MXPA00010921A - Therapeutic compositions - Google Patents

Abstract

The invention relates to a composition comprising, from 2 to 8%squalane, from 1.5to 8%cyclodextrin, and from 1.5 to 8%of a pharmaceutically and/or cosmetically acceptable acid selected from aliphatic mono-, di-and&agr;-hydroxy carboxylic acids having from 2 to 10 carbon atoms, and the balance selected from other pharmaceutically and/or cosmetically acceptable compatible anti-acne active substances as well as pharmaceutically and/or cosmetically acceptable paste, ointment or cream bases and additives. The composition has therapeutic and cosmetic effect and can be used as a cosmetic as well as for the preparation of a drug for prophylactic and curative treatment of acne. A method for the preparation of the composition as well as a method for treatment of acne is also included in the invention.

Description

THERAPEUTIC COMPOSITIONS FIELD OF THE INVENTION The present invention relates to a new composition for topical application comprising cyclodextrin, squalane, and from 1.5 to 8% of a mono-, di- and a-hydroxy carboxylic acid, aliphatic, pharmaceutically and / or cosmetically acceptable, which It has 2 to 10 carbon atoms. The balance is selected from other pharmaceutically acceptable and / or cosmetically acceptable active substances, used for the treatment of acne and paste, ointment or cream bases and pharmaceutically and / or cosmetically acceptable additives. Additionally, a method for the preparation of the new compositions is included as well as an acne treatment method. The composition can be used as a cosmetic or therapeutic, and for the preparation of a drug for the treatment of diseases caused by attacks of microorganisms, especially for the treatment of acne. 25 Ref. 124727 • -'---- ¿> ~ < »* - * ~~ > *he - - . - -.-..-...-. «-.- .. -. ^. -. ..-. : ... .. * ..,. .,. . . ,. ., ..-,. . »T - * L? , r, "BACKGROUND OF THE INVENTION Within the cosmetic field, C30H62 squalene has been used as lubricants for the skin in cosmetic and hygienic preparations and as fixatives in perfumes, in concentrations of up to 50%. US Pat. No. 5079003 A to Schadiffi A. describes creams or lotions comprising emulsions of fish oils, such as shark liver oil, squalane, and squalene, used as humectants, as bases for cosmetics, as lotions for hands and body and as preventive for sunburn. The compositions that are described also comprise numerous other ingredients with therapeutic and synergistic effects on the skin. Within the therapeutic field, squalane as well as squalene have been used as enhancers of the penetration of active substances, and in vaccine adjuvants (see for example Hoffman SL et al. Am J Trop Med Hyg 1994 Nov; 51 (5): 603-12). As components of oil-emulsion-based adjuvants in injection preparations they are considered to have anti-irritant properties (see, for example, Stone HD et al., Avian Dis 1990 Oct-Dec; 34 (4): 979-83), and as such, they also show an immunogenic effect (Allison AC, Int J Technol Assess Health Care 1994 inter: 10 (1): 107-20). In addition, both are considered to have an effect of proliferation stimulation on the dermal tissues as well as the musculus tissues. Cyclodextrin is a molecule capable of forming an inclusion complex with squalane. In this type of complex the cyclodextrin plays a function of a "host molecule", which forms a cavity that carries one or several "host molecules". In a paper entitled "Chemistry of Cyclodextrin" (Ed. Springer Verlag 1978) it is established that the cavity of the molecule of The cyclodextrin has a calculated diameter of 7A, and a depth of 7A. This can be correlated with the diameter of the "host molecule", which for the squalane molecule can be estimated approximately at 5Á and 30-35Á respectively. m ^ n ^^^^ __ ..

The co-pending patent application O9822083A1 (priority claims from the co-pending application SE 9604193-4, filed on November 15, 1996) refers to compositions comprising as active ingredient (i) one or more components derived from a crude shark liver oil extract, which includes squalane, and (ii) one or more carbohydrates that make up the inclusion and / or chelate complex, including cyclodextrin, with (i) and optionally (iii) one or more therapeutically or cosmetically active agents derived from liver oils not necessarily shark. At Example also 0.15% by weight of sorbic acid is included as a preservative. Patent application WO 9421225A1 relates to a skin care composition comprising a conjugate of derivative of vitamin A and ß-ci cl odex trina for therapeutic or prophylactic treatment of aging symptoms in the skin. The Patent Abstracts of Japan, Vol. 11, No. 69, C-407, summary of JP 61-227517 A and the European patent 0 366 154 describes compositions Cosmetics comprising cyclodextrin and squalane derivatives. However, the prior art does not provide information about new and unexpected advantages in the treatment of acne, obtained by addition, to a composition, for topical application, comprising squalane and cyclodextrin, from 1.5 to 8% mono acids -, di- and α-hydroxy carboxylic, aliphatic, pharmaceutically and / or cosmetically acceptable having from 2 to 10 carbon atoms. According to the findings herein, an amount as low as 0.15% sorbic acid does not provide any effect as anti-age.

DESCRIPTION OF THE INVENTION The present invention relates to a composition, for the treatment of acne, comprising from 2 to 8% of squalane, from 1.5 to 8% of cyclodextrin, and from 1.5 to 8% of a mono-, di- and a- aliphatic hydroxy carboxylic acid, pharmaceutically and / or cosmetically; acceptable having 2 to 10 carbon atoms, and wherein the equilibrium is selected from the -t-AÉ U ------ the _a ^ _? __- ^ - ^ - iSd ----- pharmaceutically and / or cosmetically acceptable, compatible ani-acne active substances, and paste, ointments or cream bases and additives pharmaceutically and / or cosmetically acceptable. The composition can be used as a cosmetic or drug, which creates an environment in which the growth of pathogenic microorganisms is repressed for the benefit of the growth of more harmless microorganisms. The invention also includes a method for preparing the container of compositions as a method for the treatment of acne. The term "pharmaceutically and / or cosmetically acceptable" is understood to mean that the amounts of the agent in question should be pharmaceutically and / or cosmetically acceptable. According to the acne of scientific apprehension, established, it is caused by an increased production of sebum, clogging of pores, and an inflammation caused by the bacterium Prop i on iba c t er um a cn é s. The increased production of sebum is due to an increased production of testosterone during puberty. Testosterone stimulates an increase in the size of the *** «& ** «* e * ¿, *. . . " sebaceous glands and an increased production of sebum. A cn e ro sa cea is a chronic disease that affects the skin of the nose, forehead, and 5 cheeks marked by cleansing, followed by red coloration due to dilation of the capillaries, with the appearance of papules and pustules similar to the acne. Specifically, the new composition, which is defined in the appended claims, has a prophylactic and curative effect on skin disorders such as acne and can be used as a drug or a cosmetic preparation for the prophylactic or healing treatment of acne. . The complex is which ano / cyclodextrin has a curative and anti-inflammatory effect which, in combination with the "antibacterial" effect obtained by the addition of an acid that lowers the pH of the composition to a value that suppresses the growth of pathological microorganisms and supports the growth of more harmless microorganisms, provides a drug for local application to the skin that has excellent unexpected properties on the condition of the gg ^^ MW. * .1 - - - ~ .'- • > . • '- "« «-> - - r •'" * "-" "- '' '" ~ C- "'" • * '- *' * 4tJt *** ~ * ~ u * skin mentioned above . Preferred acids are a-hydroxy acids, especially lactic acid and azelaic acid. Also the treatment of ro s with the composition according to the invention has shown excellent results with the reduction of redness, papules, and pustules after the application of the composition for only a few days. The mono-, di- and a-hydroxy carboxylic, aliphatic, pharmaceutically and / or cosmetically acceptable acids according to the invention are selected from propionic, butyric, valeric, hexanoic, heptanoic, octanoic, nonanoic and decanoic acids and any isomers thereof; oxalic, malonic, succinic, glutaric, fumaric acid; adipic, pimelic, suberic, azelaic, sebacic; glycolic, lactic, melic, tartaric, citric and gluconic acids. Especially preferred are azelaic acid, lactic acid, and the other saturated and unsaturated aliphatic α-hydroxy acids (AHA acids). The acids should be suitably included in the composition in accordance with the * - • • • invention in an amount of 1.5 to 8%, preferably 2 to 7% and more preferably 2.5 to 5%. The composition according to the invention may also contain up to 0.15% of the sorbic acid as a preservative. The squalane is a softening substance that moistens dry skin in a natural way. It adds fat to the skin without causing a greasy feeling on the skin. The squalane should be included in the composition according to the invention in an amount of 2 to 8%, preferably 3 to 7% and more preferably 4 to 6%. The cyclodextrin consists of 5, 6 or 7 glucose units connected to a-1, 4 (a-β - β-cyclodextrin) and was also described above. The cyclodextrin should be included in the composition in an amount of 1.5% to 8%, and more preferably 2 to 7%. By combining the squalane with the cyclodextrin, the inclusion or chelate complex is formed which, in combination with the aforementioned acids, provides a product ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ or cosmetic which has an unexpected effect.The compositions can be formulated as an ointment, a cream, a gel, a milk, a lotion and a powder.The suitable cosmetically and pharmaceutically acceptable bases and active substances are for example butter of sh orea As well as the assets mentioned below, an example of a suitable fatty substance is butter, which is a natural triglyceride, from the nuts of the tropical tree Sh orea s ten opt era, sometimes used to moderate an optional tilt to Irritation of other components in cosmetics.The shredding butter provides a smooth, pleasant feeling for the skin and further improves the effect of the composition by "its beneficial effect on the skin and should be included in an emulsifying amount such as up to 10%. %. The butter has an anti-acne and anti-inflammatory effect, related to the content of sterols, which improve the effect of the composition according to the invention. The starch is a substance that provides a pleasant sensation to the skin and helps to eliminate the greasy sensation which is "" "^" • "** -" ** "* easily achieved in the application of ointments and creams to the skin.The starch must be included in an amount up to 10% .For the emulsifying process, the emulsifiers are chosen to corn starch base, which have a tendency to be much lower than irritation.The type of emulsifiers is used for cosmetics that are used in the vicinity of the eyes.The examples of substances compatible with squalane as well as cyclodextrin, for the treatment of acne are, for example, the acid of Vitamin A, benzoyl peroxide, and clindamycin.An additionally preferred active ingredient is shortening of butter Therapeutically and cosmetically acceptable active ingredients should be included, by the person skilled in the art, in Therapeutically effective and cosmetically effective dosages The invention also provides a method for preparing the compositions according to the invention. ion of an aqueous phase, obtained by mixing cyclodextrin, organic acid and preservatives or preservatives, and a water base under heating or stirring, for an oily phase comprising the squalane component, stirring and, if necessary, heating up to a Homogeneous emulsion of the two components is achieved, and pharmaceutically and / or cosmetically acceptable components are optionally added to the emulsion. Water-soluble substances if the active or additives are added to the aqueous phase and the soluble oil to the oily phase. The heating temperature will be some given, in combination with the stirring, a homogeneous emulsion of the components of the composition. A variation can be from only above the ambient temperature, such as 30 ° C, to an upper limit, for example 90 ° C. The temperature must be selected to ensure that the fatty phase is a liquid state. Obviously, the upper limit of the heating temperature is adjusted by the boiling point of the mixture, but care must be taken not to unduly decompose the components of the mixture by heating excessively. ^ üaáfa?. ^ ^. . . . .. . : . - .. ***. ,. ".-. > ..- > .,.,. ». K", .. ^.,. " ±. . . . ,. ... i, t -, ari-fi .. * flft- > * The hydrophilic medium used to dissolve the cyclodextrin may comprise water or a pharmaceutically and / or cosmetically acceptable alcohol such as ethanol, propylene glycol, and various mono-, di- and trihydric alcohols, conventional to the art, as well as mixtures of any of these, in an amount of up to 20%. Any lipophilic medium used to dissolve the lipophilic component, i.a. hydrophobic, may comprise a pharmaceutically and / or cosmetically acceptable vegetable oil, or any lipid cream base such as is conventionally used within the field of the art. Depending on the relative amounts of the aqueous and oily phases, an ointment, a cream, a gel, a milk or a lotion will be obtained, as will be recognized by the person skilled in the art. The invention will now be further illustrated by means of the following non-limiting examples. In the application all parts and percentages are by weight unless otherwise stated.

EXAMPLE 1 An ointment for the treatment of acne is prepared from the following ingredients: PHASE A (oily phase Cremeol FR 36 5.60% Cre eol SH 2.00% Ascorbilpalmitate 0.01% Glucamate SSE20 1.80% Glucato SS 1.20% Squale 6.00% PHASE B (aqueous phase Water 67.24% Organic acid 0.15% Cyclodextrin 6.00% Lactic acid 5.00% Corn P04PH "B" 5.00% Total 100.0% The oily phase is heated with stirring at 75 ° C. The aqueous phase is heated with stirring at 75 ° C. To obtain the effect of ^^^^^^^^^^^^^^ fegftg ^^^^^^^^ jg ^^^^^^^^ preservation, sorbic acid is added to water and should be dissolved completely before the addition of cyclodextrin. The aqueous phase is added slowly to the oil phase under stirring. The ointment cools under agitation. At about 50 ° C the starch (Corn P04 PH "B") is added.

EXAMPLE 2 10 A skin care cream for the prophylactic treatment of acne is prepared from the following ingredients: PHASE A (oily phase) Cremeol FR36 5.60% Cremeol SH 4.00% Ascorbilpalmitate 0.01% Glucamate SSE20 1.80% 20 Glucato SS 1.20% Squale 6.00% PHASE B (aqueous phase) Water 70.74% 25 Sorbic acid 0.15% j ^ _ ^ n ^ ¿LJ * '• 6"i¿' - - *** ^ -" "• * - • '.« «-. -%« - * ..

Cyclodextrin 6.00% Lactic acid 1.50% Corn P04PH "B" 3.00% Total 100.0% The oily phase is heated with stirring at 75 ° C. The aqueous phase is heated with stirring at 75 ° C. To give the preservative effect, the sorbic acid is added to the water and it will completely dissolve before the addition of cyclodextrin. The aqueous phase is added slowly to the oily phase with stirring. The ointment cools under agitation. The starch is added at approximately 50 ° C (Corn P04 PH "B"). The chemical definitions of the substances referred to by their brands are as follows: Cremeol ™ FR 36: mono-, di-, and triglycerides of 16 to 18 carbon atoms; Cremeol ™ SH: butter of sh orea CAS no. 91770-65-9 (Botanical Classification Sh orea stenoptera) Glucamate SSE 20: ses que s metrato de glucose de methyl PEG-20; Glucate SS: Methyl Glucose Test dja u ^ H ^ uiaaii | íy < ******* - - CORN P04 PH "B" ™: cross-linked starch di-phosphate based on corn starch. The Cremeol ™ series are commercially available from Aarhus olijefabrik A / S, from Aarhus, Denmark. The Glucate ™ SS and Glucama t e ™ S S E 20 are commercially available from Amerchol Corporation, of Edison, USA. CORN P04 PH «B" TM is commercially available available from Dr. HAUSER GMBH, from Garmisch Par tenkir chen, Germany. A pilot study was conducted for 6 weeks in 11 subjects suffering from acne. Of this, 8 has had acne for a period of time between 0.5 to 3 years and 3 more than 10 years. The preparation was applied twice a day, each period, in an absorbable quantity. The results were as follows: twenty * ^, _ & - A ^ * - ü ^ - Especially surprising is that 2 of the subjects who had suffered from acne for more than ten years were healed completely within 14 days. It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, the content of the following is claimed as property.

Claims (14)

1. A composition for acne cosmetic treatment characterized in that it comprises, a) from 2 to 8% squalane, b) from 1.5 to 8% cyclodextrin, and in addition c) from 1.5 to 8% of a mono-, di- and - hydroxy carboxylic, aliphatic, pharmaceutically and / or cosmetically acceptable, having from 2 to 10 carbon atoms, and wherein d) the balance is selected from other active substances compatible, pharmaceutically and / or cosmetically acceptable for the treatment of acne, and e) paste, ointment or cream bases and pharmaceutically and / or cosmetically acceptable additives.

2. The composition according to claim 1, characterized in that in addition the mono-, di- and a-hydroxy carboxylic acids, aliphatic, are selected from propionic, butyric, valeric, hexanoic, heptanoic, octanoic, nonanoic and decanoic acids and any isomers thereof; oxalic, malonic, succinic, glutaric, fumaric acid; adipic, pimelic, suberic, azelaic, sebacic acid; glycolic, lactic, malic, tartaric, citric and gluconic acids.

3. The composition according to claims 1 and 2, characterized in that the acids are selected from azelaic, glycolic, lactic, malic, tartaric, citric and gluconic acids.

4. The composition according to claims 1 to 3, characterized in that the acids are selected from azelaic and lactic acid.

5. The composition according to claims 1 to 4, characterized in that the other compatible active substances, pharmaceutically and / or cosmetically acceptable for the treatment of acne, is selected from the - * - • - -a - ** M "- *** - * UK.My & i? At group consisting of Vitamin A acid, benzoyl peroxide, clindamycin and shorea butter.

6. A composition for therapeutic treatment of acne comprising, a) from 2 to 8% squalane, b) from 1.5 to 8% cyclodextrin, and characterized in that it also comprises c) from 1.5 to 8% mono-, di- and α-hydroxy carboxylic acids, aliphatic, pharmaceutically and / or cosmetically acceptable, having 2 to 10 carbon atoms, and wherein the remainder is selected d) from other pharmaceutically and / or cosmetically acceptable compatible active substances for the treatment of acne, and e) paste, ointment or cream bases and pharmaceutically and / or cosmetically acceptable additives.

7. The composition according to claim 6, characterized in that in addition the mono-, di- and a-hydroxy carboxylic, aliphatic acids are selected from propionic, butyric, valeric, hexanoic, heptanoic, octanoic, nonanoic and decanoic acids and any isomers of the same; oxalic, malonic, succinic, glutaric, fumaric acid; adipic, pimelic, suberic, azelaic, sebacic acid; glycolic, lactic, malic, tartaric, citric and gluconic acids.

8. The composition according to claims 6 and 7, characterized in that the acids are selected from azelaic, glycolic, lactic, malic, tartaric, citric and gluconic acids.

9. The composition according to claims 6 to 8, characterized in that the acids are selected from azelaic and lactic acid. . *. . . . t -. . ^ -. . . . »-. ~. » > . < * < *

10. The composition according to claims 6 to 9, characterized in that the other active substances compatible, pharmaceutically and / or cosmetically acceptable for the treatment of acne, are selected from the group consisting of the acid of Vitamin A, peroxide of Benzoyl, clindamycin and butter of sh orea.

11. The use of a composition comprising: a) from 2 to 8% squalane, b) from 1.5 to 8% cyclodextrin, and 15 c) from 1.5 to 8% of a mono-, di- and - hydroxy carboxylic, aliphatic, pharmaceutically and / or cosmetically acceptable, having from 2 to 10 carbon atoms, and wherein the balance or compensation is selected 20 d) from other substances pharmaceutically and / or cosmetically active, compatible, for the treatment of acne, selected from the group consisting of the acid of Vitamin A, benzoyl peroxide, clindamycin and butter of 25 shorea, and * "--- - **» »- - - - ^^! ^ Ije) paste, ointment or bases for cream and additives pharmaceutically and / or cosmetically acceptable for the preparation of a drug for the prophylactic and curative treatment of diseases caused by attacks of microorganisms on the skin.

12. The use of the composition according to claim 11 for the preparation of a drug for the treatment of acne.

13. A method for preparing the composition as defined in the above rei indications, characterized in that an aqueous phase, prepared by the mixing of cyclodextrin, organic acid and preservatives with an aqueous base under heating and stirring, is added to an oily phase comprising squalane and paste, ointment and bases for hydrophobic cream until a homogeneous emulsion is obtained and the optional water-soluble additives are added j M ^^^? ^ U M '-; J- A | J ^ ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡to the aqueous phase and additives soluble in the oil to the oily phase.

14. A method of treating acne and acne rosacea characterized by the local application of a composition as defined in any of claims 1 to 10. 10 gáft ^^ Xsá * ^: