WO2003026710A1

WO2003026710A1 - Mixture for use as a protective dressing

Info

Publication number: WO2003026710A1
Application number: PCT/IB2002/003974
Authority: WO
Inventors: Mark Hite
Original assignee: Mbs Multination Business Services (M.E.) Ltd.
Priority date: 2001-09-26
Filing date: 2002-09-26
Publication date: 2003-04-03
Also published as: EP1429815A1

Abstract

A novel mixture for use in combination with a protective dressing for the topical treatment of bleeding wounds, in particular minor or mild bleeding wounds, comprises: a pharmaceutically efficacious amount of an anesthetic being preferably either benzocaine or pramoxine hydrochloride; a pharmaceutically efficacious amount one of an antibiotic composition comprising preferably polymyxin B or neomycin or bacitracin or a combination of these components, and an antiseptic composition; at least a pharmaceutically efficacious amount of a hemostatic compound. The mixture can be incorporated in a liquid spray comprising film forming components and at least a solvent, in which the aforesaid pharmaceutically components are dispersed or solubilized. The liquid mixture forms a film adhering to and covering the wound when sprayed onto it. In its final rule, FDA listed these antibiotic active ingredients as safe and effective: --the latter two only for combination products because of their limited effectiveness against certain microorganisms when used alone, prevent neomycin overuse, FDA limits the drug to ointments and creams, the most likely dosage forms for small wounds. Also, all OTC antimicrobials must be labeled for short-term use. Five ingredients listed as tentatively effective only in combination products are ethyl alcohol (26.9 percent), eucalyptol, menthol, methyl salicylate, and thymol.

Description

Mixture for use as a protective Dressing

The present invention relates to a protective dressing composition or mixture for treating bleeding wounds, in particular minor or mild bleeding wounds, on human beings or animals.

US 5,618,515 (Singh) discloses an aerosol spray composition for the treatment of dermal burns by cooling and anesthetizing the wound. The composition comprises among other ingredients anesthetics, water and alcohol in combination with dimethyl ether. The highly volatile dimethyl ether cools the burns, when applied to the skin, and thereby improves the healing of the burns. US 5,618,515 proposes to use as active ingredients anesthetics, antibiotics and anti-inflammatory drugs. Examples of these drugs include anesthetics like benzocaine, lidocaine and dibucaine and antibiotics like polymyxin B and bacitracin. The proposed spray is exclusively designed for the treatment of burns.

DE-A-31 33 909 discloses a spray comprising a new hemostatic compound being 2- aminoheptane-monoacetate. The spray further comprises film forming compounds for generating a porous film when applied to the skin. The ingredient hexachlorophen (2,2-dimethylen-bis(3,4,6-trichlorphenol) acts as a disinfectant. Hexachlorophen is a chlorinated hydrocarbon and is highly toxic in high doses.

Object of the present invention is to provide a protective dressing, in particular in the form of an easy-to-apply spray, dressing composition, or bandage or plaster impregnated with the composition, for the treatment of bleeding wounds. Another object is to provide a dressing spray or bandage which is efficacious and can be applied by the general population. A still further object is to provide a spray or impregnated bandage which may be sold over the counter.

According to the invention these and other objects are achieved by a liquid mixture for use in combination with a protective dressing or bandage comprising a pharmaceutically efficacious amount of an anesthetic being preferably either benzocaine or pramoxine hydrochloride or a combination of these compounds; a pharmaceutically efficacious amount of one of an antibiotic composition comprising preferably one of polymyxin B and neomycin and bacitracin or a combination of two or all of these compounds and an antiseptic composition; at least a pharmaceutically efficacious amount of a hemostatic compound. The above novel mixture is particularly efficacious for the treatment of minor bleeding wounds. The inventive mixture has the advantage that pain is alleviated, infections by bacteria prevented and bleeding stopped. In addition, the wound is protected from the environment by the protective dressing. The mixture or composition preferably comprises an antiseptic composition instead of an antibiotic composition. Antiseptic compounds are nowadays preferred to antibiotics as the vast use of antibiotics may lead to resistant bacteria. Consequently, there is a concerted effort to reduce the number of antibiotics in the environment. In contrast to the spray disclosed in US 5,618,515 the inventive composition is specifically designed for the treatment of bleeding wounds or cuts. For this effect it contains at least one hemostatic compound for stopping bleeding. Stopping bleeding is of importance, as otherwise the composition applied to the wound would not adhere to the skin.

Examples of acceptable antibiotics, which can be contained in the mixture are: bacitracin zinc, chlortetracyclrne hydrochloride, tetracycline hydrochloride, neomycin sulfate, oxytetracycline hydrochloride, and polymyxin B sulfate. Nonetheless, due to their effectiveness one of polymyxin B and neomycin and bacitracin are the preferred components of the inventive mixture.

Advantageously, the protective dressing comprises film f orrning components spread with the mixture, or a film, like a cloth or plastic. The protective dressing can be a plaster onto which the inventive mixture is applied or which is impregnated therewith. According to a preferred embodiment the protective dressing is a liquid spray comprising film forming components and at least a solvent, in which the aforesaid pharmaceutically components are dispersed or solubilized, the spray forming a film adhering to and covering the wound when sprayed onto it. The protective dressing spray is easy to handle and to apply on a bleeding wound.

An advantage of the inventive mixture is that it can be sold over-the-counter as the components contained in the mixture are approved for over-the-counter use. Film forming agents can be known polymeric materials such as polymethacrylate, polyacrylate, polyacrylic acid, polymethacrylic acid, polyvinylpyrrolidone, cellulose derivatives like cellulose acetate, hydroxyethyl cellulose, polyurethance, polyvinylacetate, polyvinylalcohol, and the like. In order to make the film porous or permeable to air, further compounds or fillers may be included in the mixture, like polybutylphthalate, glycol and derivatives thereof, dialkylphthalate and the like. In addition, softeners, plasticisers etc. can also be contained in the mixture.

Preferred anesthetics incorporated in the mixture belong to the "caine" family like benzocaine, lidocaine and dibucaine. These anesthetics can be present alone or in combination with one another. Preferably, Benzocaine is used and is present in a concentration between 10% and 30% (w/v), preferably between 15% and 25% (w/v), and most preferably at about 20 % (w/v). The aforementioned concentrations alleviate pain very effectively. Alternatively, instead of benzocaine, pramoxine hydrochloride may be used. Pramoxine hydrochloride may be present in the range between 1 and 25 mg/ml, preferably between 5 and 15 mg, and most preferably between 8 and 12 mg/ l liquid mixture.

Preferably the antibiotic neomycin is present in the mixture in a concentration between 0.5 and lOmg neomycin, preferably between 2 and 5 mg neomycin, and most preferably between 3 and 4 mg neomycin per 1 ml liquid mixture. These concentrations have proved to be very efficacious. Alternatively, between 5O00 and 15O00 units of polymyxin, preferably between 8000 and 12000, and most preferably about lO'OOO units of polymyxin B in 1 ml can be used in the liquid mixture as the antibiotic. However, the best results are achieved if a combination of at least two of the antibiotics mentioned in claim 1 are used. Preferably, neomycin and polymyxin B are used in the mixture as they have a synergistic effect when used together.

The anesthetic compound, the antibiotics or antiseptics, are most preferably solubilized or dispersed in styptic collodion in case the protective dressing is in the form of a spray. Styptic collodion is e.g. described in the Merck Index, An Encyclopedia of chemical drugs, and biologicals, 12^th edition, 1996. The aforementioned disclosure is herewith incorporated by way of reference. Styptic collodion has the advantage that it contains film forming components and also hemostatic components. Styptic collodion is particularly advantageous as this dressing has already been widely used in the past with few adverse effects associated with its use. It further does not occlude the injury completely as the film formed from it has microscopic holes. Styptic collodion can be comprised as a mixture of flexible collodion with about 10 to 20% tannic acid by wt, preferably about 18% tannic acid by wt.

Preferably, Styptic collodion comprises nitrocellulose, camphor, caster oil, tannic acid, and at least a solvent. The solvent may be ether or ethanol or a combination of them. Other readily evaporable solvents may also be used. If a mixture of ether and ethanol is used, they may be present in a ratio between 1:1 to 4:1. In such a solvent mixture the active pharmaceutical components used in the mixture are readily solubilized. Further, ethanol can act as an entiseptic.

If the protective dressing comprises a film, like a cloth or plastic, spread or impregnated with the inventive mixture, then the hemostatic compound is preferably one of alum or tannic acid. The latter compounds have been found particularly efficacious when used in combination with a cloth or plastic spread with a solubilized polymer.

Preferably the antiseptic composition comprises one of benzalkonium chloride and benzethonium chloride and hexylresorcinols and mehtylbenzethonium or a combination of two or more of the aforementioned compounds. The use of one or several antiseptic compounds in the protective dressing instead of an antibiotic or antibiotic mixture is preferred as there is no risk that resistant strains of bacteria could result from the use of the inventive composition, even if the composition is used over an extended period of time.

Although it is conceivable that a combination of two or more of the aforementioned compounds are used, preferably only one antiseptic agent would be used in the composition, the concentration/ dose for each would preferably be as follows:

benzalkonium chloride between 0.003% and 0.1%, preferably 0.01% per wt. benzethonium chloride between 0.01 and 1 mg, preferably 0.1 mg per 1 ml solution hexylresorcinol between 0.05 and 20 mg, preferably 2-4 mg per 1 ml solution.

Antiseptics are defined as compounds that weaken mibrobes, but don't usually kill them. Examples of antiseptics that may well be used in the composition are: Ethyl alcohol (48 to 95 percent), benzalkonium chloride, benzethonium chloride, camphorated metacresol, camphorated phenol, phenol, hexylresorcinol, hydrogen peroxide solution, iodine tincture, iodine topical solution, povidone-iodine, isopropyl alcohol, and methylbenzethonium.

Subject of the present invention is also the use of a pharmaceutically efficacious amount of an anesthetic being either benzocaine or pramoxine hydrochloride or a combination of these compounds; - a pharmaceutically efficacious amount one of an antibiotic composition comprising one of polymyxin B and neomycin and bacitracin or a combination of two or more of these compounds and an antiseptic composition; at least a pharmaceutically efficacious amount of a hemostatic compound for the manufacture of a protective dressing for the treatment of bleeding wounds, in particular for the first aid treatment of minor or mild bleeding wounds. Surprisingly, so far nobody has proposed a composition for the first aid treatment of minor bleeding wounds, which comprises in combination a pharmaceutically efficacious amount of an anesthetic, a pharmaceutically efficacious amount an antibiotic composition or an antiseptic composition, and hemostatic compound. The novel use of such a combination provides an efficacious mixture for treating bleeding wounds. As the ingredients of the mixture are readily available and can, generally, be obtained without prescription, the mixture can be sold over-the-counter.

Preferably, said anesthetic compounds, antibiotic or antiseptic compounds, and hemostatic compounds are used for the manufacture of a liquid spray comprising film forming components and at least a solvent, in which the aforesaid pharmaceutically components are dispersed or solubilized. A spray has the advantage that it can readily be applied to the skin. In addition, due to the presence of at least one polymeric film forming material a film permeable to air will be formed on the skin when the volatile solvent evaporates.

Further subjects of the present invention is a bandage or plaster sprayed or impregnated with a mixture. Still further a liquid mixture comprising a combination of anesthetic, antibiotic or antiseptic, and hemostatic compounds, and a dispersed film forming polymeric material is claimed. Said Hquid mixture can be used as ready-to apply dressing spray.

The novel mixture is specifically designed the topical treatment of bleeding wounds, in particular minor or mild bleeding wounds of human beings or animals (pets, cats, dogs). The mixture can be provided in the form of ointments or creams. Most preferably the mixture is dissolved in a suitable, easy to evaporate solvent, which comprises also film forming polymeric materials so that the Hquid mixture can be sprayed onto the wound to form a protective dressing or barrier coating to the environment.

Claims

1. Mixture or composition for use in combination with a protective dressing for the treatment of bleeding wounds, in particular minor or mild bleeding wounds, comprising - a pharmaceuticaUy efficacious amount of an anesthetic being preferably either benzocaine or pramoxine hydrochloride or a combination of these compounds; a pharmaceuticaUy efficacious amount one of an antibiotic composition comprising preferably one of polymyxin B and neomycin and bacitracin or a combination of two or more of these compounds and an antiseptic composition; - at least a pharmaceutically efficacious amount of a hemostatic compound.

2. Mixture according to claim 1 wherein the protective dressing comprises a film, like a cloth or plastic, spread with the mixture of claim 1.

3. Mixture according to claim 1 wherein the protective dressing is a liquid spray comprising film forming components and at least a solvent, in which the aforesaid pharmaceutically components are dispersed or solubiHzed, the spray forming a film adhering to and covering the wound when sprayed onto it.

4. Mixture according to claim 1 wherein Benzocaine is present in a concentration between 10% and 30% (w/v), preferably between 15% and 25% (w/v), and most preferably at about 20 % (w/v).

5. Mixture according to claim 3 wherein the hemostatic compound and the film forming components are styptic collodion.

6. Mixture according to claim 5 wherein the styptic coUodion comprises nitroceUulose, camphor, caster oil, tannic acid, and at least a solvent.

7. Mixture according to claim 6 wherein the solvent is a mixture of solvents comprising ether and ethanol.

8. Mixture according to claim 7 wherein ether and ethanol are present in a ratio between 1:1 to 4:1.

9. Mixture according to claim 1 wherein pramoxine hydrochloride is present in the range between 1 and 25 mg/ml, preferably between 5 and 15 mg, and most preferably between 8 and 12 mg/ml.

10. Mixture according to claim 1 wherein between 5O00 and 15O00 units of polymyxin, preferably between 8000 and 12000, and most preferably about lO'OOO units of polymyxin B are comprised in 1 ml of the Hquid mixture.

11. Mixture according to claim 1 wherein neomycin is present in a concentration between 0.5 and lOmg neomycin, preferably between 2 and 5 mg neomycin, and most preferably between 3 and 4 mg neomycin per 1 ml liquid mixture.

12. Mixture according to claim 1 wherein polymyxin B and neomycin are used.

13. Mixture according to claim 2 wherein the hemostatic compound is one of alum or tannic acid.

14. Mixture according to any claim 1 to 13 wherein the antiseptic composition comprises one of benzalkonium chloride and benzethonium chloride and hexylresorcinols and mehtylbenzethonium or a combination of two or more of the aforementioned compounds.

15. Use of a pharmaceuticaUy efficacious amount of an anesthetic being either benzocaine or pramoxine hydrochloride or a combination of these compounds; a pharmaceuticaUy efficacious amount one of an antibiotic composition comprising one of polymyxin B and neomycin and bacitracin or a combination of two or more of these compounds and an antiseptic composition; at least a pharmaceutically efficacious amount of a hemostatic compound for the manufacture of a protective dressing for the treatment of bleeding wounds, in particular minor or mild bleeding wounds.

16. Use according to claim 15, wherein said anesthetic compounds, antibiotic or antiseptic compounds, and hemostatic compounds for the manufacture of a Hquid spray comprising film forming components and at least a solvent, in which the aforesaid pharmaceutically components are dispersed or solubilized.

17. Bandage or plaster sprayed or impregnated with a mixture according to any of the preceding claims 1 to 14.

18. Liquid mixture for use as dressing spray comprising a mixture according to any of the preceding claims 1 to 14 for the treatment of bleeding wounds.