Collection of scientific articles

1. NATURAL
restoration
of barrier function
of urinary bladder
in cystitis

2. 2
80 mg 50 ml
is a component of the glycosaminoglycan layer, found in high concentrations in the
sub-epithelial layer of the bladder wall;
creates a viscoelastic membrane on the mucosal surface;
regenerates and protects the damaged glycosaminoglycan layer of bladder mucosa;
accelerates regeneration of the damaged urothelium;
reduces bladder irritation and facilitates elimination of pain;
facilitates normalisation of micturition;
creates a biomembrane around the bacteria, inhibiting proliferation of micro-organisms
and reducing their virulence;

3. Hyaluronan treatment of interstitial cystitis/painful
bladder syndrome
Riedl CR 1
, Engelhardt PF 1
, Daha KL 2
, Morakis N 1
, Pflüger H 2
1. Department of Urology, Landesklinikum Thermenregion, Baden, Austria
2. Department of Urology and Ludwig Boltzmann Institute for Andrology and Urology, Vienna, Austria
Objective The aim of this study is to evaluate the efficacy of intravesical hyaluronan therapy
in interstitial cystitis/painful bladder syndrome (PBS/IC).
Methods Weekly instillations of 40 mg hyaluronate sodium have been performed in 121
patients with PUBS/IC (average duration of the disease 6.1 years). The patient’s
suitability for treatment has been assessed with urine potassium test. Positive test
findings indicated impaired tissue/urine barrier. The findings have been obtained
during an interview using a visual analogue scale (VAS). During the interview,
general symptoms of urinary bladder disease gave been assessed before and
after treatment on a scale of 0 to 10. The impact of treatment on quality of life
was assessed by using additional questions.
Results The treatment with hyaluronic acid has been noted to exert a positive impact on
PUBS/IC symptoms: the improvement of symptoms was observed in 103 (85%)
patients (≥2 points on the VAS scale). Findings on completion of treatment period:
• the mean baseline VAS score of 8.5 decreased to 3.5 (р<0.0001);
• the symptoms of urinary bladder disease were either absent or were minimally
expressed (VAS score 0-2) in 67 of 121 patients (55%);
• most patients (101 / 84%) reported significant improvements of their quality
of life;
• there were no manifestations of any symptoms of the disease in 65% of
patients during the 5 subsequent years;
• given a large total number of instillations (1521), the treatment was well-
tolerated; other than weak irritations, no adverse reactions were noted.
Conclusion Timely treatments with HA instillations may lead to complete reversal of
symptoms or cure (in a fraction of patients with PUBS/IC). Study findings indicate
that evaluating patients as candidates for HA therapy with urine potassium test
improves the outcomes of intravesical therapy and allows achieving objective
response rates above 80%.
VAS score
before treatment after treatment
8.5 3.5
The intensity of pain syndrome decreased 2.5 times

4. 4
Prevention of recurrent bacterial urinary tract
infections by intravesical of hyaluronic acid
Lipovac M1-3
, Kurz C1
, Reithmayr F3
, Verhoeven HC2
, Huber JC1
, LMHOF M1,3
1. Medical University of Vienna, Department of Obstetrics and Gynecology AKH, Vienna, Austria
2. Center for Reproductive lvledicine, Endocrinology Genetics, and Antiaging lvledicine Dûsseldorf, Germany
3. Study Center Med XlX, Vienna, Austria
Objective To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent
urinary tract infections.
Methods Twenty women with a history of recurrent urinary tract infections each received
9 intravesical instillations of hyaluronic acid over 6 months. Their status was
assessed prospectively over 47.6 weeks and compared with a retrospective
review of patient charts covering 36.2±6.2 weeks.
Results • The total numbers of urinary tract infections were 67 before and 10 after
treatment (p<0.001);
• Thirteen patients (65%) were free of recurrences until the end of the study;
• One patient had a recurrence during treatment, and 6 patients (30%) had
recurrences during follow-up;
• The number of infections per year per one patient was reduced from 4.99±0.92
to 0.56±0.82 (p<0.001);
• In women with recurrences, time to recurrence was 178.3±25.5 days,
compared with 76.7±24.6 days before treatment (p<0.001);
• The instillations were tolerated well by the patients.
Conclusion Intravesical instillation of hyaluronic acid is effective in preventing recurrent
urinary tract infections
before treatment after treatment
The number of infections 67 10
Infections per year per 1 patient 4.99 0.56
Time to recurrence, days 77 178
68 % – patients had no recurrence until the end of study

5. Prevention of urinary tract infections in palliative
radiation for vertebral metastasis and spinal
compression: A pilot study in 71 patients
Mañas A1
, Glaría L1
, Peña C1
, Sotoca A1
, Lanzós E1
, Fernandez C1
, Rivière M2
1. Servicio de Oncologia Radioterapica, Hospital Universitario Doce de Octubre, Madrid, Spain.
2. Bioniche Life Sciences Inc., Montreal, Quebec, Canada
Objective To assess the impact of bladder instillations of hyaluronic acid (HA) on the
prevalence of urinary tract infection (UTI) in patients receiving emergency
radiotherapy for metastatic spinal cord compression.
Methods Patients were recruited consecutively at one centre and assigned to usual care
(UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation
(UC + HA) (HA 40 mg in 50 mL of phosphate-buffered saline) (n = 37; mean age,
63.1 years). All patients had an indwelling catheter and received radiotherapy.
UTI status was assessed at baseline and during hospitalization.
Conclusion Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the
hospitalization period compared to UC-only patients. These results suggest that
bladder instillations of HA effectively prevent UTI in patients with indwelling
catheters receiving radiotherapy for nerve compression.
In this group of patients, infection means,
on average, around 6 more days in the hospital
than those without a UTI
Better response to the therapy in the HA group
Usual care
(34 patients)
Usual care + HA
(37 patients)
76.5 % UTI (÷ 5.7) 13.5 %

6. 6
Hyaluronic Acid in the prevention
of Radiation Induced Cystititis
Delgado Pérez JM, Samper P, Sáez Garrido J
Servicio de Oncologia Radioterapica, Hospital Militar Central de ta Defensa, Madrid
Objective To evaluate the effectiveness of intravesical HA instillations on the toxicity induced
by radiation therapy of urinary bladder and it influence on the scheduled radiation
therapy of the pelvic area.
Methods Retrospective review of medical records has been performed in 90 patients
with uterine cancer or cervical cancer at FIGO 3 stage. The patients have been
enrolled consecutively in 2001-2002 for treatment at a single centre under the
same standard outpatient radiation plan (external radiation therapy: 46-50 Gy,
brachytherapy: 20-22 Gy). The initial 45 patients received standard care. The other
45 received standard care plus intravesical instillations of HA (40 mg / 50 mL of the
solution). The instillations were performed via a urethral catheter used for bladder
contrast imaging at weekly brachytherapy planning.
Results The evaluation was performed in both groups at the onset of study, 48 hours after
each brachytherapy and monthly for 3 months.
• The mean toxicity value at Week 4 was 1.33 in the group of standard care (SC)
and 0.71 in the HA group (р<0.005); after completion of radiation therapy
the respective values were 1.24 in SC group compared to 0.71 in HA group
(р<0.004).
• Degree 3 toxicity was observed in 2 patients of SC group and in none of the
patients in the HA group (р<0.04).
• At Month 2 of follow-up Degree 1 toxicity was observed in 9 patients in the
group of standard care and in none of the patients in the HA group (р<0.002).
• The plan of radiation therapy was cancelled in 2 patients in the SC group and in
none of the patients in the HA group (р<0.04).
• Bacterial cystitis was found in 4 patients of the SC group and in none of the
patients of the HA group (р<0.002).
Conclusion Weekly intravesical HA instillations protect the urinary bladder, reduce radiation-
induced toxicity and the risk of contamination (and are likely to enhance the
quality of life) and allow completing the treatment within the scheduled time
frames
Standart care (SC)
SC + HA
meangrade
weeks

7. Sterile polymer bag with
a urethral catheter connector
in a vacuum plastic packaging
Mode of administration
Ergonomic
packaging
80 mg 50 ml
INSTYLAN is intended for intravesical
instillations once a week.
The course of treatment includes
4 to 12 instillations.
Warm the package to at least 20°С before use.
Ask the patient to empty their urinary bladder
prior to administration of INSTYLAN.
INSTYLAN is administered into the cavity
of the urinary bladder via a urological
catheter; the duration of therapeutic
exposure is from 30 minutes to
2 hours.
NATURAL
restoration
of barrier function
of urinary bladder
in cystitis

8. 8
Information on medical device INSTYLAN.
Composition: sodium hyaluronate 80 mg, phosphate buffer (pH 7.3) up to 50 mL.
Therapeutic Indications:
• Temporary protection and regeneration of vesical mucosa in various procedures
(urethrocystoscopy, radiation therapy, etc.).
• Chronic/recurrent cystitis.
• Radiation-induced cystitis.
• Interstitial cystitis.
• Hyperactive bladder.
• Urinary retention or tumours related to cystitis.
Contraindications. Hypersensitivity to any component of the product. Pregnant or nursing
women. Children.
DIACO Biofarmaceutici S.R.L.
Via Flavia 124, 34147 Trieste, Italy
www.diaco.it