FR2685202A1 - Novel method of pharmaceutical and cosmetic treatment for the regulation of seborrhoea, acne and the cutaneous flora - Google Patents

Abstract

The invention relates to a method of dermopharmaceutical and cosmetic treatment which consists in using a simple glucose ester, glucose pentaacetate or its homologues, and an enzyme system composed of glucose oxidase and lactoperoxidase incorporated in dermatological and cosmetic preparations, thereby enabling seborrhoea to be regulated and acne and other skin complaints of microbial origin to be combatted with a single product.

Description

The cutaneous flora of healthy skin and damaged skin is of a very complex composition. The regulation of cutaneous seborrhea, the genesis of juvenile acne and its bacteriology, but also the flora responsible for body odors (transformation of sweat, sebum) are all areas of active research, but still little clarified.

Nevertheless, seborrhea regulating products, anti-acne pharmaceutical products (benzoylperoxide among others) and antiperspirant products, deodorants based on a bactericidal effect, exist commercially.

The use of lactoperoxidase as an antimicrobial substance has long been described. Its use in dermopharmaceutical and cosmetic compositions for its bactericidal properties on the skin level, however, faces the following obstacle:
The action of the enzyme consists in transferring an oxygen atom onto an acceptor such as the chloride ion or the thiocyanate ion to transform it into hypochloride or hypothiocyanate, both known for their microbicidal activity. To do this, the lactoperoxidase needs a supply of active oxygen as found in hydrogen peroxide (natural substrate of the enzyme).

Ointments, creams, gels and other preparations for topical application cannot contain both the enzyme and its substrate without the reaction taking place instantly.

French patent application No. 86 09166 addresses this problem and describes a process for packaging an antibacterial composition based on the use of lactoperoxidase, lactoferrin (as a supplement to antimicrobial activity) and the thiocyanate ion as well as an oxygen donor (either glucose + glucose oxidase, or peroxide).

However, with regard to dermatological or ophthalmological applications, this patent insists on the fact of the obligation of the physical separation of the two substances (glucose or peroxide substrate and enzyme), either by offering two containers (vials, tubes, capsules ) separated, either by using a special container with multiple compartments.

The object of the present invention is the method which consists in the use, in the same preparation (cream, milk, lotion etc.) of the entire enzyme system, namely glucose oxidase and lactoperoxidase as well as the thiocyanate ion and lactoferrin, in addition to a compound derived from glucose, glucose pentaacetate or its counterparts and functional analogues. This combination incorporated into the dermopharmaceutical or cosmetic composition is stable over time. Glucose pentaacetate is not a substrate for glucose oxidase, therefore is not degraded, it is not hydrolyzed in the preparation. The enzymes thus remain inactive in the product. It is only when used on the skin that the enzymatic process is triggered; in fact, the skin, including the upper layers, contains a sufficient amount of extracellular lytic enzymes (lipolytics, proteolytics, glucosides) to deacetylate the pentaacetate from glucose, thus transforming it into a substrate for glucose oxidase. The presence of these enzymes and their activity has been demonstrated by recent biochemical analyzes. The function of glycosidases consists inter alia in deglycosylating the sphingolipids of the horny layers to form ceramides.

où R1, R2, R3, R4, R5 sont des chaines aliphatiques de 1 à 20 atomes de carbone, ramifiées ou non, saturées ou insaturées, hydroxylées ou non, peuvent être employés, soit seuls, soit en combinaison entre eux, la condition essentielle étant leur susceptibilité à l'attaque enzymatique des enzymes naturelles de la peau et/ou des microorganismes résidents sur la peau saine ou atteinte (flore acnéique, flore génératrice d'odeurs). The glucose oxidase contained in the preparation generates hydrogen peroxide from glucose, this peroxide thus released in situ will be used by the lactoperoxidase.
Other glucose esters of general formula

where R1, R2, R3, R4, R5 are aliphatic chains of 1 to 20 carbon atoms, branched or not, saturated or unsaturated, hydroxylated or not, can be used, either alone or in combination with each other, the essential condition being their susceptibility to the enzymatic attack of the natural enzymes of the skin and / or the resident microorganisms on healthy or affected skin (acne flora, flora generating odors).

To demonstrate the effectiveness of the system, we carried out an in vivo test on 8 people with oily, shiny skin prone to acne.

The application of a cream containing 120 mg / kg of lactoperoxidase, 200 mg / kg of lactoferrin, 30 mg / kg of glucose oxidase, 300 mg / kg of potassium thiocyanate, 1300 mg / kg of pentaacetate of glucose and qs 1000 g excipient, for three weeks on the skin of the face, morning and evening, leads to a noticeable decrease in seborrhea (measured with the methods of SebumeterR and SebutapeR) of approximately 30%. The acne pimples fade, the skin becomes softer, less oily and less shiny.

The same effect was observed in a test using a similar preparation, but without ester of glucose. In this case the glucose must be provided by the application of a separate solution, a severe constraint which the method which is the subject of the present patent makes it possible to eliminate.

In a different test, we prepared a hydroglycolic lotion containing double the concentrations mentioned above of each of the active components.

This lotion was used by 10 people in daily application (morning) by spray under the arm.

A qualitative evaluation of the appearance of the characteristic odor, in comparison with the untreated armpit made it possible to highlight a marked improvement by the application of the active lotion. The enzymatic reaction of the first stage, namely the release of glucose by the skin enzymes or the enzymes proper to the germs present, takes place in a sufficiently rapid manner; the germs responsible for the axillary odor are sensitive to the action of the described enzymatic system.

This method is much more practical to use than the use of two successive solutions (glucose first, then enzymes), and it does not have the disadvantages of conventional bactericidal deodorants (irritation, redness).

The concentrations of use of the active active ingredients can vary so that the concentration of glucose oxidase in the product is between 3 and 500 mg / kg, preferably between 10 and 200 mg / kg, the concentration of lactoperoxidase is between 10 and 500 mg / kg, preferably between 50 and 200 mg / kg, the concentration of lactoferrin is between 10 and 1000 mg / kg, preferably between 50 and 300 mg / kg, sodium or potassium thiocyanate .. between 10 and 1000 mg / kg, preferably between 100 and 500 mg / kg, of glucose pentaacetate or its counterparts or the like or their combinations between 1 and 50,000 mg / kg, preferably between 10 and 5000 mg / kg
These active components can be used by those skilled in the art in any dermopharmaceutical and cosmetic formulation, namely gels, O / W emulsions, W / O, creams, milks, lotions, ointments, masks, sprays, sticks. They can be associated with other active components without other limitation than chemical compatibility (reducing or destroying molecules of the enzymatic system), and can be used in vectorized form, namely in liposomes, micro- and nanocapsules, micro- and nanovesicles , liquid crystals, micro sponges.

Claims (7)

1. Dermopharmaceutical or cosmetic compositions intended for the treatment of skin problems associated with oily skin, acne skin and axillary flora generating odors, which consist of the association of one or more esters of glucose, of glucose oxidase, lactoperoxidase, a thiocyanate salt and lactoferrin and a suitable excipient. 2. Cosmetic or pharmaceutical compositions formulated and used according to claim 1, characterized in that they contain glucose oxidase, lactoperoxidase, a sodium or potassium thiocyanate salt and one or more glucose esters of general formula

 where R1, R2, R3, R4 and R5 are aliphatic chains of 1 to 20 carbon atoms, branched or not, saturated or unsaturated, hydroxylated or not. 3. Cosmetic and pharmaceutical compositions according to claim 2, characterized in that they also contain lactoferrin. 4. Cosmetic and pharmaceutical compositions according to claims 2 or 3, characterized in that the glucose ester chosen is glucose pentaacetate a or B. 5. Cosmetic and pharmaceutical compositions according to claims 2 to 4, characterized in that the concentration of glucose oxidase in the product is between 3 and 500 mg / kg, preferably between 10 and 200 mg / kg, the concentration of lactoperoxidase is between 10 and 500 mg / kg, preferably between 50 and 200 mg / kg, the concentration of lactoferrin is between 10 and 1000 mg / kg, preferably between 50 and 300 mg / kg, the concentration of thiocyanate is between 10 and 1000 mg / kg, preferably between 100 and 500 mg / kg, the concentration of glucose ester is between 1 and 50,000 mg / kg, preferably between 10 and 5,000 mg / kg. 6. Cosmetic and pharmaceutical compositions according to claims 2 to 5, characterized in that they are gels, O / W emulsions, W / O emulsions, creams, milks, lotions, ointments, masks, sprays, sticks. 7. Cosmetic and pharmaceutical compositions according to Claims 2 to 6, characterized in that the enzymes and the glucose esters are used in vectorized form, namely in liposomes, micro- or nanocapsules, micro- and nanovesicles, liquid crystals , micro sponges.