JPH01167209A - Production of fine particle of hydroxyapatite - Google Patents
Production of fine particle of hydroxyapatiteInfo
- Publication number
- JPH01167209A JPH01167209A JP32651687A JP32651687A JPH01167209A JP H01167209 A JPH01167209 A JP H01167209A JP 32651687 A JP32651687 A JP 32651687A JP 32651687 A JP32651687 A JP 32651687A JP H01167209 A JPH01167209 A JP H01167209A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- hap
- organic solvent
- hydrophilic organic
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 8
- 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 title claims abstract description 8
- 239000010419 fine particle Substances 0.000 title claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000002244 precipitate Substances 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 239000011574 phosphorus Substances 0.000 claims description 4
- 235000011007 phosphoric acid Nutrition 0.000 abstract description 6
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 abstract description 4
- 239000007836 KH2PO4 Substances 0.000 abstract description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 abstract description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 abstract description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000006467 substitution reaction Methods 0.000 abstract description 3
- YIUHYXPIVIHBAM-UHFFFAOYSA-N CO.CO.CO.OP(O)(O)=O Chemical compound CO.CO.CO.OP(O)(O)=O YIUHYXPIVIHBAM-UHFFFAOYSA-N 0.000 abstract description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 abstract description 2
- 239000001110 calcium chloride Substances 0.000 abstract description 2
- 235000011148 calcium chloride Nutrition 0.000 abstract description 2
- 229910001628 calcium chloride Inorganic materials 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 229940126062 Compound A Drugs 0.000 abstract 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 abstract 1
- 235000019255 calcium formate Nutrition 0.000 abstract 1
- 239000011575 calcium Substances 0.000 description 35
- 239000012071 phase Substances 0.000 description 13
- 239000002245 particle Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical class [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010304 firing Methods 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- -1 phosphoric acid tripropoxide Chemical compound 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 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 description 2
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 101100219382 Caenorhabditis elegans cah-2 gene Proteins 0.000 description 1
- IDCBOTIENDVCBQ-UHFFFAOYSA-N TEPP Chemical compound CCOP(=O)(OCC)OP(=O)(OCC)OCC IDCBOTIENDVCBQ-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 229910052586 apatite Inorganic materials 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940043430 calcium compound Drugs 0.000 description 1
- 150000001674 calcium compounds Chemical class 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- AMJQWGIYCROUQF-UHFFFAOYSA-N calcium;methanolate Chemical compound [Ca+2].[O-]C.[O-]C AMJQWGIYCROUQF-UHFFFAOYSA-N 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011362 coarse particle Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- ZJXZSIYSNXKHEA-UHFFFAOYSA-L ethyl phosphate(2-) Chemical compound CCOP([O-])([O-])=O ZJXZSIYSNXKHEA-UHFFFAOYSA-L 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[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 VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011163 secondary particle Substances 0.000 description 1
- 238000003746 solid phase reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/325—Preparation by double decomposition
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、単相で微粒かつ結晶性の良好な高純度ヒドロ
キシアパタイトの製造法、さらにＣａ／Ｐ（原子比の意
味、以下同じ）を再現性良く制御することのできるヒド
ロキシアパタイトの製造方法に関するものである。[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a method for producing high-purity hydroxyapatite that is single-phase, fine-grained, and has good crystallinity, and further provides a method for producing high-purity hydroxyapatite that is single-phase, fine-grained, and has good crystallinity. The present invention relates to a method for producing hydroxyapatite that can be controlled with good reproducibility.
［従来の技術］
ＣａＯＰ２ Ｏ６系アパタイトは生体材料として開発さ
れており、中でも特にヒドロキシアパタイト（以下ＨＡ
Ｐと記す）は人体の骨を形成する物質と同じ組成であり
、生体内に埋入された場合、生体との親和性が良く、自
家骨との接合性も良いので、人工骨や人工歯などの材料
として用いられている。また蛋白質との親和性やＨＡＰ
自体の有するイオン交換能を利用してクロマトグラフィ
ー用の充填材やイオン交換材などにも用いられている。[Prior art] CaOP2 O6-based apatite has been developed as a biomaterial, especially hydroxyapatite (hereinafter referred to as HA).
P) has the same composition as the material that forms bones in the human body, and when implanted in a living body, it has good compatibility with the living body and has good bonding properties with autologous bone, so it can be used as an artificial bone or artificial tooth. It is used as a material such as In addition, affinity with proteins and HAP
Utilizing its own ion exchange ability, it is also used in chromatography packing materials and ion exchange materials.
ＨＡＰの製造方法としては、
■湿式法：Ｃａ塩水溶液と燐酸塩水溶液を反応させてＣ
ａＨＰＯ４，４０〜１．６７の微結晶状の燐酸カルシウ
ムを得、これを更に特定のカルシウム化合物と反応させ
て目的のＭＡＰに変換する方法、■水熱合成法：特公昭
５９−５１４８５号（特開昭５３−１１１０００号）公
報に開示されている様にＣａＨＰＯ４・２Ｈ２０（又は
ＣａＨＰＯ４）にＣａ（ＯＨ）２を加えて、あるいはＯ
ＣＰ ［Ｃａａ Ｈ２（ＰＯ４）８ ・５Ｈ２０］にＣ
ａ化合物を加えオートクレーブ中で２００〜４００℃、
１５〜２００気圧の熱水条件下で反応させて緻密結晶構
造の結晶質ＨＡＰを製造する方法、
■乾式合成法：特公昭５９−５１４８５号（特開昭５３
−１１１０００号）公報に開示されているＣａ’６ Ｈ
２（ＰＯ４）ａ ・５Ｈ２０にＣａ化合物を加え１００
０℃〜１３００℃で固相反応させて緻密結晶構造の結晶
質ＨＡＰを製造する方法、等がある。As for the production method of HAP, ■Wet method: Ca salt aqueous solution and phosphate aqueous solution are reacted to produce C
A method of obtaining microcrystalline calcium phosphate with aHPO4.40 to 1.67 and further reacting it with a specific calcium compound to convert it into the desired MAP. ■Hydrothermal synthesis method: Japanese Patent Publication No. 59-51485 (Special Publication No. 59-51485) As disclosed in Publication No. 111000/1983, Ca(OH)2 is added to CaHPO4.2H20 (or CaHPO4), or O
CP [Caa H2(PO4)8 ・5H20]
Add compound a and heat in an autoclave at 200-400°C.
A method for producing crystalline HAP with a dense crystal structure by reacting under hydrothermal conditions of 15 to 200 atmospheres, ■Dry synthesis method: Japanese Patent Publication No. 59-51485 (Japanese Patent Publication No. 59-51485)
-111000) Ca'6 H disclosed in the publication
2(PO4)a ・Add Ca compound to 5H20 to 100
There is a method of manufacturing crystalline HAP with a dense crystal structure by performing a solid phase reaction at 0° C. to 1300° C., and the like.
［発明が解決しようとする問題点］
前記■の方法は反応速度が大きいため生成物はコロイド
状となり、取扱いや操作の面で難があり、Ｃａ ／ Ｐ
の再現性が悪く、ＨＡＰ以外の生成相が混入したり、未
反応相が残ったりする。■の方法では高温高圧を必要と
し、設備費が高くなる上に生産効率も低い。またＨＡＰ
粒子の大きいものを得るには良い方法と言えるが微粒子
状のものは得難い。■の方法では反応を完結させようと
すれば高温かつ長時間を要する。また、■と■の方法で
はＨＡＰ生成の前段階として純粋なＣａＨＰＯ４・２Ｈ
２ｏ（又はＣａ ＨＰ Ｏ４）やＣａＨ２（ＰＯ４）ａ
・５Ｈ２０を得ることが不可欠である。[Problems to be Solved by the Invention] In the method (2) above, the reaction rate is high, so the product becomes colloidal, which is difficult in terms of handling and operation.
The reproducibility is poor, and produced phases other than HAP may be mixed in, or unreacted phases may remain. Method (2) requires high temperature and high pressure, which increases equipment costs and has low production efficiency. Also HAP
This is a good method for obtaining large particles, but it is difficult to obtain fine particles. Method (2) requires high temperatures and a long time to complete the reaction. In addition, in methods ■ and ■, pure CaHPO4.2H is
2o (or Ca HP O4) or CaH2(PO4)a
-It is essential to obtain 5H20.
また、粉末を成形して焼成固化する場合において、成形
体の密度を高くするに当たっては、粉末の粒子径ができ
るだけ細かくζしかも粒度分布の狭いことが望まれてい
るにもかかわらず、前記の方法で得られるＨＡＰ粒子は
サイズが数μｍから１０μｍ以上の粗粒のものであり、
−次粒子のサイズがこのように大きいと充填率が低くな
り、密度を高めることが難しい。そこで粒子サイズを細
かくしようとすると結晶性が悪くなり、水分を多く含む
ため緻密成形体の焼成時における収縮率が大きくなり、
かつ不定になるという問題を有していた。Furthermore, when compacting powder and solidifying it by firing, in order to increase the density of the compact, it is desirable that the particle size of the powder be as fine as possible and that the particle size distribution be narrow. The HAP particles obtained are coarse particles with a size of several μm to 10 μm or more,
- If the size of the secondary particles is this large, the filling rate will be low and it will be difficult to increase the density. Therefore, if we try to make the particle size finer, the crystallinity will deteriorate and the shrinkage rate during firing of the dense compact will increase due to the high water content.
And there was a problem that it became undefined.
そこで本発明においては過酷な条件を要することなく、
また高価な装置も必要とせずにＨＡＰ単相で微粒且つ結
晶性の良好なＨＡＰを製造する方法、更にはＣａ ／
Ｐを再現性良く制御することのできるＨＡＰの製造方法
について検討した。Therefore, in the present invention, without requiring harsh conditions,
In addition, there is a method for producing fine-grained HAP with good crystallinity using a single HAP phase without requiring expensive equipment, and furthermore, a method for producing HAP with fine grains and good crystallinity without requiring expensive equipment.
We investigated a method for producing HAP that can control P with good reproducibility.
［問題点を解決するための手段］
上記問題点を解決することのできた本発明とは所定のＣ
ａ ／ Ｐとなるように非燐酸型の反応性Ｃａ化合物お
よび非Ｃａ型の燐の反応性酸素酸化合物を５０℃以下の
水および／または親水性有機溶媒に溶解し、この溶液を
水および／または親水性有機溶媒に温度７０℃以上、ｐ
Ｈ４以上（好ましくは８〜１１）に保ちつつ滴下し、生
成する沈殿物を回収することを構成要旨とするものであ
る。[Means for solving the problems] The present invention that can solve the above problems is based on a predetermined C.
A non-phosphoric acid type reactive Ca compound and a non-Ca type phosphorus reactive oxygen acid compound are dissolved in water and/or a hydrophilic organic solvent at 50°C or less so that a / P, and this solution is dissolved in water and/or a hydrophilic organic solvent. Or in a hydrophilic organic solvent at a temperature of 70°C or higher, p
The gist of the system is to drop the solution while maintaining the temperature at H4 or higher (preferably 8 to 11) and collect the generated precipitate.
［作用］
本発明で用いる非燐酸型の反応性Ｃａ化合物および非Ｃ
ａ型の反応性酸素酸化合物は水あるいは親水性有機溶媒
に可溶なものであり、例えば非燐酸型の反応性Ｃａ化合
物としてはＣａＣｌ２゜Ｃａ （ＮＯ３）２ 、Ｃａ
（ＨＣＯＯ）２ 。[Action] Non-phosphate reactive Ca compound and non-C
The a-type reactive oxygen acid compound is soluble in water or a hydrophilic organic solvent. For example, non-phosphoric acid type reactive Ca compounds include CaCl2°Ca(NO3)2, Ca
(HCOO)2.
Ｃａ （ＣＨ３Ｃｏｏ）２ 、Ｃａ （ＯＨ）２ 。Ca (CH3Coo)2, Ca (OH)2.
ＣａＣＯ３等やカルシウムジメトキシド、カルシウムジ
ェトキシド、カルシウムジブロボキシド等のＣａ−アル
コキシド類およびカルボン酸塩類等が非限定的に例示さ
れる。また非Ｃａ型の燐の反応性酸素酸化合物としては
Ｈ２ＰＯ４あるいはＫＨ２ＰＯ４、ＮＨ４Ｈ２ＰＯ４。Non-limiting examples include CaCO3, Ca-alkoxides such as calcium dimethoxide, calcium jetoxide, and calcium dibroboxide, and carboxylic acid salts. In addition, non-Ca type phosphorus reactive oxygen acid compounds include H2PO4, KH2PO4, and NH4H2PO4.
（ＮＨ４）２ ＨＰＯ４、（ＮＨ４）３Ｐ０４等の如き
燐酸塩の他、燐酸トリメトキシド、燐酸トリエトキシド
、燐酸トリプロポキシド、亜燐酸トリメトキシド、亜燐
酸トリエトキシド、亜燐酸トリプロポキシド等の各種燐
の酸素酸のアルコキシド類や燐酸トリメチル、メタ燐酸
エチル、燐酸モノエチル、燐酸ジエチル、燐酸トリエチ
ル、ピロリン酸エチル等の各種燐の酸素酸のエステル類
が非限定的に例示される。In addition to phosphates such as (NH4)2HPO4 and (NH4)3P04, various phosphorus oxygen acids such as phosphoric acid trimethoxide, phosphoric triethoxide, phosphoric acid tripropoxide, phosphorous trimethoxide, phosphorous triethoxide, and phosphorous tripropoxide are used. Non-limiting examples include alkoxides and esters of various phosphorus oxygen acids such as trimethyl phosphate, ethyl metaphosphate, monoethyl phosphate, diethyl phosphate, triethyl phosphate, and ethyl pyrophosphate.
前記非燐酸型の反応性Ｃａ化合物および非Ｃａ型の燐の
反応性酸素酸化合物を所定のＣａ ／ Ｐとなるような
配合で５０℃以下の水および／または親水性有機溶媒に
溶解させ、この溶解液を水および／または親水性溶媒に
温度７０℃以上、ｐＨ４以上（好ましくは８〜１１）に
保ちつつ滴下し、水和置換反応させてＨＡＰ沈殿物を得
る。この際溶解液の温度を５０℃以下とするのは溶解液
中での反応を抑制するためである。The non-phosphoric acid type reactive Ca compound and the non-Ca type phosphorus reactive oxygen acid compound are dissolved in water and/or a hydrophilic organic solvent at a temperature of 50°C or less in a proportion that gives a predetermined Ca/P, and this The solution is added dropwise to water and/or a hydrophilic solvent while maintaining the temperature at 70° C. or higher and the pH at 4 or higher (preferably 8 to 11) to cause a hydration displacement reaction to obtain a HAP precipitate. At this time, the temperature of the solution is set to 50° C. or less in order to suppress the reaction in the solution.
また被滴下液の温度を７０℃以上に保つとともにＫＯＨ
，ＮａＯＨ，ＮＨ４ＯＨ等のアルカリを滴下してｐＨを
４以上（好ましくは８〜１１）に保つのは、被滴下液の
温度が７０℃未満では生成ＨＡＰが非晶質相との混合晶
となってしまい、また結晶性も悪くなってしまうからで
あり、被滴下液の温度は７０℃以上とする。また被滴下
液がｐＨ４未満では沈殿物が生成せず、生成しても生成
したＨＡＰ微粒子が再溶解し、生成物の粒子形状や化学
組成が不安定になるのでｐＨ４以上（好ましくは８〜１
１）に保つことが必要である。In addition, while keeping the temperature of the dripping liquid above 70℃,
, NaOH, NH4OH, etc. to keep the pH at 4 or higher (preferably 8 to 11) is because if the temperature of the dropping liquid is below 70°C, the HAP formed will become a mixed crystal with an amorphous phase. This is because the temperature of the liquid to be dropped should be 70° C. or higher. In addition, if the dropping solution has a pH of less than 4, no precipitate will be formed, and even if a precipitate is formed, the generated HAP fine particles will be redissolved, making the particle shape and chemical composition of the product unstable.
1).
また前記Ｃａ化合物および前記Ｐ化合物を溶解する液あ
るいは溶解液を滴下する被滴下液の水以外の親水性有機
溶媒としてはメタノール、エタノール、アセトン、エー
テル等が例示され、水和反応置換に際しては溶解液およ
び被滴下液として同じものあるいは異なるものを使用し
ても良い。In addition, examples of hydrophilic organic solvents other than water for the solution dissolving the Ca compound and the P compound or the dropping solution to which the solution is dropped include methanol, ethanol, acetone, ether, etc. The liquid and the dripping liquid may be the same or different.
水和反応置換して得られるＨＡＰのＣａ ／ Ｐは配合
原料のＣａ ／ Ｐに対して第１図に示すような結果が
得られ、配合原料のＣａ ／ Ｐ≧１．３以上のもので
は単相ＨＡＰが得られる。この点は原料の如何を問わず
本発明方法によれば同様であり、再現性の良いものであ
った。またＨＡＰ粒子は分散性に優れ、サイズおよび形
状のそろった針状微粒子であった。The results shown in Figure 1 are obtained for the Ca/P of HAP obtained by hydration reaction substitution with respect to the Ca/P of the blended raw materials, and when the blended raw materials Ca/P is 1.3 or more, it is simple. Phase HAP is obtained. This point was the same according to the method of the present invention regardless of the raw material, and the reproducibility was good. Furthermore, the HAP particles had excellent dispersibility and were acicular fine particles of uniform size and shape.
［実施例］
実施例１
第１表に示す配合割合でＣａＧ１２とＫＨ２ＰＯ４を２
５℃でイオン交換水１℃に溶解し、混合溶液とした。[Example] Example 1 CaG12 and KH2PO4 were mixed at the blending ratio shown in Table 1.
It was dissolved in ion-exchanged water at 1°C at 5°C to form a mixed solution.
′ｆＳ１表
続いて７０℃のイオン交換水Ｉ℃にこの温度を保ちつつ
、ｐＨコントローラに接続したマイクロチューブポンプ
でＫＯＨ液をｐＨ４以上に保つように加えるとともに前
記混合液を滴下したところ乳白色の懸濁液を得た。該懸
濁液を２時間保持した後、メンブランフィルタ−にて濾
過し、ＡｇＮ０．液で濾液の白濁が認められなくなるま
で純水で洗浄した。得られた生成物を１００℃にて乾燥
後粉末Ｘ線回折に付した結果によると、原料のＣａ ／
Ｐが１．０のものを除いてすべてＨＡＰの単相であっ
た。また透過電子顕微鏡による粒子形状の観察ではサイ
ズのそろった針状粒子が均一に分散していた。得られた
ＨＡＰのＣ、ａ ／ Ｐと原料のＣａ ／ Ｐの関係を
第１図に示す。'fS1 Table Next, while keeping this temperature at 70°C ion-exchanged water I°C, KOH solution was added using a microtube pump connected to a pH controller to keep the pH above 4, and the above mixture was dropped, resulting in a milky white suspension. A cloudy liquid was obtained. After holding the suspension for 2 hours, it was filtered with a membrane filter and AgN0. The filtrate was washed with pure water until no cloudiness was observed in the filtrate. According to the results of drying the obtained product at 100°C and subjecting it to powder X-ray diffraction, the raw material Ca/
All of them had a single phase of HAP except for the one with P of 1.0. Furthermore, observation of the particle shape using a transmission electron microscope revealed that acicular particles of uniform size were uniformly dispersed. Figure 1 shows the relationship between C, a/P of the obtained HAP and Ca/P of the raw material.
実施例２
第２表に示すＣａ ／ Ｐの配合割合でＣａＧ１２とＨ
３Ｐ ０４ （８５％濃度）を２５℃のイオン交換水
ＩＡに溶解して混合溶液を得、実施例１と同様にして第
２表に示すＣａ ／ ＰのＨＡＰを得た。Example 2 CaG12 and H with the Ca/P blending ratio shown in Table 2
3P 04 (85% concentration) was dissolved in ion-exchanged water IA at 25°C to obtain a mixed solution, and the Ca/P HAP shown in Table 2 was obtained in the same manner as in Example 1.
得られたＭＡＰは単相で分散性に優れ、サイズのそろっ
た針状粒子であった。The obtained MAP was a single phase, had excellent dispersibility, and was acicular particles of uniform size.
第 ２ 表
実施例３
Ｃａ／Ｐ＝１．６７となるような配合割合でＣａエトキ
シドと燐酸トリメチルを２５℃のエチルアルコールに溶
解して混合溶液を得た。次いで実施例１と同様にしてＣ
ａ／Ｐ＝１．６７のＨＡ、Ｐを得た。Table 2 Example 3 Ca ethoxide and trimethyl phosphate were dissolved in ethyl alcohol at 25° C. at a mixing ratio such that Ca/P=1.67 to obtain a mixed solution. Then, in the same manner as in Example 1, C
HA and P of a/P=1.67 were obtained.
得られたＨＡＰは単相で分散性に優れ、サイズのそろフ
た微粒針状粒子であった。The obtained HAP was a single phase, had excellent dispersibility, and was fine needle-like particles with a uniform size.
比較例１
１．５にのＣａ （ＯＨ） ２スラリー（濃度ｉａ、５
ｇ／ｆｌ）に１５℃のＨ３ＰＯ４液（Ｈ３ＰＯ４濃度８
５％、濃度ｕ３ｇ／ｕ）を添加して（この時、Ｏ
Ｃａ ／ Ｐ ＝ １．６６６でＣａ ／ Ｐ ＜−と
なっている）第３表に示す条件で反応させ、得られた生
成物の化学組成ならびにＸ線回折による生成相を第３表
に示す。Comparative Example 1 Ca (OH) 2 slurry (concentration ia, 5
g/fl) at 15℃ H3PO4 solution (H3PO4 concentration 8
5%, concentration u3g/u) (at this time, O Ca / P = 1.666 and Ca / P <-) was reacted under the conditions shown in Table 3, and the obtained product was Table 3 shows the chemical composition of and the phases formed by X-ray diffraction.
第３表から明らかなように生成物は各種燐酸カルシウム
が含有されており、ＨＡＰ単相のものは得られないこと
がわかる。またＣ ａ ／ Ｐも反応条件によって異な
りている。As is clear from Table 3, the product contains various calcium phosphates, and it can be seen that a single-phase HAP product cannot be obtained. Moreover, C a /P also differs depending on the reaction conditions.
比較例２
Ｃａ （ＯＨ）２１０ｇ／ ｊ’のスラリーにＨ３ＰＯ
４１０ｇ／λをＣａ／Ｐ＝１．６７となるように添加混
合し、７０℃でＨＡＰを反応生成させた。得られたＨＡ
ＰのＣａ ／ Ｐは第２図に示すように反応ロットごと
に異なり、Ｃａ ／ Ｐの制御が不可能であった。また
粒子形状もふぞろいで結晶性も低ヰかった。Comparative Example 2 H3PO to slurry of Ca (OH) 210g/j'
410 g/λ was added and mixed so that Ca/P=1.67, and HAP was reacted and produced at 70°C. Obtained HA
As shown in FIG. 2, the Ca/P of P varied from reaction lot to reaction lot, making it impossible to control Ca/P. Furthermore, the particle shape was irregular and the crystallinity was low.
［発明の効果］
本発明は以上のように構成されているので、単相で微粒
かつ結晶性の良好な高純度のヒドロキシアパタイトを製
造することができる。またＣａ／Ｐを再現性良く制御す
ることができる。[Effects of the Invention] Since the present invention is configured as described above, it is possible to produce high-purity hydroxyapatite that is single-phase, fine-grained, and has good crystallinity. Moreover, Ca/P can be controlled with good reproducibility.
第１図は配合原料Ｃａ ／ Ｐに対する生成ＨＡＰのＣ
ａ ／ Ｐを示す図、第２図は比較例における各反応ロ
ットのＣａ ／ Ｐを示す図である。Figure 1 shows the C of produced HAP with respect to the raw materials Ca/P.
FIG. 2 is a diagram showing Ca/P of each reaction lot in a comparative example.
Claims (1)
物および非Ｃａ型の燐の反応性酸素酸化合物を５０℃以
下の水および／または親水性有機溶媒に溶解し、この溶
液を水および／または親水性有機溶媒に温度７０℃以上
、ｐＨ４以上に保ちつつ滴下し、生成する沈殿物を回収
することを特徴とするヒドロキシアパタイト微粒子の製
造方法。A non-phosphoric acid type reactive Ca compound and a non-Ca type phosphorus reactive oxygen acid compound are dissolved in water and/or a hydrophilic organic solvent at a temperature of 50°C or less so that a predetermined Ca/P is obtained, and this solution is dissolved in water and/or a hydrophilic organic solvent. and/or a method for producing hydroxyapatite fine particles, which comprises adding dropwise to a hydrophilic organic solvent while maintaining the temperature at 70°C or higher and the pH at 4 or higher, and collecting the generated precipitate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62326516A JP2572793B2 (en) | 1987-12-23 | 1987-12-23 | Method for producing hydroxyapatite fine particles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62326516A JP2572793B2 (en) | 1987-12-23 | 1987-12-23 | Method for producing hydroxyapatite fine particles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01167209A true JPH01167209A (en) | 1989-06-30 |
| JP2572793B2 JP2572793B2 (en) | 1997-01-16 |
Family
ID=18188705
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62326516A Expired - Lifetime JP2572793B2 (en) | 1987-12-23 | 1987-12-23 | Method for producing hydroxyapatite fine particles |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2572793B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR1005019B (en) * | 2004-12-23 | 2005-10-11 | Βαιμακης@Τιβεριος | Low temerature production of high crystallinity hydroxyapatite mono-crystals |
| JP2008050260A (en) * | 1997-01-16 | 2008-03-06 | Orthovita Inc | Novel minerals and methods for their production and use |
| US9220595B2 (en) | 2004-06-23 | 2015-12-29 | Orthovita, Inc. | Shapeable bone graft substitute and instruments for delivery thereof |
-
1987
- 1987-12-23 JP JP62326516A patent/JP2572793B2/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008050260A (en) * | 1997-01-16 | 2008-03-06 | Orthovita Inc | Novel minerals and methods for their production and use |
| US9220595B2 (en) | 2004-06-23 | 2015-12-29 | Orthovita, Inc. | Shapeable bone graft substitute and instruments for delivery thereof |
| US9789225B2 (en) | 2004-06-23 | 2017-10-17 | Orthovita, Inc. | Shapeable bone graft substitute and instruments for delivery thereof |
| US10441683B2 (en) | 2004-06-23 | 2019-10-15 | Orthovita, Inc. | Method for restoring bone using shapeable bone graft substitute and instruments for delivery thereof |
| GR1005019B (en) * | 2004-12-23 | 2005-10-11 | Βαιμακης@Τιβεριος | Low temerature production of high crystallinity hydroxyapatite mono-crystals |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2572793B2 (en) | 1997-01-16 |
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