JPH0625306A - Solvent-insoluble hyaluronic acid and its production - Google Patents
Solvent-insoluble hyaluronic acid and its productionInfo
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- JPH0625306A JPH0625306A JP5117782A JP11778293A JPH0625306A JP H0625306 A JPH0625306 A JP H0625306A JP 5117782 A JP5117782 A JP 5117782A JP 11778293 A JP11778293 A JP 11778293A JP H0625306 A JPH0625306 A JP H0625306A
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- Prior art keywords
- acid
- hyaluronic acid
- solvent
- fatty acid
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- Polysaccharides And Polysaccharide Derivatives (AREA)
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は溶媒不溶化ヒアルロン酸
及びその製造方法、特にヒアルロン酸のアルコール性水
酸基に脂肪酸残基を高修飾率で結合させた溶媒不溶化ヒ
アルロン酸及びその製造方法の改良に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solvent-insolubilized hyaluronic acid and a method for producing the same, and more particularly to a solvent-insolubilized hyaluronic acid in which a fatty acid residue is bonded to an alcoholic hydroxyl group of hyaluronic acid at a high modification ratio and a method for producing the same.
【０００２】[0002]
【従来の技術】ヒアルロン酸は生体由来の高分子物質で
あり、高い増粘性、粘張性、曳糸性等の特異的な物性を
有しており、しかも生体適合性が高いことから各種分野
での応用が期待されている。2. Description of the Related Art Hyaluronic acid is a polymeric substance of biological origin and has specific physical properties such as high viscosity, viscosity and spinnability, and is highly biocompatible, so it is used in various fields. Is expected to be applied.
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、ヒアル
ロン酸は強水溶性であり、このため有機溶媒系での増粘
剤、油性基剤中での各種乳化安定剤、リポソームの被覆
強化剤、生体への埋め込み基剤、カプセル基剤等への用
途が期待されていながら、充分な応用が出来ないもので
あった（特開平３−１４３５４０、特開昭５４−３６３
８８等参照）。一方でヒアルロン酸を修飾し、化学的な
いし物理的性質を改変する試みも各種なされている。例
えば特開平３−１４３５４０は、ヒアルロン酸にアシル
基を導入し、ヒアルロン酸の水ないし油への溶解性を調
整して乳化安定剤として使用するものである。However, hyaluronic acid is strongly water-soluble, and therefore, it is a thickener in an organic solvent system, various emulsion stabilizers in an oily base, a liposome coating enhancer, and a biological agent. Although it is expected to be used as a base material for embedding, a base material for capsules, etc., it could not be sufficiently applied (JP-A-3-143540, JP-A-54-363).
88 etc.). On the other hand, various attempts have been made to modify hyaluronic acid to change its chemical or physical properties. For example, JP-A-3-143540 discloses that an acyl group is introduced into hyaluronic acid to adjust the solubility of hyaluronic acid in water or oil and then used as an emulsion stabilizer.
【０００４】しかし、ここで用いられるアシル化ヒアル
ロン酸はアシル基の導入量が低く、溶媒中で膨潤などが
生じ、創傷の縫合用糸或いは保護用薄膜として用い得る
ほど安定なものではなかった。また、前記特開平３−１
４３５４０に示された方法でアシル基の導入率を高める
と、ヒアルロン酸の分解などが生じるという課題もあっ
た。本発明は前記従来技術の課題に鑑みなされたもので
あり、その目的はヒアルロン酸の本来有する機能を保持
し、しかも各種溶媒に溶解ないし膨潤しない溶媒不溶化
ヒアルロン酸及びその製造方法を提供することにある。However, the acylated hyaluronic acid used here is low in the amount of acyl group introduced, causes swelling in a solvent, and is not stable enough to be used as a suture thread for wounds or a protective thin film. Further, the above-mentioned Japanese Patent Laid-Open No. 3-1
If the introduction rate of an acyl group is increased by the method shown in 43540, there is also a problem that decomposition of hyaluronic acid occurs. The present invention has been made in view of the above problems of the prior art, and its object is to provide a solvent-insolubilized hyaluronic acid which retains the original function of hyaluronic acid and does not dissolve or swell in various solvents, and a method for producing the same. is there.
【０００５】[0005]
【課題を解決するための手段】前記目的を達成するため
に本発明者が鋭意検討した結果、触媒である無水トリフ
ルオロ酢酸に脂肪酸を溶解したのち、ヒアルロン酸を懸
濁することにより、温和な条件でアシル基をヒアルロン
酸に高率で導入可能なことを見出し、本発明を完成する
に至った。即ち、本出願の請求項１記載の溶媒不溶化ヒ
アルロン酸は、次の化２を構造を有することを特徴とす
る。Means for Solving the Problems As a result of intensive studies by the present inventors in order to achieve the above object, as a result of dissolving a fatty acid in trifluoroacetic anhydride, which is a catalyst, and then suspending hyaluronic acid, a mild reaction is obtained. The inventors have found that an acyl group can be introduced into hyaluronic acid at a high rate under the conditions, and have completed the present invention. That is, the solvent-insolubilized hyaluronic acid according to claim 1 of the present application is characterized by having the following chemical formula 2.
【化２】 尚、上記化２中、Ｒ1，Ｒ2，Ｒ3，Ｒ4は、水素またはエ
ステル結合された炭素数１２以上の脂肪酸残基を示し、
Ｒ5は水素又はアルカリ金属原子を示す。なお、該溶媒
不溶化ヒアルロン酸は、創傷縫合用糸或いは創傷保護用
薄膜などとして用いることが好適である。請求項２記載
の溶媒不溶化ヒアルロン酸の製造方法は、触媒である無
水トリフルオロ酢酸に脂肪酸を溶解し、ヒアルロン酸を
懸濁し、反応させることを特徴とする。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 represent hydrogen or an ester-bonded fatty acid residue having 12 or more carbon atoms,
R 5 represents hydrogen or an alkali metal atom. The solvent-insoluble hyaluronic acid is preferably used as a wound suture thread or a wound protection thin film. The method for producing solvent-insolubilized hyaluronic acid according to claim 2 is characterized in that a fatty acid is dissolved in trifluoroacetic anhydride serving as a catalyst, and hyaluronic acid is suspended and reacted. Hereinafter, the constitution of the present invention will be described in more detail.
【０００６】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、本発明にかかる溶媒不溶
化ヒアルロン酸の製造方法において、原料とヒアルロン
酸を予めヒアルロニダーゼ等で酵素処理することによ
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溶媒不溶化ヒアルロン酸を得ること
ができ、又エステル化反応時間を変えることにより修飾
化率を大幅に変更することができる。本発明において、
修飾を行うための遊離酸としては、ラウリン酸、ミリス
チン酸、パルミチン酸、ステアリン酸、ベヘン酸、ペラ
ルゴン酸、カプリン酸、ウンデカン酸等の炭素数１２以
上の脂肪酸から選択することができる。本発明におい
て、無水トリフルオロ酢酸は触媒として機能し、ヒアル
ロン酸と脂肪酸の反応は、例えば室温にて数時間行なえ
ば済み、温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、溶媒不溶化ヒアルロン酸を製造するこ
とができる。In the present invention, hyaluronic acid means hyaluronic acid and hyaluronic acid salts, and various molecular weights can be used. In the method for producing solvent-insolubilized hyaluronic acid according to the present invention, a wide range of solvent-insolubilized hyaluronic acid having a molecular weight of 10,000 kd or more can be obtained from oligohyaluronic acid by enzymatically treating the raw material and hyaluronic acid with hyaluronidase or the like. In addition, the modification rate can be significantly changed by changing the esterification reaction time. In the present invention,
The free acid for modification can be selected from fatty acids having 12 or more carbon atoms such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, pelargonic acid, capric acid, and undecanoic acid. In the present invention, trifluoroacetic anhydride functions as a catalyst, and the reaction between hyaluronic acid and a fatty acid may be carried out, for example, at room temperature for several hours, and the solvent is insolubilized without changing the structure of hyaluronic acid itself under mild conditions. Hyaluronic acid can be produced.
【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 ラウリン酸化ヒアルロン酸 ５００mlのガラス製ビーカーに２００mlの無水トリフル
オロ酢酸を入れ、これに５ｇのラウリン酸を溶解させ、
ついで２ｇのバイオヒアルロン酸（分子量１４００kD、
資生堂（株）製）の微細粉末を攪拌しながら少しずつ加
え、室温で一晩攪拌しながら反応させた。反応液を３０
０mlの特級ジクロロメタン中へ注ぎ込み、浮いてきた反
応物を回収した。次に、これを再び３００mlのジクロロ
エタンで、更に３００mlの精製水で充分に洗浄した。こ
の洗浄操作を３回繰り返し、未反応のラウリン酸とトリ
フルオロ酢酸を除去した。次にこれを真空乾燥してラウ
リン酸化ヒアルロン酸の白色粉末を得た。本実施例品の
赤外吸収スペクトルを図１に示す。１７３８cm-1にカル
ボニル基の、また２９００cm-1付近にＣ−Ｈ伸縮振動に
基づく吸収が現れる。EXAMPLES The present invention will be described below based on examples.
The present invention is not limited to the examples below. Example 1 200 ml of trifluoroacetic anhydride was placed in a glass beaker containing 500 ml of lauric acid-hyaluronic acid , and 5 g of lauric acid was dissolved in the beaker.
Then 2 g of biohyaluronic acid (molecular weight 1400 kD,
A fine powder of Shiseido Co., Ltd.) was added little by little with stirring, and the mixture was reacted at room temperature overnight with stirring. 30 reaction mixture
Pour into 0 ml of premium grade dichloromethane and collect the floating reaction product. Then, it was thoroughly washed again with 300 ml of dichloroethane and further with 300 ml of purified water. This washing operation was repeated 3 times to remove unreacted lauric acid and trifluoroacetic acid. Then, this was vacuum dried to obtain a white powder of lauric acid hyaluronic acid. The infrared absorption spectrum of the product of this example is shown in FIG. Absorption of a carbonyl group appears at 1738 cm −1 and absorption due to C—H stretching vibration appears at around 2900 cm −1 .
【０００８】実施例２ イソステアリン酸化ヒアルロン酸 ラウリン酸の代りにイソステアリン酸を用いる以外は実
施例１と同じ操作を行って、イソステアリン酸化ヒアル
ロン酸を得た。本実施例品の赤外吸収スペクトルを図２
に示したが、１７３８cm-1にカルボニル基の、また２９
００cm-1付近にＣ−Ｈの伸縮振動に基づく吸収が現れ
る。実施例３ ミリスチン化ヒアルロン酸 ラウリン酸の代りにミリスチン酸を用いる以外は実施例
１と同じ操作を行って、ミリスチン酸化ヒアルロン酸を
得た。本品の赤外吸収スペクトルを図３に示したが、１
７３８cm-1にカルボニル基の、また２９００cm-1付近に
Ｃ−Ｈの伸縮振動に基づく吸収が現れる。実施例４ 縫合用糸 無水トリフロオロ酢酸１００mlにステアリン酸５ｇを溶
解後、ヒアルロン酸（分子量１８０万）１ｇを分散し、
室温で反応させた。反応液が均一で透明な液となったと
ころでジクロロメタンを加え、未反応のステアリン酸を
抽出除去した。この操作を３回繰り返した後、反応液を
ガラス製注射筒に移し、注射針から純水中に押出すこと
で糸状のステアリン酸化ヒアルロン酸を得た。これを純
水及びエタノールで充分に洗浄後、５０℃で真空乾燥し
たところ、引張り強度が高く且つしなやかな糸となっ
た。 Example 2 Isostearate Hyaluronic Acid The same operation as in Example 1 was carried out except that isostearic acid was used instead of lauric acid to obtain isostearylated hyaluronic acid. The infrared absorption spectrum of the product of this example is shown in FIG.
, The carbonyl group at 1738 cm −1 , 29
Absorption due to the stretching vibration of C-H appears near 00 cm -1 . Example 3 Myristin- oxidized hyaluronic acid was obtained by the same procedure as in Example 1 except that myristic acid was used instead of myristic hyaluronic acid lauric acid. The infrared absorption spectrum of this product is shown in Fig. 3.
Absorption due to carbonyl group at 738 cm −1 and absorption due to C—H stretching vibration at 2900 cm −1 . Example 4 Suture thread 5 g of stearic acid was dissolved in 100 ml of anhydrous trifluoroacetic acid, and then 1 g of hyaluronic acid (molecular weight 1.8 million) was dispersed.
The reaction was carried out at room temperature. When the reaction liquid became a uniform and transparent liquid, dichloromethane was added to extract and remove unreacted stearic acid. After repeating this operation three times, the reaction solution was transferred to a glass syringe and extruded from an injection needle into pure water to obtain a filamentous stearic acid hyaluronic acid. This was thoroughly washed with pure water and ethanol and then vacuum dried at 50 ° C., resulting in a high tensile strength and flexible yarn.
【０００９】本実施例にかかる糸は、一般の溶媒に対し
て溶解、膨潤などを生じず、極めて安定であり、しかも
生体内においてもヒアルロニダーゼ耐性が高い。一方、
ステアリン酸及びヒアルロン酸とも生体由来の成分であ
り、糸の生体適合性が高いばかりでなく、その分解産物
もこれらステアリン酸ないしヒアルロン酸、あるいはそ
の分離物であり、安全性が極めて高いという利点を有す
る。このため、本実施例にかかる糸を創傷などの縫合用
糸として用いることが可能である。実施例５ 創傷保護用薄膜 無水トリフロオロ酢酸２００mlにパルミチン酸６ｇを溶
解後、ヒアルロン酸（分子量３６０万）２ｇを分散し、
室温で反応させた。反応液が均一で透明な粘ちょう液と
なったところで、ジクロロメタンを加え、未反応のパル
ミチン酸を抽出除去した。この操作を３回繰り返した
後、反応液を厚さ３mmとなるようにシャーレ上に流し込
み、その上に充分量の純水をゆっくりと上層させ放置す
ることで、薄膜状パルミチン酸化ヒアルロン酸を得た。
これを純水及びエタノールで充分に洗浄後、７０℃で真
空乾燥したところ、引張り強度が高く且つしなやかな薄
膜となった。[0009] The yarn according to the present example does not dissolve or swell in a general solvent, is extremely stable, and has high hyaluronidase resistance in vivo. on the other hand,
Both stearic acid and hyaluronic acid are bio-derived components, and not only the biocompatibility of the thread is high, but also the decomposition product of these is stearic acid or hyaluronic acid, or its isolated product, which is extremely safe. Have. Therefore, the thread according to the present embodiment can be used as a thread for suturing a wound or the like. Example 5 Thin film for wound protection After dissolving 6 g of palmitic acid in 200 ml of anhydrous trifluoroacetic acid, 2 g of hyaluronic acid (molecular weight 3.6 million) was dispersed,
The reaction was carried out at room temperature. When the reaction solution became a uniform and transparent viscous liquid, dichloromethane was added to extract and remove unreacted palmitic acid. After repeating this operation three times, the reaction solution was poured onto a Petri dish to a thickness of 3 mm, and a sufficient amount of pure water was slowly allowed to form an upper layer and allowed to stand to obtain a thin film palmitic acid hyaluronic acid. It was
This was thoroughly washed with pure water and ethanol and then vacuum dried at 70 ° C., resulting in a thin film having high tensile strength and flexibility.
【００１０】本実施例にかかる薄膜も、生体適合性が高
く、例えば創傷被覆などに用いることにより、創傷部分
を刺激することなく保護することができる。さらに、一
時的な人工臓器などにも適用が期待される。尚、次の表
１に実施例１ないし３の修飾ヒアルロン酸の溶媒に対す
る挙動を示す。The thin film according to the present embodiment also has high biocompatibility, and by using it for wound coating, for example, it is possible to protect the wound portion without stimulating it. Furthermore, it is expected to be applied to temporary artificial organs. The following Table 1 shows the behavior of the modified hyaluronic acid of Examples 1 to 3 with respect to the solvent.
【表１】 ──────────────────────────────────── ＨＡ ラウリン酸ＨＡ ミリスチン酸ＨＡ イソステアリン酸ＨＡ ──────────────────────────────────── ＤＭＦ × × × × ＤＭＳＯ × × × × ＣＨ2Ｃｌ2 × × × × ＣＣｌ4 × × × × Ｌｐ−Ｅ × × × × Ｄ．Ｗ． × × × × 0.2Ｍリン酸１Ｎａ ○ × × × 0.2Ｍリン酸２Ｎａ ○ × × × ３０％ＥｔＯＨ ○ × × × ８０％ＥｔＯＨ ○ × × × ＥｔＯＨ × × × × ＣＩＯ × × × × ｎ−Ｈｅｘａｎｅ × × × × ８０％Ａｃｅｔｏｎｅ × × × × アイソパーＨ × × × × ──────────────────────────────────── 以上のように本発明にかかる溶媒不溶化ヒアルロン酸
は、何れも溶媒に対して不溶であり、且つ膨潤なども生
じないものである。[Table 1] ──────────────────────────────────── HA lauric acid HA myristic acid HA isostearic acid HA ──────────────────────────────────── DMF × × × × DMSO × × × × CH 2 Cl 2 × × × × CCl 4 × × × × Lp-E × × × × D. W. × × × × 0.2M phosphoric acid 1Na ○ × × × 0.2M phosphoric acid 2Na ○ × × × 30% EtOH ○ × × × 80% EtOH ○ × × × EtOH × × × × CIO × × × × n-Hexane × × × × 80% Acetone × × × × Isopar H × × × × ─────────────────────────────────── As described above, the solvent-insolubilized hyaluronic acid according to the present invention is insoluble in any solvent and does not swell.
【００１１】[0011]
【発明の効果】以上説明したように本発明に係る溶媒不
溶化ヒアルロン酸は、温和な条件で各種分子量ヒアルロ
ン酸に脂肪酸残基を高い修飾率で結合させ、ヒアルロン
酸を通常用いられる溶媒に対し、実質的に不溶化するこ
とができる。As described above, the solvent-insolubilized hyaluronic acid according to the present invention binds fatty acid residues to various molecular weight hyaluronic acids at a high modification rate under mild conditions, and hyaluronic acid is usually used in a solvent. It can be substantially insolubilized.
【図１】実施例１にかかるラウリン酸化ヒアルロン酸の
赤外吸収スペクトル図である。FIG. 1 is an infrared absorption spectrum diagram of lauric acid hyaluronic acid according to Example 1.
【図２】実施例２にかかるイソステアリン酸化ヒアルロ
ン酸の赤外吸収スペクトル図である。FIG. 2 is an infrared absorption spectrum diagram of isostearylated hyaluronic acid according to Example 2.
【図３】実施例３にかかるミリスチン酸化ヒアルロン酸
の赤外吸収スぺクトル図である。FIG. 3 is an infrared absorption spectrum diagram of myristin-oxidized hyaluronic acid according to Example 3.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 秋間 和雄 神奈川県横浜市港北区新羽町1050番地 株 式会社資生堂第一リサーチセンター内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kazuo Akima 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Shiseido Daiichi Research Center Co., Ltd.
Claims (2)
化ヒアルロン酸。 【化１】 なお、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炭素数１２以上の脂肪酸残基を
意味し、Ｒ5は水素またはアルカリ金属原子を示す。1. A solvent insolubilized 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 represent hydrogen or an ester-bonded fatty acid residue having 12 or more carbon atoms, and R 5 represents hydrogen or an alkali metal atom.
素数１２以上の脂肪酸を溶解し、これに粉末状ヒアルロ
ン酸を懸濁し、反応させることを特徴とする溶媒不溶化
ヒアルロン酸の製造方法。2. A method for producing solvent-insolubilized hyaluronic acid, which comprises dissolving a fatty acid having 12 or more carbon atoms in a catalyst, trifluoroacetic anhydride, and suspending the powdered hyaluronic acid to react.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5117782A JPH0625306A (en) | 1992-04-21 | 1993-04-20 | Solvent-insoluble hyaluronic acid and its production |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12819992 | 1992-04-21 | ||
| JP4-128199 | 1992-04-21 | ||
| JP5117782A JPH0625306A (en) | 1992-04-21 | 1993-04-20 | Solvent-insoluble hyaluronic acid and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0625306A true JPH0625306A (en) | 1994-02-01 |
Family
ID=26455827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5117782A Withdrawn JPH0625306A (en) | 1992-04-21 | 1993-04-20 | Solvent-insoluble hyaluronic acid and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0625306A (en) |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07309902A (en) * | 1994-05-16 | 1995-11-28 | Seikagaku Kogyo Co Ltd | Production of acylated hyaluronic acid |
| WO1998008876A1 (en) * | 1996-08-29 | 1998-03-05 | Fidia Advanced Biopolymers S.R.L. | Hyaluronic acid esters, threads and biomaterials containing them, and their use in surgery |
| JP2001329002A (en) * | 2000-05-25 | 2001-11-27 | Denki Kagaku Kogyo Kk | Modified hyaluronic acid gel, its preparing method and medical material containing same |
| EP1401876B1 (en) * | 2001-06-04 | 2006-04-05 | Eurand Pharmaceuticals Ltd. | New derivatives of hyaluronan |
| 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 |
| WO2014082611A1 (en) * | 2012-11-27 | 2014-06-05 | Condipro Biotech S.R.O. | Fibres based on hydrophobized derivatives of hyaluronan, method of their preparation and use, textiles on base thereof and use thereof |
| JP2016500130A (en) * | 2012-11-27 | 2016-01-07 | コンティプロ ビオテック スポレチノスト エス ルチェニム オメゼニム | C6-C18-acylated derivative of hyaluronic acid and process for its preparation, nanomicelle composition based on it and process for its preparation, process for preparing stabilized nanomicelle composition and use thereof |
| US9403918B2 (en) | 2009-12-11 | 2016-08-02 | Contipro Pharma A.S. | Oxidized derivative of hyaluronic acid, a method of preparation thereof and a method of modification thereof |
| US9434791B2 (en) | 2009-12-11 | 2016-09-06 | Contipro Pharma A.S. | Method of preparation of an oxidized derivative of hyaluronic acid and a method of modification thereof |
| JP2016163695A (en) * | 2015-02-27 | 2016-09-08 | 大日精化工業株式会社 | Method for producing medical material, medical material, and adhesion preventive material |
| US9492586B2 (en) | 2012-02-28 | 2016-11-15 | Contipro Biotech S.R.O. | Derivatives of hyaluronic acid capable of forming hydrogels |
| CZ306354B6 (en) * | 2015-10-09 | 2016-12-14 | Contipro A.S. | Endless fibers of the core-shell type comprising combination of native and C11-C18 acylated hyaluronate or C11-C18 acylated hyaluronates, process of their preparation and use, staple, yarn and textile from these fibers and their uses |
| US9522966B2 (en) | 2012-08-08 | 2016-12-20 | Contipro Biotech S.R.O. | Hyaluronic acid derivative, method of preparation thereof, method of modification thereof and use thereof |
| US20180105610A1 (en) * | 2015-03-09 | 2018-04-19 | Contipro A.S. | Self-Supporting, Biodegradable Film Based on Hydrophobized Hyaluronic Acid, Method of Preparation and Use Thereof |
| US10023658B2 (en) | 2014-03-11 | 2018-07-17 | Contipro A.S. | Conjugates of oligomer of hyaluronic acid or of a salt thereof, method of preparation thereof and use thereof |
| US10414832B2 (en) | 2015-06-26 | 2019-09-17 | Contipro A.S | Derivatives of sulfated polysaccharides, method of preparation, modification and use thereof |
| US10618984B2 (en) | 2016-06-27 | 2020-04-14 | Contipro A.S. | Unsaturated derivatives of polysaccharides, method of preparation thereof and use thereof |
| US10617711B2 (en) | 2014-06-30 | 2020-04-14 | Contipro A.S. | Antitumor composition based on hyaluronic acid and inorganic nanoparticles, method of preparation thereof and use thereof |
| US10759878B2 (en) | 2015-06-15 | 2020-09-01 | Contipro A.S. | Method of crosslinking of polysaccharides using photoremovable protecting groups |
-
1993
- 1993-04-20 JP JP5117782A patent/JPH0625306A/en not_active Withdrawn
Cited By (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07309902A (en) * | 1994-05-16 | 1995-11-28 | Seikagaku Kogyo Co Ltd | Production of acylated hyaluronic acid |
| WO1998008876A1 (en) * | 1996-08-29 | 1998-03-05 | Fidia Advanced Biopolymers S.R.L. | Hyaluronic acid esters, threads and biomaterials containing them, and their use in surgery |
| JP2001329002A (en) * | 2000-05-25 | 2001-11-27 | Denki Kagaku Kogyo Kk | Modified hyaluronic acid gel, its preparing method and medical material containing same |
| EP1401876B1 (en) * | 2001-06-04 | 2006-04-05 | Eurand Pharmaceuticals Ltd. | New derivatives of hyaluronan |
| JP2006312725A (en) * | 2005-04-05 | 2006-11-16 | Shiseido Co Ltd | Hydroxyalkylated hyaluronic acid |
| US9434791B2 (en) | 2009-12-11 | 2016-09-06 | Contipro Pharma A.S. | Method of preparation of an oxidized derivative of hyaluronic acid and a method of modification thereof |
| US9403918B2 (en) | 2009-12-11 | 2016-08-02 | Contipro Pharma A.S. | Oxidized derivative of hyaluronic acid, a method of preparation thereof and a method of modification thereof |
| KR20120140242A (en) | 2010-02-19 | 2012-12-28 | 큐피가부시키가이샤 | / modified hyaluronic acid and/or salt thereof method for producing same and cosmetic comprising same |
| JP2012021166A (en) * | 2010-02-19 | 2012-02-02 | Q P Corp | Modified hyaluronic acid and/or salt thereof and cosmetic comprising the 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 |
| 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 |
| US9492586B2 (en) | 2012-02-28 | 2016-11-15 | Contipro Biotech S.R.O. | Derivatives of hyaluronic acid capable of forming hydrogels |
| US9522966B2 (en) | 2012-08-08 | 2016-12-20 | Contipro Biotech S.R.O. | Hyaluronic acid derivative, method of preparation thereof, method of modification thereof and use thereof |
| US20150308016A1 (en) * | 2012-11-27 | 2015-10-29 | Contipro Biotech S.R.O. | Fibres Based on Hydrophobized Derivatives of Hyaluronan, Method of Their Preparation and Use, Textiles on Base Thereof and Use Thereof |
| KR20150090167A (en) * | 2012-11-27 | 2015-08-05 | 콘티프로 바이오테크 에스.알.오. | Fibres based on hydrophobized derivatives of hyaluronan, method of their preparation and use, textiles on base thereof and use thereof |
| WO2014082611A1 (en) * | 2012-11-27 | 2014-06-05 | Condipro Biotech S.R.O. | Fibres based on hydrophobized derivatives of hyaluronan, method of their preparation and use, textiles on base thereof and use thereof |
| JP2016500130A (en) * | 2012-11-27 | 2016-01-07 | コンティプロ ビオテック スポレチノスト エス ルチェニム オメゼニム | C6-C18-acylated derivative of hyaluronic acid and process for its preparation, nanomicelle composition based on it and process for its preparation, process for preparing stabilized nanomicelle composition and use thereof |
| US9999678B2 (en) | 2012-11-27 | 2018-06-19 | Contipro A.S. | C6-C18-acylated derivative of hyaluronic acid and method of preparation thereof |
| US10023658B2 (en) | 2014-03-11 | 2018-07-17 | Contipro A.S. | Conjugates of oligomer of hyaluronic acid or of a salt thereof, method of preparation thereof and use thereof |
| US10617711B2 (en) | 2014-06-30 | 2020-04-14 | Contipro A.S. | Antitumor composition based on hyaluronic acid and inorganic nanoparticles, method of preparation thereof and use thereof |
| JP2016163695A (en) * | 2015-02-27 | 2016-09-08 | 大日精化工業株式会社 | Method for producing medical material, medical material, and adhesion preventive material |
| US20180105610A1 (en) * | 2015-03-09 | 2018-04-19 | Contipro A.S. | Self-Supporting, Biodegradable Film Based on Hydrophobized Hyaluronic Acid, Method of Preparation and Use Thereof |
| RU2712174C2 (en) * | 2015-03-09 | 2020-01-24 | Контипро А.С. | Self-sustaining biodegradable film based on hydrophobisated hyaluronic acid, method for production thereof and use thereof |
| US10689464B2 (en) | 2015-03-09 | 2020-06-23 | Contipro A.S. | Self-supporting, biodegradable film based on hydrophobized hyaluronic acid, method of preparation and use thereof |
| US10759878B2 (en) | 2015-06-15 | 2020-09-01 | Contipro A.S. | Method of crosslinking of polysaccharides using photoremovable protecting groups |
| US10414832B2 (en) | 2015-06-26 | 2019-09-17 | Contipro A.S | Derivatives of sulfated polysaccharides, method of preparation, modification and use thereof |
| CZ306354B6 (en) * | 2015-10-09 | 2016-12-14 | Contipro A.S. | Endless fibers of the core-shell type comprising combination of native and C11-C18 acylated hyaluronate or C11-C18 acylated hyaluronates, process of their preparation and use, staple, yarn and textile from these fibers and their uses |
| US10618984B2 (en) | 2016-06-27 | 2020-04-14 | Contipro A.S. | Unsaturated derivatives of polysaccharides, method of preparation thereof and use thereof |
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