CN102416198A - Preparation method for pearl active ingredient extract/hydroxyapatite bone repair material - Google Patents

Preparation method for pearl active ingredient extract/hydroxyapatite bone repair material Download PDF

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CN102416198A
CN102416198A CN2011103987191A CN201110398719A CN102416198A CN 102416198 A CN102416198 A CN 102416198A CN 2011103987191 A CN2011103987191 A CN 2011103987191A CN 201110398719 A CN201110398719 A CN 201110398719A CN 102416198 A CN102416198 A CN 102416198A
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hydroxyapatite
pearl
active
extract
material extract
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CN2011103987191A
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申玉田
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Tsinghua University
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Tsinghua University
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Abstract

The invention discloses a preparation method for a pearl active ingredient extract/hydroxyapatite bone repair material and belongs to the technical field of preparation of biomedical materials. The method is mainly characterized by comprising the following steps of: directly dry-mixing pearl active ingredient extract and hydroxyapatite which are taken as raw materials in any proportion or uniformly mixing the pearl active ingredient extract and hydroxyapatite and auxiliary media, and dehydrating and drying to obtain a pearl active ingredient extract/hydroxyapatite bone repair material finished product. The process is easy to operate, and has few requirements on equipment, and the prepared pearl active ingredient extract/hydroxyapatite bone repair material is low in preparation cost, high in human body compatibility and bone formation activity and is an excellent bone repair material.

Description

The method for preparing of active pearl material extract/hydroxyl apatite bone repairing material
Technical field
The invention belongs to the bio-medical material preparing technical field, specifically relate to a kind of method for preparing of active pearl material extract/hydroxyl apatite bone repairing material.
Background technology
Aging and the accidental injury of bone is often inevitable, and the pathological changes skeleton finally will be replaced, and bone is implanted and repaired is that a kind of tissue that is only second to blood transfusion is transplanted.Present various artificial bone is repaired substitution material and is emerged in an endless stream, but mainly plays the effect of bone support, does not have the peculiar bone-inducting active of skeletal growth factor.Liu Zhiqiang; Zhou Dongfeng, report in " research of bone defect repair and the progress " on " Guangdong dental prevention, 2004; 12 (1): 73-75 " such as Zhou Lei; In fact desired bone repair process is: multiple somatomedin and activator be controlled release at position to be repaired, induces adjacent tissue's mesenchymal cell to be divided into osteoblast or stimulating osteoblast acceleration propagation, and assembles to position to be repaired; Thereby show tangible targeted induction osteogenic activity, finally accomplish the bone reparation of specific part.In recent years, people begin to recognize gradually somatomedin irreplaceable decisive regulating and controlling effect in bone is repaired, so in the bone reparation is clinical, begin to introduce skeletal growth factor.But skeletal growth factor is very expensive, price even up to 80,000 yuan/gram.
Margarita, concha Anodonta seu Cristaria, bone are all the biomineralization product, and the three is very close in essence in formation, and its biomineralization all is regulated and control by its organic component that contains.Concha Anodonta seu Cristaria is made up of prismatic layer and nacreous layer; The concha Anodonta seu Cristaria nacreous layer is the product of Mollusca biomineralization under normal physiological condition; The organic component that contains 1.2~3.3wt.% approximately; All the other are calcium carbonate, and existing research shows that these a spot of organic matters contain the multiple signal factor relevant with osteogenesis.People such as Gerard Atlan and Evelyne Lopez are in " Sci Paris/Life Sci, 1997; 320:253-8 ". in carried out the human experimentation of concha Anodonta seu Cristaria Margarita layer powder assertorically, shown very strong osteogenic activity.At present; People Zhang Rongqing such as domestic Zhang Rongqing etc. utilize the concha Anodonta seu Cristaria nacreous layer to develop a kind of nacreous bone renovating material that contains in patent CN 1476906A " a kind of nacreous bone renovating material and preparation method thereof that contains "; Also obtained people such as good osteogenic activity and Liu Jinbiao " research of nacreous layer/polylactic acid combinatorial artificial diaphysis external contact compatibility and degradation experiment. No.1 Military Medical Univ.'s journal; 2003; 23 (2): 130-133 " in prepared degradable (concha Anodonta seu Cristaria) nacreous layer/lactic acid composite material that is suitable for as the bone defect repair, external osteoblast culture experiment has shown that material has very strong bone inducibility.
Different with the concha Anodonta seu Cristaria nacreous layer, Margarita is the special mineralization product that Mollusca forms under the positive physiological condition of the extraneous damage of opposing.Up to now, it has been found that 24 routine people's corpse pearls, so Margarita and human internal environment are fully compatible.Margarita is rich in multiple bioactive substance, is exactly a kind of natural drug with magical anti-ageing effect of aesthetic health care since ancient times.The main component of Margarita is that calcium carbonate (containing a spot of calcium phosphate, calcium silicates), protein, moisture and various trace elements comprise: Fe, Al, Mg, Zn, Se, Cu, Mn, Ge, K, Sr etc.Protein in the Margarita is a kind of shell keratin (or claiming keratoprotein) that contains seed amino acid surplus in the of 20; Content is up to 8wt.%; Be called as active pearl material, research in recent years shows that Margarita is rich in: the unique defying age factor-porphyrins (PEG), taurine (2-aminoethyl sulfonic acid), carotenoid, light base Europe phosphorus aminoacid, chitin or the like.Therefore, Margarita possibly contain the needed somatomedin of multiple osteogenesis, activator and nutrition composition, and it is active that expection has stronger induced osteogenesis.
Current, the BMP-4 of producing through technique for gene engineering (rhBMP) is all arranged both at home and abroad, wherein the activity of rhBMP2 is the strongest.Yet degraded very soon behind the simple BMP implant into body; Do not have due effect; If there is suitable carriers to make it realize sustained release in vivo, just can effectively play a role, but not only difficulty is big in the screening of carrier; And carrier and somatomedin have a lot of uncertainties again after compound, possibly find a kind of all-round carrier that is fit to multiple somatomedin simultaneously especially hardly.On the other hand; In fact the formation of bone is to realize under the effect of multiple somatomedin network cooperating; The osteoplastic somatomedin of known participation has: and bone morphogenetic protein (bone morphogenetic proteins, BMP), transforming growth factor, insulin like growth factor, basic fibroblast growth factor, platelet derived growth factor, vascular endothelial cell growth factor etc.At any time, all have more than a kind of somatomedin in the microenvironment of osteocyte, therefore with single factors stimulated growth bone formation, differing obtains significative results surely.
Therefore, ideal somatomedin operation is in the bone repair process: somatomedin is slow sustained release in whole bone repair process, and multiple somatomedin synergism.And Margarita itself is exactly one to coordinate coefficient organic whole each other as the natural carrier of multiple known and unknown type of skeletal growth factor, therefore with the peculiar active substance replacement bone growth factor in the Margarita, carries out the reparation of people's bone and has potentiality.Especially the large-scale cultivation of current mussel pearl makes Margarita replace skeletal growth factor to be used for the reparation of people's bone becomes possibility on cost, and has advantage.
China's pearl production accounts for 95% of worldwide production, but pearl production 80~85% for not having the low-grade Margarita of decorative value, comprise irregular Margarita, variegated Margarita and pearlet or the like.Current, large-scale cultivation has caused a large amount of of low-grade Margarita to overstock, and only Zhuji City annual backlog in Zhejiang is just up to 300 tons, and price sharply drops, and its price is merely 100~300 yuan/kilogram.China Margarita industry is sinked into " high yield trap " at present; How to handle effectively and utilize these low-grade Margaritas, improve the added value of low-grade Margarita, the pearl farming is increased income; Rescue Margarita industry; Revitalizing local economy, is the difficult problem that whole pearl sector development faces, and the insider recognizes that generally the follow-up industrialization development of accelerating low-grade Margarita is the only way of breaking away from present predicament.
Hydroxyapatite be present bone repair clinical in a kind of comparatively sophisticated bone renovating material; Inorganic hydroxyapatite has good human compatibility; But but do not have induced osteogenesis active, therefore giving hydroxyapatite has important and practical meanings and medical value with bone-inducting active.
List of references:
1. applicant: Tsing-Hua University.Inventor: Yutian, Shen, Zhu Jing.The auxiliary method of pulverizing of internal stress self explosion.The applying date: 2006.10.26.Application number: 200610114064.X.Publication number: CN 1943865A.
2. applicant: Tsing-Hua University.Inventor: Yutian, Shen, Zhu Jing, Ling Tao, Ruan Huajun.Margarita powder/PEEK quasi natural bone composite and preparation and application.The applying date: 2006.11.9.Application number: 200610114415.7.Publication number: CN 1943800A.
3. applicant: Tsing-Hua University.Inventor: Zhu Jing, Yutian, Shen, Ling Tao, Ruan Huajun.During bone is repaired with the controlled releasing method of active pearl material instead skeletal growth factor.The applying date: 2006.11.9.Application number: 200610114414.2.Publication number: CN 1943802A.
4. Yutian, Shen.The biomineralization mechanism of concha Anodonta seu Cristaria and osteogenic activity and the applied research of Margarita.Tsing-Hua University's post-doctoral research report, Beijing, 2005.11.
5.Shen?Yutian,Zhu?Jing,Zhang?Hongbiao,Zhao?Fei.In?vitro?osteogenetic?activity?of?pearl.Biomaterials,2006,27:281
Stone will, Li Jiashun, etc.The experimentation of implanting between carbon fiber reinforced polyether-ether-ketone composite material vertebral body.The The 2nd Army Medical College journal, 2001,22 (4): 340
7. Liu Jin marks, Chen Jianting, etc.Nacreous layer/polylactic acid combinatorial artificial diaphysis external contact compatibility and degradation experiment research.No.1 Military Medical Univ.'s journal, 2003,23 (2): 130
Summary of the invention
The objective of the invention is to utilize multiple type of skeletal growth factor and other biological active component of containing in the active pearl material extract; It is mixed with hydroxyapatite; Thereby realize the modification of hydroxyapatite; It is active with induced osteogenesis to give hydroxyapatite, overcomes the shortcoming of its osteogenic induction scarce capacity.The advantage of this method is to have guaranteed that not only prepared active pearl material extract/hydroxyl apatite bone repairing material has good osteogenic activity, and preparation technology is simple, equipment requirements is low.
The present invention realizes above-mentioned purpose through following technical scheme.Active pearl material extract/hydroxyl apatite bone repairing material of the present invention; It is characterized in that; Be raw material directly with active pearl material extract and hydroxyapatite; It is dried mixed that both are pressed arbitrary proportion, or carry out uniform mixing with assist medium, can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product behind the dehydrate.
Described active pearl material extract can be to have and keep one or more the mixture in the bioactive pearl protein of Margarita, Margarita peptide, the peculiar trace element of Margarita, other pearl active organic component.
Described hydroxyapatite is commercial micron order or nano-grade hydroxy apatite.
Described assist medium can be a kind of in deionized water, simulated body fluid, the blood plasma; The selection of assist medium is beneficial to the active pearl material extract with addition and can fully contacts with hydroxyapatite, and uniform mixing is a principle.
Described dehydrate is dehydrate below 80 ℃ 1~12 hour with mix products.
Advantage of the present invention and good effect:
Active pearl material extract/hydroxyl apatite bone repairing material of the present invention has following advantage and good effect:
(1) a kind of active pearl material extract/hydroxyl apatite bone repairing material of the present invention; Be to utilize multiple type of skeletal growth factor and other biological active component that contains in the active pearl material extract; It is mixed with hydroxyapatite; Thereby realize the modification of hydroxyapatite, it is active with induced osteogenesis to give hydroxyapatite, overcomes the shortcoming of its osteogenic induction scarce capacity.
(2) method for preparing of the present invention has guaranteed that not only prepared active pearl material extract/hydroxyl apatite bone repairing material has good osteogenic activity, and preparation technology is simple, equipment requirements is low, production cost is low.
The specific embodiment
The following example is to further explanation of the present invention and explanation, and the present invention is not constituted any limitation.
Embodiment 1:
Get 1 gram active pearl material extract, 10 gram hydroxyapatite and 15 ml deionized water, the three carries out wet, to be mixed even after, 60 ℃ of following dehydrate 6 hours can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product.
Embodiment 2:
Get 3 gram active pearl material extracts and 10 gram hydroxyapatite, the two carries out dry blending, to be mixed evenly after, 60 ℃ of following dehydrate 1 hour can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product.
Embodiment 3:
Get 5 gram active pearl material extracts, 5 gram hydroxyapatite and 5 ml deionized water, the three carries out wet, to be mixed even after, 60 ℃ of following dehydrate 6 hours can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product.
Embodiment 4:
Active pearl material extract and hydroxyapatite are mixed by mass ratio at 1: 20; Add appropriate amount of deionized water in the mixed process as assist medium; To be mixed evenly after, 60 ℃ of following dehydrate 3 hours can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product.

Claims (5)

1. the method for preparing of an active pearl material extract/hydroxyl apatite bone repairing material; It is characterized in that; Be raw material directly with active pearl material extract and hydroxyapatite; It is dried mixed that both are pressed arbitrary proportion, or carry out uniform mixing with assist medium, can obtain active pearl material extract/hydroxyl apatite bone repairing material finished product behind the dehydrate.
2. the method for preparing of active pearl material extract/hydroxyl apatite bone repairing material according to claim 1; It is characterized in that described active pearl material extract can be to have and keep one or more the mixture in the bioactive pearl protein of Margarita, Margarita peptide, the peculiar trace element of Margarita, other pearl active organic component.
3. the method for preparing of active pearl material extract/hydroxyl apatite bone repairing material according to claim 1 is characterized in that, described hydroxyapatite is commercial micron order or nano-grade hydroxy apatite.
4. the method for preparing of active pearl material extract/hydroxyl apatite bone repairing material according to claim 1 is characterized in that, described assist medium can be a kind of in deionized water, simulated body fluid, the blood plasma; The selection of assist medium is beneficial to the active pearl material extract with addition and can fully contacts with hydroxyapatite, and uniform mixing is a principle.
5. the method for preparing of active pearl material extract/hydroxyl apatite bone repairing material according to claim 1 is characterized in that, described dehydrate is dehydrate below 80 ℃ 1~12 hour with mix products.
CN2011103987191A 2011-12-02 2011-12-02 Preparation method for pearl active ingredient extract/hydroxyapatite bone repair material Pending CN102416198A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110638836A (en) * 2019-08-30 2020-01-03 广东海洋大学 Application of water-soluble pearl powder in promoting wound healing
CN111115609A (en) * 2019-12-23 2020-05-08 华中科技大学鄂州工业技术研究院 Sr-Fe co-doped HAP nano-particles and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1493365A (en) * 2003-06-20 2004-05-05 四川大学 Preparation method of nano apatite crystal composite tissue engineering support material
CN1943802A (en) * 2006-11-09 2007-04-11 清华大学 The controlled releasing method by using active pearl material instead of bone growth factors in the bone restoration
CN101496908A (en) * 2009-02-20 2009-08-05 杭州电子科技大学 Pearl powder artificial bone supporting material with multi-stage micro-nano structure and technique for producing the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1493365A (en) * 2003-06-20 2004-05-05 四川大学 Preparation method of nano apatite crystal composite tissue engineering support material
CN1943802A (en) * 2006-11-09 2007-04-11 清华大学 The controlled releasing method by using active pearl material instead of bone growth factors in the bone restoration
CN101496908A (en) * 2009-02-20 2009-08-05 杭州电子科技大学 Pearl powder artificial bone supporting material with multi-stage micro-nano structure and technique for producing the same

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110638836A (en) * 2019-08-30 2020-01-03 广东海洋大学 Application of water-soluble pearl powder in promoting wound healing
CN111115609A (en) * 2019-12-23 2020-05-08 华中科技大学鄂州工业技术研究院 Sr-Fe co-doped HAP nano-particles and preparation method thereof

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Application publication date: 20120418