CN102309523A - Dentoidin sponginum and preparation method thereof - Google Patents
Dentoidin sponginum and preparation method thereof Download PDFInfo
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- CN102309523A CN102309523A CN201110129457A CN201110129457A CN102309523A CN 102309523 A CN102309523 A CN 102309523A CN 201110129457 A CN201110129457 A CN 201110129457A CN 201110129457 A CN201110129457 A CN 201110129457A CN 102309523 A CN102309523 A CN 102309523A
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Abstract
The invention belongs to the field of pharmacy and medical technology and relates to a dentoidin sponginum and a preparation method thereof. The sponginum provided by the invention comprises 80-99wt% of dentoidin and 1-20wt% of collage sponge matrix, wherein the dentoidin is fixed on the collagen sponge through crosslinking in different weight ratios. The sponginum provided by the invention ensures that the dentoidin is filled into ill parts with bone defects, nonunion of bone, bone tissue atrophy, bone fracture, poor bone healing and the like, so that the dentoidin plays roles in inducing bone formation, promoting bone repair and promoting wound convergence.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of teeth matrix sponginum and method for preparing.This sponginum can be well moulding to teeth matrix; Sick position such as make that teeth matrix is filled into better that bone is damaged, bone does not connect, osseous tissue atrophy, fracture, knitting are bad, and bring into play it for a long time constantly with effective dose and induce osteogenesis, promote the bone reparation, promote the effect of wound astringent.
Background technology
Doctor Urist of the U.S. finds that the bone matrix of decalcification can induce the formation of bone and cartilage, and in having founded with sclerotin in nineteen sixty-five the osseous tissue of BMP form inducing action be the bone of core induce repair theoretical.After this, each scholar has carried out a large amount of research to bone reparation theory both at home and abroad, develops a series of osteogenic materials that derive from organism, mainly contains from body bone material and frozen homologous bone.But except bringing to the patient the secondary wound, cause supply the afunction in bone district toward the contact meeting from the transplanting of body bone, utilizing in addition from body bone-specific drug bone is damaged not only has limitation in a big way damaged treatment, also receives the restriction at patient's body constitution and age simultaneously; Though and the frozen homologous bone is easy to use, thereby be easier to cause that rejection causes the treatment failure.Along with to the BMP progress of research, find that BMP can induce the dystopy skeletonization.The scholar attempts with the synthetic in a large number BMP of methods such as genetic engineering and is used for the bone reparation; Though find it effect that improves skeletonization is arranged; But be easy in vivo diffusion dilution and by proteasome degradation; Be difficult to bring into play in vivo for a long time ossification, and need the suitable carriers controlling slow release, just can make playing a role of its longer time.Tooth material is exactly the biomaterial of a kind of BMP of containing and collagen protein, and I have obtained inducing osteogenesis, promotes osseous tissue to form and repaired a kind of novel bone induction material through the scientific methods proper process.This material has good effect to treatment of conditions such as bone does not connect, osseous tissue atrophy absorption, malunion of fracture and large-area bone are damaged.
Sponginum has more and more shown important function as a dosage form of medicament in clinical practice.A kind of spongy solid preparation that sponginum system is processed through foaming, curing, lyophilizing and sterilization by hydrophilic colloid solution.Sponginum substrate is divided into two types: the one, and use protein to process, like collagen sponge, gelfoam as raw material; The 2nd, the starch sponge that uses starch to process as material.It is frangible that the starch sponge quality is crisp; And collagen sponge and gelfoam matter are soft, and clinical practice is more.Sponginum is many clinically as the auxiliary hemostasis of surgery.Because sponginum has good biocompatibility, has no side effect; Advantage such as can thoroughly degrade in vivo; And Protocollagen class sponge itself has the fibroblast of inducing and epithelial cell regeneration; Promote the function of wound repair, so sponginum, in regeneration and restoration, brought into play more and more important effect.
This teeth matrix sponginum has spongiosis and the water absorption and swelling effect is arranged, and can improve teeth matrix at the damaged partial dosage of bone and for the growth of cell and cambium provides falsework, and inducing cell is realized partial directed differentiation and tissue regeneration better.
Summary of the invention
One of the object of the invention is to propose a kind of teeth matrix sponginum, and sick position such as make that teeth matrix is filled into that bone is damaged, bone does not connect, osseous tissue atrophy, fracture, knitting are bad is brought into play it and induced osteogenesis, promotes the bone reparation, promotes the effect of wound astringent.
Two of the object of the invention is the method for preparinies that propose above-mentioned teeth matrix sponginum.
One of goal of the invention of the present invention realizes through selecting a kind of teeth matrix sponginum for use.This sponginum comprise 80～99% said sponginum weight percentages teeth matrix and 1～20% collagen sponge, said teeth matrix is fixed on the collagen sponge substrate through the aldehydes cross-linking agent is crosslinked.
Said teeth matrix is the extracellular matrix material with the former tooth preparation of depleted mammal, prepares for adopting following method:
(1) soaks the former tooth raw material of mammal and stir digestion 30 minutes with 50% javelle water that is heated to 40 ℃, to remove soft tissue and sterilization;
(2) the former tooth raw material of disinfectant mammal is removed the bad tooth body of enamel, cementum and dental caries etc. through mechanical means, keeps dentin;
(3) mechanical activation comminution dentin makes it to become 10-100 purpose granule;
(4) the graininess dentin after will pulverizing set by step (1) remove its soft tissue and sterilization once more;
(5) 1: 1 chloroform formaldehyde putting into 5 times of volumes soaked 30 minutes;
(6) cleaning flowing water rinsing 0.6～0.65M HCl of putting into 5 times of volumes after 4 hours soaked 18～24 hours;
(7) sterile deionized water obtains teeth matrix after the rinsing rinsing repeatedly.
Said collagen protein is commercially available medical collagen.
Said aldehydes is formaldehyde or paraformaldehyde
Two of goal of the invention of the present invention realizes that through following technical scheme a kind of method for preparing for preparing above-mentioned teeth matrix sponginum is characterized in that this method comprises the steps:
(1) collagen protein is dissolved in 0.1%～1% acetic acid solution, processes 0.1～3% collagen solution, dialysis is to neutral in 0.2～2mM phosphate buffer (pH7.4～8.0);
(2) in above-mentioned collagen solution, add teeth matrix, stir;
(3) add a certain amount of 4%～6% formalin while stirring, be stirred to till the bubble that produces a large amount of uniform and delicate;
(4) in-80～-20 ℃ freezing 2～5 days, lyophilizing obtains spongy material;
(5) cutting, vacuum packaging, the virus of sterilizing, go out makes teeth matrix sponginum finished product.
The present invention utilizes dexterously that aldehydes is crosslinked to be fixed on the collagen sponge substrate teeth matrix is crosslinked; Utilize collagen sponge substrate RF; Imbibition and biodegradable characteristic; Strengthen the plasticity of the former teeth matrix of mammal, increase teeth matrix and damage partial dosage also for the growth of cell and cambium provides interim support at osseous tissue, inducing cell is realized partial directed differentiation and tissue regeneration better.Teeth matrix sponginum of the present invention has following advantage:
1, this sponginum is by teeth matrix and collagen protein combined effect and damaged part; Teeth matrix has the function that promotes osteoblast and chondrocyte differentiation; Collagen protein can be induced fibroblast and epithelial regeneration; Teeth matrix and collagen protein synergy like this can be repaired damaged part faster.
When 2, being applied to the osseous tissue damage, sponge substrate contacts with tissue fluid or blood and adsorbs tissue fluid or blood, is attached on rapidly on the damaged tissue, makes teeth matrix be confined to damaged part relatively, effectively improves the local bone matrix dosage of damage.
3, teeth matrix through the crosslinked fibrous reticular structure surface that is fixed on sponge substrate and wherein makes this sponge RF be similar to a support and drug storehouse storage, and it is local to greatest extent the former teeth matrix material of mammal to be fixed in the osseous tissue damage.
4, teeth matrix itself has slow-release function; Through crosslinked be fixed in the collagen sponge RF after, will further form the secondary slow release, along with the sponge host material by body degraded and progressively slowly discharge some teeth matrixes; Can be more among a small circle, the longer time is kept effective teeth matrix dosage.
5, this sponginum has designed the dosage form of different teeth matrixes of a plurality of series and collagen protein ratio; Regulate and control the slow release of teeth matrix more subtly; The teeth matrix sponge is discharged can coordinate with tissue repair more, and the dosage of teeth matrix is the extent of damage of adaptive bone more accurately.
6, this sponginum good biocompatibility has no side effect, and can thoroughly degrade in vivo, and degradable material can be by the tissue absorption utilization reparation that supporting wound healing that while sponge substrate itself has and tissue repair effect also help damaged tissue.
7, said preparation is taken packing apart and can be used, and makes things convenient for clinical practice; The said preparation production technology is simple, and the raw material source is abundant.
The specific embodiment
Embodiment 1: the preparation of teeth matrix
(1) soaks the former tooth raw material of mammal and stir digestion 30 minutes with 50% javelle water that is heated to 40 ℃, to remove soft tissue and sterilization;
(2) the former tooth raw material of disinfectant mammal is removed enamel, cementum etc. through mechanical means, keeps dentin;
(3) mechanical activation comminution dentin makes it to become 10-100 purpose granule;
(4) the graininess dentin after will pulverizing set by step (1) remove its soft tissue and sterilization once more;
(5) 1: 1 chloroform formaldehyde putting into 5 times of volumes soaked 30 minutes;
(6) the cleaning flowing water rinsing 0.6M HCl that puts into 5 times of volumes after 4 hours soaked 18 hours;
(7) sterile deionized water obtains teeth matrix after the rinsing rinsing repeatedly.
Embodiment 2: the preparation of teeth matrix
(1) soaks the former tooth raw material of mammal and stir digestion 45 minutes with 50% javelle water that is heated to 40 ℃, to remove soft tissue and sterilization;
(2) the former tooth raw material of disinfectant mammal is removed the bad tooth body of enamel, cementum and dental caries etc. through mechanical means, keeps dentin;
(3) mechanical activation comminution dentin makes it to become 10-100 purpose granule;
(4) the graininess dentin after will pulverizing set by step (1) remove its soft tissue and sterilization once more;
(5) 1: 1 chloroform formaldehyde putting into 5 times of volumes soaked 30 minutes;
(6) the cleaning flowing water rinsing 0.6M HCl that puts into 5 times of volumes after 4 hours soaked 24 hours;
(7) sterile deionized water obtains teeth matrix after the rinsing rinsing repeatedly.
Embodiment 3: the preparation of teeth matrix
(1) soaks the former tooth raw material of mammal and stir digestion 45 minutes with 50% javelle water that is heated to 40 ℃, to remove soft tissue and sterilization;
(2) the former tooth raw material of disinfectant mammal is removed the bad tooth body of enamel, cementum and dental caries etc. through mechanical means, keeps dentin;
(3) mechanical activation comminution dentin makes it to become 10-100 purpose granule;
(4) the graininess dentin after will pulverizing set by step (1) remove its soft tissue and sterilization once more;
(5) 1: 1 chloroform formaldehyde putting into 5 times of volumes soaked 30 minutes;
(6) the cleaning flowing water rinsing 0.65M HCl that puts into 5 times of volumes after 4 hours soaked 24 hours;
(7) sterile deionized water obtains teeth matrix after the rinsing rinsing repeatedly.
Embodiment 4: the preparation of teeth matrix sponginum
(1) collagen protein is dissolved in 0.1%～1% acetic acid solution, processes 0.1～3% collagen solution, dialysis is to neutral in 0.2～2mM phosphate buffer (pH7.4～8.0);
(2) in above-mentioned collagen solution, add teeth matrix, stir;
(3) add a certain amount of 4%～6% formalin while stirring, be stirred to till the bubble that produces a large amount of uniform and delicate;
(4) in-80 ℃ freezing 2 days, lyophilizing obtains spongy material;
(5) cutting, vacuum packaging, the virus of sterilizing, go out makes teeth matrix sponginum finished product.
Embodiment 5: the preparation of teeth matrix sponginum
(1) collagen protein is dissolved in 0.1%～1% acetic acid solution, processes 0.1～3% collagen solution, dialysis is to neutral in 0.2～2mM phosphate buffer (pH7.4～8.0);
(2) in above-mentioned collagen solution, add teeth matrix, stir;
(3) add a certain amount of 4%～6% formalin while stirring, be stirred to till the bubble that produces a large amount of uniform and delicate;
(4) in-20 ℃ freezing 5 days, lyophilizing obtains spongy material;
(5) cutting, vacuum packaging, the virus of sterilizing, go out makes teeth matrix sponginum finished product.
Claims (16)
1. a teeth matrix sponginum is characterized in that, this sponginum comprise 80～99% said sponginum weight percentages teeth matrix, said teeth matrix is crosslinked to be fixed on the collagen sponge substrate.
2. a kind of according to claim 1 teeth matrix sponginum is characterized in that, said teeth matrix is the teeth matrix material with the preparation of mammal tooth.
3. a kind of according to claim 1 teeth matrix sponginum is characterized in that, the particulate order number of said teeth matrix is the 10-100 order.
4. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 1～8% said sponginum weight percentage in the said collagen sponge substrate, and the order number of contained teeth matrix is the 10-30 order in the said collagen sponge substrate.
5. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 1～8% said sponginum weight percentage in the said collagen sponge substrate, and the order number of contained teeth matrix is the 30-60 order in the said collagen sponge substrate.
6. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 1～8% said sponginum weight percentage in the said collagen sponge substrate, and the order number of contained teeth matrix is the 60-100 order in the said collagen sponge substrate.
7. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 5～15% said sponginum weight percentages in the said collagen sponge substrate; The order number of contained teeth matrix is the 10-30 order in the said collagen sponge substrate.
8. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 5～15% said sponginum weight percentages in the said collagen sponge substrate; The order number of contained teeth matrix is the 30-60 order in the said collagen sponge substrate.
9. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains the collagen protein of 5～15% said sponginum weight percentages in the said collagen sponge substrate; The order number of contained teeth matrix is the 60-100 order in the said collagen sponge substrate.
10. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains collagen protein 10～20% in the said collagen sponge substrate; The order number of contained teeth matrix is the 10-30 order in the said collagen sponge substrate.
11. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains collagen protein 10～20% in the said collagen sponge substrate; The order number of contained teeth matrix is the 30-60 order in the said collagen sponge substrate.
12. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains collagen protein 10～20% in the said collagen sponge substrate; The order number of contained teeth matrix is the 60-100 order in the said collagen sponge substrate.
13. a kind of according to claim 1 teeth matrix sponginum is characterized in that, contains one or more short skeletal growth factors in the said teeth matrix sponge.
14. a teeth matrix sponginum, its preparation method is:
Collagen protein is dissolved in 0.1%～1% the acetic acid, processes 1%～20% collagen solution, add 80%～99% teeth matrix material; Stir; The formaldehyde or the paraformaldehyde solution of adding 4%～6% when stirring then are when the bubble that produces a large amount of uniform and delicate is, in-80 ℃～-20 ℃ lyophilizing; Cutting, vacuum-packed, sterilization, the teeth matrix material sponginum finished product of system.
15., it is characterized in that used collagen protein is commercially available medical collagen like the said collagen protein of claim 14.
16. like the said aldehydes cross-linking agent of claim 14 is formaldehyde or paraformaldehyde.
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| CN2011101294579A CN102309523B (en) | 2011-05-18 | 2011-05-18 | Dentoidin sponginum and preparation method thereof |
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| CN2011101294579A CN102309523B (en) | 2011-05-18 | 2011-05-18 | Dentoidin sponginum and preparation method thereof |
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| CN102309523A true CN102309523A (en) | 2012-01-11 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104800884A (en) * | 2015-02-27 | 2015-07-29 | 深圳市光明创博生物制品发展有限公司 | Decalcified human dentinal matrix material and preparation method thereof |
| CN110338944A (en) * | 2018-08-20 | 2019-10-18 | 郭建群 | Permanent teeth extract is preparing application and lower jaw packing material in lower jaw packing material |
| CN111150663A (en) * | 2020-02-26 | 2020-05-15 | 斯小燕 | Novel tooth filling material and preparation method thereof |
Citations (2)
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| CN1116121A (en) * | 1995-08-15 | 1996-02-07 | 李成林 | Decalcifying tooth matrix and making method |
| CN101612113A (en) * | 2009-06-23 | 2009-12-30 | 武汉海特生物制药股份有限公司 | A kind of nerve growth factor sponginum and preparation method thereof |
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2011
- 2011-05-18 CN CN2011101294579A patent/CN102309523B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1116121A (en) * | 1995-08-15 | 1996-02-07 | 李成林 | Decalcifying tooth matrix and making method |
| CN101612113A (en) * | 2009-06-23 | 2009-12-30 | 武汉海特生物制药股份有限公司 | A kind of nerve growth factor sponginum and preparation method thereof |
Non-Patent Citations (2)
| Title |
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| 李卫东: "脱矿人牙基质骨诱导材料修复骨缺损的实验研究", 《九江医学》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104800884A (en) * | 2015-02-27 | 2015-07-29 | 深圳市光明创博生物制品发展有限公司 | Decalcified human dentinal matrix material and preparation method thereof |
| CN110338944A (en) * | 2018-08-20 | 2019-10-18 | 郭建群 | Permanent teeth extract is preparing application and lower jaw packing material in lower jaw packing material |
| CN111150663A (en) * | 2020-02-26 | 2020-05-15 | 斯小燕 | Novel tooth filling material and preparation method thereof |
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| CN102309523B (en) | 2013-04-17 |
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