JPS63198970A - Hollow sphere of calcium phosphate - Google Patents
Hollow sphere of calcium phosphateInfo
- Publication number
- JPS63198970A JPS63198970A JP3160787A JP3160787A JPS63198970A JP S63198970 A JPS63198970 A JP S63198970A JP 3160787 A JP3160787 A JP 3160787A JP 3160787 A JP3160787 A JP 3160787A JP S63198970 A JPS63198970 A JP S63198970A
- Authority
- JP
- Japan
- Prior art keywords
- calcium phosphate
- phosphate
- hollow spheres
- slurry
- hydroxyapatite
- 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.)
- Pending
Links
- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 29
- 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 29
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 26
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 26
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 6
- 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 abstract description 6
- 239000013078 crystal Substances 0.000 claims abstract 3
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims abstract 3
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims abstract 3
- 235000019731 tricalcium phosphate Nutrition 0.000 claims abstract 3
- 229940078499 tricalcium phosphate Drugs 0.000 claims abstract 3
- 239000000463 material Substances 0.000 abstract description 8
- 239000000843 powder Substances 0.000 abstract description 7
- 239000002002 slurry Substances 0.000 abstract description 7
- 239000000969 carrier Substances 0.000 abstract description 6
- 239000004088 foaming agent Substances 0.000 abstract description 6
- 239000004156 Azodicarbonamide Substances 0.000 abstract description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract description 4
- XOZUGNYVDXMRKW-AATRIKPKSA-N azodicarbonamide Chemical compound NC(=O)\N=N\C(N)=O XOZUGNYVDXMRKW-AATRIKPKSA-N 0.000 abstract description 4
- 235000019399 azodicarbonamide Nutrition 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract description 4
- 238000010438 heat treatment Methods 0.000 abstract description 3
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 230000009172 bursting Effects 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract description 2
- 210000001519 tissue Anatomy 0.000 description 11
- 238000000034 method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 6
- 239000011521 glass Substances 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 239000004604 Blowing Agent Substances 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000002952 polymeric resin Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 229920003002 synthetic resin Polymers 0.000 description 2
- 230000008016 vaporization Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920003217 poly(methylsilsesquioxane) Polymers 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はリン酸カルシウム中空球に係わり、特に組織培
養等に使用される担体の材料として使用されるリン酸カ
ルシウム中空球に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to calcium phosphate hollow spheres, and particularly to calcium phosphate hollow spheres used as carrier materials used in tissue culture and the like.
従来、リン酸カルシウムは無毒であり、生体に対して親
和性に優れていることから、骨欠損部の充填材等に使用
されていた。しかし、組織培養担体としては、ポリマー
樹脂、ガラス材が使用され、リン酸カルシウムは使用さ
れていなかった。Conventionally, calcium phosphate has been used as a filling material for bone defects because it is non-toxic and has excellent affinity for living organisms. However, polymer resins and glass materials have been used as tissue culture carriers, and calcium phosphate has not been used.
しかしながら、前記ポリマーを使用する場合には、中空
球を作ることができないし、又ガラス材を使用する場合
には、中空球のｒｊＡ造は可能であるが、この中空球は
開孔を有していなかった。このため、組織培養担体、菌
体ｉ酵母固定化担体として使用する場合には、表面積が
小さく、一定量の組織を培養するためには、多量のガラ
ス材・ポリマー樹脂材が必要であった。However, when using the above polymer, it is not possible to make a hollow sphere, and when using a glass material, it is possible to construct a hollow sphere using RJA, but this hollow sphere has openings. It wasn't. Therefore, when used as a tissue culture carrier or a yeast immobilization carrier, the surface area is small, and a large amount of glass or polymer resin material is required to culture a certain amount of tissue.
しかも、担体の外面のみに組織を付着させることから、
担体間の接触・衝突等により組織の破壊が大量に発生す
る等の問題点を有していた。Moreover, since the tissue is attached only to the outer surface of the carrier,
This method had problems such as a large amount of tissue destruction occurring due to contact and collision between the carriers.
本発明は上記事情に鑑み創案されたものであって、その
目的とするところは、上述した従来の組織培養担体が有
する問題点を解消するため、組織培養等に特に適した、
リン酸カルシウム中空球を提供することにある。The present invention was devised in view of the above circumstances, and its purpose is to solve the problems of the conventional tissue culture carriers described above, and to provide a carrier particularly suitable for tissue culture, etc.
The purpose of the present invention is to provide calcium phosphate hollow spheres.
本発明者は、長年リン酸カルシウムの成形につき鋭意研
究し、リン酸カルシウムと多種多様な発泡剤・結合剤を
使用し、実験を行なった結果、少なくとも１個の開孔を
有するリン酸カルシウム中空球を発明することができ、
しかも、その後の研究により、同リン酸カルシウム中空
球が組織培養担体、菌体羽酵素固定化担体、吸着・分離
材としてすぐれた効果を有することを知見し、同リン酸
カルシウム中空球を組織培養担体、菌体ｉ酵素固定化担
体、吸着・分離材として使用する方法の発明をするに至
ったものである。The present inventor has spent many years intensively researching the molding of calcium phosphate, and as a result of conducting experiments using calcium phosphate and a wide variety of foaming agents and binders, the inventor was able to invent a calcium phosphate hollow sphere having at least one hole. I can do it,
Furthermore, subsequent research has revealed that the calcium phosphate hollow spheres have excellent effects as tissue culture carriers, bacterial wing enzyme immobilization carriers, and adsorption/separation materials. This led to the invention of a method for using the i-enzyme immobilization carrier as an adsorption/separation material.
本発明に係わるリン酸カルシウム中空球の製造方法は、
乾式と湿式の２方法があり以下台々について説明する。The method for producing calcium phosphate hollow spheres according to the present invention includes:
There are two methods: dry method and wet method, and each method will be explained below.
（１）乾式製造方法
細かい、望ましくは１００μ以下のリン酸カルシ・クム
粉末１００重量部に対し、例えば尿素！アゾジカルボン
アミドの有機発泡剤５０乃至２００重量部を入れ、よく
混合した後筒型の電気炉内を通過させることにより加熱
し、発泡剤の気化により、リン酸カルシウムを発泡後破
裂させ、開孔を有する中空球が形成される。その後、炉
内温度を９００℃乃至１４００℃、好ましくは１０００
’Ｃ乃至１２００℃の電気炉で３０分間以上加熱する。(1) Dry manufacturing method For example, urea is added to 100 parts by weight of fine calci-cum-phosphate powder, preferably less than 100μ. Add 50 to 200 parts by weight of an organic blowing agent of azodicarbonamide, mix thoroughly, and then heat by passing through a cylindrical electric furnace. By vaporizing the blowing agent, the calcium phosphate is foamed and ruptured to form open pores. A hollow sphere is formed. After that, the temperature inside the furnace is set to 900°C to 1400°C, preferably 1000°C.
Heat in an electric furnace at 1200°C for 30 minutes or more.
（２）湿式方法
細かいリン酸カルシウム粉末１００重量部、または、リ
ン酸カルシウム粉末１００重量部と、例えば、尿素、ア
ゾジカルボンアミドの有機発泡剤１０重量部以下の混合
物を、水８０乃至２５０重量部に、例えばポリビニール
アルコールの有機結合剤を溶解した水溶液に分散して、
スラリーを調製し、噴霧乾燥造粒機で加熱し、発泡剤お
よび水、または水のみを気化させることにより、リン酸
カルシウムを発泡後破裂させ、開孔を有する中空球が形
成される。その後９００℃乃至１４００’Ｃ好ましくは
１０００７’Ｊ至１２００℃の炉内で３０分間以上加熱
する。(2) Wet method Add 100 parts by weight of fine calcium phosphate powder, or a mixture of 100 parts by weight of calcium phosphate powder and 10 parts by weight or less of an organic blowing agent such as urea or azodicarbonamide, to 80 to 250 parts by weight of water, Dispersed in an aqueous solution containing an organic binder of vinyl alcohol,
By preparing a slurry and heating it with a spray drying granulator to vaporize the foaming agent and water, or only water, the calcium phosphate is foamed and then ruptured to form hollow spheres with open pores. Thereafter, it is heated in a furnace at 900° C. to 1400° C., preferably 10007° C. to 1200° C., for 30 minutes or more.
本発明によれば、リン酸カルシウム粉末に有機発泡剤を
混合し、又はスラリー状とし、加熱することにより、発
泡剤又は水の気化により、リン酸カルシウム粉末を中空
球とし、破裂により開孔させることができ、少なくとも
１個の開孔を有するリン酸カルシウムを創造することが
可能となった。According to the present invention, by mixing an organic foaming agent with calcium phosphate powder or making it into a slurry and heating it, the calcium phosphate powder can be made into hollow spheres by vaporization of the foaming agent or water, and the holes can be opened by bursting. It became possible to create calcium phosphate with at least one open pore.
しかも、このリン酸カルシウム中空球を組織培養担体と
して使用した結果、従来のガラス製品、ポリマー製品よ
り良い効果を得た。Moreover, the use of this calcium phosphate hollow sphere as a tissue culture carrier resulted in better effects than conventional glass products and polymer products.
以下製造方法の実施例を、説明する。 Examples of the manufacturing method will be described below.
実施例１
ヒドロキシアパタイト５０ｙと尿素５０ｇをボールミル
に入れ約１時間乾式粉砕混合し、粒の凝集を行なわせる
。その後、篩により粒径１５０μ以下の粒子を分級し、
１１５０℃に温度設定された縦型電気炉内を３秒間で通
過させる。ここで、開孔中空球は形成される。これを、
１１００℃に温度設定された電気炉内に放置し、焼結さ
せた。Example 1 50 y of hydroxyapatite and 50 g of urea were placed in a ball mill and dry-pulverized and mixed for about 1 hour to coagulate the particles. After that, particles with a particle size of 150μ or less are classified using a sieve,
It is passed through a vertical electric furnace whose temperature is set to 1150°C for 3 seconds. Here, open-hole hollow spheres are formed. this,
It was left in an electric furnace set at a temperature of 1100°C to sinter.
実施例２
ポリビニールアルコール２０９を６．７１の水に溶解し
、その後、粒径１０μのヒドロキシアパタイト２ Ｋｙ
とアゾジルカルボンアミド１ｏｏｇを投入・分散させ、
３０％濃度のスラリーを調整する。その後、入口温度１
５０℃、出口温度１００℃に設定されたスプレードライ
ヤーで、噴霧乾燥造粒した。そして、１１００’Ｃに温
度設定された電気炉内に１時間放置し、焼結させた。Example 2 Polyvinyl alcohol 209 was dissolved in 6.71% water, and then hydroxyapatite 2Ky with a particle size of 10μ was dissolved.
and 10og of azodylcarbonamide were added and dispersed,
Prepare a slurry of 30% concentration. After that, the inlet temperature 1
Spray drying and granulation were carried out using a spray dryer set at 50°C and outlet temperature of 100°C. Then, it was left in an electric furnace set at a temperature of 1100'C for 1 hour to sinter.
実施例３
ポリビニールアルコール３７．５９を６．２５１の水（
溶解し、その後、粒径１ｏμのヒドロキシアパタイト２
．５Ｋｇと、アゾジカルボンアミド１２５ｔｊを投入・
分散させ、４０％濃度のスラリーを調整する。そして、
ムロ温度２００′Ｇ出ロ温度１００℃に設定されたスプ
レードライヤーで、噴霧乾燥造粒した。その後、１００
０℃。Example 3 Polyvinyl alcohol 37.59% water (6.251%)
After dissolving, hydroxyapatite 2 with a particle size of 1oμ
．． Input 5Kg and 125tj of azodicarbonamide.
Disperse to prepare a 40% slurry. and,
Spray drying and granulation were carried out using a spray dryer set at a temperature of 200°C and a temperature of 100°C. Then 100
0℃.
１１００℃、１２００℃、１３００℃に設定された電気
炉内で１時間放置し、焼結させた。各温度における製品
の性状について、有意差はなかった。It was left to stand for 1 hour in an electric furnace set at 1100°C, 1200°C, and 1300°C to sinter. There were no significant differences in the properties of the products at each temperature.
実施例４
ポリビニールアルコール２０ｇを４．５ｆｌの水に溶解
し、その俊、粒度１０μのヒドロアパタイト２．５Ｋｇ
を投入・分散させ、５５％濃度のスラリーを調整する。Example 4 20g of polyvinyl alcohol was dissolved in 4.5fl of water, and 2.5Kg of hydroapatite with a particle size of 10μ was obtained.
to prepare a slurry with a concentration of 55%.
そして、ムロ温度２５０’Ｃ出ロ温度１３０’Ｃに設定
されたスプレードライヤーで噴霧乾燥造粒した。その後
１０００℃・１１００°Ｃ・’１２００’ｃ・１３００
’Ｃｋ：設定された電気炉内で１時間放置し、焼結させ
た。各温度における製品の性状について有意差はなかっ
た。Then, the mixture was spray-dried and granulated using a spray dryer set at a temperature of 250'C and a temperature of 130'C. Then 1000℃・1100℃・'1200''c・1300
'Ck: Sintered by leaving in the set electric furnace for 1 hour. There were no significant differences in the properties of the products at each temperature.
上記各実施例の開孔リン酸カルシウム中球の性状および
組織培養担体として、Ｔフラスコで手続ネＩｌｆ正書
詔和６２年 ２月ニア 日
特許庁長官 黒 １）明 雄 殿２、発明の
名称
リン酸カルシウム中空球
３、補正をする者
事件との関係 特許出願人
住所 〒１５０東京都渋谷区神宮前六丁目２６番１号４
、補正の対象
明細書の「発明の詳細な説明」の欄。The properties of the open-pore calcium phosphate medium spheres of each of the above-mentioned examples and the tissue culture carrier were determined using a T flask. Ball 3: Relationship with the case of the person making the amendment Patent applicant address: 6-26-1-4 Jingumae, Shibuya-ku, Tokyo 150
, "Detailed Description of the Invention" column of the specification to be amended.
５、補正の内容
（１）明細書第７頁第１５行「プリマー製品」を「ポリ
マー製品」と訂正する。5. Contents of amendment (1) "Primer product" on page 7, line 15 of the specification is corrected to "polymer product."
Claims (1)
であることを特徴とするリン酸カルシウム中空球。 ２、リン酸カルシウムが、ヒドロキシアパタイト・リン
酸三カルシウム・リン酸四カルシウムの中から選ばれた
１または２以上のものより構成されたことを特徴とする
特許請求の範囲第１項記載のリン酸カルシウム中空球。[Claims] 1. A calcium phosphate hollow sphere having at least one opening and whose wall is a plate-like crystal. 2. The calcium phosphate hollow sphere according to claim 1, wherein the calcium phosphate is composed of one or more selected from hydroxyapatite, tricalcium phosphate, and tetracalcium phosphate. .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3160787A JPS63198970A (en) | 1987-02-16 | 1987-02-16 | Hollow sphere of calcium phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3160787A JPS63198970A (en) | 1987-02-16 | 1987-02-16 | Hollow sphere of calcium phosphate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63198970A true JPS63198970A (en) | 1988-08-17 |
Family
ID=12335886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3160787A Pending JPS63198970A (en) | 1987-02-16 | 1987-02-16 | Hollow sphere of calcium phosphate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63198970A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03290183A (en) * | 1990-04-06 | 1991-12-19 | Agency Of Ind Science & Technol | Calcium phosphate carrier for culturing animal cell |
| GB2248628A (en) * | 1990-10-01 | 1992-04-15 | Mitsubishi Materials Corp | Cell culture in media comprising a calcium phosphate compound as carrier |
| WO2002081620A1 (en) * | 2001-04-03 | 2002-10-17 | Kabushiki Kaisya Advance | Three-dimensional cell culture systems |
| US7448436B2 (en) | 2003-04-21 | 2008-11-11 | Denso Corporation | Heat exchanger |
| CN105949872A (en) * | 2016-05-24 | 2016-09-21 | 上海墨传新材料科技有限公司 | Water-based UV (ultraviolet) curing printing ink and method for preparing same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60172345A (en) * | 1983-12-19 | 1985-09-05 | ユナイテッド キングドム アトミック エナ↓−ヂイ オ↓−ソリテイ | Composite substance and its production |
-
1987
- 1987-02-16 JP JP3160787A patent/JPS63198970A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60172345A (en) * | 1983-12-19 | 1985-09-05 | ユナイテッド キングドム アトミック エナ↓−ヂイ オ↓−ソリテイ | Composite substance and its production |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03290183A (en) * | 1990-04-06 | 1991-12-19 | Agency Of Ind Science & Technol | Calcium phosphate carrier for culturing animal cell |
| GB2248628A (en) * | 1990-10-01 | 1992-04-15 | Mitsubishi Materials Corp | Cell culture in media comprising a calcium phosphate compound as carrier |
| GB2248628B (en) * | 1990-10-01 | 1994-09-07 | Mitsubishi Materials Corp | Cell culturing in serum-free media |
| WO2002081620A1 (en) * | 2001-04-03 | 2002-10-17 | Kabushiki Kaisya Advance | Three-dimensional cell culture systems |
| US7448436B2 (en) | 2003-04-21 | 2008-11-11 | Denso Corporation | Heat exchanger |
| CN105949872A (en) * | 2016-05-24 | 2016-09-21 | 上海墨传新材料科技有限公司 | Water-based UV (ultraviolet) curing printing ink and method for preparing same |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107174867A (en) | Coal does new material, dedusting and improvement haze again after mixing and mix with other materials | |
| US6521258B1 (en) | Polymer matrices prepared by supercritical fluid processing techniques | |
| IE911071A1 (en) | Method for production of fluid stable aggregate | |
| US5720439A (en) | High speed agitated granulation method and high speed agitated granulating machine | |
| JPS61502963A (en) | Hollow microspheres made from dispersed particle composition, method and apparatus for producing the same | |
| JPH03501494A (en) | Method for agglomerating water-swellable polymers by calcination granulation | |
| JPH01157474A (en) | Porous inorganic material | |
| JPS5945959A (en) | Freely fluidizable dry powder composition | |
| JPS63198970A (en) | Hollow sphere of calcium phosphate | |
| JP2008531454A (en) | Method for producing foam glass granules | |
| JPH03252304A (en) | Production of porous ceramic grain | |
| JPH02297374A (en) | Polysaccharide-calcium phosphate complex gel and production thereof | |
| JPS61163963A (en) | Production of easily soluble gelatin | |
| JPS61141930A (en) | Preparation of adsorbent | |
| Wang et al. | Preparation of inverse opal hydroxyapatite and drug delivery properties | |
| JPS6087852A (en) | Adsorbent and its manufacture | |
| JPH09315877A (en) | Production of clay porous body | |
| US3311477A (en) | Method of preparing free-flowing water-insoluble solid particles | |
| JPH03174457A (en) | Preparation of polyurethane sponge | |
| RU2255058C1 (en) | Method of preparing blend for fabricating glass foam | |
| JPH01257120A (en) | Production of porous drying gel | |
| JPH0243688B2 (en) | GARASUSHITSUCHUKUTAHORYUOYOBISONOSEIZOHOHO | |
| JPS62161843A (en) | Production of colored expandable styrene resin bead | |
| KR0123019B1 (en) | Glassy carrier of porosity for fix a microorganism and process for the preparation thereof | |
| JP2544224B2 (en) | Deodorant granule and method for producing the same |