DD272414A5 - METHOD FOR PRODUCING A MEDICAMENT PREPARED FOR WOUND HEALING - Google Patents

Abstract

The invention relates to a process for the preparation of a medicament preparation which promotes wound healing. The preparation prepared according to the invention is locally applicable and contains, besides a suitable carrier, preferably a solid carrier of porous structure, 0.1 to 15% H1 and / or H2 receptor blocker as active ingredient. Preferred carriers are hydrophilic bead polymers suitable for preparing wound-spreading powders, as well as polyurethane sponges. The preparations are prepared according to the invention by preparing a solution from the H1 and / or H2 receptor blockers and treating the carrier with this solution (for example, the polymer is swollen in the solution; a polyurethane sponge or other porous surface is formed with the solution drink of).

Description

Field of application of the invention

The invention relates to a method for producing a wound healing promoting drug preparation, which consists of a suitable for covering the wound carrier and wound-healing additives.

Characteristic dw known prior art

The care of wounds-whether accidental injuries, burns, or intended procedures-is a fundamental part of medicine. For a long time wound healing was limited to the following measures:

- mechanical cleaning of the wound (which never completely succeeds),

- treatment with disinfectants,

- mechanical protection of the wound (dressing).

The healing of the wound also takes a long time, even if the mentioned work is carried out professionally. Wound healing works optimally if all wound healing-influencing conditions are met simultaneously. Among these external and internal factors are the most important ones:

Normal metabolism in the adjacent tissues (adequate blood and oxygen supply),

- keeping the wound clean (removal of pus and the remains of disintegrated tissues),

- Preventing the ingress of microorganisms.

Current wound treatment procedures take these factors into account, but in most cases it is only possible to meet one condition while others are disregarded or even worsened. For example, an ointment containing an antibiotic prevents infection of the wound, but prevents air access. For the healing it is very important that air can get to the wound. To ensure this, numerous solutions have been developed. All have in common that a porous layer is used to cover the wound. As such, simply loosely woven textiles (cotton, fabric, gauze, gauze bandages) as well as a matrix of porous structure made of natural or synthetic materials and combinations of these possibilities come into question. This carrier is then impregnated with materials that accelerate wound healing, for example, disinfectants, preservatives, etc. According to ZA-PS 68/1631, a plaster consisting of acrylic acid / acrylic acid ester copolymer is used according to US Pat. No. 3,932,602 a film of similar composition. From FR-PS 4656 M, a cotton fabric impregnated with cellulose acetate is known, and US Pat. Nos. 4,336,243 and 4,307,717, respectively, describe a silicone polymer and a matrix made of synthetic or artificial rubber.

The wound treatment methods in the classical sense have been revolutionized with the introduction of swellable, crosslinked polysaccharides as wound powder (GB-PS 1454055). The spherical particles having a diameter of 100 to 300 μm in the dry state intensively absorb liquid when they are scattered on the wound; they not only dry out the wound, but also take up pus, tissue remnants and bacteria, whereby the wound is cleaned better than is possible at all by mechanical means (US Pat. No. 4,225,580).

The next step in the quest to increase the wounding efficacy is who, on the beads or platelets of the crosslinked polymer-bearing active ingredients, primarily disinfectant compounds, for example a complex of polyvinylpyrrolidone and iodine (QB-PS 2099704) or sulfursulfadiazln (Symp. Ser 1964, 266, 181-189). These solutions are aimed primarily at ensuring the external conditions of wound healing. It was a further advance when it was recognized that adherence to a particular calcium and potassium ion concentration in the wound and its environment is important. From DE-PS 3416777 is a method Is a method is known, which is already partly directed to the provision of the internal parameters of wound healing: with the help of calcium · and <

Potassium shedding is aimed at increasing the concentration of the calcium and potassium ions to the desired value. Object of the invention

The invention is intended to provide a process for producing a medicament preparation which promotes wound healing particularly strongly.

Explanation of the essence of the invention The invention is based on the object, a the internal and external conditions of wound healing simultaneously and optimally

to develop a satisfying drug preparation.

The invention is based on the finding that the anti-inflammatory Hj receptor leuvers (for Belsp'sl Cimetidln, Ranitidine), applied to a suitable carrier, are excellently suited for topical treatment and wound healing

and dioxygen preparations prepared for this catfish are just as likely to do justice to the internal and external conditions of wound healing.

The wound healing promoting effect of the Hj receptor blocker may be selected from those used in the case of ulcer suppression, respectively

be derived in hard-healing outer wounds expiring pathological processes. In the formation of

Ulcers that essentially begin with chronic inflammatory processes are divided into three phases:

Amine phase (mediators: histamine and H 'substances,

- Klnlnphase (mediator: Bradyklnln),

PG phase (mediators: different PG fractions responsible for the inflammation).

When using the preparation according to the invention dnr: h is the local application of Hj receptor blocker the

The first phase of the repetitive processes, the enlargement and death of the wound, is stopped, the second and third phases are therefore not completed, and the wound heals much faster. The practical significance of local application

HrRezeptorblockern is that they suppress the symptoms resulting from secondary processes, their often

make very long-lasting healing superfluous, let the injury or the wound caused by other circumstances heal quickly and undisturbed.

The development of the drug preparation suitable for topical application of the Hj receptor blockers has become large Careful attention to the selection of the carrier, which should be such that it meets the external requirements of the Wound healing is largely fair, but the healthy tissue located near the wound is not superfluous

be filled with active ingredient.

In choosing the carrier, experimentation was made with liquid, pasty and fast carriers. Seemed most suitable

those carriers, in particular solid carriers, which due to their absorbency not only clean the wound, but also the

Prevent edema formation. For these reasons ' And the swellable, hydrophilic polymers based on crosslinked polysaccharides (for example with Epichlorohydrin-dense dextran or cyclodextrin bead polymers) are particularly suitable. However, there are also carriers

which are absorbent and at the same time porous; these do not seal the wound airtight. Prepared with cimetidine

Wound covers based on absorbent plastic foam and with gauze have achieved good results. It has also been found that, due to their beneficial physiological effects, H! Receptor blockers such as Dimetindenmaleate, tripelenamine, phenindamine, etc. can be used as the active ingredient. These substances reduce the Capillary permeability, inhibit the enzyme hyaluronidase and thereby moderate the weeping inflammations. According to the invention, suitable, porous, absorbent / carrier carriers are thus suitable for covering wounds

a 0.1 to 30% solution of H _r and / or Hj receptor blockers (antihistamines), then dried and finally sterilized.

Cimetidine is preferably used as the active ingredient, advantageously in the form of a 0.1 to 30% active ingredient

aqueous-alcoholic or aqueous solution. Instead of cimetidine or with this together can also be more cytoprotective

Substances to which the H ₂ receptor blockers ranitin, famotidine, burinamide or metiamide are used. According to a preferred embodiment of the invention, the wound healing preparation is prepared as follows: Hydrophilic polymer particles suitable as wound powder, for example polymer beads of eplchlorohydrin crosslinked dextran,

are swollen in the cimetidine-containing solution, they take from the preferably 0.1 to 10% solution

Active ingredient and are then dried at temperatures below SO ⁰ C and sterilized. In testing a 0.1 to 2.0% cimetidine-containing dextran bead polymer wound-spreading powder, it was found that

an effect enhancement, a synergism occurs because the duration of wound healing is significantly shortened by several days.

Other hydrophilic polymers, for example cellulose derivatives, alginates, are also used as carrier material for wound scattering powders. Cyclodextrin, etc. in question. The solid carrier may also be prepared by dampening the polymer particles swollen in the drug solution

Apply the gauze and dry to a certain moisture content. Another possibility is to have one for

Wound covering suitable polyurethane surface with a solution containing 6 to 30% active substance so long to drink through, until

has absorbed the surface per dm'10 to 200mg of active ingredient, then the flies at temperatures below 25 ⁰ C dries and In

Pieces of appropriate size intersect. The preparation can also be produced in the form of an egg. As the carrier, for example, an acrylic acid polymer

be swollen, which is swollen in a solution of p-hydroxybenzate acid methyl ester and then by addition of

(Which may be about 6 to 30% · lg) sodium hydroxide solution is at a local pr QEi Λ. The drug-containing solution is with this gel

mixed, after homogenization, the mass is filled into tubes.

The preparation may contain further additives, for example active substances important for wound healing, such as water or

contain fat-soluble chlorophyll or hexachlorofen.

AusfOhrungsbalsplele The invention will be explained in more detail with reference to the following examples, but is not limited to these examples. example 1

100 g of bead polymer (dechlorinated dechlorotrene, particle size: 120 to 320 pm) are soaked in a solution of 12 g of Clmidium in 600 ml of water whose pH had previously been adjusted to 2 with hydrochloric acid. Then the swollen to three to four times its original volume polymer is filtered off, re-suspended in 300 ml of 0.01 M sodium hydroxide solution, filtered again and then washed with 600 ml of ethanol anhydrous. The alcohol treatment is repeated twice more. Then the anhydrous polymer is dried at temperatures below SO ⁰ C and filled into shaker cans. For sterilization, a radiation dose of 20 kGy (Co ^M -sotop) or Freon gas can be used. The powder contains 0.15 to 0.2% cimetldin.

Example 2

100 g of bead polymer (dextran crosslinked with epochlorohydrin, particle size 120 to 320 μm) are moistened with 100 ml of 96% ethanol and then thoroughly impregnated with the solution of 10 g of dichloromethane in 250 ml of 96% ethyl alcohol. The moist polymer is dried at temperatures below 60 ⁰ C, care being taken that the loss on drying is not more than 8%. The powder is placed in shaker cans and sterilized using a Co ^M radiation source at a dose of 2OkGy. The powder contains 0.92% dimethytic maleate.

Example 3

1000 g of bead polymer (dextran crosslinked with epichlorohydrin, particle size 40 to 120 μm) are moistened with 100 ml of 96% ethanol and then uniformly saturated with a solution of 20 g of thenalidine in 300 ml of 96% ethanol. The wet polymer is dried at temperatures below 5O ⁰ C, taking care to ensure that the loss on drying is not greater than 8%. The dry powder is filled into bags of filter paper, welded between aluminum foils and sterilized in the manner described in Example 1. The product contains 1.85% thenalidin.

Example 4

1000 g bead polymer (epichlorohydrin crosslinked dextran, particle size 120 to 320 pm) are mixed with 100 ml of 96% ethanol

moistened and then uniformly with a solution of 5g Ranitidln in 200ml 96% ethanol durchträr '<t.

The polymer is dried at temperatures below 25 ⁰ C, wherein the drying loss may not be more than 8%. The Powder is filled in shaker cans and sterilized in the manner described in Example 2. If the whole manufacturing under

aseptic conditions, sterilization is not required. The powder contains 0.4% ranitidine.

example

Perl polymer consisting of epichlorohydrin crosslinked ¹ dextrin with a particle size of 40 to 120 pm is processed according to Example 4 into wound scattering powder. The dried product is filled into filter paper bags and these are welded between aluminum foils. The Piodukt is sterilized by radioactive irradiation, or the entire production takes place under aseptic conditions.

Examples A polyurethane sponge towel used to cover wounds is prepared with a 5% ethanol, 96% ethanol Cimetidine solution soaked. Then, the sponge cloth at temperatures below 4O ⁰ C and is dried in suitable pieces Size cut. Sterilization is with radioactive radiation or with ethylene oxide. The product contains 25mg per dm ²

Cimetidine.

Example 7

In the manner described in Example 6 is soaked with 10% Cimetidinlösung a Molinotuch. The material is cut into suitable pieces and used for the production of fast-adhesive adhesive plasters. The product contains per dm ¹ 50 mg of active ingredient.

Examples

5 g of acrylic acid polymer are swollen in a sterile environment in 600 g of sterile distilled water containing 1.6 g of p-hydroxybenzoic acid methyl ester. With the addition of 6 g of 30% sodium hydroxide solution, the polymer is stirred to a homogeneous QeI. To the QeI is added a solution of 300 g of sterile distilled water, acidified with hydrochloric acid, of 1 g of methylene chloride. Then the gel is diluted to 1000g of sterile distilled water. The QeI is packaged in tubun. The QeI contains 0.1% cimetldin.

example

1 g of water-soluble chlorophyll is homogenized with 908 g of pearl polymer (crosslinked with epichlorohydrin Destran, particle size 120 to 320pm). The mixture is then treated with a solution of 6 g of methylene chloride in 200 ml of 96% ethanol and stirred at room temperature for 2 hours. By stirring at temperatures below 6O ⁰ C is there? Product dried. It is filled into shaker cans and sterilized with a gamma radiation dose of 2OkQy. The powder contains 0.6% Clmetldln.

Example 10

2.5g of liposoluble chlorophyll were homogenized with a melt of 268.6g macrogol 400.20g macrogol 1640 and 29g polysorbate 80. The melt is cooled to 30 ° C. In the melt, 660 g of bead polymer (crosslinked with epichlorohydrin

Dextran, particle size 40 to 120mm). The bead polymer was previously in the manner described in Example 1 with 20g Cimetidone has been saturated. The raw paste is filled in portions of 10g in polyethylene-laminated aluminum foil bags and by a Gamma radiation dose of 2OkQy sterilized. The product contains 1.98% cimetidine.

Claims (8)

1. A process for the preparation of a wound healing promoting drug preparation using a suitable carrier, characterized in that the carrier, preferably a solid support of porous structure, with a 0.1 to 30, preferably 0.1 to 5.0% solution of H ₁ * and / or Hj receptor blockers (antihistamine) are treated, then dried and finally sterilized. 2. The method according to claim 1, characterized in that the solution is prepared with water or ethanol. 3. The method according to claim 1, characterized in that cimetidine or ranitidine is used as the active ingredient. 4. The method according to any one of claims 1 to 3, characterized in that the carrier is a suitable for the preparation of wound dispersing hydrophilic polymer, preferably crosslinked with epichlorohydrin! Dextran existing bead polymer, or cyclodextrin is used. 5. The method according to any one of claims 1 to 4, characterized in that the polymer is swollen in the 0.1 to 10% solution of the active ingredient. 6. The method according to any one of claims 1 to 5, characterized in that a polyurethane sponge cloth or a Molinotuch is used as the solid support. 7. The method according to claim 6, characterized in that the solid carrier is impregnated with the 5 * to 10% solution of the active ingredient. 8. The method according to claim 6 or 7, characterized in that 10 to 200 mg of active ingredient are used on 1 dm ² support surface.