CN201182778Y - Biological type bone repair material - Google Patents
Biological type bone repair material Download PDFInfo
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- CN201182778Y CN201182778Y CNU2007200596886U CN200720059688U CN201182778Y CN 201182778 Y CN201182778 Y CN 201182778Y CN U2007200596886 U CNU2007200596886 U CN U2007200596886U CN 200720059688 U CN200720059688 U CN 200720059688U CN 201182778 Y CN201182778 Y CN 201182778Y
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- bone
- biological type
- activated
- basal body
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Abstract
The utility model provides biological type bone repair material, which is composed of a biological type bone material basal body and an inducted activated modification layer coupled on the surface of the basal body; wherein, the biological type bone material basal body is formed by animal bone after being processed with the steps of degreasing, cell separating, fixing treatment, multi-directional antigen removing, prion killing, and the like; the inducted activated modification layer can be a polypeptide activated surface layer coupled on the basal body, which can non-specifically adhere to growth factors; the induced activated modification layer also can be glycosaminoglycan compound activated surface layer coupled on the basal body. The biological type bone repair material not only removes the immunogenicity effectively, but also reserves the bone matrix containing a plurality of activated components, the biological type bone repair material is provided with bone induced activity, and is more similar to human bone in the organic composition, the inorganic composition, and the multidimensional structure, and the bone tissue can be well induced to be regenerated, in addition, the using is safer, and the tissue compatibility and the mechanical performance are good.
Description
Technical field
This utility model relates to a kind of bone renovating material, is used for the reparation damaged to bone, belongs to implant the class medical apparatus and instruments, is specially biological bone renovating material.
Background technology
The caused bone of surgical operation or pathological changes is damaged to be one of surgical common disease, and the treatment that bone is damaged need be used a large amount of bone renovating materials, promptly usually said artificial bone.The bone renovating material that is studied at present and uses mainly contains two big classes: a class is the bone renovating material of being made by synthetic material, mainly contains hydroxyapatite, tricalcium phosphate, polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polycaprolactam (PA
6) etc.Outside inorganic skeleton composition in above-described artificial bone hydroxyl-removal apatite, tricalcium phosphate and the osseous tissue was similar, the composition of all the other high polymers and bone had no common ground, was as a kind of shape stent applications.Hydroxyapatite and tricalcium phosphate, no matter sinter molding or the above high polymer are made the binding agent bonding forming, and its mechanical strength is all undesirable.Low fire ceramic not only property is crisp, and too hard, and host bone tissue is difficult to grow into, and therefore difficult and osseous tissue combines together.So how present hydroxyapatite and tricalcium phosphate are used as bone filler with powdery, granule or mastic, application is restricted; Second class is to be the bone renovating material of raw material with the nature bone.What be employed the earliest is animal bone, uses after organic matter is removed in 600～800 ℃ of roastings.The effect of roasting is an organic matter of removing strong immune immunogenicity, simultaneously killing pathogenic bacteria virus.But the sclerotin of roasting is very crisp, the mechanical strength variation, and behind the burning-off bone matrix, induce the ability of osseous tissue growth, can only among a small circle, use as inserts.At present by with the most use be the corpse bone, use after generally only soaking sterilization treatment as freezing and simple ethanol, ray sterilizing or glutaraldehyde, immune rejection often takes place and influence therapeutic effect.The source of main is corpse bone scarcely is donations voluntarily, even having is voluntary donations on a small quantity, by various countries' relevant laws, the organ of donations is that can not to be used for the profit be the transaction of purpose, in the market, the problem that has an ethics, the human rights, law as the corpse bone of commodity.Along with perfecting of law legal system, the source of corpse bone will be very limited.The research of much attempting to replace with animal bone the corpse bone is arranged in recent years, and some is just just used according to the simple deep cooling and the alcohol-pickled processing of corpse bone; Some carries out a little complicated processing such as defat, hydrofluoric acid treatment, glutaraldehyde immersion etc., all fails to design the antigen measure of going accordingly at the stronger immune immunogenicity of bone matrix.Therefore, is the artificial bone repair materials of raw material at present with the animal bone, exist the immune immunogenicity of can not ignore mostly and the osseous tissue growth healing that is difficult to induce the host, the problem that repairing effect is not good enough, thereby do not accepted by the user.Although many researcheres claim that all the animal bone of oneself handling is heterogeneous bone free of antibody or does not have antigens heterogeneity bone, but it is because not enough to immunogenic essence understanding, fail targetedly deblocking or destroy epitope (claiming antigenic determinant again), take for simple deep cooling or glutaraldehyde and soak and just can effectively remove antigen.Actually this is not so, according to immunoreactive molecular biology research and immunochemical result of study are thought, the immunogenicity of xenogenesis osseous tissue is to cause that by some active group or special conformation that is in special sensitive position in the bone matrix these specific activity groups or special conformation are called as epitope or antigenic determinant.Its antigenicity to be effectively removed and the structure of epitope must be managed to seal or destroy targetedly, and can not lean on simply freezing, defat, glutaraldehyde to handle, can not be only by taking off cell because acellular connective tissue, even the collagen of purifying all has certain antigenicity.
The utility model content
The purpose of this utility model is the deficiency that exists at the above artificial bone, providing a kind of is raw material with the animal bone, it is similar to nature bone to form (containing organic and inorganic composition) and structure (comprising that micropore runs through the multidimensional structure of structure), no antigen, virus-free, histocompatibility good, can induce the biological bone renovating material of receptor bone tissue growth healing.
The technical solution of the utility model is such: biological bone renovating material by animal bone through defat, take off cell, fixing handle, multi-faceted removing form the biological bone renovating material matrix after antigen, Protein virus such as kill at step process, and the induced activity decorative layer composition that is coupled at matrix surface.
Described induced activity decorative layer is a link coupled polypeptide active surface layer that can non-specific adhesion somatomedin on matrix.
Described induced activity decorative layer is a link coupled glycosaminoglycans complex activity surface layer on matrix.
Biological bone renovating material of the present utility model is to be raw material with the animal bone, is made through following making step:
A, choose suitable animal bone: comprise compact bone and spongy bone etc.;
B, pretreatment: carry out disinfection, removal of impurity, machine cuts molding etc.;
C, defat: with the fatty impurity of organic solvent extracting animal bone inside;
D, take off cell: remove wherein cell with surfactant or protease;
E, the fixing processing: the ossein in the material is carried out crosslinked fixing as cross linking fixative with epoxide;
F, the multi-faceted antigen that removes: plurality of reagents is destroyed or the blocking antigen epi-position;
G, Protein virus are killed: kill the Protein virus that may exist;
H, induced activity are modified: can adhere to somatomedin and cell activity component, and introduce biological bone surface;
I, packing;
J, gamma-radiation radiation sterilization;
K, through the check after get product.
In the above B step, the used disinfectant of described sterilization mainly is general broad-spectrum disinfectant, as benzalkonium bromide, hibitane, Hydrazoic acid,sodium salt etc.;
In the above C step, the organic solvent of the fatty impurity of extracting animal bone inside can be acetate esters, chloroform, carbon tetrachloride, ether, acetone, dehydrated alcohol etc.;
In the above D step, take off cell and be with the surfactant elution method and in the presence of collagen is protectant enzymatic isolation method, both use separately or both should be used for realizing simultaneously; Surfactant can be ethylenediaminetetraacetic acid, benzyl fluosulfonic acid, Triton X-100 (Tritonx100), Tris (Tris), and the used enzyme of enzymatic isolation method can be trypsin and pepsin.
In the above E step, described epoxy fixedly is meant and the ossein in the material is carried out crosslinked fixing with epoxide as cross linking fixative.Here epoxide can be the carbochain epoxide
R=H, CH in the formula
3(CH
2)
n-or
N=0,1,2 ... n; It also can be carbon oxygen chain epoxide
R=C in the formula
nH
2n+1-,
R '=H, CH
3-(C
2H
5)
n-, n=0,1,2 ... n, x=0,1,2 ... x.Epoxy cross-linking is fixing than the fixed benefit of traditional glutaraldehyde cross-linking to be: because epoxy radicals is more active, crosslinkedly carry out very fully, and easily control the degree of cross linking and correlated performance by the consumption of cross-linking agent, cross-linking products is more stable, not degraded easily, under the driving that cell proliferation, tissue growth need, go out the collaborative collagenase effect of kallikrein by emiocytosis, just with its degraded and absorbed, be passive degraded state, can make degraded and tissue growth synchronous, and its catabolite non-residual toxicity, histocompatibility is good.
In the above F step, the described multi-faceted antigen that removes is meant with plurality of reagents destruction or blocking antigen epi-position.Comprise with nucleopilic reagent combining its sealing with causing antigenic specific activity group, and cause antigenic special conformation with the change of strong hydrogen bonding reagent, wherein the conformation of tropocollagen molecule is mainly formed by hydrogen bond and causes that active group described here mainly is-OH
*,-NH
2 *,-SH
*Deng.Described nucleopilic reagent can be an acyl ammonia
R=C in the formula
nH
2n+1-, n=0,1,2 ... n; Amide
R=C in the formula
nH
2n+1-, n=0,1,2 ... n; Anhydride
R=C in the formula
nH
2n+1-, n=1～10; Or epoxide
R=C in the formula
nH
2n+1-,
N=0,1～10 etc., described strong hydrogen bonding reagent mainly is guanidine compound.
In the above F step, it is to kill the Protein virus that may exist that described Protein virus is killed, and can be no less than 1 hour with 1N soaking with sodium hydroxide bone material.
In the above G step, described induced activity modification is meant and can adheres to somatomedin and cell activity component, complex as some specific polypeptide or glycosaminoglycans is introduced product surface (containing the micropore inner surface), make to adhere to somatomedin and the seed cell that enrichment body self-regeneration mechanism discharges after implanting, induce the osseous tissue growth efficiently; Also can implant at the external BMP that adheres to earlier, BMP is a bone morphogenetic protein here again.Specific polypeptide described here is the polypeptides matter that a class can non-specific adhesion somatomedin, and one of polypeptide is by for containing the polypeptide that 16 lysines (K) and glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), cysteine (C) aggregate into: K (16) GRGDSPC; The glycosaminoglycans complex can be the complex of hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, heparan etc.The method of introducing can be a coupling agent coupling mode, also can chemisorbed.Coupling agent mainly be some easily with-NH
2,-OH, the difunctional material that the active hydrogen of-SH group reacts for example can be two acid diamides, two acyl dichloros, diacid intramolecular anhydride, di-epoxide, carbodiimides etc.
Among above-mentioned main preparation process C, D, E, F, G, the H, all used high infiltration technology simultaneously, in high permeable reactive device, carried out.So-called high infiltration technology is exactly the high permeable reactive device of a sonic oscillation and vacuum pulse interlock, can effectively gas in the bone material micropore and granule foreign be discharged by sonic oscillation and vacuum pulse, reagent corresponding can be worked the infiltration into microporous depths, guarantee inside and outside effect fully.
After the packing of product that makes,, can effectively kill other known animal derived viruses except that Protein virus with the cobalt-60 gamma-radiation irradiation sterilization that is not less than 25KGy.Like this, it is similar to nature bone just to make composition and structure, aseptic, virus-free, can not cause immune rejection, and good biocompatibility can be induced the novel artificial bone material of osteanagenesis.
Biological bone renovating material of the present utility model can be made kinds of artificial bone (being that bone substitutes body) as required, comprises artificial rib, phalanges, breastbone, skulls etc. also can be made into bone screw, hone lamella, intramedullary needle, bone fixation means such as spinal fusion device also can be made into skeletal grain, the bone piece, filling material of bone such as bone bar are applied in the orthopaedics therapy.
The advantage of biological bone renovating material of the present utility model is: be raw material with the full bone of animal directly, by epoxy fix, the multi-faceted advanced technologies such as antigen and induced activity modification of removing handle, and used high osmosis process, made effective removal immunogenicity, kept the sclerotin base that contains numerous active components again, novel artificial bone material with bone-inducting active, all more approaching on organic and inorganic composition and multidimensional structure with the human body bone, can induce osteanagenesis better.And use NaOH simultaneously and kill Protein virus and use gamma-radiation irradiation and kill known viruse, make use safer.Organic matter (deproteinization) animal bone is gone in contrast, and artificial bone of the present utility model is all even better on histocompatibility, mechanical property.Antigen is handled and epoxy is fixing handles without removing specially in contrast, and the Protein virus that goes out is handled, only do that simply alcohol-pickled, defat, glutaraldehyde are fixed, the animal bone of gamma-radiation sterilization, artificial bone of the present utility model histocompatibility and safety, go aspect immunogenicity, the osteoinductive even better.
Description of drawings
Fig. 1 makes the cross-sectional view of artificial bone rib for this utility model biological bone renovating material;
Fig. 2 makes the bone screw sketch map for this utility model biological bone renovating material;
Fig. 3 makes the sketch map of spinal fusion device for this utility model biological bone renovating material.
The specific embodiment
Below in conjunction with the drawings and specific embodiments this utility model is described in detail.
Biological bone renovating material, as shown in Figure 1, by animal bone through defat, take off cell, fixing handle, multi-facetedly remove the biological bone material matrix 1 that antigen, Protein virus form killing after, and induced activity decorative layer 2 compositions that are coupled at matrix surface.The induced activity decorative layer can be a link coupled polypeptide active surface layer that can non-specific adhesion somatomedin on matrix; Described polypeptide can be polypeptide K (16) GRGDSPC that is aggregated into by 16 lysines (K) and glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), cysteine (C).It also can be link coupled glycosaminoglycans complex activity surface layer on matrix.Biological bone renovating material of the present utility model can be made kinds of artificial bone (claiming bone to substitute body again) as required, comprises artificial rib, phalanges, breastbone, skull etc.; Also can be made into bone fixation means such as hone lamella, intramedullary needle, bone screw, spinal fusion device, also can be made into skeletal grain, bone bar, bone piece, bone inserts etc.(seeing Fig. 1, Fig. 2, Fig. 3)
Below be the embodiment of the concrete processing technology of biological bone renovating material.
Embodiment 1
Biological bone renovating material is to be raw material with the animal bone, is made through following making step:
A, choose animal bone;
B, pretreatment: with 0.1% benzalkonium bromide sterilization 30 minutes, clean the back specific purpose tool,, eliminate muscular tissue and periosteum, wash clean as xyster etc.;
C, defat: wherein fatty with the acetas lixiviate in high permeable reactive device, clean then;
D, take off cell: in high permeable reactive device, take off cell, clean then with surfactant;
E, the fixing processing: in high permeable reactive device, use epoxidation reagent
Fix processing, clean R=C in the formula then
nH
2n+1-,
N=0,1,2 ... n;
F, the multi-faceted antigen that removes: in high permeable reactive device, use the acyl chlorides nucleopilic reagent
Sealing causes antigenic active group, cleans R=C in the formula then
nH
2n+1-, n=0,1,2 ... n;
G, Protein virus are killed: be no less than 60 minutes with the 1N soaking with sodium hydroxide in high permeable reactive device, clean;
H, induced activity modify: in high permeable reactive device, polypeptide K (16) GRGDSPC of non-specific adhesion somatomedin be coupled in the goods with coupling agent carbodiimides (R-N=C=N-R '), and clean;
I, packing: pack with the sterile saline liquid storage hygrometric state of going bail for;
J, gamma-radiation radiation sterilization: with the sterilization of cobalt 60 gamma-radiations, gamma ray dose is not less than 25Kgy;
K, through the check after get product.
Embodiment 2
F, the multi-faceted antigen that removes: in high permeable reactive device, use the amide nucleopilic reagent
Sealing causes antigenic active group, cleans R=C in the formula then
nH
2n+1-, n=0,1,2 ... n;
H, induced activity are modified: with coupling agent diacid intramolecular anhydride polypeptide K (16) GRGDSPC is coupled in the goods in high permeable reactive device;
All the other steps are similar, and are no longer burdensome.
Embodiment 3
B, pretreatment:, clean the back with eliminating muscular tissue and periosteum, wash clean with 0.1% peracetic acid disinfectant 30 minutes;
E, the fixing processing: in high permeable reactive device, use epoxidation reagent
Fix processing, clean R=C in the formula then
nH
2n+1-,
R '=H, CH
3-(C
2H
5)
n-, n=0,1,2 ... n, x=0,1,2 ... x;
F, the multi-faceted antigen that removes: in high permeable reactive device, use epoxide
With the antigenic active group of guanidine compound sealing causing, clean R=C in the formula then
nH
2n+1-,
N=0,1～10;
H, induced activity are modified: with coupling agent two acyl dichloros polypeptide K (16) GRGDSPC is coupled in the goods in high permeable reactive device;
All the other steps are similar, and are no longer burdensome.
In the preparation method of this utility model biological bone renovating material, specialized designs use the multi-faceted antigen technology of removing that multiple active reagent sealed and destroyed epitope from many aspects, in addition, also designed with the above gamma-radiation radiation of 25KGy and killed animal originality virus, and increased the active surface activity modification step of osteogenic induction.Consider also that in addition bone matrix mainly exists in the micropore of bone, for the reagent that makes each step reaction can go deep in the micropore and the bone matrix effect, specialized designs one cover sonic oscillation add the high permeable reactive device of vacuum pulse, guarantee that reaction reagent energy infiltration into microporous depths and bone matrix react, and guarantee that effect is more abundant more effective.Make biological bone renovating material of the present utility model aspect histocompatibility, osteogenic induction activity, practicality all than existing, be that the goods of raw material are superior with the animal bone.
Claims (3)
1, biological bone renovating material is characterized in that: by the biological bone renovating material matrix, and the induced activity decorative layer composition that is coupled at matrix surface.
2, biological bone renovating material according to claim 1 is characterized in that: described induced activity decorative layer is a link coupled polypeptide active polypeptide surface layer that can non-specific adhesion somatomedin on matrix.
3, biological bone renovating material according to claim 1 is characterized in that: described induced activity decorative layer is a link coupled glycosaminoglycans complex activity surface layer on matrix.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2007200596886U CN201182778Y (en) | 2007-11-16 | 2007-11-16 | Biological type bone repair material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2007200596886U CN201182778Y (en) | 2007-11-16 | 2007-11-16 | Biological type bone repair material |
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|---|---|
| CN201182778Y true CN201182778Y (en) | 2009-01-21 |
Family
ID=40270515
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNU2007200596886U Expired - Lifetime CN201182778Y (en) | 2007-11-16 | 2007-11-16 | Biological type bone repair material |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010009616A1 (en) * | 2008-07-22 | 2010-01-28 | Grandhope Biotech Co., Ltd. | Biological nasal bridge implant and method of manufacture |
| CN102836463A (en) * | 2012-09-12 | 2012-12-26 | 于好勇 | Heterodermic conjunctiva graft and manufacturing method thereof |
-
2007
- 2007-11-16 CN CNU2007200596886U patent/CN201182778Y/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010009616A1 (en) * | 2008-07-22 | 2010-01-28 | Grandhope Biotech Co., Ltd. | Biological nasal bridge implant and method of manufacture |
| CN102836463A (en) * | 2012-09-12 | 2012-12-26 | 于好勇 | Heterodermic conjunctiva graft and manufacturing method thereof |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: GUANGDONG GUAN HAO BIOLOGICAL SCIENCE + TECHNOLOGY Free format text: FORMER OWNER: CANTON ZHIGUANG BIOTECHNOLOGY CO., LTD. Effective date: 20090619 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090619 Address after: Room 408, D international business incubator, Guangzhou Science City, Guangdong, Guangzhou Province, 510663, postcode: Patentee after: Guangdong summit life sciences Co., Ltd. Address before: Evelyn Lu Yun Chia Street Baiyun District of Guangzhou City, Guangdong Province, No. 3, room 604, zip code: 510515 Patentee before: Zhiguang Biological Sci-Tech Co., Ltd., Guangzhou |
|
| CX01 | Expiry of patent term |
Granted publication date: 20090121 |