ASUP OIL

A Regenerative Medicine For Wound healing

Medical management of stricture

Publications

• Patankar S., Dobhada S., Bhansali M., Khaladkar S., and Mody J. “A Prospective, Randomized, Controlled study to Evaluate the Efficacy and Tolerability of Ayurvedic Formulation ‘Varun and Banana stem’ in the Management of Urinary Stones”; The Journal of Alternative and Complementary Medicine 2008,14(10): 1287-90

• Patankar S., Rasal D., Shah R., Oza N. “Open label, randomize Clinical trial to evaluate the safety and efficacy of ‘ Herbmed plus’ for ureteral stent Discomfort against Tolterodine”. Urology,78 ( Supplement 3A) :2011 ,260 .

Urethral Stricture

• A urethral stricture (US) is a urologic disorder with high

morbidity and recurrence rate following various treatments.

• The pathogenesis of US is closely associated with scar

formation including excessive collagen- rich connective

tissues.

• Fibrosis, caused by excessive collagen synthesis and

changes in the composition of the extracellular matrix is a

key event in the pathogenesis of urethral stricture.

• The up-regulation of CTGF (connective tissue growth factor)

expression may be responsible for the fibrosis process

leading to excessive collagen synthesis of urethral tissues in

US patients.*

*(Tohoku J. Exp. Med., 2008; 215: 199-206)

Exploratory studies for Management

of Urethral stricture in Laboratory

Animals

On the basis of treatments for organ fibrosis, following

studies were carried out for assessment of anti-fibrotic activity leading to limiting of urethral stricture formation by various drugs during last decade

• Halofuginone (Nagler et al., 2000; Jaidane et al., 2003; Krane et al., 2011)

• Mitomycin C ( Ali Ayyildiz et al., 2003; Mazdak et al., 2007)

• Botulinum toxin A (Khera et al., 2004)

• Somatostatin analog (Andersen et al., 2003)

• Glucocorticoid (Sciarra et al., 2005)

• Rapamycin (Tie Chong et al 2011)

• HF is a synthetic halogenated derivative of febrifugine,

found in the Chinese herb Dichroa febrifuga (Chang Shan),

a coccidiostat used in veterinary medicine.

• Urethral strictures were induced in rats using electrocautery

and effect of local use of HF was compared with systemic

use.

• HF was coated on silicone catheters and release kinetics

were measured.

• HF successfully inhibits periurethral type I collagen

deposition after urethral injury. This may become an

important therapy to prevent urethral stricture formation or

recurrence after endoscopic therapy.

*(Jaidane M, Ali-El-Dein B, Ounaies A, Hafez AT, Mohsen T,

and BazeedM(2003) The use of halofuginone in

limiting urethral stricture formation and recurrence: an

experimental study in rabbits. J Urol 170:2049–2052.)

Halofuginone (HF)

Effect of Rapamycin on Stricture

Formation in Rabbits

.

Alternative Treatment

• All the above mentioned research is restricted at pre-

clinical studies and majority of results have limitations.

• Recently exploration has started in Tissue engineering

as well as Bioengineering approach, however, presently

these are available at prohibitive cost and none of them

are full proof.

• Under these circumstances using Reverse

Pharmacology approach for Traditional systems like

Ayurveda, may help to overcome problems like healing

of wounds, strictures, fibrosis, etc. which are common

after surgical procedures.

• To explore this possibility we, at ACE Hospital Research

Center, developed a formulation based on traditional

knowledge and personal experience.

Composition of Anuradha Oil This formulation is a synergistic and effective herbal

composition comprising of therapeutically effective

proportion of extracts using natural products

a) Curcuma longa Linn. (Haldi)

Rhizomes

b) Glycyrrhiza glabra Linn. (Jeshtmadh)

Rhizomes

c) Hamiltonia suaveoleans Roxb. (Jeetsaya)

Stem bark

d) Typha angustifolia Linn. (Ramban)

Flowers

e) Azadirchta indica A. Juss. (Neem)

Leaves

f) Sesamum indicum Linn. oil ( Til)

Seed oil

254 nm

366 nm

A B C D E A B C D E Base

oil

Base

oil

Formula

tion

Formula

tion

HPTLC PLATE Of ANURADHA OIL

Under Short & Long UV Light

Pre-clinical Studies The pre-clinical safety of Oil was established in rodent by

Acute toxicity study as per OECD guidelines No. 423 and Sub-

acute study by following FDA guidelines. Efficacy was

established by excision wound model in rats at the National

Toxicology Institute, Pune; which is approved by Food and Drug

Administration (FDA), Maharashatra State.

Wound healing activity was studied in excision, incision and

dead space wound model in terms of

1) % wound contraction, epithelisation period and scar area

2) Wound breaking strength

3) Antioxidant status of granulation tissue by measuring

{Superoxide dismutase (SOD) , reduce glutathione (GSH), free

radical (Lipid peroxidation an indicator of tissue damage)}

4)Connective tissue formation and maturation (Hexuronic acid,

Hydroxiproline and Hexosamine levels )

Acute Dermal Toxicity in Rats

Subacute Dermal Toxicity in Rats

FEMALE MALE

FEMALE MALE

Group Histopathology Data Parameter Control Test Standard I Standard II

Mild Mod Sev Mild Mod Sev Mild Mod Sev Mild Mod Sev

Scab 1/6 2/6 - 2/6 2/6 - 4/6 - - 6/6 - -

RE - - - 1/6 - - 1/6 - - - - -

FP 4/6 2/6 - 1/6 4/6 1/6 5/6 1/6 - 1/6 5/6 -

CD 3/6 3/6 - 1/6 2/6 3/6 1/6 3/6 2/6 4/6 1/6 1/6

MNC 6/6 - - 4/6 2/6 - 6/6 - - 1/6 5/6 -

PMN 1/6 1/6 4/6 4/6 1/6 1/6 1/6 3/6 2/6 - 1/6 5/6

NV 3/6 3/6 - - 6/6 - 3/6 3/6 - 6/6 - -

I - 4/6 2/6 1/6 5/6 - 3/6 3/6 - 1/6 - 5/6

P 2/6 4/6 - 3/6 3/6 - 4/6 2/6 - 5/6 1/6 -

R 1/6 - - 1/6 3/6 1/6 2/6 1/6 1/6 1/6 - -

Results of preclinical studies

Showed favorable wound healing activity through

promoting various stages in general and promoting

formation as well as turnover of collagen which plays an

important role in the process of healing as well as scar

formation.

Initial studies in various types of open wounds eg. use in Buccal Mucosa Harvesting

Initial - IP

Eighth Day

Initial -

Control

Eighth Day

Incidence of stricture following

TURP

• Study of 12003 patients

• Incidence of stricture - 9.7%

• Incidence of bladder neck contracture - 2.1%

.Text book of Benign prostatic hyperplasia by Roger Kirby٭

2nd ed. 2005. Publ. Taylor& Francis

• Post TURP application of medication

• Randomized double arm Controlled Trial in 128 patients

following TURP .

• Assessment by Post Operative Symptom Score, Rate of

Wound Healing by Endoscopic Examination at 3 , 6 &

12 Weeks .

• Results -Statistically Better Results in terms of no pain,

faster rate of wound healing & absence of urethral

Stricture.

Clinical result

Initial clinical studies in stricture

urethra

• Objective - it is not substitute for patients

requiring urethroplasty

• Improve results of VIU

• Patients in grey zone - VIU ? Urethroplasty ?

• Improve results of urethroplasty reducing

incidence post surgery refibrosis

Initial results in stricture urethra

• Patients undergoing VIU - 28

• Two groups –

1. VIU only

2. VIU with application of medication for 3 weeks.

• Follow up with flowmetry and sos cystoscopy

• Initial results are better in medication group.

• Small group, short follow up - need more well designed

trials

• Future - drug coated catheter in VIU and urethral

reconstruction

Publications

• Patankar S., Mujumdar A., Kurup R. Evaluation of safety profiles of Anuradha Oil - An Herbal Wound healing Formulation in laboratory animals. IJPPS April 2015,7(4).

• Patankar S. et al. Post TURP Stricture! Urologists dilemma, can we prevent them ? A research Perspective. J. Urol. April 2014;191(4): 194

USA Patent

European Patient