FIELD OF INVENTION
The present invention relates to a wound healing bilayer dermal membrane for
humans and animals and a process for preparation thereof. The membrane
possesses potent antimicrobial, anti fungal and therapeutic properties, which
can be utilized to heal external wounds of any nature. The present invention is
provide-d in the .form of o. poly-herbal formulation which is biodegradable and
absorbable.
BACKGROUND/PRIOR ART
As is well-known in the prior art, usual methods for the cure of wounds
whether in humans or animals, involve certain well-defined steps. These are
curettage (removal of dead/ infected tissues), disinfection (with disinfectants
containing either iodine or hydrogen peroxide) and antibiotic· therapy (either
local or systemic, in the form of powder, cream or spray). Lastly, to avoid
hardening of the skin and crust formation, gauzes soaked in fatty humecants
based on silicone oils or glycerol are applied. Dressing of the wound with sterile
gauze is usually Garried out not only to prevent exposure of the wound to
infectious agents e.g. bacteria present m the environment, but also to soak
exudations and secretions from the wound. These bandages need to be
removed at regular intervals. In poor hygienic or environmental conditions e.g.
those frequently present in developing countries,. the wounds cannot. be
managed adequately . and remain exposed to dust and environmental
infestations ·which can contribute to infections of . the wound. Despite
efficacious anti-microbial treatment and improved supportive m~asures, wound
treatment still poses· immense challenges. Treatment and cure for invasive
infections, blunt injuries,. burns, radiation burns is not very effective and
leaves much to be done.
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Further, wounds of diabetics are practically unmanageable and usually
regarded as 'incurable'. In fact, diabetes is an important underlying condition
in leg ulcers. Various therapies for the treatment of leg ulcers e.g. multi-layer
compression-bandage systems, topical recombinant human platelet derived
growth factor, human skin equivalent for skin grafting etc. are in existence
which may aid in wound healing. However, these therapies F.lr~ expensive and
may be cost prohibitive for many patients. Quite often inability to treat wounds
leads to amputation of the infected limbs. Further, wound management in
animals poses additional challenges. Unlike humans, chances of exposure of
wounds to environmental infestations, in case of animals are much higher. Of
particular concern are attacks by flies which can aggravate wounds and lead to
complications. To prevent infestations by flies, a common practice adopted in
case of wounded animals is pouring a mixture of phenols and tar, on the
wounded area. This remedy though well-entrenched in animal husbandry, has
serious limitations and disadvantages. Not only it is tissue damaging and toxic,
but its 'insect protecting or repelling' action is very short-lived- barely half an
hour. Another animal husbandry practice involves direct use of insecticide.s on
the maggot infected wounds or sores. Apart from risk of acute or chronic
intoxication of the animals, the practice poses environmental threat and also
risk of contamination of the food chain, in case the animals are involved m
products for human consumption e.g. meat or milk.
Wound healing and management, wh~ther in humans or animals is an
important issue. Existing therapies of modern science have limitations when it
comes to the treatment and cure of certain wounds. External eri.viron:rpent
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conditions affect the wound treatment in humans, especially in developing
countries; where hygienic conditions are very often completely inadequate. The
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risk of complications due to parasites, bacteria etc. are a harsh reality,
especially for weak and undernourished subjects, especially children.
Several artificial wound dressing materials are in use for dressings which serve
as carrier of drugs to prevent infection and facilitate wound healing.
A lot has been proposed m regard to wound healing dressing material.
·However, conventional dressing materials do not fully entertain the problem in
the following ways-
1- Being made of synthetic materials and chemical, they have harmful effect
on the body.
2- Do not facilitate the complete process of the wound healing which
implies that it has no regulation on the repa1r process that is taking
place in wound.
Inherent wound healing capacity depends bpo~-~~ny factors such as-
1- Age . of the patient- Patient of higher age has jess wound healing
capability than the young age person.
2- Re-current of the wound at same spot- Recurrent wound normally takes
long time than the non- recurrent wound.
3- Nutritional condition of patient- In India where a majority of people
specially children are under weight and suffer from mafnutrition are
naturally less competent to effectively heal.
Wound healing is the process of repair that follows injury to the skin and other
soft tissues. Following injury, an inflammatory response occurs and the cells
below the dermis (the deepest skin layer) begin to increase collagen (connective
tissue) production. Later, the epithelial tissue (the outer skin) is regenerated.
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Thus, there are three stages to the process of wound healing: inflammation,
proliferation, and remodelling.
The proliferative phase is characterized by angiogenesis, collagen deposition,
granulation tissue formation, epithelialization, and wound contraction.
Angiogenesis involves new blood vessel gn;>wth from endothelial cells. In
.fibroplasia and granulation tissue formation, fibroblasts excrete collagen and
fibronectin to form a new, provisional extracellular matrix. Subsequently,
epithelial cells crawl across the wound bed to cover it and the wound is
contracted by myofibroblasts, which grip. the wound edges and undergo
contraction using a mechanism similar to that in smooth muscle cells.
Thus,.there is a need to develop a formulation which can address the issues of
prior art.
The present invention introduces a novel herbal composition compnsmg
aqueous extracts of neem bark along with several herbs in a mixture of natural
oils. The composition which is meant for external or topical application only,
exhibits remarkable 'antibiotic and wound- healing properties. It is particularly
effective in treating and curing wounds, whi~h are regarded as 'incurable' in
state of the art. The potency and powerful antimicrobial action of the herbal
formulation is due to the synergistic action of the corp.ponents, mainly plant
extracts, present in it.
These agents interplay in cascade of events that can roughly be divided into
three overlapping phases-inflammation, granulation tissue formation, .. g.nd
remodeling of the extracellular matrix.
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OBJECTS OF THE INVENTION
The princ~pal object of the present invention 1s to provide a wound healing
bilayer dermal membrane for humans and · animals and a process for
preparation thereof which overcomes disadvantages associated with the pnor
art.
Another object of the present invention is to provide a wound healing bilayer
dermal membrane for humans and animals and a process for preparation
thereof which is safe for use and biodegradable.
Still another object of the present invention is to provide a wound healing
bilayer dermal membrane for humans and animals and· a process for
preparation thereof which is compatiqle and partially bioabsorbabale.
Yet another object of the present invention is to provide a wound healing
bilayer dermal . membrane for humans and animals and a process for
preparation thereo.f which is. effective in curing and treating external wounds of
· any nature.
SUMMARY OF THE INVENTION
According to this invention, there is provided a wound healing bilayer dermal
. . .
membrane for humans and animals comprising of bilayer membrane including
inner chitosan layer attached to outer polyvinyl alcohol layer loaded with
extracts of Azadirachta Indica, Aloe Vera and Ficus Benghalensis having
therapeutic property.
Further according to this invention, there is provided a process for 'preparation.
of a wound healing bilayer dermal membrane for humans and animals
·comprising steps of: mixing chitosan with a plasticizer followed by blending of
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PVA .solution with chi to san solution wherein a plurality of herbal. drugs are
premixed with the blend.
DETAIL DESCRIPTION OF THE INVENTION
The invention discloses a bilayer dermal membrane constituting a poly herbal
wound healing formulation, which can be used to treat different types of
wounds and injuries in humans and animals.
The membrane compnses a plurality of polymers acting as carrier of several
herbal extracts with therapeutic property. Chitosan ·and Polyvinyl alcohol act
as carrier membrane, which are loaded with extracts of herbs namely
Azadirachita indica,. Aioe Vera and Ficus benghalensis having wound healing
property.
Thus, the present invention provides an effective and cost effective product' for
treatment of wounds and sores in the form or' polyherbal formulation based
wound healing patch, which is biodegradable and absorbable partially.
Now, composition of membrane of invention may be discussed hereinbelow:
Chitosan, .is a linear polysaccharide composed of randomly distributed 13-(1-4).:
linked D-glucosamine and N-acetyl-D-glucosamine. Chitosan, as a cationic
natural biodegradable polymer, has been widely used as a topical dressing in
wound management. It 1s antimicrobial, nont~xic, biocompatible,
biodegradable, hemostatic and accelerates healing. Chitosan also has
excellent capacity for drug delivery and drug loading, which has property of the
persistent, slow a~d continuous release of the drug therefore it ·can be used as
the ideal drug carrier.
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Polyvinyl alcohol is a synthetic polymer and non toxic, having properties like
high biodegradability, 'high tensile strength and drug carrying capacity.
Chitosan and poly vinyl alcohol (PVA) are degraded by cellular enzyme. These
degraded components are used by the wound cells which r:~re metabolically very
- · active and require extra nutrition for the rapid recovery.
Poly Vinyl Alcohol is mixed with 11-30% of water soluble extract fraCtions of
. Azadirachita indica, containing total polyphenols· as active compounds, (for
example 400mg GAE /g of dry extraCts). The extract fractions contains
polyphenolic compounds like Azadirachtin (not less than 0.0015%),. Nimbin
(not less than 260 ug/ g), Nimbidin (not less than 800 ugj g), Nimonol (not less
than 1200ug/ g) and Aloe Vera extracts of 5-10% w jv in specified fractions.
Polyphenol rich extract heals the wounds faster by increased epithilization. The
extract fractions may act as antifungal, antibacterial and antidermatophyti~.
Aloe Vera, has been studied to include wide effect on skin disease and skin
wounds as it has anti inflammatory effect with moistening property. Aqueous . . . .
extract of Aloe Vera contains specific active components like Anthraquinones
·(including Aloin A & B, as Barbolin), not less than 1 % w jv and Acemannans.
The total amount of sugars may not be less than 15 %wjw of dry extract. The
results have demonstrated that the extracts of Aloe vera gel· have anti
inflammatory activity and suggested its inhibitory action on the arachidonic
acid pathway via cyclo oxygenase. Barbolin also exhibits fibroblast activity and
collagen proliferation This leads to enhanced wound healing. The acemannan,
an immune polysaccharide, enhances the humectants property and activate
the macrophages.
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Chitosan is mixed with specific extract fractions of Ficus benghalensis (8-20%
w jv). These fractions of Ficus sp may cause accelerated granulation ·and
remodeling process. This leads tq speedy recovery with minimal side effects.
The extract fractions of Ficus sp, (not less than 4 % w jv) contain chemically
active specific components of tannins, saponins, gallic acid, anthraquinone,
gallocatechin, and flavones.
The invention discloses a wound dressing dermal patch compnsmg of two
layers including inner chitosan layer and outer PVA layer. The Inner chitosan
layer is coated with extract fractions of Ficus benghalensis extract, which
exhibits potential wound healing characteristics.
Inner chitosan layer is attached to a poly vinyl alcohol layer which contains the
extract having specific fractions of Azadirachita indica and Aloe yera. This poly
vinyal alcohol layer acts as anti-infection layer having the capability to increase
the wound healing process in a moisturized environment.
These two layers are attached together, so that ayurvedic drug components are
continuously released to the wound and facilitate the healing.
The wound healing bilayer dermal membrane of present invention can be
prepared by a process comprising of a plasticizing phase of polymers by mixing
chitosan with a plasticizer wherein plasticizer ·is 5-20%. The plasticizer
comprises ester of glycerin, lactic acid, acetic acid or a combination thereof.
The plasticization controls the surface hardness (50-120), elasticity (elastic
modulus 1000-2000 mpa) and biodegradability characteristics of the bilayer
membrane. Addition of plasticizer leads to exothermic · reaction with
temperature above 30°C and need cooling.
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Thus, chitosan solution IS prepared by dissolving in a plasticizer, which is
stirred and kept overnight at room temperature. PVA solution is filtered and
autoclaved for sterility.
Blending of PVA solution with chitosan solution can be carried out in different
ratio as shown in table herein below to form a 50ml mixture wherein necessary
drugs were premixed with the blend. This can be taken as exemplary
embodiment without restricting scope of the invention to the same.
SNO Material Chi to san PVA%(W /V) ml
PV A I Chi tosan(w I v) %(WIV)ml
1 1:1 25 25
2 1:2.5 12 38
3 1:4
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5 45
Finally, 10-15% wlw of PVA layer and 2.:.7% wlw of chitosan layer is placed
one over the other sequentially in chilled water bath through a process of
extrusion of the sheets for press processing at a temperature below 10°C. This
is followed by. curing for approximately 6 hours and drying for 60-70 hours.
The bilayered wound dressing membrane carrying suitable polyherbal extracts
can address the issues in wound management, which is degradable and
bioabsorbable partially after a suitable application time period.
Advantageous Features.
Safe for use and biodegradable
Efficient in healing wounds by means of therapeutic property
Continuous release of drug to wound to facilitate healing
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Easy to manufacture
Cost effective and effective as well
Involves no side effects owing to herbal composition.
It is to be noted that the present invention is susceptible to modifications,
adaptations and changes by those skilled in the art. Such variant embodiments
employing the concepts and features of this invention are intended to be within
the scope of the present invention, which is further set forth under the
following claims:-

We Claim:
1. A wound healing bilayer dermal membrane for humans and animals
comprising of bilayer membrane including inner chitosan layer attached
to outer polyvinyl alcohol layer . loaded with extrac.t.R fractions of
Azadirachita Indica, Aloe Vera and Ficus Benghalensis having therapeutic
property.
2. A wound healing bilayer dermal membrane for humans and animals as
claimed in claim 1 wherein the inner chitosan layer is coated with extract
fractions of Ficus benghalensis,· which exhibits potential wound healing
characteristics.
· 3. A wound healing bilayer dermal membrane for humans and animals as
claimed in claim 1 or 2 wherein the outer polyvinyl alcohol layer contains
the extract fractions of Azadirachita Indica and Aloe Vera, which acts as
anti-infection layer to accelerate the wound healing in a moisturized
environment.
4. A process for preparation of a wound healing bilayer dermal membrane
for humans and animals comprising steps of: mixing chitosan with a
plasticizer followed by blending of PVA solution with chitosan s.olution
wherein a plurality of herbal drugs are premixed with·the blend.
5. A process for preparation of a wound healing bilayer dermal membrane
for humans and animals as claimed in claim 4 wherein the plasticizer
comprises ester of glycerin,· lactic acid, acetic acid or a combination
·thereof which is 5-20%.
6. A process for preparation of a wound healing bilayer dermal membrane
for humans and animals as claimed in any of the preceding claims
wherein 10-15% wjw of PVA layer is placed on 2-7% wjw of chitosan
layer in chilled water bath through a process of extrusion of the sheets
for press processing at a temperature below 10°C, which is followed by
curing for approximately 6 hours and drying for 60-70 hours.
7. A wound healing bilayer dermal membrane for humans and animals and
a process for preparation· thereof as claimed in any of the preceding
claims wherein PVA is mi.xed with water soluble extract fractions ( 11-
30%w jv) of Azadirachita indica,, containing total polyphenols as active
compounds in which the extract fractions contain polyphenolic
compounds like Azadirachtin, Nimbin, Nimbidin and Nimonol and Aloe
· vera extracts (5-1 O%w I v), in specified fractions.
8. A wound healing bilayer dermal membrane for humans and animals and
a process for preparation thereof as claimed in any of the preceding
claims wherein the chitosan is mixed with extract fractions of Ficus ·
benghalensis (8-20%w/v) in which the extract fractions of Ficus sp not
less than 4 % w/v contain chemically active specific components of
tannins, saponns, gallic acid, anthraquinone, .gallocatechin, and
flavones.

9. A wound healing bilayer dermal membrane for humans and animals and
a process for preparation thereof as claimed in any of the preceding
claims 1s associated with the advantageous features such as herein
described.
10. A wound healing bilayer dermal membrane for humans and animals and a process for preparation thereof substantially as herein described.