JPH06298804A - Modified hyaluronic acid, its production, and emulsifier using it - Google Patents
Modified hyaluronic acid, its production, and emulsifier using itInfo
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- JPH06298804A JPH06298804A JP5112228A JP11222893A JPH06298804A JP H06298804 A JPH06298804 A JP H06298804A JP 5112228 A JP5112228 A JP 5112228A JP 11222893 A JP11222893 A JP 11222893A JP H06298804 A JPH06298804 A JP H06298804A
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- Prior art keywords
- acid
- hyaluronic acid
- modified hyaluronic
- hydrophilic
- hydrophobic
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Cosmetics (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
- General Preparation And Processing Of Foods (AREA)
- Jellies, Jams, And Syrups (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は修飾ヒアルロン酸及びそ
の製造方法、それを用いた乳化剤、特にヒアルロン酸の
アルコール性水酸基に親水性酸残基及び親油性酸残基を
結合させた修飾ヒアルロン酸及びその製造方法に関す
る。FIELD OF THE INVENTION The present invention relates to a modified hyaluronic acid and a method for producing the same, an emulsifier using the same, in particular, a modified hyaluronic acid obtained by binding a hydrophilic acid residue and a lipophilic acid residue to an alcoholic hydroxyl group of hyaluronic acid. And a manufacturing method thereof.
【０００２】[0002]
【従来の技術】各種乳化組成物を製造するため乳化剤が
用いられているが、近年乳化剤の人体に対する安全性が
問題となっており、化粧品或いは食品等生体に適用され
る乳化組成物に用いられる乳化剤には極めて高い安全性
が要求される。安全性に鑑みるのならば、天然に由来す
る乳化剤が好ましいが、これら天然の乳化剤としてはレ
シチン等少数のものが知られているに過ぎず、しかもそ
の乳化力はさほど高いものではない。これに対し、自然
物由来の物質に修飾を施し乳化剤ないし乳化安定剤を得
る技術も開発されている（特開平３−１４３５４０号公
報等）。前記公報に開示された乳化安定剤は、ヒアルロ
ン酸にアシル基を導入したものであり、未修飾ヒアルロ
ン酸が強水溶性を呈するのに対し、その修飾率によって
は疎水性をも呈するようになり、乳化安定剤の一つと考
えられている。2. Description of the Related Art Emulsifiers have been used to produce various emulsion compositions, but in recent years the safety of the emulsifiers to the human body has become a problem, and they are used in emulsion compositions applied to living bodies such as cosmetics and foods. Emulsifiers are required to have extremely high safety. From the viewpoint of safety, naturally-derived emulsifiers are preferable, but only a small number of these natural emulsifiers such as lecithin are known, and their emulsifying power is not so high. On the other hand, a technique of modifying a substance derived from a natural product to obtain an emulsifier or an emulsion stabilizer has been developed (Japanese Patent Laid-Open No. 143540/1993). The emulsion stabilizer disclosed in the above-mentioned publication is one in which an acyl group is introduced into hyaluronic acid.Unmodified hyaluronic acid exhibits strong water solubility, while it also exhibits hydrophobicity depending on its modification rate. , Is considered to be one of the emulsion stabilizers.
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、前記従
来の修飾ヒアルロン酸にあっては、アシル基の導入に伴
い水難溶化が進むが、一方で油溶化は大きくは進まず、
むしろ各種水溶性基剤ないし油溶性基剤への親和性が低
下してしまうものであった。従って、アシル基修飾率の
極めて低いものないしヒアルロン酸の分子量が極めて低
いものでは、多少の乳化安定化作用は有するものの、乳
化剤としての機能は充分なものではなかった。即ち、分
子量の大きいアシル基をヒアルロン酸に結合させると、
該ヒアルロン酸表面がアシル基で被覆されたような状態
となり、極めて高い分子量の脂質のごとくあらゆる基剤
への溶解性が低下してしまうのである。本発明は前記従
来技術の課題に鑑がみなされたものであり、その目的は
生体内に広く存在するヒアルロン酸を修飾し、優れた乳
化作用を有する修飾ヒアルロン酸ないし乳化剤を提供す
ることにある。However, in the above-mentioned conventional modified hyaluronic acid, the insolubilization in water progresses with the introduction of the acyl group, while the oil solubilization does not progress greatly.
Rather, the affinity for various water-soluble bases or oil-soluble bases was reduced. Therefore, those having an extremely low modification ratio of an acyl group or those having an extremely low molecular weight of hyaluronic acid have some emulsion stabilizing effects, but have insufficient functions as emulsifiers. That is, when an acyl group having a large molecular weight is bonded to hyaluronic acid,
The surface of the hyaluronic acid is covered with an acyl group, and the solubility in any base material such as an extremely high molecular weight lipid is lowered. The present invention has been made in view of the above-mentioned problems of the prior art, and an object thereof is to modify hyaluronic acid widely existing in the living body and to provide a modified hyaluronic acid or emulsifier having an excellent emulsifying action. .
【０００４】[0004]
【課題を解決するための手段】前記目的を達成するため
に本発明者らが鋭意検討した結果、ヒアルロン酸のアル
コール性水酸基を複数種の有機酸により修飾すること
で、優れた乳化作用が得られることを見出し、本発明を
完成するに至った。即ち、本出願の請求項１記載の修飾
ヒアルロン酸は、下記一般式化２の構造を有することを
特徴とする。Means for Solving the Problems As a result of intensive investigations by the present inventors in order to achieve the above-mentioned object, by modifying the alcoholic hydroxyl group of hyaluronic acid with a plurality of organic acids, an excellent emulsifying action can be obtained. The present invention has been completed and the present invention has been completed. That is, the modified hyaluronic acid according to claim 1 of the present application is characterized by having a structure represented by the following general formula 2.
【化２】 尚、上記化２において、Ｒ1，Ｒ2，Ｒ3，Ｒ4は、水素ま
たはエステル結合された酸残基を意味し、該酸残基とし
ては親水性酸残基と疎水性酸残基の少なくとも二種類が
存在する。Ｒ5は水素又はアルカリ金属原子を示す。
又、請求項２記載の修飾ヒアルロン酸は、前記親水性酸
残基が乳酸残基であることを特徴とする。又、請求項３
記載の修飾ヒアルロン酸は、疎水性酸残基がラウリン酸
及び／又はミリスチン酸残基であることを特徴とする。
又、請求項４記載の製造方法は、粉末状ヒアルロン酸を
疎水性酸残基を含む遊離酸に懸濁し、触媒として無水ト
リフルオロ酢酸を加え、所定時間反応させた後、親水性
酸残基を含む有機酸を加え、更に所定時間反応させたこ
とを特徴とする。請求項５記載の乳化剤は、前記修飾ヒ
アルロン酸を含むことを特徴とする。以下、本発明の構
成を更に詳細に説明する。[Chemical 2] In the above chemical formula 2 , R 1 , R 2 , R 3 , and R 4 mean hydrogen or ester-bonded acid residues, and the acid residues include hydrophilic acid residues and hydrophobic acid residues. There are at least two types. R 5 represents hydrogen or an alkali metal atom.
The modified hyaluronic acid according to claim 2 is characterized in that the hydrophilic acid residue is a lactic acid residue. Also, claim 3
The modified hyaluronic acid described is characterized in that the hydrophobic acid residues are lauric acid and / or myristic acid residues.
Further, the production method according to claim 4, wherein powdery hyaluronic acid is suspended in a free acid containing a hydrophobic acid residue, trifluoroacetic anhydride is added as a catalyst, and the mixture is reacted for a predetermined time, and then a hydrophilic acid residue is added. It is characterized in that an organic acid containing is added and further reacted for a predetermined time. The emulsifier according to claim 5 is characterized in that it contains the modified hyaluronic acid. Hereinafter, the constitution of the present invention will be described in more detail.
【０００５】本発明者らは、ヒアルロン酸のアシル化に
伴う急激な溶媒溶解性の低下に着目し、ヒアルロン酸へ
の疎水基導入とともに親水基をも導入することにより、
極めて優れた乳化力を有する修飾ヒアルロン酸が得られ
ることを見出した。本発明においてヒアルロン酸とは、
ヒアルロン酸及びヒアルロン酸塩を意味し、各種分子量
のものを用いることができる。又、本発明に係る修飾ヒ
アルロン酸の製造方法において、ヒアルロニダーゼ等の
酵素処理により、オリゴヒアルロン酸から分子量１０，
０００ｋｄ以上におよぶ広範囲の分子量の修飾ヒアルロ
ン酸を得ることができ、又前記疎水性酸残基を有する有
機酸とのエステル化反応時間ないし親水性酸残基を有す
る有機酸とのエステル化反応時間を変化させることによ
り、各疎水性酸残基ないし親水性酸残基の修飾率を大幅
に変更することが出来る。The present inventors have focused on the drastic decrease in solvent solubility associated with the acylation of hyaluronic acid, and by introducing a hydrophilic group as well as a hydrophobic group into hyaluronic acid,
It was found that a modified hyaluronic acid having an extremely excellent emulsifying power can be obtained. In the present invention, hyaluronic acid is
It means hyaluronic acid and hyaluronic acid salt, and those having various molecular weights can be used. Further, in the method for producing modified hyaluronic acid according to the present invention, the molecular weight of oligohyaluronic acid is adjusted to 10 by the enzymatic treatment with hyaluronidase or the like.
Modified hyaluronic acid having a wide range of molecular weights of 000 kd or more can be obtained, and esterification reaction time with the organic acid having the hydrophobic acid residue or esterification reaction time with the organic acid having the hydrophilic acid residue. The modification ratio of each hydrophobic acid residue or hydrophilic acid residue can be significantly changed by changing
【０００６】本発明においてヒアルロン酸を修飾するた
めの親水性酸残基を有する有機酸としては、乳酸ないし
ピルビン酸のようなヒドロキシ酸或いは多塩基酸等、ヒ
アルロン酸とエステル結合するカルボキシル基以外に親
水基を有する有機酸が好適である。又、本発明において
疎水性酸残基を有する有機酸としては、ラウリン酸、ミ
リスチン酸等の炭素数３以上の脂肪酸が好適である。特
にラウリン酸／乳酸及びミリスチン酸／乳酸でヒアルロ
ン酸を修飾した場合には、修飾ヒアルロン酸の安定性が
極めて高いという利点を有する。又、本発明において無
水トリフロオロ酢酸は触媒として機能し、ヒアルロン酸
と遊離酸の反応は、例えば室温にて数時間行えばすみ、
穏和な条件でヒアルロン酸自体の構造に変化を与えるこ
となく、修飾ヒアルロン酸を製造することができる。な
お、ヒアルロン酸に対する反応性は一般に親水性有機酸
の方が疎水性有機酸よりも高いため、始めに或いは同時
にヒアルロン酸と親水性有機酸の反応を行うと、親水性
酸残基の導入が優先して進行し、疎水性酸残基の導入が
困難となる。そこで、疎水性酸残基の導入を始めに行
い、後に親水性酸残基の導入を行うことが好適である。In the present invention, examples of the organic acid having a hydrophilic acid residue for modifying hyaluronic acid include a hydroxy acid such as lactic acid or pyruvic acid or a polybasic acid, in addition to a carboxyl group which forms an ester bond with hyaluronic acid. Organic acids having hydrophilic groups are preferred. Further, in the present invention, as the organic acid having a hydrophobic acid residue, a fatty acid having 3 or more carbon atoms such as lauric acid and myristic acid is preferable. In particular, when hyaluronic acid is modified with lauric acid / lactic acid and myristic acid / lactic acid, there is an advantage that the stability of the modified hyaluronic acid is extremely high. In the present invention, trifluoroacetic anhydride functions as a catalyst, and the reaction between hyaluronic acid and free acid may be carried out at room temperature for several hours, for example.
Modified hyaluronic acid can be produced under mild conditions without changing the structure of hyaluronic acid itself. In addition, since the reactivity of hyaluronic acid is generally higher in hydrophilic organic acids than in hydrophobic organic acids, introduction of hydrophilic acid residues may occur when the reaction of hyaluronic acid and hydrophilic organic acids is performed at the beginning or at the same time. It progresses preferentially and it becomes difficult to introduce a hydrophobic acid residue. Therefore, it is preferable to first introduce the hydrophobic acid residue and then introduce the hydrophilic acid residue.
【０００７】[0007]
【実施例】以下、本発明を実施例に基づき説明する。
尚、本発明は以下の実施例に限定されるものではない。実施例１ ラウリン酸／乳酸化ヒアルロン酸 ビーカーに採った無水トリフルオロ酢酸各５０mlに、ラ
ウリン酸を０．０５，０．１０，０．２０，０．４０，
０．８０ｇを溶解させ、次いで其々に１ｇのヒアルロン
酸（分子量２０万）を分散後、攪拌下、室温で一夜放置
した（ラウリン酸化）。次に、其々のビーカーに氷冷下
で乳酸２５ｍｌを加え、室温攪拌しながら３日放置した
（乳酸化）。反応終了後、純水を加えてセルロースチュ
ーブにて流水透析を、３日間行った。次に、透析内液を
ジクロロメタン中に落とし攪拌後、分液ロート内で静置
し、上下層に分離したところで、水層のみを回収し、凍
結乾燥してラウリン酸／乳酸化ヒアルロン酸を得た。同
時に対照として、乳酸化のみ及びラウリン酸化のみを行
ったヒアルロン酸誘導体も調製した（表１参照）。EXAMPLES The present invention will be described below based on examples.
The present invention is not limited to the examples below. Example 1 Lauric acid was added to each of 50 ml of trifluoroacetic anhydride taken in a beaker of lauric acid / lactic acid-hyaluronic acid, 0.05, 0.10, 0.20, 0.40,
0.80 g was dissolved, then 1 g of hyaluronic acid (molecular weight 200,000) was dispersed in each, and the mixture was allowed to stand overnight at room temperature with stirring (lauric acid oxidation). Next, 25 ml of lactic acid was added to each beaker under ice cooling, and the mixture was left for 3 days with stirring at room temperature (lactic acidification). After completion of the reaction, pure water was added and dialyzing with running water through a cellulose tube was performed for 3 days. Next, the dialyzed solution was dropped into dichloromethane, stirred, and allowed to stand in a separating funnel, and when separated into upper and lower layers, only the aqueous layer was recovered and freeze-dried to obtain lauric acid / lactic acid hyaluronic acid. It was At the same time, as a control, a hyaluronic acid derivative which was lactic acid-only and lauric acid-only was also prepared (see Table 1).
【０００８】なお、ラウリン酸は添加量のほぼ全量が修
飾に用いられているものと考えられ、一方乳酸はラウリ
ン酸の未反応部分に修飾される。図１は上述のラウリン
酸０．１ｇを加えたときのラウリン酸／乳酸化ヒアルロ
ン酸に対するＩＲスペクトルである。１７４０ｃｍ-1付
近にＣ＝０伸縮振動に起因する吸収が、又２９００ｃｍ
-1付近にＣ−Ｈ伸縮振動に起因する吸収が認められる
が、前者は主に乳酸化に由来し、後者は主にラウリン酸
化に由来する。表１には、これらのヒアルロン酸誘導体
の水に対する溶解性と、水／流動パラフィン＝１／１の
混合液にこれら誘導体を加えたときの乳化安定性を示
す。尚、この乳化安定性は各ヒアルロン酸誘導体の固形
分濃度が１％となるように加え、室温で５日放置したと
きの状態を示した。表１中「沈殿」とは、調製したヒア
ルロン酸誘導体が水不溶性のため沈殿していることを意
味し、「分離」とは、一時的に乳化するが経時で油水分
離を起こすことを意味している。It is considered that almost all the added amount of lauric acid is used for modification, while lactic acid is modified to the unreacted portion of lauric acid. FIG. 1 is an IR spectrum for lauric acid / lactic acid hyaluronic acid when 0.1 g of lauric acid was added. Absorption due to stretching vibration of C = 0 near 1740 cm -1 , again 2900 cm
Absorption due to C—H stretching vibration is observed near −1, but the former is mainly due to lactic acidation and the latter is mainly due to lauric oxidation. Table 1 shows the solubility of these hyaluronic acid derivatives in water and the emulsion stability when these derivatives were added to a mixed solution of water / liquid paraffin = 1/1. The emulsion stability was shown when the hyaluronic acid derivative was added at a solid concentration of 1% and left at room temperature for 5 days. In Table 1, "precipitation" means that the prepared hyaluronic acid derivative is insoluble in water and thus precipitates, and "separation" means that it temporarily emulsifies but causes oil-water separation over time. ing.
【０００９】[0009]
【表１】 ──────────────────────────────────── 試験品Ｎｏ． ラウリン酸 乳酸 水溶解性 乳化安定性 ──────────────────────────────────── 比較例１ ０ ２５ ○ 分離 比較例２ ０．０５ ０ △ 分離 比較例３ ０．１０ ０ × 分離 比較例４ ０．０５ ２５ ○ 分離 ──────────────────────────────────── 実施例１ ０．１０ ２５ ○ 乳化 実施例２ ０．２０ ２５ ○ 乳化 実施例３ ０．４０ ２５ ○ 乳化 ──────────────────────────────────── 比較例５ ０．８０ ２５ × 沈殿 ──────────────────────────────────── この表１から分かるように、分子量２０万のヒアルロン
酸から調整した誘導体を乳化剤として用いた場合、ラウ
リン酸化のみでは水溶性が低くなりすぎ、良好な乳化作
用を付与させることはできない。又、乳酸化のみでも親
油性が欠如し、水溶性は良好なものの、乳化作用は殆ど
ない。しかし、ラウリン酸化を適度に進め、更に乳酸化
も行うと、水溶性が維持されつつ、乳化作用を持たせる
ことが可能となる。[Table 1] ──────────────────────────────────── Test product No. Lauric Acid Lactic Acid Water Solubility Emulsion Stability ──────────────────────────────────── Comparative Example 1 0 25 ○ Separation Comparative Example 2 0.05 0 △ Separation Comparative Example 3 0.10 0 × Separation Comparative Example 4 0.05 25 ○ Separation ───────────────────── ─────────────── Example 1 0.10 25 ○ Emulsification Example 2 0.20 25 ○ Emulsification Example 3 0.40 25 ○ Emulsion ───────── ──────────────────────────── Comparative Example 5 0.80 25 × Precipitation ────────────── ─────────────────────── As can be seen from Table 1, when a derivative prepared from hyaluronic acid having a molecular weight of 200,000 is used as an emulsifier, Water alone The solubility is too low to give a good emulsifying action. Further, lactic acid alone lacks lipophilicity and has good water solubility, but has almost no emulsifying action. However, if lauric acid is appropriately advanced and lactation is also performed, it becomes possible to impart an emulsifying action while maintaining water solubility.
【００１０】実施例２ ラウリン酸／乳酸化ヒアルロン
酸 ビーカーに採った無水トリフロオロ酢酸各５０ｍｌに、
ラウリン酸を０．２０ｇ溶解させ、次いで其々に１ｇの
ヒアルロン酸（分子量２０万）を分散後、攪拌下、室温
で一夜放置した（ラウリン酸化）。次に、其々のビーカ
ーに氷冷下で乳酸５，１０，１５，２０，２５，３０，
４０，５０ｍｌを加え、室温攪拌しながら３日放置した
（乳酸化）。以下、実施例１と同様に処理し、ラウリン
酸／乳酸化ヒアルロン酸を調整した。その乳化作用に対
する結果を表２にまとめた。 Example 2 Lauric Acid / Lactated Hyaluron
To each 50 ml of anhydrous trifluoroacetic acid collected in an acid beaker,
0.20 g of lauric acid was dissolved, 1 g of hyaluronic acid (molecular weight 200,000) was dispersed in each, and the mixture was allowed to stand overnight at room temperature with stirring (lauric acid oxidation). Next, lactic acid 5,10,15,20,25,30, under ice-cooling in each beaker.
After adding 40 and 50 ml, the mixture was left standing for 3 days with stirring at room temperature (lactic acidation). Thereafter, the same treatment as in Example 1 was carried out to prepare lauric acid / lactic acid hyaluronic acid. The results for its emulsifying action are summarized in Table 2.
【００１１】[0011]
【表２】 ──────────────────────────────────── 試験品Ｎｏ． ラウリン酸 乳酸 乳化安定性 ──────────────────────────────────── 比較例６ ０．２ ５ 分離 ──────────────────────────────────── 実施例４ ０．２ １０ 乳化 実施例５ ０．２ １５ 乳化 実施例６ ０．２ ２０ 乳化 実施例７ ０．２ ２５ 乳化 実施例８ ０．２ ３０ 乳化 実施例９ ０．２ ４０ 乳化 実施例１０ ０．２ ５０ 乳化 ──────────────────────────────────── 前記表２より明らかなように、ラウリン酸の添加量が対
ヒアルロン酸２０重量％程度とすると、乳酸基の導入量
をかなり多くしても優れた乳化能力を呈する。[Table 2] ──────────────────────────────────── Test product No. Lauric acid Lactic acid Emulsion stability ───────────────────────────────────── Comparative Example 6 0.2 5 Separation ──────────────────────────────────── Example 4 0.2 10 Emulsification Example 5 0.2 15 Emulsification Example 6 0.2 20 Emulsification Example 7 0.2 25 Emulsion Example 8 0.2 30 Emulsion Example 9 0.2 40 Emulsion Example 10 0.2 50 Emulsion ──────── ──────────────────────────── As is clear from Table 2, the addition amount of lauric acid is about 20% by weight of hyaluronic acid. Then, even if the amount of lactic acid groups introduced is considerably increased, excellent emulsifying ability is exhibited.
【００１２】実施例３ ミリスチン酸／乳酸化ヒアルロ
ン酸 ラウリン酸の代りにミリスチン酸を用いる事を除いて、
実施例１と同様に反応させ、ヒアルロン酸のミリスチン
酸／乳酸化物を得た。結果は表１と実質的に変らなかっ
た。 Example 3 Myristic Acid / Lactated Hyaluronate
Instead of phosphate lauric acid except the use of the myristic acid,
Reaction was carried out in the same manner as in Example 1 to obtain hyruronic acid myristic acid / milk oxide. The results were substantially the same as in Table 1.
【００１３】[0013]
【発明の効果】以上説明したように本発明にかかる修飾
ヒアルロン酸によれば、ヒアルロン酸のアルコール性水
酸基を親水性酸残基及び疎水性酸残基により修飾するこ
ととしたので、極めて優れた乳化剤として用いることが
可能となる。As described above, according to the modified hyaluronic acid of the present invention, the alcoholic hydroxyl group of hyaluronic acid is modified with a hydrophilic acid residue and a hydrophobic acid residue, which is extremely excellent. It can be used as an emulsifier.
【図１】 本発明の一実施例にかかるラウリン酸／乳酸
化ヒアルロン酸のＩＲスペクトル図である。FIG. 1 is an IR spectrum diagram of lauric acid / lactic acid hyaluronic acid according to an example of the present invention.
Claims (5)
徴とする修飾ヒアルロン酸。 【化１】 尚、上記化１において、Ｒ1，Ｒ2，Ｒ3，Ｒ4は、水素ま
たはエステル結合された酸残基を意味し、該酸残基とし
ては親水性酸残基と疎水性酸残基の少なくとも二種類が
存在する。Ｒ5は水素又はアルカリ金属原子を示す。1. A modified hyaluronic acid having a structure represented by the following general formula 1. [Chemical 1] In the above chemical formula 1 , R 1 , R 2 , R 3 and R 4 mean hydrogen or ester-bonded acid residues, and the acid residues include hydrophilic acid residues and hydrophobic acid residues. There are at least two types. R 5 represents hydrogen or an alkali metal atom.
て、前記親水性酸残基が乳酸であることを特徴とする修
飾ヒアルロン酸。2. The modified hyaluronic acid according to claim 1, wherein the hydrophilic acid residue is lactic acid.
て、前記疎水性酸残基がラウリン酸及び／又はミリスチ
ン酸であることを特徴とする修飾ヒアルロン酸。3. The modified hyaluronic acid according to claim 1, wherein the hydrophobic acid residue is lauric acid and / or myristic acid.
含む有機酸に懸濁し、触媒として無水トリフルオロ酢酸
を加え、所定時間反応させた後、親水性酸残基を含む有
機酸を加え、更に所定時間反応させたことを特徴とする
修飾ヒアルロン酸の製造方法。4. A powdery hyaluronic acid is suspended in an organic acid containing a hydrophobic acid residue, trifluoroacetic anhydride is added as a catalyst, the mixture is reacted for a predetermined time, and then an organic acid containing a hydrophilic acid residue is added. In addition, a method for producing a modified hyaluronic acid, which is characterized by reacting for a predetermined time.
含むことを特徴とする乳化剤。5. An emulsifier comprising the modified hyaluronic acid according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5112228A JPH06298804A (en) | 1993-04-15 | 1993-04-15 | Modified hyaluronic acid, its production, and emulsifier using it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5112228A JPH06298804A (en) | 1993-04-15 | 1993-04-15 | Modified hyaluronic acid, its production, and emulsifier using it |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06298804A true JPH06298804A (en) | 1994-10-25 |
Family
ID=14581462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5112228A Withdrawn JPH06298804A (en) | 1993-04-15 | 1993-04-15 | Modified hyaluronic acid, its production, and emulsifier using it |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06298804A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1110971A1 (en) * | 1999-12-14 | 2001-06-27 | Kibun Food ChemiFA Co., Ltd. | Propylene glycol hyaluronate and agent for external use to skin using the same |
| US6710038B1 (en) | 1999-12-14 | 2004-03-23 | Kibun Food Chemifa Co., Ltd. | Emulsification method using propylene glycol hyaluronate |
| JP2006312725A (en) * | 2005-04-05 | 2006-11-16 | Shiseido Co Ltd | Hydroxyalkylated hyaluronic acid |
| WO2011102462A1 (en) * | 2010-02-19 | 2011-08-25 | キユーピー株式会社 | Modified hyaluronic acid and/or salt thereof, method for producing same and cosmetic comprising same |
| JP2012241007A (en) * | 2011-05-24 | 2012-12-10 | Q P Corp | Emulsifying agent |
| JP2015522366A (en) * | 2012-07-18 | 2015-08-06 | アラーガン・アンデュストリー・ソシエテ・パール・アクシオン・サンプリフィエＡｌｌｅｒｇａｎ Ｉｎｄｕｓｔｒｉｅ Ｓａｓ | Hyaluronic acid preparation containing pyruvate |
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1993
- 1993-04-15 JP JP5112228A patent/JPH06298804A/en not_active Withdrawn
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1110971A1 (en) * | 1999-12-14 | 2001-06-27 | Kibun Food ChemiFA Co., Ltd. | Propylene glycol hyaluronate and agent for external use to skin using the same |
| US6710038B1 (en) | 1999-12-14 | 2004-03-23 | Kibun Food Chemifa Co., Ltd. | Emulsification method using propylene glycol hyaluronate |
| JP2006312725A (en) * | 2005-04-05 | 2006-11-16 | Shiseido Co Ltd | Hydroxyalkylated hyaluronic acid |
| WO2011102462A1 (en) * | 2010-02-19 | 2011-08-25 | キユーピー株式会社 | Modified hyaluronic acid and/or salt thereof, method for producing same and cosmetic comprising same |
| JP4845071B2 (en) * | 2010-02-19 | 2011-12-28 | キユーピー株式会社 | Modified hyaluronic acid and / or salt thereof, process for producing the same and cosmetics containing the same |
| JP2012021166A (en) * | 2010-02-19 | 2012-02-02 | Q P Corp | Modified hyaluronic acid and/or salt thereof and cosmetic comprising the same |
| CN102770459A (en) * | 2010-02-19 | 2012-11-07 | 丘比株式会社 | Modified hyaluronic acid and/or salt thereof, method for producing same and cosmetic comprising same |
| US9107842B2 (en) | 2010-02-19 | 2015-08-18 | Kewpie Corporation | Modified hyaluronic acid and/or a salt thereof, method for producing the same, and cosmetic preparation comprising the same |
| JP2012241007A (en) * | 2011-05-24 | 2012-12-10 | Q P Corp | Emulsifying agent |
| JP2015522366A (en) * | 2012-07-18 | 2015-08-06 | アラーガン・アンデュストリー・ソシエテ・パール・アクシオン・サンプリフィエＡｌｌｅｒｇａｎ Ｉｎｄｕｓｔｒｉｅ Ｓａｓ | Hyaluronic acid preparation containing pyruvate |
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