COMPOSITIONS FOR TOPICAL USE CONTAINING POLYSACCHARIDE SULPHATES

Abstract: New cosmetic or pharmaceutical compositions for topical use in the form of gels or creams are described. The compositions contain polysaccharide sulphates, preferably carrageenins, having an average molecular weight of from 60 000 to 180 000 Daltons, preferably from 70 000 to 160 000 Dalton.

Description: COMPOSITIONS FOR TOPICAL USE CONTAINING POLYSACCHARIDE SULPHATES The present invention relates to a new polysaccharide sulphate having an average molecular weight of from 60 000 to 180 000 Daltons for use mainly in the field of cosmetics and pharmaceuticals. Polysaccharide sulphates and in particular copolymer sulphates of (l-3)-D- galactose and (l-4)-3,6-anhydro-D-galactose or (l-4)-3,6- anhydro-L- galactose, generally known as carrageenins, carrageenans or carrageens (The Merck Index, 11th Edition), have already been known and used for a long time owing to their properties of increasing the viscosity of aqueous solutions and suspensions and for their role as stabilising agents in respect of such solutions and suspensions. Therefore, polysaccharide sulphates are generally used for the preparation of gels, lotions, pastes, creams and ointments for topical use, although they are often used in other fields, such as, for example, in the food industry, especially with regard to the stabilisation of suspensions and emulsions containing milk or its derivatives, or in the paint and dyestuff industry. Carrageenins, in particular, are polysaccharide sulphates of natural origin which are normally extracted from algae and mucilage and which are classified in accordance with their structural formula as kappa, kappa II, iota, lambda, mu, nu and theta carrageenins. The commercial carrageenins generally available on the market contain all the forms in variable percentages, although the kappa, iota and lambda forms generally predominate. The literature describes numerous methods of extracting and purifying carrageenins, and also various examples of cosmetic and pharmaceutical compositions based on polysaccharide sulphates and, in particular, carrageenins. US patent No. 3,236,833 describes a process for the extraction of carrageenin from marine algae by using hydrogen peroxide, while US patent No. 4,443,486 describes a process for the depolymerisation of commercial carrageenins based on the use of an aqueous hydrogen peroxide solution at a temperature of 75°C. As evidenced in US patent No. 4,543,250, carrageenins which are generally used for the preparation of formulations for pharmaceutical or cosmetic use are characterised in that they have a molecular weight of generally from 250 000 to 500 000 Daltons. These formulations have typical viscosities of from 3000 to 20 000 mPas at ambient temperature, in the case of concentrations of the polysaccharide variable from 1.5 to 2 % by weight. These viscosity values, in particular, are of substantial importance because they permit optimum "spreadability" of the formulation, thus increasing the permeability, through the epidermis, of the active ingredients optionally contained therein. The above-mentioned US patent No. 4,543,250 of Henry J. Witt marked a turning-point of substantial importance as regards the already well established approach to the use of polysaccharide sulphates and more specifically carrageenins in the production of formulations for cosmetic use and, in particular, in the production of shampoos or lotions for hair treatment. That patent teaches the use of polysaccharides having an extremely low molecular weight which, owing to their reduced dimensions, permit a substantial increase in the speed of reaction with the proteins of the dermis and above all the hair (keratin), leading to a considerable improvement in the healing effect which confers a smooth, soft and shining appearance on the hair. According to the teaching of Henry J. Witt, these results are achieved by using highly depolymerised polysaccharide sulphates having a molecular weight of from 15 000 to 10 000 Daltons so that a 1.5 % by weight aqueous solution thereof has a viscosity not greater than 5 mPas at 75°C. The technical problem which the present invention is to solve differs substantially from those forming the main objects of the above-mentioned US patent. The aim of the present invention is to provide cosmetic or pharmaceutical compositions for topical use, in the form of gels or creams, which do not have the disadvantages which characterised and still characterise the formulations currently on the market containing polysaccharide sulphates having a high molecular weight. As already mentioned, the customary formulations in the form of gels or creams for topical use contain polysaccharide sulphates and/or carrageenins having a molecular weight of generally from 250 000 to 500 000 Daltons. However, this type of formulation has the disadvantage, which has still not been resolved satisfactorily, of creating on the epidermis a more or less rigid film which, in the majority of cases, renders the application thereof unpleasant and troublesome, causing preference to be given to the use of formulations having a lower viscosity, such as, for example, those of the already mentioned US patent No. 4,543,250. These latter formulations, owing to their lower viscosity and density, are more difficult for the epidermis to absorb, to the detriment of the cosmetic or therapeutic effect of the active ingredient contained therein. The aim of the present invention is therefore to provide new cosmetic and pharmaceutical compositions in the form of gels or creams containing polysaccharide sulphates and capable of carrying active ingredients, while avoiding both the formation of troublesome and excessively rigid films on the epidermis, and the difficulties of absorption and thus lesser therapeutic or cosmetic efficacy. This surprising result is obtained by using polysaccharide sulphates, preferably carrageenins, having an average molecular weight of from 60 000 to 180 000 Daltons, preferably from 70 000 to 160 000 Daltons. The carrageenins and, more generally, the polysaccharide sulphates used in the implementation of the present invention are obtained by the depolymerisation of polysaccharide sulphates, preferably commercial carrageenins, having a higher molecular weight. For a more advantageous implementation of the invention, the starting polysaccharide sulphates must have an average molecular weight of from 400 000 to 1 000 000 Daltons, preferably from 500 000 to 700 000 Daltons. Processes for depolymerising the polysaccharide sulphates are well known in the art and generally use hydrogen peroxide (see, for example, US patents No. 3,236,833 and No. 4,443,486) or alkalies. The preferred concentrations of the suitably depolymerised polysaccharide sulphate for the implementation of the present invention may vary from 0.2 to 10 % by weight as a function of the desired final viscosity. The gels and the creams according to the present invention may be prepared simply by soaking the depolymerised polysaccharide in an aqueous solution containing the active ingredients, and optionally also conventional excipients and adjuvants, at a temperature of from 40 to 60°C for a period of from 45 to 90 minutes. As can be seen from the data compiled in Table 1, formulations are thus obtained which have a viscosity (generally from 3000 to 9000 mPas at a temperature of 25°C when the concentration of the polysaccharide sulphate is 1.5 % by weight) comparable to that of the formulations currently available on the market, and which are therefore also spreadable but free from the disadvantages mentioned above. TABLE 1 As already mentioned, the formulations thus obtained have the ability to create surface layers which penetrate completely into the epidermis, avoiding the creation of a rigid and troublesome film thereon. In contrast, the carrageenins having a low molecular weight described in US patent No. 4,543,250 could not be used for the purposes of the present invention. It has been found that formulations containing carrageenins having a molecular weight of 48 000 - 49 000 Daltons in concentrations of 1.5 and 2 % have, respectively, viscosities of 1000 and 5000 mPas, respectively, which values are too low to ensure perfectly and easily spreadable formulations and which thus preclude a priori the use of polysaccharide sulphates having a molecular weight of approximately 10 000 - 15 000 Daltons for this purpose. The formulations of the present invention are also colourless, clear and perfectly spreadable on the epidermis with rapid and complete penetration, leaving the skin with a pleasant soft, glowing and smooth feel. The polysaccharides according to the present invention can be used in association with other gelling substances, both of synthetic nature (such as carboxypolymethylcellulose or carboxymethylcellulose) and of natural origin, thus obtaining gel-form formulations that are especially continuous, uniform and consistent, without losing the characteristics mentioned above. The formulations according to the present invention therefore lend themselves well to various uses, both in the cosmetic field and the pharmaceutical field; they can be used as carriers for one or more active ingredients or can be used directly for their moisturising and toning power. In this connection, it is important to underline that, according to the present invention, it is also possible to obtain microsuspensions in the form of homogeneous and uniform gels even in cases where water-insoluble active ingredients are used, such as, for example, sucralphate and non-steroidal anti- inflammatory drugs, in the case of active ingredients for pharmaceutical use, and Centella asiatica or liposoluble vitamins in the case of active ingredients for cosmetic use. For this particular embodiment of the invention it is, however, necessary for the active ingredient for introduction into the composition to be in the form of micronised particles having a diameter of less than 10 μ. The preparation of microsuspensions in the form of gels would be difficult if not impossible using carrageenins having a low molecular weight, such as, for example, those in US patent No. 4,543,250 because, in addition to the already- mentioned contra-indications, it would not be possible to obtain a density sufficient to maintain the microsuspension and therefore the active ingredient would precipitate. It is also important to note how the formulations of the present invention can be subjected to lyophilisation without any contra-indications. The following Examples are given purely by way of non-limiting illustration of the invention (the parts are to be understood as parts by weight). Example 1 - Day cream - Stearyl alcohol (21 ) EO : 3 % - Stearyl alcohol (2) EO : 3.5 % - Cetylstearyl alcohol : 2.5 % - Karit butter: 3 % - Octyldodecyl myristate: 7 % - Transesterified glyceryl triiso stearate (6) EO: 2 % - Dimethylpolysiloxane: 1 % - Sterile water: q.s. 100 - Acrylates: 1 % - Low MW* polysaccharide sulphate (102 000 Da): 0.5 % - Glycosamine glycans: 0.3 % - Vitamin E acetate: 1 % - Perfume: 0.25 % *MW = molecular weight Example 2 - Moisturising cream - Glyceryl stearate: 10 % - Cetylstearyl alcohol: 10 % - Hydrolysed potassium palmital protein: 10 % - Jojoba oil: 5 % - Non-hydrolysable olive oil: 4 % - Dimethylpolysiloxane: 1 % - Karit butter: 5 % - Self-oxidising mixture: 0.05 % - Sterile water: q.s. 100 - Sodium hyaluronate: 0.1 % - Low MW polysaccharide sulphate (75 000 Da): 0.6 % - Glycerol: 4 % - Perfume: 0.25 % Example 3 - Leg gel - Glycerol: 30 % - Propylene glycol 20 % - Sodium hyaluronate 0.1 % - Low MW polysaccharide sulphate (75 000 Da): 0.4 % - Glycosamine glycans: 0.3 % - Sterile water: q.s. 100 Example 4 - Moisturising gel - Glycerol: 3 % - Sodium hyaluronate: 3% - Acrylates: 0.5 % - Low MW polysaccharide sulphate (115 000 Da): 0.6 % - Sterile water: q.s. 100 - Perfume: 0.25 % Example 5 - Moisturising gel - Low MW polysaccharide sulphate (75 000 Da): 1.5 % - Sterile water: q.s. 100 - Optional addition of KC1 Example 6 - Suspension in the form of sucralphate gel - Sucralphate: 20 % - Low MW polysaccharide sulphate (162 000 Da): 0.4 % - Sorbitol: 12 % - Potassium sorbate: 0.2 % - Aspartame: 0.1 % - Pulvaroma: 1.4 % - Demineralised water: q.s. 100 These gels by themselves or with active ingredients in suspension or in solution together with other excipients give rise to crosslinked light patches keeping the active ingredients completely distributed. These patches can be used as such with bandages or in other manners.

Claims: CLAIMS I . Compositions for topical use in the form of gels or creams, characterised in that they contain polysaccharide sulphates having an average molecular weight of from 60 000 to 180 000 Daltons. 2. Compositions according to Claim 1, characterised in that the polysaccharide sulphates have an average molecular weight of from 70 000 to 160 000 Daltons. 3. Compositions according to Claim 1, characterised in that the polysaccharide sulphates are carrageenins. 4. Compositions according to Claim 1, characterised in that they contain at least one cosmetic or pharmaceutical active ingredient. 5. Compositions according to Claim 1, characterised in that the polysaccharide sulphates are obtained by the depolymerisation of polysaccharide sulphates having an average molecular weight of from 400 000 to 1 000 000 Daltons. 6. Compositions according to Claim 5, characterised in that the polysaccharide sulphates are obtained by the depolymerisation of polysaccharide sulphates having an average molecular weight of from 500 000 to 700 000 Daltons. 7. Compositions according to Claim 1, characterised in that the polysaccharide sulphates are present in a variable amount of from 0.2 to 10 % by weight. 8. Compositions according to Claim 1, characterised in that they exhibit a viscosity of from 3000 to 9000 mPas at a temperature of 25°C when the concentration of the polysaccharide sulphate is 1.5 % by weight. 9. Compositions according to Claim 8, characterised in that they exhibit a viscosity of from 3500 to 4300 mPas. 10. Compositions according to Claim 1, characterised in that they contain the conventional excipients and adjuvants. I I . Compositions according to Claim 1, characterised in that they contain water-insoluble ingredients in the form of micronised particles. 12. Compositions according to Claim 11, characterised in that the micronised particles have a diameter of less than 10 μ. 13. Compositions according to Claims 11 and 12, characterised in that they are in the form of gelled microsuspensions. 14. Compositions according to Claim 1 in lyophilised form. 15. Use of polysaccharide sulphates having an average molecular weight of from 60 000 to 180 000 Daltons for the preparation of compositions for topical use in the form of gels or creams. 16. Use according to Claim 15, characterised in that the polysaccharide sulphates have an average molecular weight of from 70 000 to 160 000 Daltons. 17. Use of polysaccharide sulphates according to Claim 15 together with cosmetic and pharmaceutical active ingredients.

Inventors: REINER ALBERTO, REINER GIORGIO, REINER, ALBERTO, REINER, GIORGIO
Applicants: APPLIED PHARMA RES, REINER ALBERTO, REINER GIORGIO, APR APPLIED PHARMA RESEARCH S.A., REINER, ALBERTO, REINER, GIORGIO
Application year: 1997
Main classification: A61K7
IPC codes: A61K8, A61K9, A61K47, A61Q19