KR20080063005A - Cosmetic composition containing piceatannol and vitamin a (retinoids) - Google Patents

Abstract

A skin cosmetic composition comprising piceatannol and vitamin A is provided to alleviate harmful actions of retinol such as skin irritation and enhance skin care effect of the retinol. A skin cosmetic composition comprises: about 0.001-5 wt.% of a vitamin A selected from the group consisting of retinol, retinyl ester, retinal, retinoic acid, retino phosphoric acid, retino phosphate, a derivative or an affinity thereof, and a mixture thereof; about 0.0001-10 wt.% of at least one selected from the group consisting of piceatannol, a dermatologically acceptable salt thereof, an ester thereof, an amide thereof, a drug-precursor thereof, an affinity thereof and a mixture thereof; and a cosmetically acceptable media. The composition is formulated into ointment, lotion, cream, emulsion, micro-emulsion, gel or solution.

Description

Cosmetic composition containing picacetanol and vitamin A (retinoids)

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cosmetic composition containing vitamins A, piaceanol and derivatives thereof, and is useful for skin care treatments aimed at improving collagen synthesis without stimulation.

Retinol (vitamin A) is an endogenous substance that exists naturally in the human body and is essential for the differentiation of epithelial cells. Natural and synthetic vitamin A derivatives are widely known as anti-wrinkle agents and are effective in reducing subcutaneous aging effects such as wrinkles, flickering, porosity, roughness, drying, and spots (excessive pigmentation) (Kingman). US Pat. No. 4,603,146 and US Pat. No. 4,877,805). It is apparent that vitamin A has an effect of reducing inflammation in the epidermis (acanthosis, skin thickening) and local edema in the epidermis causing epidermal detachment.

In formulating a vitamin A-containing formulation, care should be taken to ensure that vitamin A is released and maintained in the stratum corneum at an optimal concentration while absorption into the body circulation is minimal. It is also important that the user respond to chronic treatment. However, in existing vitamin A-containing products, drying or irritation occurs, causing excessive skin peeling. In such compositions, the user may be forced to stop using the frequent and sufficient amounts of vitamin A combination products necessary for the full effect.

The present invention is partly due to the unexpected finding that a composition combining natural or synthetic vitamin A and piaceanol as an anti-inflammatory agent is released to the skin while inhibiting dryness and / or irritation of the skin and also taking advantage of vitamin A ingredients. Is based on. This composition improves the acceptability of the user, and at the same time promotes better usability for the user with an overall improvement of the skin conditioning effect.

Piaceanol (trans-3,4,3 ', 5'-tetrahydroxystilbene) is a component recognized in many plants and is often a structurally related substance, resveratrol (trans-4,3', 5'-tree). Hydroxystilbene) is also recognized.

Both components are synthesized in plants in response to fungi and other environmental stresses and are classified as phytoalexins. Piaceanol has been identified as an active agent of the scientific name Melaleuca leucadendron (white tea tree). See, for example, Tsuruga, T., Chun, Y.T., Ebizawa, Y. & Sankawa, U. (1991) Biologically Active Composition of Melaleuca leucadendron: Inhibitors of Histamine Release from Lactic Mast Cells Chem. Pharm. Bull. (Tokyo) 39: 3276-3278.

It was also identified as an effective agonist of Cassia garretiana, (Asian legume). The literature describes Inamori, Y., Kato, Y., Kubo, M., Yasuda, M., Baba, K., & Kozawa, M. (1984), 3,3 ', isolated from heartwood of Cassia garretiana (CRAIB). Physiological Actions of 4,5'-TetrahydroxyStilbene "Chem. Pharm. Bull. Tokyo 32: 213-3218.

It was also identified as an active ingredient of Rheum undulatum. Literature includes Ko, S.K., lee, S.M., & Whang, W.K. (1999) "Antiplatelet Aggregation of Stilbene Derivatives from Rheum undulatum" Arch. Pharm. Res. 22: 401-403, and Matsuda, H., Kageura, T., Toguchida, I., Harima, S. & Yoshikawa, M. (2000) “From rhubarb on nitrogen monoxide in macrophages activated with lipopolysaccharides Action of obtained stilbene component ”Bioorg. Med. Chem. Lett. 10: 323-327. These are used in traditional Chinese medicine.

In addition, as an anti-leukemia component of the seeds of Euphobia lagascar (Euporbia), it is used for the folk treatment of cancer, tumor and nodules. Documents include Ferrigni, N.R., McLaughin, J.L., Powell, R.G., & Smith, C.R. (1984) "Use of Potatophan and Brine-Shrimp Bioassay for Isolation and Detection of Piaceanol as an Anti-Leukemia Agonist in Seeds of Newportia" J. Nat. Prod. 47: 347-352.

Teguo et al. Detected piaceanol in cell suspension culture of Vitis venifera (Vitis venifera, a kind of wine grape). See Teguo, P.w., Decendit. S., Krisa, S., Deffieux, G., Vercauteren, J. & Meri11on, J.M. (2001) Accumulation of Stilbenglycosides in Cell Suspension Cultures of Vitisvenifera J. Nat. Prod. 59: 1189-1191.

Cosmetic compositions containing resveratrol have already been described. For example, Pezzuto et al. (US Pat. No. 6,414, O37) disclose a method for the prevention or treatment of skin conditions by the composition containing resveratrol, while Pillai et al. (US Pat. No. 6,358,517) disclose resveratrol and selected vitamins A The composition of the skin care cosmetics by blending with is disclosed. The cosmetic composition using piaceanol as an active ingredient is not yet described. Scientific evidence demonstrates that the uniqueness of piaceanol and the addition of a hydroxyl group to piaceanol are not merely extensions of resveratrol.

For example, J. Immunol, Ashikawa et al. 2002 Dec 1; See 169 (11): 6490-7. Piaceanol and its derivatives are phenolic components and therefore act as powerful antioxidants.

The main invention of the present invention is the discovery of a composition for skin conditioning containing vitamin A that significantly improves skin suitability,

(a) a single vitamin A selected from the group consisting of retinol, retinyl esters, retinal, retinoic acid, retinophosphate, derivatives or analogs thereof, and combinations thereof, with a concentration of about 0.001 weight % To about 5% by weight;

(b) a combination with piceanol, dermatologically acceptable salts, esters, amides, their prodrugs and analogs, and any one thereof, the concentration of which is about 0.0001% by weight to about 10 weight percent;

(c) acceptable media as cosmetics

It is to include

The term "conditioning" used in the text refers to dry skin, light skin, wrinkles, aging, aging, acne, thin skin, psoriasis, atopic dermatitis Prevention and treatment, increased flexibility of the stratum corneum, control of sebum secretion, and general improvement of the skin. The composition can be used to improve skin lactation and cell proliferation.

By the presence of piceanol in the present invention, the action of retinol or retinyl ester is substantially improved. That is, piaceanol substantially enhances the ability of retinol or retinyl esters to act on cell proliferation. In mammals, piaceanol has antioxidant and anti-inflammatory effects that interfere with cytokine production and function (with unknown molecular level targets).

However, substantial improvement in skin utility is realized when piaceanol is combined with retinol or retinyl ester. That is, the present invention is based, at least in part, on the discovery of synergistic interactions between retinol or retinyl esters and piaceanol.

According to the present invention, by adding an effective amount of piceanol in a retinol or retinyl ester-containing composition, the functional performance of the composition is substantially improved.

In the present invention, dry skin, light skin, wrinkles, age, skin, acne, skin, psoriasis, atopic dermatosis, prevention and treatment of the skin, increased stratum corneum flexibility, sebum secretion, and skin quality The method of improvement or prevention of conditions, such as general improvement, is also included, The method also includes the method of apply | coating the composition of this invention to skin.

Although the composition of the present invention is intended for topical application to the skin of aged, lightly ill mammals with dry, crunchy wrinkles, the composition of the present invention can be prevented to prevent or alleviate the degenerative changes of normal skin. You may apply.

The present invention also includes a cosmetic method of controlling skin irritation, tingling or inflammation caused by vitamin A. In this respect, the present invention also includes a cosmetic composition containing a combination of physethanol and vitamin As.

[Overview and Definitions]

The term "piceanol" is intended to refer to either the cis isomer of piaceanol, the trans isomer of piaceanol, or a mixture of the two isomers. The term is also intended to refer to both natural active ingredients and compounds by chemical synthesis in the laboratory. In addition, the term "picetanol" in the text is intended to include dermatologically acceptable salts, esters, amides, drug precursors and analogues of piceanol.

The term "treat", such as "treating skin conditions", includes, but is not limited to, (1) prevention of conditions, i.e. prevention of any clinical symptoms of the condition, (2) inhibition of conditions, i.e. the development of clinical symptoms. Or retardation of progression, and / or (3) alleviation of the condition, ie causing regression of clinical symptoms.

"Dermatologically acceptable" means a material that is not biologically or otherwise inappropriate. That is, the substance is a substance that can be administered to the individual with the selected active ingredient and does not cause any uncomfortable biological action or cause harmful interaction with any ingredient in the composition of the medicament in which it is contained. Similarly, "dermatologically acceptable" salts or "dermatologically acceptable" esters of the active ingredients in the text are salts or esters that are not biologically or otherwise inappropriate.

"Optional" or "optionally" means a case where a situation described later occurs and a case that does not need to occur. Thus, it includes both cases where the situation occurs and cases that do not occur. For example, when an additive in a prescription is described as "optionally present," it includes both prescriptions containing and not containing those additives.

[Active ingredient for treatment]

The present invention described above includes the use of piaceanol for the prevention or treatment of skin conditions associated with the use of vitamin A.

Piaceanol can be used in its natural state, ie, isolated from grape skins, wine or other plant-derived components, and chemically synthesized in the laboratory or commercially available products such as Biomol Research Laboratories Inc. (Primos Meeting). City, PA may be used to procure. The preferred method of obtaining physethanol from natural sources is to extract this component from the bark of Tow, Germany.

This active ingredient can also be used as a dermatologically acceptable salt, ester, amide, drug sphere or softener or in combination thereof. Salts, esters, amides, drug precursors and analogues of piaceanol can be prepared by standard procedures known to those skilled in the art of organic synthesis chemistry and pharmaceutical preparations. The preparation of esters involves the functionalization of the hydroxyl groups in the molecular structure of the drug. Esters are typical acyl substituted derivatives of free alcohol groups.

That is, it is part of the carboxylic acid derivative of the formula RCOOH (R is an alkyl group, with a lower molecular alkyl group being preferred). The esters are reconverted to free acids by conventional hydrocracking or hydrolysis as necessary. The preparation of amides and drug precursors is also possible in a similar manner. The preparation of other derivatives and analogs of the active ingredient can be inferred by standard procedures known to those skilled in organic synthetic chemistry or by literature references.

Preferred derivatives of the cisethanol cis and trans forms are those in which one or more of the hydroxyl groups of the component, typically the 3-hydroxyl group, is combined with a monosaccharide or a disaccharide, generally a monosaccharide. Examples of the saccharide that may be combined with the molecule of piaceanol include, but are not limited to, glucose, galactose, maltose and saccharose. Cis-Piacetanol glucoside and trans-Peatanol glucoside (astringin) are particularly preferred.

[Prescription for cosmetics]

In a preferred formulation embodiment, the active ingredient is added to a topical compositional formulation comprising a carrier suitable for topical application and a technically known substance. As a topical carrier, one is selected so that the composition is provided in the desired form.

For example, curb, lotion, cream, microemulsion, gel, oil, solution, or the like may contain any of natural or synthetic substances. It is an essential condition that the chosen carrier must not adversely affect the active ingredient or other ingredients in the topical composition.

Suitable carriers for topical application are water, alcohols, glycols and other nontoxic organic solvents, glycerin, mineral oil, silicone, petrolatum, lanolin, fatty acids, vegetable oils, waxes and the like.

Particularly preferred topical carriers are colorless odorless solutions, lotions, creams, microemulsions and gels.

Various additives known to those skilled in the art can be included in topical formulations according to the present invention. Examples of the additives include dissolution aids, skin penetration enhancers, milk whitening agents, preservatives (e.g., antioxidants), gelling agents, buffers, surfactants (especially nonionic amphoteric surfactants), emulsifiers, emollients, thickeners, stabilizers. Although it is a wetting agent, a coloring agent, a fragrance | flavor, etc., it is not limited to these. Particular preference is given to adding dissolution aids and / or skin penetration enhancers with emulsifiers, emollients and preservatives.

Skin permeability enhancers facilitate the therapeutic concentration of the active ingredient through areas of substantial area of intact skin. Suitable enhancers are well known in the art and include, for example, 2-propanol or dimethylisosorbide.

Examples of the dissolution aid include, but are not limited to the following: 1,3-butylene glycol and dipropylene glycol.

Other active ingredients may also be included in the prescription. That is, other anti-inflammatory, analgesic, antibacterial, antifungal, antibiotic, vitamins, antioxidants or sunburn agents, but commonly used as sunburn inhibitors include titanium dioxide, zinc oxide, anthranilate, benzophenone (especially benzophenone-3). ), Camphor derivatives, cinnamon acid salts (eg octylmethoxy cinnamic acid salts), dibenzoylmethane (eg butylmethoxydibenzoylmethane), p-aminobenzoic acid (PABA) and derivatives thereof, and salicylates ( For example octylsalicylate).

In a preferred topical formulation of the present invention, the active ingredient is included in the range of about 0.005% to 10% by weight, preferably in the range of about 0.01% to 5% by weight, more preferably about 0.1% by weight In the range of 5% by weight, most preferably in the range of about 0.1% to 2% by weight.

Prescription products are, as described in the preceding paragraph, ointments, lotions, creams, microemulsions, gels, solutions, and the like, applied topically to the skin in an effective dosage range to achieve the desired results. Preferred single doses of the active ingredient range from 1 to 100 ml. Generally, the dosing regimen includes at least once daily topical administration.

Although the present invention has been described with specific formulation names, it should be understood that the above-described examples and the following are intended to illustrate the object of the present invention and are not limited thereto. Other features, advantages and improvements will be apparent to those skilled in the art of this invention.

All patents, patent data, and references cited in this document are incorporated herein by reference.

Example 1

Although an Example is shown below in order to disclose all the manufacturing methods of the prescription product based on this invention to a general skilled person, they do not mean limiting the range considered by this inventor to this invention here. Regarding numbers (for example, quantity, temperature, etc.), efforts have been made to ensure accuracy as much as possible, but there may be some errors or errors.

Unless specifically stated, the ratio is proportion by weight, the temperature is Celsius, and the atmospheric pressure is atmospheric pressure. All solvents, reagents, and additives are of pharmaceutical grade.

Example 2

This example demonstrates that the solution of piaceanol suppresses vitamin A induced stimuli and improves skin appearance.

The composition of Example 1 and Comparative Examples 1 and 2 was prepared using the component shown in Table 1.

TABLE 1

The composition was adjusted as follows: d-α-topoferol, retinyl palmitate (1.7 m. IU / g) and trans-piceanol were dissolved in dimethylisosorbide at 30 ° C. and cleared. Dipropylene glycol is added at 30 degreeC similarly at the time of solution. The operation was performed under a nitrogen blanket and all solutions were stored under nitrogen.

The intensity of the stimulus as a cosmetic for the compositions of Example 1 and Comparative Examples 1 and 2 was reviewed by a variation of the human 4-h patch test (Basketter D.A. et al., Food Chem Toxic 1 1997,: 35: 845-852). It was. The experiment applied 0.2 ml of the test solution on a 25 mm heel top chain bar with a webbrill pad (Hilltop, Cincinnati, Ohio, USA) to the skin of the upper forearms of 16 volunteers. Both arms of the subject were used, and the patches were also randomly attached to the balance.

After 24 hours the patch was removed and the test site was marked with a marker pen. The test site was observed every 24, 48 and 72 hours, and the presence or absence of a stimulus was determined by the 4 rating method (Table 2) at 24, 48 and 72 hours after patch removal.

TABLE 2

The results are shown in Table 3.

TABLE 3

When piaceanol was added, the stimulation of retinyl palmitate was clearly suppressed.

In the compositions of Example 1 and Comparative Examples 1 and 2, the effect on skin wrinkle improvement as a cosmetic was measured with a computerized laser sidemeter. The test was conducted with 16 women over 30 years of age, and the compositions of Experiment 1 and Comparative Experiments 1 and 2 were applied to the subject's face (area 2 × 2 cm 2) once daily for 9 weeks.

Next, a replica (replica) of skin wrinkles was created using a precision structural compound of plastic silicone. Changes in the skin wrinkles of the duplicates were detected with a visual skin meter (Skin Viscometer, Couage & Khazaka electronic GmbH, Germany). Three-dimensional images of the replicas were analyzed with a CCD camera. The skin wrinkle improvement effect was calculated as the average roughness (Rz) of the wrinkles according to the following equation (1):

Rz = (R1 + R2 + ‥‥‥‥‥‥ Rn-1 + Rn) / Number of wrinkles (n) (1)

In the above numerical equation, Rn denotes the roughness of each wrinkle and n denotes the number of wrinkles. The results are shown in Table 4 below.

TABLE 4

As can be seen from the table above, the height (roughness) of the wrinkles was reduced by 70% (p <0.01) after administration for 9 weeks in the composition of Example 1, and 56% after 9 weeks in the composition of Comparative Example 1 (p < 0.01) decreased. This means that in Example 1 and Comparative Example 1, the roughness of the skin wrinkles is significantly improved as compared to the placebo (Comparative Example 2). The results also indicate that piaceatanol actually enhances the action of retinol (vitamin A) on wrinkle improvement. This result also indicates that the composition as a cosmetic of the present invention exhibits a visible effect on wrinkle improvement in a short time.

Example 3

In this example, trans- (3,5,3 ', 4'-tetrahydroxystilbene) -3-0-β-d-glucopyranoside (trans-astrinzine) is a vitamin A solution solution. Demonstrates suppressing flow-induced irritation and improving skin appearance.

The composition of Example 2 was prepared using the component shown in Table 5.

TABLE 5

This composition was adjusted according to the operation of Example 1.

The intensity | strength of the skin irritation of the composition of Example 2 was compared with that of Comparative Examples 1 and 2 by the same method as the test method described in the paragraph of Example 1.

The results are shown in Table 6.

TABLE 6

Stimulation of retinyl palmitate was inhibited by the addition of piceanol glucoside (astringin). The effect on the skin wrinkle improvement of the composition of Example 2 was examined by the same method as the method described in Example 1. The results are shown in Table 7.

TABLE 7

As can be seen from the table above, the height (roughness) of the wrinkles was reduced by 67% (p <0.01) after administration for 9 weeks in the composition of Example 2. This means that in Example 1 and Comparative Example 1, the roughness of the skin wrinkles was significantly improved as compared to the placebo (Comparative Example 2). The results also indicate that astringin actually enhances the action of retinol (vitamin A) on wrinkle improvement. This result also indicates that the composition as a cosmetic of the present invention exhibits a visible effect on wrinkle improvement in a short time.

Example 4

This example demonstrates that Piaceatanole emulsion (lotion) type prescription products suppress vitamin A-induced irritation and improve skin appearance. The composition of Example 3 and Comparative Examples 3 and 4 was prepared using the component shown in Table 8.

TABLE 8

This lotion was prepared by the standard operation of the cosmetic lotion.

The intensity | strength of the skin irritation of the composition of Example 3 was compared with that of Comparative Examples 3 and 4 by the same method as the test method described in the paragraph of Example 1.

The results are shown in Table 9.

TABLE 9

Stimulation of retinyl palmitate in the lotion was clearly inhibited by the addition of piaceanol.

The effect on the skin wrinkle improvement of the composition of Example 3 was examined by the same method as the method described in Example 1. The results are shown in Table 10.

TABLE 10

As can be seen from the above table, the height (roughness) of the wrinkles decreased by 55% (p <0.01) for 9 weeks in the composition of Example 3, and 31% (p <after 9 weeks in the composition of Comparative Example 3). 0.01) decreased.

This means that in Example 3 and Comparative Example 3, the roughness of the skin wrinkles was significantly improved as compared to the placebo (Comparative Example 4). The results also indicate that piaceatol actually enhances the action of retinol (vitamin A) on wrinkle improvement.

This result also indicates that the composition as a cosmetic of the present invention exhibits a visible effect on wrinkle improvement in a short time.

Example 5

In this example, it is demonstrated that piaceanol glucoside (astrinzine) is an emulsion (lotion) type prescription product that suppresses vitamin A-induced irritation and improves skin appearance. The composition of Example 4 was prepared using the component shown in Table 11.

TABLE 11

This lotion was prepared by the standard operation of the cosmetic lotion. The intensity | strength of the skin irritation of the composition of Example 4 was examined by the method similar to the test method described in the term of Example 1. The results are shown in Table 12.

TABLE 12

Stimulation of retinyl palmitate in the lotion was clearly suppressed by the addition of astringin.

The effect on the skin wrinkle improvement of the composition of Example 4 was examined by the same method as the method described in Example 1. The results are shown in Table 13.

TABLE 13

As can be seen from the above table, the height of the wrinkles (roughness) was reduced by 65% (p <0.01) after administration for 9 weeks in the composition of Example 4. This means that the roughness of the skin wrinkles is significantly improved in Example 4 compared to the placebo (Comparative Example 4).

The results also indicate that astringin actually enhances the action of retinol (vitamin A) on wrinkle improvement, and that astringin is more efficient than piaceanol in emulsion cosmetics.

This result also indicates that the composition as a cosmetic of the present invention exhibits a visible effect on wrinkle improvement in a short time.

The composition based on the present invention is mainly intended for cosmetics that are applied topically to human skin, in particular, products that aim to condition, moisturize, smoothen, and prevent the appearance and wrinkles of wrinkles and skin, for example.

Claims (17)

(a) a single vitamin A selected from the group consisting of retinol, retinyl esters, retinal, retinoic acid, retinophosphate, derivatives or softeners thereof, and combinations thereof with any one of Is about 0.001% to about 5% by weight; (b) a combination with piceanol, dermatologically acceptable salts, esters, amides, drug precursors and analogues thereof, and any of these, wherein the concentration is from about 0.0001% to about 10% by weight Being; (c) acceptable media as cosmetics Composition of the cosmetic for skin comprising a. (a) about 0.005 to about 5 weight percent of vitamin A; (b) from about 0.001 to about 10 weight percent of piceanol and its dermatologically acceptable salts, esters, amides, drug precursors, analogs, and either Composition of the cosmetic for skin comprising a. The method of claim 2, The composition of cosmetics for skin whose active ingredient is piaceanol. The method of claim 2, The composition of the cosmetics for skins whose active ingredient is a combination of piaceanol, a monosaccharide, or a disaccharide. The method of claim 2, The composition of the cosmetics for skin whose active ingredient is piaceanol-3-0- (beta) -d-glucopyranoside (astringin). The method of claim 2, A composition of skin cosmetics comprising vitamins A selected from retinol, retinyl esters, retinal, retinoic acid, retinophosphate, and derivatives thereof, softeners and combinations thereof. The method of claim 2, A composition for cosmetics for skin, further comprising a component selected from any one of sun tanning agents and tocopherol antioxidants and combinations thereof. The method of claim 7, wherein A composition of dermatological cosmetic comprising from about 1 wt% to about 99.5 wt% of a dermatological carrier. The method of claim 8, A composition for cosmetics for the skin, which is a formulation of an ointment, lotion, cream, emulsion, microemulsion, gel or solution. (a) about 0.005 to about 5 weight percent of vitamin A; (b) from about 0.001 to about 10 weight percent of piceanol, and any dermatologically acceptable salts, esters, amides, drug precursors, analogs, and any one thereof; (c) a dermatologically acceptable medium containing from about 0.005 to about 5% by weight of said vitamin A Composition of the cosmetic for skin comprising a. The method of claim 10, The composition of cosmetics for skin whose active ingredient is piaceanol. The method of claim 11, A composition for cosmetics for skin, wherein the active ingredient is a combination of piceanol and monosaccharides or disaccharides. The method of claim 12, A composition for cosmetics for skin, wherein the active ingredient is piaceanol-3-0-β-d-glucopyranoside (astrinzine). The method of claim 10, A composition of skin cosmetics comprising vitamins A selected from retinol, retinyl esters, retinal, retinoic acid, retinophosphate, and derivatives thereof, softeners and combinations thereof. The method of claim 10, A composition of skin cosmetics comprising a component selected from any one of tanning agents and tocopherol antioxidants and combinations thereof. The method of claim 10, A composition of dermatological cosmetic comprising from about 1 wt% to about 99.5 wt% of a dermatological carrier. The method of claim 16, A composition for cosmetics for the skin, which is a formulation of an ointment, lotion, cream, emulsion, microemulsion, gel or solution.