JP2997823B2 - Method for producing collagen sponge - Google Patents
Method for producing collagen spongeInfo
- Publication number
- JP2997823B2 JP2997823B2 JP3208388A JP20838891A JP2997823B2 JP 2997823 B2 JP2997823 B2 JP 2997823B2 JP 3208388 A JP3208388 A JP 3208388A JP 20838891 A JP20838891 A JP 20838891A JP 2997823 B2 JP2997823 B2 JP 2997823B2
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- Prior art keywords
- collagen
- sponge
- organic solvent
- collagen sponge
- solution
- 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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- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
Description
【産業上の利用分野】本発明は、コラーゲン溶液を凍結
乾燥するコラーゲンスポンジの製造方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a collagen sponge by freeze-drying a collagen solution.
【従来の技術及びその課題】コラーゲンスポンジを、人
工皮膚として患部に埋植すると、その多孔質の構造によ
り線維芽細胞の増殖に適した無数の孔（空間）を提供
し、線維芽細胞の増殖を助けることで患部の治癒を促進
する作用を有する。コラーゲンスポンジの線維芽細胞の
増殖促進作用は、そのポアーサイズにより左右され、線
維芽細胞が容易に侵入し、組織の再構築を行うのに最適
の大きさの範囲が鈴木らにより報告されている（鈴木
ら，日形会誌，６，２２１−２３１，１９８６）。ま
た、一般にコラーゲンスポンジのポアーサイズは均一で
あるのが線維芽細胞の高い増殖促進作用を得るために望
ましい。このように有用な性質を有するコラーゲンスポ
ンジの製造は、従来コラーゲン溶液を直接あるいはゲル
化させた後、真空凍結乾燥することにより行うのが一般
的であった。しかし、この真空凍結乾燥法は簡単ではあ
るが、コラーゲンスポンジのポアーサイズ及びその均一
性に難点があるため、均一且つ適切なポアーサイズを有
するコラーゲンスポンジの製造方法が盛んに研究されて
いる。このような研究の一例として、コラーゲン溶液を
ホモジナイザーで発泡させた後、真空凍結乾燥を行う方
法を提案している。しかし、この方法によれば、均一な
ポアーサイズを有するコラーゲンスポンジを製造するた
めにはコラーゲン溶液を長時間ホモジナイズする必要が
あり、コラーゲンスポンジを効率的に製造することが困
難であった。特に、大量のコラーゲンスポンジを製造す
る場合には溶液を均一にホモジナイズする必要があり、
均一且つ一定範囲のポアーサイズを有するコラーゲンス
ポンジを製造するのはより一層困難であった。さらに他
の例として、コラーゲン溶液に水と相溶性のある有機溶
媒を添加する方法が提案されている（特開平２−２６５
９３５号公報参照）。しかし、水と相溶性のある有機溶
媒を添加するだけではポアーサイズのバラツキは依然と
して大きく、人工皮膚に適用されるコラーゲンスポンジ
として未だ実用的なものとはいえなかった。本発明は、
均一且つ適当な範囲のポアーサイズを有するコラーゲン
スポンジをより短時間で簡単に製造する方法を提供する
ことにある。2. Description of the Related Art When a collagen sponge is implanted as an artificial skin in an affected area, its porous structure provides a myriad of pores (spaces) suitable for fibroblast proliferation, and fibroblast proliferation. Has the effect of promoting the healing of the affected area. Suzuki et al. Reported that the collagen sponge's fibroblast proliferation-promoting effect depends on its pore size, and the optimal size range for fibroblasts to easily invade and reconstruct tissue ( Suzuki et al., Journal of the Nikkei Association, 6 , 221-231, 1986). In general, it is preferable that the pore size of the collagen sponge is uniform in order to obtain a high fibroblast growth promoting action. Collagen sponges having such useful properties have conventionally been generally produced by directly or gelling a collagen solution and then freeze-drying in a vacuum. However, although this vacuum freeze-drying method is simple, there are difficulties in the pore size of the collagen sponge and its uniformity. Therefore, a method for producing a collagen sponge having a uniform and appropriate pore size has been actively studied. As an example of such a study, a method in which a collagen solution is foamed with a homogenizer and then freeze-dried in a vacuum is proposed. However, according to this method, it is necessary to homogenize the collagen solution for a long time in order to produce a collagen sponge having a uniform pore size, and it has been difficult to efficiently produce a collagen sponge. In particular, when producing a large amount of collagen sponge, it is necessary to homogenize the solution uniformly,
It has been even more difficult to produce collagen sponges having a uniform and consistent range of pore sizes. As still another example, a method of adding an organic solvent compatible with water to a collagen solution has been proposed (Japanese Patent Laid-Open No. 2-265).
No. 935). However, the variation in pore size is still large only by adding an organic solvent compatible with water, and it has not yet been practical as a collagen sponge applied to artificial skin. The present invention
It is an object of the present invention to provide a method for easily and quickly producing a collagen sponge having a uniform and appropriate range of pore sizes.
【課題を解決するための手段】本発明者は、上記目的を
達成するため鋭意検討を重ねた結果、コラーゲン溶液に
脂溶性の有機溶媒を添加することによりコラーゲン溶液
の発泡を容易に行えることを見出し、本発明を完成し
た。即ち、本発明は、コラーゲン溶液を凍結乾燥するコ
ラーゲンスポンジの製造方法において、コラーゲン溶液
に脂溶性有機溶媒を添加し、ホモジナイズして発泡させ
ることを特徴するコラーゲンスポンジの製造方法を提供
するものである。本発明で使用されるコラーゲン溶液
は、従来のコラーゲンスポンジの原料が広く使用でき、
具体的には酸可溶性コラーゲン溶液、中性塩可溶性コラ
ーゲン溶液、酵素可溶化コラーゲン溶液などの可溶性コ
ラーゲン溶液、天然の又は化学修飾されたコラーゲン繊
維分散液、可溶性コラーゲンを不溶化した再生コラーゲ
ン繊維分散液などが挙げられる。コラーゲン繊維分散液
は酸、酵素などを用いることによりコラーゲンを溶解し
て使用する。本発明で使用されるコラーゲン溶液の濃度
は、コラーゲンスポンジの用途、脂溶性有機溶媒の種類
及び量により異なるが、脂溶性有機溶媒を加える前の状
態で好ましくは０．１〜０．５重量％であるのが良い。
上記のコラーゲンの処理は、変性温度以下で行う必要が
あるが、氷冷下で行うのが適当である。本発明で使用さ
れる脂溶性有機溶媒とは、水と混合すると２層に分離す
る性質を有する有機溶媒を意味し、具体的にはクロロホ
ルム、四塩化炭素、塩化メチレンなどのハロゲン化炭化
水素、酢酸エチル、プロピオン酸エチルなどのエステル
類、ベンゼン、トルエンなどの芳香族炭化水素類、ヘキ
サン、シクロヘキサン、などの脂肪族炭化水素類、ジエ
チルエーテル、ジイソプロピルエーテルなどのエーテル
類などが挙げられ、好ましくは、クロロホルム、四塩化
炭素、塩化メチレンなどのハロゲン化炭化水素が良い。
また、本発明では、これらの有機溶媒を２種以上組み合
わせて使用することもできる。本発明の有機溶媒は、揮
発性の溶媒であるのが後の凍結乾燥工程で除去できるた
め好ましい。また、本発明の脂溶性有機溶媒には水と混
合したときに２層に分離する範囲内でアルコール、アセ
トン等の水溶性の有機溶媒を加えることもできる。脂溶
性有機溶媒の添加量は、通常はコラーゲン溶液の全体量
に対し２．０重量％以上使用され、例えばクロロホルム
の場合には２．５〜１０重量％使用するのが良い。有機
溶媒の添加量が２．０重量％未満であると発泡時間を短
縮するという本発明の効果が得られないため好ましくな
い。また、有機溶媒の添加量が２．０重量％以上であれ
ば、発泡時間を短縮させる本発明の効果は添加量により
ほとんど左右されない。有機溶媒を添加したコラーゲン
溶液のホモジナイズは、通常のホモジナイザーを用いて
行うことができる。コラーゲン溶液を十分に発泡させる
ために必要なホモジナイズ時間は、用いた有機溶媒によ
っても異なるが、例えば６０００ｒｐｍで５分以上であ
るのが良い。ホモジナイズにより発泡させた後のコラー
ゲン溶液の凍結乾燥は常法に従い行うことができ、例え
ば、凍結するときの温度は−２０〜−６５℃である。本
発明のコラーゲン溶液には、脂溶性有機溶媒の他にコラ
ーゲンスポンジを製造する技術分野において通常使用さ
れている各種の添加剤を使用することもできる。このよ
うな添加剤としては、ヒアルロン酸、デルマタン硫酸、
コンドロイチン６−硫酸などのムコ多糖類等が挙げられ
る。Means for Solving the Problems The present inventors have made intensive studies to achieve the above object, and as a result, have found that by adding a fat-soluble organic solvent to a collagen solution, the collagen solution can be easily foamed. Heading, the present invention has been completed. That is, the present invention provides a method for producing a collagen sponge, which comprises freeze-drying a collagen solution, adding a fat-soluble organic solvent to the collagen solution, homogenizing and foaming the collagen solution. . The collagen solution used in the present invention can be widely used for conventional collagen sponge raw materials,
Specifically, a soluble collagen solution such as an acid-soluble collagen solution, a neutral salt-soluble collagen solution, an enzyme-solubilized collagen solution, a natural or chemically modified collagen fiber dispersion, a regenerated collagen fiber dispersion in which soluble collagen is insolubilized, etc. Is mentioned. The collagen fiber dispersion is used by dissolving collagen by using an acid, an enzyme or the like. The concentration of the collagen solution used in the present invention varies depending on the use of the collagen sponge, the type and amount of the fat-soluble organic solvent, but is preferably 0.1 to 0.5% by weight before adding the fat-soluble organic solvent. It is good.
The above collagen treatment needs to be performed at a denaturing temperature or lower, but is suitably performed under ice cooling. The fat-soluble organic solvent used in the present invention means an organic solvent having a property of separating into two layers when mixed with water, specifically, chloroform, carbon tetrachloride, halogenated hydrocarbons such as methylene chloride, Ethyl acetate, esters such as ethyl propionate, benzene, aromatic hydrocarbons such as toluene, hexane, cyclohexane, aliphatic hydrocarbons such as, diethyl ether, ethers such as diisopropyl ether and the like, preferably Halogenated hydrocarbons such as, chloroform, carbon tetrachloride and methylene chloride are preferred.
In the present invention, two or more of these organic solvents can be used in combination. The organic solvent of the present invention is preferably a volatile solvent because it can be removed in the subsequent freeze-drying step. Further, to the fat-soluble organic solvent of the present invention, a water-soluble organic solvent such as alcohol and acetone can be added within a range that separates into two layers when mixed with water. The amount of the fat-soluble organic solvent to be added is usually 2.0% by weight or more based on the total amount of the collagen solution. If the amount of the organic solvent is less than 2.0% by weight, the effect of the present invention of shortening the foaming time cannot be obtained, which is not preferable. When the amount of the organic solvent added is 2.0% by weight or more, the effect of the present invention for shortening the foaming time is hardly influenced by the amount added. Homogenization of the collagen solution to which an organic solvent has been added can be performed using a conventional homogenizer. The homogenization time required to sufficiently foam the collagen solution varies depending on the organic solvent used, but is preferably, for example, 5 minutes or more at 6000 rpm. Freeze-drying of the collagen solution after foaming by homogenization can be performed according to a conventional method. For example, the temperature at the time of freezing is −20 to −65 ° C. In the collagen solution of the present invention, in addition to the fat-soluble organic solvent, various additives commonly used in the technical field of producing a collagen sponge can also be used. Such additives include hyaluronic acid, dermatan sulfate,
And mucopolysaccharides such as chondroitin 6-sulfate.
【発明の効果】本発明の方法によれば、コラーゲン溶液
の発泡を短時間で行うことができ、これにより均一なポ
アーサイズを有するコラーゲンスポンジをより実用的な
方法で製造することができるようになった。本発明の方
法により製造されたコラーゲンスポンジは、ポアーサイ
ズが均一であるため人工皮膚としても有用であるが、そ
の他の線維芽細胞の増殖を必要とする治療材料としても
好適に使用できる。According to the method of the present invention, foaming of a collagen solution can be carried out in a short time, whereby a collagen sponge having a uniform pore size can be produced by a more practical method. Was. The collagen sponge produced by the method of the present invention is useful as an artificial skin because of its uniform pore size, but can also be suitably used as a therapeutic material that requires proliferation of fibroblasts.
【実施例】以下、本発明を実施例及び比較例を用いてよ
り詳細に説明する。The present invention will be described below in more detail with reference to examples and comparative examples.
【実施例１】アテロコラーゲン（商標名、新田ゼラチン
株式会社製）を原料とし、精製水及び１Ｎ−塩酸を用い
て濃度３ｍｇ／ｍｌ、ｐＨ ３．０のコラーゲン溶液を
調製した。この溶液５０ｇにクロロホルム０．５ｇを添
加し、エクセルオートホモジナイザー（商標名、日本精
機社製）を用い、６０００ｒｐｍで１分間ホモジナイズ
した。得られたクリーム状の発泡液を凍結乾燥用のステ
ンレス製枠（１１ｃｍ×８．５ｃｍ）内に流し込んだ。
ステンレス製枠を−４０℃に冷却してコラーゲン発泡液
を凍結し、真空減圧下（０．０１ｍｍＨｇ）３０℃で２
４時間凍結乾燥を行った。さらに真空減圧下（０．０１
ｍｍＨｇ）１０５℃で２４時間加熱乾燥を行い、コラー
ゲンスポンジを得た。得られたコラーゲンスポンジにシ
リコーン１００μｍを貼付し、０．２重量％のグルタル
アルデヒド／酢酸溶液中、５℃で、２４時間架橋反応を
行った。得られた架橋スポンジをイオン交換水で十分洗
浄し、以下の動物実験に供した。次に、クロロホルムの
添加量を０．５ｇ、１．２５ｇ、２．５ｇ又は５．０ｇ
に変化させ、その各々のクロロホルム添加量に対しホモ
ジナイズ時間を１分、５分、１０分および１５分に変化
（ただし、クロロホルムの添加量が０．５ｇ且つホモジ
ナイズ時間が１分の場合を除く）させた他は上記と同様
にして、さらに１５種類のコラーゲンスポンジ及び架橋
スポンジを各々得た。Example 1 A collagen solution having a concentration of 3 mg / ml and a pH of 3.0 was prepared from atelocollagen (trade name, manufactured by Nitta Gelatin Co., Ltd.) using purified water and 1N hydrochloric acid. 0.5 g of chloroform was added to 50 g of this solution, and the mixture was homogenized at 6000 rpm for 1 minute using an Excel Auto Homogenizer (trade name, manufactured by Nippon Seiki Co., Ltd.). The obtained creamy foaming liquid was poured into a stainless steel frame (11 cm × 8.5 cm) for freeze-drying.
The stainless steel frame was cooled to −40 ° C. to freeze the collagen foam solution, and the solution was heated at 30 ° C. under vacuum and reduced pressure (0.01 mmHg).
Lyophilization was performed for 4 hours. Further, under vacuum and reduced pressure (0.01
mmHg) Heat drying was performed at 105 ° C for 24 hours to obtain a collagen sponge. 100 μm of silicone was stuck to the obtained collagen sponge, and a crosslinking reaction was performed in a 0.2% by weight glutaraldehyde / acetic acid solution at 5 ° C. for 24 hours. The obtained crosslinked sponge was sufficiently washed with ion-exchanged water and subjected to the following animal experiments. Next, the amount of chloroform added was 0.5 g, 1.25 g, 2.5 g or 5.0 g.
And the homogenization time is changed to 1 minute, 5 minutes, 10 minutes and 15 minutes for each amount of chloroform added (except when the amount of chloroform added is 0.5 g and the homogenization time is 1 minute). Other than the above, 15 types of collagen sponge and cross-linked sponge were obtained in the same manner as above.
【比較例１】クロロホルムの添加量を０ｇとし、ホモジ
ナイズ時間を０分、１分、５分、１０分、１５分および
６０分に各々変化させた他は上記実施例１と同様の操作
を行い、比較例として５種類のコラーゲンスポンジ及び
架橋スポンジを各々得た。Comparative Example 1 The same operation as in Example 1 was performed except that the amount of chloroform added was 0 g and the homogenization time was changed to 0 minute, 1 minute, 5 minutes, 10 minutes, 15 minutes and 60 minutes, respectively. As a comparative example, five types of collagen sponge and cross-linked sponge were obtained.
【評価】上記実施例１及び比較例１により得られたコラ
ーゲンスポンジについて、ポアーサイズ及び生理食塩水
への浸漬後の体積変化率を測定した。また、上記実施例
１及び比較例１により得られた架橋スポンジについて人
工皮膚の効果を確認するため動物実験を行った。なお、
上記実施例及び比較例は各々５回ずつ繰り返し、その測
定も５回ずつ行った。ポアーサイズの測定 上記実施例（１６種類）及び比較例（５種類）で得たコ
ラーゲンスポンジの各５個の検体について、走査型電子
顕微鏡（日本電子株式会社製、倍率：１５０倍）を用い
て写真撮影し、その写真からポアーの直径を測定した。
ポアーの直径は、（長径＋短径）／２として計算し、結
果は、平均値±標準偏差として表した。体積変化率の測定 上記実施例（１６種類）及び比較例（５種類）で得たコ
ラーゲンスポンジの各５個の検体の厚みをまず測定し
た。次に、各コラーゲンスポンジを各々生理食塩水に３
０分間浸漬し、ステンレス製の板に載せて１０分間放置
後、コラーゲンスポンジの厚みを測定した。生理食塩水
に浸漬する前と後のコラーゲンスポンジの厚みの測定値
から、体積変化率を次式に従い計算した。 体積変化率＝（浸漬後の厚み）／（浸漬前の厚み）×１
００ この体積変化率の値は、１００に近いほどしっかりした
構造のスポンジであることを表す。測定結果は、平均値
±標準偏差として表した。ポアーサイズ及び体積変化率
の測定結果を表１に示す。表中、上段はポアーの直径
（μｍ）を示し、下段は体積変化率（％）を表す。ま
た、各測定結果は同一の実験条件における５個の検体の
各測定値から平均値と標準偏差を計算し、その値を示し
た。[Evaluation] With respect to the collagen sponges obtained in Example 1 and Comparative Example 1, the pore size and the rate of change in volume after immersion in physiological saline were measured. In addition, animal experiments were performed on the crosslinked sponges obtained in Example 1 and Comparative Example 1 in order to confirm the effect of artificial skin. In addition,
The above Examples and Comparative Examples were each repeated five times, and the measurement was also performed five times. Measurement of Pore Size Photographs of five specimens of the collagen sponges obtained in the above Examples (16 types) and Comparative Examples (5 types) were taken with a scanning electron microscope (manufactured by JEOL Ltd., magnification: 150 times). The diameter of the pore was measured from the photograph.
The diameter of the pore was calculated as (major axis + minor axis) / 2, and the results were expressed as mean ± standard deviation. Measurement of Volume Change Rate The thickness of each of the five specimens of the collagen sponges obtained in the above Examples (16 types) and Comparative Examples (5 types) was first measured. Next, each collagen sponge was placed in physiological saline for 3 times.
It was immersed for 0 minutes, placed on a stainless steel plate and left for 10 minutes, and then the thickness of the collagen sponge was measured. From the measured values of the thickness of the collagen sponge before and after immersion in physiological saline, the volume change rate was calculated according to the following equation. Volume change rate = (thickness after immersion) / (thickness before immersion) × 1
00 The value of the volume change rate is closer to 100, indicating that the sponge has a firmer structure. The measurement results were expressed as mean ± standard deviation. Table 1 shows the measurement results of the pore size and the volume change rate. In the table, the upper row shows the pore diameter (μm), and the lower row shows the volume change rate (%). For each measurement result, an average value and a standard deviation were calculated from each measurement value of five specimens under the same experimental conditions, and the values were shown.
【表１】 動物実験 上記実施例（１６種類）及び比較例（５種類）で得た架
橋スポンジの各５個の検体を、モルモットの背部に作成
した、皮下筋層を残存した全層皮膚欠損創（１．５×
１．５ｃｍ）に埋入し、３週間真皮様組織の再生を観察
した。また、埋入部の組織切片より架橋スポンジ内にお
ける線維芽細胞の侵入の程度についても調べた。真皮様
組織の再生は、ポアーの直径が８０〜９５μｍの範囲内
にある場合に特に良い結果が得られ、このことと表１の
結果から、クロロホルム添加量が１．２５ｇ以上且つホ
モジナイズ時間が５分以上（回転数：６０００ｒｐｍ）
の場合には良好な品質のスポンジが得られることが確認
された。また、この条件下では、ポアーサイズのバラツ
キも少ないものであった。さらに、この範囲のスポンジ
の体積変化率は１００に近く、人工皮膚として必要十分
な強度を有していることも明かとなった。クロロホルム
を全く添加しない場合、上記の好ましいポアーの直径を
得るために６０分間程度ホモジナイズする必要があり、
本発明の方法により必要なホモジナイズ時間が大幅に短
縮されることが明らかとなった。[Table 1] Animal Experiment Five specimens of the crosslinked sponges obtained in the above Examples (16 types) and Comparative Examples (5 types) were prepared on the back of a guinea pig, and a full-thickness skin defect wound (1. 5x
1.5 cm), and regeneration of the dermis-like tissue was observed for 3 weeks. In addition, the degree of invasion of fibroblasts into the crosslinked sponge from the tissue section of the implanted part was also examined. Regeneration of the dermis-like tissue gave particularly good results when the pore diameter was in the range of 80 to 95 μm. From this and the results in Table 1, it was found that the amount of chloroform added was 1.25 g or more and the homogenization time was 5 hours. Min. (Rotation speed: 6000 rpm)
It was confirmed that sponge of good quality was obtained in the case of. Also, under these conditions, the variation in pore size was small. Furthermore, the volume change rate of the sponge in this range was close to 100, and it became clear that the sponge had sufficient strength as an artificial skin. If no chloroform is added, it is necessary to homogenize for about 60 minutes to obtain the preferred pore diameter described above,
It has been found that the required homogenization time is significantly reduced by the method of the present invention.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平１−4629（ＪＰ，Ａ) 特開 昭55−82621（ＪＰ，Ａ) 特開 平１−11141（ＪＰ，Ａ) 特開 昭62−169837（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) C08J 9/00 - 9/42 A61L 27/00 ──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A 1-4629 (JP, A) JP-A 55-82621 (JP, A) JP-A 1-111141 (JP, A) JP-A 62 169837 (JP, A) (58) Fields investigated (Int. Cl. 7 , DB name) C08J 9/00-9/42 A61L 27/00
Claims (2)
スポンジの製造方法において、コラーゲン溶液に脂溶性
有機溶媒を添加し、ホモジナイズして発泡させることを
特徴とするコラーゲンスポンジの製造方法。1. A method for producing a collagen sponge, wherein a collagen solution is freeze-dried, wherein a fat-soluble organic solvent is added to the collagen solution, homogenized and foamed.
に対し、２．５〜１０重量％使用する請求項１に記載の
製造方法。2. The method according to claim 1, wherein the fat-soluble organic solvent is used in an amount of 2.5 to 10% by weight based on the total amount of the collagen solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3208388A JP2997823B2 (en) | 1991-08-21 | 1991-08-21 | Method for producing collagen sponge |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3208388A JP2997823B2 (en) | 1991-08-21 | 1991-08-21 | Method for producing collagen sponge |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0543734A JPH0543734A (en) | 1993-02-23 |
| JP2997823B2 true JP2997823B2 (en) | 2000-01-11 |
Family
ID=16555440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3208388A Expired - Lifetime JP2997823B2 (en) | 1991-08-21 | 1991-08-21 | Method for producing collagen sponge |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2997823B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010110067A1 (en) | 2009-03-27 | 2010-09-30 | 株式会社マルハニチロ食品 | Crosslinked material comprising elastin and collagen, and use thereof |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3871525B2 (en) * | 2001-04-26 | 2007-01-24 | ニプロ株式会社 | Biological tissue or organ regeneration device |
| JP4757413B2 (en) * | 2001-09-11 | 2011-08-24 | 株式会社高研 | Sponge made of sea cucumber or starfish collagen and method for producing the same |
| GB2399084B (en) * | 2002-07-30 | 2007-01-31 | Univ Liverpool | Porous beads and method of production thereof |
| JP2007050263A (en) * | 2006-08-23 | 2007-03-01 | Nipro Corp | Apparatus for reproducing biological tissue or organ |
| JP2016163538A (en) * | 2015-02-26 | 2016-09-05 | 株式会社日立製作所 | Inverter for factor of utilization of direct (dc) bus and method thereof |
| US11559603B2 (en) | 2016-12-28 | 2023-01-24 | Koken Co., Ltd. | High-strength collagen sponge |
| CN117695442A (en) * | 2023-12-27 | 2024-03-15 | 杭州倍朗生物科技有限公司 | Sterile collagen foam material and preparation method and application thereof |
-
1991
- 1991-08-21 JP JP3208388A patent/JP2997823B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010110067A1 (en) | 2009-03-27 | 2010-09-30 | 株式会社マルハニチロ食品 | Crosslinked material comprising elastin and collagen, and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0543734A (en) | 1993-02-23 |
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