CZ295826B6 - Wound covering material containing radical traps - Google Patents

Abstract

In the present invention, there is disclosed a material for wound covers, consisting of a polymer carrier based on lightly crosslinked hydrophilic polymers or copolymers formed from one or more monomers, a crosslinking agent and a physiological biologically active substance with radical scavenger properties wherein the monomers are selected from the group consisting of 2-hydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, poly(ethylene glycol methacrylate), glycerol methacrylate, alkyl methacrylates, acrylic or methacrylic acid and salts thereof. The crosslinking agents are represented by diacrylate or dimethacrylate esters (preferably ethylene dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate) in amounts up to 5 percent by weight in a polymerization mixture. A physiological biologically active substance with radical scavenging properties is selected from the group consisting of vitamins A, carotenoids, vitamins E, ubiquinones, flavonoids, nicotinamide, uric acid, bilirubin, lipoic acid, glutathione, and melatonin.

Description

Technical field

The present invention relates to a wound dressing material comprising radical scavengers and a method for preparation.

BACKGROUND OF THE INVENTION

A number of hydrophilic wound dressing materials are known, based on the hydrophilicity of alginates (Sorbalgon®, Hartmann-Rico), polyurethanes (Cutifilm, Biersdorf AG), cellulose derivatives (Comfeel®, Coloplast), polyvinylpyrrolidone (Aquagel) , Production and Trade Establishment of PPH KIK (VZP Code Lists, Medical Devices, Version 370, Prague 2001), which creates a moist environment on the wound that promotes healing while preventing infection from entering the wound from the outside. Some of them, especially alginate-based materials, have the ability to absorb a significant amount of wound exudate.

It is known that in the healing process, a large number of different free radicals known under the designation RONS (reactive oxygen and nitrogen species) are produced at the site of injury by a physiological process, which serve to disinfect the wound. However, the production of radicals is often redundant and radicals, in addition to foreign microorganisms, also destroy the body's own cells. This process is particularly evident in chronic inflammation, where the production of free radicals prevents wound healing. (Štípek S., Antioxidants and free radicals in health and illness, Grada Publishing, Prague 2000).

It is also known that sterically protected amines chemically coupled to a polymeric carrier promote wound healing by inactivating RONS (Vaccine J., Labsky J., CZ PV 1997-3867, A composition for preventing and healing inflammatory diseases).

SUMMARY OF THE INVENTION

SUMMARY OF THE INVENTION The present invention provides a wound dressing comprising radical scavengers comprising a polymeric carrier based on sparsely crosslinked hydrophilic polymers or copolymers that form one or more monomers and a crosslinker, and physiologically biologically active scavenger properties. radicals selected from the group of vitamins A, carotenoids, vitamins E, ubiquinones, flavonides, nicotinamide, uric acid, bilirubin, lipoic acid, glutathione, melatonin.

It is a further object of the present invention that the hydrophilic polymers and copolymers consist of monomers selected from the group consisting of 2-hydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, polyethylene glycol methacrylate, glycerine methacrylate, alkyl methacrylates, methacrylate and methacrylic acid, wt. % networked.

Diesters of acrylic acid or methacrylic acid, preferably ethylene dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, are used as crosslinkers.

It is a further feature of the invention that the polymeric carrier is in the form of a resilient film, powder, or gel with a dispersed or dissolved substance having a radical scavenger property in an amount of 0.0001 to 50% by weight.

The unique feature of the wound dressing material according to the invention is that it consists of known, long-term clinically tested components, which, in combination with the present invention, exhibit advantageous properties which have not been used in the prior art.

The wound dressing material according to the invention may take a different form according to the method of preparation, each of which is suitable for a different type of wound. The elastic films are prepared by block polymerization or polymerization in the presence of a solvent and a radical scavenger. In block polymerization, the radical scavenger is introduced into the film by swelling in a solvent with the dissolved scavenger. The solvent acts as a plasticizer in the film and allows it to adhere well to the wound. The film protects the wound from external contamination, ensures a humid environment and deactivates radicals. It is easy and painless to remove from wounds.

The wound dressing material according to the invention in powder form is prepared by precipitation polymerization. The radical scavenger is dissolved in a suspension of powder in solvent and the solvent is then evaporated. The powder performs the same function as the foil, in addition to absorbing wound exudate up to several times its original weight. The swollen powder is easily separated from the wound as a gel. If the material contains methacrylic acid or its salts, it also acts as an ion exchanger. A change in the ionic environment in the wound affects their healing (Resl V., Healing of Chronic Wounds, Grada Publishing, Prague 1997).

The wound dressing material according to the invention in the form of a gel is obtained in a powder prepared by precipitation polymerization by mixing with a thermodynamically good solvent and a radical scavenger, optionally with the addition of an emulsifier. In particular, poly (ethylene oxides) of different molecular weights and aqueous solutions thereof can be used as solvents. The gel has an excellent ability to adhere to the wound even in skin folds where application of the film is not suitable. This dosage form is very advantageous for veterinary use.

The effect of the wound dressing material according to the invention lies in the synergistic effect of wet wound dressing and the ability to deactivate RONS in all dosage forms. The wounds treated with the material according to the invention heal without complications, without secondary infections and successfully undergo epithelization.

The wound dressing material according to the invention is suitable for use in traumatic, surgical and chronic wounds. Depending on the exudation intensity, a powder for a thick, wicking wound and a foil or gel for a wound with a weak wound are used. The effect of the wound dressing material can be enhanced by the addition of other additives, in particular antimicrobial agents such as antibiotics, corticoids or disinfectants.

All forms of wound dressing can be sterilized by any of the known methods. Gamma sterilization is suitable for the powder, and steam autoclave thermal sterilization for the gel and foil.

The invention is illustrated by the following examples. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

DETAILED DESCRIPTION OF THE INVENTION

All percentages and ratios given in the examples are by weight.

Example 1

A mixture of 5.00 g of 2-hydroxyethyl methacrylate, 0.10 g of ethylene dimethacrylate, 0.050 g of benzoin ethyl ether, 4.83 g of polyethylene glycol 300 and 0.10 g of retinol acetate was stirred for 10 min. After briefly purging with nitrogen, the polymerization mixture was transferred to a polymerization apparatus consisting of two parallel polypropylene sheets of 120x120x1 mm,

-2GB 295826 B6 separated by a 0.08 mm spacer. The polymerization apparatus was placed under a UV light source for 0.5 hours. The resulting film was swollen in distilled water, then swelled in an emulsion of 47.5% distilled water, 48% polyethylene glycol 300, 4% tocopheryl acetate and 0.5% Polysorbate 80 surfactant. The film dimensions were adjusted to 10x10 cm, the film was sealed into polypropylene-coated aluminum foil and sterilized by steam sterilization for 20 min at 121 ° C.

Example 2

A mixture of 4.95 g of 2-hydroxyethyl methacrylate, 0.10 g of ethylenedimethacrylate, 2.97 g of polyethylene glycol 300, 1.98 g of distilled water, 0.40 g of tocopheryl acetate and 0.05 g of benzoin ethyl ether was stirred until all components were dissolved and then polymerized by the method. as described in Example 1. A homogeneous opaque elastic film having an elongation of 250% was obtained. The film was wrapped and sterilized as described in Example 1.

Example 3

A mixture of 2.76 g of 2-hydroxyethyl methacrylate, 1.18 g of 2,3-dihydroxypropyl methacrylate, 0.05 g of ethylenedimethacrylate, 1.00 g of glycerine, 0.025 g of Darocure 1173 photoinitiator and 0.05 g of β-carotene was mixed until all components were dissolved. and then polymerized as described in Example 1. A homogeneous yellowish flexible film was obtained, which was wrapped and sterilized as described in Example 1.

Example 4

9.90 g of 2-hydroxyethyl methacrylate, 0.10 g of ethylenedimethacrylate and 0.10 g of azobisisobutyronitrile were dissolved in a reaction vessel in 100 g of toluene. After briefly purging with nitrogen, the reaction mixture was heated to 80 ° C with stirring for 120 minutes. The product was then filtered, washed 3x with a small amount of toluene and 1x with a small amount of n-hexane and air dried for 48 hours. It was then further dried at 5 Pa at room temperature for 4 hours. The residual toluene content was 0.009%. The product, 9.40 g, was mixed with 30 g of a 1.5% tocopheryl acetate solution in petroleum ether. The petroleum ether was evaporated in air and the product further dried at 5 Pa at room temperature for 4 hours. The resulting product, a white fluffy and free-flowing powder, was packaged in 2.5 g polyethylene vials and then sterilized by gamma irradiation at a dose of 24 kGy.

At equilibrium swelling, the powder absorbed 1.15 g of saline at pH = 7.3 per 1 g of dry matter.

Example 5

In the manner described in Example 4, a powdered polymer was prepared from a solution of 9.40 g of 2-hydroxyethyl methacrylate, 0.10 g of ethylenedimethacrylate, 0.50 g of sodium methacrylate and 0.10 g of azo-bisisobutyronitrile in 100 g of toluene. in Example 4. At equilibrium swelling, the powder absorbed 3.2 g of saline solution at pH = 7.3 per 1 g of dry matter.

-3GB 295826 B6

Example 6

By the method described in Example 4, a powdered polymer was prepared from a solution of 9.40 g of 2-hydroxyethyl methacrylate, 0.10 g of ethylenedimethacrylate, 0.20 g of methacrylic acid, 0.10 g of azo-bisisobutyronitrile in 100 g of toluene. in Example 4. At equilibrium swelling, the powder absorbed 1.0 g of saline at pH = 7.3 per 1 g of dry matter.

Example 7

To 50 g of an emulsion prepared from 24.5 g of distilled water, 25.0 g of polyethylene glycol 300, 0.4 g of tocopheryl acetate and 0.10 g of Polysorbate 80 were gradually mixed 10.0 g of the powdered polymer prepared as described in Example 4. The mixture was allowed to form for 24 hours until a homogeneous opalescent gel is formed. The gel was filled into glass vials of 15 g and polypropylene blisters of 2.0 g and sterilized in a steam autoclave for 20 min at 121 ° C.

Example 8

To 50 g of an emulsion prepared from 24.5 g of distilled water, 25.0 g of polyethylene glycol 300, 0.4 g of retinol acetate and 0.10 g of Polysorbate 80 were successively blended 10.0 g of the powdered polymer prepared as described in Example 4. The mixture was allowed to form for 24 hours until a homogeneous opalescent gel is formed. The gel was filled into glass vials of 15 g and polypropylene blisters of 2.0 g and sterilized in a steam autoclave for 20 min at 121 ° C.

Example 9

A mixture of 6.92 g of 2-hydroxyethyl methacrylate, 2.96 g of 2,3-dihydroxypropyl methacrylate, 0.12 g of ethylenedimethacrylate, 2.00 g of anhydrous glycerin, 0.10 g of retinol acetate and 0.50 g of benzoin ethyl ether was stirred for 10 minutes and then polymerized. as described in Example 1. A homogeneous yellowish flexible film was obtained, which was wrapped and sterilized as described in Example 1. The film absorbed 52% of water.

Example 10

A mixture of 9.5 g of 2-hydroxyethyl methacrylate, 0.4 g of ethyl methacrylate, 0.1 g of triethylene glycol dimethacrylate, 2.00 g of anhydrous glycerin, 0.10 g of retinol acetate and 0.50 g of benzoin ethyl ether was stirred for 10 minutes and then polymerized as described in the example. A film was obtained which was wrapped and sterilized as described in Example 1. The film absorbed 38% water.

Example 11

By the method described in Example 4, a powdered polymer was prepared from a solution of 4.90 g of 2-hydroxyethyl methacrylate, 5.00 g of 2,3-dihydroxypropyl methacrylate, 0.10 g of ethylenedimethacrylate, 0.10 g of azo-bisisobutyronitrile in 100 g of toluene. At the equilibrium swelling, the powder absorbed 1.5 g of saline at pH = 7.3 per 1 g of dry matter.

-4GB 295826 B6

Example 12

To the solution prepared by mixing 25.0 g of a 0.4% aqueous solution of amoxicillin and 25.0 g of polyethylene glycol 300, 10.0 g of a powdered polymer prepared as described in Example 4 was sequentially mixed. The gel was filled into glass vials of 15 g and polypropylene blisters of 2.0 g.

Example 13

0.2 g of sodium hydroxide and 0.2 g of uric acid were successively dissolved in 24.6 g of distilled water, and 25.0 g of polyethylene glycol 300 was added. 10.0 g of powdered solution were gradually added to the resulting solution of pH = 8.1. of a polymer prepared as described in the Example

4. The mixture was left for 24 hours until a homogeneous opalescent gel was formed. The gel was filled into 15 g glass vials and polypropylene blisters of 2.0 g and sterilized in a steam autoclave for 20 min at 121 ° C.

Example 14

The powder prepared according to Example 6 was treated with a market-bruised wound on the ear lobe of a three-year-old cat after previous wound cleansing and rinsing with saline and shotapen injection. The powder was applied three times at 24-hour intervals, then the gel prepared as described in Example 8 was applied twice. A week after initiation of treatment, the wound was healed with a small central plaque of clean granulation tissue.

Example 15

The gel prepared according to Example 8 was treated with a forearm and autopodium wound of the anterior left limb with profound alterations of the periosteum and articular capsule of a six-month-old German shepherd after previous wound cleansing, rinsing with hydrogen peroxide, saline and general repair. The gel was applied twice at 24-hour intervals, the next dressing was after 48 hours. On the fifth day after initiation of treatment, the wound was free of inflammation with pure granulations. Three weeks after the start of treatment, the wound healed with scar, palpable without pain, the dog normally burdened the limb.

Claims (5)

Claims 1. A wound dressing comprising radical scavengers comprising a polymeric carrier based on sparsely crosslinked hydrophilic polymers or copolymers and a physiologically biologically active substance having radical scavenger properties selected from the group of vitamins A, carotenoids, vitamins E, ubiquinones, flavonides , nicotinamide, uric acid, bilirubin, lipoic acid, glutathiol and melatonin. 2. The wound dressing material of claim 1, wherein the hydrophilic polymers or copolymers are monomers selected from the group consisting of 2-hydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, polyethylene glycol methacrylate, glycerine methacrylate, alkyl methacrylate, alkyl methacrylate, alkyl methacrylate. % dihydroxypropyl methacrylate, acrylic acid and methacrylic acid, and salts thereof; Wound dressing material according to claims 1 and 2, characterized in that the crosslinking is diesters of acrylic or methacrylic acid, preferably ethylene dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate. The wound dressing material of claims 1-3, wherein the polymeric carrier in the form of a resilient film, powder, or gel comprises a dispersed or dissolved substance having a radical scavenger property in an amount of 0.0001 to 50% by weight. Wound dressing material according to claims 1 to 4, characterized in that the polymeric carrier, in addition to the radical scavenger, contains one or more substances selected from the group of disinfectants, antibiotics or corticoids.