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Organic/inorganic composite biomaterials and process for producing the same

外国特許コード F110005184
整理番号 A122-26US
掲載日 2011年8月25日
出願国 アメリカ合衆国
出願番号 49293702
公報番号 20050053638
公報番号 8168151
出願日 平成14年9月19日(2002.9.19)
公報発行日 平成17年3月10日(2005.3.10)
公報発行日 平成24年5月1日(2012.5.1)
国際出願番号 JP2002009592
国際公開番号 WO2003035127
国際出願日 平成14年9月19日(2002.9.19)
国際公開日 平成15年5月1日(2003.5.1)
優先権データ
  • 特願2001-322255 (2001.10.19) JP
  • 特願2002-065778 (2002.3.11) JP
  • 2002WO-JP09592 (2002.9.19) WO
発明の名称 (英語) Organic/inorganic composite biomaterials and process for producing the same
発明の概要(英語) (US8168151)
This invention provides organic/inorganic composite biomaterials constituted by composites of hydroxyapatite and collagen and having an average fiber length of 60 μm or longer, and a process for producing the same in which the calcium ion and phosphate ion concentrations in the reaction vessel are optimized through regulation of the concentration of a starting material and the flow rate.
The organic/inorganic composite biomaterials have mechanical strength and a biodegradation rate suitable for artificial bones through the introduction of crosslinking therein.
特許請求の範囲(英語) [claim1]
1. Organic/inorganic composite biomaterials, comprising: composites of hydroxyapatite and solubilized collagen,
wherein said composites are constituted of fibers having an average fiber length of 60 mu m or longer, and
wherein the composites have microporous structures in which the c-axis of hydroxyapatite is oriented along collagen fibers.
[claim2]
4. The process according to claim 3, wherein the ratio of the weight of hydroxyapatite to that of collagen generated in the reaction vessel is between 3:2 and 9:1.
[claim3]
2. The organic/inorganic composite biomaterials according to claim 1, wherein the solubilized collagen is an enzyme-solubilized collagen.
[claim4]
3. A process for producing the organic/inorganic composite biomaterials comprising composites of hydroxyapatite and collagen which are constituted of fibers having an average fiber length of 60 mu m or longer, said composite having microporous structures in which the c-axis of hydroxyapatite is oriented along collagen fibers, said process comprising: simultaneously adding to a reaction vessel an aqueous calcium salt solution and an aqueous phosphate solution containing collagen to maintain the calcium ion concentration at 3.75 mM or lower and the phosphate ion concentration at 2.25 mM or lower in the reaction vessel, and
pressing the resulting composite,
wherein the flow rates of the aqueous calcium salt solution and the aqueous phosphate solution being added to the reaction vessel are regulated such that the pH level of the reaction solution in the reaction vessel is maintained between 7 and 11, the average flow rate of the aqueous calcium salt solution being added to the reaction vessel being 5 to 25 ml/min; and
wherein the starting concentration of the aqueous calcium salt solution is 50 to 200 mM, and the starting concentration of the aqueous phosphate solution is 15 to 96 mM.
[claim5]
5. The process according to claim 3, wherein the ratio of the weight of hydroxyapatite to that of collagen generated is maintained between 70:30 and 85:15.
[claim6]
6. The process according to claim 3, wherein the temperature of the reaction solution is maintained between 35 deg. C. and 40 deg. C.
[claim7]
7. The process according to claim 3, further comprising introducing crosslinking of collagen in the organic/inorganic composite biomaterials obtained by the aforementioned process.
[claim8]
8. The process according to claim 7, wherein the crosslinking is introduced by a reaction utilizing glutaraldehyde.
[claim9]
9. The process according to claim 8, wherein 10 mu mol to 10 mmol of the glutaraldehyde is used per g of collagen in organic/inorganic composite biomaterials.
[claim10]
10. The organic/inorganic composite biomaterials according to claim 1, wherein solubilized collagen is crosslinked.
[claim11]
11. The organic/inorganic composite biomaterials according to claim 1, which are formed into sheets, sponges, or porous bodies.
[claim12]
12. The process according to claim 3, wherein said calcium ion concentration is maintained at 2.5 mM or lower and said phosphate ion concentration is maintained at 1.5 mM or lower in the reaction vessel.
[claim13]
13. The organic/inorganic composite biomaterials according to claim 1, wherein said composites are constituted of fibers having an average fiber length of 1 mm or longer.
[claim14]
14. The organic/inorganic composite biomaterials according to claim 1, wherein said composites are constituted of fibers having an average fiber length of 3 mm or longer.
[claim15]
15. The organic/inorganic composite biomaterials according to claim 1, wherein said organic/inorganic composite biomaterials are produced by simultaneously adding to a reaction vessel an aqueous calcium salt solution and an aqueous phosphate solution containing solubilized collagen to maintain the calcium ion concentration at 3.75 mM or lower and the phosphate ion concentration at 2.25 mM or lower in the reaction vessel, and pressing the resulting composite, and
wherein the starting concentration of the aqueous calcium salt solution is 50 to 200 mM, and the starting concentration of the aqueous phosphate solution is 15 to 96 mM.
[claim16]
16. The process according to claim 3, wherein the pH level of the reaction solution in the reaction vessel is maintained between 7 and 9.
[claim17]
17. The process according to claim 3, wherein the pH level of the reaction solution in the reaction vessel is maintained at pH 9+-0.3.
[claim18]
18. The process according to claim 17, wherein the temperature of the reaction solution is maintained at 40 deg. C.
[claim19]
19. The process according to claim 6, wherein the temperature of the reaction solution is maintained at 40 deg. C.
  • 発明者/出願人(英語)
  • TANAKA JUNZO
  • KIKUCHI MASANORI
  • ITO NORIICHI
  • MANDAI YOSHINOBU
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • NATIONAL INSTITUTE FOR MATERIALS SCIENCE
  • NITTA GELATIN
国際特許分類(IPC)
米国特許分類/主・副
  • 423/308
  • 427/2.27
  • 530/356
  • 623/919
参考情報 (研究プロジェクト等) CREST Creation and Functions of New Molecules and Molecular Assemblies AREA
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