ITBS980010A1 - COMPOSITION FOR COSMETIC OR PHARMACEUTICAL USE BASED ON LIPOIC ACID AND PYRUVIC ACID - Google Patents

Description

DESCRIPTION

PATENT FOR INDUSTRIAL INVENTION Having as title

"COMPOSITION FOR COSMETIC OR PHARMACEUTICAL USE BASED ON LIPOIC ACID AND PYRUVIC ACID"

The present invention relates to a new composition for cosmetic or pharmaceutical use essentially intended for external use, applied on the skin, whether damaged or intact, or on the mucous membranes, and for internal use, taken in the form of tablets, prolonged release tablets, sugared almonds. , gastro-resistant dragees, capsules, long-acting capsules, syrup, drops, suppositories or in any other pharmaceutical form, or injected intramuscularly, intra-venously, subcutaneously, intra-articularly, etc.

More precisely, the invention refers to a composition for the aforementioned use which is characterized in that it contains as an active ingredient a mixture of lipoic acid (including the reduced form to dihydrolipoic acid) and pyruvic acid which may be associated with other chemical substances which, for the sake of simplicity, will henceforth be referred to as "synergists" and this composition will be formulated with additives, excipients and supports for external use or for internal use.

When used in combination, lipoic acid (and / or the reduced form to dihydrolipoic acid) and pyruvic acid can be contained in the composition in an amount by weight of from 0.0001 to 99% each, preferably in an amount of between 0 .01 to 90% by weight.

BIOCHEMICAL PREMISES

Glucose in aerobic organisms is degraded to carbon monoxide and water. The oxidative degradation of glucose takes place up to the formation of pyruvate which allows this carbonaceous residue of carbon to enter the Krebs cycle from which the cell will be able to obtain, always in isothermal conditions, a good part of the energy still trapped in the form of a bond . Acetylcoenzyme A (a) is obtained from pyruvate: '

Pyruvate eliminates carbon dioxide; in this case the residual carbonyl does not remain at the oxidative level of the aldehyde, but is oxidized at the acid level. This reaction represents oxidative decarboxylation.

The reaction occurs at different stages involving different intermediates. In addition to NAD and CoASH, the presence of lipoic acid and FAD is in fact necessary.

Lipoic acid owes its behavior to the presence of the sulfur-sulfur bond which can easily be broken down by the attack of a suitable electron donor and which can be restored to its original form by the action of a suitable oxidizing agent.

The activity of lipoic acid is to be attributed to the presence of sulfur, in this case of the sulfur-sulfur bridge:

in lipoic acid the dihedral angle is only 60 °. In fact, in the lipoic acid ring there is a certain tension (3-6 kcal mol-1) which can account for the sensitivity of the sulfur-sulfur bond to the action of electrophilic and nucleophilic agents or to the action of radiant energy. .

RATIONAL

The rationale for the association between lipoic acid (and / or the reduced form dihydrolipoic acid) and pyruvic acid (in all their respective forms both dextrotor and levorotatory that the racemic mixtures and the cis or trans forms; respective salts as well as the esters that amides) represented by the description of the biochemical path described above is indicative but not exhaustive of the action exerted by each of the two substances and their respective combination for what concerns their chemical, physical action , chemical-physical, biological, physiological and pharmacological.

Lipoic acid (and also the reduced form to dehydrolipoic acid) are able to exert a marked antioxidant action, acting as inhibitors of ROS ("radicai oxygen species") thus inhibiting the formation at different stages and according to different mechanisms of action of free radicals (singlet oxygen radical, hydroxyl radical, nitric radical, etc.). Lipoic acid (and also the reduced form to dehydrolipoic acid) also acts as a ketant of divalent ions which, among other things, can act as accelerators in the formation of free radicals.

Lipoic acid (and also the reduced form to dehydrolipoic acid) also exerts a direct action to recover the antioxidant systems present in the body (ascorbic acid, tocopherols) and induces a substantial increase in glutathione in various human cells. The effect depends on the metabolic reduction of lipoic acid to dehydrolipoic acid capable of reducing cystine. The cysteine thus formed is rapidly used for the synthesis of glutathione. Ultimately, lipoic acid regenerates and prolongs the antioxidant activity of important nutrients such as ascorbic acid, tocopherol and glutathione.

Pyruvic acid plays a fundamental role in various biochemical systems as it is an important part in the cellular energy and respiratory process.

Pyruvic acid, if applied topically, acts as an energetic keratolytic.

SYNERGISTS

The composition based on lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid, in order to obtain a further and more detailed and incisive improvement of the chemical, physical, chemical-physical, biological, physiological and pharmacological action, in the present invention it will be extended by the association of other chemical entities (synergists) which can in turn be used (both individually and in combination) with lipoic acid or pyruvic acid, or with the mixture consisting of lipoic acid and pyruvic acid. for simplicity they are divided into the following groups;

GROUP A)

Glucosamine, Acetylglucosamine, Glucuronic acid (including its lactone), Gluconic acid (including its lactone), ethylenediamitetraacetic acid, hyaluronic acid (molecular weight between 300,000 and 3,000,000 Daltons), whether used individually or in combination, including the respective salts, esters and amides and the relative forms D-L-DL, the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight weight when the proportions between the association of lipoic acid (and also the reduced form with dehydrolipoic acid) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP B)

Asiatic acid, asiaticoside, madecassic acid, sericic acid, sericoside, madecassoside, anthocyanidins, diosmin, glycerretic acid, silymarin, silybin, whether used individually or in combination, including their respective salts, esters and amides and their D-L-DL forms , the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be comprised between 0.01% and 90% by weight.

GROUP C)

Retinol, Retinaldehyde, Tocopherol, Ascorbic Acid, Biotin, Para-aminobenzoic Acid, Betacarotene, Thiamine, Riboflavin, Pyridoxine, Pyridoxal, Niacin, Nicotinic Acid, Nicotinamide, Pantothenic Acid, Folic Acid, Whether used individually or in combination, including their respective salts, esters and amides and the relative forms D-L-DL, the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP D)

Hydroquinone, Metronidazole, Clindamycin, retinoic acid, Minocycline, triclosan (INCI name), Erythromycin, meclocycline, whether used individually or in combination, including their respective salts, esters and amides and the related D-L-DL forms, the components of which the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to acid dehydrolipoic) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP E)

Alanine, Arginine, Arginine, Aspartic Acid, Asparagine, Cysteine, Glutamic Acid, Glutamine, Glieina, Histidine, Leucine, Isoleucine, Vaiine, Lysine, Methionine, Phenylalanine, Praline, Serine, Threonine, Tryptophan, Tirasine, whether used individually in association, including the respective salts, esters and amides and the related D-L-DL forms, the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP F)

hydroxyacids selected from: hydroxyetanoic acid, 2-hydroxypropanoic acid, 2-hydroxybutanoic acid, 2,3-dihydroxypropanoic acid, 2,3-dihydroxybutanediic acid, 2-hydroxybenzoic acid, whether used individually or in combination, including their respective salts, esters and amides and the relative forms D-L-DL, the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP G)

ketoacids selected from: 2-ketopropanoic acid methyl ester, 2-ketopropanoic acid ethyl ester, 3-ketobutanoic acid, 3-ketobutanoic acid methyl ester, 3-ketobutanoic acid ethyl ester, whether used individually or in combination, including their respective salts, esters and amides and the relative forms D-L-DL, the components of the present group can be used in a percentage by weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be between 0.01% and 90% by weight.

GROUP H)

Fatty acids chosen from: lauryl acid, myristic acid, paimitic acid, stearic acid, arachidonic acid, lignoceric acid, myristoleic acid, palmitoleic acid, oleic acid, vaccenic acid, gadoleic acid, sterulic acid, linoleic acid, linolenic acid, γ- acid linolenic acid, arachidonic acid, ricinoleic acid, cerebronic acid, whether they are used individually or in combination, including the respective salts, esters and amides and the relative forms D-L-DL, the components of this group can be used in a percentage in weight from 0.01% to 30% by weight, preferably from 0.05 to 15% by weight when the proportions between the association of lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid will be between 0 , 01% and 90% by weight.

The association of the acid (and also the reduced form to dehydrolipoic acid), of pyruvic acid with suitable synergists is innovative in the cosmetic field in dealing with various phenomena related to the decay of the aesthetic parameters of the skin.

It is particularly useful, but not exclusively, for a moisturizing action, anti-aging action, anti-wrinkle action, elasticizing action, firming action, anti-cellulite action, cosmetic treatment of baldness, treatment of facial redness, treatment of telangiectasias, treatment of couperose, therapy of the "chemical peeling", nourishing action.

Its use in the pharmaceutical field is also innovative for the treatment of atopic dermatitis, seborrheic dermatitis, nummular dermatitis, exfoliative dermatitis, stasis dermatitis, neurodermatitis, acne, acne rosacea, cicatricial alopecia, hippocratic alopecia, female alopecia, toxic medicament alopecia, alopecia aerated, erythema, pseudofolliculitis, psoriasis, lichen ruber planus, ichthyosis, xerodermia, keratosis pilare, pressure ulcers, trophic ulcers, torpid sores, angiomas, nevi or vascular stars, hemangiomas, telangiecatic granuloma, keratosis, seborrheus, treatment hypertrophic scars, burn scars, telangiectasias, circulation and microcirculation alterations, venous stasis, circulatory stasis, lupus erythematosus, topical treatment of scleroderma, wound healing, keloids.

The composition of the invention containing lipoic acid and pyruvic acid possibly associated with suitable synergists of which GROUPS A), B), C), D), E) F), G), H) described above can be prepared in formulations for external use, as a water-in-oil emulsion, oil-in-water emulsions, monophasic solutions, biphasic pseudosolutions, monophasic gels, biphasic gels, anhydrous ointments, aspersone powders, etc., or for internal use as capsules, tablets, drops, syrup, intramuscular injections, intravenous, subcutaneous, intraarticular, etc. using appropriate supports or vehicles.

The composition of the invention can also find effective use for internal use in the pharmaceutical field, for example, in the treatment of degenerative forms of the amorphous component of the tissues, circulatory stasis, venous stasis and arterial stasis, rheumatoid arthritis, osteoarthritis, arthrosis, scleroderma intoxication by ROS (radicai oxygen species) etc.

The following preparation example are further illustrative of the composition of the present invention.

In them the proportions, if not otherwise indicated, are in percentage weight on the basis of the final composition.

Preparation example 1 (cosmetic use)

Ingredients (A) amount by weight% Steareth -21 2,000

Glyceride stearate 3,000

Cyclometicon 1,000

PPG-15-Stearyl ether 2,000

Beeswax 2,000

Stearic acid 1,500

6,000 sunflower oil

Cetyl alcohol 1,000

Paraffin oil 4,000

Wheat germ oil 1,000

Lipoic acid 1,000

Ingredients (B)

Pimvic acid 0.500

Preservative to taste

Perfume to taste

Water q.s.

Method of preparation:

Ingredients (A) and ingredients (B) are heated to 70 ° C separately. Then the ingredients / B) are added to the ingredients (A), mixing everything until a carefully homogenized mixture is obtained in the form of an emulsion for cosmetic use.

Preparation example 2 (pharmaceutical use)

(lotion for external use)

Ingredients

Lipoic acid 1,000

Pyruvic acid 70,000

Solubilizer q.s.

Water qba 100

Method of preparation

Solubilize the lipoic acid in water using the solubilizer, then add the pyruvic acid by mixing

Preparation example 3 (pharmaceutical use)

( injectable solution )

Ingredients

Lipoic acid 0.010

Lecithin 0.070

Pyruvic acid 0.350

Water for injections qba 10

"COMPOSITION FOR COSMETIC OR PHARMACEUTICAL USE BASED ON LIPOIC ACID AND PYRUVIC ACID".

1. A composition for cosmetic, pharmaceutical use characterized in that it contains as active ingredient at least lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid, including the respective salts, esters and amides and the relative forms D-L-DL.

2. The composition of claim 1 which contains as the active ingredient lipoic acid (and also the reduced form to dehydrolipoic acid) in an amount from 0.0001 to 90% w / w, preferably from 0.05 to 25% w / w and pyruvic acid in an amount of 0.0001 to 90% w / w, preferably 0.2 to 30% w / w.

3. Lipoic acid (and its reduced form to dehydrolipoic acid) and pyruvic acid when combined are contained in an amount from 0.01 to 90% w / w, preferably 0.02 to 30% w / p.

4. The composition of claim 1. associated with at least one of the substances selected from glucosamine, acetylglucosamine, glucuronic acid

Claims (16)

"COMPOSITION FOR COSMETIC OR PHARMACEUTICAL USE BASED ON LIPOIC ACID AND PYRUVIC ACID". CLAIMS 1. A composition for cosmetic, pharmaceutical use characterized in that it contains as active ingredient at least lipoic acid (and also the reduced form to dehydrolipoic acid) and pyruvic acid, including the respective salts, esters and amides and the relative forms D-L-DL. 2. The composition of claim 1 which contains as the active ingredient lipoic acid (and also the reduced form to dehydrolipoic acid) in an amount from 0.0001 to 90% w / w, preferably from 0.05 to 25% w / w and pyruvic acid in an amount of 0.0001 to 90% w / w, preferably 0.2 to 30% w / w. 3. Lipoic acid (and its reduced form to dehydrolipoic acid) and pyruvic acid when combined are contained in an amount from 0.01 to 90% w / w, preferably 0.02 to 30% w / p. 4. The composition of claim 1. associated with at least one of the substances selected from glucosamine, acetylglucosamine, glucuronic acid (including the relative lactone), gluconic acid (including the relative lactone), ethylenediamitetracetic acid, hyaluronic acid (molecular weight between 300,000 and 3,000,000 Daltons), including the respective salts, esters and amides and the related D-L-DL forms, said substances can be used in a percentage from 0.001% to 30% w / w, preferably from 0.05 to 15% w / p. 5. The composition of claim 1. associated with at least one of the substances selected from asiatic acid, asiaticoside, madecassic acid, madecassoside, sericic acid, sericoside, including the respective salts, esters and amides and the relative forms D-L-DL, said substances may be used in a percentage from 0.01% to 30% w / w, preferably from 0.05 to 15% w / w. The composition of claim 1. associated with at least one of the substances selected from retinol, retinaldehyde, tocopherol, ascorbic acid, biotin, para-aminobenzoic acid, linoleic acid, linolenic acid, rutin beta-carotene, thiamine, riboflavin, pyridoxine, plus niacin, nicotinic acid, nicotinamide, pantothenic acid, panthenol, folic acid. including the respective salts, esters and amides and the related D-L-DL forms, these substances can be used in a percentage from 0.01% w / w to 30% w / w , preferably from 0.05 to 15%. 7. The composition of claim 1. associated with at least one of the substances selected from hydroquinone, metronidazole, clindamycin, retinoic acid, minocycline, triclosan, erythromycin, including the respective salts, esters and amides and the relative D-L-DL forms, said substances may be used in a percentage from 0.01% w / w to 30% w / w, preferably from 0.05 w / w to 15% w / w. 8. The composition of claim 1. associated with at least one of the substances selected from alanine, arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, glycine, histidine, leucine, isoleucine, goine, lysine, methionine, phenylalanine, praline, serine, threonine, tryptophan, tyrosine, taurine, tauric acid, including the respective salts, esters and amides and the related D-L-DL forms, these substances can be used in a percentage from 0.01% w / w to 30% w / w , preferably from 0.05 w / w to 15% w / w. 9. The composition of claim 1 associated with at least one of the substances selected from hydroxyetanoic acid, 2-hydroxypropanoic acid, 2-hydroxybutanoic acid, 2,3-dihydroxypropanoic acid, 2,3-dihydroxybutanedium acid, 2-hydroxybenzoic acid, including respective salts, esters and amides and the relative forms D-L-DL, said substances can be used in a percentage from 0.01% w / w to 30% w / w, preferably from 0.05% w / w to 15% w / w . 10. The composition of claim 1. associated with at least one of the substances selected from 2-ketopropanoic acid methyl ester, 2-ketopropanoic acid ethyl ester, 3-ketobutanoic acid, 3-ketobutanoic acid methyl ester, 3-ketobutanoic acid ethyl ester, including the respective salts, esters and amides and the related D-L-DL forms, said substances can be used in a percentage from 0.01% w / w to 30% w / w, preferably from 0.05% w / w to 15% w / w. 11. The composition of claim 1. associated with at least one of the substances selected from lauryl acid, myristic acid, paimitic acid, stearic acid, arachidonic acid, lignoceric acid, myristoleic acid, palmitoleic acid, oleic acid, vaccenic acid, gadoleic acid, sterulic acid, linoleic acid, linolenic acid, γ-linolenic acid, arachidonic acid, ricinoleic acid, cerebronic acid, including the respective salts, esters and amides and the relative forms D-L-DL, these substances can be used in a percentage of 0.01 % w / w to 30% w / w, preferably 0.05% w / w to 15% w / w. 12. The composition of claim 1. and 2. associated with at least one of the substances selected from glucosamine, acetylglucosamine, glucuronic acid (including the relative lactone), gluconic acid (including the relative lactone), ethylenediamitetracetic acid, hyaluronic acid (including molecular weight between 300,000 and 3,000,000 Daltons), asiatic acid, asiaticoside, madecassic acid, madecassoside, sericic acid, sericoside, retinol, retinaldehyde, tocopherol, ascorbic acid, biotin, para aminobenzoic acid, linoleic acid, linolenic acid, rutin, beta-carotene, thiamine , riboflavin, pyridoxine, pyridoxal, niacin, nicotinic acid, nicotinamide, pantothenic acid, panthenol, folic acid, hydroquinone, metronidazole, clindamycin, retinoic acid, minocycline, triclosan, erythromycin, alanine, arginine, aspartutic acid, cysteine, asparagus , glutamine, glycine, histidine, leucine, isoleucine, goine, lysine, methionine, phenylalanine, praline, serine, threonine, tryptophan, tyrosine, taurine, tauric acid, hydroxyetanoic acid, 2-hydroxypropanoic acid, 2-hydroxybutanoic acid, 2,3-dihydroxypropanoic acid, 2,3-dihydroxybutanedioic acid, 2-hydroxybenzoic acid, 2-ketopropanoic acid methyl ester, 2- acid ketopropanoic ethyl ester, 3-ketobutanoic acid, 3-ketobutanoic acid methyl ester, 3-ketobutanoic acid ethyl ester, lauryl acid, myristic acid, paimitic acid, stearic acid, arachidonic acid, lignoceric acid, myristoleic acid, palmitoleic acid, oleic acid, vaccine acid gadoleic acid, sterulic acid, linoleic acid, linolenic acid, γ-linolenic acid, arachidonic acid, ricinoleic acid, cerebronic acid, including their respective salts, esters and amides and the related D-L-DL forms, these substances can be used in a percentage 0.01% w / w to 30% w / w, preferably 0.05% w / w to 15% w / w. 13. The composition of claim 1.-12. for use for cosmetic or pharmaceutical use essentially intended for external use, applied on the skin, whether damaged or intact, or on the mucous membranes, as a water-in-oil emulsion, oil-in-water emulsions, monophasic solutions, biphasic pseudosolutions, monophasic gels, biphasic gels, anhydrous ointments, sprinkling powders, etc. and for internal use, taken in the form of tablets, prolonged release tablets, confetti, gastro-resistant confetti, capsules, long-acting capsules, syrup, drops, suppositories or in any other pharmaceutical form, or injected intramuscularly, intra venously, sotocutaneously , intra articular, etc. 14. The composition of claims 1.-12. for cosmetic use for a moisturizing action, anti-aging action, anti-wrinkle action, eiasticizing action, firming action, anti-cellulite action, cosmetic treatment of baldness, treatment of facial redness, treatment of telangiectasias, treatment of couperose, "chemical peeling" therapy, nourishing action. 15. The composition according to claims 1.-12. for pharmaceutical use for the treatment of atopic dermatitis, seborrheic dermatitis, nummular dermatitis, exfoliative dermatitis, stasis dermatitis, neurodermatitis, acne, acne rosacea, cicatricial alopecia, hippocratic alopecia, female alopecia, toxic medicament alopecia, aerated alopecia, erythema, pseudofolitis psoriasis, lichen ruber planus, ichthyosis, xeroderma, keratosis pilare, pressure ulcers, trophic ulcers, numb sores, angiomas, vascular nevi or stars, hemangiomas, telangiecatic granuloma, seborrheic keratosis, fibrous histiocytoma, scarring, scarring, scar treatment burns, telangiectasias, alterations of the circulation and microcirculation, venous stasis, circulatory stasis, lupus erythematosus, topical treatment of scleroderma, wound healing, keloids, in the treatment of degenerative forms of the amorphous component of the tissues, circulatory stasis, venous stasis and stasis arterial, rheumatoid arthritis, osteoarthritis, arthritis yes, scleroderma, ROS intoxication (radicai oxygen species) etc. 16. Composition for cosmetic or pharmaceutical use based on lipoic acid and pyruvic acid, as substantially described above, illustrated and claimed for the specified purposes.