CN1168494C - Injection-type compound bone repairing material containing more biological factors and using animal fibrin as carrier - Google Patents
Injection-type compound bone repairing material containing more biological factors and using animal fibrin as carrier Download PDFInfo
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- CN1168494C CN1168494C CNB021145091A CN02114509A CN1168494C CN 1168494 C CN1168494 C CN 1168494C CN B021145091 A CNB021145091 A CN B021145091A CN 02114509 A CN02114509 A CN 02114509A CN 1168494 C CN1168494 C CN 1168494C
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- growth factor
- morphogenetic protein
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- bone morphogenetic
- fibrin
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Abstract
The present invention discloses injected bone repairing material compounded from various biological factors by using animal fibrin as carriers, which is widely suitable for treating fractures, nonunion, bone defect, osteoporosis, etc. The present invention uses fibrin in the blood of mammals as carriers, and gene recombination bone morphogenetic protein, fibroblast growth factors and beta-transformation growth factors are used for local injury parts; with the absorption and the degradation of the carriers, the bone morphogenetic protein and other biological factors are released out slowly and are solidified rapidly in the body. The shape of the present invention can be molded into the shape of the injury part so that the shape of new bones is fully restored to the original physiological shape to promote the growth of the new bones, to accelerate wound repair and to promote the union of fractures. Animal experiments and clinical tests prove that the present invention has exact treatment effect, wide range of application, easy operation, safety and reliability.
Description
One, affiliated field
The present invention relates to a kind of bone renovating material that clinical medicine is used, be particularly related to and a kind ofly be used for clinical fracture, bone does not connect, damaged, the osteoporosis diseases of bone, and to can be used for veterinary be the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin.
Two, background technology
The existing method of skeletal growth factor of using is for being compounded on the solid material, implant wound site, complicated operation, cost height by operation, restricted application does not especially need the case of operative treatment to be difficult to use to the maximum closed fracture of clinical appearance and other.
Three, summary of the invention
The defective or the deficiency that partly exist according to above-mentioned prior art, the objective of the invention is, provide a kind of and be used for clinical fracture, bone does not connect, damaged, the osteoporosis diseases of bone, and to can be used for veterinary be the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin.
Design of the present invention is that adopting mammalian is that raw material extracts Fibrinogen, and makes it to be converted into fibrin clot by thrombin action when using.With the slow-released carrier of fibrin clot as bone morphogenetic protein, fibroblast growth factor and β transforming growth factor, utilize the bone inductive effect of above-mentioned biotic factor and promote repair in trauma effect treatment fracture, bone does not connect, bone is damaged and osteoporosis etc.
The technical scheme that the present invention takes is:
With the animal fibrin is the injection type multiple biological factor composite bone repair materials of carrier, by the following method preparation:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin.
It is characterized in that, above-mentioned first with do not mix before second portion is in being expelled to body, but adopt marginal not to penetrate the blended mode in limit, and:
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 70mg/ml～110mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 5 μ g/ml～20 μ g/ml, 5mg/ml and 1mg/ml.
Another characteristics of the present invention are that described recombinant human bone morphogenetic protein is BMP-2, BMP-4 or the BMP-7 and their mixture of gene engineering expression.
The present invention utilize Fibrinogen with thrombin action before be dissolvable in water liquid characteristics make injection, thereby needing not only to can be used for the damaged patient of bone does not connect, bone of operative treatment, can also use ordinary syringe percutaneous direct injection, thereby can be used for closed fracture, osteoporosis etc. and do not need the case of performing the operation.Have advantages such as the clinical scope of application is extensive, easy and simple to handle, therapeutic effect is definite.Three kinds of biotic factors are produced by the genetic engineering method, are the water capacity, the purity height, and biological activity is good.Fibrin is biological material, so good biocompatibility, can be absorbed fully at short notice.Along with the absorption degraded of carrier, biotic factors such as bone morphogenetic protein slowly release, and can give full play to its biological action in the overall process of repair in trauma.Studies show that the fibrin immunogenicity is very low, have no adverse reaction after implanting.Because the mammalian such as pig, cattle that have drawn from, thereby wide material sources not only, cost is low, but also has avoided propagating the disease by blood propagation such as hepatitis, acquired immune deficiency syndrome (AIDS).
Liquid fibrinogen solution is with after the thrombin that is dissolved with biotic factor mixes, solidify rapidly in vivo, and plastotype becomes the shape of damage location arbitrarily, makes new bone shape recover the physiology shape of reason fully, and is significant for the recovery of limb function.Simultaneously, fibrinogenic hemostasis, bonding effect help preventing and treating the formation of local hematoma, quicken the soft tissue healing, for the regeneration and the healing of bone provides good local environment.
Four, the specific embodiment
The present invention is described in further detail below in conjunction with embodiment.
Embodiment 1: according to technical scheme of the present invention, is the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, and preparation by the following method:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin.
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 70mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 20 μ g/ml, 5mg/ml and 1mg/ml.
Recombinant human bone morphogenetic protein is the BMP-4 of gene engineering expression.
Embodiment 2: they according to technical scheme of the present invention, are the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, and preparation by the following method:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin.
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 110mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 10 μ g/ml, 5mg/ml and 1mg/ml.
Recombinant human bone morphogenetic protein is the BMP-2 of gene engineering expression.
Embodiment 3: they according to technical scheme of the present invention, are the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, and preparation by the following method:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin.
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 90mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 5 μ g/ml, 5mg/ml and 1mg/ml.
Recombinant human bone morphogenetic protein is the BMP-7 of gene engineering expression.
Embodiment 4: they according to technical scheme of the present invention, are the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, and preparation by the following method:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin.
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 110mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 15 μ g/ml, 5mg/ml and 1mg/ml.
Recombinant human bone morphogenetic protein is BMP-2, the BMP-4 of gene engineering expression, the mixture of BMP-7.
Instantiation 1: closed fracture of distal end of radius (Ke Shi fracture), or, can not take expectant treatment because of there being the operation indication without humerus, femur, tibiofibula closed fracture that nervus vasculairs are hindered.As follows with this repair materials therapeutic process: manual traction resets, and it is satisfied to observe the fracture end para-position under TV X-ray machine perspective, gets this material 5～10ml, and percutaneous injection is to fracture site under the perspective.In 4～6 weeks of plaster fixation, union of fracture is good.Show this material accelerating bone healing speed effectively, improve new bone mass, the generation of prevention bone delay in healing or bone does not connect.
Instantiation 2: long bone of limbs is with the open fracture of fragment (or dish-shaped piece), and operative reduction is also taked the fixing fracture of suitable mode, evenly is sprayed at fracture site with this material, and bone cips is put back into original anatomical position, and conventional method is closed wound.In this type of trauma care, this material not only can promote union of fracture, can also bring into play its adhesive effect fracture fragments and backbone are bonded together, for intactly recover the original shape of skeleton, the damaged and bone does not connect of prevention bone has good effect.
The present invention mainly uses with injection system, adopts dual barrel syringe.Before using isopyknic first and second parts are added respectively in two tubes of dual barrel syringe, external special-purpose syringe needle can percutaneous injection, use in also can performing the operation.
Advantage of the present invention is: promote the bone reparation, accelerated bone forms and the knitting definite effect; It is easy to use, Indication is extensive; Histocompatbility is good, and is safe and reliable.
The present invention the medical domain such as orthopaedics, neurosurgery, thoracic surgery, decorative sursery and be used for domestic animal, The application of animal husbandry, animal for display, the veterinary science aspects such as treatment that watch for animals has more wide prospect.
Claims (2)
1. one kind is the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, by the following method preparation:
1) the aseptic mammal anticoagulations such as pig, cattle of getting extract Fibrinogen with the low-temperature centrifugation method after the separated plasma, and the first that spongy Fibrinogen is a native system is made in lyophilizing;
2) second portion of the recombinant human bone morphogenetic protein of adding doses, fibroblast growth factor and β transforming growth factor composition native system in the thrombin;
It is characterized in that, above-mentioned first with do not mix before second portion is in being expelled to body, but adopt marginal not to penetrate the blended mode in limit, and:
3) first is solvent with the distilled water, is made into suspension before the use; Wherein fibrinogenic concentration is 70mg/ml～110mg/ml;
4) second portion is a solvent with the calcium chloride of 40mM/L, and the concentration of thrombin is 500IU/ml, and the concentration of recombinant human bone morphogenetic protein, fibroblast growth factor and β transforming growth factor is respectively 5 μ g/ml～20 μ g/ml, 5mg/ml and 1mg/ml.
2. according to claim 1 is the injection type multiple biological factor composite bone repair materials of carrier with the animal fibrin, it is characterized in that: described recombinant human bone morphogenetic protein is BMP-2, BMP-4 or the BMP-7 and their mixture of gene engineering expression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021145091A CN1168494C (en) | 2002-04-09 | 2002-04-09 | Injection-type compound bone repairing material containing more biological factors and using animal fibrin as carrier |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021145091A CN1168494C (en) | 2002-04-09 | 2002-04-09 | Injection-type compound bone repairing material containing more biological factors and using animal fibrin as carrier |
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| Publication Number | Publication Date |
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| CN1376516A CN1376516A (en) | 2002-10-30 |
| CN1168494C true CN1168494C (en) | 2004-09-29 |
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| CNB021145091A Expired - Fee Related CN1168494C (en) | 2002-04-09 | 2002-04-09 | Injection-type compound bone repairing material containing more biological factors and using animal fibrin as carrier |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102755669B (en) * | 2012-07-16 | 2014-04-30 | 姚琦 | Preparation method and application of fibrin glue composite recombinant human bone morphogenetic protein-2 (rhBMP-2) microsphere |
| CN108324928B (en) * | 2018-03-05 | 2020-09-08 | 哈尔滨医科大学 | Application of recombinant human fibroblast growth factor-5 in promoting fracture healing |
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