KR20050072716A - Hydrogel formulations for treating wounds - Google Patents

Abstract

The present invention relates to a hydrogel preparation for wound treatment, for example a trauma bandage or bandage on which hydrogel is deposited, containing water, polyacrylic acid as a water-soluble polymer, or a salt or derivative thereof, and a polyol as a moisturizing agent.

Description

Hydrogel formulations for treating wounds

The present invention relates to a hydrogel preparation for wound treatment, the hydrogel preparation having the effects of wound healing, sterilization, scar prevention and inhibition, wound recovery, etc. against burns, wounds, traumas, bedsores and skin diseases, For example, it relates to a trauma bandage or bandage on which hydrogels have been deposited.

Formulations with hydrogel properties include Canadian Patent No. 180 622 containing gelatin, polyethylene oxide and polyethyleneamine, and Federal Republic of Patent No. 28 49 570 are hydrophilic poly (meth-) in the presence of polysaccharides / proteins. Formulations containing the same have been disclosed. In addition, Federal Patent No. 30 31 304 discloses a formulation based on hydrophilic ethylenically unsaturated monomers cross-linked with bifunctional compounds, European Patent No. 0 099 758 discloses synthetic collagen or alginate and Other biopolymers, EP 0 262 405 disclose sodium polyacrylate / polyacrylic acid / acryloylamide and other acrylamide derivatives; EP 0 27 074 disclose unsaturated, carboxyl group-containing multimers and di- or For copolymers of oligosaccharides, US Pat. No. 3,249,109 discloses formulations containing gelatin, water, polyhydric alcohols and pectins, and US Pat. No. 4,243,656 containing absorbents, gelatin and water. Further, US Pat. No. 4,930,500 discloses a hydrogel containing water, reaction products of acrylamide compounds and bis crosslinkers and polyols.

However, hydrogels using synthetic polymers tend to discontinuously absorb the wound secretions, and in particular, hydrogels disclosed in US Pat. No. 4,930,500 prevent or minimize the adhesion of bandages to the wound site, resulting in wound exudates. And other body secretions are not sufficiently absorbed and cannot achieve satisfactory wound healing. In addition, upon removal of the bandage from the wound, the hydrogel material does not inhibit the progression of wound healing and breaks down into cracked residues and a portion of the gel.

In order to develop a hydrogel preparation that can exhibit effects of wound healing, sterilization, scar prevention and suppression, wound recovery, etc., against burns, wounds, traumas, bedsores, and skin diseases, compared to conventional hydrogel preparations. Ongoing studies were conducted. As a result, it was confirmed that the hydrogel preparation prepared by combining water, polyacrylic acid as a water-soluble polymer, a salt or derivative thereof, and a polyol as a moisturizing agent can achieve all the effects as described above, and completed the present invention.

It is therefore an object of the present invention to provide a hydrogel formulation containing water, polyacrylic acid as a water-soluble polymer, or a salt or derivative thereof, and a polyol as a moisturizing agent and a method for producing the same.

The present invention

Iii) water;

Ii) polyacrylic acid, or a salt or derivative thereof, as a water-soluble polymer; And

Iii) polyols as humectants:

It relates to a hydrogel formulation for wound treatment, containing.

The hydrogel formulations of the present invention may contain polyacrylic acid, or salts or derivatives thereof, alone or in combination with other natural, semisynthetic or synthetic polymers as water-soluble polymers, preferably polyacrylic acid, or salts or derivatives thereof, In particular, it contains sodium polyacrylate alone.

The hydrogel formulation of the present invention may also contain one or more selected from the group consisting of glycerin, propylene glycol, sorbitol, ethylene glycol, diethylene glycol, polyethylene glycol, polypropylene glycol and 1,3-butylene glycol as a moisturizing agent. And preferably glycerin.

In the hydrogel preparation of the present invention, the weight ratio of water: water-soluble polymer: polyol is preferably 10 to 80: 1 to 50: 3 to 60, more preferably 20 to 70: 3 to 30: 5 to 50, most. Preferably it is 25-65: 5-20: 10-45.

The hydrogel formulations of the present invention may further contain one or more selected from the group consisting of absorption accelerators, excipients, emollients, adjuvants and pH adjusters.

The hydrogel formulations of the present invention can be used for wound healing, sterilization, scar prevention and inhibition, or wound recovery for burns, wounds, traumas, bedsores or skin diseases. The hydrogel formulations of the invention can be used, for example, in the form of bandages or bandages in which hydrogels have been deposited.

Hereinafter, the present invention will be described in detail.

The present invention is directed to wound healing, disinfection, and treatment of burns, wounds, traumas, bedsores and skin diseases, which contain one or more of water, water soluble polymers and moisturizers, and optionally one or more of an absorption accelerator, an excipient, an irritant, an adjuvant and a pH adjuster. Provided are hydrogel formulations that exhibit efficacy in preventing and inhibiting scars, healing wounds, and the like.

In the present invention, polyacrylic acid or a salt or derivative thereof, particularly sodium polyacrylate, is used as the water-soluble polymer as the base component. Such polyacrylic acids, or salts or derivatives thereof, may be used alone or in combination with other natural polymers, semisynthetic polymers or synthetic polymers.

Natural polymers include gelatin, hyaluronic acid or salts thereof, collagen, xanthan rubber, acacia rubber, guar rubber, carrageenan, arginic acid, sodium arginate, agar, gum arabic, tragaganth, karaya rubber, pectin, starch, etc. Can be used.

As the semisynthetic polymer, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose sodium, soluble starch, carboxymethyl starch and dialdehyde starch may be used.

Synthetic polymers include polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl acrylate, polyethylene oxide, methyl vinyl ether-maleic anhydride copolymer and isobutylene-maleic anhydride copolymer, methacrylic acid-butyl acrylate copolymer, Oxyethylene maleic anhydride copolymer and the like can be used. Of course, the water-soluble polymer includes those treated with a known crosslinking agent or polymerizing agent.

For example, the hydrogel formulations of the present invention may contain polyacrylic acid, or salts or derivatives thereof, as a combination with gelatin, polyvinyl alcohol, carboxymethylcellulose, or polyvinylpyrrolidone, sodium polyacrylate, It is most preferable to contain sodium polyacrylate especially.

The blending amount of the water-soluble polymer is preferably 1 to 50% by weight, more preferably 3 to 30% by weight, most preferably 5 to 20% by weight, based on the total amount of the hydrogel preparation. And in proportion, in particular, the maintenance and stability of the moisture content is improved, and the adhesion to the transdermal (skin) is improved. In addition, it is possible to prevent sticking or sagging of the base, to relieve pain when peeling the trauma bandage (bandage) in which hydrogel is deposited from the skin, and to prevent the base from remaining on the skin.

In the present invention, as a moisturizing agent, glycerin, propylene glycol, sorbitol, ethylene glycol, diethylene glycol, polyethylene glycol, polypropylene glycol, 1,3-butylene glycol, and the like may be used. Or it mixes and uses 2 or more types. At this time, the blending amount of the humectant is preferably 3 to 60% by weight, more preferably 5 to 50% by weight, most preferably 10 to 45% by weight based on the total amount of the hydrogel preparation. In this range, the hydrogel formulation maintains a moderate wet state and improves sustained cooling and volatilization of moisture.

In addition, the amount of water (purified water) indispensable in the hydrogel preparation is preferably 10 to 80% by weight, more preferably 20 to 70% by weight, most preferably 25 to 65% by weight, based on the total amount of the preparation, Within this blending ratio, the stability of the hydrogel formulation is improved.

In the hydrogel preparation of the present invention, by appropriately blending the absorption promoter, it is possible to improve the absorption promotion or the sustained action of the medicinal effect in the transdermal. Or other essential oils or surfactants, such as glycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, propylene glycol monolauryl ether, monooleic acid polyoxyethylene (20EO) sorbitan (trade name: polysorbate 80), polyoxyethylene (abbreviated as POE) hardened castor oil, POE sorbitan monolaurate, POE nonylphenyl ether, POE lauryl ether, POE (40) stearate, POE (20) monostearate, lauric Acid diethanolamide, sodium lauryl sulfate, lauromacrogol or monostearate polyethylene glycol, glyceryl monooleate, glyceryl monolauryl ether, sorbitan monooleate, glyceryl trioleate, isopropyl myristate, Crotamiton or the like or other known surfactants are used. Said surfactant can mix | blend 1 or more types chosen from a normal thing.

The compounding amount of the surfactant is preferably used in the range of 0.01 to 10% by weight, more preferably 0.1 to 7% by weight, most preferably 0.3 to 5% by weight based on the total amount of the hydrogel preparation, and at this ratio It is possible to obtain a hydrogel formulation with improved sustaining action.

The hydrogel formulation of the present invention may further contain an excipient, a dissolution aid, an irritant, a drug adjuvant, a pH adjuster and the like as necessary.

First, as an excipient, fillers such as kaolin, loess, charcoal, zinc oxide, titanium, talc, bentonite and hydrous aluminum silicate; Preservatives such as thimol, methylparaben, benzalkonium chloride and ethylparaben; Antioxidants such as ascorbic acid, stearic acid ester, sodium pyrosulfite, disodium ether, dibutyl hydroxytoluene, butyl hydroxy arisole, and molten acid ester; Emulsifiers such as sorbitan fatty acid esters, glycerin fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene alkyl ethers; Phenyl salicylate, glycol salicylate, methyl paraaminobenzoate, 2-hydroxy-4-methoxybenzophenol, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone and 2-hydroxy-4-meth Ultraviolet absorbers such as oxybenzophenol-5-sulfonic acid; Alkaline earth metals such as calcium chloride, calcium carbonate, magnesium chloride, kali alum, ammonia alum, polyvalent metal salts, for example aluminum compounds such as aluminum hydroxide, aluminum sulfate, aluminum acetate, aluminum silicate, magnesium hydroxide, magnesium sulfate, magnesium acetate, and the like Calcium compounds such as magnesium compounds, calcium hydroxide, calcium carbonate, calcium chloride, calcium gluconate, calcium lactate, calcium pantothenate, antacids containing aluminum magnesium silicon compounds, potassium aluminum sulfate or other heavy metals such as calcium, magnesium, aluminum, formalin Crosslinking agents or polymers such as glyoxazole, glutaraldehyde, aldehydes of dialdehyde starch, epoxy compounds and isocyanate compounds; Or tackifiers such as polybutene, natural latex, vinyl acetate emulsion and polyacrylic acid ester emulsion, and the like. The said various excipients can be manufactured more excellent hydrogel formulation by mix | blending suitably 1 type (s) or 2 or more types.

Furthermore, antihistamines, such as diphenhydramine hydrochloride, diphenhydramine tannin, d1-maleic acid chlorophenylamine, d-maleic acid chlorophenylamine, and maleic acid chlorophenylamine, in order to alleviate the skin irritation of a hydrogel preparation; Anti-allergic agents or steroids such as anlexanox, ibsirast, azelastine, oxatomid, sodium chromoglycolate, tazanolast, terpenadine, toranirani, kemarotictofufen and repirinasto; The side effects on skin can be suppressed by mix | blending moderately emollients, such as other glycylipinic acid, the glycyretinic acid, the cyclodextrin of (alpha), (beta), (gamma), or the compound derived from cyclodextrin.

Finally, citric acid, tartaric acid, malic acid, organic acids of succinic acid, water-soluble organic amines of triethanolamine, diisopropanolamine or diethanolamine, etc., are used as pH adjusting agents to adjust the pH of the preparation to 4-8, preferably 4.5-7, and more. Preferably, by adjusting to the range of 5 to 6.5, the skin irritation can be alleviated, the stability of the base can be improved, or the adhesion can be maintained. The compounding quantity of a pH adjuster is used suitably according to pH concentration.

On the other hand, the hydrogel formulation according to the present invention can be used by depositing a hydrogel on a substrate such as a band-aid or bandage. The base layer is preferably provided with a predetermined breathability and flexibility (flexibility), for which a porous material is used. Porous materials are divided into non-fibrous or fibrous porous materials, which include membrane filters, foams (such as foamed polypropylene, foamed polyethylene, or foamed polyurethane), various porous films and meshes ( mesh) and the like, and a fibrous porous material may be used as a woven fabric, a nonwoven fabric, a collection of papers and short fibers, or the like. Herein, a woven fabric includes a woven or knitted fabric such as woven fabric or the like, and the woven fabric is any kind of material provided for practical use, for example, plain weave, serpentine and runners. ) May be used. In addition, there is no particular limitation on knitted fabrics, and weft knits, warp knits, tricots, round braids, flat braids, and weaving yarns may be used. . Even in the case of using a nonwoven fabric, the packing density (volume density) of the fiber is not particularly limited, and paper may also be used as a conventional paper material (Western paper, Japanese paper) or its antagonist or various miscellaneous paper.

Fibers constituting such non-fibrous and fibrous porous materials are, for example, cellulose fibers, cotton, linter, kapok, flax, hemp, ramie, cupra, acetate , Vinylon, acryl, polyethylene terephthalate (polyester) and chemical fibers such as polypropylene, polyurethane, polyethylene, or a combination of two or more of these natural and chemical fibers may be used. Moreover, although the thickness of these fibers changes with the kind, it is preferable that they are about 0.1-5.0 denier normally. Although the thickness of a base material layer is suitably determined according to the material, etc., Usually, it is preferable that it is about 0.05-1 mm, and it is more preferable that it is about 0.1-0.5 mm.

Hydrogel preparations according to the invention can be prepared, for example, by a method comprising the following steps:

Iii) mixing the surfactant with water (purified water) to produce a homogeneous mixture;

Ii) dissolving and mixing and dispersing the water-soluble polymer with water (purified water) and a moisturizer, and then adding excipients and other additives as necessary to prepare a homogeneous association;

Iii) adding the union of step ii) to the mixture of step iv) to produce a uniform union; And

Iii) applying the laminate on the substrate layer in a conventional manner and then attaching the release coating thereon.

In the above production method, the order of combining the respective drugs, the active ingredients or other components is merely an example and the method of preparing the hydrogel preparation of the present invention is not limited to the above-mentioned formulation procedure.

Hereinafter, the present invention will be described in detail by way of examples, but the scope of the present invention is not limited in any way by these examples.

Examples 1-12:

Water, water soluble polymers, humectants, excipients and other additives were used in the ingredients and amounts shown in Tables 1 and 2 below.

Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Purified water 70 68 57 55 46 46 Sodium polyacrylate 3 5 7 9 5 5 Non-glycerin 25 25 35 34 38 38 Tartaric acid 0.6 0.6 0.2 0.2 0.2 0.2 kaoline 10 gelatin 10 Dry Aluminum Hydroxide Gel 0.4 0.4 0.3 0.3 0.3 0.3 Sodium Edetate 0.4 0.4 0.3 0.3 0.3 0.3 Polyvinyl alcohol Titanium oxide Polyvinylpyrrolidone Polysorbate 80 0.4 0.4 0.2 0.2 0.2 0.2 Aluminum Glycinate Sodium pyrosulfite 0.1

Content Unit: g

Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Purified water 55 50 46 46 46 46 Sodium polyacrylate 6 5 5 5 5 5 Non-glycerin 35 35 38 38 3.8 3.8 Tartaric acid 0.2 0.6 0.2 0.2 0.2 0.2 kaoline 5 gelatin 2.7 3 5 5 5 Dry Aluminum Hydroxide Gel 0.4 0.3 0.3 0.3 0.3 Sodium Edetate 0.4 0.4 0.3 0.3 0.3 0.3 Polyvinyl alcohol 3 10 5 Titanium oxide Polyvinylpyrrolidone 2 5 Polysorbate 80 0.4 0.6 0.2 0.2 0.2 0.2 Aluminum Glycinate 0.3 Sodium pyrosulfite

Content Unit: g

The surfactant was mixed with purified water to prepare a homogeneous mixture. After dissolving and mixing and dispersing the water-soluble polymer with purified water and a moisturizing agent, excipients and other additives were added to prepare a uniform blend. The union was added to the mixture to prepare a uniform union, and the resulting union was applied thinly on a substrate layer (band-aid or bandage) in a conventional manner, and then a peel coating was attached thereto.

Experimental Example:

The color, clarity, elasticity, viscosity and water absorption for 24 hours of the formulations obtained in Examples 1 to 12 were measured, and the results are shown in Table 3 below.

Example number color transparency Elasticity (dynes / ㎠) Viscosity (cps) Water Absorption Rate (24 h) (wt%) One Colorless Transparency 7.65 × 10⁴  320 589 2 Colorless Transparency 6.89 × 10⁴  350 580 3 Colorless Transparency 6.92 × 10⁴  780 480 4 Colorless Transparency 6.59 × 10⁴ 1,050 480 5 White opacity 6.96 × 10⁴ 1,230 390 6 buff opacity 5.43 × 10⁴ 1.130 425 7 buff opacity 5.97 × 10⁴ 1,500 450 8 buff opacity 6.04 × 10⁴ 1,750 220 9 buff opacity 6.40 × 10⁴ 1,430 220 10 buff opacity 5.77 × 10⁴ 1,380 200 11 buff opacity 5.93 × 10⁴ 2,450 195 12 buff opacity 5.46 × 10⁴ 1,950 207

As can be seen from the results shown in Table 3, the hydrogel bandage (bandage) on which the hydrogel of the present invention is deposited rapidly absorbs wound secretions for a considerably long time, and maximizes in a relatively short time in terms of absorption performance. It is far superior to commercially available hydrogels that can absorb water (moisture absorption of commercial hydrogels: 105% by weight). The bandage for trauma in which the hydrogel of the present invention is deposited can be promoted by maintaining the wound in a constantly moist environment in combination with absorbency and high water vapor permeability. In addition, since the hydrogel of the present invention is transparent, the wound healing process can be observed, and in the case of a wound with a small amount of secretion, a trauma bandage (bandage) in which the hydrogel is deposited can be worn at a longer time interval.

The hydrogel formulation of the present invention does not leave any hydrogel, significantly improves wound healing, and in particular, appropriately absorbs wound exudates (secretions), and has excellent hydrogel strength and antibacterial function, resulting in burns, wounds and traumas. It is expected to be useful for wound healing, sterilization, scar prevention and suppression, wound recovery, etc.

Claims (12)

Iii) water; Ii) polyacrylic acid, or a salt or derivative thereof, as a water-soluble polymer; And Iii) polyols as humectants: Hydrogel formulation for wound treatment, containing. The hydrogel formulation of claim 1, comprising polyacrylic acid, or a salt or derivative thereof, alone or in combination with other natural, semisynthetic or synthetic polymers. The hydrogel formulation of claim 2 containing polyacrylic acid, or a salt or derivative thereof alone. The hydrogel formulation according to claim 2, comprising polyacrylic acid, or a salt or derivative thereof, as a combination with gelatin, polyvinyl alcohol, carboxymethyl cellulose sodium or polyvinylpyrrolidone. The hydrogel formulation of claim 1, wherein the humectant is at least one selected from the group consisting of glycerin, propylene glycol, sorbitol, ethylene glycol, diethylene glycol, polyethylene glycol, polypropylene glycol, and 1,3-butylene glycol. The hydrogel formulation of claim 1, wherein the water-soluble polymer is sodium polyacrylate and the moisturizing agent is glycerin. The hydrogel formulation according to claim 1, wherein the weight ratio of water: water soluble polymer: polyol is 10 to 80: 1 to 50: 3 to 60. The hydrogel formulation according to claim 7, wherein the weight ratio of water: water-soluble polymer: polyol is 20 to 70: 3 to 30: 5 to 50. The hydrogel formulation according to claim 8, wherein the weight ratio of water: water-soluble polymer: polyol is 25-65: 5-20: 10-45. The hydrogel formulation of claim 1, further comprising at least one selected from the group consisting of absorption accelerators, excipients, emollients, adjuvants, pH adjusters. The hydrogel formulation of claim 1 for wound healing, sterilization, scar prevention and inhibition, or wound recovery for burns, wounds, traumas, bedsores or skin diseases. The formulation of claim 1, wherein the hydrogel is deposited in a bandage or bandage.