CN101843924A - Bone repairing bracket material with controllable and slow-releasing traditional Chinese medicine and preparation method thereof - Google Patents
Bone repairing bracket material with controllable and slow-releasing traditional Chinese medicine and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a bone repairing bracket material with controllable and slow-releasing traditional Chinese medicine and a preparation method thereof. The invention provides the following technical scheme: the bone repairing bracket material with the controllable and slow-releasing traditional Chinese medicine comprises Chinese medicine with special functions, bioactive inorganic nanometer powder, polymer at the wall material of the powder, collagen and accessory materials, wherein the weight ratio of the Chinese medicine with the special functions to the bioactive inorganic nanometer powder is 99:1-50:50, the weight ratio of the accessory materials to the collagen is 1:99-10:90, the weight ratio of the bioactive inorganic nanometer powder to the collagen is 97:3-60:40, and the weight ratio of the bioactive inorganic nanometer powder to the polymer at the wall material of the powder is 99:1-50:50. The preparation method of the material comprises the followings steps of preparing a composite microcapsule with medicine, mixing, crosslinking and freeze drying. By adopting the technical scheme, the invention provides the bone repairing bracket material with the controllable and slow-releasing traditional Chinese medicine, which can provide proper three-dimensional space and stable mechanical support for the growth of cells and the formation of new bones, and the preparation method thereof.
Description
Technical field
The present invention relates to material of a kind of bone repairing support and preparation method thereof, but bone renovating bracket material of particularly a kind of controlled release Chinese medicine and preparation method thereof.
Background technology
Biodegradable scaffold material combination drug or cell growth factor are applied to the bone defect repair, for the bone reconstruction provides the thinking that conforms with principle biology, are considered to ideal bone restorative procedure.Wherein, utilize the degradable characteristic of carrier bracket that medicine is slowly discharged in vivo, reach local higher concentration, to promote osteoblastic proliferation, differentiation and functional expression, or the mitosis and the induced osteogenesis of promotion cell, thereby quicken bone defect healing, raising is implanted to power.And timbering material can support for the cell attachment growth provide mechanics at the implantation initial stage as the slow-released carrier of medicine, slowly degraded more afterwards, treat damaged healing after, support is also degraded fully, thus the misery of avoiding the second operation taking-up to bring for the patient.
Collagen-based materials is the bone renovating material of using always.Collagen is the main organic principle of bone, and type i collagen and cross filament structure thereof are the abundantest albumen in the osteocyte epimatrix.Collagen structure has inducing action to mineral deposition, and the site of mineral deposition is contained on its surface, can effectively cause and control mineralization process, promotes freshman bone tissue to form.
Bone morphogenetic protein (BMP) is the non-specific material with bone-inducing activity that Urist extracts from decalcified bone matrix first, it is the efficient bone-inducing factor of generally acknowledging at present, it has induced osteogenesis cell differentiation and the outer osteogenic ability of inductor, and finds that it can also activate or induction of vascular mesenchymal cell on every side irreversibly is divided into cartilage and osteoblast.Therefore, BMP has become active factors the most commonly used in current " carrier+somatomedin " model organism material, and all obtains remarkable result in zoopery and clinical trial.But the BMP extensive use clinically that wherein still had many problems affect.For example, its clinical application effect is not as zoopery; BMP also stimulates the hypertrophy of osteoclast in induced osteogenesis, and the hypertrophy of osteoclast is early than osteoblast; The BMP activity of separate sources is not first-class.In addition, biomaterial is as the BMP carrier at present, and the consumption of BMP is very big, often reach the milligram level, because BMP is very expensive in the market, only Sigma company is used for the BMP of experimentation, per 10 μ g prices reach 500 dollars, and expensive expense also is one of factor of its extensive use of restriction.Searching have with the similar and cheap medicine of cell growth factor effect then be the key that addresses this problem.Some effective ingredient of Chinese medicine has and similar physiologically active of cytokine and pharmacological action widely, and cheap, and physicochemical property is relatively stable, and the good prospect that is applied to the bone defect repair as cytokine and antibiotic substitute is arranged.
At present, domestic existing research worker attempts Chinese medicine is compound in the bone cement, and the calcium phosphate bone cement powder that preparation contains Chinese medicine is as bone renovating material, and has carried out relevant clinical application research.Yet, bone cement is molding in advance, grow into and formation, the growth of bone newly of pair cell can not provide suitable physiologic spaces and provide metastable mechanics to support, only can be less in order to volume, the damaged filling of position bone that blood circulation is less, but be difficult to repair large-area, especially the bone of bearing position is damaged.
Summary of the invention
Deficiency at the prior art existence, the invention provides a kind of keep implant in the local long period effectively drug level in, for cell grow into and the formation of new bone provides suitable three dimensions and stable mechanics to support, thereby but better adapt to and satisfy the bone renovating bracket material and preparation method thereof of the controlled release Chinese medicine of clinical requirement.
For achieving the above object, the invention provides following technical scheme: but a kind of bone renovating bracket material of controlled release Chinese medicine, it is characterized in that: include load specific function Chinese medicine, the polymer of biological activity inorganic nanometer powder and wall material thereof, collagen, auxiliary material, the weight ratio of described load specific function Chinese medicine and biological activity inorganic nanometer powder is 99: 1-50: 50, the weight ratio of auxiliary material and collagen is 1: 99-10: 90, the weight ratio of biological activity inorganic nanometer-powder and collagen is 97: 3-60: 40, and the weight ratio of biologic inorganic nano-powder and wall material/polymer is 99: 1-50: 50.
Wherein, load specific function Chinese medicine can be at least a in Herba Epimedii extract, Rhizoma Drynariae extract, Radix Dipsaci extract, Rhizoma Chuanxiong extract, Radix Morindae Officinalis extract, Eupolyphaga seu steleophaga extract, Radix Salviae Miltiorrhizae extract, astragalus polysaccharides, the antler polypeptide.
Wherein, the biological activity inorganic nanometer powder can be at least a in nano tricalcium phosphate, nanometer hydroxyapatite, nano-calcium carbonate hydroxyapatite, nano fluorine-contained apatite, bioactivity glass and the composite granule between them, diameter of particle scope 50～400nm.
Wherein, the wall material/polymer of biological activity inorganic nanometer powder can be a kind of in polylactic acid, poly (lactic acid-glycolic acid) copolymer, poly butyric ester, poly-propyl cellulose, ethyl cellulose, gelatin or the chitosan.
Wherein, collagen can be type i collagen that extracts from the cattle heel string or the type i collagen that extracts from Corii Bovis seu Bubali.
Wherein, auxiliary material can be wherein a kind of in hyaluronic acid and the phosphoserine.
The present invention replaces expensive bone morphogenetic protein somatomedin such as (BMP-2) with specific traditional Chinese medicine, have wide material sources, physicochemical property is stable, advantages such as easy storage, and reduce medical treatment cost greatly, carry out Bionic Design from the material The Nomenclature Composition and Structure of Complexes, have more superior bioactive and biocompatibility.
But the step of the preparation method of the bone renovating bracket material of controlled release Chinese medicine is as follows among the present invention:
1) with biological activity inorganic nanometer powder and load specific function Chinese medicine by weight 99: 1-50: 50 ratio is fully mixed, then mixture is joined in the wall material/polymer with the blended biological activity inorganic nanometer powder of medium, and adopt solvent evaporated method to be prepared into the compound microcapsule of medicine carrying of particle diameter 100-400 μ m;
2) ratio of the compound microcapsule of medicine carrying according to weight ratio 97/3～60/40 joined in the acetic acid dissolved gum original solution, add auxiliary material simultaneously, evenly stir and mix;
3) add buffer agent, adjust pH is 5.5; In mixed solution, add cross-linking agent solution is carried out crosslinking Treatment, mixture is placed at 4 ℃ carried out cross-linking reaction in 24 hours.
4) after the cross-linking reaction, insert subzero 20 ℃-subzero 80 ℃ of refrigerator and cooled and froze 10-24 hour, the freezing dried of carrying out later.
Wherein, buffer agent is an ethylene sulfonic acid, and cross-linking agent is 1-ethyl-3-carbodiimide or N-hydroxy-succinamide, and addition is 1～5mg/ml.
Adopt above-mentioned preparation method, can prepare aperture size at the inner bone renovating bracket material that connects mutually of 10～200 μ m and hole, the biological activity inorganic nanometer powder is a pharmaceutical carrier, can improve the biomechanical property of timbering material again; This material internal is compounded with given efficacy Chinese medicine, and drug distribution is even, along with the degraded medicine of material can progressively discharge.This material has proper intensity and good biocompatibility, has wide bone and repairs application prospect.
The specific embodiment
But in the present invention is a kind of bone renovating bracket material of controlled release Chinese medicine, include polymer, collagen, the auxiliary material of load specific function Chinese medicine, biological activity inorganic nanometer powder and wall material thereof, the weight ratio of described load specific function Chinese medicine and biological activity inorganic nanometer powder is 99: 1-50: 50, the weight ratio of auxiliary material and collagen is 1: 99-10: 90, the weight ratio of biological activity inorganic nanometer-powder and collagen is 97: 3-60: 40, and the weight ratio of biologic inorganic nano-powder and wall material/polymer is 99: 1-50: 50.
Load specific function Chinese medicine among the present invention can be at least a in Herba Epimedii extract, Rhizoma Drynariae extract, Radix Dipsaci extract, Rhizoma Chuanxiong extract, Radix Morindae Officinalis extract, Eupolyphaga seu steleophaga extract, Radix Salviae Miltiorrhizae extract, astragalus polysaccharides, the antler polypeptide.The biological activity inorganic nanometer powder can be at least a in nano tricalcium phosphate, nanometer hydroxyapatite, nano-calcium carbonate hydroxyapatite, nano fluorine-contained apatite, bioactivity glass and the composite granule between them, diameter of particle scope 50～400nm.The wall material/polymer of biological activity inorganic nanometer powder can be a kind of in polylactic acid, poly (lactic acid-glycolic acid) copolymer, poly butyric ester, poly-propyl cellulose, ethyl cellulose, gelatin or the chitosan.Collagen can be type i collagen that extracts from the cattle heel string or the type i collagen that extracts from Corii Bovis seu Bubali.Select for use above-mentioned material to carry out cross-over configuration, its weight ratio is 99 with the weight ratio of load specific function Chinese medicine and biological activity inorganic nanometer powder: 1-50: 50, the weight ratio of auxiliary material and collagen is 1: 99-10: 90, the weight ratio of biological activity inorganic nanometer-powder and collagen is 97: 3-60: 40, and the biologic inorganic nano-powder is 99 with the weight ratio that reaches the wall material/polymer: 1-50: 50 are as the criterion.
In the embodiment of the invention 1, be medium with the dehydrated alcohol, nano hydroxyapatite powder and icariin are pressed mass ratio 94/6 abundant mixing, after the lyophilization, standby.The above-mentioned powder body of 5g is joined in the dichloromethane solution that is dissolved with the 5g polylactic acid, the abundant dispersive suspension of ultrasound wave, then suspension is joined in 100ml 1% gelatin solution, 35 ℃ of powerful (1500r/min) 5h that stir of water-bath, microporous filter three times, distilled water wash 5 times, lyophilization, the compound microcapsule of medicine carrying of acquisition particle diameter 100～400 μ m; Get the compound microcapsule 5g of above-mentioned medicine carrying and join 100ml and contain in the acetic acid solution of 0.5～2wt% collagen protein, and add auxiliary material such as hyaluronic acid 0.5～1g, evenly stirring the back is buffer agent with ethylene sulfonic acid (MES), and adjust pH is 5.5; In mixed solution, add cross-linking agent solution carried out crosslinking Treatment, the cross-linking agent that uses be 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxy-succinamide (NHS), addition is 1～5mg/ml.Mixture was carried out cross-linking reaction in 24 hours 4 ℃ of placements.After the cross-linking reaction, inserted-80 ℃ of refrigerators freezing 24 hours, and carried out lyophilization and handle until removing solvent fully, distilled water flushing for several times, lyophilization can obtain Chinese medicine control-release function bone renovating bracket material once more.
In the embodiment of the invention 2, be medium with the dehydrated alcohol, nano hydroxyapatite powder and Rhizoma Drynariae extract are pressed mass ratio 95/5 abundant mixing, after the lyophilization, standby.The above-mentioned powder body of 5g is joined in the dichloromethane solution that is dissolved with the 5g polylactic acid, the abundant dispersive suspension of ultrasound wave, then suspension is joined in 100ml 1% gelatin solution, 35 ℃ of powerful (1500r/min) 5h that stir of water-bath, microporous filter three times, distilled water wash 5 times, lyophilization, the compound microcapsule of medicine carrying of acquisition particle diameter 100～400 μ m; Get the compound microcapsule 5g of above-mentioned medicine carrying and join 100ml and contain in the acetic acid solution of 0.5～2wt% collagen protein, and add auxiliary material such as hyaluronic acid 0.5～1g, evenly stirring the back is buffer agent with ethylene sulfonic acid (MES), and adjust pH is 5.5; In mixed solution, add cross-linking agent solution carried out crosslinking Treatment, the cross-linking agent that uses be 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxy-succinamide (NHS), addition is 1～5mg/ml.Mixture was carried out cross-linking reaction in 24 hours 4 ℃ of placements.After the cross-linking reaction, inserted-80 ℃ of refrigerators freezing 24 hours, and carried out lyophilization and handle until removing solvent fully, distilled water flushing for several times, lyophilization can obtain Chinese medicine control-release function bone renovating bracket material once more.
Need to prove, because the material that polymer, collagen and auxiliary material comprised of load specific function Chinese medicine, biological activity inorganic nanometer powder and wall material thereof is more among the present invention, its preparation process is not enumerated one by one, but its preparation method, weight is the operating mode unanimity when, is not giving unnecessary details here.
Claims (8)
1. but the bone renovating bracket material of a controlled release Chinese medicine, it is characterized in that: the polymer, collagen, the auxiliary material that include load specific function Chinese medicine, biological activity inorganic nanometer powder and wall material thereof, the weight ratio of described load specific function Chinese medicine and biological activity inorganic nanometer powder is 99: 1-50: 50, the weight ratio of auxiliary material and collagen is 1: 99-10: 90, the weight ratio of biological activity inorganic nanometer-powder and collagen is 97: 3-60: 40, and the weight ratio of biologic inorganic nano-powder and wall material/polymer is 99: 1-50: 50.
2. but the bone renovating bracket material of controlled release Chinese medicine according to claim 1 is characterized in that: described load specific function Chinese medicine can be at least a in Herba Epimedii extract, Rhizoma Drynariae extract, Radix Dipsaci extract, Rhizoma Chuanxiong extract, Radix Morindae Officinalis extract, Eupolyphaga seu steleophaga extract, Radix Salviae Miltiorrhizae extract, astragalus polysaccharides, the antler polypeptide.
3. but the bone renovating bracket material of controlled release Chinese medicine according to claim 1, it is characterized in that: described biological activity inorganic nanometer powder can be at least a in nano tricalcium phosphate, nanometer hydroxyapatite, nano-calcium carbonate hydroxyapatite, nano fluorine-contained apatite, bioactivity glass and the composite granule between them, diameter of particle scope 50～400nm.
4. but the bone renovating bracket material of controlled release Chinese medicine according to claim 1 is characterized in that: the wall material/polymer of described biological activity inorganic nanometer powder can be a kind of in polylactic acid, poly (lactic acid-glycolic acid) copolymer, poly butyric ester, poly-propyl cellulose, ethyl cellulose, gelatin or the chitosan.
5. but the bone renovating bracket material of controlled release Chinese medicine according to claim 1 is characterized in that: described collagen can be type i collagen that extracts from the cattle heel string or the type i collagen that extracts from Corii Bovis seu Bubali.
6. but the bone renovating bracket material of controlled release Chinese medicine according to claim 1 is characterized in that: described auxiliary material can be wherein a kind of in hyaluronic acid and the phosphoserine.
7. but the preparation method of the bone renovating bracket material of a controlled release Chinese medicine is characterized in that: may further comprise the steps:
1) with biological activity inorganic nanometer powder and load specific function Chinese medicine by weight 99: 1-50: 50 ratio is fully mixed, then mixture is joined in the wall material/polymer with the blended biological activity inorganic nanometer powder of medium, and adopt solvent evaporated method to be prepared into the compound microcapsule of medicine carrying of particle diameter 100-400 μ m;
2) ratio of the compound microcapsule of medicine carrying according to weight ratio 97/3～60/40 joined in the acetic acid dissolved gum original solution, add auxiliary material simultaneously, evenly stir and mix;
3) add buffer agent, adjust pH is 5.5; In mixed solution, add cross-linking agent solution is carried out crosslinking Treatment, mixture is placed at 4 ℃ carried out cross-linking reaction in 24 hours;
4) after the cross-linking reaction, insert subzero 20 ℃-subzero 80 ℃ of refrigerator and cooled and froze 10-24 hour, the freezing dried of carrying out later.
8. but the preparation method of the bone renovating bracket material of controlled release Chinese medicine according to claim 7 is characterized in that: described buffer agent is an ethylene sulfonic acid, and cross-linking agent is 1-ethyl-3-carbodiimide or N-hydroxy-succinamide, and addition is 1～5mg/ml.
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Cited By (9)
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| CN103272282A (en) * | 2013-05-15 | 2013-09-04 | 福州大学 | Nanometer hydroxyapatite/chitosan/fish skin collagen composite scaffold |
| CN103477478A (en) * | 2011-03-30 | 2013-12-25 | 吉坤日矿日石能源株式会社 | Carbon material for negative electrode of lithium ion secondary battery, and production method thereof |
| CN107158461A (en) * | 2017-04-21 | 2017-09-15 | 芜湖扬展新材料科技服务有限公司 | A kind of polylactic acid composite biological tissue renovation material and preparation method thereof |
| CN108025107A (en) * | 2015-05-29 | 2018-05-11 | 朗克帕德医疗有限责任公司 | For being adhered to the composition and method on surface |
| CN108144110A (en) * | 2017-12-12 | 2018-06-12 | 王建东 | A kind of preparation method of promoting healing type head injury titanium net composite material |
| CN109620964A (en) * | 2018-12-26 | 2019-04-16 | 临沂市人民医院 | A kind of new method of " damage-reparation " Process Duty drug based on self-repair material structure |
| CN110227183A (en) * | 2019-07-12 | 2019-09-13 | 福建省华杭生物科技开发有限公司 | Rush knitting material and preparation method thereof based on pilose antler natural activity component |
| CN110612129A (en) * | 2017-10-19 | 2019-12-24 | 执行生物制药有限公司 | Autologous bone graft substitute |
| CN111330085A (en) * | 2020-02-27 | 2020-06-26 | 华东理工大学 | Traditional Chinese medicine regulation and control type composite active bone scaffold and preparation method and application thereof |
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| CN103477478A (en) * | 2011-03-30 | 2013-12-25 | 吉坤日矿日石能源株式会社 | Carbon material for negative electrode of lithium ion secondary battery, and production method thereof |
| CN103477478B (en) * | 2011-03-30 | 2016-08-10 | 吉坤日矿日石能源株式会社 | The carbon material for negative electrode of lithium rechargeable battery and manufacture method thereof |
| CN103272282A (en) * | 2013-05-15 | 2013-09-04 | 福州大学 | Nanometer hydroxyapatite/chitosan/fish skin collagen composite scaffold |
| CN108025107A (en) * | 2015-05-29 | 2018-05-11 | 朗克帕德医疗有限责任公司 | For being adhered to the composition and method on surface |
| CN107158461A (en) * | 2017-04-21 | 2017-09-15 | 芜湖扬展新材料科技服务有限公司 | A kind of polylactic acid composite biological tissue renovation material and preparation method thereof |
| CN110612129A (en) * | 2017-10-19 | 2019-12-24 | 执行生物制药有限公司 | Autologous bone graft substitute |
| CN108144110A (en) * | 2017-12-12 | 2018-06-12 | 王建东 | A kind of preparation method of promoting healing type head injury titanium net composite material |
| CN109620964A (en) * | 2018-12-26 | 2019-04-16 | 临沂市人民医院 | A kind of new method of " damage-reparation " Process Duty drug based on self-repair material structure |
| CN110227183A (en) * | 2019-07-12 | 2019-09-13 | 福建省华杭生物科技开发有限公司 | Rush knitting material and preparation method thereof based on pilose antler natural activity component |
| CN110227183B (en) * | 2019-07-12 | 2021-12-21 | 福建省华杭生物科技开发有限公司 | Bone healing promoting material based on natural active components of pilose antler and preparation method thereof |
| CN111330085A (en) * | 2020-02-27 | 2020-06-26 | 华东理工大学 | Traditional Chinese medicine regulation and control type composite active bone scaffold and preparation method and application thereof |
| WO2021169759A1 (en) * | 2020-02-27 | 2021-09-02 | 华东理工大学 | Traditional chinese medicine regulation and control type composite active bone scaffold, preparation method therefor and application thereof |
| CN111330085B (en) * | 2020-02-27 | 2024-02-13 | 华东理工大学 | Traditional Chinese medicine regulation type composite active bone scaffold and preparation method and application thereof |
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Application publication date: 20100929 |