JPH0212961B2 - - Google Patents
Info
- Publication number
- JPH0212961B2 JPH0212961B2 JP62043998A JP4399887A JPH0212961B2 JP H0212961 B2 JPH0212961 B2 JP H0212961B2 JP 62043998 A JP62043998 A JP 62043998A JP 4399887 A JP4399887 A JP 4399887A JP H0212961 B2 JPH0212961 B2 JP H0212961B2
- Authority
- JP
- Japan
- Prior art keywords
- chitosan
- ultrafine
- chitin
- water
- solution
- 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.)
- Expired - Lifetime
Links
- 229920001661 Chitosan Polymers 0.000 claims description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000011882 ultra-fine particle Substances 0.000 claims description 14
- 239000012298 atmosphere Substances 0.000 claims description 13
- 239000003637 basic solution Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 230000002378 acidificating effect Effects 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 6
- 238000005507 spraying Methods 0.000 claims description 6
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 239000003495 polar organic solvent Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000000397 acetylating effect Effects 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims 1
- 239000002245 particle Substances 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 229920002101 Chitin Polymers 0.000 description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000008187 granular material Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 5
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000003929 acidic solution Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000238557 Decapoda Species 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 229960005215 dichloroacetic acid Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 238000004438 BET method Methods 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000010299 mechanically pulverizing process Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Description
【発明の詳細な説明】
〓産業上の利用分野〓
本発明は、クロマトグラフイー用充填材，固定
化生理活性物質用担体，及び医薬用助剤等に好適
な多孔質超微小粒状体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 porous ultrafine particle suitable for use as a packing material for chromatography, a carrier for immobilized physiologically active substances, a pharmaceutical auxiliary agent, etc. This relates to a manufacturing method.
〓従来の技術〓
キチンは海老，蟹等の甲殻類の外皮他自然界に
広く分布して存在し、該キチン及びキチンより得
られるキトサンは、クロマトグラフイー用充填
材，各種物質用担体として用いることができる。
キチン及びキトサンの超微小粒状体を得る方法と
しては種々の試みがなされており、超微小粒状キ
トサンを得る方法として、キトサンフレークを機
械的に粉砕する方法，特公昭59−30722号公報に
開示されたキトサンの酸性水溶液に乳化剤を含む
疎水性溶剤を入れ、撹拌してエマルジヨン化し、
このものをアルカリ水溶液中で撹拌しながら凝固
析出する方法が知られているが、何れも形状が不
規則，若しくは粒径の分布が広い範囲に分布した
ものとなる等の欠点がある。又、キチンの超微小
球状物を得る方法としては特開昭58−127736号公
報及び特開昭59−86640号公報に記載のようにキ
チンを機械的に粉砕する方法が知られているが、
このようにして得られたキチンは不規則な形態の
粒子であり、分散性に欠けるものであつた。〓Prior art〓 Chitin is widely distributed in the natural world, including the outer skin of crustaceans such as shrimp and crabs, and chitin and chitosan obtained from chitin can be used as fillers for chromatography and as carriers for various substances. Can be done.
Various attempts have been made to obtain ultrafine granules of chitin and chitosan.As a method for obtaining ultrafine chitosan particles, a method of mechanically crushing chitosan flakes is disclosed in Japanese Patent Publication No. 30722/1983. A hydrophobic solvent containing an emulsifier is added to an acidic aqueous solution of the disclosed chitosan, and the mixture is stirred to form an emulsion.
A method is known in which this material is coagulated and precipitated while being stirred in an aqueous alkaline solution, but all of these methods have drawbacks such as irregular shapes or particle size distribution over a wide range. Furthermore, as a method for obtaining ultrafine chitin spherules, a method of mechanically pulverizing chitin as described in JP-A-58-127736 and JP-A-59-86640 is known. ,
The chitin thus obtained was irregularly shaped particles and lacked dispersibility.
〓発明が解決しようとする問題点〓
本発明者等は、キトサンを酸性水溶液中に溶解
して得た溶解液を塩基性溶液中で凝固再生し、生
成した凝固物を水中に粉砕分散せしめ、該分散液
を高温雰囲気中に加圧空気と共に吐出乾燥する超
微小球状キトサンの製造方法を発明し、特願昭60
−203006号として出願を行つた。また、超微小球
状キチンの製造方法として、上記のようにして凝
固再生したキトサンを更にアセチル化して得た再
生キチン等の再生キチンを水中に粉砕分散せし
め、該分散液を高温雰囲気中に吐出乾燥する方法
を発明し、特願昭60−240896号として出願を行つ
た。これらの方法により、一旦再生したキトサン
又はキチンを水中に分散せしめて該分散液を高温
雰囲気中に吐出乾燥する方法によると、平均粒径
が20μｍ以下であつて、しかも粒度分布の小さな
超微小球状キトサン又はキチンを得ることができ
る。しかしながら得られた超微小球状キトサン又
はキチンは比表面積が小さく、例えば酵素，蛋白
質等の固定化担体としては、その固定化量が少な
くなり、その結果バイオリアクターとしての活性
が低いという欠点がある。<Problems to be Solved by the Invention> The present inventors coagulate and regenerate the solution obtained by dissolving chitosan in an acidic aqueous solution in a basic solution, pulverize and disperse the resulting coagulate in water, He invented a method for producing ultrafine spherical chitosan in which the dispersion was discharged together with pressurized air into a high-temperature atmosphere, and filed a patent application in 1983.
-The application was filed as No. 203006. In addition, as a method for producing ultra-fine spherical chitin, regenerated chitin, such as regenerated chitin obtained by further acetylating the coagulated and regenerated chitosan as described above, is pulverized and dispersed in water, and the dispersion is discharged into a high-temperature atmosphere. He invented a drying method and filed an application as Japanese Patent Application No. 1983-240896. By these methods, once regenerated chitosan or chitin is dispersed in water and the dispersion is discharged and dried in a high-temperature atmosphere, ultra-fine particles with an average particle size of 20 μm or less and a small particle size distribution can be obtained. Spherical chitosan or chitin can be obtained. However, the obtained ultrafine spherical chitosan or chitin has a small specific surface area, and has the drawback that, for example, as an immobilization carrier for enzymes, proteins, etc., the amount of immobilization is small, and as a result, the activity as a bioreactor is low. .
本発明は、このような欠点をなくし、平均粒子
径が20μｍ以下であつて、しかも比表面積の大き
いキトサン又はキチンの多孔質超微小粒状体の製
造方法を提供することを目的とする。 The object of the present invention is to eliminate such drawbacks and provide a method for producing porous ultrafine particles of chitosan or chitin having an average particle diameter of 20 μm or less and a large specific surface area.
〓問題点を解決するための手段〓
本発明の方法は、キトサンを酸性水溶液中に溶
解し、該酸性水溶液を高温雰囲気中に噴霧し、乾
燥させることにより超微小粒状キトサン酸塩を
得、該超微小粒状キトサン酸塩を塩基性溶液中で
中和し、更に中性になるまで充分に水洗すること
によつて多孔質超微小粒状キトサンを得るもので
ある。また、上記のようにして塩基性溶液中で中
和し、中性になるまで充分に水洗した多孔質超微
小粒状キトサンを、アルコールで水置換後、有機
溶媒中でアセチル化試薬と接触反応させて再度ア
ルコールで洗浄後水洗すれば多孔質超微小粒状キ
チンを製造することができる。<Means for solving the problems> The method of the present invention involves dissolving chitosan in an acidic aqueous solution, spraying the acidic aqueous solution into a high-temperature atmosphere, and drying it to obtain ultrafine particulate chitosanate; Porous ultrafine chitosan is obtained by neutralizing the ultrafine chitosanate in a basic solution and washing thoroughly with water until it becomes neutral. In addition, the porous ultrafine particulate chitosan was neutralized in a basic solution as described above and thoroughly washed with water until it became neutral, and after replacing the water with alcohol, it was contacted with an acetylation reagent in an organic solvent. Then, by washing again with alcohol and then with water, porous ultra-fine granular chitin can be produced.
本発明方法において用いるキトサンは、通常フ
レーク状のものを使用し、平均分子量10000〜
230000の低分子量キトサンを使用すると、添加剤
等を加えずに高濃度の酸性水溶液が得られるので
好ましい。キトサンは、酢酸，ジクロール酢酸，
蟻酸の単独，若しくは混合物の水溶液に溶解す
る。キトサン酸性水溶液の濃度は１〜20％が好ま
しい。 The chitosan used in the method of the present invention is usually in the form of flakes and has an average molecular weight of 10,000 to 10,000.
It is preferable to use chitosan with a low molecular weight of 230,000 because a highly concentrated acidic aqueous solution can be obtained without adding any additives. Chitosan is made of acetic acid, dichloroacetic acid,
Dissolves in an aqueous solution of formic acid alone or as a mixture. The concentration of the chitosan acidic aqueous solution is preferably 1 to 20%.
キトサン酸性水溶液は高温雰囲気中に噴霧し、
乾燥される。高温雰囲気中の温度は、超微小粒状
キトサンが乾燥されるに充分な温度で、100〜200
℃の範囲で自由に選択できる。得られる粒状物の
粒径は、高温雰囲気中に噴霧する際、二流体ノズ
ル方式においては吐出量と吐出圧、デイスク型遠
心噴霧方式においては供給量と回転数を適宜調節
することによつて、任意に選択することができ
る。乾燥凝固した超微小キトサン酸塩は塩基性溶
液中で中和して多孔質の超微小粒状キトサンを再
生する。中和を行う塩基性溶液の組成は、苛性ソ
ーダ，エチレンジアミン，水酸化カリウム等の塩
基性物質にメタノール，エタノール，ジメチルホ
ルムアミド等の極性を有する有機溶媒を添加して
調製する。該塩基性溶液は、水を加えずに調製す
る。水を加えるとキトサン粒状体が膨潤し、互い
に粘着，凝集をしてしまう。このようにして得た
多孔質超微小粒状キトサンは、水で中性になるま
で充分洗浄する。 Chitosan acidic aqueous solution is sprayed into a high temperature atmosphere,
dried. The temperature in the high temperature atmosphere is 100-200°C, which is sufficient to dry the ultrafine chitosan particles.
Can be freely selected within the range of °C. The particle size of the obtained granules can be determined by appropriately adjusting the discharge amount and discharge pressure in a two-fluid nozzle method, and the supply amount and rotation speed in a disk type centrifugal spray method, when spraying into a high-temperature atmosphere. Can be selected arbitrarily. The dried and coagulated ultrafine chitosanate is neutralized in a basic solution to regenerate porous ultrafine chitosan particles. The composition of the basic solution for neutralization is prepared by adding a polar organic solvent such as methanol, ethanol, dimethylformamide, etc. to a basic substance such as caustic soda, ethylenediamine, and potassium hydroxide. The basic solution is prepared without adding water. When water is added, the chitosan particles swell, causing them to stick and aggregate with each other. The porous ultrafine particulate chitosan thus obtained is thoroughly washed with water until it becomes neutral.
また、多孔質超微小粒状キチンを得るには、上
記のようにして得られた多孔質超微小粒状キトサ
ンを、水洗後アルコールで水置換し、例えばエタ
ノール中で無水酢酸を用いて反応させ、Ｎ―アセ
チル化を行つて再生キチンを得る。得られた多孔
質超微小粒状キチンはアルコールで洗浄後、水洗
する。 In order to obtain porous ultrafine chitin, the porous ultrafine chitosan obtained as described above is washed with water, replaced with water, and reacted with acetic anhydride in ethanol, for example. , N-acetylation is performed to obtain regenerated chitin. The obtained porous ultrafine chitin particles are washed with alcohol and then with water.
このようにして得られた本発明のキトサン又は
キチン多孔質超微小粒状体は、平均粒径が20μｍ
以下であつて、しかも粒度分布の小さい多孔性の
粒状体である。 The chitosan or chitin porous ultrafine particles of the present invention thus obtained have an average particle size of 20 μm.
Moreover, it is a porous granular material with a small particle size distribution.
〓実施例〓
実施例 １
脱アセチル化度95％，平均分子量42000のキト
サン70ｇを、35ｇの酢酸を含む水930ｇに溶解し
て、キトサン酸性溶液を得た。この溶液の20℃に
おける粘度は、回転粘度計で測定したところ
2300cpであつた。このキトサン酸性溶液を4.0
Kg／cm2の加圧空気と共に17.6ml／分の液量で、
180〜185℃の高温雰囲気中に噴霧して乾燥し、乾
燥物64ｇをサイクロンコレクターに補集した。こ
の凝固物１ｇを、エチレンジアミン10％，エタノ
ール90％からなる塩基性溶液20ml中で、室温で60
分間中和した後、これをトミー精工(株)RD―20
型遠心分離機を用いて、1500rpmで10分間遠心
し、上澄み液を除去した。これに水20mlを加え
て、同じ操作を中性になるまで繰り返し、超微小
粒状多孔質キトサン0.7ｇを得た。これを走査型
電子顕微鏡で調べたところ、平均粒径10μｍ，粒
径分布３〜20μｍであつた。又、比表面積は78.0
m2／ｇであつた。比表面積は、試料を液体窒素中
で急冷凍結し、10-4トール（Torr），−40℃，８
時間真空乾燥し、140℃，40分間脱ガス後比表面
自動測定装置（島津マイクロメリテツクス220形）
にてBET法で測定した。Examples Example 1 70 g of chitosan having a degree of deacetylation of 95% and an average molecular weight of 42,000 was dissolved in 930 g of water containing 35 g of acetic acid to obtain an acidic chitosan solution. The viscosity of this solution at 20℃ was measured using a rotational viscometer.
It was 2300 cp. This chitosan acidic solution 4.0
With a liquid volume of 17.6ml/min with Kg/ cm2 of pressurized air,
It was dried by spraying in a high temperature atmosphere of 180 to 185°C, and 64 g of the dried product was collected in a cyclone collector. 1 g of this coagulated material was added to 20 ml of a basic solution consisting of 10% ethylenediamine and 90% ethanol for 60 minutes at room temperature.
After neutralizing it for a minute, use Tommy Seiko Co., Ltd. RD-20.
The mixture was centrifuged at 1500 rpm for 10 minutes using a type centrifuge, and the supernatant was removed. 20 ml of water was added to this and the same operation was repeated until the mixture became neutral, yielding 0.7 g of ultrafine porous chitosan particles. When this was examined using a scanning electron microscope, the average particle size was 10 μm, and the particle size distribution was 3 to 20 μm. Also, the specific surface area is 78.0
m 2 /g. The specific surface area was determined by rapidly freezing the sample in liquid nitrogen, 10 -4 Torr, -40℃, 8
After vacuum drying for 40 minutes and degassing at 140℃ for 40 minutes, automatic specific surface measuring device (Shimadzu Micromeritics Model 220)
Measured using the BET method.
実施例 ２
脱アセチル化度82％，平均分子量58000のキト
サン55ｇに、ジクロル酢酸を含む水950ｇを加え
て溶解し、キトサン酸性溶液を得た。この溶液の
20℃における粘度は、回転粘度計で測定したとこ
ろ5000cpであつた。このキトサン酸性溶液を180
〜190℃の高温雰囲気中に、回転数29000rpmのデ
イスクよりフイード量17ml／分で遠心噴霧し、乾
燥微小粒状体47ｇを、サイクロンコレクターで補
集した。この粒状体１ｇを、50mlの遠沈管に入
れ、水酸化カリウム10％及びメタノール90％から
なる塩基性溶液20mlを加え、室温で60分間振とう
して中和した後、中性になるまで充分水洗して、
超微小粒状多孔質キトサン0.6ｇを得た。これを
走査型電子顕微鏡で調べたところ、平均粒径15μ
ｍ，粒径分布５〜30μｍであつた。又比表面積は
27.4m2／ｇであつた。Example 2 950 g of water containing dichloroacetic acid was added to 55 g of chitosan having a degree of deacetylation of 82% and an average molecular weight of 58,000 and dissolved to obtain an acidic chitosan solution. of this solution
The viscosity at 20°C was 5000 cp as measured by a rotational viscometer. Add this chitosan acidic solution to 180%
Centrifugal spraying was performed at a feed rate of 17 ml/min from a disc rotating at 29,000 rpm in a high temperature atmosphere of ~190°C, and 47 g of dried fine particles were collected with a cyclone collector. Put 1 g of this granular material into a 50 ml centrifuge tube, add 20 ml of a basic solution consisting of 10% potassium hydroxide and 90% methanol, and neutralize by shaking at room temperature for 60 minutes. Wash with water,
0.6 g of ultrafine porous chitosan particles were obtained. When this was examined using a scanning electron microscope, the average particle size was 15μ.
m, particle size distribution was 5 to 30 μm. Also, the specific surface area is
It was 27.4m 2 /g.
実施例 ３
実施例１と同様にして得た超微小粒状多孔質キ
トサン１ｇを、50mlの遠沈管に入れ、エタノール
で四回置換（水をアルコールに置換）した後、三
倍モルの無水酢酸を用いて常温で24時間反応させ
た。無水酢酸による反応を三回繰り返した後、エ
タノールで洗浄水洗し、0.5N苛性ソーダでエス
テル結合切断の為、室温で１時間反応させ水洗し
て超微小粒状多孔質キチン0.6ｇを得た。これを
走査型電子顕微鏡で調べたところ、平均粒径8μ
ｍ，粒径分布３〜18μｍであつた。又、比表面積
は72.6m2／ｇであつた。Example 3 1 g of ultrafine porous chitosan obtained in the same manner as in Example 1 was placed in a 50 ml centrifuge tube, and after replacing with ethanol four times (replacing water with alcohol), three times the mole of acetic anhydride was added. was used to react at room temperature for 24 hours. After repeating the reaction with acetic anhydride three times, the mixture was washed with ethanol, washed with water, reacted with 0.5N caustic soda for 1 hour at room temperature to cleave the ester bonds, and washed with water to obtain 0.6 g of ultrafine porous chitin. When this was examined using a scanning electron microscope, the average particle size was 8μ.
m, particle size distribution was 3 to 18 μm. Further, the specific surface area was 72.6 m 2 /g.
比較例 １
実施例１と同様にして得たキトサン酸性溶液
を、10％苛性ソーダと30％メチルアルコール、及
び水60％からなる塩基性水溶液中に、孔径0.25mm
のノズルより落下させて、キトサンを凝固再生
し、中性になるまで十分水洗して、粒径0.7〜2.0
mmの粒状物を得た。該粒状物600mlをとり、日本
精機(株)製AM・３型ホモジナイザーを用いて、
15000rpmの回転数で７分間撹拌して、乳状の懸
濁液とし、更に水を加えて全量を1000mlとした。
これを撹拌しながら分散状態を保ちつつ、3.0
Kg／cm2の加圧空気と共に、毎分17.6mlの液量で、
180℃の高温雰囲気中に噴霧して乾燥し、平均粒
径10μｍの微小粒状キトサン35ｇを得た。これの
比表面積は1.2m2／ｇであつた。Comparative Example 1 A chitosan acidic solution obtained in the same manner as in Example 1 was placed in a basic aqueous solution consisting of 10% caustic soda, 30% methyl alcohol, and 60% water with a pore size of 0.25 mm.
Drop the chitosan from the nozzle to solidify and regenerate it, wash thoroughly with water until it becomes neutral, and reduce the particle size to 0.7 to 2.0.
Granules of mm were obtained. Take 600 ml of the granular material and use a Nippon Seiki Co., Ltd. AM/3 type homogenizer.
The mixture was stirred at a rotational speed of 15,000 rpm for 7 minutes to form a milky suspension, and water was further added to bring the total volume to 1,000 ml.
While stirring this to maintain a dispersed state,
With pressurized air of Kg/ cm2 , the liquid volume is 17.6ml per minute.
The mixture was sprayed and dried in a high temperature atmosphere of 180° C. to obtain 35 g of microparticulate chitosan with an average particle size of 10 μm. The specific surface area of this was 1.2 m 2 /g.
比較例 ２
比較例１で得た粒径0.7〜2.0mmの粒状物400ml
を、400mlのエタノールで４回撹拌（水をアルコ
ールに置換）したのち、３倍モルの無水酢酸を用
いて常温で24時間反応させた。この操作を３回繰
り返した後、エタノールで洗浄、水洗し、0.5N
苛性ソーダでエステル結合切断のため室温で１時
間反応させて水洗した。該再生キチン200mlに水
100mlを加えてホモジナイザーで17000rpm4分間
撹拌し、更に水を加えて400mlとし、濃度3.5％の
懸濁液とした。これを14.5ml／min.の吐出量で、
４Kg／cm2の加圧空気とともに、180℃の高温雰囲
気中に噴霧し乾燥して、平均粒径3μｍの微小粒
状キチン11.2ｇを得た。これの比表面積は、1.0
m2／ｇであつた。Comparative Example 2 400ml of granular material with a particle size of 0.7 to 2.0 mm obtained in Comparative Example 1
was stirred four times with 400 ml of ethanol (water was replaced with alcohol), and then reacted with 3 times the mole of acetic anhydride at room temperature for 24 hours. After repeating this operation three times, wash with ethanol, wash with water, and use 0.5N
The mixture was reacted with caustic soda at room temperature for 1 hour to cleave the ester bonds, and then washed with water. Add 200ml of the regenerated chitin to water.
100 ml was added and stirred for 4 minutes at 17000 rpm using a homogenizer, and water was further added to make 400 ml to obtain a suspension with a concentration of 3.5%. At a discharge rate of 14.5ml/min.
The mixture was sprayed and dried in a high temperature atmosphere of 180° C. with pressurized air of 4 kg/cm 2 to obtain 11.2 g of microparticulate chitin with an average particle size of 3 μm. The specific surface area of this is 1.0
m 2 /g.
〓発明の効果〓
本発明によるキトサン又はキチン多孔質超微小
粒状体は、キトサン酸性水溶液から超微小粒状キ
トサン酸塩を得、このものを塩基性溶液中で中和
することによつて多孔質の超微小粒状キトサンを
再生せしめ、必要に応じて、更にアセチル化を行
えば、多孔質の超微小粒状キチンが得られるもの
である。<Effects of the Invention> The porous ultrafine particles of chitosan or chitin according to the present invention are obtained by obtaining ultrafine particulate chitosanate from an acidic chitosan aqueous solution and neutralizing this in a basic solution to make the porous ultrafine particles. By regenerating quality ultrafine chitosan and further acetylating it if necessary, porous ultrafine chitin can be obtained.
従つて、実施例にも記載のように、本発明の方
法によつて得られたキトサン又はキチン多孔質超
微小粒状体は、平均粒子径が20μｍ以下という超
微小粒子で、粒径分布の小さい粒度の揃つたもの
であり、しかも比表面積が極めて大きいので、ク
ロマトグラフイー用充填材，固定化生理活性物質
用担体，医薬用助剤等に極めて好適なものであ
る。 Therefore, as described in the Examples, the chitosan or chitin porous ultrafine particles obtained by the method of the present invention are ultrafine particles with an average particle size of 20 μm or less, and a particle size distribution. Since it has a uniform small particle size and an extremely large specific surface area, it is extremely suitable for use as a packing material for chromatography, a carrier for immobilized physiologically active substances, a pharmaceutical aid, and the like.
Claims (1)
て乾燥させた後、塩基性溶液中で中和させること
を特徴とする多孔質超微小粒状体の製造方法。 ２ 該塩基性溶液が、塩基性物質を極性を有する
有機溶媒中に添加したものである特許請求の範囲
第１項に記載の多孔質超微小粒状体の製造方法。 ３ 極性を有する有機溶媒が、メタノール，エタ
ノール，ジメチルホルムアミドの何れか、又はこ
れらの混合物からなる特許請求の範囲第２項に記
載の多孔質超微小粒状体の製造方法。 ４ キトサン酸性水溶液を高温雰囲気中に噴霧し
て乾燥させた後、塩基性溶液中で中和させ、次い
でアセチル化することを特徴とする多孔質超微小
粒状体の製造方法。 ５ 該塩基性溶液が、塩基性物質を極性を有する
有機溶媒中に添加したものである特許請求の範囲
第４項に記載の多孔質超微小粒状体の製造方法。 ６ 極性を有する有機溶媒が、メタノール，エタ
ノール，ジメチルホルムアミドの何れか、又はこ
れらの混合物からなる特許請求の範囲第５項に記
載の多孔質超微小粒状体の製造方法。[Claims] 1. A method for producing porous ultrafine particles, which comprises spraying an acidic chitosan aqueous solution into a high-temperature atmosphere, drying it, and then neutralizing it in a basic solution. 2. The method for producing porous ultrafine particles according to claim 1, wherein the basic solution is one in which a basic substance is added to a polar organic solvent. 3. The method for producing porous ultrafine particles according to claim 2, wherein the polar organic solvent is composed of methanol, ethanol, dimethylformamide, or a mixture thereof. 4. A method for producing porous ultrafine particles, which comprises spraying an aqueous chitosan acid solution into a high-temperature atmosphere, drying it, neutralizing it in a basic solution, and then acetylating it. 5. The method for producing porous ultrafine particles according to claim 4, wherein the basic solution is one in which a basic substance is added to a polar organic solvent. 6. The method for producing a porous ultrafine particle according to claim 5, wherein the polar organic solvent comprises methanol, ethanol, dimethylformamide, or a mixture thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62043998A JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62043998A JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63210101A JPS63210101A (en) | 1988-08-31 |
| JPH0212961B2 true JPH0212961B2 (en) | 1990-04-03 |
Family
ID=12679382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62043998A Granted JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63210101A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999062974A1 (en) | 1998-06-04 | 1999-12-09 | Kao Corporation | Polymer emulsion and process for producing the same |
| EP1172097B1 (en) | 1999-04-12 | 2004-09-08 | Shionogi & Co., Ltd. | Process for producing medicinal composition of a basic hydrophobic medicinal compound |
| KR100470715B1 (en) * | 2002-04-04 | 2005-03-08 | 주식회사 자광 | A capsule of porous bead of water soluble chitosan and the preparation method thereof |
| KR100486042B1 (en) * | 2002-04-18 | 2005-04-29 | 강대인 | Method for preparing chitin hydrolysates having low molecular weight and oligosaccharides by the enzyme treatment |
| KR20050055643A (en) * | 2005-04-25 | 2005-06-13 | 조석형 | Diet agent containing chitosan microparticle and the preparation method thereof |
| CN102352047B (en) * | 2011-06-27 | 2013-04-03 | 张会艳 | Preparation method of chitin balls |
| WO2024095351A1 (en) * | 2022-10-31 | 2024-05-10 | 綜研化学株式会社 | Precursor polysaccharide-containing particles, polysaccharide-containing particles, and method for producing polysaccharide-containing particles |
-
1987
- 1987-02-26 JP JP62043998A patent/JPS63210101A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63210101A (en) | 1988-08-31 |
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