TW307682B - - Google Patents

Description

307682 V. Description of the invention (1) The present invention is a group consisting of adding at least one selected from hydrocarbons, lipids, hardened or unhardened oils and fats to an agent containing kojic acid and / or its derivatives and ultraviolet absorbers, In order to improve the stability of the preparation of kojic acid and / or its derivatives, and make it a drug with performance. The representative dosage forms of Piru topical agents are 0 / W emulsions. Although the composition ratio or physical properties of water or oil are different from W / 0 emulsions, they all contain surfactants and can become water phase and oil phase. A uniform preparation that is emulsified and dispersed stably. As for the kojic acid and its derivatives that the applicant has been studying for many years in this case, they are well-known to have various excellent properties and high usefulness. The technical achievements have been disclosed in, for example, JP-A5 5-1 5 7 5 0 9 Gazette No. 5, 6-1 8 5 6 9 Gazette, Gazette No. 5 8-2 2 1 5 1 Gazette, Gazette No. 5 8-2 2 1 5 2 Gazette, Gazette No. 5 8 — 3 4 4 4 Bulletin No. 6, JP 6 0 — 7 9 6 No. 1, Bulletin No. 6 0 — 9 7 2 No. 2, JP No. 6 printed by the Employee Consumer Cooperative of the Central Standard Falcon Bureau of the Ministry of Economic Affairs No. 0 — 1 〇〇〇5, JP 6 0 — 1 3 7 2 5 No. 3, JP 6 1 — 1 〇4 4 No. 7, JP 6 1 — 6 0 8 0 1 Gazette No. 6-2 — 5 9 0 9 Gazette, Gazette No. 6 2 — 3 8 2 0 Gazette, Gazette No. 63—27322 Gazette, 83. 3.10,000 (Please read the notes on the back first Please fill in this page for details) This paper scale is applicable to China National Standard (CNS) A4 (210X297mm) 307682 V. Description of Invention (2) Japanese Patent Application No. 1 — 1 3 2 5 0 2 Gazette and Special Fairness 5 — 3 0 4 2 No. 2 Wait. However, to the best of our knowledge, this kojic acid and its derivatives (hereinafter collectively referred to as "kanoic acid") are drugs that are difficult to ensure their stability. For example, when you want to mix kojic acid in the above-mentioned o / w type emulsion or w / 〇 type emulsion for formulation, the prescription design must be a very high technology, so the development of wood will destroy the sense of use and can withstand the circulation of severe conditions. The preparation technology of the process has become a face-to-face topic in the preparation of kojic acid. When kojic acid is blended in various dosage forms, it will be exposed to ultraviolet rays that may cause kojic acid coloration and decomposition. For this reason, there are proposals for proper blending of ultraviolet absorbers, for example, Japanese Unexamined Patent Publication No. 6 2 _ 1 0 8 8 0 4, Japanese Unexamined Patent Publication No. 6.4-8 3 0 0 8 and Special Fair Publication No. 4-4 6 9 2 Bulletin 4 etc. However, most of these ultraviolet absorbers have solubility problems and often precipitate out in the formulation. Therefore, not only can the effects of the original ultraviolet absorbers not be fully exerted, but also the stability of kojic acid can be reduced. In order to solve this shortcoming, although appropriate dissolution aids are used, when a large amount of oily additives are printed by the Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, they will produce a sticky feeling, which will have an adverse effect on the use of the agent. When using kojic acid externally, there are nonionic surfactants that are more suitable for use in terms of coloring stability, feeling of use, and safety of the skin. However, nonionic surfactants are used. Not only does it not have the same strong emulsifying properties as ionic surfactants, but it is also often affected by highly polar components or P Η value, and has the disadvantage of reducing emulsifying power, so for 83. 3.10,000 (please read the back side first (Notes and fill in this page again) This paper scale is applicable to China National Standards (CNS) Α4 specification (210Χ297mm) Printed by the Consumer Standardization Bureau of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs A 7 B7 V. Description of invention (3) often need to be adjusted p Η For kojic acid preparations with a value of 4 to 5, when blending a highly polar ultraviolet absorber, there is often a problem of lowering the emulsion stability over time. The present invention is to provide non-ultraviolet absorption by adding at least one kind selected from hydrocarbons, lipids, and hardened or unhardened oils and fats to external preparations containing kojic acid and / or its derivatives and ultraviolet absorbers Precipitation of the agent, and can improve the decomposition and discoloration of kojic acid, and it has excellent stability after a long period of time, and it is an external preparation with excellent skin characteristics for improving the performance of the drug. According to the present invention, it is possible to provide an external agent containing kojic acid and / or its derivatives and an ultraviolet absorber by adding at least one group selected from hydrocarbons, lipids, and hardened or unhardened oils and fats, thereby making it UV-free The precipitation of the absorbent, and can improve the decomposition of kojic acid color due to heat, and it still has excellent stability after a long time, and improves the sustained effect of the drug. The kojic acid used in the present invention as the first component (5-oxo-2-oxomethyl-? *-Pyrone) can be used 5-oxo-2-oxomethyl-r-pyrone The pure product is a fermented liquid containing lysic acid as the main component, a concentrated liquid of the fermented liquid obtained from the cultivation of well-known strains capable of producing ferric acid, and the fermented fermented fermented liquid from the fermented liquid. The kojic acid derivative may be, for example, one or a combination of two or more of Japanese Patent Publication No. 6 0-1 0 0 0 5, Japanese Patent Laid-Open No. 1-4 5 4 7 2, and Japanese Patent No. 3-7 4 2 2 9 , Japanese Unexamined Patent Publication No. 5 8 — 2 2 1 5 1 and Japanese Unexamined Patent Publication No. 5 8 — 2 2 1 5 2 etc., the esterified compounds of kojic acid and the -C H2〇H group at the two positions of kojic acid are bonded The size of the sugar paper is based on the Chinese National Standard (CNS) A4 specification (210X297mm) 83. 3.10,000 (please read the precautions on the back before filling this page) --------- book ------ Line "------ 307682 V. Description of the invention (4) Acids, derivatives and other well-known ones. 1 〜5 重量 ％ 范围。 For the formulation, the amount of kojic acid and / or its derivative is for all external preparations for 001 ~ 10 reset%, preferably 0.1 ~ 5 wt% range. The ultraviolet absorber used as the second component in the present invention is not particularly limited, but may be 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy, of the benzophenone series Benzophenone sulfonic acid, sodium oxymethoxy benzophenone sulfonate, dihydroxydimethoxy benzophenone, etc., salicylic acid ethylene glycol, salicylic acid high ester, salicylic acid benzene Esters, urinary acid and ethyl urinary acid, p-methoxycinnamic acid 2-ethylhexyl ester of carnitic acid series, methoxy * cinnamic acid octyl ester, etc., p-aminobenzene of p-aminobenzoic acid series Glycerol formate, 2-ethylhexyl p-dimethylaminobenzoate, 4-dibutylmethane 4-tertiary butyl 4 >-methoxydibenzoylmethane, etc. or benzotriazole Part 2-(2-hydroxy-5-tolyl) benzotriazole is more suitable, and these can be used alone or in combination of two or more. In addition, other well-known animals having ultraviolet absorption energy can be combined with plant extracts as appropriate. 1 001〜10 重量 ％ ， 优选 为 0.1 ~ 5 wt%. As the hydrocarbon used as the third component of the present invention, for example, α-olefin oligomers, flowing isoparaffins, plastic base material Plastibase, manufactured by Squeeve Co., Ltd.), polyisobutylene, polybutene and other chains can be suitably used. Alkane hydrocarbons or olefin hydrocarbons, especially those with a low polarity of more than 10 carbons, 83.3.10,000 (please read the precautions on the back before filling out this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) A7 B7 307682 V. Description of invention (5) Lipids are most suitable for phospholipids, specifically, phospholipid choline, phospholipid muscle extracted from natural products such as yolk, soybean, corn, etc. Alcohol, phosphatidylethanolamine, phosphatidylserine and other glycerophospholipids, sphingomyelin, sphingosine, aminoethylphosphoric acid, and other sphingomyelins, sphingolipids, distearoylphosphatidylcholine, choline, dipalmitoside Synthetic phospholipids based on phospholipids such as cholesteryl phosphatidylcholine. The hardened or unhardened oils and fats are, for example, polyoxyethylene hardened castor oil, triisostearic acid polyoxyethylene hardened castor oil, isostearic polyoxyethylene hardened castor oil, lauric acid polyoxyethylene hardened castor oil, polyoxyethylene Hardened castor oil, polyoxyethylene sorbitol beeswax, etc. are suitable for fully hardened castor oil with a degree of polymerization of about 40 to 1,000. These can be used alone or in combination of two or more. The compounding amount of the third component of these inventions varies depending on the kind, but it is usually 〇: ο 〇 1 ~ 2 0 reset% for the total amount of external agent, preferably 0.1 ~ 10% by weight. When the above-mentioned external preparations with the first to third component groups as essential components are manufactured according to a well-known manufacturing method, a stable and stable emulsified preparation can be obtained without precipitation of ultraviolet absorbers. In addition, it can significantly improve the shortcomings of discoloration and decomposition of kojic acid in this preparation. In addition, it can also improve its transdermal absorption capacity. Therefore, it can provide a skin external preparation that can continuously exert the efficacy of kojic acid. The above-mentioned preparation of the present invention is of course not limited to emulsion types such as 0 / W emulsions and W / 0 emulsions, and can also be applied to transparent formulations by selecting ingredients. In addition, the other can also be used as W / 0 emulsion or the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the precautions on the back before filling this page) Iη ------ Order --- Line C — Printed by the Consumer Labor Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 83.3. 10,000 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economics Α7 Β7 V. Description of the invention (6) 0 / W type multi-layer emulsification Utilize the basic technology for the preparation of type preparations or microcapsules. The skin external preparation of the present invention is not particularly limited as long as it can be suitable for external use, and can be used as, for example, a hot compress, an incubator, a paste, a cream, an incubator, a spray, an emulsion, a lotion, an emulsion, Flavors, facial masks, gels, powder foundations, sunscreens, bath essences, etc. are widely used as well-known forms such as pharmaceuticals, non-medicinal products, and cosmetics. When the external preparation of the present invention is prepared, various commonly known effective ingredients such as hexyl chloride, cephalanthin, vitamin E, vitamin E, hexanoic acid, etc. may be appropriately added according to the purpose. Peripheral vasodilators such as nicotinic acid, nicotinic amide, benzyl nicotinate, raw corydine, capsaicin, camphor, menthol, peppermint, etc., hinokitiol, benzalkonium chloride, Antimicrobial agents such as undecylenic acid, pararenal corticosteroids, e-aminocaproic acid, lysozyme chloride, glycyrrhizin, allantoin and other anti-inflammatory agents, white agents such as ascorbic acid and arbutin, placenta extract, liver extract , Radix extract, lactic acid bacteria culture extracts, etc. from animals, plants, microorganisms and other extracts. In addition, the above-mentioned substitute medicines, non-pharmaceutical products, and cosmetics can be added with base ingredients such as fats and oils in addition to known effective ingredients. In addition, known moisturizers, preservatives, antioxidants, Various additives such as sequestering agents, pH modifiers, fragrances, colorants, etc. Secondly, experiments and prescription examples are disclosed to illustrate the present invention, but these examples are only to disclose the preferred embodiments of the present invention, and the invention is not limited to this. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm ) 83.3.10,000 (please read the precautions on the back before filling in this page). Line, 307682 V. Description of the invention (7) [Experiment 1] Experimental method of stability test of the preparation: According to the prescription conditions disclosed in Table 1, various creams are prepared separately Preparation (p Η value about 45). After filling these formulations in 4 ounce cylindrical bottles, they were stored under severe temperature conditions of 50 ° C for two months while irradiating ultraviolet rays. Two months later, the color difference (ΛΕ) was measured (using Japan Denshoku Industries Z1 001 DP color difference meter). At this time, the appearance change (presence or absence of ultraviolet absorber, emulsification stability) was observed, and the feeling of use was evaluated together. Experimental results As shown in Table 1, the preparation of the present invention in which ingredients 1 to 8 are added is a method without UV absorber, and the emulsification stability is also excellent. In addition, the coloring stability of @ ^ in the preparation is also good, and it is maintained in an excellent state of use. * ^ ϋ · In «V. ^^ 1«--li ^^ 1 nn fa (please read the ^ fliv item on the back and then fill in this I) Order _ Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy 83. 3. 10,000 paper scales are applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) -10 V. Description of invention (8) A7 B7 Employee's Consumer Cooperation Cooperative Printed Table 1-1 for trial and experiment Results Test Results Ingredient Name Example 1 2 3 4 5 6 7 8 • Period m 5.00 5.00 2.00 _ _ • Soybean phospholipid one 2.00 — 1 " »_ one 2.00 —- • Phosphatidylcholine — _ 5.00 — 0.50 — __. Nerve sheath surface one — one 0.50 one _. Polyoxyethylene hardened na oil — — — — 1.50 —-__. Isostearic polyoxyethylene hardened castor oil (60E. 0.) — _ — _ 0.50 .__ ^-.Polyoxyethylene suspected oil-one one-1.50 _ _. Polyoxyethylene sorbitol beeswax one _ one-3.00 • Μ 庚 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 〇. 2-hydroxy one 4-Methoxy: Benzophenone 1.50-0.80. One _ 1 4-T-butyl-4'-methoxy One one 1.00 0.50 one — 0.20 __ Dibenzomethane 2. Glyceryl p-aminobenzoate one — 0.20 — — 0.10 1.50 ^. Ί Warm ethylene glycol — One 1.00 — — 4. Methoxy cinnamon Drunken Ester One One One One One One One One One One 0.50 One One One One One One One One One One One One Vitamin E 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 y. Polyoxyethyl hexadecanoic acid (2 5 E. 0.) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 〇. Polyoxyethyl acetyl stearate (2 0 E. 0.) 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70 1. Carboxyvinyl heteropoly 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 2 .d) -Secretone complete liquid 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3. Ethylenediamine tetra Dina Acetate 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 4 · Lime-faced cage weaving the tortoise ugly seam 5 · Lemon-aged inner cage weaving the tortoise 6 · Refined water Ί 1—- Following the weaving tortoise ugly WS. External ultraviolet Shed precipitation — no precipitation precipitation precipitation precipitation precipitation precipitation milky state (with or without separation) 〇〇〇〇 „〇: good △:-partial separation X: separation U 〇 color difference (ΛΕ 値) 3.2 3.1 3.0 2.3 3.0 2.9 2.5 2.3 Use feeling fWS scale ◦: Good raw sugar 〇〇〇〇〇〇〇〇 test: almost no problem sticky feeling 〇〇〇〇-test △: slightly problem U 〇X: poor lion sex 0 〇〇 〇〇〇〇 (please read the "quote-v item on the back and then fill in this page) 83. 3.! 0, 〇〇〇-y 4Γ! Order-11-V. Description of invention (q component name A7 B7 Table 1 -2 for ^^ and the experimental results of the previous preparations of the proportion of the festival comparison example 3 comparison example 4 comparison example 5 thief section ratio example ratio 1. dead base 2. soybean dish lipid 3 · miscellaneous_ gallbladder 4. nerve sheath surface 5 .Polyoxyethylene hardened very sesame oil 6 · Isolated acid polyoxyethylene hardened _ oil (60E.0.) 7. Polyoxyethylene suspected sesame oil 8 · Polyoxyethylene sorbitol honey sensitive 9. Ascorbic acid 10. 2 —Hydroxy-4-methoxybenzophenone 1 1.4 A third butyl 4, a methoxy Benzene dibenzomethane 1 2 · Glyceryl p-aminobenzoate 1 3. Ethylene glycol salicylate 14 · Octyl methoxycinnamate-ο ο 8 5 0 · 0 · (Please read the notes on the back first (Fill in this page again)-! Two 50 10 50110 1 5. Honey withdrawal 1 6. Vaseline 1 7. Jojoba oil 1 8 · Natural vitamin E 1 9. Polyoxyethylene hexadecanoic acid (2 5 E · 0. ) 2 0. Polyoxyethylene ΙΜΙ purpose ether (2 0E. 〇.) 21. Carboxyethylene polymer 2 2. ≪ Π _ 妣 slightly finely finished liquid 2 3. Ethylenediaminetetraacetic acid dioxin 2 4. wm . 2 5. wmm 2 6. Refined water 000400802fctt 580057000JJJ 4.27 · ° · 1 < 00-6 ° -Weihuiyu 000400802SSS 580057000 Tun ^^^^^^^ Mild suitable 0 0 0 4 0 5 8 0 0 5 4 2 7-0 ·? 70080002®® quantity I0 · 0 · 6 · 0 · Xi Baizhai 000400802S6S 58005700033i 4.2 70-10-0-6 ° -slightly suitable ο ο 5 8 0 4 2 7 400802acfcs 057000Jii 0 · 1 ° · ° · 60 · Hui Huiqiu 0004 008026Ϊ-6 580057000JJS 427 · 010 · 0 · 60 · Weifushi 000400802S &-& & 580057000ii_s 4 · 2 7 · 0 · 1 ° · ο · 6 · 0 · Hui Weigui ο ο ο 5 8 0 4 2 > 400802 Euro £ > 057000jj3: 0 · 10060 Printed test results of the Employees ’Cooperatives of the Bureau of Appearance Appearance of using the test UV absorber to determine the milk shedding state (with or without separation) ○: Good △ • Partial separation X: Separation color difference (ΔΕ 値) Evaluation of use feeling 〇: Good 〇 : There are few problems △: Slight problems X: Poor coarse sugar sticky feeling lion-like without deletion, deletion, deletion, contact 000400802-ε-ε-κ ΠΡ 580057000 «^ s« 3 UU 4.27 · 0 · .- · 0 · 0 · 6 · 0 · ^^ 1 · Analysis △ △ △

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X △ 83. 3.! 0, 〇〇〇 307682 ^ V. Description of the invention (ίο) [Experiment 2] The effect of guinea pigs to suppress ultraviolet pigmentation. A yellow-brown guinea pig was used to investigate the improvement of pigmentation.示 结果 于 表 2。 The results are shown in Table 2. It can be seen from Table 2 that the preparation of the present invention has an excellent pigmentation inhibitory effect 'and it is confirmed to be a preparation that can maintain the medicinal effect for a long time. Re-test method uses the back skin of a yellow-brown guinea pig and removes it with a clipper (shave) The hair on the back of the guinea pig is then shaved with an electric razor. Cover the back of the guinea pig with aluminum foil with four square (2.0X2.0cm) openings, and irradiate UV-B (3 SE lamps, 1 4 OmJ / cm2) for 90 seconds every three days. 4 exposures. After the start of irradiation, the preparation prepared in Experiment 1 was applied to the tested part of the guinea pig three times a day for 10 consecutive days. Pigmentation was measured on day 10 and day 20 after the start of application. The degree of darkening of the skin color can be measured with the naked eye according to the following criteria. Judgment: Printed by an employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 3: No pigmentation shock at all 2: Slight pigmentation 1: A moderate degree of pigmentation can be confirmed: Same as the control part (untreated) — 1: There is deeper pigmentation than the control part (untreated). 83. 3.10,000 (please read the precautions on the back and then fill out this page) This paper size is suitable for China National Standard (CNS > A4 specification (210X297mm)

Printed by the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (11) Table 2 -1 Experimental results Example 1 2 3 4 5 6 7 8 1. Plastic base 5.00 5.00 2.00 2. Soybean phospholipid — 2.00 — — — — 2.00 — 3. Scale fat unitary _ 鹸 — — 5.00 — 0.50 — — — 4. Nerve sheath surface 5. Polyoxyethylene hardened Na oil _______ — ______ 0.50 1.50 — — — 6. Isostearic acid Polyoxyethylene hardened very hemp oil (60E.O.) — — — — — 0.50 — — 7. Polyoxyethylene suspected oil — — — — — — 1.50 — 8 • Polyoxyethylene sorbitol honey beetle — — — — — — 3.00 9.. Ascorbic acid 1. ⑻ 1.00 1.00 1.00 1.00 1.00 1.00 1.00 10.2- -Hydroxy-4—methoxydibenzoyl_ 1.50 — 0.80 11.4- -Third butyl-4, —methoxy-1- 1.00 0.50 — — — 0.20 — Dibenzoylmethane 1 2 · Glyceryl p-aminobenzoate — — —— 0.20 — — 0.10 1.50 13. · Glycol — — — 1.00 — — — 1 4. A Octyl oxycinnamate 0.50-0.10 1 5. Honey catfish 4.50 4.50 4.50 4.5 0 4.50 4.50 4.50 4.50 1 β. Vaseline 2.80 2.80 2.80 2.80 2.80 2.80 2.80 2.80 1 7. Jojoba oil 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 1 8 Natural Vitamin E 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 1 9 .Polymer Oxyethine hexadecyl ether (2 5 Ε .0.) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 2 0 .Polyoxyethylene ethoxystearyl ether (2 0 Ε. 0.) 0.70 0.70 0.70 0,70 0.70 0.70 0.70 0.70 2 1. Carboxyethylene polymer 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 2 2. D] 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 2 3 _ ethylenediaminetetraacetic acid dina 2 2. Acid 2 5. 0.02 Limian 0.02 Follow surface 0.02 雠 観 0.02 follow 0.02 face follow 0.02 face 0.02 cage face 0.02 ms. WM. 2 6. Refined water follow mm. Face to follow the appropriate amount of leg seam measurement Day 10 0 0 0 0 0 0 0 0 0 Day 2 0 3 3 3 3 3 3 3 3 --------------- ^ ______ 丁 ______ 泉-, v * hair / (Please read the precautions on the back first (Fill in this page) This paper size is applicable to China National Standards (CNS) A4 specification (210X297mm) 83. 3. 10,000 307682 g V. Description of invention (l2) Table 2-2 for testing Materials and Experimental Results Conventional Preparations Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Comparative Example 9 1. Plastic Base — _ — — — — — — — 2. Soybean Phospholipid-3 · Phospholipid gallbladder---------4. Nerve sheath _---5. Polyoxyethylene hardened chopped oil — 6. Isostearic acid polyoxyethylene hardened sesame oil ( 60E.O.) 7. Polyoxyethylene sesame oil 8. Polyoxyethylene sorbitol honey beetle-9-Ascorbic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 10.2- -Methyl-4-methoxydibenzene Methyl ketone — 1.50 — 0.80 — — — — — 11.4- -Third butyl 4 ′ —Methoxy mono — 1.00 0.50 — — — 0.20 —— Dibenzoylmethane 1 2. P-aminobenzophenone Oil esters — — 0.20 — — 0.10 1.50 1 3. Ethylene glycol salicylate 1.00 — — — 1 4. Methoxycinnamic octanoate 0.50 _ 0.10 1 5. Honey tender 4.50 4.50 4.50 4.50 4.50 4.50 4.50 4.50 4.50 1 β. Vaseline 2.80 2.80 2.80 2.80 2.80 2.80 2.80 2.80 2.80 1 7. Jojoba oil 7.00 7.00 7.00 7.00 7.00 7_⑻ 7.00 7.00 7.00 1 8. Natural Vitamin E 0.04 0.04 0.04 0.04 0.04 0.04 0,04 0.04 0.04 1 9 .Polyoxygen Ethylene hexadecyl ether (2 5 Ε. 0.) 1.50 1.50 1.50 1.50 1,50 1.50 1.50 1.50 1.50 2 0 Polyoxyethylene stearate (2 0 Ε. 0.) 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70 0.70 2 1. Carboxyethylene polymer 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0; 08 2 2. D 1 Yiliuyuan Ketone Complete Solution 6.00 6.00 6.00 6.00 '6.00 6.00 6.00 6.00 6.00 2 3. Ethylenediaminetetraacetic acid Disodium 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 2 4. Lazy brewing followed by awakening WM. 観 ms. Following 2 5. mmm cage following 雠 followed by sarcasm trace amount η 2 6. Refined water appropriate amount suitable child appropriate amount appropriate amount appropriate amount Determination of the effect of the right amount of the right amount of pigmentation brewing Day 1 0 0 0 0 0 0 0 0 0 0 0 Day 2 0 1 1 1 1 1 I1 1 1 1 1 The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm ) 83. 3.10,000 (Please read the notes on the back first Then fill page) A7 B7 V. invention is described in (13)] [Formulation weighing ο ο IX to the body so that all parties may refer to the amount of square-based side adapted from Example J Γ out hair, the present exemplified below. Take the% of punishment --- Ί i ^ ---- ^ ------ order ------ line ((please read the precautions on the back before filling out this page) Staff of Central Bureau of Standards, Ministry of Economic Affairs The paper printed by the consumer cooperative uses the Chinese national standard (CNS> A4 size (210X297mm> 83.3. 10,000 BQ7682__V. Description of the invention (l4)) [Prescription Example 1] Face cream (1)% Amount of heavy hemp ether Hexa I Idecadecylcholene hydroxyacetate I Lipoxygen 2 Phosphate poly 4 ketotolyloxymethyl E ο 4 ο E 5 2 Sour oil, fat, pear, hard case, apricot liquid, sodium carboxylate Sodium ketoacid, alkyl, methyl, ethyl, pyrrol, tetrapyrylamine, water, I, hydroxy, 2, 1, ethyl, d.. _ Ooooooooool 05000000020 (please read the precautions on the back before filling this page) Appropriate amount of consumption by the Ministry of Economic Affairs Central Standards Bureau The paper printed by the cooperative is used in the Chinese National Standard (CNS) A4 specification (210X297 mm) 83. 3.10,000 17-A7 B7 5. Description of the invention (15) [Prescription Example 2] Face cream (2) Weight% Koji ο ο 4 Carboxylic acid ethyl ethyl phenoxyl oxygen oxy-charged phosphorous polyplastic polyhexylamine amine butadiene methanol methanol triethylene vinyl Moonhair sheep oil 4 base oxymethine ο ο ο ο 2 ο ο ο ο ο ____________ (please read the precautions on the back before filling in this page) Central Government Bureau of Economic Affairs Employee Consumer Cooperative Printed liquid soluble sodium alkane Sodium alkoxide, dioxygen, oxygen, E, acid, silicon, silicon, silicon, life quality, Ethylene tetramer, Gelatin, Tetracyclic Cyclic, Vitramine, Aqueous, Aqueous,%, Koji, A, A, A, 2, 1, Deer, Essence, 18, ο ο ο ο ο ο 4 ο ο ο ο ο IX ο Appropriate amount-the size of the paper edition is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 83. 3.10,000 18-A7 B7 5. Description of the invention (16) [Prescription Example 3] Emulsion (1) P-methoxycinnamic acid 2-ethylhexyl squalane squalane neuroamide polyoxyethylene cetyl ether (25E. Polyoxyethylene oleyl stearate shea butter fat casein Pear oil. Parabens. Oak seed extract. Xanthan gum. Disodium edetate. Purified water reset% 1.00 0 〇0 0 0 0 0 0 0 0 0 0 0 Appropriate amount (please read the back first Please pay attention to this page and then fill out this page.) The printed standard paper of the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs is applicable to the Chinese country. Standard (CNS) A4 specification (? 10X297mm) 83. 3. 10,000 -19-307682_ V. Description of the invention (l7) [Prescription Example 4] Emulsion (2)% amount of heavy wax honey ester alcohol octyl sorbitol Guishan Dimethoxyethyl Acetate Oxymethoate Meglucan ο 5 ο ο ο ο 5 I Acid Acid Waxic Acid Sodium Methionate Ethyl Fatty Acid Tetamic Acid Tetrakinic Acid Vitamin Matrigel Water Flow Oleic Acid Cardamom Ranran Hydroxylamine Proton Fat Bean Pear Sky Pair Trans Han Yi Jing Light Coconut Hard Meat Case ... Acetoacetate as sodium suitable ο ο ο ο ο 5 ο 5 ο ο 4 ο ο 2 ο ο 4 1 1 ο amount ( Please read the precautions on the back before filling out this page) The paper standard printed by the Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs is applicable to the Chinese National Standard (CNS> A4 specifications (210X297 mm) 83. 3.10,000 20 A7 B7 V. Description of the invention (IS) [. Prescription Example 5] Make-up water (% by weight) Butyric acid methyl ethyl ethyl spermidine base blood lemon% triacid triphenyl I Guixi ginseng hydroxycarbohydrate 5 ethyl alcohol second month poly When people fight ... _ 〇 ester · hex E acid oil Q Guima 6 meat M 丨 I based ether. Oxydane oil 4 alkyl methene hexaglycol I A to ethyl decahydrate Acetyloxyalkenyloxymethyl hydrolysate sodium water diester leucoic acid egg ethyl methyl sodium tetrabenzoate ammonium hydroxide water suitable ο ο ο ο 5 0 0 ο ο ο ο ο ο 5 ο ο ο IX IX 0〇 ο ο IX ο amount

Bt ^ i · n ^ i leu I i''J ・ im ^ in (please read the notes on the back first and then fill in this page) Thread- ^ Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. The paper size is applicable to China National Standard (CNS) Α4 specification (210 X 297 mm) 83. 3. 10,000 A7 B7 5. Description of the invention (l9) [Prescription Example 6] Ethyl ethyl methacrylate 4-third butyl 4 methoxy Dibenzoylmethane triisostearic acid polyoxyethylene hardened sesame oil (1 Ο Ο E.〇.) Phosphatidyl inositol stearic acid diethanol amide stearic acid myristic acid coconut oil natural vitamin E. para-hydroxyl Benzoate d 1 Pyrrolidone Carboxylic Acid Sodium Solution Ethylenediaminetetraacetic acid disodium purified water (% by weight) 2.00 0.50 2.00 5.00 5.00 5.00 0.50 5.00 0.04 0.20 5.00 0.01 Appropriate amount (please read the precautions on the back before filling this page) iv

a ^ m vm-^ —Β ^ ϋ m ^ i ^^^^ 1 —Bn m > R k— ·, \ $ Fa J The Central Standards Bureau of the Ministry of Economic Affairs of the People ’s Consumer Cooperative printed this paper. The standard of the paper is China National Standards (CNS ) A4 specification (210X297mm) 83.3. 10,000 A7 B7 V. Description of the invention (2〇) [Prescription Example 7] Ointment (wt%) Sulfonyl Toluene Disodium Amino Acid Sulfonate Sodium Methone Ethyl Ketone Dimethyl I Acid 4 Acid Methyl Ethyl Benzoate I Fatty Benzene Tetrayl Ester Based Fatty Oleyl Rape Amino Hydroxyphenoxy Oxylinoleic Acid Hydroxylargine Dicarboxylic Acid I Acid Methylstearic Acid Olive Pyrol Koji 2 Salicylic Hydrocarbon Plastic Hard Oil......... 0 12 3 4 12345678911111

ooooooooooool 0140000000200 quantity 1001250510050 suitable for 1X IX

Hu IL 1- tv-i ^ lm ^ — ^ —B ^ — ^^^^ 1 ^ m tm ^^^^ 1 mu ^ in — ^ m ml n ^ i (Please read the notes on the back before filling in this Page) The paper standard printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs conforms to the Chinese National Standard (CNS) A4 specification (210X297 mm) 83. 3. 10,000 23 307682_ V. Description of invention (21) [Prescription Example 8] Hot compress Agent% amount of heavy oil enamine glycine oxyalcohol glyceryl methyl ethyl benzoate diacyl fatty acid amine stearic acid to the different hardness ο 5 dagger said linseed acid allylic poly 2 ο ο ο ο ο ο ο ο 物} Extraction of diol extract acid dihydrate ethyl sodium 丨 {tetraspermine spermine dipropylene dipropylene yellow ethylene 0 5 5 1 ο ο ο ο (please read the notes on the back before filling this page) Chlorine-concentrated oxygen concentrate made from aluminum oil titanium hydration and glycation 2 suitable ο ο ο 3 0 0

Line J--S The paper standard printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs is applicable to the Chinese National Standard (CNS) Α4 specification (210Χ297 mm) 83. 3. 10,000 307682 A7 ____B7 V. Description of the invention (22) [prescription example 9〕 Percentage of fragrances. Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 1. Ascorbic acid 2. Uric acid 3. 2-ethylhexyl p-methoxycinnamate 4. Flowing isoparaffin 5. Dipalmityl Phospholipid cholesterin 6. Coconut oil fatty acid-acetamide acetate 7. Stearic acid 8. Linolenic acid 9. Avocado oil 1 〇. G oil 1 1. Natural vitamin E 1 2. Paraben 1 3. 1% hydroxyethylene polymer aqueous solution 14. Xanthan gum 15. Disodium ethylenediaminetetraacetic acid 1 6 · Purified water The above-mentioned prescription examples 1 to 9 are all confirmed to be preparations with the data disclosed in the table that can satisfy the object of the present invention. Appropriate amount 1 and Table 2 [Effects of the invention] According to the present invention, it can be provided that the Chinese national standard (CNS) A4 specification (210X297 mm) is applicable to the standards containing kojic acid and / or the paper. 83. 3.10,000 ——Ί3- --- i 丨 I (Please read the precautions on the back before filling in the purchase) Threading < * 25-3〇7682 A7 ___B7_ V. Description of the invention (23) Adding at least one of the external agents for thread absorbent It is selected from the group consisting of hydrocarbons, lipids, and hardened or unhardened oils and fats. The external preparation is a skin-care agent, which is, more preferably, extremely effective. The fixation of Dingan is extremely effective after a long period of time. The medicine will be used for a long time, and the solution will be analyzed separately. , There is a change that will not be removed I --- ir 1 ---- ^ ------ order ------ line, (please read the precautions on the back before filling this page) Ministry of Economic Affairs Printed by the Central Bureau of Standards' Staff Consumer Cooperative 83.3.10,000 This paper standard applies to China National Standard (CNS) A4 (210X297mm)

Claims (1)

Α8 Β8 C8 D8 々, Patent Application No. 83 103796, Chinese Patent Application, Amendment of Patent Scope Amended in April 1986 1. A stabilizing skin Λ external treatment composition containing 0.1% to 5% by weight of kojic acid and / 1 ~ 10% by weight of at least one selected from the group consisting of paraffinic hydrocarbons with carbon number of 10 or more Or alkene-based hydrocarbons: ② selected from phospholipids grouped by phospholipid choline, soybean phospholipid, dipalmitoyl phosphatidyl phosphatidyl choline, ceramide, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. Class: ③ selected from polyoxyethylene hardened hemp oil with a polymerization degree of 40 to 100, triisostearic acid polyoxyethylene hardened hemp oil, isostearic polyoxyethylene hardened hemp oil, lauric acid polyoxyethylene Oils grouped by hardened hemp oil, polyoxyethylene hardened hemp oil, and polyoxyethylene sorbitol beeswax. (Please read the precautions on the back before filling in this page) Pack. Order Λ Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. The paper size is applicable to China National Standard (CNS) Α4 specification (210Χ297 mm)