JP2008162937A - Cosmetic composition containing piceatannol and vitamin a (retinoids) - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for skin cosmetics effective for mitigating the harmful action of retinol such as skin stimulation and improving the skin care effect of retinol. <P>SOLUTION: The skin conditioning composition containing vitamin A compounds and effective for remarkably improving the skin compatibility contains the following components. (a) A single vitamin A selected from retinol, retinyl esters, retinal, retinoic acid, retinoic acid salts, their derivatives or analogs and a group compounded with either one of the compounds and having a concentration of from about 0.001% to about 5%; (b) piceatannol, its dermatologically acceptable salts, esters, amides, their prodrugs and analogs and a formulation with either one of the compounds at a concentration of from about 0.0001% to about 10%; and (c) a medium acceptable as cosmetics. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a cosmetic composition containing vitamins A and piceatanol and derivatives thereof, and is useful for skin care treatments that improve collagen synthesis without irritation.

  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-epileptic substances and are effective in reducing subcutaneous aging effects such as wrinkles, rust, porosity, roughness, dryness, mottle (hyperpigmentation) (for Kingman) (See Patent Documents 1 and 2). It is self-evident that vitamin A has an action to reduce inflammation that causes thickening of the epidermis (acanthosis, skin hypertrophy) and local intracellular edema that causes epidermal detachment.

When formulating a composition containing vitamin A, care must be taken to ensure that the vitamin A is released and retained in the stratum corneum at the optimal concentration, while absorption into the systemic circulation is minimal. . Furthermore, it is also important to cope with the case where the user handles chronically. However, existing vitamin A-containing products become dry and irritated, resulting in excessive skin peeling. With such a composition, the user may be forced to stop using the frequent and sufficient amount of vitamin A-containing product necessary for maximum effect.
U.S. Pat. No. 4,603.146 U.S. Pat. No. 4,877.805

  In the present invention, a composition comprising natural or synthetic vitamin A and piceatanol as an anti-inflammatory agent is well released to the skin while well controlling the dryness and / or irritation of the skin and taking advantage of the vitamin A component. This is based in part on the unexpected knowledge that These compositions improve user acceptance, thus promoting better usability for the user with a general improvement in skin conditioning effects.

  Piceatanol (trans-3,4,3 ', 5'-tetrahydroxystilbene) is a component found in many plants and is often a structurally related substance resveratrol (trans-4,3', 5 ' -Trihydroxystilbene) is also observed.

  Both components are synthesized in plants in response to mold and other environmental stresses and are classified as phytoalexins (plant complements). Piceatanol has been identified as an effective agent under the scientific name Melaleuca leucadendron (white tea tree). Literature is Tsuruga, T., Chun, YT, Ebizawa, Y. & Sankawa, U. (1991) "Biologically active components of Melaleuca leucadendron: Inhibitors of induced histamine release from rat mast cells" Chem. Pharm. Bull (Tokyo) 39: 3276-3278.

  It was also identified as an effective agent of Cassia garretiana, (Asian legume). The literature is Inamori, Y., Kato, Y., Kubo, M., Yasuda, M., Baba, K., & Kozawa, M. (1984) `` I isolated from the core material of Cassia garretiana (CRAIB) 3, Physiological action of 3 ', 4,5'-tetrahydroxystilbene "Chem. Pharm. Bull. (Tokyo) 32: 213-3218.

  It was also identified as an active ingredient in Rheum undulatum. Literature is Ko, SK, lee, SM, & Whang, WK (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) "Effects of stilbene components from Daihuang on nitric oxide in macrophages activated with lipopolysaccharide," Bioorg. Med. Chem. Lett. 10: 323-327. These are used in traditional Chinese medicine.

  In addition, it is used as an anti-leukemia component of Euphobia lagascar seeds in the private treatment of cancer, tumors and aneurysms. Literature is Ferrigni, NR, McLaughin, JL, Powell, RG, & Smith, CR (1984), “Potato plates and brine shrimp bio for isolation and detection of piceatanol as an anti-leukemia agent in Euphorbia seeds. Assay Use "J. Nat. Prod. 47: 347-352.

  Teguo et al. Detected Piceatanol in a cell suspension culture of Vitis venifera. Literature is Teguo, Pw, Decendit.S., Krisa, S., Deffieux, G., Vercauteren, J. & Merillon, JM (2001) `` Accumulation of stilbene glycosides in cell suspension cultures of Vitis venifera. '' Nat. Prod. 59: 1189-1191.

  Cosmetic compositions containing resveratrol have already been described. For example, Pezzuto et al. (US Pat. No. 6,414,037) discloses a method for the prevention or treatment of skin conditions with a resveratrol-containing composition, and Pillai et al. (US Pat. No. 6,358,517) discloses vitamin A selected as resveratrol. The composition of skin care cosmetics is disclosed by blending with a product. A cosmetic composition using piceatanol as an active ingredient has not yet been described. Scientific evidence demonstrates that the uniqueness of piceatanol and the addition of a hydroxy group to piceatanol is not a simple extension of resveratrol.

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

The main invention of the present invention is the discovery of a vitamin A-containing skin conditioning composition that significantly improves skin compatibility, including:
(A) A single vitamin A selected from the group consisting of retinol, retinal esters, retinal, retinoic acid, retinoic acid salts, derivatives or analogs thereof, and combinations thereof with any of these concentrations. From about 0.001% to about 5%;
(B) Piceatanol, dermatologically acceptable salts, esters, amides, prodrugs and related substances thereof, and combinations thereof with any of these, having a concentration of about 0.0001% to about 10%;
(C) Medium acceptable as cosmetics

  The term “conditioning” used in the text means dry skin, light-damaged skin, wrinkle expression, age group, aging skin, acne, light skin, psoriasis, prevention and treatment of atopic skin disease, Increased stratum corneum flexibility, control of sebum secretion, and general improvement of skin quality. The composition can be used to improve skin desquamation and cell proliferation.

  The presence of piceatanol in the product of the present invention substantially improves the action of retinol or retinyl ester. That is, piceatanol substantially enhances the ability of retinol or retinyl ester to affect cell proliferation. In mammals, piceatanol exerts antioxidant and anti-inflammatory effects that interfere with cytokine production and function (although molecular targets are unknown).

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

  In accordance with the present invention, the addition of an effective amount of piceatanol into a retinol or retinyl ester containing composition substantially improves the potency of the composition.

  The present invention includes dry skin, light-damaged skin, wrinkle expression, aging spots, aging skin, acne, pale skin, psoriasis, prevention and treatment of atopic dermatoses, increased flexibility of the stratum corneum, Methods for improving or preventing conditions such as control of sebum secretion and general improvement of skin quality are also included, and the method also includes a method of applying the inventive composition to the skin.

  The composition of the present invention is intended for topical application to the skin of already dried, crunchy, wrinkled, senile, light-damaged mammalian skin, but the composition of the present invention prevents the regression of healthy skin. Alternatively, it may be applied prophylactically for mitigation.

  The present invention further includes cosmetic methods for controlling skin irritation, tingling or inflammation that may result from vitamin A. In this regard, the invention also includes cosmetic compositions containing a combination of piceatanol and vitamin A.

[Overview and definition]
The term “piceatanol” is intended to refer to either the cis isomer of piceatanol or the trans isomer of piceatanol, or a mixture of both isomers. The term is also intended to refer to both natural active ingredients and chemical compounds in the laboratory. Furthermore, the reference to “piceatanol” in the text is intended to encompass the dermatologically acceptable salts, esters, amides, prodrugs and related substances of piceatanol.

  The term “treat” such as “treat skin condition” includes (1) prevention of condition, ie prevention of any clinical symptoms of condition, (2) suppression of condition, ie clinical symptoms. It is intended to encompass the prevention or progression of progression and / or (3) alleviation of conditions, i.e., causing regression of clinical symptoms.

  “Dermatologically acceptable” means a substance that is not biologically or otherwise inappropriate. That is, the substance is administrable to an individual with the selected active ingredient and does not cause any adverse biological effects or causes harmful interactions with any ingredient in the composition of the pharmaceutical in which it is contained. It is a substance that does not. Similarly, a “dermatologically acceptable” salt or “dermatologically acceptable” ester of an active ingredient in the text means a salt or ester that is not biologically or otherwise inappropriate. It is.

  “Selective” or “selectively” means when a situation described later occurs or not. Thus, it includes both cases where the situation occurs and cases where it does not occur. For example, if an additive in a formulation is described as “optionally present”, it includes both formulations containing and not containing the additive.

[Active ingredients for treatment]
The invention described above includes the use of piceatanol for preventing or treating skin conditions associated with the use of vitamin A.

  Piceatanol can be used as is, ie isolated from grape skin, wine or other plant-derived ingredients, chemically synthesized in the laboratory or commercially available, eg Biomall Research Laboratories, Inc. (Plymouth Meeting, Pennsylvania) May be procured and used. A desirable way to obtain piceatanol from natural resources is to extract the component from German Spruce bark.

  The active ingredient can also be used as a dermatologically acceptable salt, ester, amide, prodrug or related substance or in combination. Piceatanol salts, esters, amides, prodrugs and related substances can be produced by standard processes known to those skilled in the art of synthetic organic chemistry and pharmaceutical preparation. The production of esters involves the functionalization of hydroxy groups in the molecular structure of the drug. Esters are typical acyl-substituted derivatives of free alcohol groups.

  That is, it is part of a carboxylic acid derivative of the chemical formula RCOOH (R is an alkyl group, preferably a lower molecular weight alkyl group). Esters are reconverted to free acids by conventional hydrogenolysis or hydrolysis as required. The production of amides and prodrugs is possible in a similar manner. The production of other derivatives and related substances of the active ingredient can be inferred by standard processes known to those skilled in the art of synthetic organic chemistry or by literature reference

  Desirable cis- and trans-forms of piceatanol are those in which one or more of the hydroxyl groups of the component, typically 3-hydroxyl groups, are conjugated to monosaccharides or disaccharides, generally monosaccharides at position 1 It is. Examples of sugars that may be conjugated to the piceatanol molecule include, but are not limited to, glucose, galactose, maltose, and saccharose. Cis-piceatanol glucoside and trans-piceatanol glucoside (astridine) are particularly desirable.

[Cosmetics for cosmetics]
In a preferred formulation example, the active ingredient is added to a topical composition formulation containing a carrier suitable for topical application and materials known in the art. A topical carrier is selected that provides the desired composition.

  For example, ointments, lotions, creams, microemulsions, gels, oils, solutions, etc. may contain any naturally derived or synthetic substances. It is an essential requirement that the selected 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 non-toxic organic solvents, glycerin, mineral oil, silicone, petrolatum, lanolin, fatty acids, vegetable oils, waxes and the like.

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

  Various additives known to those skilled in the art can be included in the topical formulations according to the invention. Examples of additives include solubilizers, skin penetration enhancers, opacifiers, preservatives (eg antioxidants) gelling agents, buffers, surfactants (especially nonionic amphoteric surfactants), Examples include, but are not limited to, emulsifiers, emollients, thickeners, stabilizers, wetting agents, coloring agents, and fragrances. It is particularly desirable to add solubilizers and / or skin penetration enhancers along with emulsifiers, emollients and preservatives.

  A skin penetration enhancer facilitates the therapeutic concentration of the active ingredient to pass through a significant area of undamaged skin. Suitable enhancers are well known in the art and include, for example, 2-propanol and dimethylisosorbide.

  Examples of solubilizers include, but are not limited to: 1,3-butylene glycol, dipropylene glycol.

  Other active ingredients may also be included in the formulation. In other words, other anti-inflammatory agents, analgesics, antibacterial agents, antifungal agents, antibiotics, vitamins, antioxidants and sunscreens, but the components commonly used in sunscreens include Titanium, zinc oxide, anthranilate, benzophenone (especially benzophenone-3), camphor derivative, cinnamate (eg octylmethoxycinnamate), dibenzoylmethane (eg butylmethoxydibenzoylmethane), p-aminobenzoic acid ( PABA) and their derivatives, and salicylates (eg octylsalicylate).

  In preferred topical formulations of the present invention, the active ingredient is included in the formulation 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. % To 5% by weight, most preferably from about 0.1% to 2% by weight.

〔use〕
The composition according to the present invention is intended primarily for cosmetics that are topically applied to human skin, in particular products for skin conditioning, moisturizing, smoothing, and preventing and deterring wrinkles and aging skin.

  The formulation is applied topically to the skin as described in the previous section, as an ointment, lotion, cream, microemulsion, gel, solution, etc., in a dosage range effective to obtain the desired result. The preferred single dose of active ingredient is in the range of 1 to 100 ml. In general, the dosage regimen will include a local dose of at least once daily.

  Although the invention has been described with specific dosage form names, it is to be understood that the above-described examples and those described below are for purposes of illustration and are not intended to be limiting. Other features, advantages, and improvements will be apparent to those skilled in the art relating to the invention.

All patents, patent documents, and references cited in this document are described in this document as references.

  In order to fully disclose a method for preparing a prescription product based on the present invention to general skilled technicians, examples are shown below, but they are not meant to limit the scope that the inventors regard as the invention. Efforts have been made to ensure accuracy with respect to numbers (eg, quantity, temperature, etc.) as much as possible, but there may be some errors and errors.

  Unless otherwise stated, ratios are by weight, temperatures are in degrees Celsius, and atmospheric pressure is atmospheric pressure. All solvents, reagents and additives are pharmaceutical grade.

This example demonstrates that a solution of piceatanol suppresses vitamin A-induced irritation and improves skin appearance.
The compositions of Example 1 and Comparative Examples 1 and 2 were prepared using the components shown in Table 1.

  The composition was adjusted as follows: When d-α-tocopherol, retinyl palmitate (1.7 m. IU / g) and trans-piceatanol were dissolved in dimethyl isosorbide at 30 ° C to form a clear solution. Add dipropylene glycol at 30 ° C. The operation was carried out under a nitrogen blanket and all solutions were stored under nitrogen.

  A modified version of the human 4-h patch test (Basketter D.A. et al., Food Chem Toxicl 1997 ,: 35: 845-852) for the intensity of cosmetic stimulation for the compositions of Example 1 and Comparative Examples 1 and 2. It examined in. In the experiment, 0.2 ml of the test solution on a 25 mm Hilltop chain bar with a webrill pad (Hilltop, Cincinnati, Ohio, USA) was applied to the skin of the upper outer arms of 16 volunteers. The subject's arms were used, and the patches were applied in a balanced and random manner.

結果を表3に示す。

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 stimulation was determined by the 4-point method (Table 2) at 24, 48, and 72 hours after patch removal.

The results are shown in Table 3.

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

The effects of Example 1 and Comparative Examples 1 and 2 on the improvement of skin wrinkles as cosmetics were measured with a computerized laser profilometer. The test was performed on 16 women over 30 years old, and the composition of Experiment 1 and Comparative Experiments 1 and 2 was applied to the subject's face (area 2 × 2 cm ² ) 0.05 g once a day for 9 weeks.

  A replica of the skin wrinkle was then made using a plastic silicon precision structure compound. Changes in the skin wrinkles of the duplicates were detected with a visual skin meter (Skin Visiometer manufactured by Couage & Khazaka electronic GmbH, Germany). The duplicate 3D images were analyzed with a CCD camera. The skin wrinkle improvement effect was calculated as the average wrinkle roughness (Rz) according to the following equation 1:

Rz = (R1 + R2 + ……… + Rn-1 + Rn) / number of wrinkles (n) (1)

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

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

この組成は実施例1の操作に従って調整した
In this example, trans- (3,5,3 ', 4'-tetrahydroxystilbene) -3-O-beta-d-glucopyranoside (trans-astridine) suppresses vitamin A-induced irritation in solution-type formulations And demonstrate improved skin appearance.
The composition of Example 2 was prepared using the components shown in Table 5.

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

The skin irritation intensity of the composition of Example 2 was compared with that of Comparative Examples 1 and 2 in the same manner as the test method described in Example 1.
The results are shown in Table 6.

Addition of piceatanol-glucoside (astridine) suppressed retinyl palmitate irritation.
The effect of the composition of Example 2 on skin wrinkle improvement was examined by the same method as described in Example 1. The results are shown in Table 7.

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

This example demonstrates that piceatanol can suppress vitamin A-induced irritation and improve skin appearance in emulsion (lotion) type formulations.
The compositions of Example 3 and Comparative Examples 3 and 4 were prepared using the ingredients shown in Table 8.

The lotion was prepared by standard procedures for cosmetic lotions.
The skin irritation intensity of the composition of Example 3 was compared with that of Comparative Examples 3 and 4 in the same manner as the test method described in Example 1.
The results are shown in Table 9.

Addition of piceatanol clearly inhibited the stimulation of retinyl palmitate in the lotion.
The effect of the composition of Example 3 on skin wrinkle improvement was examined by the same method as described in Example 1. The results are shown in Table 10.

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

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

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

This example demonstrates that piceatanol glucoside (astridine) suppresses vitamin A-induced irritation and improves skin appearance in emulsion (lotion) type formulations.
The composition of Example 4 was prepared using the ingredients shown in Table 11.

The lotion was prepared by standard procedures for cosmetic lotions.
The strength of skin irritation of the composition of Example 4 was examined by the same method as the test method described in Example 1. The results are shown in Table 12.

The addition of astringin clearly suppressed the stimulation of retinyl palmitate in the lotion.
The effect of the composition of Example 4 on skin wrinkle improvement was examined by the same method as described in Example 1. The results are shown in Table 13.

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

  The results also show that astridine actually enhances the action of retinol (vitamin A) on wrinkle improvement and that astridine is more efficient than piceatanol in emulsion cosmetics.

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

Claims (17)

Dermal cosmetic composition comprising:
(A) a single vitamin A selected from the group consisting of retinol, retinal esters, retinal, retinoic acid, retinoic acid salts, derivatives or analogs thereof, and combinations thereof with any of these, From about 0.001% to about 5%;
(B) Piceatanol, dermatologically acceptable salts, esters, amides, prodrugs and related substances thereof, and combinations thereof with any of these, having a concentration of about 0.0001% to about 10%;
(C) Medium acceptable as cosmetics Dermal cosmetic composition comprising:
(A) about 0.005 to about 5% by weight of vitamin A (b) piceatanol and its dermatologically acceptable salts, esters, amides, prodrugs, related substances, and any of these about 0.001 About 10% by weight   3. The cosmetic composition for skin according to claim 2, wherein the active ingredient is piceatanol.   The composition for skin cosmetics according to claim 2, wherein the active ingredient is a conjugate of piceatanol and a monosaccharide or disaccharide.   The skin cosmetic composition according to claim 2, wherein the active ingredient is piceatanol-3-O-beta-d-glucopyranoside (astridine).   The composition of a dermatological cosmetic composition according to claim 2, comprising vitamin A selected from retinol, retinal esters, retinal, retinoic acid, retinoic acid salts and derivatives thereof, related substances, and formulations containing any of these. object.   The composition of claim 2, wherein the composition according to claim 2 comprises one of a sunscreen and tocopherol antioxidant and a component selected from the combination thereof.   The dermatological cosmetic composition of claim 7, comprising from about 1% to about 99.5% of a dermatological carrier.   9. A dermatological cosmetic composition according to claim 8, in the form of an ointment, lotion, cream, emulsion, microemulsion, gel or solution. Dermal cosmetic composition comprising:
(A) about 0.005 to about 5% by weight of vitamin A (b) piceatanol and its dermatologically acceptable salts, esters, amides, prodrugs, related substances, and any of these about 0.001 (C) a dermatologically acceptable medium containing from about 0.005 to about 5% by weight of the above vitamin A   The composition for skin cosmetics according to claim 10, wherein the active ingredient is piceatanol.   The composition for skin cosmetics according to claim 11, wherein the active ingredient is a conjugate of piceatanol and a monosaccharide or disaccharide.   The composition for skin cosmetics according to claim 12, wherein the active ingredient is piceatanol-3-O-beta-d-glucopyranoside (astridine).   The composition of a skin cosmetic according to claim 10, comprising vitamin A selected from retinol, retinal esters, retinal, retinoic acid, retinoic acid salts and derivatives thereof, related substances, and formulations containing any of these. object.   11. A dermatological cosmetic composition according to claim 10, comprising a component selected from one of a sunscreen and a tocopherol antioxidant and a combination thereof.   11. A dermatological cosmetic composition according to claim 10, comprising from about 1% to about 99.5% of a dermatological carrier.   17. A cosmetic composition for skin according to claim 16, in the form of an ointment, lotion, cream, emulsion, microemulsion, gel or solution.