[0001] The present invention relates to hydrogels for chronic wounds. Specifically, the present invention relates to novel sprayed nanocomposite hydrogels for chronic wounds. The present invention further relates to process for preparation of novel sprayed nanocomposite hydrogels for chronic wounds.

BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Hydrogels are vastly hydrophilic macromolecular networks, which are produced by chemical or physical cross linking of soluble polymers. Due to peculiar properties of hydrogels such as, high-sensitive to physiological environments, hydrophilic nature, soft tissue-like water content and adequate flexibility, make them excellent candidates for biomedical applications. Hydrogels are reportedly the best choice compared to other dressing forms as hydrogels can absorb and retain the wound exudates, which promote fibroblast proliferation and keratinocyte migration. One of the disadvantages of hydrogels is their poor mechanical stability at swollen state, which has been addressed by using “composite or hybrid hydrogel membranes” system consisting of more than one polymer in the dressing composition.
[0004] Additionally, hydrogels structure allows transporting bioactive molecules e.g. antibiotics, and pharmaceuticals to wound centre, which can be entrapped into hydrogel networks during gelling process, and exchanged with absorbing the wound exudates during the sustainable release process after contacting hydrogels with the wound surface.
[0005] The success of hydrogel dressings is thought to be due to their ability to maintain an optimum wound healing environment, which is warm and moist, rather than dry whilst keeping out infective agents. They are capable of superseding conventional dressings such as natural or synthetic cotton, lint, and gauze bandages, which have had one or more disadvantages, including the need for frequent removal, difficulty in adhesion, improper mechanical properties, or difficulty in application.
[0006] The practical limitations associated with hydrogels include their preparations, mode of applications, biodegradability, thickness and strength-based problems. Also, the application of hydrogels on the ulceration area leads to abrasion and hampering on the nascent tissue and also interferes with healing process.
[0007] Although numerous hydrogel-based dressings are already on the market, new wound care treatment options are urgently required to address the growing number of severe, acute and chronic wounds experienced by today’s aging society. There is, therefore, a need to develop novel nanocomposite hydrogels for chronic wounds and processes for their preparation that can overcome deficiencies associated with the known arts.

OBJECTS OF THE INVENTION
[0008] An object of the present invention is to provide novel hydrogels for chronic wounds and processes for their preparation that can overcome deficiencies associated with the known arts.
[0009] An object of the present invention is to provide novel hydrogels that can be sprayed onto a wound to form hydrogel in situ.
[0010] Yet another object of the present invention is novel hydrogels that possess high mechanical strength, 100 % biodegradation (in biological tissues), excellent swelling property, low toxicity, and improved antimicrobial activity.
[0011] Another object of the present invention is to provide novel hydrogels that resembles the natural tissues and enzymatic degradation.
[0012] Yet another object of the present invention is novel hydrogels that can be easily prepared by a facile synthetic method.
[0013] The other objects and preferred embodiments and advantages of the present invention will become more apparent from the following description of the present invention when read in conjunction with the accompanying examples and figures, which are not intended to limit scope of the present invention in any manner.

SUMMARY OF THE INVENTION
[0014] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in Detailed Description section. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
[0015] The present invention relates to hydrogels for chronic wounds. Specifically, the present invention relates to novel sprayed nanocomposite hydrogels for chronic wounds. More specifically, the present invention is directed to hydrogels for chronic wounds that can be sprayed onto a wound to form hydrogel in-situ.
[0016] In one aspect, the present invention relates to novel hydrogels comprising polymers, silver nanoparticles and cross-linkers.
[0017] In another aspect, the present invention relates to novel hydrogels wherein the polymers are chitosan, sodium alginate and polyvinyl alcohol.
[0018] In another aspect, the present invention relates to novel hydrogels wherein the cross-linkers are glutaraldehyde, calcium chloride and boric acid.
[0019] In one aspect, the present invention relates to novel hydrogels that have increased biomedical significance towards high mechanical strength.
[0020] In another aspect, the present invention relates to novel hydrogels that are 100 % biodegradable in biological tissues.
[0021] In another aspect, the present invention relates to novel hydrogels that exhibit excellent swelling property, low toxicity and improved antimicrobial activity.
[0022] The sprayed hydrogel films according to the embodiments of the present invention offer the advantage of being versatile and resemble exactly the natural tissues and enzymatic degradation.
[0023] In one aspect, the present invention relates to a process for preparation of novel that can be sprayed onto a wound to form hydrogel in-situ.
[0024] In another aspect, the present invention relates to a process for preparation of novel hydrogels that can be sprayed onto a wound to form hydrogel in-situ, the process comprising the steps of:
a) Mixing the polymer solution along with silver nanoparticles and spraying onto the infected wound; and
b) Spraying the mixture of chemical cross-linker on the polymer mixture resulting in formation of sprayed hydrogel film.
[0025] In another aspect, the present invention relates to a process for preparation of novel hydrogels wherein the spraying is carried out by using sprinkler sprays.
[0026] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

BRIEF DESCRIPTION OF DRAWINGS THE INVENTION
[0027] The following drawings form part of the present specification and are included to further illustrate aspects of the present disclosure. The disclosure may be better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein.
Figure 1: illustrates triple layer sprayed hydrogels with uniform layers and flexibility.
Figure 2: illustrates spraying device used for spraying mixture of polymers and cross-linkers.
Figure 3: illustrates swelling of sprayed hydrogels in (A) distilled water and (B) in buffer solution with pH 6.8
Figure 4: illustrates complete degradation of synthesized sprayed hydrogels in (A) Distilled water and (B) in buffer solution with pH 6.8
Figure 5: illustrates mechanical strength of synthesized sprayed hydrogels in terms of its flexibility and breaking strength.

DETAILED DESCRIPTION
[0028] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0029] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
[0030] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0031] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.”Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0032] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise.Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0033] Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
[0034] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0035] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
[0036] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[0037] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.
[0038] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[0039] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[0040] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing
[0041] The term “hydrogel” as used herein refers to a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. The three-dimensional solid results from the hydrophilic polymer chains held together by cross-links.
[0042] The term “nanocomposite” as used hereinrefers toa multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometers (nm) or structures having nano-scale repeat distances between the different phases that make up the material.
[0043] The term “silver nanoparticles” as used here in refers to are nanoparticles of silver of between 1 nm and 100 nm in size. Silver nanoparticles are broad spectrum antimicrobial agents against resistant species and are economically available.
[0044] The present invention relates to hydrogels for chronic wounds. Specifically, the present invention relates to novel sprayed nanocomposite hydrogels for chronic wounds. More specifically, the present invention is directed to hydrogels for chronic wounds that can be sprayed onto a wound to form hydrogel in-situ.
[0045] In one embodiment, the present invention relates to novel hydrogels comprising polymers, silver nanoparticles and cross-linkers in the ratio of 1:1:1.
[0046] In another embodiment, the present invention relates to novel hydrogels wherein the polymers are chitosan, sodium alginate and polyvinyl alcohol.
[0047] In yet another embodiment, the present invention relates to novel hydrogels wherein the polymers chitosan, sodium alginate and polyvinyl alcohol are present in the ratio of 1:1:1.
[0048] In still another embodiment, the present invention relates to novel hydrogels wherein chitosan is dissolved in 3% glacial acetic acid v/v and is present as 1% w/v by weight of the total composition.
[0049] In still another embodiment, the present invention relates to novel hydrogels wherein sodium alginate is present as 3% w/vby weight of the total composition.
[0050] In still another embodiment, the present invention relates to novel hydrogels wherein polyvinyl alcohol is present as 10% w/vby weight of the total composition.
[0051] In another embodiment, the present invention relates to novel hydrogels wherein the cross-linkers are chemical cross linkers glutaraldehyde, calcium chloride and boric acid.
[0052] In yet another embodiment, the present invention relates to novel hydrogels wherein the chemical cross linkers glutaraldehyde, calcium chloride and boric acid are present in the ratio of 1:1:1.
[0053] In still another embodiment, the present invention relates to novel hydrogels wherein glutaraldehyde is present as 3% v/vby weight of the total composition.
[0054] In still another embodiment, the present invention relates to novel hydrogels wherein calcium chloride is present as 3% w/v by weight of the total composition.
[0055] In still another embodiment, the present invention relates to novel hydrogels wherein boric acid is present as 8% w/vby weight of the total composition.
[0056] In yet another embodiment, the present invention relates to novel hydrogels wherein silver nanoparticles are prepared from silver nitrate using green synthesis by using plant extract as a reducing agent.
[0057] The hydrogels, thus prepared as per the embodiments of the present invention are triple layer sprayed hydrogels with uniform layers and flexibility as shown in Figure 1. The spraying device used for spraying mixture of polymers and cross-linkersfor the in-situ formation of hydrogels is shown in Figure 2.
[0058] In another embodiment, the present invention relates to novel hydrogels that exhibit excellent swelling property as illustrated in Figure 3. The hydrogels according to the embodiments of the present invention also exhibit low toxicity and improved antimicrobial activity.
[0059] In another embodiment, the present invention relates to novel hydrogels that are 100 % biodegradable in biological tissues as illustrated in Figure 4.
[0060] In one embodiment, the present invention relates to novel hydrogels that have increased biomedical significance towards high mechanical strength as illustrated in Figure 5.
[0061] The sprayed hydrogel films according to the embodiments of the present invention offer the advantage of being versatile and resemble exactly the natural tissues and enzymatic degradation. The sprayed hydrogel films according to the embodiments of the present invention provide ease of application, are cost effective, maintain moisture content, provide aseptic surface area, optimum thickness, and ease of application. The sprayed hydrogels according to the embodiments of the present invention offer 100% biodegradability (as shown in Figure 5) and there is no need to remove the hydrogels after application.
[0062] In one embodiment, the present invention relates to a process for preparation of novel that can be sprayed onto a wound to form hydrogel in-situ.
[0063] In another embodiment, the present invention relates to a process for preparation of novel hydrogels that can be sprayed onto a wound to form hydrogel in-situ, the process comprising the steps of:
a) Mixing the polymer solution along with silver nanoparticles and spraying onto the infected wound; and
b) Spraying the mixture of chemical cross-linker on the polymer mixture resulting in formation of sprayed hydrogel film.
[0064] In another embodiment, the present invention relates to a process for preparation of novel hydrogels wherein the spraying is carried out by using sprinkler sprays. The spraying process leads to cross-linking of polymeric solution with that of chemical cross-linker.
[0065] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
[0066] The present invention is further explained in the form of following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention.
[0067] All the raw materials are easily available and were purchased commercially. Polyvinyl alcohol (Mol. Weight ~77,000 g/mol) and Chitosan were purchased from Himedia laboratories, Mumbai. Calcium chloride, Boric Acid 99.5% (w/w) and aqueous solution of Gluteraldehyde, 25% (v/v)were purchased from Merck specialties Pvt. Ltd. India. Sodium alginate was purchased from Loba Chemie, Mumbai, India, Silver nitrate (AgNO3) was purchased from Qualikems Fine Chem. Pvt. Ltd.

[0068] Example 1: Composition for Sprayed nanocomposite hydrogel films
Sr. No Polymers (1:1:1) Chemical Crosslinker (1:1:1) Silver Nanoparticle (1% v/v)
1 Chitosan, 1% w/v (Dissolved in 3% Glacial acetic acid v/v) Glutaraldehyde (3 %v/v) 1% v/v
2 Sodium Alginate (3%w/v) Calcium Chloride (3 % w/v) 1% v/v
3 Polyvinyl Alcohol (10% w/v) Boric Acid (8% w/v) 1% v/v

[0069] Example 2: Preparation of polymeric nanocomposite hydrogel
[0070] Aqueous solutions of Boric Acid (8% w/v), Glutaraldehyde (3 %v/v) and Calcium Chloride (3% w/v) were prepared by heating at a temperature of about 80 °C. Aqueous solution of Polyvinyl alcohol (10 % w/v) and Sodium alginate (3 %w/v) were prepared by dissolving in distilled water whereas solution of Chitosan (1% w/v) was prepared by dissolving in 3% v/v glacial acetic acid. For the preparation of triple layered sprayed hydrogels, varying ratio of Polyvinyl alcohol: Sodium alginate: Chitosan (1:1:0, 1:0:1, 0:1:1, 1:1:2, 1:2:1, 2:1:1, 1:1:3, 1:3:1:, 3:1:1, 0:0:1 (CH alone), 0:1:0 (SA alone), 1:0:0 (PVA alone)) containing precise amount of silver nanoparticles (based on Minimum Inhibitory concentration) were mixed thoroughly. Polyvinyl alcohol, Sodium alginate, Chitosan and Polyvinyl alcohol, Sodium alginate, Chitosan containing silver nanoparticles loaded triple layered sprayed hydrogels were prepared by squirting the either blend of polymers or by spraying the individual mixture of each polymer followed by its cross-linking by related cross-linkers instantaneously on a glass slide. The synthesized hydrogels were peeled out and kept in freezer (4 °C) for further use.
[0071] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

ADVANTAGES OF THE PRESENT INVENTION
[0072] The present invention provides novel hydrogels that can be sprayed onto a wound to form hydrogel in situ.
[0073] The present invention provides novel hydrogels that possess high mechanical strength, 100 % biodegradation (in biological tissues), excellent swelling property, low toxicity, and improved antimicrobial activity.
[0074] The present invention provides novel hydrogels that resembles the natural tissues and enzymatic degradation.
[0075] The present invention providesnovel hydrogels that can be easily prepared by a facile synthetic method.

Claims:1. A novel sprayed nanocomposite hydrogel for chronic wounds, comprising polymers, silver nanoparticles and cross-linkers in the ratio of 1:1:1.
2. The hydrogel as claimed in claim 1, whereinthe polymers are chitosan, sodium alginate and polyvinyl alcohol.
3. The hydrogel as claimed in claim 2, wherein the polymers chitosan, sodium alginate and polyvinyl alcohol are present in the ratio of 1:1:1.
4. The hydrogel as claimed in claim 2, wherein chitosan is dissolved in 3% glacial acetic acid v/v and is present as 1% w/v by weight of the total composition.
5. The hydrogel as claimed in claim 2, whereinsodium alginate is present as 3% w/vby weight of the total composition.
6. The hydrogel as claimed in claim 2, whereinpolyvinyl alcohol is present as 10% w/vby weight of the total composition.
7. The hydrogel as claimed in claim 1, wherein the cross-linkers are chemical cross linkers glutaraldehyde, calcium chloride and boric acid.
8. The hydrogel as claimed in claim 7, wherein the chemical cross linkers glutaraldehyde, calcium chloride and boric acid are present in the ratio of 1:1:1.
9. The hydrogel as claimed in claim 8, wherein glutaraldehyde is present as 3% v/vby weight of the total composition.
10. The hydrogel as claimed in claim 8, wherein calcium chloride is present as 3% w/vby weight of the total composition.
11. The hydrogel as claimed in claim 8, wherein boric acid is present as 8% w/vby weight of the total composition.
12. A process for the preparation of novel hydrogels as claimed in claims 1-11, that can be sprayed onto a wound to form hydrogel in-situ, the process comprising the steps of:
a) Mixing the polymer solution along with silver nanoparticles and spraying onto the infected wound; and
b) Spraying the mixture of chemical cross-linker on the polymer mixture resulting in formation of sprayed hydrogel film.