CN101204593A - Aqueous solution of BMP-2 tropocollagen, process for preparing same and application thereof on bone grafting material - Google Patents
Aqueous solution of BMP-2 tropocollagen, process for preparing same and application thereof on bone grafting material Download PDFInfo
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- CN101204593A CN101204593A CNA2006101476097A CN200610147609A CN101204593A CN 101204593 A CN101204593 A CN 101204593A CN A2006101476097 A CNA2006101476097 A CN A2006101476097A CN 200610147609 A CN200610147609 A CN 200610147609A CN 101204593 A CN101204593 A CN 101204593A
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Abstract
The invention discloses BMP-2 protein collagen aqueous solution, a preparation method and application thereof in bone implant materials. In the BMP-2 protein collagen aqueous solution the density of BMP-2 protein is 10mg to 20mg/ml, weight concentration of the collagen is 0.5 to 5 percent, optimization is 1 to 3 percent, special optimization is 1 percent, and pH regulator leads pH of the BMP-2 protein collagen aqueous solution to 3 to 6. The invention well solves a dissolving problem of BMP-2, thus solving a difficult problem of BMP-2 being difficult to compound with all kinds of materials. The collagen is protein with extremely low antigenicity, and is endowed with performance of compounding BMP-2 and promoting activity of BMP-2, thus generating no drug side effect when being compounded and used with BMP-2 in the body, and being beneficial for performance of the activity of BMP-2.
Description
Technical field
The present invention relates to a kind of BMP-2 Protocollagen aqueous solution and preparation method and the application in bone-grafting material thereof.
Background technology
Said BMP-2 albumen, be a kind of cytokine---bone morphogenetic protein (Bone Morphogenetic Protein that osteogenesis and reparation is had obvious biological activity, BMP), BMP is multi-functional morphogenetic factor, have simultaneously the outstanding bone osteogenic activity that lures again, have huge basic research value and broad clinical application prospect.Up to the present, found 20 kinds of BMP, difference called after BMP-1, BMP-2 ....
BMP-2 can purify (p-BMP2) in animal tissue, and also available genetic engineering makes up reconstitution cell and expresses synthetic (rhBMP-2).As in Urist[UAnn Thorac Surg in 1979,1990; 49 (6): 864-5] MP-2 of rabbit that taken the lead in from the calcium bone of running away like a hare successfully separation and purification of leader's group, from Os Bovis seu Bubali, extract Bovine Bone Morphoge Protnetin (bBMP) in nineteen eighty-two, Urist[Clin Orthop Relat Res. in 1987,1987 (214): 295-304] set up a cover extracts BMP from people and Os Bovis seu Bubali standard step.At present, pBMP-2 extracts from the normal bone of animals such as cattle, pig, sheep, horse, rabbit, Mus mostly.The golden generation bone grafting spirit ﹠amp that Zhongjin Pharmaceutical Co., Ltd, Tianjin produces; Reg; The osteogenic induction factor in the reconstituted bone xenograft (RBX) is extracted from Os Bovis seu Bubali exactly, and then forms with the Os Bovis seu Bubali matrix composite, is used for the treatment of delayed fracture and connects, do not connect and bone defect healing.
Utilizing gene engineering method to produce people BMP-2, not only can guarantee mass production, also can avoid immunological rejection, is the method that has development prospect and captivation.From Wozney in 1988 etc. is the BMP-2 gene in source with the Os Bovis seu Bubali, and in recombination bacillus coli after the successful expression, genetic engineering mass production people's BMP-2 also just becomes possible (Wozney JM, Rosen V, Celeste AJ, etal, Novel regulators of bone formation:molecular clones and activities, science, 1988; 242 (4885): 1525-34).At present, be used for the existing eucaryon of system of expressed BMP-2 gene, prokaryotic cell is also arranged, two kinds of expression systems respectively have pluses and minuses.
BMP-2 albumen can make up with bone-grafting material, is used for osteogenesis and reparation.But, no matter be the BMP-2 albumen of natural extract, or the BMP-2 albumen of prokaryotic gene expression, in general buffer, can not dissolve, can only be dissolved in high concentration urea or the guanidine hydrochloride.And carbamide or guanidine hydrochloride can not use in vivo, and this just gives the clinical use of this medicine and brings very big difficulty with bone-grafting material compound.This also is one of difficult problem of studying both at home and abroad at present the BMP-2 application technology, has limited the application clinically of BMP-2 albumen greatly.
Summary of the invention
The technical issues that need to address of the present invention are to disclose a kind of BMP-2 Protocollagen aqueous solution, to overcome the above-mentioned defective that prior art exists.
Another technical problem that the present invention need solve is the preparation method that discloses described BMP-2 Protocollagen aqueous solution.
Another technical issues that need to address of the present invention are the application in bone-grafting material of open BMP-2 Protocollagen aqueous solution.
In the said BMP-2 Protocollagen of the present invention aqueous solution:
The proteic concentration of BMP-2 is 10mg～20mg/ml, and the weight concentration of collagen is 0.5～5%, and is preferred 1～3%, preferred especially 1%, and comprise that the pH that makes said BMP-2 Protocollagen aqueous solution is the pH regulator agent of 3-6;
Said BMP-2 albumen is selected from the BMP-2 albumen that the natural B MP-2 that extracts or prokaryotic gene are expressed from animal tissue;
Term " collagen " refers to the collagen protein that extracts purification from osseous tissue of cattle or pig or muscle tendon, and purity should reach electrophoresis purity.
Said pH regulator agent is selected from a kind of in the glacial acetic acid of dilution or the hydrochloric acid, and weight concentration is 5～30%;
The preparation method of BMP-2 Protocollagen aqueous solution of the present invention comprises the steps:
According to above-mentioned ratio, BMP-2 dry powder and collagenic aqueous solution are mixed, add the pH regulator agent and regulate pH to 3-6, obtain said BMP-2 Protocollagen aqueous solution; The weight concentration of collagenic aqueous solution is 0.5～5%, preferred 1～3%, preferred especially 1%;
The said BMP-2 Protocollagen of the present invention aqueous solution can be compound with bone-grafting material, with the form of compositions, needs carried out the bone grafting treatment.
In the compositions that said BMP-2 Protocollagen aqueous solution and bone-grafting material are compounded to form, BMP-2 Protocollagen aqueous solution is decided according to different bone-grafting materials with the ratio of bone-grafting material;
Animal experiment proves, said BMP-2 Protocollagen aqueous solution avirulence, with said bone-grafting material compound after, can adopt conventional method that the patient is treated.
The present invention has well solved the problems of dissolution of BMP-2, is difficult to a compound difficult problem thereby solved with various materials.Collagen is the extremely low albumen of antigenicity, and has in conjunction with BMP-2, promotes the active effect of BMP-2, therefore not only can not bring side effects of pharmaceutical drugs with the compound use of BMP-2 in vivo, and help the active performance of BMP-2.
The specific embodiment
Embodiment 1
With BMP-2 dry powder and weight concentration is that 1% collagenic aqueous solution mixes, and adds weight concentration and is 10% hydrochloric acid and regulate pH to 6, obtains said BMP-2 Protocollagen aqueous solution;
In the BMP-2 Protocollagen aqueous solution:
The proteic concentration of BMP-2 is 20mg/ml, and BMP-2 albumen is selected from the natural B MP-2 that extracts from animal tissue.
Embodiment 2
With BMP-2 dry powder and weight concentration is that 3% collagenic aqueous solution mixes, and adds weight concentration and is 25% glacial acetic acid and regulate pH to 3, obtains said BMP-2 Protocollagen aqueous solution;
In the BMP-2 Protocollagen aqueous solution:
The proteic concentration of BMP-2 is 10mg/ml;
BMP-2 albumen is selected from the natural B MP-2 that extracts from animal tissue.
Claims (7)
1. BMP-2 Protocollagen aqueous solution, component and concentration are:
The proteic concentration of BMP-2 is 10mg～20mg/ml, collagen weight concentration be 0.5～5%.
2. BMP-2 Protocollagen aqueous solution according to claim 1 is characterized in that, said BMP-2 albumen is selected from the BMP-2 albumen that the natural B MP-2 that extracts or prokaryotic gene are expressed from animal tissue.
3. BMP-2 Protocollagen aqueous solution according to claim 1 is characterized in that, collagen weight concentration be 1～3%.
4. BMP-2 Protocollagen aqueous solution according to claim 3 is characterized in that the weight concentration of collagen is 1%.
5. BMP-2 Protocollagen aqueous solution according to claim 1 is characterized in that, said pH regulator agent is selected from a kind of in the glacial acetic acid of dilution or the hydrochloric acid.
6. the preparation method of BMP-2 Protocollagen aqueous solution according to claim 1, it is characterized in that, comprise the steps: proportionally, BMP-2 dry powder and collagenic aqueous solution are mixed, add the pH regulator agent and regulate pH to 3-6, obtain said BMP-2 Protocollagen aqueous solution.
7. claim 1 or the 2 described BMP-2 Protocollagen aqueous solutions application in the preparation bone-grafting material.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101476097A CN101204593A (en) | 2006-12-20 | 2006-12-20 | Aqueous solution of BMP-2 tropocollagen, process for preparing same and application thereof on bone grafting material |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101476097A CN101204593A (en) | 2006-12-20 | 2006-12-20 | Aqueous solution of BMP-2 tropocollagen, process for preparing same and application thereof on bone grafting material |
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| CN101204593A true CN101204593A (en) | 2008-06-25 |
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| CNA2006101476097A Pending CN101204593A (en) | 2006-12-20 | 2006-12-20 | Aqueous solution of BMP-2 tropocollagen, process for preparing same and application thereof on bone grafting material |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200254061A1 (en) * | 2018-03-21 | 2020-08-13 | Warsaw Orthopedic, Inc. | Injectable bone morphogenetic protein |
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- 2006-12-20 CN CNA2006101476097A patent/CN101204593A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200254061A1 (en) * | 2018-03-21 | 2020-08-13 | Warsaw Orthopedic, Inc. | Injectable bone morphogenetic protein |
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Open date: 20080625 |