topical lotion [0017] In one embodiment of the invention, the method
minoxidil is also used to arrest the progression of hair loss. further comprises sub-fractionating the n-hexane fraction to
obtain at least one sub-fraction. The n-hexane sub-fraction is
[0005] There remains a need for naturally-sourced products
optionally sub-fractionated using chromatography, solvent
for treating hair loss. A natural formulation to treat hair loss
partitioning or any other method known in the art or any
and promote hair growth with minimal side effects is highly
combination thereof.
desirable.
[0018] In one embodiment of the invention, the methods
described above involve the further step of topically admin-
Hair Follicles istering one or more of the fractions and/or sub-fractions to a
mammal to increase hair growth on the mammal or to
[0006] All parts of the hair follicle are cyclically re-gener-
decrease hair loss on the mammal.
ated. The hair follicle is an entirely epidermally derived struc-
[0019] In another embodiment, the methods involve the
ture (including the sebaceous gland) and is produced by epi-
further step of exposing hair follicles in vitro to one or more
dermal stem cells (eSC) residing in the epidermal bulge.
of the fractions to increase the viability of the hair follicles. In
Cross talk between mesenchyma derived dermal papilla (DP)
another embodiment, the methods involve the further step of
cells and the epidermal eSC is crucial for cell differentiation
exposing hair follicles in vivo to one or more of the fractions
and proliferation (Morris, 2004; Blanpain and Fuchs, 2006). to increase the viability of the hair follicles. In another
[0007] Balding, or hair loss, is a consequence of hair fol- embodiment, the methods involve the further step of exposing
licle miniaturization. Normally, a hair follicle cycles through hair follicle cells, in vivo or in vitro, to one or more of the
phases including the anagen (growth) phase, the catagen fractions to increase the viability of the hair follicle cells.
(transition) phase and the telogen (resting or quiescent) [0020] In a further embodiment of the method, the Ficus is
phase. In the miniaturization process, the hair follicle enters a Ficus benghalensis.
prolonged lag phase following the telogen stage. Thus, one [0021] In another embodiment of the method, the method
aim of hair loss therapies is to push or coax the hair follicle further comprises the use of the ethyl acetate fraction to
after telogen to quickly enter anagen similar to a normal hair increase the viability of hair follicle cells, optionally outer
follicle (Cotsaleris and Millar, 2001). root sheath cells or epidermal stem cells. The hair follicle
23. US 2012/0128796 A1 May 24, 2012
2
cells are optionally cells in vitro or in vivo. In another [0035] The invention also relates to a sub-fraction of the
embodiment, the method comprises the use of the ethyl n-hexane fraction, wherein the sub-fraction is obtained by
acetate fraction to rejuvenate skin. [0036] a. sub-fractionating the fraction, and
[0022] The invention also relates to the use of a crude
[0037] b. isolating a sub-fraction comprising the follow-
extract, optionally a total aqueous extract, of an aerial root
ing compounds: lupeol, cycloartenol, ct-amyrin, sam-
portion, optionally an aerial root tip, ofa Ficus plant, option-
rated ester wax, 5-methoxypsoralen, stigmasterol, [3-si-
ally Ficus Benghalensis, for increasing hair growth, decreas-
tosterol, betulinic acid, betulonic acid, palmitic acid,
ing hair loss, rejuvenating skin, increasing the viability of a
[3-hydroxy-9,11-octadecadieonic acid and cerebrosides.
hair follicle, or increasing the viability of a hair follicle cell.
[0023] The invention further relates to an ethyl acetate frac- [0038] In one embodiment, the isolated sub-fraction com-
tion from a crude extract of an aerial root portion, optionally prises at least 0.3% by weight lupeol, 0.4% by weight
an aerial root tip, of a Ficus plant, optionally Ficus Bengha- cycloartenol, 0.4% by weight ct-amyrin, 0.7% by weight sam-
lens&, wherein the fraction is obtained by rated ester wax, 1.2% by weight 5-methoxypsoralen, 5% by
[0024] a. performing a n-hexane extraction on the crude weight stigmasterol and [3-sitosterol, 0.3% by weight bem-
extract to obtain a n-hexane fraction and a first residue, linic acid, 0.8% by weight bemlonic acid, 0.46% by weight
[0025] b. performing a dichloromethane extraction on palmitic acid, 0.1% by weight 13-hydxoxy-9,11-octadec-
the first residue to obtain a dichloromethane fraction and adieonic acid and 0.4% by weight cerebrosides.
a second residue, and [0039] Optionally, the n-hexane fraction is sub-fractioned
[0026] c. performing an ethyl acetate extraction the sec- by solvent partitioning, chromatography or any combination
ond residue to obtain an ethyl acetate fraction. thereof. In one embodiment, the chromatography is high per-
[0027] The invention also relates to the use of the ethyl formance liquid chromatography, optionally high perfor-
acetate fraction to increase the viability of hair follicle cells, mance liquid chromatography with a 19×300 mm C18 col-
optionally outer root sheath cells or epidermal stem cells. The umn, a gradient elution with 0.1% HCOOH in water and 0.1%
invention further relates to the use of the ethyl acetate fraction HCOOH in acetonitrile and flow rate 18 mL/min.
to rejuvenate skin.
[0040] In another embodiment, the chromatography is
[0028] The invention also relates to a fraction from a crude vacuum-assisted liquid chromatography, optionally vacuum-
extract of an aerial root portion ofa Ficus plant, optionally the assisted liquid chromatography with sequential elution using
portion comprising an aerial root tip, whereby the fraction is solvent mixtures from 100% hexane to 100% chloroform to
obtained by extracting the crude extract with a solvent having 100% methanol.
a dielectric constant of 1.1 to 4.0. In another embodiment, the
[0041] The invention also relates to the use of a sub-fraction
dielectric constant is 1.5 to 2.5.
of the n-hexane fraction to increase hair growth. Optionally,
[0029] In a further embodiment, the solvent is n-hexane. In the hair is a hair follicle in vitro or in vivo. The invention
yet another embodiment, the Ficus is Ficus benghalensis.
further relates to the use of a composition comprising the
[0030] The invention further relates to the use of a compo- sub-fraction of the n-hexane fraction to decrease hair loss or
sition comprising the n-hexane fraction to increase hair to increase the viability of a hair follicle cell, optionally a hair
growth. In another aspect of the invention, the hair is a hair follicle cell in vitro or in vivo.
follicle in vitro or in vivo. The invention also relates to the use
[0042] In another embodiment, the invention relates to the
of a composition comprising the n-hexane fraction to
use of a fraction or sub-fraction from a crude extract of an
decrease hair loss or to increase the viability of a hair follicle
aerial root portion ofa Ficus plant for increasing hair growth
cell, in vitro or in vivo. or decreasing hair loss wherein the fraction or sub-fraction
[0031] The invention further relates to a composition com- comprises a compound selected from the group consisting of:
prising the n-hexane fraction and a pharmaceutically accept- cerebrosides, terpenes, saturated fatty acids, unsaturated fatty
able carrier. Optionally, the composition comprises 1 pg/ml to acids, polar disaccharides, octadecenoic acids, psoralen, cou-
50 pg/ml of the n-hexane fraction, optionally 5 to 15 pg/ml of matins, azelaic acid, waxes, sterols, lupeol, cycloartenol,
the n-hexane fraction. The invention also relates to the use of ct-amyrin, saturated ester wax, 5-methoxypsoralen, stigmas-
the composition increase hair growth, optionally wherein the terol, [3-sitosterol, bemlinic acid, bemlonic acid, palmitic acid
hair is a hair follicle in vitro or in vivo. The invention further and 13-hydroxy-9,11 -octadecadieonic acid.
relates to the use of the composition to decrease hair loss
[0043] In yet another embodiment, the invention relates to
and/or increase the viability of a hair follicle cell. In one
the use of a sub-fraction from a crude extract of an aerial root
embodiment, the n-hexane fraction is for use in an amount of
portion ofa Ficus plant for increasing hair growth or decreas-
1 to 100 pg/day, optionally 10 to 30 pg/day.
ing hair loss wherein the sub-fraction comprises or consists
[0032] The invention also relates to a sub-fraction of the essentially of the following compounds: lupeol, cycloartenol,
n-hexane fraction, wherein the sub-fraction is obtained by ct-amyrin, saturated ester wax, 5-methoxypsoralen, stigmas-
[0033] (a) sub-fractionating the fraction, and terol, [3-sitosterol, bemlinic acid, betulonic acid, palmitic
[0034] (b) isolating a sub-fraction comprising a com- acid, 13-hydxoxy-9,11-octadecadieonic acid and cerebro-
pound selected from the group consisting of: cerebro- sides. In another embodiment, the sub-fraction comprises
sides, terpenes, saturated fatty acids, unsaturated fatty 0.3% by weight lupeol, 0.4% by weight cycloartenol, 0.4% by
acids, polar disaccharides, octadecenoic acids, psoralen, weight ct-amyrin, 0.7% by weight saturated ester wax, 1.2%
coumarins, azelaic acid, waxes, sterols, lupeol, by weight 5-methoxypsoralen, 5% by weight stigmasterol
cycloartenol, ct-amyrin, saturated ester wax, 5-methox- and [3-sitosterol, 0.3% by weight bemlinic acid, 0.8% by
ypsoralen, stigmasterol, [3-sitosterol, betulinic acid, weight bemlonic acid, 0.46% by weight palmitic acid, O. 1%
betulonic acid, palmitic acid and [3-hydroxy-9,11-octa- by weight 13-hydroxy-9,11-octadecadieonic acid and 0.4%
decadieonic acid. by weight cerebrosides.
24. US 2012/0128796 A1 May 24, 2012
[0044] The invention also relates to a composition compris- BRIEF DESCRIPTION OF THE DRAWINGS
ing a plurality of sub-fractions of the n-hexane fraction,
wherein the plurality of sub-fractions are obtained by: [0052] Embodiments of the invention will be shown in
[0045] (a) partitioning the n-hexane fraction with chlo- relation to the drawings in which the following is shown:
roform to obtain a chloroform partitioned fraction; [0053] FIG. 1: Total aqueous extract of E benghalensis
[0046] (b) loading the chloroform partitioned fraction aerial roots (TR1) increases hair follicle explant growth at
into a chromatography column, optionally a silica gel 0.01 mg/ml and 0.1 mg/ml.
vacuum-assisted liquid chromatography column; [0054] FIG. 2: Total aqueous extract of E benghalensis
[0047] (c) eluting the chloroform partitioned fraction aerial roots (TR1) increases hair follicle explant growth at
through sequential elution using solvent mixtures from 0.01 mg/ml.
100% hexane to 100% chloroform to 100% methanol to [0055] FIG. 3: Total aqueous extract of E benghalensis
obtain a plurality of sub-fractions; aerial roots (TR1) increases dermal papilla cell viability.
[0048] (d) collecting and combining the plurality of sub- [0056] FIG. 4A-D: A patient (B.D.) treated for 6 months
fractions. with a topical formulation containing total aqueous extract of
[0049] The invention also relates to a composition compris- E benghalensis aerial roots (TR1) shows an approximately
ing sub-fractions eluted at each of the solvent gradients listed 146% increase in terminal hair density averaged over all
in column 2 of Table 9. In a preferred embodiment, compo- zones of the scalp. The scalp zone referenced in each chart is
sition does not contain a sub-fraction eluted at 97% chloro- also indicated (see also FIG. 4G).
form: 3% methanol. In another embodiment, the composition [0057] FIG. 4E: A patient (B.D.) treated for 8 months with
does not contain a sub-fraction comprising unsaturated fatty a topical formulation containing total aqueous extract of E
acids. In another embodiment, the composition does not benghalensis aerial roots (20 pg/day TR1 for 6 months and
include a sub-fraction that decreases the viability, optionally 100 pg/day TR1 for months 9 to 11) shows an increase in
by at least 5%, at least 10%, at least 20%, at least 30% or at terminal hair density and a corresponding decrease in vellus
least 50% of explant hair follicles at 1 pg/ml. In another and miniaturized hair density. The formulation was applied to
preferred embodiment, the composition comprises the fol- zone 3-Right (3R) of the patient’s scalp. Extract dosage is
lowing compounds: lupeol, cycloartenol, ct-amyrin, saturated depicted in the horizontal axis in micrograms per day. Cumu-
ester wax, 5-methoxypsoralen, stigmasterol, [3-sitosterol, lative increase in terminal hair density (black solid rect-
angles) as a % of before treatment is also shown; treatment
betulinic acid, betulonic acid, palmitic acid, 13-hydroxy-9,
duration in months (m) represented in the x-axis.
11-octadecadieonic acid and cerebrosides. In yet another
embodiment, the composition comprises at least 0.3% by [0058] FIG. 4F: A patient (B.D.) treated in scalp zone 3R
weight lupeol, 0.4% by weight cycloartenol, 0.4% by weight with a topical formulation containing total aqueous extract of
ct-amyrin, 0.7% by weight saturated ester wax, 1.2% by E benghalensis aerial roots (TR1) and TR3 shows increased
hair growth. The patient was treated with 20 pg/day of the
weight 5-methoxypsoralen, 5% by weight stigmasterol and
TR1 extract up to month 6, had no treatment from the 6ti’
[3-sitosterol, 0.3% by weight betulinic acid, 0.8% by weight
month to the 9ti’ month and was treated with 100 pg/day of
betulonic acid, 0.46% by weight palmitic acid, 0.1% by
TR1 from the 9ti’ month to the 10ti’ month followed by 26
weight 13-hydroxy-9,11-octadecadieonic acid and 0.4% by
pg/day of TR3 from the 10ti’ to 12ti’ month.
weight cerebrosides
[0059] FIG. 4G: A depiction of the hair loss zones referred
[0050] The invention also relates to the use of the compo- to in FIGS. 4A-F.
sition described above to increase hair growth. Optionally, the
[0060] FIG. 5A-SB: A patient (B.D.) treated for one month
hair is a hair follicle in vitro or in vivo. The invention further
with a topical formulation containing total aqueous extract of
relates to use of the composition described above to decrease
E benghalensis aerial roots (TR1 ; 100 pg/day) shows growth
hair loss or to increase the viability of a hair follicle cell,
of new hairs and thickening of pre-existing hairs (SA, before
optionally a hair follicle cell in vitro or in vivo.
treatment; 5B, after treatment).
[0051] The invention also relates to a composition compris- [0061] FIG. 6: Hexane extracted fraction E1 of crude
ing lupeol, cycloartenol, ct-amyrin, saturated ester wax, extract ofE benghalensis (also referred to as TR2) increases
5-methoxypsoralen, stigmasterol, [3-sitosterol, betulinic acid, hair follicle explant viability at 1 pg/ml.
betulonic acid, palmitic acid, 13-hydroxy-9,11-octadec-
[0062] FIG. 7: Water extracted fraction E5 of crude extract
adieonic acid and cerebrosides and to the use of the compo-
ofE benghalensis increases dermal papilla (DP) cell viabil-
sition to increase hair growth or decrease hair loss. The inven-
ity.
tion also relates to a composition consisting essentially of
[0063] FIG. 8: Ethyl acetate extracted fraction E3 of crude
lupeol, cycloartenol, ct-amyrin, saturated ester wax, 5-meth-
extract ofE benghalensis increases outer root sheath (ORS)
oxypsoralen, stigmasterol, [3-sitosterol, betulinic acid, betu-
cell viability.
lonic acid, palmitic acid, 13-hydxoxy-9,11-octadecadieonic
acid and cerebrosides and to the use of the composition to [0064] FIG. 9: Hair follicle explant viability assay of the
increase hair growth or decrease hair loss. Optionally, the total aqueous extract of E benghalensis (TR1), the hexane
composition comprises at least 0.3% lupeol, 0.4% extracted fraction E1 (TR2) and TR3 at 1 pg/ml.
cycloartenol, 0.4% ct-amyrin, 0.7% saturated ester wax, 1.2% [0065] FIG. 10: A patient (M.A.F.) treated for one month
5-methoxypsoralen, 5% stigmasterol and 13-sitosterol, 0.3% with a topical formulation containing hexane extracted frac-
betulinic acid, 0.8% betulonic acid, 0.46% palmitic acid, tion E1 of crude extract ofE benghalensis (TR2; 20 pg/day)
0.1% 13-hydroxy-9,11-octadecadieonic acid and 0.4% cere- shows an increase in terminal hair density and vellus and
brosides. miniaturized hair density.
25. US 2012/0128796 A1 May 24, 2012
4
[0066] FIG. 11 A-B: A patient (M.A.F.) treated for one tion eluted with dichloromethane. An "ethyl acetate fraction"
month with a topical formulation containing hexane extracted is a fraction eluted with ethyl acetate. A "methanol fraction"
fraction E1 of crude extract of E benghalensis (TR2; 20 is a fraction eluted with methanol. A "water fraction" is a
p.g/day), shows growth of new hairs and thickening of pre- fraction eluted with water.
existing hairs (llA, before treatment; llB, after treatment). [0079] The term"sub-fraction" refers to a fraction obtained
[0067] FIG. 12: HPLC/UV chromatogram depicting sub- during the sub-fractionation of a fraction of a crude extract.
fractionation of n-hexane extracted fraction E1 (TR2). Sub-fractionation is optionally performed by chromatogra-
[0068] FIG. 13: Sub-fractions e7, ell, e21, e23 and e24 phy such as high performance liquid chromatography
have higher hair follicle viability promoting activity com- (HPLC) or vacuum assisted liquid chromatography or any
pared to the hexane extracted parent fraction, E1 (TR2). other method known in the art. In another embodiment, sub-
[0069] FIG. 14: Hair follicle viability assay for large scale fractionation is performed through solvent partitioning. A
E1 (TR2) fractions. E1 (TR2) was sequentially partitioned sub-fraction may be sub-fractionated into further sub-frac-
and the resulting chloroform fraction was further separated tions.
into sub-fractions by vacuum-assisted liquid chromatogra-
[0080] The terms "active extract", "active fraction" or
phy. "active sub-fraction" relate to an extract, fraction or sub-
[0070] FIG. 15: Hair follicle explant viability assay on 5 fraction that is alternatively at least 5%, 10%, 20%, 50% or
sub-fractions ofhexane extracted fraction E1 (TR2). more than 100% more active per unit weight than its parent
[0071] FIG. 16: Hair follicle viability assay for large scale fraction, as measured by a hair follicle explant growth assay,
E1 (TR2) fractions, normalized with respect to the relative a hair follicle explant viability assay or any other assay
weight of the fractions. designed to measure hair-growth promoting activity. In one
[0072] FIG. 17: Depiction of fractionation scheme for E1 embodiment, a"hair follicle explant growth assay" is an assay
(hexane extracted fraction). that analyzes the growth of explant hair follicles in vitro. In
[0073] FIG. 18. The Norwood scale of hair loss. another embodiment, a "hair follicle explant viability assay"
[0074] FIG. 19. Percentage increase in hair density in scalp is an assay that analyzes the viability of explant hair follicles
zones 1R, 1L, 1M, 2M and 3M following three months of in vitro.
treatment with TR3. Results averaged over 20 subjects.
[0081] In another embodiment, an "active extract", "active
fraction" or "active sub-fraction" is an extract, fraction or
DETAILED DESCRIPTION
sub-fraction that is alternatively at least 5%, 10%, 20%, 50%
[0075] The present application relates to natural product or more than 100% more active per unit weight than the crude
extracts, fractions and compounds from Ficus plants useful extract from which it was originally derived, as measured by
for increasing hair growth and decreasing hair loss. a hair follicle explant growth assay, a hair follicle explant
[0076] The term "Ficus" refers to any species of the Ficus viability assay or any other assay designed to measure hair-
genus. The term "Ficus having an aerial root" refers to plants growth promoting activity.
of the species Ficus with at least one aerial root. One example [0082] In another embodiment, an "active extract", "active
of such a plant is Ficus benghalensis. Other Ficus plants that fraction" or "active sub-fraction" is an extract, fraction or
may grow aerial roots include, but are not limited to, Ficus sub-fraction that contains at least 5%, 10%, 20%, 50%, 75%
benjamina, Ficus microcarpa, Ficus citrifolia and Ficus or 100% of active compound(s). An active compound is a
retusa. compound that promotes hair growth as measured by a hair
[0077] The term"aerial root" refers to a root growing above follicle explant growth assay, a hair follicle explant viability
the ground and exposed to air. Aerial roots grow rapidly due assay or any other assay designed to measure hair-growth
to the presence of root meristem cells. The term "aerial root promoting activity.
tip" refers to the end of the aerial root, typically located on the [0083] The terms "increases hair growth" and "promotes
portion of the aerial root furthest from the trunk of the tree hair growth" include, but are not limited to, activity that
depending on the direction of growth. The term "aerial root increases the number of hairs on a mammal, maintains the
portion" refers to any portion of an aerial root. Optionally, the number of hairs in a given area of scalp on a mammal that
aerial root portion comprises the tip of an aerial root. Option- would otherwise experience net hair loss, grows hair on a
ally, the aerial root portion comprises the outer 5 to 15 centi- mammal, re-grows hair on a mammal, increases the length or
meters of an aerial root including the tip. Optionally, the aerial thickness of hair on a mammal, improves the health of hair on
root portion comprises the outer 10 centimeters orthe outer 5 a mammal, treats baldness (for example, male pattern bald-
centimeters or less of an aerial root including the tip: ness, female pattern baldness, genetic alopecia) and/or
[0078] The term "crude extract" refers to a concentrated
increases hair follicle density. The term "increasing hair
preparation of vegetation that has not been subjected to any
growth" includes activity that stimulates growth of a single
solvent extractions. For example, a crude extract can consist
hair in a follicle or growth of a group of hairs in hair follicles
in specified area of epidermis. Increasing hair growth option-
of vegetation that has been dried and processed into a powder
ally occurs, for example, by increasing the number of hairs
form. The terms "extract", "fraction" or "sub-fraction" refer
present in an area of epidermis of a mammal or maintaining
to a concentrated preparation of plant material that has been
the number of hairs present in an area of epidermis of a
obtained by removing active constituents with a suitable sol- mammal that would otherwise experience net hair loss (op-
vent. Numerous extracts, fractions and/or sub-fractions can tionally measured per square cm). Increasing hair growth
be obtained from a single crude extract. In one embodiment of optionally causes growth of a new hair in a follicle (e.g. after
the invention, the "crude extract" is a total aqueous extract or a hair has fallen out) or increases rate of growth of an existing
a water extract. Optionally, the total aqueous extract is hair (length and/or width) of a hair in a follicle on a mammal.
obtained by pulverizing the aerial root of a Ficus and boiling Increasing hair growth optionally increases hair length.
the resulting powder. A "n-hexane fraction" is a fraction Increasing hair growth prevents (reduces) and/or treats bald-
eluted with n-hexane. A "dichloromethane fraction" is a frac- ness and/or balding. It optionally has other effects such as
26. US 2012/0128796 A1 May 24, 2012
increasing hair follicle density in an area and/or the appear- [0087] The term "rejuvenating skin" includes increasing
ance of thickness of hair in an area. Increasing hair growth the health of skin, improving the appearance of skin, decreas-
optionally also improves the health of hair and hair follicles ing signs of skin aging, for example, decreasing the presence
on a mammal. Typically the increase in the foregoing param- or appearance of wrinkles, fine lines or age spots or increasing
eters that are quantifiable will be at least: 5%, 10%, 20%, the viability of skin cells. Typically the increase or decrease in
50%, 100% or 150% compared to untreated hair follicles (or the foregoing parameters will be at least: 5%, 10%, 20%,
epidermis) that do not experience the present methods and 50%, 100% or 150% compared to untreated skin which does
compositions that increase hair growth. These percentage not experience the present methods and compositions that
increases are optionally measured in a single hair or single
rejuvenate skin.
hair follicle (e.g. rate of increased growth, increase in length
or thickness per day) or in a plurality of hairs or hair follicles [0088] Ficus benghalensis is also known as Bengal fig,
in a specified area (e.g. increase in number of hairs per square Indian fig, East Indian fig, Banyan, Bargad or Bod (Kala et al.,
cm or in length of hairs growing per square cm). 2004). It is a species of Ficus that is typically found in high
concentrations in Bangladesh, India and Sri Lanka, though it
[0084] The term "increasing hair growth" optionally refers
can be cultivated in other places. E benghalensis produces
to increasing the viability of hair follicles in vivo or in vitro.
The term "increasing hair growth" also optionally refers to aerial roots, which grow downwards as slender vine. Once
increasing the viability of an isolated hair follicle, i.e. an these roots reach the ground, they take root and grow into
isolated hair follicle in culture (in vitro). Increasing the viabil- woody trunks that can become indistinguishable from the
ity of hair follicles in vitro can be measured through a hair main trunk.
follicle explant growth assay, a hair follicle explant viability [0089] The aerial roots ofE benghalensis typically grow a
assay or any other method known in the art. Typically the few centimeters per day. Optionally the aerial roots grow at
increase in the foregoing parameters will be at least: 5%, least 0.5 cm per day in length in soil or hydroponic conditions
10%, 20%, 50%, 100% or 150% compared to untreated hair
that support Ficus growth. The growth and differentiation of
follicles that do not experience the present methods and com-
meristem cells or plant stem cells is supported by various
positions that increase hair growth.
growth promoting factors in these areas (Tucker and Laux,
[0085] The term "decreases hair loss" includes, but is not
2007). Without being bound by theory, the longevity and fast
limited to, activity that maintains the number of hairs or hair
follicles on a mammal that would otherwise experience net incessant growth of E benghalensis aerial roots may reflect
hair loss (optionally measured as the number of hairs or hair the presence of such stem cell mobilizing factors.
follicles measured per square cm), reduces the rate of balding [0090] In one aspect of the invention, aerial roots ofa Ficus
and/or reduces the rate of hair follicle miniaturization. plant are dried and powdered to obtain a crude extract. The
Decreasing hair loss optionally decreases the rate of hair loss, method of extraction optionally includes extracting a portion
hair follicle loss and/or hair follicle miniaturization by at least of the aerial root. The portion of the aerial root extracted can
5%, 10%, 20%, 50%, 100% or 150% compared to untreated
be the end portion of the aerial root that is actively growing in
hair follicles (or epidermis) that do not experience the present
length. The method of extraction optionally includes extract-
methods and compositions that decrease hair loss. These per-
ing the outer 5 to 15 centimeters of the root length (the end of
centage increases are optionally measured in a single hair or
single hair follicle or in a plurality of hairs or hair follicles in the root tip and the 5 to 15 centimeters proximate to the end),
a specified area. or optionally the outer 10 centimeters or outer 5 centimeters,
or less of the root length (the end of the root tip and the 5 or 10
[0086] The term "increases cell viability" refers to increas-
centimeters proximate to the end). The method of extracting
ing the viability of cells, whether in vivo or in vitro. The term
also optionally includes extracting a portion of the Ficus
"increases isolated cell viability" refers to increasing the
aerial root that has grown in length over the 15 day period
viability of isolated cells in culture (in vitro). The term can
prior to cutting or any time period therein (for example, the 2
refer to increasing the growth of one or more hair follicle cells
day period prior to cutting, the 5 day period prior to cutting or
such as dermal papilla cells, outer root sheath cells, epidermal
the 10 day period prior to cutting).
stem cells, dermal sheath cells or epidermal matrix cells. In
one example, cell viability is determined by incubating cells [0091] In one embodiment of the invention, fractions of the
with methanethiosulfonate (MTS) reagents and measuring crude extract are extracted by methods known in the art.
optical density (OD) 490 nm spectrophotometrically. Option- Optionally, the crude extract is fractionated by performing a
ally, increased cell viability is indicated by an increase in the Soxhlet extraction with a series of solvents. In one aspect of
percent survival of treated cells versus non-treated cells. Typi- the invention, the crude extract is fractioned with 250 to 750
cally, the increase in cell viability will be quantifiable, for ml of each solvent. In another aspect of the invention, the
example, 110%, 120%, 150%, 200% or 500% viability com- crude extract is fractionated with approximately 500 ml of
pared to a control. The term "increases hair follicle viability" each solvent per 100 g of crude extract. The solvents can
refers to increasing the viability of hair follicles, whether in include, but are not limited to, n-hexane, dichloromethane,
vivo or in vitro. The term "increases isolated hair follicle ethyl acetate, methanol and water. The extraction of the vari-
viability" refers to increasing the viability of isolated hair ous fractions can occur in the following sequence: n-hexane
follicles in culture (in vitro). Optionally, increased hair fol- extraction, dichioromethane extraction, ethyl acetate extrac-
licle viability is indicated by an increase in the percent sur- tion, methanol extraction and water extraction. Other types of
vival of treated hair follicles versus non-treated hair follicles. extractions and solvents will be readily apparent.
Typically, the increase in hair follicle viability will be quan- [0092] The crude extract can be fractionated with a solvent
tifiable, for example, 110%, 120%, 150%, 200% or 500% with a dielectric constant of 1.1 to 4.0, typically 1.5 to 2.5.
viability compared to a control. Hair follicle viability is Most typically, the crude extract is fractionated with n-hex-
assessed by any method known in the art to quantify hair ane, which has a dielectric constant of 1.9. The crude extract
follicle viability, optionally a hair follicle explant assay. can also be fractionated with solvents having similar physico-
27. US 2012/0128796 A1 May 24, 2012
6
chemical properties to those of n-hexane. Optionally, the [0102] The invention also provides a sub-fraction compris-
method of extraction includes fractionating with hexane or ing the following compounds: lupeol, cycloartenol,
any of its isomers. ct-amyrin, saturated ester wax, 5-methoxypsoralen, stigmas-
[0093] The crude extract or any one of the fractions of the terol, [3-sitosterol, betulinic acid, betulonic acid, palmitic
crude extract of aerial roots of a Ficus plant can be used to acid, 13-hydloxy-9,11-octadecadieonic acid and cerebro-
increase hair growth or decrease hair loss. In particular, the sides. Optionally, the sub-fraction comprises at least 0.3% by
n-hexane extracted fraction, the ethyl acetate extracted frac- weight lupeol, 0.4% by weight cycloartenol, 0.4% by weight
tion or the water extracted fraction are useful to increase hair ct-amyrin, 0.7% by weight saturated ester wax, 1.2% by
growth or decrease hair loss. The extracts and fractions weight 5-methoxypsoralen, 5% by weight stigmasterol and
directly useful to increase hair growth or decrease hair loss [3-sitosterol, 0.3% by weight betulinic acid, 0.8% by weight
can be formulated in a composition. In one embodiment, the betulonic acid, 0.46% by weight palmitic acid, 0.1% by
composition comprises the n-hexane fraction, the dichlo- weight 13-hydloxy-9,11-octadecadieonic acid and 0.4% by
romethane fraction, the ethyl acetate fraction and/or the weight cerebrosides.
methanol fraction. In another embodiment, the composition [0103] The invention also provides a plurality of sub-frac-
consists of, or consists essentially of the n-hexane fraction, tions of the n-hexane fraction, wherein the plurality of sub-
the dichloromethane fraction, the ethyl acetate fraction and/ fractions are obtained by partitioning the n-hexane fraction
or the methanol fraction. with a solvent, optionally chloroform, loading the solvent
[0094] In another aspect of the invention, the n-hexane partitioned fraction into a chromatography column and elut-
fraction of the crude Ficus extract (TR2) is sub-fractioned ing the solvent partitioned fraction through sequential elution
into a number of sub-fractions. The sub-fractionation is to obtain a plurality of sub-fractions. Optionally, the solvent
readily performed by chromatography, such as high perfor- partitioned fraction is eluted using solvent mixtures ranging
mance liquid chromatography, or any other separation from 100% hexane to 100% chloroform to 100% methanol. In
method known in the art. one embodiment, the chromatography is vacuum assisted
[0095] The invention provides a sub-fraction of the n-hex- liquid chromatography. In one specific embodiment, the plu-
ane fraction of the crude Ficus extract (TR2) containing cere- rality of sub-fractions are the 30 sub-fractions listed in Table
brosides. Cerebrosides are glycosphingolipids that consist of 9 (also known as TR3). The invention also provides a com-
a ceramide (composed of sphingosine and a fatty acid) with a position comprising the plurality of sub-fractions. In a pre-
single sugar residue at the 1 -hydroxyl moiety. ferred embodiment, the composition does not contain a sub-
fraction eluted at 97% chloroform: 3% methanol. In another
[0096] The invention also provides a sub-fraction contain-
embodiment, the composition does not contain a sub-fraction
ing terpenes, saturated fatty acids and unsaturated fatty acids.
comprising unsaturated fatty acids, optionally 85-90% unsat-
Terpenes are a large class of hydrocarbons produced prima-
urated fatty acids. In yet another embodiment, the composi-
rily by plants. Terpenes are derived biosynthetically from
tion does not include a sub-fraction that decreases the viabil-
units of isoprene. Isoprene has the molecular formula CsH8.
ity, optionally by at least 5%, at least 10%, at least 20%, at
[0097] The invention also provides a sub-fraction compris- least 30% or at least 50%, ofexplant hair follicles at 1 tg/ml.
ing psoralen. Psoralen is the parent compound in a family of
[0104] In another embodiment, the invention provides a
natural products known as furocoumarins.
composition comprising the chloroform partititioned fraction
[0098] The invention further provides a sub-fraction con- wherein a sub-fraction eluted at 97% chloroform:3% metha-
taining polar disaccharide and a sub-fraction containing cou- nol has been removed. Optionally, the removed sub-fraction
matins. Coumarins are a group of compounds found in many comprises unsaturated fatty acids, optionally 85-90% unsat-
plants. Psoralen and its derivatives belong to the coumarin urated fatty acids. In yet another embodiment, the removed
class of compounds. sub-fraction decreases the viability, optionally by at least 5%,
[0099] In another aspect of the invention, the n-hexane at least 10%, at least 20%, at least 30% or at least 50%, of
fraction of the crude Ficus extract is sub-fractioned through explant hair follicles at 1 tg/ml.
solvent partitioning. In a further aspect of the invention, the [0105] The invention also relates to the use of a composi-
n-hexane fraction of the crude Ficus extract is partitioned
tion comprising or consisting the plurality of sub-fractions to
with chloroform to give a chloroform soluble fraction. increase hair growth or to decrease hair loss. The composition
[0100] In yet another aspect of the invention, the chloro- may comprise or consist of the 30 sub-fractions listed in Table
form soluble fraction is further sub-fractionated into a num- 9 (also known as TR3) in a suitable carrier. In one embodi-
ber of sub-fractions. In a preferred embodiment, the chloro- ment, the carrier is a cosmetic carrier. In another embodiment,
form soluble fraction is further sub-fractionated using the composition comprises the following compounds: lupeol,
preparative VLC (silica gel) fractionation. The further sub- cycloartenol, alpha-amyrin, saturated ester wax, 5-methox-
fractions obtained from the preparative VLC (silica gel) frac- ypsoralen, stigmasterol, [3-sitosterol, betulinic acid, betulonic
tionation may be further fractionated again by chromatogra- acid, palmitic acid, 13-hydroxy-9,11-octadecadieonic acid
phy, such as high performance liquid chromatography, or any and cerebrosides. In another embodiment, the composition
other method known in the art. consists essentially of the following compounds: lupeol,
[0101] The invention provides a further sub-fraction of the cycloartenol, ct-amyrin, saturated ester wax, 5-methoxypso-
choloroform soluble fraction containing any one of the fol- ralen; stigmasterol, [3-sitosterol, betulinic acid, betulonic
lowing compounds: saturated fatty acids, psoralen, 5-meth- acid, palmitic acid, 13-hydroxy-9,11-octadecadieonic acid
oxypsoralen, psoralen analogues, cerebrosides, glucosylce- and cerebrosides. Optionally, the compounds are present in
ramide, terpenes, octadecenoic acids, betulinic acid, the composition in at least the percentage amounts listed in
betulonic acid, palmitic acid, 13-hydroxy-9,11-octadecadi- Table 8.
enoic acid and 18-hydroxy-9-octadecenoic acid, saturated [0106] The invention also relates to the use of a composi-
ester waxes (for example, hexacosyl tetracosanoate, hexaco- tion comprising an extract, fraction or sub-fraction of Ficus
syl hexacosanoate, hexacosyl tetracosanoate and hexacosyl which has activity to increase hair growth or decrease hair
docosanoate), cycloartenol, ct-amyrin, lupeol, stigmasterol, loss, singly or together, to increase hair growth or decrease
[3-sitosterol and 5-methoxypsoralen. hair loss. The invention further relates to the use ofa compo-
28. US 2012/0128796 A1 May 24, 2012
7
sition consisting of, or consisting essentially of an extract, which has activity to increase hair growth or decrease hair
fraction or sub-fraction ofFicus which has activity to increase loss, alone or in combination, to increase the viability of hair
hair growth or decrease hair loss, singly or together, to follicle cells, for example, outer root sheath cells, epidermal
increase hair growth or decrease hair loss. stem cells, dermal papilla cells, dermal sheath cells and epi-
[0107] In addition, the invention relates to the use, singly dermal matrix cells.
and together in any combination, of a composition compris- [0114] In one embodiment, the compositions of the inven-
ing a compound or class of compound described above which tion are topical compositions that are typically applied to the
has activity to increase hair growth or decrease hair loss to scalp or skin by spraying or coating. The compositions for
increase hair growth or decrease hair loss. The invention external dermal applications can be formulated as liquids,
further relates to the use, singly and together in any combi- milky lotions, gels, creams, aerosols, sprays, powders, cos-
nation, of a composition consisting of, or consisting essen- metics or rinses. There are no limitations to the method by
tially of a compounds or class of compound described above which the compositions can be applied. For example, 1 to 5
which has activity to increase hair growth or decrease hair ml of the compositions could be applied to scalp or skin
loss to increase hair growth or decrease hair loss. surface areas 1 to 3 times per day.
[0108] The invention further relates the use of a composi-
[0115] Optionally, the compositions of the invention are
tion comprising, consisting or, or consisting essentially of an
formulated in a suitable dermal penetration carrier or phar-
extract, fraction, sub-fraction or compound described above
maceutically acceptable carrier. Optionally, the carrier is a
which has activity to increase hair growth or decrease hair
cosmetic carrier. The carrier may contain antioxidants, vita-
loss, alone or in combination, to generate new hair on a
mins, preservatives, anti-microbials, colorants, moisturizers,
subject. In one aspect of the invention, a new hair is generated
thickeners and preservatives that do not interfere with the
from a pre-existing follicle. In another aspect of the invention,
desired effects of the present invention.
a follicle giving rise to a new hair is generated. The generation
of new hair may comprise increasing the density of individual [0116] Suitable pharmaceutically acceptable carriers
hairs and/or hair follicles within a specified area of a patient’s include essentially chemically inert and nontoxic composi-
scalp. Optionally, hair density is increased by 5%, 10%, 20%, tions that do not interfere with the effectiveness of the bio-
50% or more than 100%. In one embodiment of the invention, logical activity of the pharmaceutical or cosmetic composi-
a composition comprising, consisting of, or consisting essen- tion. Examples of suitable pharmaceutical or cosmetic
tially of an extract, fraction, sub-fraction or compound carriers include, but are not limited to, water, saline solutions,
described above which has activity to increase hair growth or glycerol solutions, ethanol, N-(l(2,3-dioleyloxy)propyl)N,
decrease hair loss, alone or in combination, is topically N,N-trimethylammonium chloride (DOTMA), diolesylphos-
applied to a subject for use in generating new hair. photidyl-ethanolamine (DOPE), and liposomes. Such com-
positions should contain a therapeutically effective amount of
[0109] The invention further relates the use of a composi-
tion comprising, consisting or, or consisting essentially of any the compound(s), together with a suitable amount of carrier
so as to provide the form for administration to the subject.
of the extracts, fractions, sub-fractions and compounds
described above, alone or in combination, to thicken a hair [0117] In one embodiment of the invention, the carrier is
shaft on a subject. Optionally, the diameter of a thickened hair WE-basic medium plus 25% glycerol. In another embodi-
shaft is increased by 5%, 10%, 20%, 50% or more than 100% ment, the carrier is a basic oily carrier, optionally a basic oily
following treatment with a composition of the invention. carrier comprising the following ingredients: dicapryl ether,
Optionally, the diameter of a thickened hair shaft is increased octyldodecanol, oryza sativa bran oil, prunus amygdalus dul-
by at least 10-100 grn, optionally 20-50 pm. cis oil, lecithin, tocopherol, ascorbyl palmitate and citric acid.
[0110] The invention further relates the use of a composi- [0118] The compositions of the invention optionally con-
tion comprising, consisting or, or consisting essentially of an tain between 0.0001% to 100% by weight of the active
extract, fraction, sub-fraction or compound described above, extract, fraction, sub-fraction and/or compound. Optionally,
alone or in combination, to increase the rate of hair growth on the compositions of the invention contain between 0.001%
a subject. Optionally, the rate is increased by 5%, 10%, 20%, and 1% by weight of the active extract, fraction, sub-fraction
50% or more than 100% following treatment with a compo- and/or compound. Optionally, the compositions of the inven-
sition of the invention. tion contain between 1 tg/ml to 0.1 mg/ml, optionally 10
[0111] The invention further relates the use of a composi- tg/ml to 100, 150, 200 or 250 tg/ml, of the active extract,
tion comprising, consisting or, or consisting essentially an fraction, sub-fraction and/or compound.
extract, fraction, sub-fraction or compound described above [0119] In one particular embodiment, the invention relates
which has activity to increase hair growth or decrease hair to a composition comprising 0.1 tg/ml to 250 tg/ml TR1
loss, alone or in combination, to increase the longitudinal hair (total aqueous extract of E benghalensis), optionally 0.1
growth of a subject. Optionally, longitudinal hair growth is tg/ml to 100, 150, 200 or 250 tg/ml TR1, preferably 1 tg/ml
increased by 5%, 10%, 20%, 50% or more than 100% follow- to 100 tg/ml TR1, preferably 10 tg/ml to 50 tg/ml TR1.
ing treatment with a composition of the invention. Typically, a TR1 composition is administered to a subject in
[0112] The invention also relates to the use of a composi- order to increase hair growth or decrease hair loss at a dosage
tion comprising, consisting or, or consisting essentially of an of 1 tg to 200 tg TR1 per day, preferably 20 tg to 100 tg per
extract, fraction, sub-fraction or compound described above day.
which has activity to increase hair growth or decrease hair [0120] In another particular embodiment, the invention
loss, alone or in combination, to increase the viability of hair relates to a composition comprising 0.1 tg/ml to 250 tg/ml
follicles in vitro. TR2 (hexane extracted fraction of F.. benghalensis), option-
[0113] The invention also relates to the use of a composi- ally 0.1 tg/ml to 100, 150, 200 or 250 tg/ml TR2, preferably
tion comprising, consisting or, or consisting essentially of an 1 tg/ml to 100 tg/ml TR2, preferably 10 tg/ml to 50 tg/ml
extract, fraction, sub-fraction or compound described above TR2. Typically, a TR2 composition is administered to a sub-
29. US 2012/0128796 A1 May 24, 2012
ject in order to increase hair growth or decrease hair loss at a the invention relates to a method of increasing the length or
dosage of 1 pg to 200 gg TR2 per day, preferably 20 gg to 100 viability of hair follicles in vitro by maintaining the hair
pg per day. follicles in media comprising a composition described herein.
[0121] In another particular embodiment, the invention
relates to a composition comprising 0.1 pg/ml to 250 pg/ml EXAMPLES
TR3, optionally 0.1 gg/ml to 100, 150, 200 or 250 pg/ml TR3,
preferably 1 pg/ml to 100 gg/ml TR3, preferably 10 gg/ml to [0128] Embodiments of the present invention will be illus-
50 gg/ml TR3. Typically, a TR3 composition is administered trated in a non-limiting way by reference to the examples
below.
to a subject in order to increase hair growth or decrease hair
loss at a dosage of 1 gg to 200 pg TR3 per day, preferably 20
Example 1
pg to 100 pg per day.
[0122] Optionally, the compositions of the invention are Total Aqueous Extracts ofF. benghalensis Aerial
administered subcutaneously, subdermally, intramuscularly Root Tips
or intravenously.
[0123] The dosage of the compositions vary according to Sample Collection
the specific form of the external application, age and the type
[0129] F. benghalensis var. benghalensis (Banyan) trees
and degree of hair loss. FIG. 20 depicts the seven classes of
grown in rural non-residential area far from industries and
hair loss as defined by the Norwood scale of hair loss. Option-
heavy traffic roads were selected. Samples were obtained
ally, the compositions of the invention are administered to
from at least 5 trees located at least 100 meters apart. The trees
subjects with hair loss as classified by the Norwood scale as
were confirmed to be species F. benghalensis at a certified
class 2 (mild hair loss), class 3 (mild to moderate hair loss),
botanic centre. Ten centimeter long intact aerial root tips were
class 4 (moderate hair loss), class 5 (moderate to large hair
collected from longer prop roots (roots originating from
loss), class 6 (large hair loss) or class 7 (complete hair loss).
higher branches but yet reaching the ground). The collected
Optionally, the compositions of the invention are adminis-
intact root tips from each tree separately weighed at least 500
tered to subjects with no hair loss (class 1) in order to prevent
future hair loss. grams.
[0124] In one aspect of the invention, the compositions are
Sterilization
used for treating hair loss or baldness. Optionally, the com-
positions are also used for preventing or reducing hair loss or [0130] Aerial root tips of each E benghalensis tree were
baldness (e.g. stopping or slowing hair loss progression). rinsed with sterile double distilled water, immersed in 70%
Since the compositions are natural products with no known aqueous ethanol for 60 seconds, rinsed three times with sterile
side effects, they are also useful for individuals with no signs double distilled water three times, surface sterilized with a
of hair loss at all who wish to use the product to prevent or 5% (w/v) NaOC1 solution for 10 minutes and rinsed again
reduce risk of hair thinning or hair loss on a prophylactic three times with sterile double-distilled water (Sokmen et al.
basis. The compositions are therefore useful by themselves or 2004; Liqing Z. et al. 2005).
as additives to products such as shampoo, conditioner,
mousses, gels or creams as well as other cosmetics and drugs Total Aqueous Extracts (Crude Extracts)
(typically over the counter drugs). These products are topi-
cally administered according to methods described herein. [0131] Sterilized root tips were shade-dried for 5-7 days
[0125] In another aspect of the invention, the compositions and pulverized using a pestle and mortar. The pulverized parts
are used conjunction with hair transplant surgery. Optionally, may be stored in cellophane bags at room temperature. 100 g
the compositions are administered to a patient prior to sur- of the root tip powder was subjected to exhaustive Soxhlet
gery, during surgery, or following surgery. The invention extraction in 500 ml of distilled water for 72 hours. Each
therefore relates to a method of transplanting hair in a subject extract was concentrated in a water bath until a constant color
by implanting a hair follicle in the subject and contacting the residue was obtained (Garba et al. 2006). The extract was
hair follicle with a composition described herein. The hair further lyophilized and stored in a tightly capped container in
follicle of the subject can be contacted with the composition the freezer (Channabasavaraj et al. 2008).
prior to, during, or after transplantation. The follicle trans-
plant is typically made onto a human scalp and the composi- Preparation of Stock and Test Solutions
tions are optionally used for at least one week, four weeks or [0132] Stock solution of the aqueous extract was prepared
at least 52 weeks. by dissolving the lyophilized powder in Ca2÷- and Mg2÷-free
[0126] In one embodiment of the invention, the composi- phosphate buffered saline (PBS). The stock solution had a
tions are used to promote the viability of cells derived from final concentration of 250 mg/ml and was stored at 4° C.
hair follicles. Cells derived from hair follicles include, but are Aqueous extracts for the required treatment regimens were
not limited to, dermal papilla cells, outer root sheath cells, freshly prepared by serially diluting the stock solution with
dermal sheath cells and epidermal matrix cells. In one aspect cell culture medium (Garba et al. 2006).
of the invention, the compositions are added to cell culture
medium to increase the viability of hair follicle cells in vitro. Example 2
In another embodiment of the invention, the compositions are
E benghalensis Extract Increases Hair Follicle
used to promote the viability of skin cells.
Explant Growth
[0127] In another embodiment of the invention, the com-
positions are used to promote the viability of explant hair [0133] Hair follicles were obtained through standard surgi-
follicles in vitro. In another aspect, the compositions are used cal procedures and placed in Petri dishes containing 5x anti-
to increase the length of explant hair follicles in vitro. The biotic/PBS for 20 minutes at room temperature. After wash-
invention therefore relates to a method of increasing the ing in saline or phosphate buffered saline, the hair follicles
length or viability of hair follicles in vitro by contacting the were transferred to Williams’ E growth media (WE; Invitro-
hair follicle with a composition described herein. Optionally, gen) and placed inside the incubator until ready for use. The
30. US 2012/0128796 A1 May 24, 2012
9
follicles were cut below the epidermis, leaving an intact hair [0139] Hair density measurements were taken once every
follicle bulb with dermal papilla, hair fiber, and outer root two weeks for each area. Hairs with a diameter less than 40
sheath. tm were classified as vellus & miniaturized hairs; hairs with
[0134] Growth of the follicles was measured with Zeiss a diameter greater than 40 tm were classified as terminal
DV4 Stereo Microscope equipped with a reticle. Whole hair hairs. Treatment with the TRl-formulation for 6 months
follicle length was measured before treatment and after incu- resulted in an approximately 146% increase in overall termi-
bating under the defined conditions for 7 to 8 days at 37° C., nal hair density. FIGS. 4A-D depict the density of vellus,
5% CO2. miniaturized, terminal and total hairs over the 6 month treat-
[0135] FIG. 1 shows growth of hair follicles as a percentage ment in zones 1 R and L, 1M, 2 and 3, respectively (zones are
of the initial length for each treatment. Each experimental depicted in FIG. 4G).
point represents a summary of 3 to 4 individual experiments [0140] FIG. 4E depicts the density ofvellus and miniatur-
in different patients. Data are the mean_+SEM (SEM, standard ized hair, terminal hair and total hair over 10 months of
error of mean) of at least 4 individual patients. The media only treatment with the TR1 -formulation over a varying dosage as
control consists of WE substituted with L-glutamine (2 depicted in the horizontal axis.
retool/L), hydacocortisone (10 ng/ml) and antibiotic solution [0141] FIG. 4F shows a visualization of the hair growth in
1 x (100 units/ml penicillin, 100 btg/ml streptomycin and 0.25 the patient described above. The patient was treated with 20
btg/ml amphotericin). The "Growth factor 10 mixture" con- tg/day TR1 up to month 6, had no treatment from the 6ti’
tains IGF-I, FGF-2, FGF-10, PDGF-AA, Wnt-3A, Noggin, month to the 9ti’ month and then was treated with 100 tg/day
Ephrin-A3, SHH, !3MP-6 each at 20 ng/ml, and hypoxanthine TR1 from the 9ti’ month to the 10ti’ month followed by 26
at 2 btmol/L (2 btM) final concentration. TR1 refers to the total tg/day TR3 from the 10ti’ month to the 1Ui’ month.
aqueous extract of E benghalensis. The TR1 extract pro-
moted hair follicle (HF) explant growth at concentrations of Example 5
0.01 mg/ml and 0.1 mg/ml.
[0136] FIG. 2 shows a hair follicle explant growth assay Topical Application of TR1 Results in New Hairs
performed as described for FIG. 1. The GF7 treatment con- and Thickened Hairs
sists of 7 growth factors (IGF-1, FGF-2, PDGF-AA, Wnt-3a,
Noggin, !3MP-6; at 10 ng/ml; hypoxanthine at 1 btmol/L). [0142] 2 ml of a 50 btg/ml (100 btg per day) TR1 (total
TR1 at 0.01 mg/ml induced more growth compared to the aqueous extract ofF. benghalensis) formulation was topically
control as well as the GF7 treatment. applied on a daily basis to the whole balding area of the scalp
of a patient for four weeks. Patient presented with male pat-
tern baldness in the crown area (Zone 3-right). Prior to the
Example 3
treatment, a 0.789 cm2 area was shaved to such that the hairs
F. benghalens& Extract Promotes Dermal Papilla were 0.5 mm in length and phototrichographic measurements
Cell Viability of the area were taken including hair density and hair thick-
ness. Hair density and thickness was measured using the
[0137] Dermal papilla (DP) cells were isolated from hair Tricoscan® system (phototrichography system from
follicles. The cells were plated and treated with the total FotoFinder Systems Inc. MA, USA). Following four weeks of
aqueous extract ofE benghalens& (TR1) for different dura- treatment, the area was shaved to 0.5 mm again and photo-
tions by incubating at 37° C. with 5% CO2. To assess cell graphs were taken and each hair follicle unit was manually
viability after treatment, a MTS (methanethiosulfonate) enumerated at 40x magnification for both new hair and
viability assay was performed: 5 tl MTS reagents (Promega, increase in thickness of hair.
WI) were added per 100 tl cells. Cells were incubated further [0143] FIG. 5A depicts the treatment zone prior to treat-
for 2.5 hrs at the end of which OD at 490 nm was measured ment and FIG. 5t3 depicts the treatment zone after 4 weeks of
spectrophotometrically. The color developed at this wave- treatment. New hairs that appeared after treatment are indi-
length is directly proportional to the viability of cells in the cated by numbered triangles and hairs that appeared thick-
medium. As shown in FIG. 3, increased DP cell viability was ened after treatment are indicated by numbered squares. In
observed from 0.1 to 10 tg/ml TR1. all, 9% of the hair follicles in the study area contained hair that
was thickened and 10% of the hair follicles in the study area
Example 4 contained new hair. Table 1 contains a detailed analysis of the
numbered hair follicles in FIGS. 5A and 5t3. Bracketed num-
Topical Application of Total F. benghalensis Extract
bers in the "Increased number" column indicate the number
Increases Hair Density
of new hairs at a follicle. Numbers marked with an asterix
[0138] A patient’s scalp was mapped to 4 specific bald indicate an entirely new hair (i.e., either a new hair from a new
zones: 1) 1R+IL (Zone 1 Right and Left), 2) 1M (Zone 1 follicle or a new hair from a follicle not previously growing a
Middle), 3) Zone-2 and 4) Zone-3, as shown in FIG. 6G. A 1.1 hair).
2
cm area of each zone was shaved followed by a measurement
of hair density (hairs per cm 2 ) for each type of hair: thin hair TABLE 1
(vellus or miniaturized hair; VH; thickness<40 gm); thick
Analysis of the hair follicles in FIGS. 5A and 5B following 4 weeks
hair (terminal hair; TH; thickness>40 grn) and total hair (VH+
of treatment with TR1.
TH) with a Phototrichographic system (Folliscope; Hans-
derma, USA). One ml of a total aqueous extract ofF. bengha- Changes
lens& (TR1) formulation (10 tg/ml final concentration of
TR1 in Williams E basic medium (Williams E basic medium Hair follicle Increased Increased
number thickness Increased number thickness + number
substituted with L-glutamine (2 mmol/L); 1 x antibiotic (100
units/ml penicillin, 100 gg/ml streptomycin and 0.25 gg/ml 1
amphotericin) and hydlocortisone (10 ng/ml))+25% glycerol 2 A(1)
(v/v)) was topically applied about twice-a-day (i.e., 20 tg of 3
total dose per day).
31. US 2012/0128796 A1 May 24, 2012
10
Example 7
TABLE 1-continued
Analysis of Solvent Fractions
Analysis of the hair follicles in FIGS. 5A and 5B following 4 weeks
[0151] Each of the five fractions described in Example 6
of treatment with TR1.
were tested using a hair follicle explant viability assay (FIG.
Changes 6 and Table 2).
[0152] Hair follicle explant viability assays were per-
Hair follicle Increased h1 creased
h1 creased number formed as follows: Hair follicles (HF) surgically extracted
number thickness thickness + number
from volunteers were processed as described before (Ex-
4 ample 2). The extracted follicles were plated in 100 btl of
5 A(1) appropriate media and incubated for 72 hrs at 37° C. with 5%
6 A(1)
7 1
CO2. To assess hair follicle cell viability after treatment, a
A(1)
8 A(1) 1 MTS (methanethiosulfonate) viability assay was performed:
9 A(1) 1 5 btl MTS reagents (Promega, Wis.) were added per 100 btl HF
10
containing media. Hair follicles were incubated further for 2
11
12
hrs at the end of which OD at 490 nm was measured spectro-
13 A(1) photometrically
14 [0153] Results shown are the Mean_+SEM from eight inde-
15 pendent experiments performed on hair follicles from eight
16 A(1)
17
different patients. In each experiment, at least 4-6 hair fol-
18 A(2)* licles were used per treatment per patient. Hence each experi-
19 A(1) mental point represents the Mean_+SEM of 8 independent
2O A(1) experiments performed on hair follicles from 8 different
21 K(1)*
22 A(2) patient samples. The different treatments are labeled as fol-
23 lows:
24 A(1) [0154] TR1 (Crude Extract), Total aqueous extract of
25 A(1)
E benghalensis
26 A(1)
27 A(1)
[0155] TR2 (El), n-Hexane extracted fraction
28 A(2) [0156] E2, Dichloromethane (DCM) extracted fraction
29 A(1) [0157] E3, Ethyl acetate (EtOAc) extracted fraction
30
[0158] E4, Methanol (MeOH) extracted fraction
31
32 [0159] E5, Water extracted fraction
[0160] WE-basic refers to Williams-E basic medium
Total 20 22 7 (Sigma-Aldrich, Canada), WE+GFC refers to nine growth
%Increase -9% -10% -3%
factors each at 20 ng/ml and hypoxanthine at 2 btM final
concentration.
[0161] Treatment with TR2 (hexane extracted fraction-E1)
Example 6 resulted in an approximately 14% increase in hair follicle
viability at 1 btg/ml compared to the untreated control. The
Initial Fractionation ofF. benghalensis Extract total aqueous extract ofE benghalensis (TR1), demonstrated
an approximately 10% increase in HF viability at 10 btg/ml
[0144] E benghalensis aerial root tips were oven dried for 2 (compared to 1 btg/ml for TR2).
days at 50° C. until the moisture level was less than 10%. The
dried extract was powdered and fractionated by a sequential TABLE 2
Soxhlet extraction with five solvents (n-hexane, dichlo-
Hair follicle viability assay for solvent fractions TR1 TR2 (El) and E2-5
romethane, ethyl acetate, methanol and water). Approxi-
mately 500 ml solvent for each 500 g of &ded powder or Overall viability
(% control)
residue was used. Fractions were extracted for 5 hr and fil-
tered under reduced pressure. Filtrates were dried with nitro- Treatment Mean SEM
gen gas except for the water extract where freeze drying was
WE-basic 100 10.33909
used.
WE + GFC 125.0721 5.162223
[0145] The fractionation was performed as follows: TR1 10 btg/ml 109.5897 4.179249
TR2 1 btg/ml 113.776 4.505491
[0146] (A) An n-hexane extraction was performed on the E2 10 btg/ml 90.21753 6.321347
dried root tips. E3 10 btg/ml 95.0384 5.156974
E4 10 btg/ml 97.25792 7.175035
[0147] (B) The residue from the hexane extract was further
E5 10 btg/ml 101.3029 7.33428
extracted with dichloromethane.
[0148] (C) The residue from the dichloromethane extrac-
[0162] Dermal papillae (DP) cell viability assays were per-
tion was further extracted with ethyl acetate.
formed as described above in Example 3 (FIG. 7). Each
[0149] (D) The residue from the ethyl acetate extraction experimental point represents the Mean_+SEM of eight repli-
was further extracted with methanol. cates from pooled cells of eight patients. "Ctl" refers to basic
[0150] (E) The residue from the methanol extraction was medium; "complete medium" is optimum cell culture
further extracted with water. medium for human DP cells; "GFC" is basic medium plus