Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2000-06-14
2002-11-12
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S004100, C536S124000, C435S074000
Reexamination Certificate
active
06479461
ABSTRACT:
The present invention concerns the use of alkylmonoglucosides and more particularly n-butyl-&agr;-D-monoglucopyranose, named hereafter &agr;-butylglucoside as molecular vector, and the preparation of new compounds obtained by grafting &agr;-butylglucoside onto certain compounds and their uses.
We have noted that a need existed to modify numerous cosmetic or pharmaceutical active ingredients and/or food ingredients in order to improve:
their bioavailability
their toxicity
their liposolubility
their hydrosolubility
The present invention proposes to respond to these needs. It concerns the use, in pharmaceutical, dermatological, cosmetic or food domains, of alkylmonoglucosides as transcutaneous or transmucous membrane molecular vectors having the general formula:
in which R
1
is a C
2
to C
18
alkyl, linear or branched radical.
By “molecular vector” a compound is meant, which after chemical reaction with an active compound gives a vectorized active compound which penetrates the skin or a mucous membrane more easily than the initial active compound.
The invention also concerns the use, in a pharmaceutical, dermatological, cosmetic or food composition, of vectorized active ingredients with the general formula:
where R
2
is a —CO—R group where R is a hydrocarbonated, linear, branched, saturated or unsaturated ethylene radical; a group derived from retinol (vitamin A) or from one of its derivatives, notably retinoic acid, ascorbic acid (vitamin C) or one of its derivatives, of a tocopherol amongst which are vitamin E and the D vitamins; a group derived from polyphenols, for example a residue of polyhydroxylated derivatives of flavan; or a radical
where X is an aliphatic chain which is functionalized or not.
In these vectorized active ingredients, the active molecule is linked by covalence to position 6 of the vector. The invention stems from the fact that we have reduced the toxicity of exfoliant agents used in cosmetics and/or dermatology by grafting onto &agr;-butylglucoside.
Cosmetic and/or dermatological compositions have, amongst others, a vocation of acting on the protection function of the skin which necessitates the direct influence of the condition of the corneal layer. It is known that if this corneal layer contains too many dead cells, it doesn't protect any more. It must then be removed to allow another layer of cells to maintain an efficient barrier against external aggressions, and the cosmetic and dermatological active ingredients to penetrate it. Such is the known and allotted role of Alpha Hydroxy Acids or AHA.
The AHA are organic acids with an alcohol function on the neighbouring carbon of the one (in alpha position) carrying the carboxylic acid function. We group together more particularly glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, gluconic acid as well as certain analogues of AHA like salicylic acid and serine in this family of compounds.
These AHA have recognised and measurable efficacy but they also present some drawbacks. These AHA are often irritants and have a poor bioavailability: they sometimes penetrate too rapidly into the deep layers of the skin. In Parfums Cosmétiques Arômes 122,66-72 (April, May 1995) improvements proposed by the suppliers of raw cosmetic materials are described to make these compounds less irritant and to slow down their penetration into the skin.
A proposed improvement attempt consists of encapsulating these AHA in capsules in order to slow down the diffusion of AHA. Unfortunately, it is difficult to know with exactitude the percentage of active ingredients encapsulated and even more difficult to evaluate the percentage of active ingredients liberated into the skin.
Another attempt consists of lipophilising these AHA by grafting a lipophile compound (fatty alcohol, alkyl chains) by esterification. However, the action of these compounds is reduced because of their lipophile nature. In fact, they diffuse only with great difficulty into the stratum corneum into which they are stopped by the presence of aqueous compartments in the intercorneocytory spaces.
We have expanded this reflection to saturated and unsaturated fatty acids. In fact, the corneal layer is made up of a compact mass of 20 layers of inactive cells, embedded in a system of double lamellar layers of lipids. This structure of the stratum corneum as well as the lipophile nature of the lipid barrier protects the skin against the drying out provoked by the imperceptible loss of transepidermal water. Cosmetic and/or dermatological compositions have, amongst others, a vocation of acting on the protection function of the skin and to improve the appearance. If the intercellular lipids of the corneal layer are altered, the skin no longer protects.
Unsaturated fatty acids, such as linoleic acid, are an important factor for the construction and repair of the lipid barrier. They function as precursor molecules for the synthesis of a signal substance which controls the proliferation and the activity of the cells.
In addition, unsaturated fatty acids also directly take part in the regulation of the cutaneous permeability. These are non occlusive lipophile substances capable of making a more or less continuous film at the cutaneous surface but above all likely to incorporate themselves in the intercellular cement thus playing an active role in the regulation of hydration. Their biological activity is regulated by the position of the double link closest to the terminal methyl group.
The clinically observed cases of cutaneous alteration like acne show that a sufficient supply of unsaturated fatty acids in the skin is necessary to maintain the functioning of the lipid barrier.
Unsaturated fatty acids thus have an essential role in the physiology of the skin. Their topical administration however poses problems, problems that we propose to resolve by vectoring them.
The action of these compounds are reduced as they only diffuse with difficulty into the stratum corneum: they are stopped by the presence of aqueous compartments contained in the intercorneocytary spaces. The grafting of these acids onto &agr;-butylglucoside increases the hydrophile nature and thus optimises the penetration of these active ingredients into the epidermis.
In addition, the penetration of these compositions into the epidermis poses a problem because of their lipophile nature. Their introduction into emulsions stabilised by a monolayer of tensioactives practically does not improve this state of fact given that these emulsions break as soon as they are applied onto the skin. An oily phase containing the unsaturated fatty acids thus rests on the surface of the skin. Thanks to the invention the increase of the hydrophilic nature by the hydroxyl functions free from the glucose part improves penetration and allows an optimised usage of unsaturated fatty acids in water in oil or oil in water emulsions.
By extension, this principle can be applied to numerous active lipophile compounds with a physiological action on the skin. As an example, we can cite the esterifiable derivatives of the lipophile vitamins A,D,E or F, essential oils, solar filters, anti-inflammatories as well as bio-stimulant agents of lipids and/or protein syntheses. The document FR-A-94 12005 exposes different solutions consisting of preparing oil emulsions in specific water.
Certain cosmetic, dermatological pharmaceutical active ingredients and/or food ingredients are unstable as they are sensitive to exterior factors like light or heat.
Moreover, different means have been used to stabilise these compounds. One of these means lies for example in blocking the sensitive site by esterification with phosphate, sulphate, and alkyl derivatives and to employ these derivatives instead of the non-modified compound. These derivatives have a less good activity and are sometimes more toxic than the active ingredient free by the presence of phosphated, sulphated or alkyl residues.
Another means consists of blocking the site with a glycosidic derivative. A precursor of active ingredients is thus obtained which after application on th
Boures Emmanuel
Bousquet Marie Pierre
Messager Arnaud
Monsan Pierre
Willemont Rene-Marc
Maier Leigh C.
Ulice
Wilson James O.
Young & Thompson
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