1. The document describes the industrial production process of recombinant human insulin. Researchers insert the human insulin gene into bacteria like E. coli, which then produce human insulin that is purified for use in treating diabetes.
2. There are two main methods - growing the insulin A and B chains separately, or using the proinsulin gene. In both, the gene is inserted into bacteria which are then fermented to produce insulin. Various purification techniques are used to isolate the insulin.
3. Quality control testing ensures the purity and structure of the insulin batches before being approved for use. Future directions include improved drug delivery methods like inhaled insulin, buccal insulin, and insulin patches.
Contents
1. Insulin Molecule
2. Effect of Insulin in Body
3. History of Insulin
4. Recent Trends in Insulin Productions and Types
4.1 Animal Insulins
4.2 Long-Acting Insulins
4.3 Human Insulins
4.4 Insulin Analogues
4.5 Biosimilar Insulins
5. Insulin Production (Chain A and Chain B Method)
5.1 Upstream Processing
5.2 Downstream Processing
6. The Proinsulin Process
7. Insulin Available in Market with Different Brand Names
8. References
The 1st recombinant drug .
A protein chain or peptide hormone.
A dimer of an A-chain & a B-chain linked together by disulfide bonds, composed of 110 aa & molecular mass is 5808 Da.
A product of commercially important fermentation process that produce recombinant products.
Naturally produced by beta cells of the islets of Langerhans in the pancreas & by Brockmann body in some teleost fish.
The preproinsulin precursor of insulin is encoded by the INS gene.
Important for metabolism and utilization of energy from the ingested nutrients – especially glucose.
Failure of control of insulin level causes diabetes mellitus.
Contents
1. Insulin Molecule
2. Effect of Insulin in Body
3. History of Insulin
4. Recent Trends in Insulin Productions and Types
4.1 Animal Insulins
4.2 Long-Acting Insulins
4.3 Human Insulins
4.4 Insulin Analogues
4.5 Biosimilar Insulins
5. Insulin Production (Chain A and Chain B Method)
5.1 Upstream Processing
5.2 Downstream Processing
6. The Proinsulin Process
7. Insulin Available in Market with Different Brand Names
8. References
The 1st recombinant drug .
A protein chain or peptide hormone.
A dimer of an A-chain & a B-chain linked together by disulfide bonds, composed of 110 aa & molecular mass is 5808 Da.
A product of commercially important fermentation process that produce recombinant products.
Naturally produced by beta cells of the islets of Langerhans in the pancreas & by Brockmann body in some teleost fish.
The preproinsulin precursor of insulin is encoded by the INS gene.
Important for metabolism and utilization of energy from the ingested nutrients – especially glucose.
Failure of control of insulin level causes diabetes mellitus.
in this presentation, what are the steps and strategies involved the gene cloning and i was focused only on the 1st two steps of gene cloning.they are generation of foreign DNA molecules and selection of suitable vectors.
Peptide vaccine containing only epitopes capable of inducing positive, desirable T cell and B cell mediated immune response.
Peptides‖ used in these vaccines are 20–30 amino acid sequences that are synthesized to form an immunogenic peptide molecule representing the specific epitope of an antigen.
sufficient for activation of the appropriate cellular and humoral responses
Eliminating allergenic and/or reactogenic responses.
Cell culture based vaccine??
Cell cultures involve growing cells in a culture dish, often with a supportive growth medium. A primary cell culture consists of cells taken directly from living tissue, and may contain multiple types of cells such as fibroblasts, epithelial, and endothelial cells.
In the United States, 10 different vaccines for chicken pox, hepatitis A, polio, rabies, and rubella are cultured on aborted tissue from two fetal cell lines known as WI-38 and MRC-5. These vaccines are chicken pox, hep-A, hep-A, hep-A/hep-B, polio, rabies, rubella, measles/rubella, mumps/rubella, and MMR II (measles/mumps/rubella).
in this presentation, what are the steps and strategies involved the gene cloning and i was focused only on the 1st two steps of gene cloning.they are generation of foreign DNA molecules and selection of suitable vectors.
Peptide vaccine containing only epitopes capable of inducing positive, desirable T cell and B cell mediated immune response.
Peptides‖ used in these vaccines are 20–30 amino acid sequences that are synthesized to form an immunogenic peptide molecule representing the specific epitope of an antigen.
sufficient for activation of the appropriate cellular and humoral responses
Eliminating allergenic and/or reactogenic responses.
Cell culture based vaccine??
Cell cultures involve growing cells in a culture dish, often with a supportive growth medium. A primary cell culture consists of cells taken directly from living tissue, and may contain multiple types of cells such as fibroblasts, epithelial, and endothelial cells.
In the United States, 10 different vaccines for chicken pox, hepatitis A, polio, rabies, and rubella are cultured on aborted tissue from two fetal cell lines known as WI-38 and MRC-5. These vaccines are chicken pox, hep-A, hep-A, hep-A/hep-B, polio, rabies, rubella, measles/rubella, mumps/rubella, and MMR II (measles/mumps/rubella).
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.
Explanation on the industrial production of penicillin covering the history, fermentors, specific conditions required for penicillin production, how to increase yield amongst others.
Insulin is a two chain polypeptide having 51 amino acids and molecular weight about 6000.
It has two amino acid chains called α and β chains, which are linked by disulfide bridges. The α-chain of insulin contains 21 amino acids and β-chain contains 30 amino acids.
It is primary hormone which is responsible for controlling the storage and utilization of cellular nutrients.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
2. 2
Industrial production of recombinant human insulin
Introduction
Impaired insulin production in the beta cells of pancreas leads to the condition known as
Diabetes Miletus. The bovine and porcine insulin are used to treat Patients with diabetes
mellitus. But the composition of bovine and porcine insulin are slightly different from the human
insulin, consequently the patient's immune system produced antibodies against animal origin
insulin and also these antibodies induced inflammatory response at injection sites. Antibodies
also neutralised the biological action of animal origin insulin. To overcome all these problems
researchers produced Humulin using recombinant DNA technology by inserting human insulin
gene into a vector (E. coli).
Raw Materials
Human insulin is grown in the lab inside common bacteria. Escherichia coli is by far the most
widely used type of bacterium, but yeast is also used.
Researchers need the human protein that produces insulin. Manufacturers get this through an
amino-acid sequencing machine that synthesizes the DNA. Manufacturers know the exact order
of insulin's amino acids (the nitrogen-based molecules that line up to make up proteins). There
are 20 common amino acids. Manufacturers input insulin's amino acids, and the sequencing
machine connects the amino acids together. Also necessary to synthesize insulin are large tanks
to grow the bacteria, and nutrients are needed for the bacteria to grow. Several instruments are
necessary to separate and purify the DNA such as a centrifuge, along with various
chromatography and x-ray crystallography instruments.
The Manufacturing Process
Synthesizing human insulin is a multi-step biochemical process that depends on basic
recombinant DNA techniques and an understanding of the insulin gene. DNA carries the
instructions for how the body works and one small segment of the DNA, the insulin gene, codes
for the protein insulin. Manufacturers manipulate the biological precursor to insulin so that it
grows inside simple bacteria. While manufacturers each have their own variations, there are two
basic methods to manufacture human insulin.
Working with human insulin
1. The insulin gene is a protein consisting of two separate chains of amino acids, an A
above a B chain, that are held together with bonds. Amino acids are the basic units that
build all proteins. The insulin A chain consists of 21 amino acids and the B chain has 30.
3. 3
2. Before becoming an active insulin protein, insulin is first produced as preproinsulin. This
is one single long protein chain with the A and B chains not yet separated, a section in the
middle linking the chains together and a signal sequence at one end telling the protein
when to start secreting outside the cell. After preproinsulin, the chain evolves into
proinsulin, still a single chain but without the signaling sequence. Then comes the active
protein insulin, the protein without the section linking the A and B chains. At each step,
the protein needs specific enzymes (proteins that carry out chemical reactions) to produce
the next form of insulin.
Starting With A And B
3. One method of manufacturing insulin is to grow the two insulin chains separately. This
will avoid manufacturing each of the specific enzymes needed. Manufacturers need the two
mini-genes: one that produces the A chain and one for the B chain. Since the exact DNA
sequence of each chain is known, they synthesize each mini-gene's DNA in an amino acid
sequencing machine.
4 . These two DNA molecules are then inserted into plasmids, small circular pieces of DNA
that are more readily taken up by the host's DNA.
5. Manufacturers first insert the plasmids into a non-harmful type of the bacterium E. coli.
They insert it next to the lacZ gene. LacZ encodes for 8-galactosidase, a gene widely used in
recombinant DNA procedures because it is easy to find and cut, allowing the insulin to be
readily removed so that it does not get lost in the bacterium's DNA. Next to this gene is the
amino acid methionine, which starts the protein formation.
6. The recombinant, newly formed, plasmids are mixed up with the bacterial cells. Plasmids
enter the bacteria in a process called transfection. Manufacturers can add to the cells DNA
ligase, an enzyme that acts like glue to help the plasmid stick to the bacterium's DNA.
7. The bacteria synthesizing the insulin then undergo a fermentation process. They are grown
at optimal temperatures in large tanks in manufacturing plants. The millions of bacteria
replicate roughly every 20 minutes through cell mitosis, and each expresses the insulin gene.
8. After multiplying, the cells are taken out of the tanks and broken open to extract the DNA.
One common way this is done is by first adding a mixture of lysozome that digest the outer
layer of the cell wall, then adding a detergent mixture that separates the fatty cell wall
membrane. The bacterium's DNA is then treated with cyanogen bromide, a reagent that splits
protein chains at the methionine residues. This separates the insulin chains from the rest of
the DNA.
9. The two chains are then mixed together and joined by disulfide bonds through the
reduction-reoxidation reaction. An oxidizing agent (a material that causes oxidization or the
4. 4
transfer of an electron) is added. The batch is then placed in a centrifuge, a mechanical
device that spins quickly to separate cell components by size and density.
10. The DNA mixture is then purified so that only the insulin chains remain. Manufacturers
can purify the mixture through several chromatography, or separation, techniques that exploit
differences in the molecule's charge, size, and affinity to water. Procedures used include an
ion-exchange column, reverse-phase high performance liquid chromatography, and a gel
filtration chromatography column. Manufacturers can test insulin batches to ensure none of
the bacteria's E. coli proteins are mixed in with the insulin. They use a marker protein that
lets them detect E. coli DNA. They can then determine that the purification process removes
the E. coli bacteria.
Proinsulin Process
11. Starting in 1986, manufacturers began to use another method to synthesize human
insulin. They started with the direct precursor to the insulin gene, proinsulin. Many of the
steps are the same as when producing insulin with the A and B chains, except in this method
the amino acid machine synthesizes the proinsulin gene.
12. The sequence that codes for proinsulin is inserted into the non-pathogenic E. coli
bacteria. The bacteria go through the fermentation process where it reproduces and produces
proinsulin. Then the connecting sequence between the A and B chains is spliced away with
an enzyme and the resulting insulin is purified.
13. At the end of the manufacturing process ingredients are added to insulin to prevent
bacteria and help maintain a neutral balance between acids and bases. Ingredients are also
added to intermediate and long-acting insulin to produce the desired duration type of insulin.
This is the traditional method of producing longer-acting insulin. Manufacturers add
ingredients to the purified insulin that prolong their actions, such as zinc oxide. These
additives delay absorption in the body. Additives vary among different brands of the same
type of insulin.
Analog insulin
In the mid 1990s, researchers began to improve the way human insulin works in the body by
changing its amino acid sequence and creating an analog, a chemical substance that mimics
another substance well enough that it fools the cell. Analog insulin clumps less and disperses
more readily into the blood, allowing the insulin to start working in the body minutes after an
injection. There are several different analog insulin. Humulin insulin does not have strong bonds
with other insulin and thus, is absorbed quickly. Another insulin analog, called Glargine, changes
the chemical structure of the protein to make it have a relatively constant release over 24 hours
with no pronounced peaks.
Instead of synthesizing the exact DNA sequence for insulin, manufacturers synthesize an insulin
gene where the sequence is slightly altered. The change causes the resulting
5. 5
Figure : A diagram of the manufacturing steps for insulin
proteins to repel each other, which causes less clumping. Using this changed DNA sequence, the
manufacturing process is similar to the recombinant DNA process described.
Quality Control
After synthesizing the human insulin, the structure and purity of the insulin batches are tested
through several different methods. High performance liquid chromatography is used to determine
if there are any impurities in the insulin. Other separation techniques, such as X-ray
crystallography, gel filtration, and amino acid sequencing, are also performed. Manufacturers
also test the vial's packaging to ensure it is sealed properly.
Manufacturing for human insulin must comply with National Institutes of Health procedures for
large-scale operations. The United States Food and Drug Administration must approve all
manufactured insulin.
6. 6
The Future
The future of insulin holds many possibilities. Since insulin was first synthesized, diabetics
needed to regularly inject the liquid insulin with a syringe directly into their bloodstream. This
allows the insulin to enter the blood immediately. For many years it was the only way known to
move the intact insulin protein into the body. In the 1990s, researchers began to make inroads in
synthesizing various devices and forms of insulin that diabetics can use in an alternate drug
delivery system.
Manufacturers are currently producing several relatively new drug delivery devices. Insulin pens
look like a writing pen. A cartridge holds the insulin and the tip is the needle. The user set a
dose, inserts the needle into the skin, and presses a button to inject the insulin. With pens there is
no need to use a vial of insulin. However, pens require inserting separate tips before each
injection. Another downside is that the pen does not allow users to mix insulin types, and not all
insulin is available.
For people who hate needles an alternate to the pen is the jet-injector. Looking similar to the
pens, jet injectors use pressure to propel a tiny stream of insulin through the skin. These devices
are not as widely used as the pen, and they can cause bruising at the input point.
The insulin pump allows a controlled release in the body. This is a computerized pump, about the
size of a beeper, that diabetics can wear on their belt or in their pocket. The pump has a small
flexible tube that is inserted just under the surface of the diabetic's skin. The diabetic sets the
pump to deliver a steady, measured dose of insulin throughout the day, increasing the amount
right before eating. This mimics the body's normal release of insulin. Manufacturers have
produced insulin pumps since the 1980s but advances in the late 1990s and early twenty-first
century have made them increasingly easier to use and more popular. Researchers are exploring
the possibility of implantable insulin pumps. Diabetics would control these devices through an
external remote control.
Researchers are exploring other drug-delivery options. Ingesting insulin through pills is one
possibility. The challenge with edible insulin is that the stomach's high acidic environment
destroys the protein before it can move into the blood. Researchers are working on coating
insulin with plastic the width of a few human hairs. The coverings would protect the drugs from
the stomach's acid.
In 2001 promising tests are occurring on inhaled insulin devices and manufacturers could begin
producing the products within the next few years. Since insulin is a relatively large protein, it
does not permeate into the lungs. Researchers of inhaled insulin are working to create insulin
particles that are small enough to reach the deep lung. The particles can then pass into the
bloodstream. Researchers are testing several inhalation devices much like that of an asthma
inhaler.
Another form of aerosol device undergoing tests will administer insulin to the inner cheek.
Known as buccal (cheek) insulin, diabetics will spray the insulin onto the inside of their cheek. It
is then absorbed through the inner cheek wall.
7. 7
Insulin patches are another drug delivery system in development. Patches would release insulin
continuously into the bloodstream. Users would pull a tab on the patch to release more insulin
before meals. The challenge is finding a way to have insulin pass through the skin. Ultrasound is
one method researchers are investigating. These low frequency sound waves could change the
skin's permeability and allow insulin to pass.
Other research has the potential to discontinue the need for manufacturers to synthesize insulin.
Researchers are working on creating the cells that produce insulin in the laboratory. The thought
is that physicians can someday replace the non-working pancreas cells with insulin-producing
cells. Another hope for diabetics is gene therapy. Scientists are working on correcting the insulin
gene's mutation so that diabetics would be able to produce insulin on their own.
8. 8
REFERENCES
1. Roifman C M, Mills G B, Chu M, Gelfand E W. Functional comparison of
recombinant interleukin 2 (IL-2) with IL-2-containing preparations derived from
cultured cells. Cell Immunol. 1985;95(1):146–156.
2. Discovery of Insulin Web Page. 16 November 2001.
<http://web.idirect.com/~discover >.
3. Eli Lilly Corporation. Humulin and Humalog Development. CD-ROM, 2001.
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