IE55502B1

IE55502B1 - Composition for the treatment of wounds

Info

Publication number: IE55502B1
Application number: IE1632/83A
Authority: IE
Original assignee: Smith And Nephew Medical Limit
Priority date: 1982-07-14
Filing date: 1983-07-13
Publication date: 1990-10-10
Also published as: PT77020B; EP0099074A2; DE3226754A1; NO158781C; IL69200A; FI78237C; IL69200A0; PT77020A; JPS5973512A; CA1222455A; ES8604025A1; AU1669583A; ES524059A0; FI832466L; NO158781B; EP0099074A3; ZA835148B; GB8318991D0; AU575778B2; NO832555L

Abstract

An agent for the treatment of wounds comprising in the range of from 2 to 20% by weight of a graft copolymer of starch and hydrolysed polyacrylonitrile, of which in the range of from 5 to 90% of the carboxy groups are neutralised with aluminium, suspended in a physiologically tolerable lipophilic liquid or paste containing, e.g. one, two or three, surfactants, has a strong imbibing or wicking action and encourages rapid heating of a wound to which it is applied. [EP0099074A2]

Description

-2- SasOS The present invention relates to a composition for the treatment of wounds.

Compositions for the treatment of wounds, for example inflammations of wounds, are known and have been described 5 in literature. For example, in addition to the conventional textile dressings, inter alia a product based on granular dextran may be used in the treatment of wounds (US Patent Specification No. 4,225,580). This material has the disadvantage, however, that it is relatively difficult to 10 apply, and, moreover, the disadvantage that it is relatively difficult to remove from a wound, since small grains of dextran easily adhere to the edges of the wound.

We have now found certain compositions for the treatment of wounds which have substantially more favourable properties 15 than those already known and suggested for the same use.

Accordingly the present invention provides a composition for the treatment of wounds, which comprises in the range of from 2 to 20¾ by weight of a graft copolymer of starch -3- and hydrolysed polyacrylonitrile, of which in the range of from 5 to 90% of the carboxy groups have been neutralised with aluminium, suspended in a physiologically tolerable lipophilic liquid or paste, which is a paraffin or a vegetable or animal oil, wax, or fat, containing one, or more, especially one, two or three, surfactants.

The graft copolymer of starch and hydrolysed polyacrylonitrile, of which in the range of from 5 to 90% of the carboxy groups' hydrogen atoms have been substituted by aluminium, comprised in the composition of the invention, may be prepared, for example, in accordance with the instructions given in US Patent Specification No. 4,302,369 by, under the conditions described therein, reacting a starch suspension with acetonitrile in the presence of a chemical initiator such as ceric ammonium nitrate, hydrolysing the resulting graft copolymer with a strong base, for example sodium or potassium hydroxide, and then reacting with an aluminium salt and/or aluminium hydroxide. The resulting product can then be dried, washed with alcoholic ammonia solution and adjusted to the desired pH value of in the range of from 6.0 to 7.5 with hydrochloric acid. Alternatively, however, it is also possible to obtain this product commeric-ally, for example under the name SGP 157 M (as sold by the Henkel Corporation, Minneapolis).

For the preparation of a composition of the invention, a graft copolymer having one or more of the following features is suitable: a molar ratio of the starch component to the acrylate and 5 acrylamide components which is preferably in the range of from 1:3 to 1:0.9; a molar ratio of carboxy groups to amino groups which is preferably in the range of from 2:1 to 9:1; apolymerisate in which preferably in the range of from 25 to 75% of the carboxy groups are neutralised with 10 aluminium.

There may be used as lipophilic liquids paraffin hydrocarbons, for example paraffins, and petroleum jelly, and also vegetable and animal oils, waxes, or fats, for example Jojoba oil, olive oil, peanut oil, coconut oil, almond oil, 15 sunflower oil, lanolin, fine bone oil, beeswax, and wool fat.

Both non-ionic and ionic surfactants are suitable as the physiologically tolerable surfactants. The following are suitable as non-ionic surfactants: lecithins, lecithin 20 fractions and modified products thereof, polyoxyethylene fatty acid esters, for example polyoxyethylene fatty alcohol ether, polyoxyethylated sorbitan fatty acid esters, glycerin-polyethylene glycol oxystearate, glycerin-polyethylene glycol ricinoleate, ethyoxylated soya sterols, 25 ethoxylated castor oils and hydrated derivatives thereof, cholesterol and polyoxyethylenepolyoxypropylene polymers; 5- polyoxyethylenepolyoxypropylene polymers having a molecular weight of in the range of from 6800 to 8975, for example Pluronic F 68, being preferred.

Surfactants in the following group: surfactants having 5 polyethylene groups, fatty alcohol sulphates, fatty alcohols or cholesterol, have proved to be especially suitable surfactants for use in compositions of the invention.

Surfactants containing polyethylene groups that are suitable for the manufacture of the compositions are, for example, 10 polyethylene glycols having a molecular weight of above approximately 1000, polypropylene glycols that are sparingly soluble in water, and block polymers of both compounds, as customary in commerce under the name Pluronic. Especially suitable is the surfactant customary in commerce under the 15 name Pluronic F 68, which may be used in a composition of the invention in a concentration of up to 5% by weight based on the composition itself. Other surfactants containing polyethylene groups that are suitable for the manufacture of a composition of the invention are, for example, the 20 preparations customary in commerce under the name Cremophor EL.

Also particularly suitable as surfactants are fatty alcohol sulphates, for example the preparation customary in commerce under the name Lanette E or N.

As fatty alcohol or cholesterol-containing surfactants that are suitable for the manufacture of a composition of the invention, the following may be mentioned by way of example stearyl alcohol, palmityl alcohol, mixtures of stearyl and 5 palmityl alcohol, the surfactant commercially customary under the name, for example, of Lanette 0, or the cholesterol contained in lanolin.

As it is soTely the properties of the surfactant and not only the chemical structure that are important, mixtures 10 of several surfactants are as suitable as a single surfactant. Apart' from the surfactants, a composition according to the invention may contain an additional lipophilic liquid or paste that consists of a paraffin or a vegetable or animal oil, wax or fat.

Paraffins suitable as components for a composition of the invention are the thinly liquid, viscous, wax-like or solid paraffins customarily used in galenical pharmacy, inter alia also those that are customary commercially under the name Vaseline. Suitable substances are also those paraffins 20 that are emulsified with wool fat alcohols, such as the products customary commercially under the name Eucerin.

Two or more such components may be present in a composition of the present invention.

The words "Pluronic", "Cremophor", "Lanette", "Vaseline" and "Eucerin" used herein are all trade marks.

From the individual components that are used in a composition of the invention in addition to the graft copolymers, 5 under the conditions well known to the person skilled in galenical pharmacy, mixtures are produced that are each adjusted to the desired field of application of the composition.

A composition according to the invention as regards its 10 intended purpose, is suitable not only for the treatment of wounds in the narrower sense but, like the compositions for treating wounds mentioned in the "Rote Liste - 1980" published by the Bundesverband der pharmazeutischen Industrie e.v., D-6000 Frankfurt/Main, is suitable for the 15 treatment of numerous inflammations of wounds of the skin or mucous membrane which are associated with secreted material. Such diseases or wounds are, for example cuts, blows, lacerations, contused wounds, burns, frost wounds, sores, grazes, sunburn, eczema and haemorrhoids.

The compositions according to the invention may, in addition, also contain the additives and auxiliary substances (for example perfumes) customary for such compositions, as well as, in therapeutically active amounts further active substances customarily used in these compositions. Such active substances are, for example, bacteriostatics, 25 -8- antimycotics and local anaesthetics. Suitable bacteriostatics are sulphonamides, for example suldacine and sulphatolamide, or antibiotics for example penicillin. Suitable antimycotics are salicylic acid and derivatives 5 thereof, for example salicylhydroxamic acid, salicylamide, miconacol and isoconacol. Suitable local anaesthetics are alkaloids, for example morphine, and esters of jj.-aminobenzoic acid, for example the methyl ester and the ethyl ester.

The present invention further provides a process for the preparation of a composition of the invention, which comprises mixing together in the range of from 2 to 20¾ by weight of a graft copolymer of starch and hydrolysed polyacrylonitrile, of which in the range of from 5 to 90¾ 15 of the carboxy groups have been neutralised with aluminium, and a physiologically tolerable lipophilic liquid or paste, which is a paraffin or a vegetable or animal oil, wax, or fat, containing one or more surfactants, and, if desired, sterilising the resulting product.

To produce the compositions, the components may be, for example, homogeneously mixed by means of a suitable mill and sterilised by means of heat. Sterilisation can, of course, be carried out prior to the use of the material on site, in a hospital for example. When mixed with the 25 liquid or paste, the copolymer forms a gel which is in the form of pasty mass.

The composition should be applied directly to the area of the body to be treated and, if need be, covered, for example, with gauze.

The present invention also provides a preparation for 5 the treatment of wounds, which comprises a composition of the invention located in or on a permeable support material, for example a fibrous material.

The composition according to the invention has been found to be distinguished by an extraordinary imbibing or wicking 10 action and consequently encourages rapid healing of a wound as a result of the removal of water.

The lipophilic components and surfactants contained in the composition of the invention have the effect of preventing the compositions from drying out owing to low vapour 15 pressure. As a result, adhesion of the wounds or edges of wounds is avoided, so that these compositions can be removed without any problem. Furthermore, these components have the effect of making the preparation more pasty and it may thus be applied more easily.

The following Examples illustrate the invention.

Example 1 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, are ground in a ball mix for 30 minutes with 0.8 g of Pluronic F 68 and 10 g of Pur-oba oil, -10- resulting In a homogeneous dispersion.

Example 2 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, are ground in a ball mix for 5 5 minutes with 1 g of thinly liquid paraffin. 3 g of paraffin are then added, grinding is continued for a further 5 minutes a further 6 g of paraffin and 1 g of Pluronic F 68 are added and grinding is continued for a further 20 minutes until a homogeneous dispersion is formed.

Example 3 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, with a grain size of less than 0.063mm, and 5 g of Pluronic F 68, with a grain size of less than 0.075 mm, are triturated with 20 g of thinly 15 liquid paraffin. 50 g of white petroleum jelly and 25 g of viscous paraffin are then added and the mixture is triturated until a uniform homogeneous dispersion is obtained Example 4 2g of the graft copolymer SGP 157 M from the firm Henkel 20 Corporation, Minneapolis, are triturated with 10 g of Cremophor EL. 90 g of white petroleum jelly are then added in portions to the mixture and the mixture is triturated until a homogeneous dispersion is obtained.

Example 5 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, are triturated with 10 g of Cremophor EL and 10 g of polethylene glycol (MW 400). 80 g of white petroleum jelly are then added in portions and the mixture is triturated until a homogeneous dispersion is formed.

Example 6 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.063 mm, and 0.8 g of Pluronic, having a grain size of less than 0.075 mm, are triturated with 6 g of Cremophor EL. 36 g of white petroleum jelly are then added in portions, and the mixture is triturated until a homogeneous dispersion is obtained.

Example 7 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.036 mm, and 0.8 g of Pluronic F 68 having a grain size of less than 0.075 mm, are triturated with 4 g of Cremophor EL and 4 g of polyethylene glycol (MW 400). 4.8 g of white petroleum jelly are then added in portions, and the mixture is triturated until a homogeneous dispersion is formed.

Example 8 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.063 mm, and 0.8 g of Pluronic F 68, having a grain size 5 of less than 0.075 mm, are triturated with 20 g of Eucerin Anhydr. until a homogeneous dispersion is formed.

Example 9 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 10 0.063mm, and 0.8 g of Pluronic F 68, having a grain size of less than 0.075mm, are triturated with 4 g of Cremophor EL. 16 g of Eucerin Anhydr. are then added in portions, and the mixture is triturated until a homogeneous dispersion is formed.

Example 10 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.063 mm, and 0.8 g of Pluronic F 68, having a grain size of less than 0.075 mm, are triturated with 4 g of Z0 Cremophor EL and 4g of polyethylene glycol (MW 400). 4.8 g of Eucerin Anhydr. are then added in portions, and the mixture is triturated until a homogeneous dispersion is formed.

Example Π 2g of the graft copolymer SGP 1S7 M from the firm Henkel Corporation, Minneapolis having a grain size of less than 0.063 mm, and 0.8 g of Pluronic F 68 are triturated with 20g 5 of ointment base material to form a homogeneous dispersion.

The ointment base material used is produced as follows: 35 g of viscous paraffin, 35 g of white petroleum jelly and 30 g of Lanette N are melted at 90°C and stirred until the mixture has cooled.

Example 12 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.063 mm, and 0.8 g of Pluronic F 68, are triturated with 20 g of ointment base material until a homogeneous dispersion 15 is formed.

The ointment base material used is produced as follows: 6.0 g of wool wax, 0.5 g of Lanette 0, 10.0 g of viscous paraffin and 83.5 g of white petroleum jelly are melted at 90°C and stirred until the mixture has grown cold.

Example 13 2g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain size of less than 0.063 mm, are triturated with 0.8 g of Pluronic F 68, having 5 a grain size of less than 0.075 mm, and 4 g of Cremophor EL. 16 g of the ointment base material prepared in accordance with Example II are then added in portions and the mixture is triturated until a homogeneous dispersion is formed.

Example 14 10 Under the conditions described in Example 13, but using the ointment base material prepared in accordance with Example 12, a homogeneous dispersion is produced.

Other wound treatment compositions based on the graft copolymer specified herein are described and claimed in 15 our co-pending patent application no. 1631/83

Claims

1. A composition for the treatment of wounds, which comprises in the range of from 2 to 20% by weight of a graft copolymer of starch and hydrolysed polyacrylonitrile, 5 of which in the range of from 5 to 90% of the carboxy groups have been neutralised with aluminium, suspended in a physiologically tolerable lipophilic liquid or paste, which is a paraffin or a vegetable or animal oil, wax or fat, containing one or more surfactants. 10

2. A composition for the treatment of wounds as claimed in claim 1, which contains at least one surfactant in a maximum concentration of 5% by weight in a physiologically tolerable lipophilic liquid.

3. A composition for the treatment of wounds as claimed 15 in claim 1 or claim 2, which contains, as one component, a surfactant containing polyethylene groups.

4. A composition for the treatment of wounds as claimed in any one of claims 1 to 3, which contains, as one component, a fatty alcohol sulphate as surfactant. 20

5. A composition for the treatment of wounds as claimed in any one of claims 1 to 4, which contains, as one component, a fatty alcohol or cholesterol as surfactant.

6. A composition for the treatment of wounds as claimed in any one of claims 1 to 5, which contains an additional paraffins or vegetable or animal oil, wax or fat.

7. A composition for the treatment of wounds as claimed in any one of claims 1 to 6, which contains, in addition, one or more active substances suitable for use in wound treatment compositions.

8. A composition for the treatment of wounds as claimed in claim 7, wherein an active substance additionally present is a bacteriostatic.

9. A composition for the treatment of wounds as claimed in claim 7 or claim 8, wherein an active substance additionally present is an antimycotic.

10. A composition for the treatment of wounds as claimed in any one of claims 7 to 9, wherein an active substance additionally present is a local anaesthetic.

11. Π. A composition for the treatment of wounds as claimed in any one of claims 3 to 10, wherein, in addition to the graft copolymer, it contains in the range of from 2 to 8 of the additional components. -17-

12. A composition as claimed in any one of claims 1 to 11, which is sterilised.

13. A composition as claimed in claim 1, which is substantially as described in any one of Examples 1 to 14 5 herein.

14. A process for the preparation of a composition as claimed in claim 1, which comprises mixing together in the range of from 2 to 20% by weight of a graft copolymer of starch and hydrolysed polyacrylonitrile, of which in the 10 range of from 5 to 90% of the carboxy groups have been neutralised with aluminium, and a physiologically tolerable lipophilic liquid or paste, which is a paraffin or a vegetable or animal oil, wax, or fat, containing one or more surfactants, and, if desired, sterilising the resulting 15 product. 15. A process as claimed in claim 14, which is carried out as described in any one of Examples 1 to 14 herein.

15. A composition as claimed in claim 1, whenever prepared by a process as claimed in claim 14 or claim 15. 20 17. A preparation for the treatment of wounds, which comprises a composition as claimed in any one of claims 1 to 13 and 16 located in or on a permeable supporting material. -18- DATED THIS 13th DAY OF JULY 1983 CRUICKSHANK AND COMPANY Agents for the Applicants 1 Holies Street Dublin 2