DESC:FORM 2

THE PATENTS ACT 1970
(SECTION 39 OF 1970)

&
THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(SECTION 10)

PROCESS FOR THE PREPARATION OF ANTIMICROBIAL HYDROGEL

We, AZISTA INDUSTRIES PVT LTD,
a company incorporated under the companies act, 1956 having address at
Sy. No. 80-84, 4th Floor, C Wing, Melange Towers, Patrika Nagar, Madhapur, Hyderabad, Telangana- 500 081, India.

The following specification particularly describes the invention and the manner in which it is to be performed:
FIELD OF INVENTION
The present invention relates to an antimicrobial hydrogel comprising polyvinyl alcohol (PVA), povidone, glycerine and silver salt. The present invention specifically relates to a simple process for the preparation of efficient antimicrobial hydrogel, wherein the process comprising steps of crosslinking, conversion of silver salt into silver nanoparticles and sterilization of solution in pouch by using of gamma irradiation.
BACKGROUND OF INVENTION
Burn injuries are critical condition and difficult to manage, due to significant loss of fluids, tissue damage and results deep wounds. Further, it may hinder the important functions of skin. The compromised skin cannot prevent the microbial invasion which leads to infectious wounds.
According to WHO, more than 30,000 deaths occur in each year as a consequence of different types of burns caused by chemicals, radiation and electricity. In the case of burn injuries, appropriate treatment should be given to increase the survival chances of patient.
Ideally, wound dressing should provide moist environment, acts as a barrier to prevent invasion of contaminants, provide antimicrobial action, promote wound healing, application and removal should be easy, non-toxic and non-allergic. Hydrogels are class of wound dressings applied on injuries/wounds associated with burns. Hydrogels are stabilized macromolecular networks by means of physical or chemical interactions among the polymer chains. Due to hydrophilic nature and polymeric network structure, which are able to retain large amounts of water in their mesh structure.
Polymeric hydrogels importance has increased significantly for the treatment of burns and other skin lesions. In case of burns, cleaning under running water will not provide enough satisfaction. Application of hydrogels onto burn area is the best way to provide coolness and in order to minimize the extent of damage and reduce pain.
The drawbacks associated with conventional antimicrobial gel/ointment formulations for burn treatment include requirement of applicator to deliver medicament, which may liquefy or soften after some time of application and migrate or move away from injured area. In contrast, the hydrogel gives pleasant cooling sensation, soothe pain, absorb wound exudate, non-sticky to wound, easy of removal/replacement without any damage, are sterile and acts as barrier, Further The hydrogel would reside on the required region for a long time, resulting in better patient compliance and therapeutic effects. Furthermore, hydrogel transparency allows instant monitoring of healing process.
Furthermore, wound dressing hydrogel for burn care should be sterile and with antimicrobial action to accelerate wound healing.
CN 102698313 discloses nano silver antimicrobial hydrogels and their preparation, wherein the antimicrobial hydrogel contain a natural polymer or a derivative thereof, a synthetic polymer, nano silver and water containing silver ions. This patent also discloses the process for the preparation, wherein process comprising a powder of natural / synthetic polymer was mixed with an aqueous silver nitrate solution and stirred uniformly with a defoaming stirrer to obtain a solid content of 10% aqueous solution. The aqueous solution was filled into the test tube; the bubbles were removed, sealed and then irradiated with 60Co gamma rays for 30 kGy to obtain nano silver antibacterial hydrogel.
CN 103623453 discloses a process for preparing a silver ion hydrogel dressing, said process comprising 15g of polyvinyl alcohol and 85g water can be heated investment, stirring and vacuum degassing the reactor, the temperature and stir until completely dissolved, the feed liquid was cooled to room temperature to obtain an aqueous solution of a hydrophilic polymer; system hydrophilic polymer solution was injected into the mold, the upper surface is covered from the film, semi-finished products to obtain hydrogel material; the prepared hydrogel material semi-finished products by cobalt 60 radioactive sources of high-energy radiation dose of 30kgy radiation, to prepare a hydrogel material; hydrogel material is immersed in the silver ion concentration of 0.05% by weight of the silver nitrate solution, the hydrogel material weight silver ion content of 0.005%, the silver ions to prepare a hydrogel dressing. It also discloses the hydrogel is prepared by using high energy radiation dose of 10-100 kGy a Cobalt 60 radioactive source.
KR 101242574 discloses a process for preparing hydrogel dressing for wound care comprising biocompatible polymer and nanoparticles involves following steps. 1. Biocompatible polymer (PVA) is added to purified water to obtain aqueous solution. 2. Pour the aqueous solution of step 1 into the tray and moulded to the hydration gel of the sheet form. 3. Formed hydration gel of step 2 is cross-linked by irradiating with radiation. 4. Formed crosslinked hydration gel of step 3 is dipped into silver nitrate aqueous solution to form nanosilver particles within the hydration gel. 5. Wrapping the hydration gel of step 4 and sterilization is used in manufacturing hydration gel. It also discloses dose of radiation is preferably 2-200 kGy.
WO 2007/002705 discloses process of making hydrogel having antimicrobial properties comprising polyvinyl alcohol as hydrogel-forming polymer and silver antimicrobial agent. It also discloses cross linking of polyvinyl alcohol and water to form hydrogel using gamma radiations. Then the silver flakes were dispersed into a hydrogel, and the composite was crosslinked using an electron-beam, die cut and packaged.
WO 2012/005759 discloses hydrogel is being formed in situ on the wound surface using a free radical initiation system or redox reaction. The composition includes a PVA macromer that can quickly crosslink to form a hydrogel dressing on a wound, aqueous media, redox components, stabilizers for the redox components, and one or more antimicrobial agents preferable silver salts, and may include additives such as an absorbent, and other active agents.
US 2013/0052257 A1 discloses antimicrobial hydrogel wound dressing using polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and agar, all components were dissolved in distilled water, the solution mixture was crosslinked by gamma radiation. Prior to crosslinking by gamma radiation, an effective amount of a pair of antibiotics, polymyxin B sulfate and neomycin are added to the solution at room temperature. The prepared hydrogel has good mechanical strength, water absorption capability and antimicrobial action against various types of microorganisms.
Oliveira et al., Interface Focus 2013, 1-11 discloses process for the preparation of polyvinyl alcohol nano-silver hydrogel wound dressing involves PVA aqueous solutions were obtained by dissolving 10 g of PVA in 100 ml of distilled and deionized water at 90°C for 2 h, under mechanical stirring. For PVA-Ag samples, 10 g of PVA was dissolved in 70 ml of distilled and deionized water at 90°C C for 2 h, under mechanical stirring, and the AgNO3 solutions were obtained by dissolving the correct amount of AgNO3 in 30 ml of distilled and deionized water at room temperature in the dark, under magnetic stirring for 2 h. The AgNO3 solutions were mixed with the PVA solutions under mechanical stirring, in the dark, at room temperature for 30 min, resulting in solutions containing 10 g of PVA and 0.00%, 0.25% or 0.50% AgNO3 (relative to the weight of the polymer), in 100 ml H2O. The resulting solutions were exposed to ultrasonic waves (Ultrasonic Clear, USC 750, Unique) in the dark for 30 min to remove the remaining air from the solution. Then, 20 ml of the final solutions were poured into Petri dishes (diameter = 150 mm) and dried in the dark, at room temperature, under constant air flow for 48 h. After drying, the samples were irradiated under ambient conditions with a Co-60 g-source at a dose rate of 1.5 kGy h-1 for 10 h.
J Polym Res (2012) 19:9835 discloses a series of polyvinyl alcohol/polyvinyl pyrrolidone based hydrogels containing the silver nanoparticles. This article also discloses preparation of different hydrogel compositions by gamma irradiation.
The use of PVA based hydrogels has gained great importance due to its low toxicity, non-carcinogenicity and high biocompatibility. There are various methods have been reported for crosslinking of PVA, including chemical methods using crosslinking agents, physical methods using complexing agent and radiation methods using ?-radiation, electron beams, or ultraviolet light (Hennink and Nostrum, 2002; Elbadawy et al., 2015).
All the prior art references shows polymeric hydrogels are used significantly for the treatment of burns and other skin lesions, the process for preparation of silver ion hydrogel dressing, hydrogel dressing for wound care, hydrogel wound dressing, hydrogel having antimicrobial properties, polyvinyl alcohol nano-silver hydrogel wound dressing, antimicrobial wound dressing. However, the inventors of the present invention have developed an antimicrobial hydrogel dressing comprising PVA, povidone, glycerine and silver salt which is prepared by gamma irradiation for crosslinking, conversion of silver salt into silver nanoparticles and sterilization which limits number of unit operations by reducing process time and process cost.
OBJECTIVE OF INVENTION
The objective of the present invention is to provide an antimicrobial hydrogel comprising polyvinyl alcohol, povidone, glycerine and silver salt.
Another objective of the present invention is to provide a simple effective process for the preparation of antimicrobial hydrogel, wherein process comprises crosslinking, conversion of silver salt into silver nanoparticles and sterilization using gamma irradiation in single step.
SUMMARY OF INVENTION
One embodiment of the present invention provides antimicrobial hydrogel comprising polyvinyl alcohol, povidone or povidone derivatives, glycerine and silver salts.
Another embodiment of the present invention provides antimicrobial hydrogel comprising polyvinyl alcohol as matrix hydrogel base material, povidone or povidone derivatives as a stabilizer to prevent nanoparticle aggregation, glycerine as humectant and plasticizer and silver salt as antimicrobial precursor.

Another embodiment of the present invention provides antimicrobial hydrogel comprising polyvinyl alcohol, povidone or povidone derivatives, glycerine, wherein the silver salt converts into silver nanoparticles and soluble silver during process operations.
Another embodiment of the present invention provides a process for the preparation of antimicrobial hydrogel comprising polyvinyl alcohol as matrix hydrogel base material, povidone as stabilizer to prevent nanoparticle aggregation, glycerine as humectant and plasticizer and silver salt as antimicrobial precursor.
Another embodiment of the present invention provides a process for the preparation of antimicrobial hydrogel, wherein the process comprising crosslinking, conversion of silver salt into silver nanoparticles and sterilization of hydrogel solution in pouch using gamma irradiation in single step process which reduces process time and process cost.
Another embodiment of the present invention provides a process for preparing antimicrobial hydrogel, wherein the process comprising steps of:
a) dissolving polyvinyl alcohol in water and stirring at 60ºC to obtain the polyvinyl alcohol solution,
b) adding povidone to the above polyvinyl alcohol solution under stirring,
c) cooling the obtained polyvinyl alcohol / povidone solution mixture to the room temperature,
d) adding glycerine to the above mixture under stirring,
e) adding silver salt to the above polyvinyl alcohol/povidone/glycerine mixture and stirring at room temperature in order to get homogenous mixture,
f) transferring the homogenous mixture in to tray or pouch and
g) irradiating the tray or pouch with gamma irradiation polymerization by 60 Co source at the doses of 17 and 25 kGy where crosslinking, conversion of silver salt into silver nanoparticles and sterilization takes place in single step.
Another embodiment of the present invention provides a hydrogel package comprising:
(a) An individual package in which the hydrogel product is stored prior to usage and is packed in peel able / non-peel able triple laminated aluminium pouch, or LDPE pouch as primary packaging,
(b) The packaging material should withstand gamma irradiation, and
(c) The hydrogel primary pack is further packed in triple laminated aluminium pouch as secondary packaging.
DETAILED DESCRIPTION OF THE INVENTION
Hydrogel is a type of hydrophilic polymer three-dimensional network that swells in water but does not dissolve in water and retains a certain amount of water (more than 20%) inside its structure. In addition to its good biocompatibility, it also has a high water permeability, a certain degree of strength, the surface is similar to the soft tissue of the organism, these features make the hydrogel can be used as biological materials. Hydrogel has excellent physical and chemical properties and biological properties can control the drug release, and bioadhesive, biocompatible and biodegradable properties, has been used for slow release, pulse release, trigger release and other new to drug system development.
Hydrogel wound dressings provide several advantages over conventional wound dressings. Hydrogel polymers are hydrophilic, so that they absorb water, keeping the environment moist, thereby promoting healing, rehydrating dead tissues, and enhancing autolytic debridement. Hydrogel dressings are often cool on the surface of the wound, helping to relieve pain. By absorbing water, hydrogels permit the transport of drugs through the network of crosslinked polymer.
Preparation of hydrogels using natural polysaccharides often prone to degradation of polysaccharide over time, result in shortening of hydrogel dressing life time and it may allow the growth of microorganisms. Preparation of hydrogels using synthetic or semisynthetic polymers is relatively better to control and optimize the process parameters.
The use of PVA based hydrogels has gained great importance due to its low toxicity, non-carcinogenicity and high biocompatibility. There are various methods that have been reported for crosslinking of PVA, including chemical methods using crosslinking agents, physical methods using complexing agent and radiation methods using ?-radiation, electron beams, or ultraviolet light.
Hydrogel transparency, integrity and flexibility, which may depend on the crosslink density of the polymer network, molecular weight of polymer and gamma irradiation dose.
Hydrogels offer a useful starting point to engineer antimicrobial materials. They are a class of highly hydrated biomaterial, usually produced from natural or synthetic polymers. Polysaccharides such as alginate, dextran, and chitosan, along with the proteins gelatin and fibrin, are examples of natural polymers that form well-studied hydrogels. Poly(vinyl alcohol) (PVA), polyethylene oxide (PEO), and poly(acrylic acid) (PAA) are examples of hydrogel-forming synthetic polymers. Preferably Poly(vinyl alcohol) (PVA).
The concentration of the polyvinyl alcohol is 5% to 20% w/w, preferably 10% to 15% w/w, most preferably 12.5%.
Polyvinyl alcohol used in the present invention has a molecular weight of at least 10,000. As an upper limit, the polyvinyl alcohols may have a molecular weight of up to 1,000,000. Preferably, the polyvinyl alcohols have a molecular weight of 31,000 to about 1,90,000 g/mol, especially preferably up to approximately about 1,60,000 g/mol.
Silver based compounds are already proven to be effective antimicrobial agents against various types of microorganisms. Compared to other metals, silver is less toxic to mammalian cells and is being used in numerous biomedical applications including wound dressings to treat infections.
Silver is active in charged (Ag+) and uncharged (Ag) form. The uncharged form of silver is available in nanoparticle form. The ionic form of silver has inherent antimicrobial effect by disrupting bacterial cell wall, in the membranes and nucleic acids of bacterial cell. Silver nanoparticles (AgNP) also has been shown to effective antiseptic and multi-level antimicrobial action. Although the antimicrobial action of AgNP is well described, their mechanism of action is not clear so far.
Silver salt is selected from but not limited to silver thiocyanate, silver oxide, silver sulfate, silver alkyl carboxylate (Cl to C12), silver aryl sulfonate (Cl to C4 alkyl phenyl), silver nitrate, silver carbonate, silver sulfide, silver phosphoranilide, silver phosphate, silver hydroxide, silver hyaluronate, silver benzoate, silver tartarate, silver thiosulfate complex, silver laurate, silver zeolite, silver zirconium phosphate, silver alginate, silver ascorbate, silver folate, silver gluconate, silver salicylate, silver para amino benzoate, silver para amino salicylate, silver acetyl salicylate, silver EDTA, silver laurate, silver zeolite, silver zirconium phosphate, silver alginate, silver ascorbate, silver folate, silver iodate, silver oxalate, silver palmitate, silver perborate, silver stearate, silver succinate, silver thioglycolate, silver hydantoin complex, silver barbiturate, silver allantoinate, silver amine complexes (primary amine, tetiary amine), silver salicylate, silver para amino benzoate, silver para amino salicylate, silver acetyl salicylate, silver EDTA, or silver gluconate. The concentration of silver salt used in the present invention is about 0.001% - 0.1% w/w, preferably 0.002 % (w/w).
Povidone or its derivatives are used as a stabilizer to prevent nanoparticle aggregation and Povidone or its derivatives are selected from plasdone S630, povidone 90, povidone K30 and/ or mixture thereof. The concentration of Povidone or its derivatives used in the present invention is about 0.25 % to about 1% (w/w), preferably 0.5 % (w/w).
Glycerine is used as humectant and plasticizer and the concentration of glycerine is about 0.1 % to about 0.5% (w/w). preferably 0.25 % (w/w).
Purified water is used as a solvent in the concentration of about 80-95% w/v.
There is an increase of multi-drug resistant microbial infections in wound areas, which requires the development of new generation of wound dressing to overcome the problem. Specially, in the treatment of burns, hydrogel dressings play a significant role. Hydrogels are polymer network system which mimic biological tissues because of presence of high amounts of water and flexibility. In addition to advantages, hydrogel dressing may cause microbial infection in wound area is due to moist environment. Hence, it is necessary to develop sterile anti-microbial hydrogel dressing.
Use of antibiotics indiscriminately can cause resistance to microorganisms in wound area, further required higher and stronger dose leads to toxicity. So, maintaining moist environment, sterility and antimicrobial effect is key factor for ideal antimicrobial hydrogel dressing.
Use of free radical initiators for the formation of hydrogel may contain residual amounts in the final product, which may be harmful and toxic. Further, the formed hydrogel may not be sterile and have insufficient mechanical properties.
Gamma and electron beam polymerization involves high energy electromagnetic irradiation as crosslinker. These high energy radiations can crosslink water-soluble monomer or polymer chain ends without the addition of a crosslinker. During irradiation, using a gamma or electron beam, aqueous solutions of monomers are polymerized to form a hydrogel. Gamma and electron beam polymerizations also involves the initiation, propagation, and termination steps as in the free radical polymerization. Hydroxyl radicals are formed and initiate free radical polymerization among the vinyl monomers which propagate in a rapid chain addition fashion. The hydrogel is finally formed once the network reaches the critical gelation point. This process has an advantage over other crosslinking methods since it can be performed at room temperature and in physiological pH without using toxic and hard to remove crosslinking agents such as potassium persulfate. Chemical cross-linking is a highly versatile method to improve the mechanical property of the hydrogels. However, cross-linking agents are often toxic compounds and not environmental friendly. They give unwanted reactions with the bioactive substances present in the hydrogel matrix. The adverse effects of chemical cross-linking can be avoided by the process of physical cross linking using radiation or electron beam method.
Among those methods, an advantage of gamma radiation method are noticed in that the method can cause crosslinking as well as sterilization of the materials through container in which the materials are completely enclosed and besides the method is effective for bacterial spores high in heat resistance bacteria. Further, gamma sterilization method is considered to have high reliability in sterilization. Hydrogels prepared by gamma radiation method does not require operation for removal of residual toxin, unlike hydrogels prepared using chemical crosslinking agents may contain unreacted chemical crosslinking agent, which may be toxic and further requires purification or neutralization or sterilization procedures.
The present invention relates to preparation of sterile antimicrobial hydrogel dressing to treat burns and wounds. Use of one step gamma radiation can cause crosslinking of polyvinyl alcohol to form hydrogel with simultaneous reduction of silver nitrate to silver nanoparticles for effective antimicrobial action. Furthermore, the antimicrobial hydrogel dressing is being sterilized during gamma irradiation.
Gamma irradiation polymerization of PVA
[Chen and Bao, 1985, Danno A, et.al; 1958, Rosiak JM, et.al; 1991]
According to literature, when PVA solution is irradiated by gamma radiations, following events can occur.
Activation:
1. PH----------PH*
2. H2O----------HOH*
Free radical formation
3. PH*----------P* + H*
4. HOH*----------HO* + H*
Gas evolution
5. H* + H*----------H2
Recombination
6. P* + H*----------PH
7. HO* + H*----------H2O
Energy transfer
8. PH + HOH*----------PH* + H2O
9. PH* + H2O----------PH + HOH*
Radical transfer
10. PH + *OH----------P* + H2O
11. P* + H2O----------PH + *OH
Crosslinking
12. P* + PH----------P*- PH
Degradation
13. P* - PH----------P*+ PH
PH is PVA long chain and P is PVA short chain
The chemical changes occurring during gamma irradiation of PVA solution result either from direct or indirect effects via the solvent. When dilute solution is irradiated, its viscosity rises and intact gel structure is formed. If the gel structure is further irradiated, the equilibrium degree of swelling is reduced until the gel exudes the excess water and breaks away from the container wall. Evolution of hydrogen gas according to reaction 5 given above, during the irradiation of PVA solution will lead to either clear PVA gel or to a gel with entrapped hydrogen bubbles. Polymer radicals are formed either by reaction 3 or by reaction 10 and a large number of solvent radicals can lead to increase in the number of radicals formed. There may be further degradation of PVA crosslinks due to oxygen evolution but other additives in PVA hydrogel protect polymer against degradation by radical transfer and recombination of radicals produced from irradiation of water.
When PVA mixed with silver salt, the ionic silver is attracted by the chains’ hydroxyl groups. After gamma-irradiation, silver is reduced, and nanoparticles are formed close to the OH- groups, remaining entrapped in the PVA network. In addition, through the hydroxyl groups, the PVA chains can be cross-linked when irradiated.
Formulations were developed using various concentrations of PVA and AgNO3 exposed to different gamma irradiation doses. Further, we also studied the influence of polymer molecular weight on hydrogel formation and its physical and mechanical properties has also been studied. The compositions resulted in stable and homogenous hydrogels, which are evaluated for their description, thickness, water absorption capacity, percentage elongation, tensile strength, silver content and sterility.
The following examples describes the nature of the invention and are given only for the purpose of illustrating the present invention in more detail and are not limitative and relate to solutions which have been particularly effective on a bench scale.
Example 1
S.No. Ingredient Concentration (% w/w)
1 Polyvinyl alcohol 12.5
2 Povidone 0.5
3 Glycerin 0.25
4 Silver nitrate (AgNO3) 0.002
5 Purified water 86.748

Manufacturing process
? Polyvinyl alcohol was added to purified water under stirring at 60o C to obtain homogenous solution.
? Povidone was added to polyvinyl alcohol solution under stirring at same temperature. The obtained solution was allowed to cool down to room temperature.
? Glycerine and silver nitrate were added to obtained polyvinyl alcohol - povidone solution mixture under stirring at room temperature to obtain homogenous mixture.
? The obtained homogenous solution was filled into LDPE pouches of predetermined fill weight.
? The filled pouches were irradiated with gamma irradiation by 60Co source at the doses of 25 kGy for crosslinking of PVA and conversion of silver salt into silver nanoparticles along with sterilization.
? Finally, LDPE pouch containing PVA hydrogel was packed in triple laminated aluminum secondary package.
Evaluation tests for hydrogels
Description: Description of the hydrogel was evaluated by visual observation.
Size : Size of the hydrogel sample was measured using digital Vernier calliper
Thickness: Thickness of the hydrogel was measured using digital Vernier calliper
Weight: Weight of the hydrogel sample was measured using digital weighing balance
Water uptake capacity: Water Absorption capacity of hydrogel was measured by taking known weight of hydrogel sample was immersed in excessive distilled water at room temperature for 24 h. Then the swollen samples were collected carefully and blotted with tissue until no free water remained. The water absorption of the hydrogels was derived from the mass change before and after swelling.
Wt. after immersion - Initial wt. of hydrogel
% water uptake = -------------------------------------------------------------- X 100
Initial wt. of hydrogel
Adherence to the skin: Hydrogel sample was placed or applied on skin and checked for whether sample was adhering to skin or not.
Tensile strength: Tensile strength of hydrogel samples were measured using universal testing machine.
Water vapour transmission rate: Water vapour transmission rate (WVTR), is a measure of the passage of water vapour through the material. It is also known as moisture vapour transmission rate (MVTR). It is the mass of water vapour transmitted through a unit area in a unit time under specified conditions of temperature and humidity.
Weight at diff. time interval - Initial Weight of hydrogel
WVTR = ------------------------------------------------------------------------ X 100
Initial Weight of hydrogel

Silver content: Silver content in hydrogel sample was measured using Inductively coupled plasma mass spectrometry (ICP-MS).
Sterility test: Sterility testing was performed according to USP general chapter < 71 >.
Antimicrobial effectiveness testing: Antimicrobial effectiveness was performed for optimized formulations with silver content in the range of 0.001% to 0.1%. The testing was performed according to USP General Chapter (51).
Bacterial Endotoxin Test: Bacterial Endotoxin Test was performed for optimized formulation. The testing was performed according to USP General Chapter < 85 >.

Table 1. Specifications for antimicrobial hydrogel dressing.
S.No. Test SPECIFICATION
1 Description Light yellow to light brown transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch
2 Size (cm) 16 x 16
3 Thickness (mm) 5 ± 1.5
4 Weight (gm) 150 ± 5
5 Water uptake capacity (%) NLT 40 % of weight of PVA dressing
6 Adherence to the skin Should slightly adhere to the skin
7 Tensile strength (kgf/cm2) NLT 0.10
8 Water vapor transmission rate (% w/w) NMT 0.5
9 Silver content (%) NLT 70 % of label claim (0.002 % AgNo¬¬¬¬3)
10 Sterility To pass the test as per USP
11 Anti-microbial performance To pass the test as per USP
12 Bacterial endotoxins NMT 300 IU/g of PVA hydrogel

The PVA hydrogel formulation prepared as per the example 1 of the present invention is evaluated for the above characters at different conditions and the data is given below tables:

Table 2
Stability Condition: 25°C/60% RH
Tests Specification Initial 3 Month
Description Light yellow to light brown transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch Light yellow transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch Light yellow transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch
Size 16 cm x 16 cm 16 cm X 16 cm 16 cm X 16 cm
Thickness 5 mm ± 1.5 mm 4.09 mm 4.49 mm
Weight 150 g ± 5 g 151 g 152 g
Water uptake capacity NLT 40 % of weight of PVA dressing 69.93% 55.53%
Adherence to the skin Should slightly adhere to the skin Slightly adhered to the skin Slightly adhered to the skin
Tensile Strength NLT 0.10 kgf/cm2 0.177 kgf/cm2 0.347 kgf/cm2
Water vapor transmission rate NMT 0.5 % w/w 0.04% 0.05%
Silver content NLT 70 % of label claim (0.002 % AgNO3) 76.34 % 74.67%
Sterility To pass the test as per USP Pass -
Anti-microbial performance To pass the test as per USP Pass -
Bacterial Endotoxin test NMT 300 IU/g of PVA hydrogel Complies -
Table 3
Stability Condition: 40°C/75% RH
Tests Specification Initial 3 Month
Description Light yellow to light brown transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch Light yellow transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch Light yellow transparent and flexible hydrogel filled in transparent pouch and further packed in triple laminated aluminum pouch
Size 16 cm x 16 cm 16 cm X 16 cm 16 cm X 16 cm
Thickness 5 mm ± 1.5 mm 4.09 mm 4.75 mm
Weight 150 g ± 5 g 151 g 152 g
Water uptake capacity NLT 40 % of weight of PVA dressing 69.93% 56.35%
Adherence to the skin Should slightly adhere to the skin Slightly adhered to the skin Slightly adhered to the skin
Tensile Strength NLT 0.10 kgf/cm2 0.177 kgf/cm2 0.195 kgf/cm2
Water vapor transmission rate NMT 0.5 % w/w 0.04% 0.16%
Silver content NLT 70 % of label claim (0.002 % AgNO¬¬¬¬3) 76.34 % 73.87%
Sterility To pass the test as per USP Pass -
Anti-microbial performance To pass the test as per USP Pass -
Bacterial Endotoxin test NMT 300 IU/g of PVA hydrogel Complies -
,CLAIMS:WE CLAIMS
1. Antimicrobial hydrogel comprising polyvinyl alcohol, povidone or povidone derivatives, glycerine and silver salts.
2. The composition of claim 1, wherein the silver salt is silver nitrate.
3. The composition of claim 1, wherein silver salt in the process converts into silver nanoparticles and soluble silver.
4. The composition of claim 1, wherein the composition comprises about 5 % to about 20% (w/w) of the polyvinyl alcohol.
5. The composition of claim 1, wherein said PVA has a molecular weight ranging from about 31,000 to about 1,90,000 g/mol.
6. The composition of claim 1, wherein the composition comprises about 0.002 % (w/w) of the silver salt.
7. The composition of claim 1, wherein the composition comprises about 0.25 % to about 1% (w/w) of povidone.
8. The composition of claim 1, wherein the composition comprises about 0.1 % to about 0.5% (w/w) of glycerine.
9. A process for preparing antimicrobial hydrogel, wherein the process comprising steps of:
a) dissolving polyvinyl alcohol in water and stirring at 60ºC to obtain the polyvinyl alcohol solution,
b) adding povidone to the above polyvinyl alcohol solution under stirring,
c) cooling the obtained polyvinyl alcohol / povidone solution mixture to the room temperature,
d) adding glycerine to the above mixture under stirring,
e) adding silver salt to the above polyvinyl alcohol/povidone/glycerine mixture and stirring at room temperature in order to get homogenous mixture,
f) transferring the homogenous mixture in to tray or pouch and
g) irradiating the tray or pouch with gamma irradiation polymerization by 60 Co source at the doses of 17 and 25 kGy where crosslinking, conversion of silver salt into silver nanoparticles and sterilization takes place in single step.
10. A hydrogel package comprising:
(a) An individual package in which the hydrogel product is stored prior to usage and is packed in peel able / non-peel able triple laminated aluminium pouch, or LDPE pouch as primary packaging,
(b) The packaging material should withstand gamma irradiation, and
(c) The hydrogel primary pack is further packed in triple laminated aluminium pouch as secondary packaging.

Date this Tenth (10th) day of March, 2018.

__________________________________
Dr. S. Padmaja
Agent for the Applicant
IN/PA/883