FR2503561A1 - CONTINUOUS FLEXIBLE FILM FOR COSMETIC AND PHARMACEUTICAL USE CONTAINING POLYPEPTIDES - Google Patents

Abstract

The film material is composed of a mixture of a polypeptide, a plasticiser and a film-forming flexible polymer. When the film comes into contact with water, it liberates the polypeptides.

Description

 The present invention relates to flexible continuous films containing polypeptides. Polypeptides containing polyamino acids have been found useful in the fields of cosmetics and pharmaceuticals. It is recognized that the polypeptides present in the formulation of cosmetics confer a beneficial effect on creams and preparations applied topically. The polypeptides are normally formulated into such creams and topical preparations and the preparation is applied in a fluid form which can remain in contact with the skin of the user for a predetermined period. Among the polypeptides that have been found useful are polyamino acids derived from proteins and the proteins themselves. Two particularly useful proteins that have been incorporated into cosmetics are collagen and elastin, and their derivatives. Collagen has been found to exert beneficial effects when applied topically at the same time as the polyamino acids derived therefrom. Likewise, elastin has been proposed and used in such cosmetic preparations.

 In another aspect, it has been found that when collagen is formulated with antiseptics and the like, it promotes healing of the skin and more specifically promotes healing of burns. Such pharmaceutical preparations require a sterile environment for their production from the moment of their preparation until the moment when they are applied to a burned person. Therefore, extreme care must be taken during processing and transportation to ensure the sterility of the product.

 It has long been desirable to find a preparation containing polypeptides which is easy to use at a controlled dose, using a material conveniently applied. However, because of the high molecular weight of polypeptides and their special chemical structure, it has been difficult to form films of them, because they tend to be brittle and difficult to apply. Furthermore, any film containing polypeptides intended for topical application must be extremely flexible to conform to the outline of the particular region of the body to be treated.

 The present invention provides polypeptides in the form of a continuous film which is tough and flexible and which allows the transfer of the polypeptides to the skin of the person to be treated.

 A flexible continuous film is formed from a mixture of a polypeptide, a plasticizer and a flexible film-forming polymer. When the film is moistened, it exudes the polypeptide.

 The term "polypeptide" used herein refers to polyamino acids derived from a protein as well as the proteins themselves. The polyamino acids useful in the implementation of the invention are polyamino acids which have a molecular weight of at least 5000. Preferably, the polyamino acids are derived from collagen.

 Collagen constitutes the connective tissue and represents the main type of fibrous protein in higher vertebrates. Collagen exists in its natural state in the form of a helix of triple chains with a constant periodicity between aligned triple chains. The triple helix configuration of collagen is sometimes called the fibril and the fibrils line up with an axial periodicity of approximately 64.0 nm.

In young animals, there is a weak intermolecular or interfibrillary crosslinking which gives a certain degree of solubility to the collagen. However, during the aging process, both intermolecular and interfibrillar crosslinking takes place, making the collagen insoluble. In order to process insoluble collagen to form polyamino acids, the long chains must be broken at the same time as the intermolecular and interfibrillary bonds. These polyamino acids derived from collagen are formed by enzymatic digestion of the protein so as to produce short-chain oligopeptides, i.e. polyamino acids. Another method of forming polyamino acids from collagen is the method described in United States patent application NO 113,694 filed January 21, 1980 in the name of Gheorghe Cioca et al, entitled "Oligopeptides
Derived From Collages. In this process for producing polyamino acids, collagen is hydrolyzed to form oligopeptides in a molecular weight range of about 5000 to 20,000. This preferred procedure gives polyamino acids which are substantially pure and which are useful in the implementation of the invention, both in cosmetic applications and in pharmaceutical applications. In addition to the polyamino acids, soluble collagen in its own form can be incorporated into the continuous film of the invention. Thus, the collagen which is present in young animals can advantageously be incorporated into the film, whereas when the collagen comes from old animals, it must be treated to form a soluble product. Such a method of forming soluble collagen is described in the patent application of
United States of America NO 074 738 filed on behalf of
Gheorghe Cioca and entitled "Process for Preparing
Macromolecular Biologically Active Collagen ". In accordance with the process described in said application, soluble collagen is prepared which can be easily incorporated into the continuous film in accordance with the present invention.

 Preferably, the polyamino acids are incorporated into the film in a proportion of 25 to 75% by weight and in particular from 40 to 60% by weight. When soluble collagen is incorporated into the film, it is present in a proportion of 3 to 5% by weight.

 The plasticizers useful in the implementation of the invention include those which are water-soluble and preferably non-irritant locally, and which have high boiling points, that is to say above 1500C. Examples of plasticizers which can be used in the implementation of the invention are glycerol, dipropylene glycol, diethylene glycol, etc.

Preferably, the plasticizers are present in a proportion of 20 to 40% by weight and in particular from 30 to 40% by weight. The plasticizer is necessary so that the continuous film is flexible during processing and transport and so that it retains its flexibility during use. Other plasticizers known to those skilled in the art can also be used, provided that they give the film the desired flexibility and that they are water-soluble and non-volatile.

 The film-forming polymer useful in the implementation of the invention is a polymer which is also water-soluble and which is capable of forming a homogeneous solution with the polypeptide and the plasticizer in water.

A very popular polymer is polyvinyl alcohol.

Polyvinyl alcohol is preferred because of its solubility in hot water and its insolubility in cold water. Thus, polyvinyl alcohol can be dissolved in water together with the plasticizer and the polypeptide and the solution is heated to form a flowable mixture. After film formation and subsequent evaporation of water and other solvents which may be present in the mixture, the polymer forms a tenacious flexible film together with the polypeptide and the plasticizer. On contact with cold water, the polyvinyl alcohol does not dissolve, but the polypeptide is mobilized and passes by exudation, from the film on the skin of the person being treated. In addition, although polyvinyl alcohol is soluble in water, it does not have sufficient acidity or basicity to react with the skin in a detrimental manner. Preferably, the film-forming polymer is present in a proportion of 10 to 20% by weight.

 In a representative example of formulation and procedure for the preparation of the flexible continuous film in accordance with the invention, an aqueous solution at 5-15% by weight of film-forming polymer is prepared.

In addition to water, other solvents such as methanol, ethanol, butanol, etc. can be added. The polymer solution is mixed with a solution of the polypeptide and, in the case of polyamino acids, with a 30% solution of the polyamino acids in water and, if necessary, in a lower alcohol having up to 4 carbon atoms. The plasticizer is then added and the components form a homogeneous solution or dispersion. The solution or dispersion can then be applied by conventional techniques, and the water and the other solvent (alcohol in this case) are evaporated to form the flexible continuous film. An example of such a process is the application of the solution or dispersion to tear-off paper using a printing roller. The film thus applied can be wet laminated on a porous non-woven or woven material. and the composite can be dried until it is freed from solvent and water. After drying, the composite can be covered with a solution and dried to form a film of the desired thickness.

 The woven or non-woven material against its integrity to the final film, by reinforcing its mechanical resistance and its toughness for shipment and use. The nonwoven material may be in the form of a tulle or a thin veil of natural or synthetic fiber and, preferably, a synthetic fiber of "Nylon" or the like. The woven or non-woven material preferably has a thickness of 74 to 125 ssm and an approximate surface weight of 40.1 g / m2.

 Other methods known to those skilled in the art for coating can be used to form the flexible film of the invention.

 Other details of the invention appear from the following examples.

EXAMPLE 1
The following are loaded into a suitable container: 100 parts by weight of an 8% solution of polyvinyl alcohol in a mixture of water and 70/30 ethanol; 100 parts by weight of a 30% solution of polyamino acids derived from collagen having a molecular weight range from 2000 to 5000 in a 70/30 water / ethanol mixture; and 25 g of glycerol. The ingredients are mixed until homogeneous at room temperature to form a physical mixture of components.

 The above solution is applied using a printing roller to Daubert "1-55 SCK-1" transfer paper, in a thickness of 0.127 mm in the wet state. The coated paper is laminated in the wet state with a non-woven polyester "Kendall" NO 9605 having the characteristics indicated below. The above composite is dried in 3 to 5 minutes at 850C. The composite is coated with a layer of the same solution using a printing roller, which applies 0.305 mm of solution in the wet state. The sample is again dried for 5 to 10 minutes at 85 C. The material is again coated with the same solution in a thickness of about 0.254 mm in the wet state. The sample is dried for 10 minutes at 850C and for 3 to 5 minutes at 1490C. After drying, the material is allowed to cool to room temperature and cut into sheets which are placed in the package.

 In a particular application of the invention, perforations are made in the manner of a mask so that the material can be used as a cosmetic facial mask. When the material is used as a facial mask, it is wetted with cold water and applied to the face. Moisture causes the film polypeptides to exude and transfer to the face along with the glycerol. The polyvinyl alcohol remains in the form of a continuous film and, after a period of 10 minutes to one hour of application to the face, the mask is removed.

EXAMPLE 2
The procedure of Example 1 is repeated, except that 3.5 parts, based on the weight of the sheet material, of biologically active macromolecular collagen produced in accordance with Example 1 of the United States patent application. United States of America No. 074 738 cited above are added in the form of a 2.75% solution in dipropylene glycol. The continuous flexible film prepared in accordance with Example 2 can also be used as a cosmetic facial mask.

EXAMPLES 3, 4 and 5
The procedure of Example 2 is repeated except that it incorporates into the solution, before the application of the coating, 0.00001% of merthiolate for Example 3, iodine for Example 4 and silver salt of sulfodiazine for Example 5. The flexible continuous films are cut to the appropriate dimensions, moistened and used to dress burns. Collagen, whose value is recognized in the treatment of burns, is released in a period of up to approximately 30 days, thus promoting the healing of burns of the skin.

EXAMPLE 6
The procedure of Example 1 is repeated, except that 3.5 parts by weight of elastin are added to the solution. The product of Example 6 can be used as a cosmetic facial mask.

 Accordingly, the present invention provides a flexible continuous film containing polypeptides which exude from the film when the latter is moistened. The film of the invention can be used in the treatment of burns and in other pharmaceutical and cosmetic applications.

 It goes without saying that the present invention has been described for explanatory purposes but is in no way limiting and that numerous modifications can be made thereto without departing from its scope.

Claims (10)

 1. Flexible continuous film, characterized in that it consists of a physical mixture  of a polypeptide  a plasticizer; and  a film-forming polymer  said film, when moistened, allowing said polypeptide to exude.  2. Flexible continuous film according to claim 1, characterized in that the polypeptide is chosen from the group comprising collagen and polypeptides derived from collagen.  3. Flexible continuous film according to claim 1, characterized in that the polypeptide is present in a proportion ranging from 25 to 75% by weight, preferably in the range from 40 to 60% by weight.  4. Flexible continuous film according to claim 1, characterized in that the film-forming polymer is present in a proportion of 10 to 20% by weight.  5. Flexible continuous film according to claim 1, characterized in that the film-forming polymer is polyvinyl alcohol.  6. Flexible continuous film according to claim 1, characterized in that the plasticizer is present in a proportion of 20 to 40% by weight.  7. flexible continuous film according to claim 1, characterized in that the plasticizer is present in a proportion of 30 to 40% by weight.  8. Flexible continuous film according to claim 1, characterized in that the plasticizer is glycerol.  9. flexible continuous film according to claim 1, characterized in that it is mounted on a support, preferably in textile material, in particular in a non-woven material.  10. Flexible continuous film according to claim 1, characterized in that the polypeptide is chosen from the group comprising elastin and polypeptides derived from elastin.