CN1056509C - Patches for percutaneous administration of skin-whitening materials - Google Patents
Patches for percutaneous administration of skin-whitening materials Download PDFInfo
- Publication number
- CN1056509C CN1056509C CN93102465A CN93102465A CN1056509C CN 1056509 C CN1056509 C CN 1056509C CN 93102465 A CN93102465 A CN 93102465A CN 93102465 A CN93102465 A CN 93102465A CN 1056509 C CN1056509 C CN 1056509C
- Authority
- CN
- China
- Prior art keywords
- methacrylate
- skin
- acrylate
- acid
- patch
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Abstract
公布了含有使皮肤变白物质的新剂型，本发明公布了用于经皮给药的含有一种或多种具有抑制酪氨酸酶活性的使皮肤变白的物质的贴剂。该贴剂可以是由敷盖层、贮库一粘着层(含有使皮肤变白物质和增透剂)和可去掉的保护层所构成的床型贴剂。也可以是由敷盖层、含使皮肤变白物质的贮库、控释层、粘着层和可去掉的保护层所构成的囊型贴剂，使皮肤变白物质可以选自：抗坏血酸及其衍生物，糖胺，氢醌及其衍生物，含疏基的化合物，丁羟甲苯和丁羟茴香酮。Novel formulations containing skin-whitening substances are disclosed, and the present invention discloses patches for transdermal administration containing one or more skin-whitening substances having tyrosinase-inhibiting activity. The patch may be a bed-type patch consisting of a covering layer, a reservoir-adhesive layer (containing a skin-whitening substance and a penetration enhancing agent), and a removable protective layer. It can also be a capsule patch consisting of a covering layer, a reservoir containing a skin-whitening substance, a controlled-release layer, an adhesive layer and a removable protective layer. The skin-whitening substance can be selected from the group consisting of: ascorbic acid and Derivatives, sugar amines, hydroquinone and its derivatives, sulfhydryl-containing compounds, butylated hydroxytoluene and butylated hydroxyanisone.
Description
The present invention relates to make the novel form of the cosmetic material of whiteness of skin, particularly percutaneous is given so that the patch of skin-whitening materials, what contain in this patch that one or more have a tyrosinase inhibitory activity makes skin-whitening materials as effective ingredient, and in during prolonging these active compounds is released on the skin.
Usually there is multiple factor can make skin darkening.One of them factor is melanic generation in the body, is that skin is exposed to the result that tryrosinase under the sunlight acts on tyrosine, and skin darkening is played a crucial role.
So far, for example ascorbic acid and derivant, kojic acid and derivant thereof, N-glucamine or hydroquinone and the blended cosmetic composition of derivant thereof have been used for treating skin darkening or facial wrinkles with having the active active compound of restraint of tyrosinase.Yet these routines are used for some problem of cosmetic composition of whiteness of skin.For example, the most frequently used reactive compound ascorbic acid is unstable in aqueous medium, contacts with air and is oxidized to hydroascorbic acid easily.Long term store also can overstrike.
For the stability of improving ascorbic acid had once been done many trials, for example, announced among the patent disclosure NO.Phyung 1-283208 of Japanese not substantive examination phosphate to be added in the ascorbic acid method that the reuse magnesium salt is transformed.Japan not substantive examination patent disclosure No.Phyung 1-228977,1-228978 and 1-228989 have narrated the method with fatty acid such as stearic acid or Palmic acid esterification ascorbic acid.
These methods can be improved the stability of ascorbic acid to a certain extent.Yet because ascorbic acid inherent instability, the low solubility in beauty treatment usefulness substrate and low absorbability of skin in aqueous medium, these chemical compounds fail to provide satisfied whiteness of skin effect.
The Japan not patent disclosure No.Sho 64-79105 of substantive examination has also proposed ascorbic acid is added in the facial film.But with the whiteness of skin effect that the facial film form obtains is unsatisfied.
In addition, also attempt oral have make whiteness of skin character reactive compound so that whiteness of skin.Yet this oral way is inappropriate because these reactive compounds before arrive desired area and present its effect in liver by metabolism, therefore can not take the reactive compound of high effective dose.
Like this, need provide a kind of new dosage form, can in the long time, give the skin-whitening materials that makes of high effective dose, and can not produce any stimulation skin.
In addition, the drug research person provides medical patch, and it can transfer heavy dose of medicine at the long period transdermal.For example Gale etc. has announced that in USP 4615699 transdermal that can transfer nitroglycerin (a kind of effective vasodilator) transfers system, and the transdermal amount is very high.Gale etc. have narrated in USP 4698062 and can carry out the therapy equipment that the pulsed transdermal transfers to bioactivator.USP 4738670 has announced the anti-inflammatory agent plaster, and it is made up of coat, bin-storing layer and the protective layer that can remove.
Yet the patch of the therapeutic purposes that relate in all these patents all designs for transdermal transfers medicine such as anti-inflammatory agent and vasodilator.Therefore, the present invention provides to contain the patch preparation that makes skin-whitening materials first.
The purpose of this invention is to provide a kind of novel form that is used to make the cosmetic material of whiteness of skin.
Another object of the present invention provides the patch that containing of a kind of percutaneous medication makes the material of whiteness of skin, and this class material can be controllably in a long time, with the percutaneous absorption of big effective dose ground.
Another object of the present invention provides that a kind of percutaneous is given so that the patch of skin-whitening materials, and this patch is by a coat, and a bin-storing layer and a protective layer that can remove are formed.
Another object of the present invention provides that a kind of percutaneous is given so that the patch of skin-whitening materials, and this patch is by a coat, a bin-storing layer, the film of a sustained release speed, and an adhesion coating and a protective layer that can remove are formed.
Fig. 1 is the transverse section of patch of the present invention (bed type) example;
Fig. 2 is the transverse section of patch of the present invention (capsule type) example;
Fig. 3 is the mapping that ascorbic acid penetrates through guinea pig skin in the patch of embodiment 1 (circle) and embodiment 2 (point).
The invention provides a kind of new preparation that makes skin-whitening materials.According to the present invention, provide and contain the patch that one or more make the percutaneous dosing of whiteness of skin.
Here used " making skin-whitening materials " is meant through various mechanism the chemical compound that suppresses the melanin generative capacity, and it can be used in the beautification product.Particularly they can be selected from following compounds: ascorbic acid and derivant thereof, and kojic acid and derivant thereof, glucamine, hydroquinone and derivant thereof contain chemical compound, butylated hydroxytoluene and the fourth hydroxyl fenchone (butylhydroxy anisone) of mercapto.These chemical compounds all have the activity of restraint of tyrosinase.
Can improve the stability of reactive compound according to patch of the present invention, owing to protected chemical compound to avoid surrounding air or dampness by the Oxidation of oxygen or air.
Of the present inventionly contain that the patch that the skin-whitening materials percutaneous is penetrated gets so that the local concentration of active substance increases, so that can obtain the satisfied effect that makes whiteness of skin.
In the time of in addition on being used for skin, can not produce stimulation to skin.
A preferred embodiment of the patch of representing in Fig. 1 of the present invention (bed type) is (to contain reactive compound by coat (1), storage storehouse-adhesion coating (2); the hydrophobicity medicinal adhesive; transparent agent, stabilizing agent, solubilizing agent and skin irritation alleviant) and the protective layer (6) that can remove.
Coat is made of a kind of material or multiple combinations of substances, the composition in waterproof basically, air and the storage storehouse-adhesion coating (2).For example layer (1) is that aluminum applies the polyethylene terephthalate film of lid or the thin film that is made of polymer, and polymer for example has ethylene vinyl acetate, polypropylene, polyethylene, polyurethane or polrvinyl chloride.The effect of coat is the protective layer of patch, keeps the composition in storage storehouse-adhesion coating (2) can not deviate from from patch, and plays the structural support effect.
The protective layer that can remove (6) is only being taken off from patch with preceding.This layer (6) is to be made of material strippable, not saturating compositions (2), for example is polyester film or paper or the polyphenyl dioctyl phthalate ethyl ester film that siloxanes or fluorine apply lid.
Storage storehouse compositions, based on the gross weight of said composition, comprise 0.1 to 30% one or more make the material of whiteness of skin; The medicinal hydrophobicity sticker of one or more of 8 to 99.68%, one or more transparent agents of 0.1 to 30%, one or more weak acid of 0.01 to 2% be as stabilizing agent, one or more solubilizing agents of 0.1 to 20%, 0.01 to 10% skin irritation alleviant.
Have the active material of whiteness of skin that makes of the melanin of inhibition generation and can include (but being not limited thereto) ascorbic acid and derivant thereof, as the ascorbic acid monopalmitate, Vitamin C dipalmitate, ascorbyl stearate, ascorbic acid-ethylhexoate, ascorbic acid diethyl alkyl caproate, ascorbic acid-caprylate, the ascorbic acid diisopstearate, magnesium ascorbyl phosphate and sodium ascorbate; Kojic acid and contain the alkyl derivative of 5-20 carbon atom; Osamine class such as glucamine, galactosamine and mannosamine; The hydroquinone or derivatives thereof is as HQG and hydroquinone monobenzyl ether class; Contain-chemical compound such as the glutathion and the cysteine of SH base; Butylated hydroxytoluene (BHT) and fourth hydroxyl fenchone; Propyl gallate, methionine or lecithin.These make the material of whiteness of skin can use also available its mixture separately.Making the consumption of skin-whitening materials is 0.1 to 30% by weight, is preferably 1.0 to 30%.
Transparent agent can improve the skin that sees through that makes skin-whitening materials, includes (more than that): dimethyl sulfoxide, dodecyl sulfoxide; the monomethyl acetamide, dimethyl acetylamide, N-ethoxy lactim; high-carbon fatty acid ester, salicylic acid, Sorbitol; polyoxyethylene sorbitan fatty acid ester, sorbitan esters of fatty acids, pyrrolidinone derivatives; the butanediol ether, dodecyl pyrrolidone, urea; glycerol, Squalene, squalane; acetylated lanolin, lauric acid hexadecane ester, olive oil; Oleum Ricini, lauric acid, oleic acid; lauryl alcohol, oleyl alcohol, VOLPO S20; white oil, vaseline, 1-menthol; Camphora; fatty glyceride, fatty acid single (or two) ethanolamine ester, ethylene glycol monomethyl ether; polyoxyethylene alkyl ether; polyxyethylated ester, polyoxypropylene alkyl ether, propylene glycol only (or 2 1) alkyl ether or the like.In addition, the present invention also uses easily and refers to the fat acid esters, monooleate glyceride for example, glyceryl dioleate or monooleate propylene glycol ester, the fatty acid ester that contains 2 to 20 mole ethylene oxides, the fatty acid ester of anhydro sorbitol or contain the fatty acid esters of sorbitan of 10 to 100 mole ethylene oxides is used for improving the skin absorbs that makes skin-whitening materials.
Moreover, in practical application of the present invention, also use skin irritation alleviant such as glycerol or bisabolol easily, to reduce the skin irritation that the patch composition causes.
The few stable agent that makes skin-whitening materials can be in patch, added, (more than that) weak acid can be included, as citric acid and succinic acid.
Can be used for increasing the dissolubility that makes skin-whitening materials and promote that its solubilizing agent of transferring includes (more than that): 1,3 butylene glycol, propylene glycol, glycerol, polyalcohols such as Polyethylene Glycol or Polyethylene Glycol-propylene glycol copolymers, alcohols such as ethanol, methanol, isopropyl alcohol or butanols.
Can add among the present invention one or more medicinal hydrophobicity stickers in storage storehouse-adhesion coating with fixing patch and avoid making skin-whitening materials to contact with dampness.Medicinal hydrophobicity sticker includes (more than that): acrylic acid, siloxanes, polyisobutylene and synthetic or caoutchouc resin sticker, the acrylic compounds sticker can include (methyl) acrylic acid alkyl ester polymer, wherein alkyl has 4 to 18 carbon atoms, and (methyl) alkyl acrylate and other functional monomer's copolymer.
The example of (methyl) acrylic acid alkyl ester polymer can include: butyl acrylate, Isobutyl 2-propenoate, Hexyl 2-propenoate, 1-Octyl acrylate, 2-EHA, Isooctyl acrylate monomer, decyl acrylate, isodecyl acrylate, the acrylic acid Lauryl Ester, stearyl acrylate acyl ester, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, methacrylic acid 2-Octyl Nitrite, 2-Propenoic acid, 2-methyl-, isooctyl ester, decyl-octyl methacrylate, isodecyl methacrylate, methacrylic acid Lauryl Ester, methacrylic acid stearoyl ester or the like.
The functional monomer can comprise, for example contains the monomer of hydroxyl, as (methyl) acrylic acid 2-hydroxy methacrylate and (methyl) Hydroxypropyl acrylate; The monomer that contains carboxyl is as α-or beta-unsaturated carboxylic acid (as acrylic acid, methacrylic acid), maleic acid mono alkyl ester (as the maleic acid butyl ester), maleic acid, fumaric acid and .beta.-methylacrylic acid; The monomer that contains amide groups, as alkyl (methyl) acrylamide (as acrylamide, DMAA, the diethyl acrylamide), alkyl ethyl methylol (methyl) acrylamide is (as butoxymethyl acrylamide, ethoxy methacrylamide), diacetone acrylamide and vinylpyrrolidone; Contain amino monomer, as the dimethylamino acrylate.Can use monomer such as vinyl acetate in addition, styrene, α-Jia Jibenyixi, vinyl chloride, acrylonitrile, ethylene, butadiene and propylene are to obtain the copolymer of (methyl) acrylic acid-Arrcostab.
The acrylic type sticker can contain (methyl) alkyl acrylate by weight more than 50% easily.
The rubber resin sticker can include, natural rubber for example, polyisoprene, polyisobutylene, polyvinylether, polyurethane, polybutadiene, SB, styrene-isoprene copolymer, styrene-isoprene-butene block copolymer or the like.
The silicone resin binding agent is crosslinked for well with silicate rubber (60% weight) and polydimethylsiloxaneresins resins (40% weight).
If necessary, in sticker, can contain auxiliary agent, viscosifier for example, as abietic resin, polyterpene resin, benzofuran-terpene resin, Petropols and terpene-phenolic resin; Plasticizer such as liquid polybutene, mineral oil, lanoline, liquid isoprene and liquid polyacrylate; Filler, age resister or the like.
The content of the medicinal hydrophobicity sticker in storage storehouse-adhesion coating (2) can be 8 to 99.68% by weight.
Bed type patch of the present invention shown in Figure 1 can followingly be made:
Storage storehouse preparation of compositions method is at organic solvent such as hexane, in ethyl acetate or the chloroform, one or more of dispersion 0.1 to 30% (weight) make skin-whitening materials, 0.1 one or more penetration promoters to 30% (weight), 0.01 one or more stabilizing agents to 2%, 0.01 one or more stimulation alleviants to 10% (weight), 0.1 one or more solubilizing agents to 20% (weight), the medicinal hydrophobicity sticker of one or more of 8 to 99.68% (weight), stir mixture more than 1 hour, after making uniform mixing, room temperature is placed and is made lather collapse.With spreader the mixture that obtains is coated on the paper or polyethylene terephthalate film (6) of siloxanes or the deposited plating of fluorine equably, the thickness of coating is 10 to 200 μ m.Then paper or the placement of film room temperature were made solvent evaporation more than 1 hour.If need, with paper or film in hot air dryer (80 ℃) dry 10 minutes more again.
After solvent evaporates fully, be selected from for example polyethylene terephthalate film of the deposited plating of aluminum, or the coat of ethylene vinyl acetate films or polypropylene screen seals on the film that storage storehouse compositions is housed that obtains like this through bonding or sealing by fusing method.Then the thin slice of sealing is put into incubator (37 ℃) and made ripening in 12-24 hour, and to be cut into the surface area that applies on skin be 0.1-500cm
2Patch.
Another preferred examples of the present invention is a scrotiform thin slice shown in Figure 2; it is that peripheral bond by coat (1) is on the film (4) of controlled release speed; separate and have living space at the film of the middle body of coat and controlled release speed; film (4) applies lid with sticker (5), has the protective layer (6) that can remove to constitute on (5).Make the compositions (3) of skin-whitening materials in the capsule abrim.
The constituent material of coat (1) and the protective layer that can remove (6) is identical with the constituent material of patch shown in Figure 1.Sticker (5) can be selected from the material described in the storage storehouse-adhesion coating (2) of patch shown in Figure 1.
The formation of compositions (3), gross weight by said composition is counted: one or more of 0.1 to 30% (weight) make skin-whitening materials, 0.1 one or more transparent agents to 30% (weight), 0.01 one or more stabilizing agents to 2% (weight), 0.01 to one or more stimulation alleviants of 10% (weight), the solubilizing agent of 28 to 99.78% (weight).
Rate of release controlling diaphragm (4) is a kind of microporous membrane, is used for controlling the speed that skin-whitening materials and transparent agent are discharged from storage storehouse (3).This film usable polymers constitutes, as polypropylene, and Merlon, polrvinyl chloride and ethylene vinyl acetate.
The controlled release percutaneous that makes skin-whitening materials that this patch shown in Figure 2 is specially adapted to effective dose that need be bigger penetrates.
Capsule type thin slice patch of the present invention shown in Figure 2 can be prepared as follows:
Be dissolved in the suitable organic solvent by one or more stickers of foregoing selection (5), the solution that obtains is coated on equably with siloxanes or fluorine with spreader and applies on the paper or polyethylene terephthalate film (6) of plating, and thickness is 10 to 200 μ m.Then paper or film room temperature are placed more than 1 hour so that solvent evaporation.If necessary, also can be with paper or film about 10 minutes of drying in hot air dryer (80 ℃) in again.
After solvent evaporates fully, paper or film are encapsulated in the microporous membrane (4).
In addition, will make skin-whitening materials, transparent agent, stabilizing agent, stimulation alleviant and solubilizing agent stir into homogeneous phase after mixing, and make storage storehouse compositions (3).Then said composition is put in coat (1) and by microporous membrane (4), in the blister cavities between the thin slice that adhesion coating (5) and the protective layer (6) that can remove are formed, and with all layer periphery heat-sealing.
It is 0.1 to 500cm that thin slice can be tailored the surface area that becomes to apply on skin
2Patch, make skin-whitening materials be preferably about 0.01 to 50 μ g/cm through the permeability of application on human skin
2/ hr.Preferred embodiment of the present invention
The present invention specifies with following example.Yet these examples should not thought to limit the scope of the invention just for illustrative purposes.Following claim has been done suitable explanation to the scope of the invention.Embodiment 1 to 5
(% weight)
Above-mentioned substance mixes the back and stirs until becoming homogeneous phase.The mixture that obtains evenly is applied to siloxanes with spreader applies on the paper of plating, thickness is approximately 50 μ m.Then paper is at room temperature placed more than 1 hour so that solvent evaporation.The paper sealing by fusing that is loaded with compositions is applied on the polyethylene terephthalate film of plating in aluminum.Thin slice is put in thermophore (37 ℃) made its ripening in middle 12-24 hour, tailor into about 20cm again
2Bed type patch.Embodiment 6-9
(% weight)
According to the method for embodiment 1-5, make about 30cm
2Bed type patch.Embodiment 10-13
(% weight)
According to the method for embodiment 1-5, just apply the polyester film and the polyethylene film that plate and replace the paper of the deposited plating of siloxanes and aluminum to apply the polyethylene terephthalate film of plating respectively with fluorine, make about 30cm
2Bed type patch.Embodiment 14～17
(% weight)
According to the method for embodiment 10～13, make about 30cm
2Bed type patch.
Embodiment 18-21
(% weight)
Form embodiment 18 embodiment 19 embodiment 20 embodiment 21
76 76 76 76 rubber resins, 11 ascorbic acid, 11 ASCORBYL MONOPALMITATEs, 11 Vitamin C dipalmitates, 111 kojic acids, 11 gucosamines, 1 quinhydrones, 5555 polyethylene glycol-propylene glycol copolymers 5555
(connecing following table) (continue and go up table) N-ketopyrrolidine 555 5-olein 5555 polyoxyethylene (3) lauryl ether 5555 citric acids 0.1 0.1 0.1 0.1 α-bisabolol 0.9 0.9 0.9 0.9
According to the method for embodiment 1～5, make about 20cm
2Bed type patch.Embodiment 22-25
(% weight)
Form embodiment 22 embodiment 23 embodiment 24 embodiment 25 ascorbic acid 33 ASCORBYL MONOPALMITATE 33 oleic acid, 10 10 polyoxyethylene (3) oleoyl ethers 10 10 citric acids 0.1 0.1 0.1 0.1 α-bisabolol 1111
Above-mentioned substance is mixed, stir into homogeneous mixture.
In addition, butyl acrylate and decyl-octyl methacrylate are dissolved in the hexane, and this solution is coated on the siliconised paper with spreader, place paper under the room temperature more than 1 hour, more about 10 minutes of drying in hot air dryer (80 ℃) in.The protective layer that adhesion coating one can be removed combines and is attached on the one side of microporous polypropylene membrane that thickness is 25 μ m then.
The compositions that obtains is above filled envelope capsule machine with molding and is sealed between the polyethylene terephthalate coat of calorize and the protective layer thin slice that above-mentioned microporous membrane one adhesion coating one can remove, again with all layer periphery heat-sealing.What obtain cuts into about 20cm again by 5 layers of thin slice that constitutes
2Capsule type patch.Experimental example 1: percutaneous rate
The Cavia porcellus of heavily about 350g is removed the hair of abdominal part with clippers, cuts one and does not have a hair skin of abdomen, is stored in the ice chest (below 20 ℃), and the time spent thaws.
A skin is placed the central authorities of bag type diffusion cell, and the horny layer that makes skin upwards.The glycerine water solution that adds 50% volume in the container.2.5cm
2Circular plate-like embodiment 1-9 and the patch of 18-21 are affixed on the skin chunk, the solution in 30 ℃ of 600rpm speed stirring containers.On this external skin chunk also coating contain 3% ascorbic acid, 3% ascorbic acid monopalmitate, 3% Vitamin C dipalmitate, 3% ascorbyl stearate or 3% ascorbic acid-ethylhexoate conventional cosmetic composition (skin lotion) in contrast.
Solution in the container is every sampling in 1 hour, with the concentration that makes skin-whitening materials in high pressure liquid chromatography (HPLC) (HPLC) analytical solution.
Can calculate percutaneous rate by concentration, list in the table 1.
Table 1
| Given the test agent | Percutaneous rate (μ g/cm 2/hr) |
| 3% contains ascorbic acid powder 3% contains ASCORBYL MONOPALMITATE composition 3% and contains Vitamin C dipalmitate composition 3% and contain the patch " 5 " " 6 " " 7 " " 8 " " 9 " " 18 " " 19 " " 20 " " 21 " of | 1.3 2.1 1.8 1.0 0.7 6.7 7.3 8.3 8.2 8.6 7.8 8.1 7.2 7.5 9.3 9.1 8.8 8.9 |
As shown in table 1, patch of the present invention is compared with the cosmetic composition that makes whiteness of skin of routine usefulness, makes skin-whitening materials that bigger permeability be arranged.Experimental example 2: pigmentation suppresses ability
20 healthy volunteers' forearm encases with aluminium foil, only exposes 2 * 2cm
2For ultra-vioket radiation, expose portion washs with 70% isopropanol water solution, shines simultaneously with L 20S BLB and L 20S E-30 lamp (Toshiba, Japan), and lamp and arm are at a distance of 10cm, with 0.8 * 10
7Erg/cm
3Every day irradiation was once carried out ultra-vioket radiation in continuous three days.
Irradiation is finished, and coats irradiation place with the cosmetic composition that tried in the experimental example 1, every day 2 times, or with patch subsides every day one of experimental example 1, after one month, the evaluation given the test agent is to being tried the inhibition ability of position pigmentation.
Counting suppresses the produce effects of pigment, effective and invalid number, lists in table 2.
Table 2
| Given the test agent | The observation number | ||
| Significantly suppress pigmentation | Suppress pigmentation | Do not suppress pigmentation | |
| 3% contains ascorbic acid powder 3% contains ASCORBYL MONOPALMITATE composition 3% and contains Vitamin C dipalmitate composition 3% and contain the patch " 2 " " 3 " " 4 " " 5 " " 6 " " 7 " " 8 " " 9 " that ascorbyl stearate composition 3% contains ascorbic acid- | 0 0 0 0 0 5 4 8 7 12 5 5 6 6 | 2 4 3 4 4 12 11 11 13 8 13 12 12 11 | 18 16 17 16 16 3 5 1 0 0 2 3 2 3 |
Table 2 (continuing)
| Given the test agent | The observation number | ||
| Significantly suppress pigmentation | Suppress pigmentation | Do not suppress pigmentation | |
| The patch of embodiment 18 " 19 " " 20 " " 21 " " 22 " " 23 " " 24 " " 25 " | 10 8 9 13 7 7 10 7 | 9 12 10 7 13 13 10 13 | 1 0 1 0 0 0 0 0 |
As shown in the table 2, patch of the present invention is more effective to the cosmetic composition of the conventional usefulness of the sedimentary inhibition specific activity of pigment.Experimental example 3: the stability of reactive compound
Cosmetic composition listed in the table 3 and patch are stored in 50 ℃ of thermophores 2 months, with its reactive compound of methanol extraction.Titre with high pressure liquid chromatography (HPLC) (HPLC) mensuration reactive compound the results are shown in table 3.
Table 3
| Given the test agent | Titre (%) |
| 3% contains ascorbic acid powder 3% contains ASCORBYL MONOPALMITATE composition 3% and contains Vitamin C ester dipalmitate composition 3% and contain the patch " 2 " " 3 " " 4 " " 5 " " 6 " " 7 " " 8 " " 9 " " 18 " " 19 " " 20 " " 21 " that ascorbyl stearate composition 3% contains ascorbic acid one | 12 58 67 59 15 98 97 99 99 98 98 99 99 99 97 97 98 97 |
As shown in the table 3, patch of the present invention is deposited 2 months cosmetic compositions than conventional usefulness at 50 ℃ and has been kept higher titre, shows that the long-time interior maintenance reactive compound of patch of the present invention is stable.Experimental example 4: the preliminary irritant test of skin
20 healthy volunteers paste 2cm listed in the table 4 on forearm
2The circular discoid patch, paste every day one.The cosmetic composition of the listed routine usefulness of coating table 4 on this external volunteer's forearm, every day secondary, the part of the thing that is combined coating covers with metal cap.
After 1,3 days or 7 days, press the zest of following standard evaluation to skin.
| Score | The stimulation degree |
| 0 1 2 3 4 | Non-stimulated small stimulation slightly stimulates (erythema) degree of depth to stimulate (erythema, edema) special degree of depth to stimulate (erythema edema) |
Table 4
| Given the test agent | Skin irritation (%) | ||
| After 1 day | After 3 days | After 7 days | |
| 3% contains ascorbic acid powder 3% contains ASCORBYL MONOPALMITATE composition 3% and contains Vitamin C dipalmitate composition 3% and contain the patch " 2 " " 3 " " 4 " " 5 " " 6 " " 7 " " 8 " " 9 " " 18 " " 19 " " 20 " " 21 " that ascorbyl stearate composition 3% contains ascorbic acid- | 0.5 0.5 1.0 0.8 1.0 0.8 0.5 1.0 0.8 1.0 0.5 0.8 1.0 0.8 1.0 0.8 1.0 0.8 | 0.5 0.5 0.8 1.0 1.0 0.8 0.8 0.8 0.8 0.8 0.5 1.0 1.3 1.0 1.3 1.0 1.0 1.3 | 0.5 0.8 1.0 0.8 0.8 1.0 0.8 1.0 1.0 0.8 1.0 1.0 1.3 1.3 1.3 1.3 1.3 1.0 |
As shown in the table 4, contain the patch of the present invention that stimulates alleviant α-bisabolol to the cosmetic composition of the weak stimulation of skin and routine the same a little less than.Therefore, patch of the present invention can be affixed on the skin safely for making whiteness of skin.
Claims (4)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR19933699 | 1992-03-06 | ||
| KR1993-3699 | 1992-03-06 | ||
| KR1019920003699A KR960006859B1 (en) | 1992-03-06 | 1992-03-06 | Improved method for stability of ageing comprising thirosinase inhibitor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1076110A CN1076110A (en) | 1993-09-15 |
| CN1056509C true CN1056509C (en) | 2000-09-20 |
Family
ID=19330034
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93102465A Expired - Fee Related CN1056509C (en) | 1992-03-06 | 1993-03-06 | Patches for percutaneous administration of skin-whitening materials |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP2655983B2 (en) |
| KR (1) | KR960006859B1 (en) |
| CN (1) | CN1056509C (en) |
| GB (1) | GB2265086B (en) |
| MY (1) | MY109939A (en) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2706143B1 (en) | 1993-06-07 | 1995-08-11 | Oreal | Method for molding a makeup composition and makeup product obtained. |
| FR2723316B1 (en) * | 1994-08-04 | 1996-10-04 | Thorel Jean Noel | SKIN DEPIGMENTING COMPOSITIONS AND PREPARATIONS FOR PHARMACEUTICAL OR COSMETIC USES |
| AU3339395A (en) * | 1994-09-14 | 1996-03-29 | Kuyus-Stiftung | Cosmetic process |
| AU4282096A (en) * | 1994-11-15 | 1996-06-06 | Osmotics Corporation | Skin care compositions and methods |
| FR2737122B1 (en) * | 1995-07-25 | 1997-09-12 | Oreal | STABLE COMPOSITION CONTAINING ASCORBIC ACID |
| FR2737116B1 (en) * | 1995-07-25 | 1997-08-22 | Oreal | STABLE COMPOSITION CONTAINING A WATER SENSITIVE COSMETIC AND / OR DERMATOLOGICAL ACTIVE |
| ES2183017T3 (en) * | 1996-11-04 | 2003-03-16 | Childrens Hosp Medical Center | COMPOSITIONS TO CLEAR THE SKIN. |
| JPH11116435A (en) * | 1997-10-06 | 1999-04-27 | Nitto Denko Corp | Skin-whitening sheet and its use |
| US6419935B1 (en) | 1998-07-30 | 2002-07-16 | L'oreal S.A. | Cosmetic skin treatment method and cleansing treatment patch |
| DE19911262C2 (en) * | 1999-03-13 | 2003-04-10 | Scs Skin Care Systems Gmbh | Device for dispensing cosmetic active ingredients |
| KR100535261B1 (en) * | 1999-03-29 | 2005-12-09 | 주식회사 태평양 | A cosmetic having hydrogel matrix adsheive sheet type |
| EP1210077A4 (en) * | 1999-06-15 | 2002-12-18 | Benjamin D Gordon | Compositions and systems for the treatment of hyperpigmentation |
| US6458379B1 (en) * | 1999-10-15 | 2002-10-01 | Nitto Denko Corporation | Sheet for whitening cosmetics and method for using the same |
| FR2805720B1 (en) | 2000-03-03 | 2002-08-16 | Oreal | DEVICE INCLUDING AN APPLICATOR AND / OR A MAGNETIC SPINNER |
| US7658942B2 (en) | 2000-04-12 | 2010-02-09 | The Procter & Gamble Company | Cosmetic devices |
| CA2382142C (en) | 2000-07-12 | 2005-08-23 | L'oreal | Device for packaging and/or applying a product containing fibres comprising at least a magnetised or magnetizable element |
| CA2415882A1 (en) * | 2000-07-13 | 2002-01-24 | Skinmedica, Inc. | Composition for topically delivering vitamin c |
| DE10054479A1 (en) * | 2000-11-03 | 2002-05-08 | Henkel Kgaa | Cosmetic plasters for skin lightening |
| KR100479741B1 (en) * | 2000-12-30 | 2005-03-30 | 주식회사 엘지생활건강 | Cosmetic for skin whitening containing acyl substituted derivatives of glucose or sucrose |
| JP2002284705A (en) * | 2001-01-19 | 2002-10-03 | Shiseido Co Ltd | Torpent |
| FR2822711B1 (en) | 2001-03-28 | 2003-06-13 | Oreal | TREATMENT DEVICE COMPRISING AN ENVELOPE DEFINING A CAVITY IN WHICH A PART OF THE BODY MAY BE ENGAGED |
| JP2002293714A (en) * | 2001-03-30 | 2002-10-09 | Fancl Corp | Skin cosmetic |
| US7189759B2 (en) | 2001-05-23 | 2007-03-13 | Medicis Pharmaceutical Corporation | Compositions for the treatment of pigmentation disorders and methods for their manufacture |
| JP2003048832A (en) * | 2001-08-02 | 2003-02-21 | Kosumedei:Kk | Patch for skin conditioning |
| ITMI20020509A1 (en) * | 2002-03-11 | 2003-09-11 | Carlo Ghisalberti | COSMETIC DEPIGMENTANT COMPOSITIONS |
| KR20030082765A (en) * | 2002-04-18 | 2003-10-23 | 한국화학연구원 | Transdermal drug delivery matrix type system contained hydroquinone and cosmetic ingredients |
| JP2007119405A (en) * | 2005-10-28 | 2007-05-17 | Sansho Kaken Kk | Skin care plaster |
| KR20090075864A (en) | 2006-10-26 | 2009-07-09 | 오노 야꾸힝 고교 가부시키가이샤 | Attachment |
| US20080147022A1 (en) * | 2006-12-15 | 2008-06-19 | Kimberly-Clark Worldwide, Inc. | Skin care delivery device having a releasable backing |
| JP2011173851A (en) * | 2010-02-25 | 2011-09-08 | Kazki International:Kk | Patch for beautification |
| DE102013204070A1 (en) * | 2013-03-11 | 2014-09-11 | Beiersdorf Ag | Use of cosmetically or dermatologically acceptable substituted Michael acceptors for the prevention, reduction or prophylaxis of the tyrosinase activity of the human skin and / or its lightening |
| JP6212320B2 (en) * | 2013-08-01 | 2017-10-11 | ポーラ化成工業株式会社 | Topical skin preparation |
| CN114712334A (en) * | 2022-04-08 | 2022-07-08 | 季华实验室 | A kind of traumatic oil gel patch and preparation method thereof |
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| US4615699A (en) * | 1985-05-03 | 1986-10-07 | Alza Corporation | Transdermal delivery system for delivering nitroglycerin at high transdermal fluxes |
| JPH01199916A (en) * | 1988-02-04 | 1989-08-11 | Sansho Seiyaku Co Ltd | Drug for external use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6078912A (en) * | 1983-10-06 | 1985-05-04 | Shiseido Co Ltd | Cosmetic |
| DE3409079A1 (en) * | 1984-03-13 | 1985-09-19 | Bayer Ag, 5090 Leverkusen | MEDICAL PLASTER |
| JPS61194008A (en) * | 1985-02-25 | 1986-08-28 | Shiseido Co Ltd | Cosmetic |
| US4698062A (en) * | 1985-10-30 | 1987-10-06 | Alza Corporation | Medical device for pulsatile transdermal delivery of biologically active agents |
| JPS62153214A (en) * | 1985-12-26 | 1987-07-08 | Nitto Electric Ind Co Ltd | Pharmaceutical preparation |
| JPS62169723A (en) * | 1986-01-22 | 1987-07-25 | Teisan Seiyaku Kk | Sustained release preparation |
| JPH02149514A (en) * | 1988-04-06 | 1990-06-08 | Nitto Denko Corp | Material for medicine |
| JPH0278616A (en) * | 1988-09-14 | 1990-03-19 | Sekisui Chem Co Ltd | Plaster |
-
1992
- 1992-03-06 KR KR1019920003699A patent/KR960006859B1/en not_active Expired - Fee Related
-
1993
- 1993-02-18 MY MYPI93000266A patent/MY109939A/en unknown
- 1993-03-04 JP JP5044136A patent/JP2655983B2/en not_active Expired - Fee Related
- 1993-03-05 GB GB9304519A patent/GB2265086B/en not_active Expired - Fee Related
- 1993-03-06 CN CN93102465A patent/CN1056509C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4615699A (en) * | 1985-05-03 | 1986-10-07 | Alza Corporation | Transdermal delivery system for delivering nitroglycerin at high transdermal fluxes |
| JPH01199916A (en) * | 1988-02-04 | 1989-08-11 | Sansho Seiyaku Co Ltd | Drug for external use |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2655983B2 (en) | 1997-09-24 |
| KR960006859B1 (en) | 1996-05-23 |
| KR930019201A (en) | 1993-10-18 |
| CN1076110A (en) | 1993-09-15 |
| GB2265086B (en) | 1996-03-06 |
| JPH07258060A (en) | 1995-10-09 |
| MY109939A (en) | 1997-10-31 |
| GB2265086A (en) | 1993-09-22 |
| GB9304519D0 (en) | 1993-04-21 |
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