CN106139255A - A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate - Google Patents
A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate Download PDFInfo
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- CN106139255A CN106139255A CN201510193633.3A CN201510193633A CN106139255A CN 106139255 A CN106139255 A CN 106139255A CN 201510193633 A CN201510193633 A CN 201510193633A CN 106139255 A CN106139255 A CN 106139255A
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- Prior art keywords
- calcium phosphate
- collagen
- tcp
- mesh
- collagen protein
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 43
- 102000008186 Collagen Human genes 0.000 title claims abstract description 36
- 108010035532 Collagen Proteins 0.000 title claims abstract description 36
- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 26
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 23
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 23
- 239000000463 material Substances 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 12
- 210000001519 tissue Anatomy 0.000 claims abstract description 9
- 206010061363 Skeletal injury Diseases 0.000 claims abstract description 3
- 229920001436 collagen Polymers 0.000 claims description 24
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 15
- 239000002245 particle Substances 0.000 claims description 14
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 14
- 239000000084 colloidal system Substances 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 238000012216 screening Methods 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 230000002035 prolonged effect Effects 0.000 claims description 3
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 3
- 239000002808 molecular sieve Substances 0.000 claims description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 1
- 238000000280 densification Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 230000000451 tissue damage Effects 0.000 abstract 1
- 231100000827 tissue damage Toxicity 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 210000000845 cartilage Anatomy 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000005251 gamma ray Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241001421714 Olynthus Species 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000000515 collagen sponge Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
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- Materials For Medical Uses (AREA)
Abstract
The present invention is new material and the preparation method of a kind of medical sponge support as raw material with collagen protein and calcium phosphate.The present invention describes a kind of collagen protein and combines the new material of medical sponge support and the preparation method of calcium phosphate.Belong to biological medicine Material Field.When mainly solving to treat osteocartilaginous and subchondralo bone injury at present, can not carry out cartilaginous tissue reparation and problem that cartilaginous tissue to be repaired connected bone densification position (i.e. os osseum position) merges, the bone renovating material overcoming the most clinical collagen protein/calcium phosphate can not repair the phenomenon of osteochondral tissue damage well simultaneously.
Description
Technical field
The present invention relates to a kind of collagen protein and combine the new material of medical sponge support and preparation method, the glue of preparation of calcium phosphate
Olynthus support can be used for repairing the damage of osteochondral tissue.
Background technology
Disease or wound can cause the cartilage layers (also known as bone cartilage) of people's skeleton to be damaged, and clinic can be similar to cartilage by implantation
Substitute, for repairing or the cartilaginous tissue of regeneration of damaged wound, especially has the collagen protein of biocompatibility and biological degradability.
Collagen protein can induce the cell promoting blood vessel and nervous tissue's growth to adhere at cartilaginous lesion site as support, migrates and grows, entering
And promote the regeneration of cartilaginous tissue.Calcium phosphate is the host inorganic phase chemical composition of osseous tissue, particularly hydroxyapatite (chemistry point
Minor Ca5(PO4)3OH, English hydroxyapatite, write a Chinese character in simplified form HA) and bata-tricalcium phosphate (chemical molecular formula Ca3(PO4)2, English β
-tricalcium phosphate, writes a Chinese character in simplified form β-TCP) it is the height similar substance of osseous tissue composition, porosity is similar to bone sponge very much
Shape tissue, has the performance of good bone conduction and self-bone grafting, and therefore by HA, or β-TCP, or HA and β-TCP mixture (is write a Chinese character in simplified form
HA/ β-TCP), and collagen protein is used in mixed way the reparation for bone injury.The collagen protein of Clinical practice combines calcium phosphate at present
The bone repairing support of (writing a Chinese character in simplified form collagen/calcium phosphate), has good bone compact part repair, but is difficult to owing to hardness is higher moulding
And be not suitable for repairing cartilage and include osseocartilaginous damage.For overcoming this problem, by adding certain grain in collagen matrices
HA or β-TCP or the HA/ β-TCP of footpath and certain content is prepared as the sponge bracket of semi-solid, it is achieved one end hardness is high like solid
Body can stick bone compact part, and other end elasticity can fill up the damage space of cartilage like sponge, has so simultaneously facilitated osseocartilaginous
Regeneration and the fusion with bone compact part.
Summary of the invention
It is an object of the present invention to provide and a kind of there is good bio-compatible performance, biodegradability and osteochondral tissue repairing performance
The sponge bracket preparation method of semi-solid of collagen/calcium phosphate, for treating the damage of osteochondral tissue.Its step is as follows:
(1) with the molecular sieve mesh screen of suitable mesh selected from system or commercially available HA or β-TCP, ＜ 0.1mm (150 is obtained
Mesh), 0.1-0.3mm (between 150 mesh and 50 mesh) and the powder of ＞ 0.3mm (50 mesh) three groups of different-grain diameters or granule.If
With HA/ β-TCP, in specific weight ratio (optional any ratio between 80%: 20% to 20%: 80%), screening is obtained
Both same particle size are homogenously mixed together.
(2) in a container, weigh self-control or commercially available collagen protein, join injection pure water, arrive with acetic acid regulation pH value
3.0-4.5, is prepared as the suspension of 1-1.5% collagen solution (w/v, w/v), be divided into that volume is identical four parts.Vacuum is taken out
Rate removes bubble removing.
(3) calcium phosphate powder of each particle diameter above-mentioned or granule are individually added in the way of weight ratio (w/w) a collagen molten
In liquid, the agitation of agitator low speed forms suspension, more some hours of prolonged agitation is until being swelled into colloid, obtains accounting for collagen/calcium phosphate
Gross weight ratio is respectively three kinds of colloid solution of 15% (＜ 0.1mm HA), 45% (0.1-0.3mm HA) and 75% (＞ 0.3mm HA).
(4) by the colloid solution containing different-grain diameter calcium phosphate according to particle diameter order from big to small, one layer cover one layer on side
Formula is evenly laid out in a reservoir, topmost adds the 1-1.5% collagen solution without calcium phosphate.
(5) due to the collagen colloid solution very thickness of 1-1.5%, will not quickly merge between every layer, before fusion by container in
-20 DEG C of rapid cooled and solidified become solid.
(6) vacuum lyophilization obtains the sponge bracket of semi-solid, and apparent high for one end hardness, one end elasticity is high.
(7) sponge bracket is placed in the cross-linking agent solutions such as glutaraldehyde immersion, takes out and air-dry.
(8) sponge bracket cutting into required size, packaging, gamma-ray irradiation is degerming makes end product.
Detailed description of the invention
Example one
Weigh 15g collagen powder, add 1000ml injection pure water and dissolve the solution being made into 1.5%, with acetic acid regulation pH value be
3.8.By volume it is divided into quarter.Vacuum pumping rate removes bubble removing.In first part, add particle diameter ＜ 0.1mm HA reach to account for collagen/HA
The 15% of weight ratio, second part adds particle diameter 0.1-0.3mm HA and reaches to account for the 45% of collagen/HA weight ratio, and second part adds grain
Footpath ＞ 0.3mm HA reaches to account for the 75% of collagen/HA weight ratio.Agitator stirs with 500rpm speed low speed until being formed uniform
HA suspension, prolonged agitation is allowed to be swelled into colloid for some hours.The collagen containing particle diameter ＞ 0.3mm HA is poured gently in a container
/ HA colloid, pours the collagen containing particle diameter 0.1-0.3mm HA/HA colloid into, the most gently successively containing particle diameter ＜ 0.1mm HA
Collagen/HA colloid, and the collagen solution without HA.Container is put into-20 DEG C is frozen into solid rapidly.Vacuum lyophilization obtains
The collagen sponge scaffold of semi-solid, apparent high for one end hardness, one end elasticity is high.Sponge bracket is placed in the cross-linking agent such as glutaraldehyde
Solution soaks, takes out and air-dry；Sponge bracket cuts into required size, and packaging, gamma-ray irradiation is degerming makes end product.
Claims (1)
1. it is used for making collagen protein and combines the new material of medical sponge support and the preparation method of calcium phosphate (collagen/calcium phosphate),
Product is used for treating osseocartilaginous damage tissue, and calcium phosphate kind can be hydroxyapatite (HA) or bata-tricalcium phosphate (β-TCP)
Or the mixture (HA/ β-TCP) of hydroxyapatite and bata-tricalcium phosphate, select including by HA or β-TCP molecular sieve mesh screen
Obtaining powder or the granule of ＜ tri-kinds of particle diameters of 0.1mm, 0.1-0.3mm and ＞ 0.3mm, the collagen solution being added separately to 1-1.5% is made into
HA or β-TCP accounts for collagen/calcium phosphate gross weight than respectively 15% (＜ 0.1mm), 45% (0.1-0.3mm) and 75% (＞ 0.3mm)
The colloid solution of collagen/calcium phosphate, according to calcium phosphate powder or the size of granule, one layer cover one layer on mode by upper
State colloid solution be laid in make sponge bracket container in, if with HA/ β-TCP, the HA of the same particle size that screening is obtained with
β-TCP mixes equably, and both weight ratios can be any ratio between 80%: 20% to 20%: 80%, it is characterised in that system
Standby process includes following each step:
(1) take from system or commercially available HA or β-TCP screening obtain ＜ 0.1mm (150 mesh), 0.1-0.3mm (150 mesh and 50 mesh it
Between) and the powder of ＞ 0.3mm (50 mesh) three kinds of particle diameters or granule；If with HA/ β-TCP, weight ratio in specific proportions (can
Select any ratio between 80%: 20% to 20%: 80%), both same particle size screening obtained are homogenously mixed together；
(2) by the HA of three kinds of particle diameters, or β-TCP, or HA/ β-TCP powder or granule are separately added to the collagen solution of a 1-1.5%
In, the agitation of agitator low speed forms suspension, and prolonged agitation obtains accounting for gross weight ratio respectively for some hours until being swelled into colloid
It is 15% (＜ 0.1mm), three kinds of colloid solution of 45% (0.1-0.3mm) and 75% (＞ 0.3mm)；
(3) by the above-mentioned collagen colloid solution containing different-grain diameter calcium phosphate according to particle diameter order from big to small, one layer cover one layer on
Mode evenly laid out in a reservoir, topmost add the collagen solution of the 1-1.5% without calcium phosphate, be placed in-20 DEG C of refrigerators immediately
It is cooled to solid；
(4) vacuum lyophilization obtains the sponge bracket of collagen/calcium phosphate, and one end hardness High Availabitity is in sticking bone compact part, and one end is elastic
High Availabitity is in filling up osteocartilaginous and subchondralo bone injury position.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510193633.3A CN106139255A (en) | 2015-04-17 | 2015-04-17 | A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510193633.3A CN106139255A (en) | 2015-04-17 | 2015-04-17 | A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate |
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| Publication Number | Publication Date |
|---|---|
| CN106139255A true CN106139255A (en) | 2016-11-23 |
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| CN201510193633.3A Pending CN106139255A (en) | 2015-04-17 | 2015-04-17 | A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106729986A (en) * | 2016-12-28 | 2017-05-31 | 上海市第六人民医院 | Mix the preparation method of zinc calcium phosphate microsphere collagen composite biomimetic scaffolds |
| CN114425104A (en) * | 2021-12-21 | 2022-05-03 | 中国人民解放军空军军医大学 | Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof |
| EP4382141A1 (en) | 2022-12-05 | 2024-06-12 | Ustav materialoveho vyskumu Slovenskej Akademie vied, verejna vyskumna institucia | Composite biocement system |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1207753A (en) * | 1995-11-09 | 1999-02-10 | 威廉·邦菲尔德 | Bioactive composites for hard and soft tissue repair |
| CN1943801A (en) * | 2006-11-01 | 2007-04-11 | 华中科技大学 | A gradient laminated composite supporting frame material based on bionic structures and its preparation method |
| CN101163512A (en) * | 2005-03-04 | 2008-04-16 | 法恩扎Fin-陶瓷股份公司 | Cartilaginiform and osteochondral sustitute comprising a multilayer structure and use thereof |
| CN101628131A (en) * | 2009-08-25 | 2010-01-20 | 华中科技大学 | Method for preparing ultra-thin porous lamination gradient composite support of tissue engineering |
| CN102294052A (en) * | 2011-07-27 | 2011-12-28 | 东南大学 | Preparation method of medical high polymer based silver nano material |
-
2015
- 2015-04-17 CN CN201510193633.3A patent/CN106139255A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1207753A (en) * | 1995-11-09 | 1999-02-10 | 威廉·邦菲尔德 | Bioactive composites for hard and soft tissue repair |
| CN101163512A (en) * | 2005-03-04 | 2008-04-16 | 法恩扎Fin-陶瓷股份公司 | Cartilaginiform and osteochondral sustitute comprising a multilayer structure and use thereof |
| CN1943801A (en) * | 2006-11-01 | 2007-04-11 | 华中科技大学 | A gradient laminated composite supporting frame material based on bionic structures and its preparation method |
| CN101628131A (en) * | 2009-08-25 | 2010-01-20 | 华中科技大学 | Method for preparing ultra-thin porous lamination gradient composite support of tissue engineering |
| CN102294052A (en) * | 2011-07-27 | 2011-12-28 | 东南大学 | Preparation method of medical high polymer based silver nano material |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106729986A (en) * | 2016-12-28 | 2017-05-31 | 上海市第六人民医院 | Mix the preparation method of zinc calcium phosphate microsphere collagen composite biomimetic scaffolds |
| CN114425104A (en) * | 2021-12-21 | 2022-05-03 | 中国人民解放军空军军医大学 | Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof |
| CN114425104B (en) * | 2021-12-21 | 2023-03-03 | 中国人民解放军空军军医大学 | A drug-loaded bone conduction/induction composite structure and its preparation method and application |
| EP4382141A1 (en) | 2022-12-05 | 2024-06-12 | Ustav materialoveho vyskumu Slovenskej Akademie vied, verejna vyskumna institucia | Composite biocement system |
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Application publication date: 20161123 |
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