JP2007016025A - Topical composition for skin and method - Google Patents

Topical composition for skin and method Download PDF

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JP2007016025A
JP2007016025A JP2006160635A JP2006160635A JP2007016025A JP 2007016025 A JP2007016025 A JP 2007016025A JP 2006160635 A JP2006160635 A JP 2006160635A JP 2006160635 A JP2006160635 A JP 2006160635A JP 2007016025 A JP2007016025 A JP 2007016025A
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vitamin
skin
acne
carotene
distilled water
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Towa Rin
東和 林
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Lotus Pharmaceutical Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355Tocopherols, e.g. vitamin E
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • A61K8/673Vitamin B group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • A61K8/676Ascorbic acid, i.e. vitamin C
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • A61K8/678Tocopherol, i.e. vitamin E
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Abstract

<P>PROBLEM TO BE SOLVED: To provide a topically used composition used for recuperation and moisture retaining of skin, removal of acne, acne vulgaris and comedones äopen comedones (blackheads), closed comedones (whiteheads), papules or pustules} and anti-oxidation without containing vitamin A acid readily causing adverse effects on the skin. <P>SOLUTION: The topically used composition for skin is composed of principal ingredients of vitamin C in an amount accounting for 1-45 wt.%, vitamin B group in an amount accounting for 1-5 wt.%, carotene in an amount accounting for 0.1-3 wt.%, vitamin E in an amount accounting for 2-90 wt.%, a perfume in an amount accounting for 0.1-2 wt.%, a thickener in an amount accounting for 1-5 wt.%, a surfactant in an amount accounting for 1-8 wt.% and the balance of an adequate amount of distilled water. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

本発明は皮膚の局部使用の外用組成物に関し、特に局部的に皮膚の保養、保湿、ざ瘡、にきび、青春痘及び抗酸化に使用されるビタミンA酸を含まない組成物に関する。   The present invention relates to a topical composition for topical use of the skin, and more particularly to a composition containing no vitamin A acid used locally for skin nourishing, moisturizing, acne, acne, youthful wrinkles and antioxidants.

人の皮膚の構造は表皮、真皮、皮下脂肪組織、皮脂腺、汗腺、毛髪及び爪を包括し、そのうちで真皮は表皮下面厚さの一層であり、毛髪は周囲の毛嚢により囲まれ、その側面には皮脂腺がある。皮脂腺が皮脂を分泌すると、皮脂は毛髪及び毛嚢を経由して皮膚表面に浸透し、しかる後、脂肪薄膜となり、皮膚表面に付着して皮膚を保護する。皮脂腺の多寡により皮膚は類別され、通常、油性皮膚、乾性皮膚及び混合性皮膚に区分される。   The structure of human skin encompasses the epidermis, dermis, subcutaneous adipose tissue, sebaceous glands, sweat glands, hair and nails, of which the dermis is a single layer of epidermal thickness, and the hair is surrounded by the surrounding hair follicle Has sebaceous glands. When the sebaceous glands secrete sebum, the sebum penetrates the skin surface through the hair and hair follicles, and then becomes a fat thin film that adheres to the skin surface and protects the skin. The skin is classified according to the number of sebaceous glands and is usually classified into oily skin, dry skin and mixed skin.

ざ瘡は通常にきび、青春痘として認められ、一種の毛嚢、皮脂腺の慢性炎症に属する。しかしながら青春痘は通常前額、鼻翼四周、両頬、甚だしくは背部、前胸、太股等の全身にわたって毛嚢のあるところに現われるもので、その現われる症状に応じて、にきび型、発赤腫型及び嚢腫型に区分される。青春期における男女は性腺が成熟し始めると、睾丸及び卵巣、腎上腺の雄性ホルモン含量が増加するので、人の皮膚の皮脂腺を刺激してそれを肥大させ、大量の皮脂を分泌して皮脂腺、毛嚢に堆積し、細菌作用により発赤する。通常先に黒頭にきび又は白頭にきびを形成してから、にきびが更に細菌の感染を受けて丘疹、膿疱、結節、嚢腫等の症候が発現するのが青春痘である。また他に、男性ホルモンの分泌が多すぎると面部のT字部位及び眼皮下面の皮膚に赤、痒、熱、やけど、脱皮が現われる可能性があり、時にははっきりした毛管現象が現われる。これを脂漏性皮膚炎と称する。   Acne is usually recognized as acne and youth buds, and belongs to a kind of chronic inflammation of the hair follicle and sebaceous glands. However, youth buds usually appear in places with hair follicles throughout the body, such as the forehead, four nose wings, both cheeks, back, front chest, thighs, etc.Acne type, redness type and Divided into cyst type. Men and women in adolescence, when the gonads begin to mature, the male hormone content in the testicles, ovaries, and suprarenal glands increases. It deposits on the surface and reddens by bacterial action. Adolescent pupae usually have blackheads or baldheads first, and then acne is further infected with bacteria to develop symptoms such as papules, pustules, nodules, and cysts. In addition, if too much male hormone is secreted, red, wrinkles, heat, burns, and molting may appear on the T-shaped part of the face and the skin on the subcutaneous surface of the eye, and sometimes a distinct capillary phenomenon appears. This is called seborrheic dermatitis.

通常、外用剤は皮膚の清潔、及び殺菌作用を発生させ、皮膚水分の蒸発を防止して保湿作用を増進する等が期待されている。例えば特許文献1には塩化ナトリウム成分を含むことにより肌膚を柔らかくして、すべすべにできるバルサムが記載されており、特許文献2には鉱物質塩類を含むことにより肌膚を衛生的に清浄させることが開示されている。特許文献3には葡萄糖を混合して肌膚を潤滑できる糖類が記載されており、特許文献4には葡萄糖水溶液を用いてひげを剃ることが記載されている。   Usually, an external preparation is expected to generate skin cleansing and bactericidal action, prevent evaporation of skin moisture, and enhance moisturizing action. For example, Patent Document 1 describes a balsam that can soften and smooth the skin by containing a sodium chloride component, and Patent Document 2 can cleanse the skin hygienically by containing mineral salts. It is disclosed. Patent Document 3 describes sugars that can be mixed with sucrose to lubricate the skin, and Patent Document 4 describes shaving using a sucrose aqueous solution.

塩化ナトリウムは体液浸透圧を維持する主体となれ得て、特に0.9%溶液は生理的食塩水と称されているけれども、高濃度の塩化ナトリウム溶液を皮膚より吸収できないので却って皮膚の粘膜を刺激して脱水作用を引起す。したがって塩化ナトリウムを添加すれば皮膚を刺激又は細菌できるが皮膚水分の蒸発を防止して保湿作用を促進する作用効果の改善は極めて困難である。   Sodium chloride can be the main body that maintains the body fluid osmotic pressure. Especially, 0.9% solution is called physiological saline, but it cannot absorb high concentration sodium chloride solution from the skin. Cause dehydration. Therefore, the addition of sodium chloride can irritate the skin or bacteria, but it is extremely difficult to improve the effect of preventing moisture evaporation and promoting the moisturizing action.

葡萄糖は糖分の原質を向上し、全身の細胞機能を亢進させて生物体代謝機能を増進する営養であるが消毒作用をも有している。けれども経口補給でなければ、静脈注射又は肌膚注射を通して補給を提供する。直接皮膚に貼る外用剤にたとえ葡萄糖を添加してもこれら葡萄糖が特有効果を奏することを期待できない。   Sucrose improves the quality of sugar and enhances cell functions throughout the body to enhance the metabolic function of the organism, but it also has a disinfecting effect. But if not oral supplementation, supplementation is provided through intravenous or skin injection. Even if sucrose is added to an external preparation directly applied to the skin, it cannot be expected that these sucrose will have a specific effect.

各種の局部使用の薬学活性剤は経皮吸収増進剤が添加されるが通常ヘキサンジオン酸ジブチル及びヘキサンジオン酸と豆蒄(Amomum costatum)酸イソプロピルとの混合物が採用されている。豆蒄酸イソプロピルは既に局部調合の浸透促進剤であることが知られている。しかしながら出願人はいかなる先行技術からもDBA及びIPM組成物の皮膚浸透促進の協合効果を発見していない。   Various locally used pharmaceutically active agents are added with a percutaneous absorption enhancer, and usually dibutyl hexanedioate and a mixture of hexanedioic acid and isopropyl bean (Amomum costatum) are employed. It is known that isopropyl bean succinate is already a locally formulated penetration enhancer. However, the applicant has not found from any prior art the combined effect of promoting skin penetration of DBA and IPM compositions.

各種の治療剤及び化粧剤、例えば異位性皮膚炎における掻痒及び赤色斑点に用いられる水素化コーチソン、皮膚ばい菌感染用のsulconazol nitrate,光老化用のtretinoin,ならびに乾癬および皮膚癌用の5-フッ化ウラシルが数種の皮膚症状の治療処理に用いられる。皮膚病の治療は通常浸透促進剤、例えばジメチルスルホキシド(DMSO,ジメチルホルムアミド、メチルデシルスルホキシド(特許文献5)、ジメチルアセトアミド(特許文献6)及びN−アルキル−2−カンフェニロン(特許文献7)が添加される。けれども上記浸透促進剤は少なからず欠点が発生する。例えばジメチルスルホキシドは異味及び体臭があり、皮膚においてやけど及び赤色斑点をもたらし、水晶体皮膚の透明性を低減、甚だしくは動物の組織壊死を来たす(非特許文献1)。ジメチルホルムアミド及びジメチルアセトアミドも皮膚においてやけど及び赤色斑点を引起す。   Various therapeutic and cosmetic agents, such as hydrogenated cortisone for pruritus and red spots in anaplastic dermatitis, sulconazol nitrate for dermatophyte infection, tretinoin for photoaging, and 5-fluorine for psoriasis and skin cancer Uracil is used in the treatment of several skin conditions. For the treatment of skin diseases, penetration enhancers such as dimethyl sulfoxide (DMSO, dimethylformamide, methyl decyl sulfoxide (Patent Document 5), dimethylacetamide (Patent Document 6) and N-alkyl-2-camphenylone (Patent Document 7) are usually added. However, the penetration enhancers have a number of drawbacks, such as dimethyl sulfoxide, which has a nasty taste and body odor, causing burns and red spots in the skin, reducing the transparency of the lens skin and severely causing animal tissue necrosis. (Non-patent Document 1) Dimethylformamide and dimethylacetamide also cause burns and red spots in the skin.

Trebosc達の特許文献8には含改良カフェイン派生物を活性剤とした化粧組成物の公開された調合は“良好且つ長期効果の脂肪分解の性質を有しているので痩身計画及び皮脂粒子の治療上極めて有効である”とのことが証明されている。Mausner、特許文献9はmethylsilanol theophyllinacetate alginate及びmethylsilanol mannuronateを使用して去脂肪(anti-cellulite)の成分としている。   Trebosc et al. In US Pat. No. 6,037,099 published compositions of cosmetic compositions containing modified caffeine derivatives as active agents have “good and long-lasting lipolytic properties, so slimming plans and sebum particles It has been proven to be “very effective in therapy”. Mausner, Patent Document 9, uses methylsilanol theophyllinacetate alginate and methylsilanol mannuronate as components of anti-cellulite.

局部に例えばKligmanの特許文献10のレチレンを施用すれば有限的に脂肪粒を改善することができる。Kligmanは皮膚厚さの増加、新血管の増加、及びひねり試験(第6欄、第50〜61行)から中度ないし鮮明な改善を観察できると称している。特許文献11はアミノ左旋糖酸光力療法(aminolevulinic acid-photodynamic therapy)“Topicalaminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris”を開示した。特許文献12は水、グリコールを使用するざ瘡治療組成物を開示した。特許文献13はreveratrol(3,4’,5-trihydroxy-trans-stil bene), melatonin, ビタミンD,E,Aを使用するざ瘡治療組成物を開示した。特許文献14は生物素(biotin)、生物素エステル類(biotin ester)、ヒドロキシカルボキシ酸、抗酸化剤(antioxidant)を使用し、そして特許文献15はビタミンB群ビタミン、ビタミンE、ビタミンC、燐脂質(phospholipid)を使用して皮膚を保護することを開示した。   For example, if the retylene of Kligman of Patent Document 10 is applied locally, fat grains can be finitely improved. Kligman says that moderate to sharp improvements can be observed from increased skin thickness, increased new blood vessels, and twist test (column 6, lines 50-61). Patent Document 11 discloses aminolevulinic acid-photodynamic therapy “Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris”. Patent Document 12 discloses a composition for treating acne using water and glycol. Patent Document 13 discloses a composition for treating acne using reveratrol (3,4 ', 5-trihydroxy-trans-stil bene), melatonin, vitamins D, E, and A. Patent Document 14 uses biotin, biotin ester, hydroxycarboxylic acid, antioxidant, and Patent Document 15 discloses vitamin B group vitamins, vitamin E, vitamin C, phosphorus Disclosed using phospholipids to protect the skin.

上記の資料から、少なからずの特許はざ瘡の治療、脂肪の除去、数種の皮膚症状の処理についての治療作用を有していると主張しているが、いずれも本発明のビタミンA酸を含まない局部使用組成物と相違している。本発明の主たる目的は局部にビタミンA酸を含まない組成物を使用して皮膚を保養、保湿し及びざ瘡、にきび、青春痘及び抗酸化を治療することにある。
アメリカ特許3,574,854号明細書 ドイツ特許3,327,840号明細書 アメリカ特許3,859,436号明細書 アメリカ特許3,777,597号明細書 アメリカ特許第3,527,864号明細書 アメリカ特許第3,472,931号明細書 アメリカ特許第3,696,516号明細書 アメリカ特許第5,030,451号明細書 アメリカ特許第5,215,759号明細書 アメリカ特許第5,051,449号明細書 アメリカ特許出願公開第20020099094号公報 アメリカ特許出願公開第20020061855号公報 アメリカ特許出願公開第20010056071号公報 アメリカ特許第5,710,177号明細書 アメリカ特許第4,938,960号明細書 Mart idale, The Extra Pharmacopeia, pages1461〜1463,Twenty-Seventhedition, 1977)
From the above materials, a number of patents allege that they have therapeutic effects on acne treatment, fat removal, and treatment of several skin conditions, all of which are vitamin A acids of the present invention. It is different from the local use composition which does not contain. The main purpose of the present invention is to rejuvenate, moisturize and treat acne, acne, youthful wrinkles and antioxidants using a composition that does not contain vitamin A acid locally.
US Patent 3,574,854 German patent 3,327,840 US Patent 3,859,436 US Patent 3,777,597 US Pat. No. 3,527,864 U.S. Pat. No. 3,472,931 US Pat. No. 3,696,516 US Patent 5,030,451 US Pat. No. 5,215,759 US Pat. No. 5,051,449 US Patent Application Publication No. 20020099094 US Patent Application Publication No. 20020061855 US Patent Application Publication No. 20010056071 US Pat. No. 5,710,177 US Pat. No. 4,938,960 (Mart idale, The Extra Pharmacopeia, pages 1461 to 1463, Twenty-Seventhedition, 1977)

本発明はビタミンA酸を含まない局部使用の皮膚用外用組成物を開示するもので皮膚の保養、保湿ざ瘡、にきび、青春痘の治療に用いられる組成物である。shapirossとsalioucは2001年Nutrition第17巻第10期第839ページ〜第444ページにおいてビタミンA、ビタミンD及びその派生物をビタミンC,ビタミンE,コエンチームQ等の抗酸化物と調合することで皮膚を改善、ざ瘡を治療できると説明した。しかしながら全体的に実施できる処方を提供していない。なぜならば、上記ビタミン類は人体の生理活性を生ずる重要物質であるからである。   The present invention discloses a topical skin-use composition that does not contain vitamin A acid, and is a composition used for the treatment of skin rejuvenation, moisturizing acne, acne, and youthful wrinkles. shapiross and saliouc were prepared by blending vitamin A, vitamin D and its derivatives with antioxidants such as vitamin C, vitamin E and coenteam Q in 2001 Nutrition Vol. 17, 10th pp. 839-444. Explained that it can improve and treat acne. However, it does not provide an overall practicable formulation. This is because the above vitamins are important substances that cause the physiological activity of the human body.

ビタミンA酸はTretinoin, Retnoidsとも称され、構造上ビタミンAの一種の派生物に属する。A酸の主要作用は角質の薬品を除去することにあり、該A酸は表皮の角質層の最上層の角質を除去するので、毛細孔の阻塞を改善できるほか、皮膚のしわ、顔周辺の循環血流を改善でき、且つ色素斑痕を減少し皮膚角化の作用を断絶することにより、上皮細胞の取替を促進し、脱落を促進して角質の合成を抑制すると共に面疱の形成を防止することができる。しかしながら多数のビタミンA酸製品には肌膚に光敏感を発生させ、過度に使用すると皮膚の乾燥、はれ、発熱、発痒、皮膚炎等を生じる副作用が存在している。   Vitamin A acid is also called Tretinoin, Retnoids, and belongs to a kind of derivative of vitamin A structurally. The main effect of A acid is to remove keratin chemicals. The A acid removes the uppermost stratum corneum of the stratum corneum of the epidermis, so that it can improve the blockage of hair pores, skin wrinkles, Improves circulating blood flow, reduces pigment scars and disrupts skin keratinization, promotes replacement of epithelial cells, promotes shedding, suppresses synthesis of keratin, and reduces formation of facets Can be prevented. However, many vitamin A acid products cause photosensitivity to the skin, and when used excessively, there are side effects that cause dry skin, peeling, fever, itchiness, dermatitis and the like.

ビタミンB群ビタミンは単一な種類ではなく、十数種を組合わせたビタミンであり、ビタミンB1(thiamin)、ビタミンB2(riboflavin)、ニアシン、ビタミンB5(pantothenic acid)、ビタミンB6(pyridoxal)、葉酸(tolic acid)、ビタミンB12(cobalamin)、ビオチンを包括する。その主要機能はコエンチームの機能であり、葡萄糖の酸化、脂肪及び蛋白質のエネルギー釈放を担う。神経系統の正規機能を維持し、生長、細胞の再生及び核蛋白とミエリンとの合成に不可欠であり、葉酸を活性化し、酵素を補助することにより赤血球の生成を促進することができる。   Vitamin B group vitamins are not a single type, but a combination of dozens of vitamins, including vitamin B1 (thiamin), vitamin B2 (riboflavin), niacin, vitamin B5 (pantothenic acid), vitamin B6 (pyridoxal), It contains folic acid (tolic acid), vitamin B12 (cobalamin), and biotin. Its main function is that of coenteam, responsible for sucrose oxidation and fat and protein energy release. It maintains the normal function of the nervous system and is essential for growth, cell regeneration, and synthesis of nuclear proteins and myelin. It can promote the production of red blood cells by activating folic acid and assisting the enzyme.

ビタミンEは抗酸化剤とも認められており、血小板の凝集を抑制し、赤血球細胞膜の酸化を防止してそれが破壊されて貧血を引起すとのような事を避けることができ、組織内において細胞膜の完整を維持すると共に亜麻油酸の正規機能を促進する。肌及び神経組織の構造及び機能を保護して端末血管の血流量を増加することにより、効果的に状況を改善することができる。ビタミンAは上記の活性を具備しているが最近の市販銘柄中、例えばビタミンEにWal Greenを組合わせた商品はビタミンEのLoreal Furtur E又はJasom Natural Cosmeticsを含んでいるが皮膚の保養、又はざ瘡、にきび、青春痘の治療及び抗酸化の機能を有しているとは記載されていない。且つ、本発明の「局部使用組成物」の活性試験から本発明の組成物の主要成分により調合された例は、良好な効果を具備していると示めされている。したがって強調しなければならないのは本発明の「局部使用組成物」は、ビタミンC、ビタミンB群、カロチン、ビタミンEと香料、増稠剤、界面活性剤により組成されているが、従来の技術から示唆又は推定できるものでない。   Vitamin E is also recognized as an antioxidant, which suppresses platelet aggregation, prevents oxidation of erythrocyte cell membranes and prevents it from being destroyed and causing anemia. Maintains cell membrane integrity and promotes normal function of flax oil. By protecting the structure and function of the skin and nerve tissue and increasing the blood flow of the terminal blood vessel, the situation can be effectively improved. Vitamin A has the above-mentioned activity, but among recent commercial brands, for example, a product that combines vitamin E with Wal Green contains vitamin E, Loreal Furtur E or Jasom Natural Cosmetics, It is not described as having the function of treating acne, acne, youthful candy and antioxidant. In addition, examples prepared from the main component of the composition of the present invention from the activity test of the “topical use composition” of the present invention are shown to have a good effect. Therefore, it should be emphasized that the “locally used composition” of the present invention is composed of vitamin C, vitamin B group, carotene, vitamin E and a fragrance, a thickener, and a surfactant. It cannot be suggested or estimated from.

本発明の「局部使用組成物」は主としてビタミンC、ビタミンB群、カロチン、ビタミンEと香料、増稠剤、界面活性により組成される。該組成物中の一部分の成分はいずれも人体必須のビタミンであり、且つ主要成分にはビタミンA酸を含まないので、長期間使用しても過量又は骨質弛緩の疑慮がない。ビタミンは体内で需要量が少ないが、その関係する機能が極めて重要であるにもかかわらず、人体は自己合成できないために外界の提供に依頼しなければならない。ビタミンCは人体中において過酸化脂質の発生を防止し、コラーゲンの形成を促進して多くの酵素のコエンチームとして細胞老化の機能を弛緩すると共に黒色素を徐々に還元することができる。したがって皮膚の再生に寄与すると認められており、黒色素の発生を抑制できるほか免疫力を増強する。   The “topical use composition” of the present invention is composed mainly of vitamin C, vitamin B group, carotene, vitamin E, flavor, thickener, and surface activity. Since some of the components in the composition are vitamins essential to the human body and the main component does not contain vitamin A acid, there is no doubt of overdose or bone relaxation even after long-term use. Vitamins are in low demand in the body, but despite their vital function, the human body cannot be self-synthesized and must be offered to the outside world. Vitamin C prevents the formation of lipid peroxide in the human body, promotes the formation of collagen, relaxes the function of cell aging as a coenteam of many enzymes, and can gradually reduce black pigment. Therefore, it is recognized that it contributes to the regeneration of skin, and it can suppress the generation of black pigment and enhance immunity.

アメリカ特許第5,834,445号にカロチン及びビタミンを含むと粘膜のlangerhans細胞がこれにより局部免疫作用を増進すると記載されている。しかしながらカロチンが頗る濃厚な色沢を含有し且つ脂溶性に属しているので一部のバルサム、乳剤、美顔クリーム皮膚又は化粧品薬剤中には技術問題が存在している。本発明の「局部使用組成物」の主要成分の重量%は、ビタミンCが1〜45%、ビタミンB群が1〜5%、カロチンが0.1〜5%、ビタミンEが2〜90%、香料が0.1〜2%、増稠剤1〜5%、界面活性剤が1〜8%を占め、その他に残余の適量の蒸留水が組成されている。そして主要成分の好適な割合は重量%でビタミンCが4〜15%、ビタミンB群が1〜3%、カロチンが0.1〜3%、ビタミンEが20〜65%を占めている。   US Pat. No. 5,834,445 describes that mucosal langerhans cells enhance local immunity by including carotene and vitamins. However, technical problems exist in some balsams, emulsions, facial cream skins or cosmetic agents because carotene contains a rich color tone and belongs to fat solubility. The weight% of the main components of the “locally used composition” of the present invention is 1 to 45% for vitamin C, 1 to 5% for vitamin B group, 0.1 to 5% for carotene, 2 to 90% for vitamin E, and flavoring 0.1 to 2%, thickener 1 to 5%, surfactant 1 to 8%, and the remaining appropriate amount of distilled water. The preferred proportion of the main components is 4% by weight of vitamin C, 1 to 3% of vitamin B group, 0.1 to 3% of carotene, and 20 to 65% of vitamin E.

本発明はビタミンA酸を含まない組成物に関するもので、上記の組成により皮膚の保養、保湿及びざ瘡、にきび、青春痘の治療効果を奏する。本発明の組成物はビタミンC、ビタミンB群、カロチン、ビタミンE、香料、増稠剤及び界面活性剤により組成された完整処方であるので、従来の経口単一ビタミン類化合物により呈される活性と相違している。且つ本発明は直接ざ瘡、にきび、青春痘の患部に塗抹するので、抗酸化及びざ瘡、にきび、青春痘を除去する効果を有し、そして皮膚、顔面等肢体の局部位置に使用して皮膚の保養、保湿の効果を達成している。   The present invention relates to a composition that does not contain vitamin A acid. With the above composition, the skin rejuvenation, moisturizing and acne, acne, and youthful moxibustion are effective. Since the composition of the present invention is a complete formulation composed of vitamin C, vitamin B group, carotene, vitamin E, fragrance, thickener and surfactant, the activity exhibited by conventional oral single vitamin compounds Is different. In addition, since the present invention is applied directly to the affected area of acne, acne and youthful buds, it has the effect of antioxidant and removal of acne, acne and youthful folds, and is used in the local position of skin, face and other limbs. Achieves skin rejuvenation and moisturizing effects.

本発明は必要の場合各種の賦形剤、担体又は希釈剤を添加し、直接患部に軟骨、乳剤、洗剤又は貼剤が塗布される。これらの塗り剤は従来の製剤方法に従って澱粉、カルボキシ酸メチルセルロースナトリウム等の粘合剤を添加し、又は燐酸塩等の緩衝液で酸アルカリ度を調整してそのpH値を適当な程度に達しさせている。これら塗り剤は従来の製剤方法に従い、又は浸透促進剤を添加し、甘草等の天然植物の抽出物を選択使用することもできる。   In the present invention, various excipients, carriers or diluents are added if necessary, and cartilage, emulsion, detergent or patch is directly applied to the affected area. These coatings are made by adding a viscosity agent such as starch or sodium methylcellulose carboxylate according to the conventional formulation method, or adjusting the acid alkalinity with a buffer solution such as phosphate to reach an appropriate pH value. ing. These coating agents can be selected from natural plant extracts such as licorice by adding a penetration enhancer according to a conventional formulation method.

本発明は上記の組成により皮膚の保養、保湿及びざ瘡、にきび、青春痘の治療効果を奏する。本発明の組成物はビタミンC、ビタミンB群、カロチン、ビタミンE、香料、増稠剤及び界面活性剤により組成される処方であり、従来の経口単一ビタミン類化合物により奏される活性と相違している。且つ本発明は直接ざ瘡、にきび、青春痘の患部に塗抹するので、抗酸化及びざ瘡、にきび、青春痘を除去する効果を有し、そして皮膚、顔面等肢体の局部位置に使用して皮膚の保養、保湿の効果を達成している。   The present invention has the therapeutic effects on skin rejuvenation, moisturizing and acne, acne and youth buds by the above composition. The composition of the present invention is a formulation composed of vitamin C, vitamin B group, carotene, vitamin E, fragrance, thickener and surfactant, and is different from the activity exhibited by conventional oral single vitamin compounds. is doing. In addition, since the present invention is applied directly to the affected area of acne, acne and youthful buds, it has the effect of antioxidant and removal of acne, acne and youthful folds, and is used in the local position of skin, face and other limbs. Achieves skin rejuvenation and moisturizing effects.

全体の局部使用組成物の各種実施の態様、及びその達成する目的と効果を説明した後、更に続いて局部使用組成物の整備方法及び活性実験に基づいて本発明の詳細内容を説明する。   After describing various embodiments of the overall topical use composition, and the objects and effects achieved, the details of the present invention will be further explained based on the maintenance method and activity experiment of the topical use composition.

処方 LO-107

Figure 2007016025
Formula LO-107
Figure 2007016025

上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し蒸留水量を補足する。   The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-108

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-108
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-109

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-109
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-110

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-110
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-122

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-122
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-130

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-130
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-18

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formulation LO-18
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-27

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formulation LO-27
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-22

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formulation LO-22
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

処方 LO-39

Figure 2007016025
上記原料ビタミンC、ビタミンB-complexを少量の蒸留水と相互溶解する。他にビタミンB-カロチン、ビタミンE、香料、界面活性剤、増稠剤を混合する。しかる後、両溶液を混合し、蒸留水量を補足する。 Formula LO-39
Figure 2007016025
The above raw material vitamin C and vitamin B-complex are mutually dissolved with a small amount of distilled water. In addition, vitamin B-carotene, vitamin E, fragrance, surfactant and thickener are mixed. Thereafter, both solutions are mixed to supplement the amount of distilled water.

活性実験
試験1:ざ瘡病患にLo-108を使用した治療効果評価を採用し2001年2月から8月までの半年内外来患者のざ瘡病患60名(男性30名、女性30名、年齢17才〜42才、平均25才)を選択した。Lo-108を使用して局部塗面治療計6ヶ月治療し、毎日少なくとも3時間、最長8時間塗抹してから除去した。2週間ごとに1回回診し、ざ瘡数量及び性質の変改を記録した。詳細の使用は次の通りである。
Activity test 1: 60 patients (30 males and 30 females) with acne disease in a half-year outpatient from February to August 2001 using Lo-108 treatment effect assessment for acne disease patients , Age 17-42 years, average 25 years). Lo-108 was used to treat the local surface treatment for a total of 6 months, smeared daily for at least 3 hours, and a maximum of 8 hours, then removed. A visit was made once every two weeks and changes in acne quantity and properties were recorded. The use of details is as follows.

1.患部は先ず洗面クリーム(石鹸)で洗浄した後、皮膚が乾燥してから塗薬を塗り付ける。
2.塗薬量は2ml左右、更に四周に溢れないようにガーゼで被せる。
3.薬(軟膏)を3時間以上塗りつけてから洗浄する。この場合なんらの保湿乳液をもこすって拭いてはいけない。
4.もしも膿疱があれば先に潰してから薬を塗り付ける。もし病患に膿疱があれば経口抗生素を配合する:テトラシクロモルジン又はVibramycinで一週間治療し、余りの時間は多種のざ瘡治療法、例えばビタミンA酸の経口又は外用、もしくはホルモン治療法の使用を禁止した。
1. The affected area is first washed with a wash cream (soap), and then the skin is dried and then applied.
2. The amount of coating is 2ml left and right, and it is covered with gauze so that it does not overflow all four rounds.
3. Apply medicine (ointment) for at least 3 hours before washing. In this case, do not wipe off any moisturizing emulsion.
4). If there are pustules, crush them first before applying the medicine. If the disease has pustules, add oral antibiotics: treat with tetracyclomordine or Vibramycin for a week, and for the rest of the time, various acne treatments such as oral or topical vitamin A acid or hormonal treatment The use of was prohibited.

結果の評価は医者及び病患本人よりその、にきび数、丘疹数、膿疱数、腫れ程度を検定し、厳重クラス及び改善程百分率を求めた。   The results were evaluated by examining the number of acne, papules, pustules, and swelling from the doctor and the patient, and determined the severity and percentage of improvement.

結果
結果は表1に示すように、黒頭にきび及び白頭にきびは8週間の治療後、数量がはっきり平均43.5個から平均20.1個(P < 0.01)に下った。そして毛細孔の開口縮小が見られ、発赤性丘疹は更に顕著な数量減少を表わした。平均21.0個から2.1個への降下はP < 0.001を示した。膿疱及び嚢腫の赤腫現象の消失は平均数8.9及び0.8から半個もない程度に降下し、僅かに一部の赤色斑点及び凹陷した傷跡が残留したのみであった。実際には赤腫は使用前4週間の時に大部分の受験者は既に鮮明な改善を感じているので、継続的にLo-108を使用して彼らのざ瘡を治療したいとの願望を示した。評価中、Lo-108が消炎、降温、消赤腫の能力を有するほか、皮膚の過度角質化増長の現象も減少の状況が見られ、皮膚を比較的スムーズに変わらせた。凹陷した傷跡の改善は僅かに腫物のある者のみが幾らか改善した。これは腫物が消失した後に得られた現象である。
Results As shown in Table 1, the number of blackhead and whitehead acne clearly decreased from an average of 43.5 to 20.1 (P <0.01) after 8 weeks of treatment. And the opening reduction of the hair pore was seen, and the redness papule showed a more remarkable quantity reduction. The average descent from 21.0 to 2.1 showed P <0.001. The disappearance of the erythematous phenomenon of pustules and cysts dropped from an average of 8.9 and 0.8 to less than half, with only a few red spots and concave scars remaining. In fact, erythoma is already clearly improving at 4 weeks before use, and the desire to continually treat their acne using Lo-108 is shown. It was. During the evaluation, Lo-108 has the ability of extinguishing, lowering the temperature, and erythema, and the phenomenon of excessive keratinization and growth of the skin also decreased, and the skin was changed relatively smoothly. The improvement of the concave scars was somewhat improved only by those with a slight tumor. This is a phenomenon obtained after the disappearance of the tumor.

過去に使用された去角質外用薬もしくは抗生素外用薬は常に皮膚の乾燥脱皮により起る痛み、甚だしくは腫等の不良な感受を引起していたがLo-108が保湿効能を兼有している故に、このような状況が発生していない。けれども一部の受験者はその顔色及び味が比較的忍びにくいと認めていながら、その効用にかんがみ我慢してきた。   The exfoliated topical or antibiotic topical drugs used in the past have always caused pains caused by dry molting of the skin, severe perceptions such as swelling, but Lo-108 has a moisturizing effect. Therefore, such a situation has not occurred. However, some test takers have put up with their benefits, admitting that their complexion and taste are relatively difficult to perceive.

以上のデータを総合すれば、Lo-108はざ瘡の治療効果を有していると認定できる。その作用は一歩進んで各種類のテストを進行して探討する必要がある。これは例えば去角質作用、皮脂分泌量の減少、殺菌消炎の可能性があると共に、角質含水量作用の増加を有することにより達成される。   By combining the above data, it can be recognized that Lo-108 has a therapeutic effect for acne. The action needs to go one step further and explore each type of test. This is achieved, for example, by having an increase in the keratin water content effect as well as the potential for keratinization, a decrease in sebum secretion, the possibility of bactericidal anti-inflammation.

試験2:皮脂溢出抑制能力の対照評価
20個健康の志願者がこの項の臨床試験に参与した。これら年齢が18〜25才の間にある受験者の前額部位の皮膚は左右両側に分けられ、その中一側はLo-108を塗抹し、他側は塗抹せず、両者を比較対照した。塗抹の方式は毎日夜1ml〜2mlのLo-108を3時塗抹した後、洗浄した。このような方式で合計4週間塗抹した。一週間ごとに回診して左、右、両前額の各自の皮脂量を検査計測した。毎回いずれも同一固定時間区間内で検査計測を受けた。
Test 2: Control evaluation of ability to suppress sebum overflow
Twenty healthy volunteers participated in the clinical trial in this section. The skin of the forehead of those who are between the ages of 18 and 25 is divided into left and right sides, one of which is smeared with Lo-108 and the other is not smeared. . As a smearing method, 1 ml to 2 ml of Lo-108 was smeared every night at 3 o'clock and then washed. This method was used for smearing for a total of 4 weeks. A round visit was made every week, and the amount of sebum in each of the left, right, and forehead was examined and measured. Each time, each received a test measurement within the same fixed time interval.

皮脂溢出量の試験は皮脂測量器Sebometer810PC(Courage and Khazaka Ltd, Germany)を用いて皮膚表面の油脂量を測定したが左右皮脂量百分率差の測定であるので多くの干渉変数を最低限度に減じた。皮脂測量の原理は器具先端の0.1mm厚さ、64mm2面積の不透明プラスチック物質を皮膚表面に30秒圧した後、吸収された皮脂をして透明度を増加せしめ、且つ皮脂量と線状的に増加でき、つまり皮脂が多ければ多いほど透明度が高くなる正比例関係をなすことによる。光度計の測量は公式を通してミリク゛ラム/cm2に転換することができる。 In the sebum overflow test, sebometer 810PC (Courage and Khazaka Ltd, Germany) was used to measure the amount of oil on the surface of the skin. . The principle of sebum surveying is to press 0.1mm thick, 64mm 2 area opaque plastic material at the tip of the instrument on the skin surface for 30 seconds, and then absorb the sebum to increase the transparency, and linearly with the amount of sebum By increasing the amount of sebum, the higher the transparency, the higher the transparency. The photometer survey can be converted to milligram / cm 2 through the formula.

結果
本試験組及び対照組は同一人の額部であるので、左右側の油脂の測定は、気候中の温度、温度変化、受験人の運動程度、流汗程度の干渉因素を除去した。ANOVA(Analysis of variance)の統計方法を利用してデータを得たところ、試験組の額部油脂は明らかに制御組よりも低いことを示した。図1に示すように毎週間の平均差異はますます鮮明になる傾向があるが、表2に示すようにANOVA統計法によるLo-108の皮脂量データ表から、皮脂量の増減は一種間の使用で既に統計学上の鮮明差異(Pr > F0.001)が見られた。しかしながら、もし時間で計算すれば表3に示すように時間の長短に応じて発生した油脂量の差異は使用の時間が長ければ長い程相似の結果を示し、時間の経過に応じて増加していず、異議のない交互関係(Pr > F0.2854)が発生している。以上の結果からLo-108は効果的に油脂分泌を12時間以上除去又は抑制して、皮脂腺の開口皮脂量(ざ瘡の発生主因の一つ)を暫時弛緩させ得ることを示した。このような効能は短期内に達成でき、使用が多ければ多いほど作用が大きいということを実証できないが、もし毎日使用すれば皮脂の抑制効能が4週間以上維持できた。
Results Since the test group and the control group are the forehead of the same person, the measurement of oil on the left and right sides removed the interfering factors such as temperature in the climate, temperature change, degree of exercise of the examinee, and degree of sweating. The data was obtained using the statistical method of ANOVA (Analysis of variance), and it was shown that the forehead oil in the test group was clearly lower than the control group. As shown in Fig. 1, the average difference between weeks tends to become clearer. However, as shown in Table 2, according to the ANOVA statistical data table of Lo-108 sebum amount, the increase or decrease in the amount of sebum is between one type. There was already a clear statistical difference in use (Pr> F0.001). However, if calculated in terms of time, as shown in Table 3, the difference in the amount of fat and oil generated according to the length of time shows a similar result as the time of use increases, and increases with the passage of time. Therefore, there is an alternating relationship (Pr> F0.2854) without objection. From the above results, it was shown that Lo-108 can effectively remove or suppress oil secretion for more than 12 hours and relax the amount of open sebum (one of the main causes of acne) of the sebaceous glands for a while. Such an effect can be achieved within a short period of time, and it cannot be proved that the more it is used, the greater the effect is. However, if used daily, the inhibitory effect of sebum could be maintained for 4 weeks or more.

試験3:火傷及び傷跡復元の動物実験
本実験に使用された8週大きさの雄性ラット(wistar種)は、平日南部唯一の国外の要求(SPF)に合った動物培育単位である成功大学動物中心で飼養されている。ラットは空気調整を有すると共に室温が25±1℃に維持された動物室で飼養され、凡ゆるラットはいずれも自由に飲食できるようにしている。
Test 3: Animal experiment of burn and scar restoration The male rat (wistar species) 8 weeks in size used in this experiment is a successful university animal that is the only animal breeding unit that meets the overseas requirements (SPF) of the weekdays. It is kept in the center. Rats are housed in an animal room with air conditioning and room temperature maintained at 25 ± 1 ° C. so that any rat can freely eat and drink.

火傷実験
本実験のステップは主としてkistle達の実験方法を参照してなされたもので、動物自体を使用し、対照比較して観察した。実験において(a)毎匹のラットは先ず65mg/kgのpentobarbitalで麻酔して昏睡させた後、背部を4固定区域(各区域は4cm2)に分け;(b)かみそりで各区域の鼠毛を綺麗に剃り落とし;(c)しかる後、それぞれ高熱の鉄板(温度約80〜85℃左右)を背部の4区域に約10秒置き、ラットの背部に火傷を引起させるステップを取った。これらステップが結束した後、鉄片をはずし、オキシドール(37%)で簡単に消毒して傷口を清潔にした。しかる後、区域の区画に応じてそれぞれ不同の処理を取り、対照用の区域は薬を投与しないほか、余の三区域はそれぞれビタミンE、製品基剤及びテスト製品を傷口面積を基準にした投与量で傷口に均一に塗抹した。塗布した後、傷口が細菌に感染されないようにすぐガーゼで緊密に包んで傷口を保護した。毎日定時的に薬を一回替えてラットの傷口変化を観察し、毎日定期的に写真を撮って証拠とした。連続7日後、動物を殺して4区域の組織を取り、病理切片を作った。そして新光医学中心の病理専家李進成博士に委託して創面病理学の変化を評価してもらった。
Burn Experiment The steps of this experiment were mainly made with reference to the experimental method of kistle et al., Using the animals themselves and observed in comparison with controls. In the experiment, (a) each rat was first anesthetized with 65 mg / kg pentabarbital and comatose, then the back was divided into 4 fixed areas (each area was 4 cm 2 ); (b) lashes in each area with a razor (C) After that, a high heat iron plate (temperature of about 80 to 85 ° C. left and right) was placed in four areas on the back for about 10 seconds to take a step of causing burns on the back of the rat. After these steps were united, the iron pieces were removed and the wounds were cleaned by simple disinfection with oxidol (37%). After that, the treatment is different according to the division of the area, and the control area does not receive the drug, and the other three areas receive vitamin E, the product base and the test product based on the wound area, respectively. The amount was smeared evenly on the wound. After application, the wound was protected by wrapping tightly with gauze immediately so that the wound was not infected with bacteria. The drug was changed once a day every day to observe changes in the wounds of the rats, and photographs were taken every day for evidence. After 7 consecutive days, the animals were killed and 4 sections of tissue were taken and pathological sections were made. He was commissioned by Dr. Shin Cheng Li, a pathologist specializing in Shinko Medicine, to evaluate changes in wound pathology.

結果
火傷の回復状況から見れば製品処理の部位において炎症の変化が比較的減少している。結果、対照部位の炎症と製品基剤処理部位の炎症は大きな差異がないことを示した。しかし、製品処理の部位は比較的炎症の変化がなかった。
Result From the burn recovery situation, the change in inflammation is relatively reduced at the site of product treatment. The results showed that there was no significant difference between the inflammation at the control site and the product base-treated site. However, the site of product treatment was relatively unchanged in inflammation.

傷口復元実験
本実験も8週大きさの雄性ラット(wistar種)を使用し、上記の実験ステップに従って、麻酔されたラットの背部を4固定区域(各区域は約4cm2)に分け、かみそりで各区域の鼠毛を綺麗に剃り落とした。しかる後、それぞれメスで背部の各区域において肌肉層の傷跡が見える程度に約1cm長さ切開した。続いてオキジドール(37%)で消毒して傷口を清潔にした。同様に区域の区画に応じてそれぞれ不同の処理を取り、対照用の区域は薬を投与しないほか、余の三区域はそれぞれビタミンE、製品基剤及びテスト製品を、傷口面積を基準にした投与量で傷口に均一に塗抹した。塗布した後、傷口が細菌に感染されないようにすぐガーゼで緊密に包んで傷口を保護した。毎日定時的に薬を一回替えてラットの傷跡の復元状況を観察し、毎日定期的に写真を撮って証拠とした。最後、復元から正常になるまでに必要な日数に基づいて相互比較し、日数が少なければ少ないほど復元が早いことを示した。
Wound Restoration Experiment This experiment also uses male rats (wistar species) that are 8 weeks in size. According to the above experimental steps, the anesthetized rat's back is divided into 4 fixed areas (each area is approximately 4 cm 2 ) with a razor. I shaved off the eyelashes in each area. After that, an incision was made about 1 cm long so that scars of the flesh layer could be seen in each area of the back with a scalpel. Subsequently, the wound was cleaned by disinfection with Okididol (37%). In the same manner, the treatments are different depending on the division of the area, and the control area does not receive the drug. In the other three areas, vitamin E, the product base and the test product are respectively administered based on the wound area. The amount was smeared evenly on the wound. After application, the wound was protected by wrapping tightly with gauze immediately so that the wound was not infected with bacteria. Each day, the drug was changed once a day to observe the recovery of the rat's scars, and photographs were taken every day for evidence. Finally, we compared each other based on the number of days required from restoration to normality, and showed that the smaller the number of days, the faster the restoration.

結果
切傷の回復状況から見れば製品処理の部位では復元の日数が短く、約7.13±1.27日(N=8)のみである。しかし対象部の傷跡の復元は11.00±2.24日(N=8)を要し、製品基剤処理部位の10.13±1.62日(N=8)と差異が少ない(P > 0.05)。
Results In terms of the recovery status of the cut, the number of days for restoration is short at the site of product processing, only about 7.13 ± 1.27 days (N = 8). However, the restoration of the scar on the target area took 11.00 ± 2.24 days (N = 8), and there was little difference from 10.13 ± 1.62 days (N = 8) of the product base treatment site (P> 0.05).

試験4:細菌抑制実験
本実験は金葡萄球菌(Staphylococus aureus, Met hicillin Restant (ATCC 33591)), Staphylococcus aureus, ざ瘡菌(Propionibacterium acnes (ATCC6919))の3種の菌株を使用して、それぞれ適用の培養基を通して培養した後、0.03 ul/ml, 0.1 ul/ml, 0.3 ul/ml, 1 ul/ml, 3 ul/ml, 10ul/ml, 30ul/ml, 100ul/mlのLo-110で分析したところ、その細菌抑制濃度は100 ul/mlであった。
Test 4: Bacterial inhibition experiment This experiment was applied using three strains of Staphylococus aureus, Methicillin Restant (ATCC 33591), Staphylococcus aureus and Acne (Propionibacterium acnes (ATCC6919)). And then analyzed with 0.03 ul / ml, 0.1 ul / ml, 0.3 ul / ml, 1 ul / ml, 3 ul / ml, 10 ul / ml, 30 ul / ml, 100 ul / ml Lo-110 However, the bacterial inhibitory concentration was 100 ul / ml.

試験5:皮膚保湿効果
年齢20〜40才の中、過去曽って皮膚に対する薬物過敏反応がなく、且つ3ヶ月内皮膚疾病もなく、両頬に傷跡がない健康な男女各12名、合わせて24名篩別した。受験者は試験前及び試験の進行期間内実験部位に如何なる物質をも塗抹していけないと共に、両頬部位の流汗及び日焼を減少し、試験同意書にサインした後、以下の実験を進行した。
第1群12名の男女はLo-127処方を塗抹し、第2群12名の男女はLo-108処方を塗抹した。各受験者左右両頬の部位において、実験組である左半部(約15cm2)に1mlの製剤を均一に塗抹し、対照組である右半部には塗抹しなかった。
受験者は午後4時に試験地点に到着し、中性洗液で顔を洗浄して15分間後皮膚含水量ベースラインを測量し、製品を塗抹した。塗抹時間30分間経過後、皮膚表面残余の製剤は湿ペーパーで軽く塗り付けると共に、中性洗液で洗浄し15分間後皮膚含水量(data)を測量した。皮膚含水量は皮膚含水測定儀Corneometer CM 825 (Courage and Khazaka Ltd. Germany)で、左右両頬の各2個位置における含水量を測定した。皮膚含水量はANOVA (Analysis of yariance)で分析を行った。
Test 5: Skin moisturizing effect Among 20 to 40 years old, 12 healthy men and women who had no drug hypersensitivity reaction to the skin in the past, no skin disease within 3 months, and no scar on both cheeks, combined 24 people were screened. Candidates must not smear any substance on the test site before or during the test period, reduce sweating and sunburn on both cheeks, sign the test consent form, and proceed with the following experiment. did.
The first group of 12 men and women smeared the Lo-127 prescription, and the second group of 12 men and women smeared the Lo-108 prescription. In each tester's left and right cheeks, 1 ml of the preparation was uniformly smeared on the left half (about 15 cm 2 ) of the experimental group, and not smeared on the right half of the control group.
Candidates arrived at the test site at 4 pm, washed their face with a neutral wash, and after 15 minutes weighed the skin moisture baseline and smeared the product. After 30 minutes of smearing time, the preparation on the skin surface was lightly applied with wet paper and washed with a neutral washing solution. After 15 minutes, the skin water content (data) was measured. The moisture content of the skin was measured with Corneometer CM 825 (Courage and Khazaka Ltd. Germany). The skin water content was analyzed by ANOVA (Analysis of yariance).

結果
結果、Lo-107, Lo-108二種類の処方を顔部前額部位に使用した場合、皮膚保湿効果が低い方に片寄り、頬部位に使用した場合、鮮明に皮膚含水量が増加したことを発見した。
Results As a result, Lo-107, Lo-108 two types of prescriptions were applied to the forehead area of the face. I discovered that.

Figure 2007016025
Figure 2007016025

Figure 2007016025
註:20名病人の左顔頬にLo-108を塗抹するのを処理組とし、右顔頬に基剤をすりつけるのを対照組とする。
Figure 2007016025
Note: The treatment group is smearing Lo-108 on the left face cheek of 20 patients, and the control group is rubbing the base on the right face cheek.

Figure 2007016025
Figure 2007016025

Lo-107処方を顔部前額部位に使用した皮膚保湿効果を示す図である。It is a figure which shows the skin moisturizing effect which used Lo-107 prescription for the frontal part of the face. Lo-107処方を頬部位に使用した皮膚保湿効果を示す図である。It is a figure which shows the skin moisturizing effect which used Lo-107 prescription for the cheek part. Lo-108処方を顔部前額部位に使用した皮膚保湿効果を示す図である。It is a figure which shows the skin moisturizing effect which used Lo-108 prescription for the forehead part of the face. Lo-108処方を頬部位に使用した皮膚保湿効果を示す図である。It is a figure which shows the skin moisturizing effect which used Lo-108 prescription for the cheek part.

Claims (6)

重量%で主要成分が1〜45%を占めるビタミンCと1〜5%を占めるビタミンB群と0.1〜3%を占めるカロチンと2〜90%を占めるビタミンEと、0.1〜2%を占める香料と1〜5%を占める増稠剤と1〜8%を占める界面活性剤と残余の蒸留水とにより組成される局部使用組成物。   Vitamin C, whose main ingredient is 1 to 45% by weight, vitamin B group, 1-5%, carotene, 0.1-3%, vitamin E, 2-90%, and fragrance, 0.1-2% And a 1 to 5% thickener, a 1 to 8% surfactant and the remaining distilled water. 重量%で主要成分の好適な割合がビタミンCが4〜15%、ビタミンB群が1〜3%、カロチンが0.1〜2%、ビタミンEが15〜65%を占める請求項1記載の局部使用組成物。   The topical use according to claim 1, wherein the preferred proportion of the main ingredients is 4 to 15% by weight, vitamin C is 1 to 3%, carotene is 0.1 to 2%, vitamin E is 15 to 65% Composition. ざ瘡、にきび、青春痘の治療作用を有し、重量%でその主要成分が1〜45%を占めるビタミンCと1〜5%を占めるビタミンB群と0.1〜3%を占めるカロチンと、2〜90%を占めるビタミンEと0.1〜2%を占める香料と1〜5%を占める増稠剤と1〜8%を占める界面活性剤と残余の蒸留水とにより組成される局部使用組成物。   Vitamin C, which has a therapeutic effect on acne, acne, and youth moxibustion, and whose main component is 1 to 45% by weight, vitamin B group that accounts for 1 to 5%, and carotene that accounts for 0.1 to 3%, 2 A topical composition composed of -90% vitamin E, 0.1-2% fragrance, 1-5% thickener, 1-8% surfactant and the remaining distilled water. 皮膚の保養作用を有し、重量%でその主要成分が1〜45%を占めるビタミンCと、1〜5%を占めるビタミンB群と0.1〜3%を占めるカロチンと2〜90%を占めるビタミンEと0.1〜2%を占める香料と1〜5%を占める増稠剤と1〜8%を占める界面活性剤と残余の蒸留水とにより組成される局部使用組成物。   Vitamin C, which has skin rejuvenation and whose main component is 1 to 45% by weight, vitamin B group that accounts for 1 to 5%, carotene that accounts for 0.1 to 3%, and vitamins that account for 2 to 90% A locally used composition comprising E, a perfume occupying 0.1-2%, a thickener occupying 1-5%, a surfactant occupying 1-8% and the remaining distilled water. 皮膚、顔面等の人類肢体の局部位置に使用される請求項1記載の局部使用組成物。   The composition for local use according to claim 1, which is used at a local position of a human limb such as skin or face. 抗酸化作用を有し、重量%でその主要成分が1〜45%を占めるビタミンCと、1〜5%を占めるビタミンB群と、0.1〜3%を占めるカロチンと、2〜90%を占めるビタミンEと、0.1〜2%を占める香料と1〜5%を占める増稠剤と、1〜8%を占める界面活性剤と残余の蒸留水とにより組成される局部使用組成物。   Vitamin C, which has an antioxidant effect and its main component accounts for 1 to 45% by weight, vitamin B group that accounts for 1 to 5%, carotene that accounts for 0.1 to 3%, and 2 to 90% A topical composition comprising vitamin E, a fragrance occupying 0.1-2%, a thickener occupying 1-5%, a surfactant occupying 1-8%, and the remaining distilled water.
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ZA (1) ZA200605597B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008297241A (en) * 2007-05-31 2008-12-11 Fujifilm Corp Anti-acne skin agent for external use
JP2013056866A (en) * 2011-09-09 2013-03-28 Pias Arise Kk EXPRESSION ACTIVATING AGENT OF Bmal1 GENE AND METHOD FOR ACTIVATING EXPRESSION OF Bmal1 GENE

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JPS6140210A (en) * 1984-06-01 1986-02-26 ロシデイ・イスマイル Skin treating and protecting drug
JP2003226637A (en) * 2001-05-18 2003-08-12 Kanebo Ltd Cleansing sheet
JP2005179243A (en) * 2003-12-18 2005-07-07 Shiseido Co Ltd Laminin-5 production promotor containing pantothenic acid or its derivative as active ingredient

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6140210A (en) * 1984-06-01 1986-02-26 ロシデイ・イスマイル Skin treating and protecting drug
JP2003226637A (en) * 2001-05-18 2003-08-12 Kanebo Ltd Cleansing sheet
JP2005179243A (en) * 2003-12-18 2005-07-07 Shiseido Co Ltd Laminin-5 production promotor containing pantothenic acid or its derivative as active ingredient

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008297241A (en) * 2007-05-31 2008-12-11 Fujifilm Corp Anti-acne skin agent for external use
JP2013056866A (en) * 2011-09-09 2013-03-28 Pias Arise Kk EXPRESSION ACTIVATING AGENT OF Bmal1 GENE AND METHOD FOR ACTIVATING EXPRESSION OF Bmal1 GENE

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KR20070006626A (en) 2007-01-11
AU2006202906A1 (en) 2007-01-25
TW200701990A (en) 2007-01-16
ZA200605597B (en) 2008-08-27

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