JPH06304240A - Collagen film - Google Patents
Collagen filmInfo
- Publication number
- JPH06304240A JPH06304240A JP5117561A JP11756193A JPH06304240A JP H06304240 A JPH06304240 A JP H06304240A JP 5117561 A JP5117561 A JP 5117561A JP 11756193 A JP11756193 A JP 11756193A JP H06304240 A JPH06304240 A JP H06304240A
- Authority
- JP
- Japan
- Prior art keywords
- collagen
- film
- calcium
- collagen film
- hydroxyapatite
- 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.)
- Pending
Links
- 102000008186 Collagen Human genes 0.000 title claims abstract description 74
- 108010035532 Collagen Proteins 0.000 title claims abstract description 74
- 229920001436 collagen Polymers 0.000 title claims abstract description 74
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 22
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011575 calcium Substances 0.000 claims abstract description 13
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 13
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 239000001506 calcium phosphate Substances 0.000 claims description 25
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical group [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 25
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 24
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical group [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 24
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 24
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 24
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 24
- 239000012528 membrane Substances 0.000 claims description 10
- 239000000835 fiber Substances 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 abstract description 6
- 102000004169 proteins and genes Human genes 0.000 abstract description 4
- 108090000623 proteins and genes Proteins 0.000 abstract description 4
- 239000012744 reinforcing agent Substances 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract 2
- 230000008929 regeneration Effects 0.000 abstract 1
- 238000011069 regeneration method Methods 0.000 abstract 1
- 239000012763 reinforcing filler Substances 0.000 abstract 1
- 102000013373 fibrillar collagen Human genes 0.000 description 12
- 108060002894 fibrillar collagen Proteins 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 6
- 102000057297 Pepsin A Human genes 0.000 description 5
- 108090000284 Pepsin A Proteins 0.000 description 5
- 239000000512 collagen gel Substances 0.000 description 5
- 229940111202 pepsin Drugs 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000034656 Contusions Diseases 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 108010025899 gelatin film Proteins 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZZPYUKWXDLMGI-UHFFFAOYSA-N 1,6-diisothiocyanatohexane Chemical compound S=C=NCCCCCCN=C=S VZZPYUKWXDLMGI-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- -1 hormonal agents Substances 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、火傷、熱傷、擦過傷、
挫傷などの治療に使用する被覆材に関し、生体親和性を
保持し、かつ引張り強度の高いコラーゲン膜に関するも
のである。BACKGROUND OF THE INVENTION The present invention relates to burns, burns, abrasions,
The present invention relates to a coating material used for treatment of bruises and the like, and relates to a collagen film which maintains biocompatibility and has high tensile strength.
【０００２】[0002]
【従来の技術】コラーゲン膜は火傷、熱傷、擦過傷、挫
傷などの治療に用いるため、シート状やスポンジ状に加
工され、薬剤と共に使用されている。しかし膜の引張り
強度が弱いため伸縮性に乏しく取り扱いにくいので、広
範囲の用途に普及していないのが現状と云える。このた
め、特開昭５６−１０９５８５号公報は、架橋材を使用
して膜の強度を充分維持する方法を、特公昭５８−４１
０５４号公報は、合成高分子材料にコラーゲン膜層を被
覆させた材料を、特公昭５８−５２６６２号公報は、コ
ラーゲンの分散ゲルを通気性の基布に付着させた基材を
開示している。又本出願人も「強化コラーゲン線維膜及
びその調製法」（特願平３−２９２０００号）で、ペプ
シン処理コラーゲンを精製してえた精製コラーゲンをコ
ラーゲン再構成化を行い、架橋材により架橋することに
より強化コラーゲン線維膜をえる方法を開示した。2. Description of the Related Art Collagen membranes are used for treatment of burns, burns, abrasions, bruises, etc., so that they are processed into sheets or sponges and used together with drugs. However, since the tensile strength of the film is weak and the film has poor elasticity and is difficult to handle, it is said that it is not widely used in a wide range of applications. Therefore, JP-A-56-109585 discloses a method of using a cross-linking material to sufficiently maintain the strength of the film.
Japanese Patent Publication No. 054 discloses a material in which a collagen membrane layer is coated with a synthetic polymer material, and Japanese Patent Publication No. 58-52662 discloses a base material in which a collagen dispersion gel is attached to a breathable base cloth. . In addition, the applicant of the present invention also "reinforces collagen fibrous membrane and its preparation method" (Japanese Patent Application No. 3-292000) to reconstitute the purified collagen obtained by purifying pepsin-treated collagen and crosslink it with a crosslinking agent. Disclosed a method for obtaining a reinforced collagen fiber membrane.
【０００３】上記のように、コラーゲン膜はその強度が
弱いため強度の高い他の基材との複合膜として多く用い
られている。それらは強度的には問題はないが、基材と
コラーゲンとが均質に密着したものをえることがむつか
しく、加えて架橋処理などの特殊な工程を必要としてい
る。又コラーゲンのみを架橋して強化コラーゲン膜をえ
ることも提案されているが、その強度は充分に高いとは
云いがたい。一方コラーゲン膜を人工皮膚として、或は
体内に埋込んで使用する場合などには、最終的にコラー
ゲン以外の基材を取出して排除する必要がある。従って
強度が高くコラーゲンだけで、或は生体親和性が良く取
出して排除する必要のない成分とコラーゲンとより作ら
れた膜の開発が望まれる。As described above, the collagen film is often used as a composite film with another substrate having high strength because of its weak strength. Although they have no problem in strength, it is difficult to obtain a material in which the base material and collagen are intimately adhered to each other, and in addition, a special process such as crosslinking treatment is required. It has also been proposed to crosslink only collagen to obtain a reinforced collagen film, but it cannot be said that its strength is sufficiently high. On the other hand, when the collagen film is used as artificial skin or when it is used by being embedded in the body, it is necessary to finally take out and remove the base material other than collagen. Therefore, it is desired to develop a membrane made of collagen which has high strength and collagen alone, or which has good biocompatibility and does not need to be taken out and eliminated.
【０００４】[0004]
【発明が解決しようとする課題】本発明は強度が高く人
工皮膚として、或は体内に埋込んで使用する場合にも上
記のような問題を生じることがなく、安全に使用でき、
かつ簡単に製造できるコラーゲン膜を提供することを課
題としている。The present invention has a high strength and can be safely used as artificial skin or when it is used by being implanted in the body without causing the above problems.
Another object is to provide a collagen film that can be easily manufactured.
【０００５】[0005]
【課題を解決するための手段】上記のようなコラーゲン
膜を研究した結果、リン酸及びカルシウムよりなる化合
物をコラーゲン中に配合することにより、安全で引張り
強度の強いコラーゲン膜がえられることを認めた。[Means for Solving the Problems] As a result of studying the above collagen film, it was confirmed that a collagen film having a safe and high tensile strength can be obtained by incorporating a compound consisting of phosphoric acid and calcium into collagen. It was
【０００６】リン酸及びカルシウムよりなる化合物、特
に骨伝導能をもつリン酸３カルシウム及びハイドロキシ
アパタイト、は生体親和性がよく、従来からカルシウム
補強剤又は骨充填剤として生体に無害に使用されている
物質であり、蛋白質との親和性も良好であるので、リン
酸３カルシウムやハイドロキシアパタイトを均質にコラ
ーゲンに分散させたコラーゲン膜が容易にえられる。Compounds composed of phosphoric acid and calcium, particularly tricalcium phosphate and osteopatite, which have osteoconductivity, have good biocompatibility and have been conventionally used harmless to the living body as a calcium reinforcing agent or bone filler. Since it is a substance and has a good affinity with proteins, a collagen film in which tricalcium phosphate and hydroxyapatite are uniformly dispersed in collagen can be easily obtained.
【０００７】コラーゲンとしては、通常使用されている
ゲル状コラーゲン、線維状コラーゲン、及びそれらより
形成されたコラーゲン膜いずれでも使用できる。コラー
ゲンは元来、抗原性の低い蛋白質であるが、その種によ
っては抗原性を示すことがあるので限定ペプシン消化法
により処理してえられる免疫原性のないペプシン処理コ
ラーゲンを使用することが好ましい。As the collagen, any of commonly used gel-like collagen, fibrillar collagen, and collagen film formed from them can be used. Collagen is originally a protein with low antigenicity, but depending on its species, it may show antigenicity, so it is preferable to use non-immunogenic pepsin-treated collagen obtained by treatment with the limited pepsin digestion method. .
【０００８】例えばコウシの皮膚から真皮を常法により
分離し、液体窒素法にて粉砕し、0.０２Ｍ Na2HPO4、次
いで4.０Ｍ NaCl で充分洗浄してえられた微粒真皮を２
０℃でペプシン限定消化法によって可溶化し、ペプシン
可溶化コラーゲンを0.０２ＭNa2HPO4溶液に透析してコ
ラーゲンを沈殿として分離する。分離したコラーゲン、
或はそれを更に0.５Ｍ酢酸に溶解し、これを0.７Ｍ NaC
l を含む0.５Ｍ酢酸に透析して生成した高純度のコラー
ゲンを0.０５〜0.１％の濃度になるよう0.５Ｍ酢酸に溶
解し、４℃にて0.１５Ｍ NaCl を含むpH7.４の0.０１Ｍ
−リン酸緩衝液に透析する。完全に透析が終了したとこ
ろで、この溶液を４℃で、0.０２Ｍ Na2HPO4に透析し
て、天然型の太いコラーゲン線維をえ、更にこの線維を
0.０２Ｍ Na2HPO4でよく洗浄する。このコラーゲン線維
をヘキサメチレンイソチオシアネート又はグルタルアル
デヒドのような架橋材で常法により処理して架橋強化し
た線維状コラーゲンをえる。For example, the dermis is separated from the skin of calf by a conventional method, crushed by the liquid nitrogen method, thoroughly washed with 0.02M Na 2 HPO 4 , and then 4.0M NaCl to obtain 2 fine dermis.
It is solubilized by pepsin limited digestion method at 0 ° C., and pepsin-solubilized collagen is dialyzed against 0.02M Na 2 HPO 4 solution to separate collagen as a precipitate. Collagen isolated,
Alternatively, it is further dissolved in 0.5M acetic acid, and this is dissolved in 0.7M NaC.
High-purity collagen produced by dialysis against 0.5 M acetic acid containing 1 L was dissolved in 0.5 M acetic acid to a concentration of 0.05 to 0.1%, and pH was adjusted to pH 7 containing 0.15 M NaCl at 4 ° C. .4 of 0.01M
-Dialysis into phosphate buffer. When the dialysis was completed, the solution was dialyzed against 0.02M Na 2 HPO 4 at 4 ℃ to obtain natural thick collagen fibrils,
Wash well with 0.02M Na 2 HPO 4 . This collagen fiber is treated with a cross-linking material such as hexamethylene isothiocyanate or glutaraldehyde by a conventional method to obtain cross-link-reinforced fibrillar collagen.
【０００９】上記の線維状コラーゲンを蒸留水または緩
衝液中に懸濁させ、微細に粉砕されたリン酸３カルシウ
ム又はハイドロキシアパタイトを添加し、激しく攪拌し
て線維状コラーゲンに充分担持させる。ハイドロキシア
パタイトやリン酸３カルシウムは前記した如く蛋白質と
の親和性が良好であるので、この操作によりこれらの物
質は線維状コラーゲンに強く担持され、線維状コラーゲ
ンから脱離することがない。リン酸３カルシウム又はハ
イドロキシアパタイトを担持させた線維状コラーゲンは
濾別され充分に洗浄して遊離のリン酸３カルシウム又は
ハイドロキシアパタイトを除去する。使用するリン酸３
カルシウム又はハイドロキシアパタイトは粒子が微細で
ある程好ましいが、１００μm 以下の粒子であれば充分
使用可能である。然しながら少量の添加で高い効果を得
るためには、２０μm 以下の粒子の使用が好ましいと云
える。担持させるリン酸３カルシウム又はハイドロキシ
アパタイトの量は、使用するそれらの量及び攪拌時間を
適宜選択することにより調製可能である。リン酸３カル
シウム又はハイドロキシアパタイトの線維状コラーゲン
への担持量に比例して、えられるコラーゲン膜の強度が
高くなるが、担持量が多すぎると得られる膜が硬くな
り、しなやかさがなくなるので、その担持量は、コラー
ゲンに対して0.１〜５０重量％、好ましくは0.５〜３０
重量％の範囲に調製する。The above-mentioned fibrillar collagen is suspended in distilled water or a buffer solution, and finely pulverized tricalcium phosphate or hydroxyapatite is added and vigorously stirred to sufficiently support the fibrillar collagen. Since hydroxyapatite and tricalcium phosphate have a good affinity with proteins as described above, these substances are strongly supported on the fibrillar collagen by this operation and are not detached from the fibrillar collagen. Fibrous collagen carrying tricalcium phosphate or hydroxyapatite is filtered off and thoroughly washed to remove free tricalcium phosphate or hydroxyapatite. Phosphoric acid used 3
The finer particles of calcium or hydroxyapatite are preferable, but particles of 100 μm or less can be sufficiently used. However, in order to obtain a high effect with a small amount of addition, it can be said that the use of particles of 20 μm or less is preferable. The amount of tricalcium phosphate or hydroxyapatite to be supported can be adjusted by appropriately selecting the amount to be used and the stirring time. The strength of the obtained collagen film increases in proportion to the amount of tricalcium phosphate or hydroxyapatite loaded on the fibrous collagen, but if the loaded amount is too large, the resulting film will become rigid and lose its flexibility. The supported amount is 0.1 to 50% by weight, preferably 0.5 to 30% with respect to collagen.
Prepare in the range of wt%.
【００１０】このようにして得られたリン酸３カルシウ
ム又はハイドロキシアパタイトを担持させた線維状コラ
ーゲンを７０％エタノール中に懸濁させ、テフロン布を
敷いたブフナー濾過器で濾過すると仝時に、平坦な圧縮
子で圧縮して必要な厚さに成形し、その後１００％エタ
ノールで洗浄する。この処理により、線維状コラーゲン
を膜に形成し、凍結乾燥することにより、リン酸３カル
シウム又はハイドロキシアパタイトを担持させたコラー
ゲン膜がえられる。The tricalcium phosphate or hydroxyapatite-supported fibrous collagen thus obtained was suspended in 70% ethanol and filtered with a Buchner filter covered with a Teflon cloth to flatten the surface. Compress to the required thickness with a compressor and then wash with 100% ethanol. By this treatment, fibrous collagen is formed into a film and freeze-dried to obtain a collagen film carrying tricalcium phosphate or hydroxyapatite.
【００１１】上記の線維状コラーゲンにリン酸３カルシ
ウム又はハイドロキシアパタイトを担持させた後、それ
を膜状に形成してリン酸３カルシウム又はハイドロキシ
アパタイトを担持させたコラーゲン膜の形成法を記した
が、コラーゲンゲルにリン酸３カルシウム又はハイドロ
キシアパタイトを担持させた後線維状コラーゲンを形成
することも可能であり、或は一般のコラーゲンゲル膜又
はコラーゲンゲルに直接リン酸３カルシウム又はハイド
ロキシアパタイトを担持させ必要に応じて常法により成
形して膜にすることも可能である。これら方法において
リン酸３カルシウム又はハイドロキシアパタイトの担持
法は上記の方法に準じて容易に行うことができる。The method for forming a collagen film in which tricalcium phosphate or hydroxyapatite is carried on the above-mentioned fibrous collagen and then formed into a film to carry tricalcium phosphate or hydroxyapatite is described. It is also possible to form fibrous collagen after supporting tricalcium phosphate or hydroxyapatite on a collagen gel, or by directly supporting tricalcium phosphate or hydroxyapatite on a general collagen gel membrane or collagen gel. If necessary, it can be formed into a film by a conventional method. In these methods, the method of supporting tricalcium phosphate or hydroxyapatite can be easily performed according to the above method.
【００１２】以下に実施例を示して具体的に本発明を説
明する。The present invention will be specifically described below with reference to examples.
【実施例１】前記した如く、コウシの真皮からペプシン
限定消化法によりえられた可溶性コラーゲンを精製し、
精製コラーゲンより天然型の太いコラーゲン線維をえ、
グルタルアルデヒドで架橋して線維状コラーゲンを形成
して、原料線維状コラーゲンとして使用した。線維状コ
ラーゲンを蒸留水に懸濁させ、２０μm 以下の粒子のリ
ン酸３カルシウム又はハイドロキシアパタイトを夫々添
加して常温で激しく攪拌して夫々を担持した線維状コラ
ーゲンを採取し、それを前記の如く処理してリン酸３カ
ルシウム又はハイドロキシアパタイトを夫々の量担持し
たコラーゲン膜をえた（１−７〜１−１２）。一方従来
のコラーゲン膜を蒸留水に懸濁させ、２０μm 以下の粒
子のリン酸３カルシウム又はハイドロキシアパタイトを
夫々添加して常温で激しく攪拌して夫々を担持させた
後、えられたコラーゲン膜を凍結乾燥してハイドロキシ
アパタイト又はリン酸３カルシウムを担持したコラーゲ
ンゲル膜をえた（１−１〜１−６）。えられたコラーゲ
ン膜のリン酸３カルシウム又はハイドロキシアパタイト
の担持量を表１に示した。表中％はコラーゲンに対する
重量％である。Example 1 As described above, the soluble collagen obtained from the calf dermis by the pepsin limited digestion method was purified,
Natural thick collagen fibers are obtained from purified collagen,
It was cross-linked with glutaraldehyde to form fibrillar collagen and used as a raw fibrillar collagen. The fibrillar collagen was suspended in distilled water, tricalcium phosphate or hydroxyapatite particles with a particle size of 20 μm or less were added, respectively, and vigorously stirred at room temperature to collect the fibrillar collagen carrying each of them, as described above. The treatment was performed to obtain collagen membranes carrying respective amounts of tricalcium phosphate or hydroxyapatite (1-7 to 1-12). On the other hand, a conventional collagen film was suspended in distilled water, tricalcium phosphate or hydroxyapatite particles of 20 μm or less were added, respectively, and vigorously stirred at room temperature to support each, and then the collagen film obtained was frozen. It was dried to obtain a collagen gel film supporting hydroxyapatite or tricalcium phosphate (1-1 to 1-6). The amount of tricalcium phosphate or hydroxyapatite supported on the obtained collagen film is shown in Table 1. In the table,% is weight% with respect to collagen.
【００１３】[0013]
【表１】 [Table 1]
【００１４】[0014]
【実施例２】実施例１で作成したコラーゲン膜の引張り
強度を測定し、測定結果を表２に示した。比較のため、
従来のコラーゲンゲル膜での結果を比較例１−１に、線
維状コラーゲンより作成した線維状コラーゲン膜での結
果を比較例１−２に示した。Example 2 The tensile strength of the collagen film prepared in Example 1 was measured, and the measurement results are shown in Table 2. For comparison,
The results of the conventional collagen gel film are shown in Comparative Example 1-1, and the results of the fibrillar collagen film prepared from fibrillar collagen are shown in Comparative Example 1-2.
【００１５】[0015]
【表２】 [Table 2]
【００１６】上記の結果より、リン酸３カルシウム又は
ハイドロキシアパタイトをコラーゲン膜中に添加するこ
とによりコラーゲン膜の引張り強度が強くなること、リ
ン酸３カルシウムの添加より、ハイドロキシアパタイト
の添加の方がより効果が高いこと、多量に添加してもさ
ほど効果の向上がみられないことがわかる。又線維状コ
ラーゲン膜ではハイドロキシアパタイト５０％添加で、
膜のしなやかさにかけるため、かえって引張り強度が減
少してくるようである。From the above results, the tensile strength of the collagen film becomes stronger by adding tricalcium phosphate or hydroxyapatite into the collagen film, and the addition of hydroxyapatite is more preferable than the addition of tricalcium phosphate. It can be seen that the effect is high, and the effect is not so much improved even if added in a large amount. For fibrous collagen membrane, add 50% hydroxyapatite,
It seems that the tensile strength is rather reduced because of the flexibility of the film.
【００１７】[0017]
【発明の効果】本発明のコラーゲン膜は、ハイドロキシ
アパタイトやリン酸３カルシウムなどの骨伝導能をもち
生体親和性のよいリン酸カルシウムが含まれているた
め、引張り強度が強く、使用し易いばかりでなく、皮膚
の治療においては皮膚との接着性がよく、骨、歯根など
の治療に使用すると短期間での骨の再生が期待できると
ともに、膜中に他の薬剤の添加も可能であり、例えば抗
炎症剤、ホルモン剤、高血圧治療剤、糖尿病治療剤、抗
生物質、抗菌剤、抗腫瘍剤、ニトログリセリンなどの狭
心治療剤などや、ＢＭＰなどの骨形成タンパク質を添加
することにより、より優れた治療用材料となりえる。INDUSTRIAL APPLICABILITY The collagen film of the present invention contains calcium phosphate having osteoconductivity and good biocompatibility, such as hydroxyapatite and tricalcium phosphate, so that it has high tensile strength and is easy to use. In the treatment of skin, it has good adhesion to the skin, and when it is used for treatment of bones, tooth roots, etc., it can be expected to regenerate bones in a short period of time, and it is also possible to add other drugs to the membrane, for example, By adding inflammatory agents, hormonal agents, antihypertensive agents, antidiabetic agents, antibiotics, antibacterial agents, antitumor agents, angina therapeutic agents such as nitroglycerin, and bone morphogenetic proteins such as BMP Can be a therapeutic material.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 37/12 ＡＤＡ 8314−4Ｃ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location A61K 37/12 ADA 8314-4C
Claims (5)
よりなる化合物を含有させたことを特徴とするコラーゲ
ン膜。1. A collagen film comprising a compound consisting of phosphoric acid and calcium in the collagen film.
ムよりなる化合物を含有させてえられたことを特徴とす
るコラーゲン膜。2. A collagen membrane obtained by containing a compound consisting of phosphoric acid and calcium in collagen fibers.
ハイドロキシアパタイトである請求項１又は２のコラー
ゲン膜。3. The collagen film according to claim 1, wherein the compound consisting of phosphoric acid and calcium is hydroxyapatite.
が、リン酸３カルシウムである請求項１又は２のコラー
ゲン膜。4. The collagen film according to claim 1, wherein the compound consisting of phosphoric acid and calcium is tricalcium phosphate.
ムよりなる化合物の含有量が0.１〜５０重量％である請
求項１乃至４のいずれか１項記載のコラーゲン膜。5. The collagen film according to claim 1, wherein the content of the compound consisting of phosphoric acid and calcium with respect to collagen is 0.1 to 50% by weight.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5117561A JPH06304240A (en) | 1993-04-22 | 1993-04-22 | Collagen film |
| CA002121192A CA2121192A1 (en) | 1993-04-21 | 1994-04-13 | Collagen membranes |
| EP94302748A EP0621044A3 (en) | 1993-04-21 | 1994-04-18 | Collagen membranes. |
| AU60588/94A AU678211B2 (en) | 1993-04-21 | 1994-04-20 | Collagen membranes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5117561A JPH06304240A (en) | 1993-04-22 | 1993-04-22 | Collagen film |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06304240A true JPH06304240A (en) | 1994-11-01 |
Family
ID=14714865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5117561A Pending JPH06304240A (en) | 1993-04-21 | 1993-04-22 | Collagen film |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06304240A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08155023A (en) * | 1994-12-08 | 1996-06-18 | Asahi Optical Co Ltd | Scratch pad |
| KR100563476B1 (en) * | 1998-07-03 | 2006-03-27 | 이진용 | Bone regeneration material |
| JP2010500905A (en) * | 2006-08-17 | 2010-01-14 | ウォーソー・オーソペディック・インコーポレーテッド | Medical implant sheet useful for tissue regeneration |
| WO2013084817A1 (en) * | 2011-12-05 | 2013-06-13 | 日立化成株式会社 | Membrane for inducing regeneration of bone/tissue, and method for producing same |
-
1993
- 1993-04-22 JP JP5117561A patent/JPH06304240A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08155023A (en) * | 1994-12-08 | 1996-06-18 | Asahi Optical Co Ltd | Scratch pad |
| KR100563476B1 (en) * | 1998-07-03 | 2006-03-27 | 이진용 | Bone regeneration material |
| JP2010500905A (en) * | 2006-08-17 | 2010-01-14 | ウォーソー・オーソペディック・インコーポレーテッド | Medical implant sheet useful for tissue regeneration |
| WO2013084817A1 (en) * | 2011-12-05 | 2013-06-13 | 日立化成株式会社 | Membrane for inducing regeneration of bone/tissue, and method for producing same |
| US9877808B2 (en) | 2011-12-05 | 2018-01-30 | Hitachi Chemical Company, Ltd. | Membrane for inducing regeneration of bone/tissue, and method for producing same |
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