DE10009424A1 - Use of flavone and isoflavone compounds, especially of plant origin, for the treatment of cellulite - Google Patents

Abstract

A flavone, isoflavone or a glycoside is used for the cosmetic treatment of cellulite or for stretching the skin. An Independent claim is also included for the use of a flavone or isoflavone or one of their glycosides for the production of a pharmaceutical preparation for the therapeutic treatment of cellulite.

Description

The invention relates to the use of a flavone, isoflavone or one Glycoside thereof in compositions for cosmetic or pharmaceutical Treatment of cellulite.

Cellulite (synonyms: panniculosis, lipodystrophy, status protrusis cutis, Orange peel) represents a local accumulation of fat and water in body tissues represents a predominantly aesthetic problem that with dimples and deepening of the skin and nodulation of the subcutaneous adipose tissue especially on the thighs and buttocks. As part of the The present invention also includes local cellulite Fat overweights included. In advanced stages of cellulite you can pain in the area of the nodules also occurs. Differentiate clearly from the Cellulite is cellulite (panniculitis), which is an inflammation of the subcutaneous Adipose tissue and thus, in some cases, severe and life-threatening Represents disease.

The causes of cellulite are not exactly known. Various hypotheses are discussed, especially one

• a) local reduced blood flow in the subcutaneous adipose tissue due to enlarged Blood vessels with the consequence of a slowed blood flow, which in turn leads to Builds up fat cells and thus leads to fat cell hypertrophy, as well as a
• b) Change in the connective tissue structure, the morphology being characterized by a Fat storage is changed.

Cellulite is usually considered a cosmetic problem. However, there is also voices in the specialist literature that cellulite as a pathological Consider the condition that needs therapy. This approach is justified on the one hand, to pain conditions, particularly in the area of Lymphatic vessels of heavily fatty subcutaneous tissue have their origin. On the other hand, the psychological burden associated with cellulite can change manifest psychosomatic disorders requiring treatment.

The conventional treatment methods for cellulite try to promote blood circulation and have a positive influence on the connective tissue structure, for example through

• - massage
• - lymphatic drainage
• - Diet and / or exercise, although there is even a worsening of the Condition can occur
• - magnetic fields
• - Liposuction (liposuction)
• - Enzyme therapy, for example with hyaluronidase
• - Taking medication to promote lipolysis or
• A topical treatment with agents such as steroids and / or Contain caffeine.

Of the procedures for stimulating lipolysis, that is the most best known and most widely used, which is the enzyme Inhibit phosphodiesterase to prevent degradation of the cyclic AMP or at least slow it down. The phosphodiesterase destroys the cyclic AMP by converting it to 5'-AMP, which is no longer able to to activate lipolysis. So it is important to see the effects of phosphodiesterase in to inhibit the way that a high concentration of adipocytes cyclic AMP is achieved with the aim of stimulating lipolysis. Among the  various phosphodiesterase inhibitors, for example as Weight loss agents that are recommended are the xanthine bases, in particular Caffeine, to name a few.

In practice, substances with a lipolysis effect, especially phosphodiesterase Inhibitors and certain plant extracts, for example those from ivy, arnica, Rosemary or St. John's wort, often containing at least one substance accompanied by blood pressure or vasodilatory effects.

These substances include in particular nicotinic acid and its salts and Esters and paprika extracts. Some of these substances are irritating to the skin Effect and cause a slight warming of the skin. After the apprenticeship the prior art is achieved in that in the cellulite tissues trapped water can drain better and the removal of the at Lipolysis favored fatty acids. In addition, favor one possibly caused heating the diffusion of the active ingredients.

JP 0229350 contains capsaicin and vanillyl nonylamide as constituents Skin cosmetic preparations are known which have a feeling of warmth on the skin cause. However, the Scripture gives no evidence that this Preparations for the treatment of cellulite could be suitable.

Furthermore, plant extracts, growth factors, Inositol phosphate, alpha-hydroxycarboxylic acids and vitamin C for the treatment of Cellulite recommended.

FR 2740681 describes cosmetic compositions for the treatment of Cellulite, which contains caffeine and an extract from the bark or leaves of Plants of the genus Viburnum included. As part of this extract Amentoflavon described, a consisting of two apigenin units Biflavonoid. Amentoflavon represents one according to the teaching of this writing  characteristic ingredient of Viburnum and serves to standardize the Dosage of the viburnum extract in the compositions according to the invention. The document gives the expert no indication that the amentoflavone for Anti-cellulite effect of the compositions causally or jointly responsible could be.

FR 2609395 describes xanthine-containing pharmaceutical or cosmetic Compositions with a local slimming effect on their intracellular phosphodiesterase inhibitory effect is attributed. The Compositions such as glycosides as additional ingredients for example, contain bioflavonoids. Which substances or groups of substances under the the term bioflavonoids, which is known to be contradictory in the professional world are not to be understood. The skilled person will not be able to do this offset, a composition corresponding to the teaching of Scripture with a Prepare content of a bioflavonoid, which has a locally slimming Effect. The document also gives no evidence that the bioflavonoids to the slimming properties of the invention Compositions could contribute.

From JP-0237172 substances obtained from plant material are known which may contain capsaicin, flavonoids and / or isoflavones in addition to other substances. The substances described there serve to regulate plant growth in the Agriculture, other applications are not mentioned.

The substances and methods for treating the known from the prior art Cellulite is unsatisfactory, especially as to the extent and the Speed of the treatment effect is concerned.

The object of the invention was to remedy the shortcomings of the prior art and to provide improved agents for treating cellulite.  

The object of the invention is achieved by using a flavon, Isoflavones or a glycoside thereof for the cosmetic treatment of cellulite.

The object of the invention is further achieved by the provision pharmaceutical preparations for the therapeutic treatment of cellulite, which contain a flavone, isoflavone or a glycoside thereof.

The invention accordingly furthermore relates to the use of a flavon, Isoflavones or a glycoside thereof for the manufacture of a pharmaceutical Preparation for the therapeutic treatment of cellulite.

For the purposes of the present invention, flavones are understood to mean substances which Hydrogenation, oxidation or substitution products of 2-phenyl-4H-1- represent benzopyrans, a hydrogenation in the 2,3-position of Carbon skeleton can be present, an oxidation with formation of a Carbonyl group can be in the 4-position, and substitution substitution one or more hydrogen atoms by hydroxyl or methoxy groups understand is. In this definition, flavans, flavan-3-ole (catechins), Flavan-3,4-diols (leukoanthocyanidins), flavones, flavonols and flavanones in conventional sense included. The flavones according to the invention include for example chrysin, galangin, apigenin, fisetin, luteolin, kaempferol, quercetin, Morin, Robinetin, Gossypetin, Taxifolin, Myricetin, Rhamnetin, Isorhamnetin, Naringenin, eriodyctiol, hesperetin, liquiritigenin, catechin and epicatechin. As Flavones are preferred are quercetin and luteolin.

In the flavone glycosides according to the invention, the flavones are above at least a hydroxy group is glycosidically linked to at least one sugar. As sugar come mono- and oligosaccharides, especially D-glucose, D-galactose, D- Glucuronic acid, D-galacturonic acid, D-xylose, D-apiose, L-rhamnose, L-arabinose and rutinose into consideration. Examples of the flavone glycosides according to the invention are rutin, hesperidin and naringin.  

For the purposes of the present invention, isoflavones are understood to mean substances which Hydrogenation, oxidation or substitution products of 3-phenyl-4H-1- represent benzopyrans, a hydrogenation in the 2,3-position of Carbon skeleton can be present, an oxidation with formation of a Carbonyl group can be in the 4-position, and substitution substitution one or more hydrogen atoms by hydroxyl or methoxy groups understand is. The isoflavones according to the invention include, for example Daidzein, Genistein, Prunetin, Biochanin, Orobol, Santal, Pratensein, Irigenin, Glycitein, Biochanin A and Formononetin. Preferred isoflavones are daidzein, Genistein, glycitein and formononetin.

In the isoflavone glycosides according to the invention, the isoflavones are over at least one hydroxy group with at least one sugar glycosidic connected. Monosaccharides or oligosaccharides, in particular D- Glucose, D-galactose, D-glucuronic acid, D-galacturonic acid, D-xylose, D-apiose, L- Rhamnose, L-arabinose and rutinose. Preferred examples of the isoflavone glycosides according to the invention are daidzin and genistin.

It is further preferred according to the invention if the flavones, isoflavones and the glycosides of which are components of a plant Mixture of substances, in particular a vegetable extract, in the Preparations are included. Such vegetable substance mixtures can in familiar to the person skilled in the art, for example by pressing or extracting can be obtained from plants such as soy, red clover or chickpeas. Especially isoflavones or are preferred in the preparations according to the invention Isoflavone glycosides are used in the form of extracts derived from soybeans as they are for example under the product name Soy Protein Isolate SPI (Protein Technology International, St. Louis) or Soy Phytochemicals Concentrate SPC (Archer Daniels Midland, Decatur) are commercially available.  

In a further embodiment, the invention relates to the use of a Flavons, isoflavones or a glycoside thereof in combination with one Phosphodiesterase inhibitor for the cosmetic treatment of cellulite or for Manufacture of a pharmaceutical preparation for therapeutic treatment of cellulite.

According to the invention, the phosphodiesterase inhibitors used are, for example Inhibitors into consideration as described in R. M. Di Salvo, Controlling the Appearance of Cellulite, Cosmetics and Toiletries Magazine 110, pp. 50-59 (1995) or in L. Stryer, Biochemie, Spektrum Akademischer Verlag GmbH, Heidelberg 1991, p. 482.

According to the invention, xanthine is preferably used as the phosphodiesterase inhibitor or a methylxanthine, where methylxanthine is a substance in which one or more hydrogen atoms is replaced by methyl groups. As Theophylline, theobromine and caffeine are preferred, especially methylxanthine caffeine is preferred.

In a further embodiment, the invention relates to the use of a Flavons, isoflavones or a glycoside thereof in combination with one Phosphodiesterase inhibitor and / or a substance that stimulates C-nerve fibers and / or depolarized, for the cosmetic treatment of cellulite or for Manufacture of a pharmaceutical preparation for therapeutic treatment of cellulite.

The C-nerve fibers, also called polymodal C-nerve fibers, play in the play an important role in the sensory functions of the human organism Body, especially the skin. They are primarily perception for example of warmth, cold and itching as well as the sensation of pain (e.g. Heat pain, cold pain, stinging pain, burning pain) involved. A The polymodal C nerve fibers have a special position as a subgroup of the C-  Nerve fibers because they can respond to several different stimuli and furthermore by the release of mediators in turn in the Can intervene in stimulus events. Located on the surface of the C nerve fibers different receptors such as capsaicin, bradykinin and 5- Hydroxytryptamine receptors, as well as ion channels such as calcium and sodium channels through which the C nerve fibers are stimulated and / or depolarized can be. About this stimulation and / or depolarization sensory stimulus triggered, which can be, for example, burning, tingling, warmth, Sensation of cold or pain. In the sense of the present According to the invention, it is preferred to stimulate and / or depolarize the C- Nerve fibers of the skin, in particular by stimulating the capsaicin Receptors of these nerve fibers, a tingling sensation, a slight burning sensation or a warmth or trigger a feeling of cold.

In the context of the present invention, substances influencing C nerve fibers are to be understood, for example:

• - capsaicin
• - Red pepper or cayenne pepper extracts
• - Vanillyl nonylamide (nonivamide)
• Acid amides of 4-hydroxy-3-methoxy-benzylamine with carboxylic acids R-COOH, wherein the carboxylic acids are selected from the group formed by straight-chain or branched alkylcarboxylic acids with 1 to 22 Carbon atoms
• - Ginger extracts
• - In addition to the substances listed above in JP 11060460 described substances that cause a feeling of warmth

as well as glycosides of the aforementioned substances, insofar as these are used to form Glycosides are capable. In these glycosides are those mentioned above Substances insofar as they contain one or more hydroxyl groups, at least a hydroxy group is glycosidically linked to a sugar. Come as sugar especially D-glucose, D-galactose, D-glucuronic acid, D-galacturonic acid, D-  Xylose, D-apiose, L-rhamnose, L-arabinose and D-maltose are considered. Further Suitable substances are described in P. D. Wall and R. Melzack (Eds.), Textbook of Pain, Churchill Livingstone Verlag, Edinburgh 1994, pp. 13 to 37 and 58 to 72.

Capsaicin, N-Vanillyl are preferred as substances influencing C-nerve fibers nonanamide and their glycosides.

In addition to triggering a sensory stimulus that the Users of the preparation according to the invention feel a The substances influencing the C-nerve fibers have mediated onset of action some other desired effects. So they promote blood circulation to the treated tissue and thus favor the penetration of the ingredients of the Preparation in the skin. Furthermore, the removal of the degradation products can thereby are promoted, which arise in the course of lipolysis by the Application of the preparation is effected. In addition, the in severe Cases of cellulite pain occurring are dampened. For example, this is the Case when nonivamide is used as the substance influencing the C-nerve fibers becomes.

The active compounds are used according to the invention in such concentrations that the toxicologically permissible use concentration in preparations or at Application should not be exceeded.

The cosmetic use of the flavon, isoflavone or Glycoside thereof is preferably carried out together with a physiologically acceptable one Carrier in the form of a cosmetic preparation.

The physiologically compatible carrier of the cosmetic or pharmaceutical Preparations comprise one or more adjuvants, as are usually described in such preparations are used, such as. B. thickeners, moisturizing and / or moisturizing substances, surfactants, emulsifiers,  Plasticizers, foam brakes, greases, oils, waxes, silicones, Sequestering agents, anionic, cationic, nonionic or amphoteric Polymers, alkalizing or acidifying agents, alcohols, polyols, softeners, Adsorbents, light stabilizers, electrolytes, organic solvents, Preservatives, bactericides, antioxidants, fragrances, flavors, Sweeteners, colors and pigments.

Cosmetic preparations include, for example, oils, ointments, aqueous gels, alcoholic gels, O / W emulsions, W / O emulsions and multiple emulsions, preferably with the appearance of a cream or milk.

The pharmaceutical preparations according to the invention are topical or on enteral, parenteral or rectal route. With topical They can be administered in various forms, such as creams or ointments are present, especially in anhydrous form such as one Oil or a balm or in the form of an oil-in-water or water-in-oil Emulsion, which can be, for example, a cream or milk, in the form of Suspensions, solutions, powders or plasters. If the preparations in in anhydrous form, the carrier can be a vegetable or animal oil Mineral oil or a synthetic oil or mixtures of such oils. For administration via the enteral route, the pharmaceutical Preparations in the form of tablets, capsules, dragees, syrups, suspensions, Solutions, powders, granules or emulsions are available. For administration The preparations can be administered parenterally in the form of solutions or Suspensions for perfusion or injection are available. For administration on rectally, the preparations can be in the form of suppositories.

According to the invention contain cosmetic or pharmaceutical Preparations in total 0.1 to 20% by weight, and preferably 1 to 10% by weight one or more flavones, isoflavones or their glycosides, based on the Total weight of the preparation.  

In a further embodiment of the invention, the cosmetic or pharmaceutical preparations additionally a total of 1 to 15 wt .-%, and preferably 5 to 10% by weight of one or more phosphodiesterase inhibitors, based on the total weight of the preparation.

In a further embodiment of the invention, the cosmetic or pharmaceutical preparations additionally a total of 0.0001 to 3, and preferably 0.005 to 0.5% by weight of one or more of the C-nerve fibers stimulating and / or depolarizing substances, based on the total weight the preparation.

In particular, it was surprisingly found that the combination according to the invention consists of

• a) one or more flavones, isoflavones or their glycosides
• b) one or more phosphodiesterase inhibitors
• c) one or more stimulating and / or stimulating the C nerve fibers depolarizing substances

show an unexpectedly high effect in treating cellulite like they only can be explained by a synergistic effect of the components.

In a further embodiment of the invention, the cosmetic or pharmaceutical preparations contain

• a) 0.1 to 20, and preferably 1 to 10 wt .-% of one or more Flavones, isoflavones or their glycosides
• b) 1 to 15, and preferably 5 to 10 wt .-% of one or more Phosphodiesterase inhibitors
• c) 0.0001 to 3, and preferably 0.005 to 0.5 wt .-% of one or more the C-nerve fibers stimulating and / or depolarizing substances

each based on the total weight of the preparation.  

The cosmetic preparations used according to the invention are suitable preferred for the cosmetic treatment of cellulite and local Fat overweights, but also for use in so-called "slimming Products "and for tightening the skin, especially the skin of legs, Cleavage, neck or face area.

Another object of the invention is the use of a flavone, isoflavone or a glycoside thereof in combination with a phosphodiesterase inhibitor for the preparation of a preparation for the therapeutic treatment of cellulite.

Another object of the invention is the use of a flavone, isoflavone or a glycoside thereof in combination with a phosphodiesterase inhibitor as well as a substance that stimulates and / or depolarizes C-nerve fibers Preparation of a preparation for the therapeutic treatment of cellulite.

The active ingredients of the three can be used to produce pharmaceutical preparations groups mentioned above, optionally in combination with others Active substances, together with one or more inert customary carriers and / or diluents, e.g. B. with cornstarch, milk sugar, cane sugar, Sorbitol, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, Citric acid, tartaric acid, water, water / ethanol, water / glycerin, water / sorbitol,  Water / polyethylene glycol, propylene glycol, carboxymethyl cellulose or fatty substances such as hard fat or their suitable mixtures, in usual pharmaceutical preparations such as tablets, coated tablets, capsules, powders, suspensions, Work in drops, ampoules, juices or suppositories. The one to achieve one corresponding effect required in pharmaceutical applications daily Dosage of the active ingredient or mixture of active ingredients is advantageously 0.1 to 10 mg / kg body weight, preferably 0.5 to 2 mg / kg body weight.

The pharmaceutical preparations according to the invention are preferably suitable for the therapeutic treatment of cellulite.  

The following examples are intended to illustrate the present invention. All Unless otherwise stated, percentages are based on the total weight of the Preparations related.  

Examples

example 1

Recipes

Anti-cellulite gels

Anti-cellulite creams

Anti-cellulite lotions

Example 2 Test results

The anti-cellulite gel according to Example 1 was tested in a four-week test with the formulation Gel-5 for its effectiveness in relation to the cellulite phenomenon and tested its cosmetic acceptance in 25 women (half-side test against Placebo). The test participants became immediately after the use test Effectiveness of the product and cosmetic acceptance in standardized Way questioned.

Over 80% of the subjects felt a tingling and warming Skin feeling. After four weeks of use, 28% of women were able to get one 40% of women notice improvement in cellulite symptoms noted an improvement in skin firmness. 84% were with the Skin tolerance of the product satisfied and 72% could imagine that Continue to use product.

Claims (14)

1. Use of a flavone, isoflavone or a glycoside thereof for cosmetic treatment of cellulite or to tighten the skin. 2. Use of a flavone, isoflavone or a glycoside thereof for Production of a pharmaceutical preparation for therapeutic Treatment of cellulite. 3. Use according to one of claims 1 or 2, characterized in that the flavone, isoflavone or glycoside thereof is part of one from a plant obtained mixture of substances, in particular a vegetable extract. 4. Use according to claim 3, characterized in that it is in the Substance mixture is a soy extract. 5. Use according to one of claims 1 to 4, characterized in that the flavone or flavone glycoside is selected from the group that is formed of quercetin, rutin, hesperidin and their mixtures. 6. Use according to one of claims 1 to 4, characterized in that the isoflavone or isoflavone glycoside is selected from the group formed is used by Daidzein, Genistein, Glycitein, Formononetin, Daidzin, Genistin and their mixtures. 7. Use according to one of claims 1 to 6, characterized in that the preparation additionally contains a phosphodiesterase inhibitor. 8. Use according to claim 7, characterized in that the Phosphodiesterase inhibitor is selected from xanthine and methylxanthines.   9. Use according to one of claims 1 to 8, characterized in that the preparation also contains a substance that the C-nerve fibers of the Skin stimulated and / or depolarized. 10. Use according to claim 9, characterized in that the C- Nerve fiber stimulating substance is selected from the group that is formed is from capsaicin, N-vanillylnonanamide, their glycosides and their Mixtures. 11. Use according to one of claims 1 to 10, characterized in that the preparation in total 0.1 to 20% by weight and preferably 1 to 10% by weight on one or more flavones, isoflavones or their glycosides, in each case based on the total weight of the preparation. 12. Use according to one of claims 7 to 10, characterized in that the preparation in total 1 to 15% by weight and preferably 5 to 10% by weight on one or more phosphodiesterase inhibitors, each based on the Total weight of preparation. 13. Use according to one of claims 9 or 10, characterized in that the preparation a total of 0.0001 to 3% by weight and preferably 0.005 to 0.5% by weight contains one or more substances that the C-nerve fibers of Stimulate and / or depolarize the skin, each based on the Total weight of the preparation. 14. Use according to one of claims 1 and 3 to 13, characterized characterized in that the cosmetic preparation in the form of an oil, a Ointment, a gel or in the form of an oil-in-water or water-in-oil emulsion with the appearance of a cream or milk.