CN1345228A

CN1345228A - Dermatological topical composition

Info

Publication number: CN1345228A
Application number: CN00805583A
Authority: CN
Inventors: 中山宏基
Original assignee: Pentapharm AG
Current assignee: DSM Nutritional Products AG
Priority date: 1999-03-26
Filing date: 2000-03-24
Publication date: 2002-04-17
Also published as: AU4396500A; KR20010102468A; WO2000057840A2; JP2000281555A; EP1165039A2; CA2362388A1; WO2000057840A3

Abstract

Dermatological topical composition, comprising at least a mixture of uva-ursi and L-ascorbic acid and/or a derivative of L-ascorbic acid, or a mixture of an uva-ursi extract and L-ascorbic acid and/or a derivative of L-ascorbic acid further containing at least one compound selected from UV absorbers, allantoin or its derivatives, and pantethine-S-sulfonate or a salt thereof. The composition is useful as whitening and pigmentation reducing agent, preferably for the topical treatment of the human skin, preferably for effectively reducing skin problems caused by pigmentation such as liver spots, freckles and dark complexion.

Description

Dermatological topical composition

The present invention relates to dermatological topical composition, said composition contains uva ursi (uva-ursi) and L-ascorbic acid and/or L-ascorbic acid derivates or contains the uva ursi extract and L-ascorbic acid and/or L-ascorbic acid derivates, and said composition also contains at least a chemical compound that is selected from ultraviolet absorber, allantoin or derivatives thereof and PPS or its salt in addition.

The flat 6-166609 of TOHKEMY discloses uva ursi and extract can be used as brightening agent and pigmentation subtracts the active component that takes off agent (pigmentation reducing agents).Disclosed content is hereby incorporated by among the flat 6-166609 of TOHKEMY.

It is reported that for example moth patch, freckle and the dark colour of skin are because melanin over-deposit in skin is caused to the skin problem that is caused by pigmentation.Open among the flat 6-166609 invention disclosed JP-spy and show that uva ursi and extract thereof are that effective brightening agent and pigmentation subtract and take off agent, its effect is equivalent to for many years the synthetic arbutin as brightening agent.

The objective of the invention is: utilize uva ursi and extract thereof brighten and the effect that loses lustre prepares dermatological topical composition, the effect of described compositions than those uva ursis and/or its extract with can to work in coordination with the known product that the composition that increases or strengthen its effect is used in combination stronger.

The present invention relates to a kind of dermatological topical composition, it is characterized in that: described compositions contains the mixture of at least a uva ursi and L-ascorbic acid and/or L-ascorbic acid derivates, the mixture of perhaps a kind of uva ursi extract and L-ascorbic acid and/or L-ascorbic acid derivates, and contain at least a chemical compound that is selected from ultraviolet absorber, allantoin or derivatives thereof and PPS or its salt.

The invention still further relates to the preparation method of dermatological topical composition, according to the present invention, described method comprises: a kind of compositions is provided, described compositions contains at least the mixture of (i) uva ursi and L-ascorbic acid and/or L-ascorbic acid derivates, or the (ii) mixture of uva ursi extract and L-ascorbic acid and/or L-ascorbic acid derivates, toward wherein adding at least a chemical compound that is selected from ultraviolet absorber, allantoin or derivatives thereof and PPS or its salt.

The invention still further relates to described compositions and subtract the application of taking off agent, to reduce effectively skin problem that pigmentation causes for example moth patch, freckle and the dark colour of skin are arranged especially for the topical therapeutic application on human skin as brightening agent and pigmentation.

Yet, dermatological topical agent of the present invention can be prepared as follows: the order with any needs adds described component, preferably, at least a following compounds is joined in the mixture of uva ursi and L-ascorbic acid and/or its derivant, perhaps join in the mixture of uva ursi extract and L-ascorbic acid and/or its derivant: ultraviolet absorber, allantoin or derivatives thereof and PPS or its at least a salt.

Preferably, uva ursi or uva ursi extract are prepared as follows: dry back is rolled over Folium Vaccinii vitis-idaeae (arctostaphylos uva-ursi) leaf and is broken to required size.The rolling that obtains minced places aqueous extraction solvent, and room temperature was extracted 24 hours, and described extraction is preferably under agitation carried out.The mixture that contains preferred organic solvent of water extraction solvent and water like this, for example alcohol or the mixture of polynary alcohol and water, wherein alcohol is 1 with the ratio of water: 10-10: 1, preferred 1: 4-4: 1.Yet preferably, the scope of the invention comprises that also the mixture of acetone and water extracts solvent, and wherein the ratio of acetone and water is 1: 10-10: 1, preferred 1: 5-5: 1.Carefully the filtrate of containing uva ursi is concentrated into driedly, preferably under the temperature below 50 ℃, carries out.Dry extract is dissolved in the aqueous solvent, it is carried out ultrafiltration.Concentrate, filter and use resulting penetrant according to the present invention.

The L-ascorbic acid that joins in uva ursi of the present invention or its extract is commonly called vitamin C, and known its has the effect that promotes that Cellular respiration, enzyme activation and collagen form, and can come the vat black pigment by its potent reduction.Known ascorbic acid derivates comprises: L-ascorbic acid mono alkyl ester is L-ascorbic acid monostearate, L-ascorbic acid monopalmitate and L-ascorbic acid monoleate for example; L-ascorbic acid monoester derivates is L-ascorbic acid phosplate and L-Ascorbic acid 2-sulfate for example; L-ascorbic acid diester deriv is for example L-Ascorbic acid distearate, L-Vitamin C dipalmitate and L-ascorbic acid dioleate of L-ascorbic acid bisphosphate for example; The trialkyl ester is L-ascorbic acid tristearate, L-ascorbic acid tripalmitate and L-ascorbic acid trioleate for example; With L-ascorbic acid three ester derivants L-ascorbic acid triguaiacyl phosphate for example.The present invention can select one or both or multiple joining in the present composition in these derivants.Wherein the proportion of uva ursi and vitamin C and/or its derivant is about 20: 0.5 to 20: 5, preferred about 20: 0.5 to 20: 2, more preferably from about 20: 1.

Containing uva ursi or its extract will be described in further detail below as active component and toward the dermatological topical agent of the present invention that wherein adds L-ascorbic acid or derivatives thereof.

Can join the ultraviolet absorber of any routine in the dermatological compositions of the present invention.The example of ultraviolet absorber is for example p-aminobenzoate (PABA), PABA monoglyceride, N of benzoate ultraviolet absorber, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA amyl group ester and N, N-dimethyl PABA octyl group ester.

The example of ultraviolet absorber can also be the o-aminobenzoa ultraviolet absorber, for example monomethyl-N-acetyl group o-aminobenzoa, high  base (homomenthyl)-N-acetyl group o-aminobenzoa.Other examples be salicylate UV absorbers for example amyl salicylate, methyl salicylate, the high menthyl ester of salicylic acid, ethylhexyl salicylate, phenyl salicytate, benzyl salicylate and salicylic acid to the isopropyl alcohol phenylester.

Also having some examples in addition is the cinnamate ultraviolet absorber, cinnamic acid monooctyl ester for example, 4-isopropyl ethyl cinnamate, 2,5-diisopropyl methyl cinnamate, 2,4-diisopropyl ethyl cinnamate, 2,4-diisopropyl methyl cinnamate, the p-methoxycinnamic acid propyl ester, the p-methoxycinnamic acid isopropyl ester, iso-amyl p-methoxycinnamate, the p-methoxycinnamic acid isopropyl ester, iso-amyl p-methoxycinnamate, p-methoxycinnamic acid monooctyl ester (p-methoxycinnamic acid-2-ethyl hexyl ester), p-methoxycinnamic acid-2-ethoxy ethyl ester, the p-methoxycinnamic acid cyclohexyl, alpha-cyano-beta-phenyl ethyl cinnamate, alpha-cyano-beta-phenyl cinnamic acid-2-Octyl Nitrite and di-p-methoxy cinnamic acid glycerol list-2-ethyl hexanoyl ester.

Also having some examples is benzophenone UV absorbers for example 2, the 4-dihydroxy benaophenonel, 2,2 '-dihydroxy-4-methoxy benzophenone, 2,2 '-dihydroxy-4,4 '-dimethoxy-benzophenone, 2,2 '-4,4 '-tetrahydroxybenzophenone, 2-hydroxyl-4-methoxy benzophenone, 2-hydroxyl-4-methoxyl group-4 '-the methyldiphenyl ketone, 2-hydroxyl-4-methoxy benzophenone-5-sulfonate (ester), the 4-phenyl benzophenone, 2-ethylhexyl-4 '-phenyl benzophenone-2-carboxylate, Octabenzone and 4-hydroxyl-3-carboxyl benzophenone.

Other useful ultraviolet absorbers are 3-(4 '-methyl benzal)-d; l-Camphora; 3-benzal-d; l-Camphora; urocanic acid; the urocanic acid ethyl ester; 2-phenyl-5-Jia base benzoxazole; 2; 2 '-hydroxyl-ethyl benzotriazole; 2-(2 '-hydroxyl-5 '-the t-acetylphenyl) benzotriazole; 2-(2 '-hydroxyl-5 '-aminomethyl phenyl) benzotriazole; dibenzaladine; two methyl phenyl ethers anisole methane (dianisoilmethane); 4-methoxyl group-4 '-tert-butyl group two benzoilmethane; 5-(3, the 3-dimethyl-2-norbolnilidene)-3-pentane-2-ketone.

For with the uva ursi being active component and toward wherein adding L-ascorbic acid or derivatives thereof or being active component and toward the dermatological topical composition of the present invention that wherein adds L-ascorbic acid or derivatives thereof with the uva ursi extract, the content of ultraviolet absorber without limits.Yet preferably, the content of ultraviolet absorber is the 0.05%-10% of this dermatological topical formulations gross weight, preferred 0.5%-8%.On the one hand, if the content of ultraviolet absorber is too low, then it can not prevent that sunlight is tanned, thereby has offseted the whitening effect of uva ursi or its extract; On the other hand, if the uv absorption agent content is too much, then it may influence the stability of this dermatological topical composition.

Except that the above-mentioned neccessary composition of mentioning, can also join other known cosmetics commonly used and medicine component in the dermatological topical formulations of the present invention as neccessary composition.Such composition is for example oil, antioxidant, surfactant, humidizer, flavoring agent, water, alcohols, viscosifier, antibacterial, coloring agent, powder and medicine.

Can be prepared into any dosage form to dermatological topical formulations of the present invention, comprise: solubilized formulation (for example health lotion), emulsification preparation (emulsion or cream frost), ointment and dispersion.

To be described below by the allantoin derivant being joined the uva ursi or the preparation-obtained dermatological topical composition of the present invention of its extract that contain L-ascorbic acid or derivatives thereof.Used for this purpose allantoin derivant comprises allantoic acid dihydroxy aluminum (dihydroxyalluminum allantoinate) and allantoic acid chlorine hydroxy Al.In order to implement the present invention, select allantoin or its 12 or multiple derivant as neccessary composition.Its content range should be the 0.01%-5.0% (preferred 0.1%-3.0%) of this dermatological topical composition gross weight.

Through finding, the present composition be by can having synergism to allantoin or derivatives thereof and the uva ursi or its extract use in conjunction that contain L-ascorbic acid and/or its derivant to wound, thereby promoted the healing of wound significantly.In addition, even the used matrix compounds of described dermatological topical formulations normally suppresses wound healing process, said preparation also can show good wound healing effect.This characteristics help to produce, because according to the purpose of each dermatological topical formulations, can select any substrate.

By the allantoin or derivatives thereof being joined in the dermatological topical composition of the present invention for preparing in the uva ursi that contains L-ascorbic acid or derivatives thereof or its extract, for example can add following ingredients as necessary component: surfactant, oil, humidizer, ultraviolet absorber, antioxidant, antibacterial, flavoring agent, water, alcohols, chelating agen, pH regulator agent and/or viscosifier.

Dermatological topical composition of the present invention not only can be cream frost form (for example nourishing cream, hand cream, protective skin cream and massage cream), nutrition breast lotion, packing specification (packs) and hygienic liquid, can also be Hiar treatment compositions, particularly anti-scurf compositions.

Contain the dermatological topical composition of the present invention for preparing in the L-ascorbic acid or derivatives thereof and will be described below by PPS (PPS) or its salt are joined.PPS is a compound known, and its chemical structure of general formula is suc as formula shown in (I).HOCH ₂C(CH ₃) ₂CH(OH)CONHCH ₂CH ₂CONHCH ₂CH ₂SSO ₃H (I)

At nature, formula (I) chemical compound is present in the Radix Dauci Sativae, and known its is a factor that can promote the bifidobacterium growth.Known its also has whitening effect.

PPS can use with free acid form or its salt form.Though can use acylate or inorganic acid salt in the wide region, advantageous applications alkali metal salt or alkali salt.According to the present invention, the ratio of using PPS and/or its salt and uva ursi is: the weight ratio of PPS and/or its salt and uva ursi is 1: 0.1 or higher, and its preferred weight ratio is 1: 0.1-1: 10, more preferably 1: 0.5-1: 5.Less than 1: 0.1 ratio was unfavorable, because can not obtain enough stablizing effects like this.

Except that uva ursi, PSS or its salt, can also cosmetics, medicine and other products for example following products composition commonly used join in the dermatological topical composition of the present invention as neccessary composition.Product shown in it is: water constituent, powder composition, surfactant, humidizer, viscosifier, ultraviolet absorber, coloring agent, medicine and flavoring agent.Certainly, the character of these compositions and consumption standard must be able to not influence the effect of the present composition.Dermatological topical composition of the present invention can be any dosage form, comprises such topical formulations dosage form commonly used for example ointment, cream frost, emulsion and lotion.

Embodiment 1

100 parts of uva ursis under 75 ℃ of temperature dry 24 hours, roll over and be broken into fine powder.The powder that obtains mixes with 300 parts of water/acetone mixture (80 parts of water, 20 parts of acetone), stirs room temperature placement down 24 hours.Filtering mixt then, vacuum concentration is to 1/3 amount of its initial volume under 45 ℃ of temperature.In ultracentrifuge, handle concentrate so that isolate any branch that is fine into.Then concentrate further is concentrated into about 50 ml volumes, under 5 ℃ of temperature, places, obtain the crystalline product of uva ursi.Crystalline product and gained concentrate are used to prepare the present composition.

Claims

1, dermatological topical composition, it is characterized in that described compositions contains: the mixture of at least a uva ursi and L-ascorbic acid and/or L-ascorbic acid derivates, the mixture of perhaps a kind of uva ursi extract and L-ascorbic acid and/or L-ascorbic acid derivates, described in addition compositions also contain at least a chemical compound that is selected from ultraviolet absorber, allantoin or derivatives thereof and PPS or its salt.

2, the compositions of claim 1, wherein uva ursi or uva ursi extract are by obtaining with containing water extraction solvent extraction uva ursi, wherein saidly contain the mixture that the water extraction solvent contains water and organic solvent, described organic solvent is alcohol, polyhydric alcohol or acetone, preferred acetone.

3, the compositions of claim 2 wherein contains the mixture that the water extraction solvent is acetone and water, and wherein the ratio of acetone and water is 1: 10-10: 1, preferred 1: 5-5: 1.

4, the compositions of claim 2 wherein obtains uva ursi by crystallization, represents crystalline material.

5, any one compositions of claim 1-4, wherein the ratio of uva ursi and vitamin C and/or its derivant is 20: 0.5-20: 5, preferred 20: 0.5-20: 2, more preferably from about 20: 1.

6, any one compositions of claim 1-4, wherein ultraviolet absorber is benzoate ultraviolet absorber, o-aminobenzoa ultraviolet absorber, salicylate UV absorbers, cinnamate ultraviolet absorber or benzophenone UV absorbers.

7, any described compositions of claim 1-6, wherein the content of ultraviolet absorber is the 0.05%-10% of composition total weight, preferred 0.5%-8%.

8, any described compositions of claim 1-7, wherein said compositions also contains: oil, antioxidant, surfactant, humidizer, flavoring agent, water, alcohols, viscosifier, antibacterial, flavoring agent, powder and medicine.

9, any described compositions of claim 1-8, wherein said compositions are solubilized formulation (for example health lotion), emulsification preparation (emulsion or cream frost preparation), ointment or dispersion.

10, any one compositions of claim 1-9, wherein said compositions contains the allantoin or derivatives thereof, and its content is the 0.01%-5.0% of dermatological topical formulations gross weight, preferred 0.1%-3.0%.

11, any described compositions of claim 1-10, wherein said compositions contains allantoin and/or its derivant, also contains surfactant, oil, humidizer, ultraviolet absorber, antioxidant, antibacterial, flavoring agent, water, alcohol, chelating agen, pH regulator agent and/or viscosifier.

12, any one compositions of claim 1-11, its form are cream frost (for example nourishing cream, hand cream, protective skin cream and massage cream), nutrition breast washing liquid, packing specification and hygienic liquid and Hiar treatment compositions.

13, any one compositions of claim 1-12, it contains PPS and/or its salt, and wherein the weight ratio of PPS and/or its salt and uva ursi is 1: 0.1 or higher, preferred 1: 0.1-1: 10, more preferably 1: 0.5-1: 5.

14, any one method for compositions of preparation claim 1-13, wherein said method comprises provides a kind of compositions, said composition contains at least the mixture of (i) uva ursi and L-ascorbic acid and/or L-ascorbic acid derivates, or the (ii) mixture of uva ursi extract and L-ascorbic acid and/or L-ascorbic acid derivates, and toward wherein adding at least a chemical compound that is selected from ultraviolet absorber, allantoin or derivatives thereof and PPS or its salt.

15, any one compositions of claim 1-14 subtracts the application of taking off agent as brightening agent and pigmentation, is preferred for the Local treatment of application on human skin.

16, the application of claim 15, it reduces the skin problem that caused by pigmentation for example moth patch, freckle and the black colour of skin effectively.