JP5025253B2 - Formulation for basic cosmetics and basic cosmetics - Google Patents
Formulation for basic cosmetics and basic cosmetics Download PDFInfo
- Publication number
- JP5025253B2 JP5025253B2 JP2006344970A JP2006344970A JP5025253B2 JP 5025253 B2 JP5025253 B2 JP 5025253B2 JP 2006344970 A JP2006344970 A JP 2006344970A JP 2006344970 A JP2006344970 A JP 2006344970A JP 5025253 B2 JP5025253 B2 JP 5025253B2
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- JP
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- Prior art keywords
- basic
- dna
- skin
- basic cosmetic
- salmon
- 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.)
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Images
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- A61K8/0212—Face masks
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/987—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Description
本発明は基礎化粧品用配合剤並びに基礎化粧品に関し、更に詳しくは、細胞賦活効果及び血行促進効果を有する、ＤＮＡの酵素分解生成物又は加水分解生成物を有効成分として含有する基礎化粧品用配合剤、並びに該基礎化粧品用配合剤を含有する基礎化粧品に関す
るものである。
The present invention relates to formulations and basic cosmetics for basic skin care, more particularly, having a cell activation effect and blood circulation promoting effects, enzymatic degradation products of D NA or hydrolysis product comprising as an active ingredient basis cosmetic formulations In addition, the present invention relates to a basic cosmetic containing the compounding agent for basic cosmetics.
肌荒れ、しみ、そばかす、しわ等は、加齢による女性ホルモンのバランスの影響、日光からの紫外線の刺激、体内の過酸化物濃度の高まりによる表皮への悪影響、皮脂の過剰分泌、表皮への血流量の低下、栄養不良、精神的なストレスなど種々の事柄が原因で起こると考えられている。
顔の肌荒れ、しみ、そばかす、しわ等が人々の美容上の重大な関心事であることは、近年、女性向けに限らず、男性向け基礎化粧品の製品数の増加にも現れている。顔が他人への第一印象を与える大きな要素となることから、老若男女を問わず艶やかで張りのある肌（美肌）や白く透き通った肌（美白）になりたいと切に願う人は多く、それ故、肌荒れ、しみ、そばかす、しわ等を改善する基礎化粧品に関する世間一般の関心がさらに高まっている。
Rough skin, spots, freckles, wrinkles, etc. are caused by the effects of the balance of female hormones due to aging, stimulation of ultraviolet rays from sunlight, adverse effects on the epidermis due to increased peroxide concentration in the body, excessive secretion of sebum, blood to the epidermis It is thought to be caused by various things such as decreased flow, malnutrition, and mental stress.
The fact that rough skin, spots, freckles, wrinkles, and the like are serious cosmetic concerns of people has recently appeared in an increase in the number of basic cosmetic products for men as well as for women. Because the face is a big factor that gives a first impression to others, there are many people who want to have glossy and firm skin (beautiful skin) or white and clear skin (whitening) regardless of age or gender. Therefore, there is a growing public interest in basic cosmetics that improve rough skin, spots, freckles, wrinkles and the like.
従来の化粧品で「基礎化粧品」の範疇にある製品においては、グリセリン等の保湿剤や油成分を入れることにより、肌の保湿効果を高め、艶やかな肌とすることが多く試みられていた。最近では肌への美白効果を意図して、メラニン生成を抑制する働きを有するＬ−アスコルビン酸及びその誘導体や、ハイドロキノン誘導体を含有する化粧品が登場している。 In conventional cosmetics that are in the category of “basic cosmetics”, many attempts have been made to enhance the moisturizing effect of the skin by adding a moisturizing agent such as glycerin or an oil component to make the skin glossy. Recently, cosmetics containing L-ascorbic acid and derivatives thereof having a function of suppressing melanin production and hydroquinone derivatives have been introduced with the intention of whitening the skin.
ところで、近年、健康に対する世間一般の関心の高まりを反映して、デオキシリボ核酸（ＤＮＡ）、リボ核酸（ＲＮＡ）又は核タンパク質を原料又は有効成分として用いた健康食品が提供されている。高分子量の核タンパク質を水可溶性及び易消化性とするために、低分子化することも提案されている（特許文献１）。
デオキシリボ核酸（ＤＮＡ）、リボ核酸（ＲＮＡ）又は核タンパク質は老化防止効果を有することは知られているが、基礎化粧品に適用する試みは充分に成されていない。
Although deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or nucleoprotein is known to have an anti-aging effect, attempts to apply it to basic cosmetics have not been made sufficiently.
肌荒れ、しみ、そばかす、しわ等肌のトラブルの原因は、顔面の皮膚の老化、血行不良、紫外線の影響、ストレスなど種々であるが、皮膚の細胞の新陳代謝が低下し、新しい細胞の再生機能が落ちることが直接的な原因である。
従来の基礎化粧品は、皮膚細胞の新陳代謝のメカニズムに働きかけて機能を発揮するものではなく、単に肌の表面上の効果を追求しているに過ぎなかった。このため、肌荒れ、しみ、そばかす、しわ、美白等に対して充分といえるまでの効果は得られていない。
また、前述したメラニン生成を抑制する働きを有するＬ−アスコルビン酸及びその誘導体においては、安定的でなく且つ紫外線炎症防止効果が不十分であり、ハイドロキノン誘導体は安全性に問題がある。したがって、上記化合物が有するメラニン生合成抑制効果やメラニン漂白作用を、化粧品の有効成分として直接的に求めることは困難である。
すなわち、細胞賦活及び血行促進により新しい細胞の再生を促し、肌荒れ、しみ、そばかす、しわ等を防止する、皮膚美白効果の高い製品が望まれているが、従来の基礎化粧品におけるその効果はまだ充分でない。
それ故、細胞自体を賦活し、生き生きとした肌にする新たな基礎化粧品の開発が望まれていた。
Causes of skin troubles such as rough skin, spots, freckles, wrinkles, etc. are various factors such as facial skin aging, poor blood circulation, influence of ultraviolet rays, stress, etc., but skin cell metabolism decreases and new cell regeneration functions Falling is a direct cause.
Conventional basic cosmetics do not work by acting on the metabolism mechanism of skin cells to exert their functions, but merely pursue effects on the surface of the skin. For this reason, the effect until it can be said sufficient with respect to rough skin, a spot, freckles, wrinkles, whitening, etc. is not acquired.
In addition, the above-described L-ascorbic acid and its derivatives, which have a function of suppressing melanin production, are not stable and have insufficient ultraviolet inflammation prevention effects, and hydroquinone derivatives have a safety problem. Therefore, it is difficult to directly obtain the melanin biosynthesis inhibitory effect and melanin bleaching action of the above compounds as active ingredients in cosmetics.
That is, a product with a high skin whitening effect that promotes the regeneration of new cells by cell activation and blood circulation promotion and prevents rough skin, spots, freckles, wrinkles, etc. is desired, but the effect in conventional basic cosmetics is still sufficient. Not.
Therefore, there has been a demand for the development of a new basic cosmetic product that activates the cells themselves to make the skin alive.
本発明者らは、肌荒れ、しみ、そばかす、しわ等の防止効果、皮膚美白効果を有する新たな基礎化粧品を得るべく鋭意研究した結果、ＤＮＡを酵素分解処理又は加水分解処理して得られたデオキシオリゴヌクレオチドを含有する分解生成物に、優れた肌荒れ、しみ、そばかす、しわ等の防止効果及び皮膚美白効果があることを見出し、本発明を完成させた
。
The present inventors have rough, blotches, freckles, preventing effect such as wrinkles, results to have intensively studied to obtain a new basic cosmetics with skin-whitening effect was obtained by a D NA treated enzymatic degradation or hydrolysis the decomposition product containing deoxy oligonucleotide, excellent skin roughness, blotches, freckles, found that there is a preventing effect and skin whitening effects, such as wrinkles, thereby completing the present invention.
即ち、本発明の基礎化粧品用配合剤は、ＤＮＡを酵素分解処理又は加水分解処理により低分子化して得られた分子量１０００乃至３０００の画分であって、鎖長が２乃至１２のデオキシオリゴヌクレオチドを２０乃至５０％含有するＤＮＡ分解生成物を有効成分として含有することを特徴とする、基礎化粧品用配合剤である。
前記ＤＮＡ分解生成物は、好ましくは、鎖長が２乃至１２のデオキシオリゴヌクレオチドを３１％含有するものであることが好ましい。
That is, basic cosmetics for formulations of the present invention is a fraction of the resulting molecular weight of 1000 to 3000 with low molecular by enzymatic degradation or hydrolysis processes D NA, deoxyoligonucleotides of chain length 2 to 12 characterized in that it contains the DNA degradation product containing 20 to 50% of nucleotides as an active ingredient, a basic cosmetic formulations.
The DNA degradation product preferably contains 31% deoxyoligonucleotide having a chain length of 2 to 12.
本発明の基礎化粧品用配合剤の好ましい態様において、前記ＤＮＡは鮭、鱒、鰊、鰹及び鱈などの魚類の白子から得ることが好ましい。 In a preferred embodiment of the basic cosmetic formulations of the present invention, before Symbol D NA salmon, trout, herring, it is preferably obtained from milt of fishes such as bonito, and cod.
さらに本発明の基礎化粧品は、前記基礎化粧用配合剤を含有することを特徴とする。
該基礎化粧品は、ローション、乳液、クリーム、ジェル、ゼリー、エッセンス、リップクリーム、パック又はマスクからなる群より選択されることが好ましい。
Furthermore, the basic cosmetic of the present invention is characterized by containing the above basic cosmetic compounding agent.
The basic cosmetic is preferably selected from the group consisting of lotion, milky lotion, cream, gel, jelly, essence, lip balm, pack or mask.
本発明の基礎化粧品用配合剤は、ＤＮＡの酵素分解処理又は加水分解処理により低分子化して得られた分子量１０００乃至３０００の画分であって、鎖長が２乃至１２のデオキシオリゴヌクレオチドを２０乃至５０％含有するＤＮＡ分解生成物を有効成分として含有するものである。該デオキシオリゴヌクレオチドは分子量が比較的小さいので経皮的に吸収され易く、またそれらは経皮的に吸収されたとき細胞賦活作用及び血行促進作用を有する。したがって、顔面の表皮に適用した場合、優れた肌荒れ、しみ、そばかす、しわ等を防止し、皮膚美白効果を奏する。 Basic cosmetics for formulations of the present invention is a fraction having a molecular weight of 1000 to 3000 was obtained by low-molecular by enzymatic degradation or hydrolysis treatment of D NA, chain length from 2 to 12 deoxyoligonucleotides It contains a 20 to 50% DNA degradation product as an active ingredient. Easy to be absorbed percutaneously since the oligodeoxynucleotide molecular weight is relatively small, and they have a cell-activating action and blood circulation promoting effect when absorbed percutaneously. Therefore, when applied to the epidermis of the face, excellent skin roughening, spots, freckles, wrinkles and the like are prevented, and a skin whitening effect is achieved.
また本発明の基礎化粧品は、上記基礎化粧用配合剤を含んでなるので、顔面の表皮に適用した場合に該基礎化粧品配合剤が有する優れた肌荒れ、しみ、そばかす、しわ等を防止し、皮膚美白効果を奏する。 Further, since the basic cosmetic composition of the present invention comprises the above-mentioned basic cosmetic compounding agent, when applied to the epidermis of the face, the basic cosmetic compounding agent has excellent rough skin, spots, freckles, wrinkles, etc. Provides a whitening effect.
本発明の基礎化粧品用配合剤の有効成分である鎖長が２乃至１２のデオキシオリゴヌクレオチドはＤＮＡを酵素分解処理又は加水分解処理して得ることができる。 Oligodeoxynucleotide chain length which is the active ingredient of basic cosmetic formulations of the present invention is 2 to 12 The DNA can give isosamples treated enzymatic degradation or hydrolysis.
ＤＮＡは、例えば、魚類の白子から抽出し、精製することにより得ることができる。前記魚類は、例えば、鮭、鱒、鰊、鰹及び鱈であり、とりわけ、鮭が好ましい。 DNA can be obtained , for example, by extracting and purifying from a fish larva. Examples of the fish include salmon, salmon, salmon, salmon, and salmon, and salmon is particularly preferable.
以下、ＤＮＡについて更に詳しく説明する。
本発明の基礎化粧品用配合剤の製造原料であるＤＮＡは種々の態様のものでよく、例えば、二本鎖、一本鎖又は環状のＤＮＡであってよい。ＤＮＡの供給源は、動物、植物、微生物等の様々な生物である。水産加工上の廃棄物である魚類、特に鮭、鱒、鰊、鰹及び鱈の精巣（白子）は、とりわけＤＮＡを多く含むが、従来、資源として有効に利用されず、多くが廃棄されていた。それ故、廃棄物の資源化という観点から、これらの精巣由来のＤＮＡを利用することが望ましい。また、哺乳動物や鳥類、例えばブタ、ニワトリ等の胸腺から得られるＤＮＡを使用することができる。更に、合成ＤＮＡもまた使用することができる。
Hereinafter, DNA will be described in more detail.
The DNA which is the raw material for producing the basic cosmetic compounding agent of the present invention may be in various forms, for example, double-stranded, single-stranded or circular DNA. The source of DNA is various organisms such as animals, plants, and microorganisms. Fish, which are wastes from marine processing, especially salmon, salmon, salmon, salmon and salmon testes (white larvae) contain a lot of DNA, but they have not been effectively used as resources and have been discarded in the past. . Therefore, it is desirable to use DNA derived from these testes from the viewpoint of recycling waste. Moreover, DNA obtained from thymus of mammals and birds, for example, pigs, chickens, etc. can be used. In addition, synthetic DNA can also be used.
なお、魚類白子からＤＮＡを得るには、特開２００５−２４５３９４号公報に記載の抽出・精製方法を用いることができる。
具体的には、まず魚類白子を粗砕し、粗砕した魚類白子にＤＮＡが分解しない条件下で
タンパク質分解酵素（プロテアーゼ）処理を行い、酵素処理した溶液を濾過する。そして分画分子量が２，０００〜１，０００，０００である中空糸膜を用いて濾液に透析処理を行い、分解したタンパク質及びイオン類を除去すると共にＤＮＡを濃縮する。さらに、透析処理を行った溶液からＤＮＡ塩として沈殿させるかあるいは溶液を濃縮し、これら沈殿物あるいは濃縮物を回収する。
上記方法により得られたＤＮＡ塩を乾燥させた粉末状ＤＮＡ塩を、本発明の基礎化粧品用配合剤の製造原料として用いることができる。
魚類白子からＤＮＡを得るのは、この方法に限らず、公知の方法を用いても良い。
In addition, in order to obtain DNA from a fish white child, the extraction / purification method described in JP-A-2005-245394 can be used.
Specifically, firstly, the larvae of the fish are crushed, the crushed fish larvae are subjected to a proteolytic enzyme (protease) treatment under conditions where DNA is not degraded, and the enzyme-treated solution is filtered. The filtrate is dialyzed using a hollow fiber membrane having a molecular weight cut off of 2,000 to 1,000,000 to remove decomposed proteins and ions and concentrate DNA. Furthermore, it precipitates as a DNA salt from the solution which performed the dialysis process, or concentrates a solution, and collect | recovers these precipitates or concentrates.
A powdered DNA salt obtained by drying the DNA salt obtained by the above method can be used as a raw material for producing the basic cosmetic compounding agent of the present invention.
It is not limited to this method to obtain DNA from fish larvae, and a known method may be used.
ＤＮＡを処理する酵素は、例えば、ヌクレアーゼであり、例えばアオカビ由来のヌクレアーゼが好ましい。 The enzyme that treats DNA is, for example, a nuclease, and for example, a nuclease derived from blue mold is preferable.
前記ヌクレアーゼは、デオキシリボ核酸（ＤＮＡ）の３’，５’−ホスホジエステル結合を加水分解し、オリゴ体重合の５’−デオキシヌクレオチドを生成する。該ヌクレアーゼの性質について特に制限はないが、ある程度の熱安定性を備えることが好ましい。このようなヌクレアーゼは、例えば天野エンザイム株式会社（旧天野製薬株式会社）、シグマ社等から市販品として入手可能である。 The nuclease, 3 deoxyribonucleic acid (DNA) ', 5'-phosphodiester bond by hydrolysis, to produce a oligos polymerization 5'de Oki sheet nucleotides. Although there is no restriction | limiting in particular about the property of this nuclease, It is preferable to provide a certain amount of thermal stability. Such a nuclease is commercially available from, for example, Amano Enzyme Co., Ltd. (former Amano Pharmaceutical Co., Ltd.), Sigma Co., etc.
前記ヌクレアーゼを用いたＤＮＡの加水分解処理において重要なのは、反応を行う温度である。反応温度は６０〜７５℃の範囲内でなければならず、７０℃が最も好ましい。該温度範囲より低い温度で反応を行うと、ＤＮＡの低分子化が十分に進行せず、分解物が水溶性とならない。一方、該温度範囲より高い温度で行うと、低分子化が過度に進行し、優れた効果を失う惧れがある。 What is important in the hydrolysis treatment of DNA using the nuclease is the temperature at which the reaction is carried out. The reaction temperature must be in the range of 60-75 ° C, most preferably 70 ° C. When the reaction is carried out at a temperature lower than the temperature range, the molecular weight reduction of DNA does not proceed sufficiently, and the degradation product does not become water-soluble. On the other hand, when it is performed at a temperature higher than the above temperature range, the molecular weight reduction is excessively advanced, and the excellent effect may be lost.
以上のようにＤＮＡをヌクレアーゼを用い６０〜７５℃で行う加水分解によって処理することにより、分子量が１０００乃至３０００である画分を２０乃至５０％含有し、そして分子量が１０００以下である画分を、通常、分子量１０００乃至３０００の画分の量よりも多い量、例えば３０乃至５０％含有する程度まで低分子化することができ、これにより、水可溶性及び経皮吸収性を兼ね備えたＤＮＡ分解生成物を製造できる。
以上の処理により得られたＤＮＡ分解生成物には、低分子化されたデオキシオリゴヌクレオチド及びデオキシモノヌクレオチドが主要な部分もしくは大部分として含まれ、そして低分子化が不十分なデオキシヌクレオチド等がごく少量の部分として含有されている。
従って、これら分解生成物に含まれるデオキシヌクレオチド類（デオキシオリゴヌクレオチド、デオキシモノヌクレオチド）は、そのほぼ全て乃至その大部分が、本来らせん鎖を取らないモノ体、完全な一本鎖のオリゴ体、並びに、二重らせん構造を一部にしか有しないオリゴ体で構成される。言い換えると、上述の低分子化が十分に進行しなかったような場合を想定したとしても、上記の分解生成物に含まれるデオキシヌクレオチド類の二重らせん率が２０％を超えることはない。
As described above, the DNA is treated by hydrolysis using a nuclease at 60 to 75 ° C., whereby a fraction having a molecular weight of 1000 to 3000 is contained in an amount of 20 to 50%, and a fraction having a molecular weight of 1000 or less. typically an amount greater than the amount of the fraction having a molecular weight of 1000 to 3000, can be depolymerized to the extent that it contains for example 30 to 50%, thereby, DN a component that combines water soluble and transdermal absorptive A solution can be produced.
The D NA decomposition product obtained by the above process, the low molecular weight deoxynucleoside oligonucleotides and deoxy mononucleotide is included as a major portion or the majority, and a low molecular weight is insufficient deoxynucleotide etc. It is contained as a very small part .
Therefore, deoxynucleotides contained in these decomposition products (oligodeoxynucleotide deoxy mononucleotide) is almost all or most of its mono body takes no inherent helical strands, complete oligos of single-stranded, In addition, it is composed of an oligo body having only a part of a double helical structure. In other words, even if it is assumed that the above-described molecular weight reduction has not progressed sufficiently, the double helix ratio of deoxynucleotides contained in the above degradation product does not exceed 20% .
本発明の基礎化粧品用配合剤の有効成分として、ＤＮＡを酵素分解処理又は加水分解処理して得られた分解生成物を、そのまま（精製することなく）使用することができる。前記分解生成物中に、例えば、アミノ酸などが含まれていてもよい。
また、本発明の基礎化粧品用配合剤の有効成分として、ＤＮＡ分解生成物から慣用の分離手段及び／又は精製手段を用いて分離した以下の化合物：デオキシオリゴヌクレオチド
、デオキシモノヌクレオチドを使用することができる。
このとき、ＤＮＡ分解生成物に含まれるか、又は、該分解生成物から慣用の分離手段及び／又は精製手段を用いて分離・精製されたデオキシオリゴヌクレオチドの鎖長は２乃至１２のものであることが好ましい。
As an active ingredient of basic cosmetic formulations of the present invention, a degradation product obtained by DNA enzymatic decomposition treatment or hydrolysis treatment, as it is (without purification) may be used. In the decomposition product, for example, an amino acid or the like may be contained.
Also, as an active ingredient of basic cosmetic formulations of the present invention, DN A decomposition from the product of customary separating means and / or the following compounds were separated using purification means: using oligodeoxynucleotide deoxy mononucleotide be able to.
In this case, either included in the D NA decomposition product, or, chain length of deoxyoligonucleotides separated and purified using separation means and / or purification conventional means from the decomposition products intended 2-12 It is preferable that
前記分解生成物及び前記化合物は、それぞれ単独で使用してもよいし、又は、これらの化合物あるいは少なくとも２種類を混合して使用してもよい。前記分解生成物や前記化合物を混合して使用する場合は、その混合比率は適宜選択し得る。
このとき、前記分解生成物及び前記化合物として、鎖長が２乃至１２の前記デオキシオリゴヌクレオチドを含み、並びに鎖長が２乃至１２の前記デオキシオリゴヌクレオチドの含有量の合計が、前記分解生成物および前記化合物の全合計量に対して２０％以上であることが特に好ましい。
また、前記分解生成物や前記化合物を更に、基礎化粧品用配合剤の慣用の添加成分と所定比率で組み合わせて使用してもよい。
The decomposition product and the compound may be used alone, or these compounds or at least two kinds may be mixed and used. When the decomposition product or the compound is used in combination, the mixing ratio can be appropriately selected.
In this case, as the decomposition products and the compounds, wherein the oligodeoxynucleotide chain length 2 to 12, and chain length total content of the oligodeoxynucleotide 2 to 12, wherein the decomposition products and It is particularly preferably 20% or more based on the total amount of the compounds.
Moreover, you may use the said decomposition product and the said compound in combination with the conventional additive component of the basic cosmetic compounding agent in a predetermined ratio.
本発明の基礎化粧品用配合剤における有効成分（前記分解生成物及び／又は前記化合物）の濃度は適宜選択し得る。 The concentration of the active ingredient (the decomposition product and / or the compound) in the formulation for basic cosmetics of the present invention can be appropriately selected.
また、本発明の基礎化粧品は、前記基礎化粧品用配合剤を含有してなる。
本発明の基礎化粧品が採り得る剤型は、皮膚に適用可能な剤型であれば適宜選択可能である。好ましくは、基礎化粧品はローション、乳液、クリーム、ジェル、ゼリー、エッセンス、リップクリーム、パック又はマスクであることが望ましい。
Moreover, the basic cosmetic of the present invention contains the above-mentioned compounding agent for basic cosmetics.
The dosage form that can be taken by the basic cosmetic of the present invention can be appropriately selected as long as it is a dosage form applicable to the skin. Preferably, the basic cosmetic is a lotion, emulsion, cream, gel, jelly, essence, lip balm, pack or mask.
本発明の基礎化粧品には、前記基礎化粧用配合剤に加えて既存の基礎化粧品に配合され得る公知の成分を配合することができる。例えば香料や保湿剤等を、単独又は組み合わせて配合することができる。 In the basic cosmetic of the present invention, in addition to the basic cosmetic compounding agent, known components that can be mixed into existing basic cosmetics can be blended. For example, a fragrance | flavor, a moisturizer, etc. can be mix | blended individually or in combination.
また、本発明の基礎化粧品には、薬剤成分として、ビタミンＥ又はその誘導体、例えばビタミンＥアセテート；アセチルコリン誘導体等の血管拡張剤；セファランチン等の皮膚機能亢進剤；グリチルレチン酸又はその誘導体；エストラジオール、エストロン等の女性ホルモン剤；セリン、メチオニン、アルギニン等のアミノ酸類；ビタミンＡ、ビタミンＢ1、ビタミンＢ6、ビオチン、パントテン酸又はその誘導体等のビタミン類を単独又は組み合わせて配合することができる。 The basic cosmetics of the present invention include vitamin E or a derivative thereof such as vitamin E acetate; a vasodilator such as an acetylcholine derivative; a skin function-enhancing agent such as cephalanthin; glycyrrhetinic acid or a derivative thereof; Female hormone agents such as: amino acids such as serine, methionine, and arginine; vitamins such as vitamin A, vitamin B 1 , vitamin B 6 , biotin, pantothenic acid, and derivatives thereof can be used alone or in combination.
更に、本発明の基礎化粧品には、必要に応じて、通常、化粧品や医薬品等の皮膚外用剤に用いられる添加剤、例えば、油分、防腐剤、界面活性剤、分散安定剤、増粘剤、湿潤剤、紫外線吸収剤、酸化防止剤、ｐＨ調整剤、精製水及びアルコール等を単独又は組み合わせて配合することができる。 Furthermore, in the basic cosmetics of the present invention, if necessary, additives usually used for external preparations for skin such as cosmetics and pharmaceuticals, such as oils, preservatives, surfactants, dispersion stabilizers, thickeners, Wetting agents, ultraviolet absorbers, antioxidants, pH adjusters, purified water, alcohols, and the like can be used alone or in combination.
以下に示す実施例及び比較例において、本発明を具体的且つ更に詳細に説明する。下記実施例は本発明の説明のためのみのものであり、これらの実施例により本発明の技術的範囲が限定されるものではない。
以下の実施例及び比較例における配合量は、全体量に対する質量％である。又、実施例で用いた試作品１（ＤＮＡを酵素分解処理して得られた分解生成物をそれぞれ含有するもの）の量は固形分量として示す。
In the following examples and comparative examples, the present invention will be described in detail and in detail. The following examples are for illustrative purposes only and are not intended to limit the technical scope of the present invention.
The compounding amount in the following Examples and Comparative Examples is mass% with respect to the total amount. Also, the amount of Example prototype used in articles 1 (DNA those containing respectively the decomposition products obtained by enzymatic degradation) are shown as solid content.
１．（デオキシ）オリゴヌクレオチドの製造
鮭白子由来のＤＮＡに対して、食品添加物として認可されているヌクレアーゼ［例えば、酵素製剤ヌクレアーゼ「アマノ」（天野エンザイム（旧天野製薬）社製）］を用いて限
定分解を行った。産生したデオキシモノヌクレオチドとデオキシオリゴヌクレオチドを電気泳動装置で分析して最適条件を決定した。
具体的には、６５℃前後に調整した温水に原料として粉末状ＤＮＡ−Ｎａ塩を投入し、撹拌後、更に７０℃に加温し、原料に対してヌクレアーゼを０．０５乃至０．２５％の範囲で適量を加えて３時間反応させた。次に、８５℃で１０分間加熱してヌクレアーゼを失活させた後、遠心分離し、上澄み液にスプレードライ法を適用して、デオキシオリゴヌクレオチドを含む乾燥粉末（分解生成物）を得た。
1. Manufacture of (deoxy) oligonucleotides Restricted by using a nuclease [for example, the enzyme preparation nuclease “Amano” (Amano Enzyme (former Amano Pharmaceutical Co., Ltd.)), which is approved as a food additive, for DNA derived from silkworm Decomposition was performed. The produced deoxymononucleotide and deoxyoligonucleotide were analyzed with an electrophoresis apparatus to determine the optimum conditions.
Specifically, powdered DNA-Na salt is added as raw material to warm water adjusted to around 65 ° C., stirred, and further heated to 70 ° C., and nuclease is 0.05 to 0.25% based on the raw material. An appropriate amount was added within the range of 3 to react for 3 hours. Next, after heating at 85 ° C. for 10 minutes to inactivate the nuclease, the mixture was centrifuged, and spray drying was applied to the supernatant to obtain a dry powder (degradation product) containing deoxyoligonucleotide.
２．（デオキシ）オリゴヌクレオチドの分析
６５℃前後に調整した温水に原料として鮭白子由来の粉末状ＤＮＡ−Ｎａ塩を投入し、撹拌後、更に７０℃に加温し、原料に対して酵素製剤ヌクレアーゼ「アマノ」（天野エンザイム（旧天野製薬）社製）を０．０５％加えて３時間反応させて分解生成物を得た。次に、８５℃で１０分間加熱してヌクレアーゼを失活させた後、分解生成物をＨＰＬＣで分析した。
図１に、ＨＰＬＣ（高速液体クロマトグラフィー）による、分解生成物のデオキシオリゴヌクレオチドの分析例を示す。図１において、５’−デオキシモノヌクレオチド及び３’−デオキシモノヌクレオチドはピーク２０までに溶出しており、以降の比較的大きなピーク、すなわちピーク２６以後をデオキシオリゴヌクレオチドの吸収とみなすことができる。また、ピーク４１以後は分子量が３０００を超える分解生成物の吸収とみなすことができる。このため、ピーク２６乃至４１のピーク強度から算出した結果、本例では分解生成物全体に対して、３１％のデオキシオリゴヌクレオチド（分子量１０００〜３０００）の分画が含まれていることがわかった。
2. Analysis of (deoxy) oligonucleotides Powdered DNA-Na salt derived from white coconut was added as raw material to warm water adjusted to around 65 ° C., stirred, and further heated to 70 ° C. Amano ”(Amano Enzyme (former Amano Pharmaceutical Co., Ltd.)) was added at 0.05% and reacted for 3 hours to obtain a decomposition product. Next, the nuclease was inactivated by heating at 85 ° C. for 10 minutes, and then the decomposition product was analyzed by HPLC.
FIG. 1 shows an analysis example of deoxyoligonucleotides as degradation products by HPLC (high performance liquid chromatography). In FIG. 1, 5′-deoxymononucleotide and 3′-deoxymononucleotide are eluted up to peak 20, and the subsequent relatively large peak, that is, peak 26 and later, can be regarded as absorption of deoxyoligonucleotide. Further, after the peak 41, it can be regarded as absorption of a decomposition product having a molecular weight exceeding 3000. For this reason, as a result of calculating from the peak intensities of the peaks 26 to 41, it was found that in this example, a fraction of 31% deoxyoligonucleotide (molecular weight 1000 to 3000) was contained with respect to the entire decomposition product. .
３．（デオキシ）オリゴヌクレオチドを用いた基礎化粧品の製造
前記製造方法にて得たデオキシオリゴヌクレオチドを含む乾燥粉末（分解生成物）を試作品１とし、この試作品１を用いて、本発明の基礎化粧品を以下のように製造した。また対照として、試作品１を含有しない基礎化粧品を製造した。これらの組成を下記表１にまとめて示す。
［実施例１］
９５％エタノールに精製水を加え、これにポリオキシエチレン（２５モル）硬化ヒマシ油エーテル、グリセリン、プロピレングリコールを加えて攪拌後、試作品１を加えて攪拌溶解し、透明液状の実施例１の基礎化粧品を得た。
［比較例１］
試作品１の代わりに同量のグリセリンを用い、実施例１と同様の製法で比較例１の基礎化粧品を得た。
3. Manufacture of basic cosmetics using (deoxy) oligonucleotide A dry powder (decomposition product) containing deoxyoligonucleotide obtained by the above production method is designated as prototype 1, and using this prototype 1, basic cosmetic of the present invention Was manufactured as follows. As a control, a basic cosmetic product containing no prototype 1 was produced. These compositions are summarized in Table 1 below.
[Example 1]
Purified water is added to 95% ethanol, and polyoxyethylene (25 mol) hydrogenated castor oil ether, glycerin and propylene glycol are added and stirred. A basic cosmetic was obtained.
[Comparative Example 1]
A basic cosmetic of Comparative Example 1 was obtained in the same manner as in Example 1 except that the same amount of glycerin was used instead of Prototype 1.
４．血流量測定試験
実施例１の基礎化粧品と比較例１の基礎化粧品をそれぞれ、ヒト上腕に１０μＬ塗布し、塗布１時間後に、レーザードップラー計で血流量を測定した。試験結果の判定は、下記判定基準により行った。
＋＋：比較例に比べて血流量が極めて増加した（著効）
＋ ：比較例に比べて血流量が増加した（有効）
± ：比較例に比べて血流量がやや増加した（やや有効）
− ：比較例に比べて血流量が同等以下であった（無効）
結果を下記表１にまとめて示す。
4). Blood flow measurement test Each 10 μL of the basic cosmetic of Example 1 and the basic cosmetic of Comparative Example 1 were applied to the human upper arm, and the blood flow was measured with a laser Doppler meter one hour after the application. The test results were determined according to the following criteria.
++: The blood flow increased significantly compared to the comparative example (high effect)
+: Blood flow increased compared to the comparative example (effective)
±: The blood flow increased slightly compared to the comparative example (somewhat effective)
−: The blood flow was equal to or less than that of the comparative example (invalid)
The results are summarized in Table 1 below.
５．肌荒れの改善試験
下肢に肌荒れを有する中高年女性１０名を被試験対象として、実施例１の基礎化粧品と比較例１の基礎化粧品をそれぞれ、左右の下肢の異なる場所に、入浴後に約１ｇ／１回／１日、塗布した。
試験実施前と１ヵ月後の塗布した箇所の皮膚の状態により、以下の判定基準を用いて、皮膚の剥離状態と水分状態の観点から試験結果の判定を行った。
５−１．皮膚剥離の判定基準及び有効性の判断
試験実施前後の皮膚の剥離の状態を以下の判定基準で判断した。
０：剥離なし １：剥離軽度 ２：剥離中程度 ３：剥離重度
上記判定により、試験実施後の判定が実施前より１段階改善されたものを「やや有効」とし、２段階以上改善されたものを「有効」とし、同レベル又は悪化したものは「無効」とした。
５−２．水分状態の判定基準
１ヶ月後の皮膚の水分状態（保湿性）を保湿計によって測定し、下記基準により判定を行った。
＜水分状態の判定基準＞
＋＋：塗布した部分の保湿性が試験実施前より５％以上増加した（著効）
＋ ：塗布した部分の保湿性が試験実施前より２〜５％増加した（有効）
± ：塗布した部分の保湿性が試験実施前より０〜２％増加した（やや有効）
− ：塗布した部分の保湿性が試験実施前と同等以下であった（無効）
結果を下記表１にまとめて示す。
5. Skin roughness improvement test 10 middle-aged and elderly women with skin roughness in the lower limbs were tested, and the basic cosmetic of Example 1 and the basic cosmetic of Comparative Example 1 were each placed at different locations on the left and right lower limbs about 1 g / time after bathing. / Applied for 1 day.
The test results were judged from the viewpoints of the peeled state and moisture state of the skin, using the following judgment criteria, depending on the state of the skin at the place where the test was applied and one month later.
5-1. Criteria for skin peeling and judgment of effectiveness The state of skin peeling before and after the test was judged according to the following criteria.
0: No peeling 1: Mild peeling 2: Moderate peeling 3: Peeling severity Based on the above judgment, the result after the test was improved by one level from the level before the test was regarded as “slightly effective” and improved by two or more levels. Was “valid”, and those with the same level or worsened were “invalid”.
5-2. Criteria for determination of moisture state The moisture state (moisturizing property) of the skin after one month was measured with a moisturizer, and determined according to the following criteria.
<Judgment criteria for moisture status>
++: The moisturizing property of the applied part increased by 5% or more from before the test (high effect)
+: The moisturizing property of the applied part increased by 2 to 5% (effective) from before the test.
±: Moisturizing property of the applied part increased by 0 to 2% from before the test (slightly effective)
−: The moisture retention of the applied part was equal to or less than that before the test (invalid)
The results are summarized in Table 1 below.
６．試用による評価試験
中高年女性を対象に、一重盲検にて、実施例１の基礎化粧品並びに比較例１の基礎化粧品の評価試験を行った。なお各化粧品の被試験者は１０名ずつとした。評価は被試験者に対するアンケートで、「滑らかさ」、「肌理の細かさ」、「美白の状態」、「皮膚の弾力性」、「しみそばかすの改善」の５項目を、使用前と１ヶ月使用後に回答を得た。
得られた回答より、試験結果の判定は、下記判定基準により行った。
＋＋：使用前に比べて改善した（有効）
＋ ：使用前に比べてやや改善した（やや有効）
± ：使用前に比べて同等以下だった（無効）
結果を下記表１にまとめて示す。
6). Evaluation test by trial The evaluation test of the basic cosmetic of Example 1 and the basic cosmetic of Comparative Example 1 was conducted in a single-blind manner for middle-aged women. The number of examinees for each cosmetic product was 10. The evaluation is a questionnaire for the examinees. Five items, “smoothness”, “fineness of texture”, “whitening condition”, “elasticity of skin” and “improvement of freckles” are used before and 1 month. The answer was obtained after use.
Based on the obtained answers, the test results were determined according to the following criteria.
++: Improved compared to before use (effective)
+: Slightly improved compared to before use (somewhat effective)
±: Less than or equal to before use (invalid)
The results are summarized in Table 1 below.
表１に示した結果より、以下のことが判った。
（１）実施例１の化粧品の血流量測定試験の評価は＋＋［比較例に比べて血流量が極めて増加した（著効）］であり、実施例１の化粧品の有効成分がヒトの皮膚から浸透して血流量を著しく増加させることは明らかである。
（２）実施例１の化粧品の肌荒れ改善試験では、試作品１を含んでいる化粧品は有効性が顕著であった。なお、対照として塗布しなかった左下肢には肌荒れの改善が殆ど認められず、試作品１を含んだ化粧品の有効性が明らかとなった。
（３）表１に示した試験結果において、試作品１（ＤＮＡ分解生成物）を含んだ化粧品による化粧品の試用による評価試験は、特に「滑らかさ」「肌理の細かさ」「皮膚の弾力性」において顕著な改善効果が認められるとする評価結果であった。
（４）一方、実施例１における試用による評価試験では、「美白効果」「しみそばかすの改善」は一部の被試験者で認められたが、皮膚の新陳代謝等を考慮すると、もう少し長期の使用が求められるとする結果となった。
From the results shown in Table 1, it was found that below.
(1) The evaluation of the blood flow measurement test of the cosmetic product of Example 1 is ++ [the blood flow rate is extremely increased compared with the comparative example (highly effective)], and the active ingredient of the cosmetic product of Example 1 is derived from human skin. It is clear that it penetrates and significantly increases blood flow.
(2) In the rough skin recovering testing cosmetic Example 1, cosmetics containing the prototype 1 efficacy was remarkable. It should be noted, was not observed most of the improvement of the rough on the left leg that did not applied as a control, the effectiveness of including a prototype 1 cosmetics became clear.
(3) In the test results shown in Table 1, the evaluation test based on the trial use of cosmetics including the trial product 1 (DNA degradation product) is particularly “smoothness”, “fineness of texture”, “elasticity of the skin” It was an evaluation result that a remarkable improvement effect was recognized .
(4) On the other hand, in the evaluation test by trial that in Example 1, but "whitening effect""improvement of stain freckles" was observed in some of the test person, considering the metabolism and the like of the skin, a little more long-term The result was that use was required.
なお、実施例１では、有効成分として試作品１（ＤＮＡ塩分解生成物）を使用したが、試作品１の代わりに、それから分離・精製したデオキシオリゴヌクレオチド、デオキシモノヌクレオチドを単独で又は組み合わせて使用しても、試作品１を使用した場合と同様に効果が認められた。 In the embodiment 1, it was used a prototype 1 (DNA salt degradation product) as an active ingredient, instead of prototype 1, it either et separated and purified oligodeoxynucleotide deoxy mononucleotide alone Even when used in combination, the effect was recognized as in the case of using prototype 1 .
すなわち本実施例から、デオキシオリゴヌクレオチド、デオキシモノヌクレオチドを含有する基礎化粧品用配合剤並びに該基礎化粧用配合剤を含有する基礎化粧品は、血流量の増加、肌荒れ改善効果、並びに肌の滑らかさ、肌理の細かさ、皮膚の弾力性を改善する効果を有することが認められた。 That is, from this example, deoxy oligonucleotide, basic cosmetics compounding ingredients containing deoxy mononucleotide and basic cosmetics containing the basic cosmetic compounding ingredients, increased blood flow, rough skin improving effect, and skin smoothness, It was recognized that it had the effect of improving the fineness of the texture and the elasticity of the skin.
以下に、上記試作品１を用いた基礎化粧品の処方例を、実施例２乃至実施例４として示す。なお、以降に記載した「試作品（類）」とは、試作品１の意味を表すものとする。
いずれの実施例においても血流量の増加、肌荒れ改善効果、並びに肌の滑らかさ、肌理の細かさ、皮膚の弾力性を改善する効果を有することが認められた。
Examples of prescription of basic cosmetics using the prototype 1 are shown as Examples 2 to 4 below. It should be noted, was a "prototype (s)" is described hereinafter, it is assumed that the meaning of the prototype 1.
In any of the examples, it was confirmed that the blood flow rate was increased, the rough skin was improved, and the skin smoothness, fine texture, and skin elasticity were improved.
実施例２：リップクリーム
上記配合成分のうち香料以外の成分を混合、溶解した後、香料を加えて撹拌混合した後、型に流し込み冷却してリップクリームを調製した。
Example 2 : Lip balm
After mixing and dissolving components other than the fragrance among the above blended components, the fragrance was added and stirred and mixed, then poured into a mold and cooled to prepare a lip balm.
実施例３：コールドクリーム
精製水に試作品（類）、石鹸粉末を加え加熱溶解して７０℃に保った（水相）。他の成分を混合し、加熱融解して７０℃に保った（油相）。水相に油相を撹拌しながら徐々に加え、終了後、ホモミキサーで均一に乳化し、乳化後よく撹拌しながら３０℃まで冷却し、
コールドクリームを調製した。
Example 3 : Cold cream
Prototype (s) and soap powder were added to purified water and dissolved by heating and kept at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). Gradually add the oil phase to the aqueous phase with stirring, and after completion, emulsify uniformly with a homomixer, cool to 30 ° C. with good stirring after emulsification,
Cold cream was prepared.
実施例４：クレイパック
１，３−ブチレングリコール、グリセリン、セスキステアリン酸ＰＥＧ−２０セチルグルコース、キサンタンガム、防腐剤、精製水を混合・撹拌して全体を均一とした。
これをホモミキサーで撹拌しながら、試作品（類）及びカオリンを加え、全体を均一とし、さらにエタノールを加えて撹拌・混合し、クレイパックを調製した。
Example 4 : Clay pack
1,3-butylene glycol, glycerin, PEG-20 cetyl glucose sesquistearate, xanthan gum, preservative, and purified water were mixed and stirred to make the whole uniform.
While stirring this with a homomixer, the prototype (s) and kaolin were added to make the whole uniform, and ethanol was further added and stirred and mixed to prepare a clay pack.
Claims (5)
The basic cosmetic according to claim 4, wherein the basic cosmetic is selected from the group consisting of lotion, milky lotion, cream, gel, jelly, essence, lip balm, pack or mask.
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| Application Number | Priority Date | Filing Date | Title |
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| JP2006344970A JP5025253B2 (en) | 2006-03-31 | 2006-12-21 | Formulation for basic cosmetics and basic cosmetics |
| KR1020070031896A KR101353628B1 (en) | 2006-03-31 | 2007-03-30 | Compounding ingredients for basic cosmetics and basic cosmetics |
| US11/902,763 US20080161229A1 (en) | 2006-12-21 | 2007-09-25 | Compounding ingredients for basic cosmetics and basic cosmetics |
| EP07019176A EP1938867A2 (en) | 2006-12-21 | 2007-09-28 | Compounding ingredients for basic cosmetics and basic cosmetics |
| CN2007101691914A CN101254160B (en) | 2006-12-21 | 2007-09-29 | Compounding ingredients for basic cosmetics and basic cosmetics |
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| JP2006098131 | 2006-03-31 | ||
| JP2006344970A JP5025253B2 (en) | 2006-03-31 | 2006-12-21 | Formulation for basic cosmetics and basic cosmetics |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP5025254B2 (en) * | 2006-08-09 | 2012-09-12 | 日生バイオ株式会社 | Cosmetic preparations and cosmetics for improving the skin groove density |
| FR3043695B1 (en) * | 2015-11-17 | 2019-10-25 | ISP Investments LLC. | PROCESS FOR OBTAINING AQUEOUS EXTRACT ENRICHED IN SMALL RNA FROM PLANT MATERIAL AND EXTRACTS FROM THE PROCESS |
| KR102011362B1 (en) * | 2017-12-04 | 2019-08-16 | 주식회사 비알팜 | Manufacturing method of high purity DNA fragments mixtures |
| JP6555674B1 (en) | 2018-07-24 | 2019-08-07 | ジェネティックバイオラボ株式会社 | Anti-aging agent for skin and anti-aging-related gene expression regulating agent |
| KR101904702B1 (en) * | 2018-07-30 | 2018-11-21 | 트러스메틱스주식회사 | Composition for immune enhancement and method the same |
| KR102084003B1 (en) * | 2018-10-22 | 2020-03-03 | 에스케이바이오랜드 주식회사 | Method for preparing nucleotides of lactic acid bacteria inclusion-complexed with low-molecular functional biomaterial and Cubisome prepared thereby |
| JP7015064B2 (en) * | 2019-08-05 | 2022-02-02 | 日生バイオ株式会社 | Keratin plug remover |
| WO2022191339A1 (en) * | 2021-03-08 | 2022-09-15 | 주식회사 노아바이오텍 | Cosmetic composition comprising pdrn and follicular fluid isolated from trout |
| KR102346895B1 (en) * | 2021-05-28 | 2022-01-04 | 주식회사 노아바이오텍 | Method for PDRN extraction |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2324293A1 (en) * | 1975-04-29 | 1977-04-15 | Orlane | Cosmetic product comprising vehicle or support contg. nucleotides - prepd. by hydrolysis of protein material, pref. yeast |
| IT1222701B (en) * | 1987-09-23 | 1990-09-12 | Crinos Industria Farmaco | COMPOSITION FOR TOPICAL USE HAVING TRICHOGEN, ANTI-DANDRUFF AND ANTI-SEBORRHEIC ACTIVITY |
| IT1232318B (en) * | 1989-09-07 | 1992-01-28 | Crinos Industria Farmaco | TOPICAL COMPOSITIONS CONTAINING DEPOLYMERATED NUCLEIC ACIDS FOR SKIN AND BODY COSMETICS. |
| JPH0931093A (en) * | 1995-07-22 | 1997-02-04 | Nippon Suisan Kaisha Ltd | Dna salt originating from soft roe of fish and having excellent water solubility and its production |
| DE19911053B4 (en) * | 1999-03-12 | 2004-10-28 | Biotec Asa | Cosmetic and / or pharmaceutical preparations |
| FR2804960B1 (en) * | 2000-02-11 | 2005-06-24 | Lvmh Rech | NOVEL OLIGONUCLEOTIDES AND USE OF OLIGONUCLEOTIDES MODULATING THE EXPRESSION OF TYROSINASE AND TYROSINASE-RELATED-PROTEIN 1 AS DEPIGMENTING AGENTS |
| GB2381451A (en) * | 2001-11-01 | 2003-05-07 | New Technology Res Ltd | Pharmaco-dietary preparation having nutrition-supplementing and nutrition-enhancing effect |
| JP3978716B2 (en) * | 2002-04-18 | 2007-09-19 | 日生バイオ株式会社 | Gene oxidative damage inhibitor |
| JP2004016142A (en) * | 2002-06-18 | 2004-01-22 | Ls Corporation:Kk | Formulation containing collagen and water soluble decomposed product of nucleoprotein |
| JP2004016143A (en) * | 2002-06-18 | 2004-01-22 | Ls Corporation:Kk | Method for producing water soluble decomposed product of nucleoprotein |
| BR0305435A (en) * | 2002-07-10 | 2005-01-11 | Oreal | Use of at least one polynucleotide fragment, at least one marker and a combination of at least two polynucleotide fragments, method for diagnosing a predisposition to early tanning in an individual, and, kit |
| JP2005245394A (en) * | 2004-03-08 | 2005-09-15 | Nissei Bio Kk | Method for extraction and purification of double stranded dna from milt of fish |
| JP4599518B2 (en) * | 2005-06-13 | 2010-12-15 | 日生バイオ株式会社 | Hair care preparations |
| FR2890074B1 (en) * | 2005-09-01 | 2007-11-23 | Lvmh Rech | NEW ANTI-GENE OLIGONUCLEOTIDES SPECIFIC TO TYROSINASE AS DEPIGMENTING AGENTS |
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| KR20070099450A (en) | 2007-10-09 |
| KR101353628B1 (en) | 2014-01-20 |
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