CA1222455A

CA1222455A - Agent for the treatment of wounds

Info

Publication number: CA1222455A
Application number: CA000432362A
Authority: CA
Inventors: Karl Wundisch; Ingfried Zimmermann
Original assignee: Schering AG
Current assignee: Bayer Pharma AG
Priority date: 1982-07-14
Filing date: 1983-07-13
Publication date: 1987-06-02
Also published as: ES8604025A1; AU575778B2; GR79607B; PT77020A; IL69200A; NO158781B; IL69200A0; GB2124488A; NO832555L; DE3226754A1; EP0099074A3; GB8318991D0; FI832466A0; IE831632L; ZA835148B; DK322683A; FI78237B; EP0099074A2; AU1669583A; PT77020B

Abstract

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.

Description

i 2~2~7S

The present invention relates to an agent for the treatment of wounds.
Agents for the treatment of wounds, for example inflammations of wounds, are known and have been described in literature. For example, in addition to the conventional textile dressings, inter alia a product based on granular dextran may be u~ed in the treatment of wounds (US Patent Specification No. 4,225,580).
This material has the disadvantage, however, that it is relatively difficult to apply, and, moxeover, the disadvantage that it is relatively difficult to remove from ~ wound, since small grains of dextran easily adhere to the edges of the wound.
We have now found certain agents for the treatment of wounds which have substantially more favourable properties than the agents already known and suggested for the same use.
Accordingly the present invention provides an agent for the trea~ment of wounds, which comprises 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 90/0 of the carboxy .

2 ~55i groups have been neutralised with aluminium, suspended in a physiologically tolerable lipophilic liquid or paste 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 agent of the invention, may be prepared, for example, in accordance with the instructions given in US Patent Specification No. 4,302,36g 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 2~5~i -- 2a ~

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commercially, for example under the-~e SGP 157 M
(as sold by the Herlkel Corporation, Minneapolis).
For the preparation of an agent of the invention, a graft copolymer having one or more of the following features is suitable:
a ratio of the starch component to the acrylat~
and acrylamide components t~hich is preferably in the range of from ~:3 to 1:0.9 a ratio of carboxy groups to a~ino groups whlch is preferably in the range of from 2:1 to 9:1 a polymerisate in which preferably in the range of from 25 to 75 % of the carboxy groups are neutrali.sed with aluminium.

There may be used as lipophilic li~uids hydro-carbons, for example paraffin3, petroleum jelly, stearin, and also vegetable and animal oils, waxes or fats, for example Jojoba oil, olive oil, peanut oil, coconut oiL, almond oil, 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 a3 non-ionic surfactants:
lecithins, lecithin 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, ethoxylated soja sterols, ethoxylated castor oils and hydrated derivatives thereof, cholesterol and polyoxyethylenepolyoxypropylene polymers, poly-oxyethylenepolyoxypropylene polymers having a molecular weight of in the range of from 6800 to 8975, for example Pluronic F 68, being pre~erred.

Surfactants in the following group: surfactants having polyethylene groups, fatty alcohol sulphates, fatty alcohols or cholesterol, have proved to be especially suitable surfactants for use in the agents ; 25 of the invention.

Surfactants containing polyethylene groups that are suit~ble for the manufacture of the agents are, for example, polyethylene glycols having a molecular weight of above approximately 1000, polypropylene glycols that are sparingly soluble in water, and block polymers of both compound ~ as customary in commerce under the name Pluronic. ~specially suitable is the surfactant customary in commerce under the name Pluronic F 68, which may be used in the agen~ of the invention in a concentration of up to 5 % by weight based on the agent itself. Other surfactants containing polyethylene groups that are suitable for the manufacture of the agent of the invention are, for example, the 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 Lanekte E or N.
As fatty alcohol or cholesterol-containing surfactants that are suitable for the manufacture of the agent of the invention, the following may be mentioned by way of example: stearyl alcohol, palmityl alcohol, mixtures of stearyl and palmltyl alcohol the surfactant commercially customary under the name, for examp]e, of Lanette O, or the cholesterol contained in lanolin.

2 2 ~ S 5;

A~ it i~ 301ely the properties of the surfactant and not the chemical structuxe that are important, mixtures of several ~urfactants are as suitable as a single surfactant. Apart from the surfactants, an agent according to the invention may contain, in addition, lipophilic liquids or pastes that preferably con~ist of a high-boiling paraffin or a vegeta~le or animal oil, wax or fat.
High-boiling paraffins suitable as components for an agent of the invention are the thinly liquid, viscous, wax-like or solid paraffins customarily used in galenical pharmacy, inter alia also those that are commercially custo~ary under the name Vaseline.
Suitab~e substances are also those paraffins that are emulsified with wool fat alcohols, such as the products commercially customary under the name Eucerin.
The words "Pluronic", "Cremophor", "Lanette", "Vaseline" and "Eucerin" used herein are all trade marks.
Components suitable for the agent ac~ording to the invention are, for example, the vegetable or animal oils, waxes or fats that have already been mentioned above.
From the individual components that are used in an agent of the invention in addition to the graft copolymers, under the conditions well known to the r-~

person skilled in aalenical plla~maCy, mixtu~es are produced that are each adjusted to the desired field of aDplication of the agent.
The aaent according to the invention as regards its intended purpose, is suitable not only for the treatment of wounds in the narrower sense but, like the agents for treating wounds mentioned in the "Rote Liste - 1980" published by the Bundesverband der pharmazeutischen Industrie e.v., D-6000 Fran~furt/Main, is suitable for the treatmer.t of numerous inflammations or wounds of the s~in or mucous mernbrane whlch are associated with secreted material. Such diseases or wounds are, for example cuts, blows, lacerations, contused ounds, burns, frost wounds, sores, grazes, sunburn, eczema and haemorrhoids.
The agents according to the invention may, in addition, also con~ain the additives and au~iliary substances ~for example perfumes) customary for such agents, as well as, in therapeutically active amounts further active substances customarily used in these a~ents. Such active substances are, for e~ample, 2~Si -- ~C

bacteriostatics, antimycotics and local anaesthetics.
Suitable bacteriostatics are sulphonamides, for example suldacine and sulphatolarnide, or antibiotics, for example penicillin. Suitable antimycotics are salicylic acid and derivatives thereof, for example salicylhydroxamic acid, salicylamide, miconacol and isoconacol. Suitable local anaesthetics are alkaloids, for example morphine, and esters of p-aminobenzoic acid, for example the methyl ester and the ethyl ester.
The present invention further provides a process for the preparation of an agent of the invention, which cornprises mixing together in the range of from 2 to 20 %

~f~ ~s by weight of a graft copolymer of starch and hydrolysed polyacrylonitrile, of which in the range of from 5 to 90~0 of the carboxy groups have been neutralised with aluminium, and a physiologically tolerable lipophilic S liquid or paste containing one or more surfactants, and, if desired, ~terilising the resulting product.
To produce the agents, 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 or the like. When mixed with the liquid or paste, the copolymer forms a gel which is in the form of a pasty mass.
The agent 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 the treatment of wounds, which comprises an agent of the invention located in or on a permeable support 20 material, for example a fibxous material.
The agent according to the invention has been found to be distinguished by an extraordinary imbibing or wicking action and consequently encourages rapid healing of a wound as a result of the removal of water.

The lipophili~ components and surfactants contained in the agent of the invention have the effect of preventing the agents from drying out owing to low vapour pressure.
As a result, adhesion of the wounds or edges of wounds is avoided, so that these agents 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 2 g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, are ground in a ball mill for 30 minutes with 0.8 g of Pluronic F 68 and 10 g of Pur-oba oil, resulting in a homogeneous dispersion.

Example 2 2 g of the graft copolymer SGP 157 M from the firm Henkel CorporationO Minneapolis, are ground in a ball mill for 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.

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xample 3 2 g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis~ with a grain size of less than 0.063 mm, and 5 g of Pluronic F 68, with a grain size of less than 0.075 mm, are triturated with 20 g of thinly 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 2 g of the graft copolymer SGP 157 M from the firm Henkel 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 2 g of the graft copolymer SGP 157 M from the firm ~Ienkel Corporation, Minneapolis, are triturated with 10 9 of Cremophor EL and 10 g of polyethylene 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.

'~3 Example 6 2 g 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 i3 triturated until a homogeneous dispersion is obtained.

Example 7 2 g of the graft copolymer SGP 157 M from the firm ~enkel Corporation, Minneapolis, having a grain size of les3 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 ~ g of poly-ethylene glycol tMW 400). 4.8 g of white petroleum jelly are then added in portions, and the mixture is triturated until a homogeneous dispersion i3 formed.

Example 8 2 g 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 20 g of Eucerin Anhydr. until a homogeneous dispersion is formed.

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Exam~ple 9 2 g of the graft copolymer SGP 157 M from the firm Henkel Corporation, Minneapolis, having a grain ~ize of les~ 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 Cremophor EL. 16 g of Eucerin Anhydr. are then added in portions, and the mixture is triturated until a homogeneou~ di~persion is formed.

Example 10 2 g of the graft copolymer SGP 157 M from the firm HenXel Corporation, Minneapolis, having a grain size of less than 0.063 mm, and 0.8 g of Pluronic F 68, having a grain ~ize 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 Eucerin Anhydr. are then added in portions, and the mixture is triturated until a homogeneous dispersion i~ formed.

Example 11 2 g 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 ~ of ointment base material to form a homogeneous di~persion.

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

Example 12 2 g 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 is formed.
The ointment base material used is produced as ~ollows:
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 90C and stirred until the mixture has grown cold.

Example 13 2 g of the graft copolymer SGP 157 M from the firm Henkel Corporation, ~inneapolis, having a grain size of less than 0.063 mm, are triturated with 0.8 g of Pluronic F 68, having 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 l1 are then added in portions and the mixture is triturated until a homogeneous dispersion is formed.

Exa~ple 14 Under the conditions described in Example 13, but using the ointment base material prepared in accordance with Example 12, a homogeneou~ dispersion is produced.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:-

1. An agent 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, 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 containing one or more surfactants.

2. An agent 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. An agent for the treatment of wounds as claimed in claim 1 which contains, as one component, a surfactant containing polyethylene groups.

4. An agent 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.

5. An agent for the treatment of wounds as claimed in any one of claims 1 to 3, which contains, as one component, a fatty alcohol or cholesterol as surfactant.

6. An agent for the treatment of wounds as claimed in any one of claims 1 to 3, which additionally contains a paraffin having a high boiling point.

7. An agent for the treatment of wounds as claimed in claim 1, 2 or 3, which additionally contains a vegetable or animal oil, wax or fat.

8. An agent for the treatment of wounds as claimed in claim 1, which contains, in addition, one or more active substances suitable for use in wound treatment agents.

9. An agent for the treatment of wounds as claimed in claim 8, wherein an active substance additionally present is a bacteriostatic.

10. An agent for the treatment of wounds as claimed in claim 8 or 9, wherein an active substance additionally present is an antimycotic.

11. An agent for the treatment of wounds as claimed in claim 8 or 9, wherein an active substance additionally present is a local anaesthetic.

12. An agent for the treatment of wounds as claimed in claim 3, wherein, in addition to the graft copolymer, it contains in the range of from 2 to 8 of the additional com-ponents.

13. An agent as claimed in claim 1, 2 or 3, which is sterilised.

14. A process for the preparation of an agent 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 a hydrolysed polyarcylonitrile, of which in the range of from 5 to 90% of the carboxy groups have been neutralised with aluminium, and a physiologically tolerable lipophilic liquid or paste containing one or more surfactants and, when required, sterilising the resulting product.

15. A preparation for the treatment of wounds, which comprises an agent as claimed in claim 1, 2 or 3 located in or on a permeable supporting material.