CN101462707A - Natural high-purity nano hydroxylapatite leaching technology - Google Patents
Natural high-purity nano hydroxylapatite leaching technology Download PDFInfo
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- CN101462707A CN101462707A CNA200710302171XA CN200710302171A CN101462707A CN 101462707 A CN101462707 A CN 101462707A CN A200710302171X A CNA200710302171X A CN A200710302171XA CN 200710302171 A CN200710302171 A CN 200710302171A CN 101462707 A CN101462707 A CN 101462707A
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Abstract
The invention relates to a process for leaching a natural high-purity nanometer hydroxyapatite biomaterial. The hydroxyapatite keeps the basic crystal structure not damaged, and is a base biomaterial, the performance of the base biomaterial is closer to the biological performance of a bone, and the crystal structure is more suitable for the growth of bone cells and osteoclasts. The leaching process adopts a physical leaching method and a chemical leaching method which are alternately applied; and by the pure solute dissolution flow and chemical reactions under specific conditions and in specific solvents, organic compositions in the bone are dissolved, and the used solvents include water, ethanol, ketone or other organic solvents such as amine and the like. In the leaching process, the control temperature is adjusted, and the boiling water is repeatedly washed so as to ensure the purity and the nanometer crystal property of the natural hydroxyapatite.
Description
Technical field
The present invention relates to a kind of leaching technology of natural high-purity nano hydroxylapatite biomaterial, belong to the preparation field of biomedical material.
Background technology
In the mammalian bones such as ox, pig, sheep, hydroxyapatite content reaches 50～60%.This natural hydroxyapatite exists with very fine crystalline structure form in organism.This crystalline structure form is a kind of weak crystallization, irregular, lamellar morphology, thickness 5-10nm, and length 10-50nm is a kind of natural nano structure.Its calcium contents is 37.5%～38.0%, and phosphorus content is 15.5～19.0%, and this suitable calcium/phosphorus is than having determined the good chemical property in its surface.This crystallization mode is the basic substance of the superperformance of histoorgan, being difficult to chemical synthesis process is replicated external, therefore, if can extract highly purified natural hydroxyapatite and keep its basic crystalline structure not to be destroyed, just will obtain a kind of more near the basic biomaterial of bone biology performance.Test confirms that this crystalline structure is more suitable for the growth of scleroblast and osteoclast.
Bones such as ox, pig, sheep obtain easily, and the source is abundant, and its inorganic components and nature bone trabecularism and skeleton are quite approaching, are therefore paid attention to by people for a long time as bone grafting material always.But its organic composition (albumen, collagen etc.) is transplanted to bone always and is brought puzzlement, the mad cow disease that the rejection that the biological example consistency causes, PrPC cause etc.Remove these organic compositions and keep preferably that trabecular bone structure just can obtain better bone grafting material.
The method that tradition obtains the high purity inorganic components of animal bone generally all is by calcining.Calcining temperature generally will arrive more than 600 ℃.Recrystallization process widely can take place in hydroxyapatite crystal under this temperature, forms coarse macrobead crystalline structure, and the meticulous weak crystalline texture of hydroxyapatite under the havoc native state makes its forfeiture biological agents basis.At this coarse macrobead plane of crystal, scleroblast and osteoclast are difficult to form new bone forming and inorganic bone absorbs such running balance.
In addition, the method for some degreasing deproteinated bones in the past, just part is gone out organic composition, and most of collagen composition and a small amount of protein ingredient still exist, and can't obtain high purity hydroxyapatite composition.
Also have certain methods animal bone to be melted fully, extracting the bone crystallisate by crystallization method with alkali lye.This method basically completely destroy the hydroxyapatite crystal structure, the crystallisate composition that obtains has completely lost nature bone trabecular support structure.
The hydroxyapatite of natural high-purity can not only be directly as the graft materials of bone, can also be as good adsorbent, slow-released carrier etc., compound again with the organic macromolecule structure as collagen, functional protein or microbiotic etc., form novel biomaterial.Also can be used as food, cosmetics additive.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of preparation method of natural high-purity nano hydroxylapatite is provided.By this leaching technology, not only solve the recrystallize problem that calcining causes, thoroughly remove organic composition simultaneously, reach requirement of high purity, and can also the retained part trabecular bone structure.
Leaching technology is the unit operation that separates soluble constituent and residue with solvent impregnated solid mixture, claims liquid-solid extraction again.It is bone through the ox of handling early stage, pig, sheep that handled material is leached in the present invention.Adopt physics leaching, the multiple method of chemistry leaching to replace, by simple solute dissolution process, and specified conditions down and in the specific solvent chemical reaction with the organic composition dissolving that is contained in the bone, reclaim residue, can obtain the higher natural hydroxyapatite of purity, used solvent has other organic solvents such as water, alcohol, ketone, ammonia or amine.In leaching process, adjust controlled temperature, boiling water cleans repeatedly, guarantees the feature of natural hydroxyapatite purity and nanocrystal.
Concrete technological operation is as follows:
1, handles the early stage of material
Get animal femurs such as fresh bovine, pig, sheep, thoroughly peel off soft tissue, femur two ends spongy bone and femoral shaft cortex bone separate treatment.Animal bone is cut into the ossiculum piece of 8-20mm specification.In pressure pan, 100 ℃, under 5-10kg pressure, boiled 2 hours, carry out preliminary slaking degreasing.Drying is 8-10 hours in 60-80 ℃ of loft drier, under the room temperature, places 24 hours.
Also can adopt the chemical degreasing method.The bone piece was soaked in 30% superoxol 48 hours, the hydrogen peroxide that more renewed in 24 hours once, soft tissue is removed in the flowing water flushing, puts into the ether degreasing 24 hours.
2, leaching method is separated organic substance in the bone
The material that handle well early stage is put into soxhlet's extractor, add the toluene circulation and extracted 24 hours.Separation and Recovery material residue, with flowing water flushing 3 times, Air drying was used alcohol immersion 24 hours again, removed organic solvent.
Secondary liquid-solid extraction technology.The material residue is put into soxhlet's extractor, add in the azeotropic mixture of quadrol and water (85:15), the azeotropic cycling extraction 5～8 days of heating, azeotropic mixture for several times can according to circumstances be changed in the centre, there is not considerable change up to the solvent color, till the no organic substance extraction.
Also can according to circumstances adopt ultrasonic wave or centrifugal extractor to carry out liquid-solid extraction.
3, slightly wash technology
It is inferior slightly to be given a baby a bath on the third day after its birth with 100 ℃ of hot water in material residue taking-up back, and each scavenging period is 4 hours, has cleaned once with heat exchange water cleaning once more after whizzer drying, the drying.Boiling water cleans repeatedly and can guarantee that organic solvent and dissolved substance thoroughly remove, and also can guarantee natural hydroxyapatite crystal structure simultaneously.
According to inventory, can repeat above-mentioned liquid-solid extraction process once more in case of necessity.
4, fine purifiation technology
Use the deionized water flow wash, flow velocity 1L/ hour, flowing water flushing material residue at least three days was detected until organic solvent-free.
5, drying process
The material residue is dry in 150 ℃ of baking boxs, be warmed to 250～300 ℃ of further dryings 20 hours then.Thereby obtain the high-purity natural hydroapatite particles.Can further remove residual and organic matters matter by this drying means, improve hydroxyapatite purity.
6, pulverize
Pulverize according to product standard and type.Generally can wear into 0.2～2mm left and right sides particle, be used for bone and fill.Also can wearing into it more with colloidal mill etc., fine particle be used for organic macromolecules such as composite collagen, Mierocrystalline cellulose, the new biological implantation material of framework again.
7, packing sterilization
According to sclerotin source, particle size, weight, in the packing polyethylene bottle, the gamma-rays radiation sterilization.
Embodiment
By following examples the present invention is described for example further, and do not limit the present invention in any way, under the prerequisite that does not deviate from technical solution of the present invention, any change or change that those of ordinary skills that the present invention did are realized easily all will fall within the claim scope of the present invention.
Embodiment 1
Choose bulls bone in fresh 1 years old age, remove soft tissue, and femur two ends spongy bone and femoral shaft cortex bone are handled respectively.Cortex bone is cut into the big ossiculum piece of 1cm * 1cm, and spongy bone cuts into the big ossiculum piece of 1.5cm * 1.5cm.In pressure pan, 100 ℃, under 5-10kg pressure, boiled 2 hours, carry out preliminary slaking degreasing.Drying is 8-10 hours in 60-80 ℃ of loft drier, under the room temperature, places 24 hours.
The material that handle well early stage is put into soxhlet's extractor, add the toluene circulation and extracted 24 hours.Separation and Recovery material residue, the flowing water flushing, Air drying was used alcohol immersion 24 hours again, removed organic solvent.
Get 2000g degreasing bone piece, insert in the soxhlet's extractor, add 1000ml 99% quadrol and 150ml deionized water.Repeat to mix.The azeotropic extraction of heating begins to change vapor of mixture liquid 1 time 3 day every day, and liquid color is gradually by dark red thin out, and the solvent color did not change in the 4th, 5 day.。
It is inferior slightly to be given a baby a bath on the third day after its birth with 100 ℃ of hot water in material residue taking-up back, and each scavenging period is 4 hours, has cleaned once to dry with whizzer heat exchange water cleaning once more behind the Air drying.Use deionized water, flow velocity 1L/ hour, flowing water flushing material residue 5 days was detected to organic solvent-free.
The material residue is dry in 150 ℃ of baking boxs, be warmed to 250～300 ℃ of further dryings 20 hours then.Obtain the high-purity natural hydroapatite particles.Particulate product is worn into 0.2～2mm left and right sides small-particle, and packaging sterilizing.
Embodiment 2
Finished particle among the embodiment 1 is detected.Detection comprises X-ray diffraction analysis, scanning electron microscope, purity testing etc.
Its major ingredient of sample X-x ray diffraction analysis x is purer hydroxyapatite.Can observe the hydroxyapatite crystal structure under the scanning electron microscope is irregular, lamellar morphology, thickness 5-10nm, and length 10-50nm meets the hydroxyapatite crystal structure of fresh bone fully, in addition, does not find organic substance residues under the Electronic Speculum.
Purity testing: be to judge by total nitrogen and oxyproline analysis.Protein content＜0.06%, collagen content＜0.05%.
Claims (9)
1, a kind of leaching technology of natural high-purity nano hydroxylapatite biomaterial.This hydroxyapatite keeps its basic crystalline structure not to be destroyed, and is a kind of more near the basic biomaterial of bone biology performance, and this crystalline structure is more suitable for the growth of scleroblast and osteoclast.Adopt physics leaching, the multiple method of chemistry leaching to replace in the leaching technology, by simple solute dissolution process, and chemical reaction is with the organic composition dissolving that is contained in the bone under the specified conditions and in the specific solvent, and used solvent has other organic solvents such as water, alcohol, ketone, ammonia or amine.In leaching process, adjust controlled temperature, boiling water cleans repeatedly, guarantees natural hydroxyapatite purity and nanocrystal feature.Its technology comprises leaching treatment process, leaching technology, washing process and the drying process etc. in early stage.
2, the leaching technology earlier stage processing method of natural high-purity nano hydroxylapatite according to claim 1, its feature comprise the processing (cortex bone spongy bone separate treatment) of bone piece, 100 ℃ of poach slakings of 5-10kg pressure degreasing method.
3, the leaching technology of natural high-purity nano hydroxylapatite according to claim 1 is characterized in that adopting soxhlet's extractor, adds the toluene circulation and extracts 24 hours.Separation and Recovery material residue, with flowing water flushing 3 times, Air drying, alcohol immersion 24 hours is removed organic solvent.
4, the leaching technology of natural high-purity nano hydroxylapatite according to claim 1 is characterized in that adopting secondary liquid-solid extraction technology or liquid-solid extraction technology repeatedly.
5, secondary according to claim 4 or repeatedly liquid-solid extraction technology, it is characterized by in the azeotropic mixture of soxhlet's extractor adding quadrol and water (85:15), heat azeotropic cycling extraction 5～8 days, azeotropic mixture for several times can according to circumstances be changed in the centre, there is not considerable change up to the solvent color, till the no organic substance extraction.
6, the leaching technology of natural high-purity nano hydroxylapatite according to claim 1 adopts and slightly washes hydroxyapatite purity and the crystalline structure that guarantees preparation with fine purifiation technology.
7, the technology of slightly washing according to claim 6 is characterized in that 100 ℃ of hot water slightly give a baby a bath on the third day after its birth time, and each scavenging period is 4 hours, has cleaned once with heat exchange water cleaning once more after whizzer drying, the drying.Boiling water cleans repeatedly and can guarantee that organic solvent and dissolved substance thoroughly remove, and also can guarantee natural hydroxyapatite crystal structure simultaneously.
8, fine purifiation technology according to claim 6 is characterized in that using the deionized water flow wash, and flow velocity 1L/ hour, flowing water flushing material residue at least three days was detected until organic solvent-free.
9, the leaching technology of natural high-purity nano hydroxylapatite according to claim 1, the drying process feature of its utilization are dry in 150 ℃ of baking boxs, are warmed to 250～300 ℃ of further dryings 20 hours then.Thereby obtain the high-purity natural hydroapatite particles.Can further remove residual and organic matters matter by this drying means, improve hydroxyapatite purity.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA200710302171XA CN101462707A (en) | 2007-12-18 | 2007-12-18 | Natural high-purity nano hydroxylapatite leaching technology |
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| CNA200710302171XA CN101462707A (en) | 2007-12-18 | 2007-12-18 | Natural high-purity nano hydroxylapatite leaching technology |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206608A (en) * | 2011-04-27 | 2011-10-05 | 哈尔滨工业大学 | Preparation method of three-dimensional bone-like tissue used for study of microgravity effect stimulation |
| CN106082155A (en) * | 2016-06-07 | 2016-11-09 | 广西壮族自治区药用植物园 | Utilize the method that fishbone prepares hydroxyapatite |
| CN110606477A (en) * | 2018-06-14 | 2019-12-24 | 诺一迈尔（苏州）医学科技有限公司 | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material |
-
2007
- 2007-12-18 CN CNA200710302171XA patent/CN101462707A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206608A (en) * | 2011-04-27 | 2011-10-05 | 哈尔滨工业大学 | Preparation method of three-dimensional bone-like tissue used for study of microgravity effect stimulation |
| CN102206608B (en) * | 2011-04-27 | 2012-08-01 | 哈尔滨工业大学 | Preparation method of three-dimensional bone-like tissue used for study of microgravity effect stimulation |
| CN106082155A (en) * | 2016-06-07 | 2016-11-09 | 广西壮族自治区药用植物园 | Utilize the method that fishbone prepares hydroxyapatite |
| CN106082155B (en) * | 2016-06-07 | 2018-04-06 | 广西壮族自治区药用植物园 | The method that hydroxyapatite is prepared using fish-bone |
| CN110606477A (en) * | 2018-06-14 | 2019-12-24 | 诺一迈尔（苏州）医学科技有限公司 | Preparation method of hydroxyapatite, composite material containing hydroxyapatite and application of composite material |
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Open date: 20090624 |