JP2006045299A - Chitosan gel and method for producing chitosan gel - Google Patents
Chitosan gel and method for producing chitosan gel Download PDFInfo
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本発明は、キトサンのみからなる水和ゲル、特に酸性水溶液中でゲルとなるキトサンゲル、及びキトサンゲルの製造方法に関する。 The present invention relates to a hydrated gel composed solely of chitosan, particularly a chitosan gel that forms a gel in an acidic aqueous solution, and a method for producing the chitosan gel.
キトサンは、一般的には、甲殻類、昆虫等の外骨格生物や、菌類等の微生物の細胞等に存在するキチンを脱アセチル処理して得られる天然高分子であり、工業的には、カニ殻や、エビ殻、イカの甲を原料として製造され、酸性水溶液に溶解し、カチオン性電解質ポリマーとして機能する。また、生分解性、凝集能、徐放性等の機能を有し、成形性にも優れており、繊維、フィルム、ビーズ等に加工することができるので、抗菌材料や医用材料、化粧品材料、食品添加材、分離材料、農業資材、シート材料、水処理材等の幅広い分野において利用が期待されている。このようなキトサンの利用態様の一つとしてゲル化があり、従来より様々なキトサンゲルの製造方法が考案されている。 Generally, chitosan is a natural polymer obtained by deacetylation treatment of chitin present in exoskeleton organisms such as crustaceans and insects and microbial cells such as fungi. Manufactured from shell, shrimp shell and squid shell, dissolved in acidic aqueous solution, it functions as a cationic electrolyte polymer. In addition, it has functions such as biodegradability, aggregability, and sustained release, is excellent in moldability, and can be processed into fibers, films, beads, etc., so antibacterial materials, medical materials, cosmetic materials, It is expected to be used in a wide range of fields such as food additives, separation materials, agricultural materials, sheet materials, and water treatment materials. One of the utilization modes of such chitosan is gelation, and various methods for producing chitosan gel have been devised conventionally.
例えば、キトサンに架橋剤としてポリ（Ｎ−ビニルラクタム）を反応させ、キトサン分子鎖を水素結合により網目構造にするキトサンゲルの製造方法がある。この方法によれば、簡単な方法で、所定の粘性値を有するキトサンゲルを調整することができるとされている（特許文献１参照）。 For example, there is a method for producing chitosan gel in which chitosan is reacted with poly (N-vinyl lactam) as a cross-linking agent so that chitosan molecular chains have a network structure by hydrogen bonding. According to this method, it is said that chitosan gel having a predetermined viscosity value can be adjusted by a simple method (see Patent Document 1).
また、キトサンと酸性のキレート化剤とを水に溶解した後、カルボン酸や硫酸の二価金属塩の水溶液を添加することにより、キレート結合を生じさせてゲル生成するキトサンゲルの製造方法がある。この方法によれば、ゲルを製造するにあたって、高価な装置、工程を必要としないとされている（特許文献２参照）。 In addition, there is a method for producing a chitosan gel in which chitosan and an acidic chelating agent are dissolved in water, and then an aqueous solution of a divalent metal salt of carboxylic acid or sulfuric acid is added to generate a chelate bond to form a gel. . According to this method, it is said that an expensive apparatus and a process are not required when manufacturing a gel (refer patent document 2).
また、キトサンを、カードランや澱粉のように水に不溶性で加熱により粘性を得る多糖類と混合して加熱することによりゲル化成形物としたゲル状キトサン成形物がある。該ゲル状キトサン成形物によれば、キトサンを食品に含有させる場合の食感を良くし、収斂味をなくすことができるとされている（特許文献３参照）。 In addition, there is a gel-like chitosan molded product obtained by mixing chitosan with a polysaccharide such as curdlan or starch that is insoluble in water and obtaining viscosity by heating and then heating it. According to the gel-like chitosan molded product, it is said that the texture when chitosan is contained in food can be improved and the astringent taste can be eliminated (see Patent Document 3).
しかし、従来のキトサンゲルは、キトサン以外の他の物質を導入することによりゲル化されたものなので、キトサンゲルの使用目的に応じて導入する物質を選択しなければらならない。特に、食品添加材や化粧品材料、医用材料のような人体に直接関係するような用途にキトサンゲルを用いる場合には、キトサンの効能の他に、導入物質の安全性を確認することが必須となる。したがって、従来のキトサンゲルは、導入物質の安全性等が確認されている限りにおいて、又はそれぞれ限られた用途において有用であるに過ぎず、キトサンに期待されている幅広い利用分野のすべてにおいて有用なものではなかった。また、キレート結合によるキトサンゲル等のように、ゲル状態を維持できる環境が限られたものでは、キトサンゲルを担体として医用材料や化粧品材料として利用する場合に、キトサンゲルに含有させる薬品等が限定されるという問題もある。 However, since the conventional chitosan gel is gelated by introducing a substance other than chitosan, the substance to be introduced must be selected according to the intended use of the chitosan gel. In particular, when using chitosan gel for applications directly related to the human body such as food additives, cosmetic materials, and medical materials, it is essential to confirm the safety of the introduced substance in addition to the efficacy of chitosan. Become. Therefore, the conventional chitosan gel is useful only in the limited use as long as the safety of the introduced substance is confirmed, or in each limited application, and is useful in all of the wide range of applications expected of chitosan. It was not a thing. In addition, in the case where the environment where the gel state can be maintained is limited, such as chitosan gel by chelate bond, when chitosan gel is used as a medical material or cosmetic material as a carrier, the chemicals to be included in chitosan gel are limited. There is also the problem of being.
本発明は、これらの点に鑑みてなされたものであり、キトサンのみでゲル化したキトサンゲル、特に酸性水溶液中でゲル状態を維持できるキトサンゲル、及びキトサンゲルの製造方法を提供することを目的とする。 The present invention has been made in view of these points, and an object thereof is to provide a chitosan gel gelled only with chitosan, particularly a chitosan gel capable of maintaining a gel state in an acidic aqueous solution, and a method for producing the chitosan gel. And
本発明に係るキトサンゲルは、キトサン分子鎖が無水結晶構造により接合した接合領域と、キトサン分子鎖が接合していないほぐれ領域とを有するものであることを特徴とする。 The chitosan gel according to the present invention is characterized in that it has a joining region where chitosan molecular chains are joined by an anhydrous crystal structure and a loose region where chitosan molecular chains are not joined.
また、本発明は、前記キトサンゲルが、酸性水溶液中でゲル化したものであることを特徴とする。 Further, the present invention is characterized in that the chitosan gel is gelated in an acidic aqueous solution.
また、本発明に係るキトサンゲルの製造方法は、酸性水溶液中に溶解させたキトサンをアルカリ中和して、キトサン分子鎖が水和結晶構造により接合した接合領域とキトサン分子鎖が接合していないほぐれ領域とを有する水和結晶再生キトサンとし、該水和結晶再生キトサンを水熱処理して、前記接合領域の水和結晶構造を無水結晶構造に転移した無水結晶再生キトサンとし、該無水結晶再生キトサンを酸性水溶液に浸漬してゲル化することを特徴とする。 In addition, the method for producing a chitosan gel according to the present invention is such that chitosan dissolved in an acidic aqueous solution is alkali-neutralized so that the chitosan molecular chain is bonded to the bonded region by the hydrated crystal structure and the chitosan molecular chain is not bonded. A hydrated crystal regenerated chitosan having a loosened region, and the hydrated crystal regenerated chitosan obtained by hydrothermally treating the hydrated crystal regenerated chitosan to transfer the hydrated crystal structure of the joining region to an anhydrous crystal structure. It is characterized by gelling by immersing in an acidic aqueous solution.
また、本発明は、前記キトサンゲルの製造方法において、キトサンを溶解した酸性水溶液をアルカリ性水溶液に注ぎ込むことにより前記水和結晶再生キトサンを析出させることを特徴とする。 Further, the present invention is characterized in that, in the method for producing the chitosan gel, the hydrated crystal regenerated chitosan is precipitated by pouring an acidic aqueous solution in which chitosan is dissolved into an alkaline aqueous solution.
また、本発明は、前記キトサンゲルの製造方法において、析出した前記水和結晶再生キトサンを水洗処理により中和した後、水熱処理することを特徴とする。 The present invention is also characterized in that, in the method for producing the chitosan gel, the precipitated hydrated crystal regenerated chitosan is neutralized by a water washing treatment and then hydrothermally treated.
また、本発明は、前記キトサンゲルの製造方法において、前記水熱処理は、水和結晶再生キトサンを純水に浸漬した状態で１２０℃以上に加熱することを特徴とする。 In the method for producing a chitosan gel according to the present invention, the hydrothermal treatment is performed by heating to 120 ° C. or more in a state where the hydrated crystal regenerated chitosan is immersed in pure water.
本発明に係るキトサンゲルによれば、キトサン分子鎖が無水結晶構造により接合した接合領域と、キトサン分子鎖が接合していないほぐれ領域とを有するので、ゲル化するための他の物質を導入することなくキトサンのみでゲルとなる。したがって、キトサンに期待されている幅広い利用分野のすべてにおいて利用することができ、特に、食品添加材や化粧品材料、医用材料としての利用が期待される。 According to the chitosan gel according to the present invention, since the chitosan molecular chain has a bonded region bonded by an anhydrous crystal structure and a loosened region where the chitosan molecular chain is not bonded, another substance for gelation is introduced. It becomes a gel only with chitosan without. Therefore, it can be used in all of the wide application fields expected of chitosan, and in particular, it is expected to be used as a food additive, cosmetic material, or medical material.
また、本発明によれば、キトサンゲルを酸性水溶液中でゲル化したものなので、酸性水溶液中でもゲル状態を維持することができ、酸性の薬品等を含有させる担体として、医用材料や化粧品材料等の利用が期待される。 In addition, according to the present invention, since chitosan gel is gelled in an acidic aqueous solution, the gel state can be maintained even in an acidic aqueous solution, and as a carrier containing acidic chemicals or the like, medical materials, cosmetic materials, etc. Expected to be used.
また、本発明に係るキトサンゲルの製造方法によれば、酸性水溶液中に溶解させたキトサンをアルカリ中和して、キトサン分子鎖が水和結晶構造により接合した接合領域とキトサン分子鎖が接合していないほぐれ領域とを有する水和結晶再生キトサンとし、該水和結晶再生キトサンを水熱処理して、前記接合領域の水和結晶構造を無水結晶構造に転移した無水結晶再生キトサンとし、該無水結晶再生キトサンを酸性水溶液に浸漬してゲル化することとしたので、ゲル化するための他の物質を含まないキトサンのみで構成されたゲルを得ることができる。 In addition, according to the method for producing a chitosan gel according to the present invention, chitosan dissolved in an acidic aqueous solution is alkali-neutralized so that the junction region in which chitosan molecular chains are joined by a hydrated crystal structure and chitosan molecular chains are joined. Hydrated crystal regenerated chitosan having an undisentangled region, and hydrothermally treating the hydrated crystal regenerated chitosan to obtain anhydrous crystal regenerated chitosan in which the hydrated crystal structure of the bonding region is transferred to an anhydrous crystal structure, and the anhydrous crystal Since the regenerated chitosan is gelled by immersing it in an acidic aqueous solution, a gel composed only of chitosan not containing other substances for gelation can be obtained.
また、本発明によれば、前記キトサンゲルの製造方法において、キトサンを溶解した酸性水溶液をアルカリ性水溶液に注ぎ込むことにより前記水和結晶再生キトサンを析出させることとしたので、ゲル化するに適した低結晶度且つ低配向性の水和結晶再生キトサンを得ることができる。 Further, according to the present invention, in the method for producing the chitosan gel, the hydrated crystal regenerated chitosan is precipitated by pouring an acidic aqueous solution in which chitosan is dissolved into an alkaline aqueous solution. A hydrated crystal regenerated chitosan having crystallinity and low orientation can be obtained.
また、本発明によれば、前記キトサンゲルの製造方法において、析出した前記水和結晶再生キトサンを水洗処理により中和した後、水熱処理することとしたので、キトサンゲルが塩等を含有しない。 According to the present invention, in the method for producing chitosan gel, the precipitated hydrated crystal regenerated chitosan is neutralized by a water washing treatment and then hydrothermally treated, so that the chitosan gel does not contain a salt or the like.
また、本発明によれば、前記キトサンゲルの製造方法において、前記水熱処理は、水和結晶再生キトサンを純水に浸漬した状態で１２０℃以上に加熱することとしたので、効率的且つ確実に水和結晶構造を無水結晶構造に転移することができる。 Further, according to the present invention, in the method for producing the chitosan gel, the hydrothermal treatment is performed at a temperature of 120 ° C. or more in a state where the hydrated crystal regenerated chitosan is immersed in pure water. The hydrated crystal structure can be transferred to the anhydrous crystal structure.
〔キトサン〕
キトサンは、Ｎ−アセチルグルコサミンがβ−１，４結合で直鎖状に連なったキチンの脱アセチル化物であり、β１，４−ポリ−Ｄ−グルコサミンと定義されている。本発明に係るキトサンとしては、工業的に得られた市販のキトサンやキトサン誘導体から得られたものを用いることができる。その分子量は特に限定されないが、分子量が少なければキトサンゲルが包埋する水量が少なくなって用途が限定的となり、一方、分子量が多ければ酸性水溶液への溶解時間等が長くなる。したがって、分子量は２万以上のものが好ましく、より好ましくは約１０万〜１００万の範囲のものである。また、脱アセチル化度が低ければ酸性水溶液への溶解が困難となることから、脱アセチル化度が７０％以上のものが好適である。
[Chitosan]
Chitosan is a deacetylated product of chitin in which N-acetylglucosamine is linked in a straight chain with β-1,4 bonds, and is defined as β1,4-poly-D-glucosamine. As the chitosan according to the present invention, those obtained from commercially available chitosan or chitosan derivatives obtained industrially can be used. The molecular weight is not particularly limited, but if the molecular weight is small, the amount of water embedded in the chitosan gel is small and the application is limited. On the other hand, if the molecular weight is large, the dissolution time in an acidic aqueous solution becomes long. Accordingly, the molecular weight is preferably 20,000 or more, more preferably in the range of about 100,000 to 1,000,000. In addition, if the degree of deacetylation is low, it becomes difficult to dissolve in an acidic aqueous solution, so that a degree of deacetylation of 70% or more is suitable.
〔キトサン水溶液〕
キトサンは、まず、酸性水溶液に溶解される。キトサンは構成単位であるグルコサミン残基に遊離の一級アミノ基をもつ高分子電解質であり、無機酸、有機酸に溶解する。したがって、キトサンを溶解する酸性水溶液は、塩酸や硝酸のような無機酸の水溶液、酢酸やクエン酸、アスコルビン酸のような有機酸の水溶液を用いることができ、その濃度は、例えば酢酸水溶液であれば０．１〜２．０％程度である。キトサンの溶解濃度は分子量に合わせて調整するが、キトサンを完全に溶解できれば濃度は特に限定されるものではない。
[Chitosan aqueous solution]
Chitosan is first dissolved in an acidic aqueous solution. Chitosan is a polyelectrolyte having a free primary amino group in the glucosamine residue, which is a constituent unit, and is soluble in inorganic acids and organic acids. Therefore, as the acidic aqueous solution for dissolving chitosan, an aqueous solution of an inorganic acid such as hydrochloric acid or nitric acid, or an aqueous solution of an organic acid such as acetic acid, citric acid, or ascorbic acid can be used. If it is 0.1 to 2.0%. The dissolution concentration of chitosan is adjusted according to the molecular weight, but the concentration is not particularly limited as long as chitosan can be completely dissolved.
〔水和結晶再生キトサン〕
キトサンを酸性水溶液に溶解して得たキトサン水溶液を、アルカリ性水溶液に攪拌しながら注ぎ込むことによりアルカリ中和して、水和結晶再生キトサンを析出させる。アルカリ性水溶液としては、例えば、水酸化ナトリウムや水酸化カルシウム等を用いればよい。酸性水溶液に溶解していたキトサンがアルカリ中和によって再び結晶構造をとるために溶液中に析出するのであるが、析出したキトサンの結晶化度や配向性は、酸性水溶液に溶解する前の結晶キトサンより低下しており、キトサン分子鎖が部分的に水和結晶構造により接合しており、その他の部分はキトサン分子鎖が結晶構造をとっていない状態である。このように、キトサン分子鎖が結晶構造により接合した接合領域と接合していないほぐれ領域とを有する状態のキトサンを、本発明において再生キトサンと呼ぶ。また、前述したように析出した再生キトサンは、接合領域の結晶構造が水和結晶であり、この水和結晶構造により部分的に接合された再生キトサンを水和結晶再生キトサンと呼ぶ。この水和結晶再生キトサンは、アルカリ性水溶液中で繊維状又は粒子状の形状で得られ、一般には、使用したキトサンの分子量が大きい場合は繊維状であり、分子量が小さい場合には粒子状となる。このような繊維状又は粒子状の水和結晶再生キトサンは、その周囲はアルカリ中和され易い一方、芯部はアルカリ性水溶液が浸透するのに時間がかかりアルカリ中和され難いので、芯部までアルカリ中和すべくアルカリ水溶液中で数時間から一昼夜攪拌を行う。アルカリ中和が不十分であれば、再生キトサンの接合領域が酸塩を含んだ結晶構造となり、無水結晶への転移に不適である。このようにして得られた水和結晶再生キトサンは、ろ過や遠心分離により回収して水洗する。繊維状の水和結晶再生キトサンはろ過により容易に回収できるが、ろ過により回収が困難な粒子状の水和結晶再生キトサンの場合は遠心分離により回収する。水洗は、ろ過の場合はろ液が中性になるまで、遠心分離の場合は上清が中性になるまで行う。
[Hydrocrystal regenerated chitosan]
Chitosan aqueous solution obtained by dissolving chitosan in acidic aqueous solution is alkali neutralized by pouring into alkaline aqueous solution while stirring to precipitate hydrated crystal regenerated chitosan. For example, sodium hydroxide or calcium hydroxide may be used as the alkaline aqueous solution. The chitosan dissolved in the acidic aqueous solution is precipitated in the solution because of re-establishing the crystal structure by alkali neutralization. The chitosan molecular chain is partially bonded by a hydrated crystal structure, and the other parts are in a state where the chitosan molecular chain does not have a crystal structure. As described above, the chitosan in which the chitosan molecular chain has a joining region joined by a crystal structure and a loose region that is not joined is referred to as regenerated chitosan in the present invention. In addition, the regenerated chitosan deposited as described above has a hydrated crystal structure in the junction region, and the regenerated chitosan partially joined by this hydrated crystal structure is referred to as a hydrated crystal regenerated chitosan. This hydrated crystal regenerated chitosan is obtained in a fibrous or particulate form in an alkaline aqueous solution, and is generally fibrous when the molecular weight of the chitosan used is large, and is particulate when the molecular weight is small. . Such fibrous or particulate hydrated crystal regenerated chitosan is easily neutralized with alkali at its periphery, but the core part takes time for the alkaline aqueous solution to permeate and is difficult to alkali neutralize. Stir for several hours to one day in an alkaline aqueous solution to neutralize. If the alkali neutralization is insufficient, the joined region of the regenerated chitosan has a crystal structure containing an acid salt, which is not suitable for transition to anhydrous crystals. The hydrated crystal regenerated chitosan thus obtained is recovered by filtration or centrifugation and washed with water. Fibrous hydrated crystal regenerated chitosan can be easily recovered by filtration. In the case of particulate hydrated crystal regenerated chitosan that is difficult to recover by filtration, it is recovered by centrifugation. Washing with water is carried out until the filtrate is neutral in the case of filtration and until the supernatant is neutral in the case of centrifugation.
〔無水結晶再生キトサン〕
得られた水和結晶再生キトサンを耐熱ボトル中で純水に浸漬し１２０℃以上に加熱する。加熱は、加圧下で加熱できる高温高圧水蒸気釜や、オートクレーブ等の加圧釜を用いる。純水はイオン交換水程度の純度であればよい。この水熱処理により再生キトサンの水和結晶構造を無水結晶構造に転移させる。本発明では、このように無水結晶構造によりキトサン分子鎖が部分的に接合した再生キトサンを無水結晶再生キトサンと呼ぶ。水和結晶構造から無水結晶構造への転移を起こさせるには加熱温度は１２０〜３００℃が好ましく、使用したキトサンの分子量や、得られたキトサンゲルが包埋する水の量等、目的とするキトサンゲルの性質により加熱温度及び加熱時間を調整する。一般に、加熱温度を高く、加熱時間を長くすれば、無水結晶構造への転移度が高くなると考えられ、食品添加材や化粧品材料、医用材料として汎用性の高いキトサンゲルを得るには、加熱温度は１４０〜２５０℃が好適であり、加熱時間は１０〜６０分が好適である。加熱温度及び加熱時間をあまりに大きくすると、確実に水和結晶構造を無水結晶構造に転移させることができると考えられるが、キトサン分子鎖の加水分解が促進される一方、無水結晶構造による接合領域が多くなり、得られたキトサンゲルは包埋水量が少なく柔軟性のないものとなり易い。また、２００℃を超えるような高温の加熱温度を実現できる加圧釜等の装置は高価であり、加熱時間が長くなれば製造コストが高くなる。また、加熱温度及び加熱時間の調整によるキトサンゲルの性質の制御を容易にするために、水洗後の水和結晶再生キトサンは、湿潤状態で水熱処理することが好ましい。
[Anhydrous crystal regenerated chitosan]
The obtained hydrated crystal regenerated chitosan is immersed in pure water in a heat-resistant bottle and heated to 120 ° C. or higher. For the heating, a high-temperature high-pressure steam kettle that can be heated under pressure or a pressure kettle such as an autoclave is used. The pure water may be as pure as ion-exchanged water. By this hydrothermal treatment, the hydrated crystal structure of regenerated chitosan is transferred to an anhydrous crystal structure. In the present invention, such a regenerated chitosan in which chitosan molecular chains are partially joined by an anhydrous crystal structure is referred to as anhydrous crystal regenerated chitosan. In order to cause the transition from the hydrated crystal structure to the anhydrous crystal structure, the heating temperature is preferably 120 to 300 ° C. The molecular weight of the chitosan used, the amount of water embedded in the obtained chitosan gel, etc. The heating temperature and heating time are adjusted according to the properties of chitosan gel. Generally, if the heating temperature is increased and the heating time is lengthened, it is considered that the degree of transition to an anhydrous crystal structure increases, and in order to obtain chitosan gel having high versatility as a food additive, cosmetic material, or medical material, the heating temperature Is preferably 140 to 250 ° C., and the heating time is preferably 10 to 60 minutes. If the heating temperature and the heating time are too large, it is considered that the hydrated crystal structure can be surely transferred to the anhydrous crystal structure, but the hydrolysis of the chitosan molecular chain is promoted, while the junction region due to the anhydrous crystal structure is increased. The resulting chitosan gel tends to be inflexible with a small amount of embedded water. In addition, an apparatus such as a pressure kettle capable of realizing a high heating temperature exceeding 200 ° C. is expensive, and the manufacturing cost increases as the heating time increases. Moreover, in order to facilitate the control of the properties of the chitosan gel by adjusting the heating temperature and the heating time, the hydrated crystal regenerated chitosan after washing with water is preferably hydrothermally treated in a wet state.
〔無水結晶構造の確認〕
無水結晶再生キトサンが無水結晶構造による接合領域を有するか否かはＸ線解析法で確認できる。図１は、水熱処理後の無水結晶再生キトサンのＸ線回折ディフラクションカーブであり、横軸の１５°付近の回折ピークが無水結晶構造の１１０面を示している。水熱処理において、目的とする加熱温度に達してからの加熱時間が長くなるにつれて１５°付近の回折ピークが高くなっており、水和結晶構造から無水結晶構造への転移が促進されていることがわかる。キトサンは一般に水和結晶構造をとるので酸性水溶液中では溶解するが、無水結晶構造は酸性水溶液中でも容易に緩まらないので溶解し難くなる。この無水結晶構造による接合領域とほぐれ領域とを有することにより、キトサン分子鎖が水分子を包埋してゲル化できる網目構造となる。
[Confirmation of anhydrous crystal structure]
Whether or not anhydrous crystal regenerated chitosan has a junction region with an anhydrous crystal structure can be confirmed by X-ray analysis. FIG. 1 is an X-ray diffraction diffraction curve of anhydrous crystal regenerated chitosan after hydrothermal treatment, and the diffraction peak near 15 ° on the horizontal axis indicates the 110 plane of the anhydrous crystal structure. In hydrothermal treatment, the diffraction peak near 15 ° increases as the heating time after reaching the target heating temperature increases, and the transition from the hydrated crystal structure to the anhydrous crystal structure is promoted. Recognize. Since chitosan generally has a hydrated crystal structure, it dissolves in an acidic aqueous solution. However, an anhydrous crystal structure is not easily loosened even in an acidic aqueous solution, and is difficult to dissolve. By having the junction region and the loose region due to this anhydrous crystal structure, the chitosan molecular chain has a network structure in which water molecules are embedded and gelled.
〔キトサンゲル〕
得られた無水結晶再生キトサンを酸性水溶液に浸漬することによりゲル化する。前述したように、無水結晶再生キトサンは、無水結晶構造による接合領域とほぐれ領域とを有することにより、酸性水溶液中で網目構造を維持し、ほぐれ領域において水和することにより膨潤してゲルとなる。なお、無水結晶構造も酸性水溶液中で時間の経過とともに緩まるので、無水結晶再生キトサンもやがては酸性水溶液に溶解するが、この溶解速度は水和結晶再生キトサンと比較して極めて遅く、数時間から数日間はゲル状態を維持する。この溶解速度は、キトサンの分子量や水熱処理の加熱温度及び加熱時間で調整できる。したがって、流動性をもつキトサンゲルも、水熱処理の条件やキトサンの分子量によって得ることができる。このようにして得られたキトサンゲルは、ゲル化するために他の物質を導入することなくキトサンのみで構成されているので、キトサンに期待されている幅広い利用分野のすべてにおいて利用することができ、特に、人体への安全性を確保する必要がある食品添加材や化粧品材料、医用材料としての利用が期待される。また、酸性水溶液中でもゲル状態を維持することができ、酸性の薬品等を含有させる担体として、医用材料や化粧品材料等への利用が期待される。
[Chitosan gel]
The obtained anhydrous crystal regenerated chitosan is gelled by immersing it in an acidic aqueous solution. As described above, anhydrous crystal regenerated chitosan has a junction region and a loosening region due to an anhydrous crystal structure, thereby maintaining a network structure in an acidic aqueous solution, and swelling into a gel by hydration in the loosening region. . Since anhydrous crystal structure also relaxes in acidic aqueous solution over time, anhydrous crystal regenerated chitosan eventually dissolves in acidic aqueous solution, but this dissolution rate is extremely slow compared to hydrated crystal regenerated chitosan, several hours The gel state is maintained for several days after. This dissolution rate can be adjusted by the molecular weight of chitosan and the heating temperature and heating time of hydrothermal treatment. Therefore, fluid chitosan gel can also be obtained depending on the conditions of hydrothermal treatment and the molecular weight of chitosan. The chitosan gel obtained in this way is composed only of chitosan without introducing other substances for gelation, so it can be used in all of the wide range of applications expected of chitosan. In particular, it is expected to be used as a food additive, cosmetic material, or medical material that needs to ensure safety to the human body. Moreover, the gel state can be maintained even in an acidic aqueous solution, and it is expected to be used for medical materials, cosmetic materials and the like as a carrier containing acidic chemicals and the like.
〔実施例１，２〕
実施例１としてキトサンＤＡＣ１００（甲陽ケミカル、Ｍｗ＞１０００，０００）を、実施例２としてキトサンＳＫ−１０（甲陽ケミカル、Ｍｗ≒１００，０００）を用い、各キトサンを乾燥重量５．０ｇで２．０％の酢酸水溶液に溶解して一昼夜放置した後、ガーゼでろ過してキトサン溶液を得た。これらキトサン溶液を、１．０ｌの５．０％水酸化ナトリウム水溶液中に攪拌しながら緩やかに注ぎ込んで水和結晶再生キトサンを析出させ、水酸化ナトリウム水溶液中で室温で一昼夜攪拌した。得られた水和結晶再生キトサンを純水で洗浄し、ろ液が中性になるまで純水で洗浄及びろ過を繰り返した。その後、ろ紙上で吸引ろ過して水分量約９０％まで脱水した。
乾燥重量に換算して１．６ｇの水和結晶再生キトサンを、パッキン付きスクリューコック式耐熱瓶（２５０ｍｌ）に採り、全量が２００ｍｌとなるように純水を加えた。これに蓋をして、高温高圧水蒸気釜（日阪製作所）に入れて、加熱温度を１２０〜２００℃の所定温度、昇温時間２０分、温度保持時間２０分で高温高圧水蒸気により加熱して無水結晶再生キトサンを夫々得た。なお、実施例で用いた高温高圧水蒸気釜は、昇温速度、温度保持時間等の条件を任意の条件に制御可能なものである。
Examples 1 and 2
Chitosan DAC100 (Koyo Chemical, Mw> 1,000,000) was used as Example 1, Chitosan SK-10 (Koyo Chemical, Mw≈100,000) was used as Example 2, and each chitosan was dried at a weight of 5.0 g. After dissolving in a 0% aqueous acetic acid solution and allowing it to stand overnight, it was filtered through gauze to obtain a chitosan solution. These chitosan solutions were gently poured into 1.0 l of 5.0% sodium hydroxide aqueous solution while stirring to precipitate hydrated crystal regenerated chitosan, and stirred in an aqueous sodium hydroxide solution at room temperature for a whole day and night. The obtained hydrated crystal regenerated chitosan was washed with pure water, and washing and filtration were repeated with pure water until the filtrate became neutral. Thereafter, the solution was suction filtered on a filter paper and dehydrated to a water content of about 90%.
1.6 g of hydrated crystal regenerated chitosan in terms of dry weight was put into a screw cock type heat-resistant bottle (250 ml) with packing, and pure water was added so that the total amount became 200 ml. Cover this, put it in a high-temperature and high-pressure steam kettle (Hisaka Seisakusho), and heat it with high-temperature and high-pressure steam at a predetermined temperature of 120 to 200 ° C, a heating time of 20 minutes, and a temperature holding time of 20 minutes. Anhydrous crystal regenerated chitosan was obtained respectively. Note that the high-temperature and high-pressure steam kettle used in the examples can control conditions such as a rate of temperature rise and a temperature holding time to arbitrary conditions.
〔実施例３〕
実施例１と同様にして、前記キトサンＤＡＣ１００を再生処理、水洗処理して水和結晶再生キトサンを得た後、加熱温度を１８０℃、温度保持時間を６０分とし、他は実施例１と同様の条件で水熱処理をして無水結晶再生キトサンを得た。
Example 3
In the same manner as in Example 1, the chitosan DAC 100 was regenerated and washed with water to obtain a hydrated crystal regenerated chitosan. Then, the heating temperature was 180 ° C. and the temperature holding time was 60 minutes. Hydrothermal treatment was carried out under the conditions described above to obtain anhydrous crystal regenerated chitosan.
〔比較例１，２〕
前記２種類のキトサンＤＡＣ１００，ＳＫ−１０を、再生処理することなく、即ち酢酸水溶液に溶解した後、水酸化ナトリウムで析出させることなく、乾燥状態のままで、室温及び１２０〜２００℃の所定温度で一昼夜オーブン内で加熱して乾燥加熱処理キトサンを得た。
[Comparative Examples 1 and 2]
The two kinds of chitosan DAC100 and SK-10 are not regenerated, that is, dissolved in an acetic acid aqueous solution, and then precipitated in sodium hydroxide and kept in a dry state at room temperature and a predetermined temperature of 120 to 200 ° C. And heated in an oven for a whole day and night to obtain a dry heat-treated chitosan.
〔比較例３，４〕
前記実施例１，２と同様にして、２種類のキトサンＤＡＣ１００，ＳＫ−１０を用いて水和結晶再生キトサンを夫々生成し、該水和結晶再生キトサンを乾燥状態で、即ち純水に浸漬することなく、室温及び１２０〜２００℃の所定温度で一昼夜オーブン内で加熱して乾燥加熱処理再生キトサンを得た。
[Comparative Examples 3 and 4]
In the same manner as in Examples 1 and 2, hydrated crystal regenerated chitosan was produced using two kinds of chitosan DAC100 and SK-10, respectively, and the hydrated crystal regenerated chitosan was immersed in pure water, that is, in pure water. Without heating, it was heated in an oven for a whole day and night at room temperature and a predetermined temperature of 120 to 200 ° C. to obtain a dried and heat-treated recycled chitosan.
〔比較例５，６〕
前記２種類のキトサンＤＡＣ１００，ＳＫ−１０を、再生処理することなく純水に浸漬し、１２０〜２００℃の所定温度、昇温時間２０分、温度保持時間２０分で高温高圧水蒸気により加熱して水熱処理キトサンを得た。
[Comparative Examples 5 and 6]
The two kinds of chitosan DACs 100 and SK-10 are immersed in pure water without being regenerated, and heated with high-temperature and high-pressure steam at a predetermined temperature of 120 to 200 ° C., a heating time of 20 minutes, and a temperature holding time of 20 minutes. Hydrothermally treated chitosan was obtained.
〔確認〕
実施例１〜３で得られた各無水結晶再生キトサンをＸ線回折により分析した結果、１２０℃以上で水熱処理をしたものについて、無水結晶構造の１１０面を示す１５°付近の回折ピークが確認できた。
〔Confirmation〕
As a result of analyzing each anhydrous crystal regenerated chitosan obtained in Examples 1 to 3 by X-ray diffraction, a diffraction peak near 15 ° indicating the 110 plane of the anhydrous crystal structure was confirmed for those subjected to hydrothermal treatment at 120 ° C. or higher. did it.
〔評価〕
実施例１，２及び比較例１〜４で得られた無水結晶再生キトサン、乾燥加熱処理キトサン、乾燥加熱処理再生キトサン、水熱処理キトサンを、各々２．０％の酢酸水溶液に添加して攪拌し、溶解性を観察した。その結果を表１に示す。
[Evaluation]
The anhydrous crystal regenerated chitosan, dry heat-treated chitosan, dry heat-treated regenerated chitosan, and hydrothermally-treated chitosan obtained in Examples 1 and 2 and Comparative Examples 1 to 4 were each added to a 2.0% acetic acid aqueous solution and stirred. The solubility was observed. The results are shown in Table 1.
実施例１の無水結晶再生キトサンは、水熱処理温度が１４０℃のものでは水溶液が粘調となり、１６０，１８０℃のものでゲル状となった。また、水熱処理温度が２００℃のものでは水溶液が膨潤状態となった。また、実施例２の無水結晶再生キトサンは、水熱処理温度が１４０，１６０℃のもので水溶液がゲル状となり、１８０℃のものでは膨潤状態となった。一方、水熱処理温度が２００℃のものは酢酸水溶液に不溶であった。このように、無水結晶再生キトサンは、酢酸溶液に溶解しても完全に溶解せずゲル状態を維持することが確認された。また、本実施例では、水熱処理温度が１４０〜１８０℃の範囲でゲル状態が確認でき、処理温度が低くなると酢酸水溶液中ではゲル状態ではなく高い粘度の状態、即ち粘調となり、室温では完全に溶解した。一方、水熱処理温度が高くなると膨潤状態となり、不溶となる場合も確認された。このことから、水熱処理温度によって、得られた無水結晶再生キトサンの無水結晶構造による接合領域の範囲に違いができることが想定され、この水熱処理温度を適宜調整することにより所望のゲル状態となる無水結晶再生キトサンを得ることができると考えられる。 The anhydrous crystal regenerated chitosan of Example 1 had a viscous aqueous solution when the hydrothermal treatment temperature was 140 ° C., and became a gel at 160 and 180 ° C. Further, when the hydrothermal treatment temperature was 200 ° C., the aqueous solution was in a swollen state. Further, the anhydrous crystal regenerated chitosan of Example 2 had a hydrothermal treatment temperature of 140,160 ° C., and the aqueous solution became a gel, while that of 180 ° C. was swollen. On the other hand, the hydrothermal treatment temperature of 200 ° C. was insoluble in the acetic acid aqueous solution. Thus, it was confirmed that anhydrous crystal regenerated chitosan was not completely dissolved even in an acetic acid solution and maintained in a gel state. Further, in this example, the gel state can be confirmed when the hydrothermal treatment temperature is in the range of 140 to 180 ° C. When the treatment temperature is low, the gel is not in a gel state but is in a high viscosity state, that is, a viscous tone in an aqueous acetic acid solution. Dissolved in. On the other hand, it was confirmed that when the hydrothermal treatment temperature was increased, it was swollen and insoluble. From this, it is assumed that the range of the bonding region due to the anhydrous crystal structure of the obtained anhydrous crystal regenerated chitosan can be varied depending on the hydrothermal treatment temperature, and the anhydrous gel that becomes a desired gel state by appropriately adjusting the hydrothermal treatment temperature. It is considered that crystal regenerated chitosan can be obtained.
比較例１，２の乾燥加熱処理キトサン、及び比較例３，４の乾燥加熱処理再生キトサンは、１２０〜２００℃のすべての処理温度のもので、酢酸水溶液に不溶であった。これより、乾燥状態での加熱処理では、酢酸水溶液中でゲル化するような、無水結晶構造による接合領域とほぐれ領域とが形成されないと考えられる。一方、室温で処理したものは酢酸水溶液に溶解することから、水和結晶構造から無水結晶構造への転移が起こらなかったと推測される。 The dry heat-treated chitosan of Comparative Examples 1 and 2 and the dry heat-treated regenerated chitosan of Comparative Examples 3 and 4 were at all treatment temperatures of 120 to 200 ° C. and were insoluble in the acetic acid aqueous solution. From this, it is considered that the heat treatment in the dry state does not form a bonding region and a loosening region with an anhydrous crystal structure that gel in an acetic acid aqueous solution. On the other hand, since the thing processed at room temperature melt | dissolves in acetic acid aqueous solution, it is estimated that the transition from a hydrate crystal structure to an anhydrous crystal structure did not occur.
比較例５の水熱処理キトサンは、水熱処理温度が１４０℃のものは水溶液が粘調となり、１６０℃以上で不溶であった。また、比較例６の水熱処理キトサンは、水熱処理温度が１４０℃のものは水溶液が粘調となり、１８０℃のものは膨潤状態、１８０℃以上で不溶であった。このことから、キトサンを再生処理することなく水熱処理を行っても、酸性水溶液中でゲル状態となるキトサンを得ることは難しいと考えられる。 The hydrothermally treated chitosan of Comparative Example 5 had a hydrothermal treatment temperature of 140 ° C., and the aqueous solution became viscous, and was insoluble at 160 ° C. or higher. Moreover, as for the hydrothermally-treated chitosan of Comparative Example 6, when the hydrothermal treatment temperature was 140 ° C., the aqueous solution became viscous, and when it was 180 ° C., the swollen state was insoluble at 180 ° C. or higher. From this, it is considered that it is difficult to obtain chitosan that is in a gel state in an acidic aqueous solution even if hydrothermal treatment is performed without regenerating chitosan.
また、実施例１において１８０℃で水熱処理を行って得られた無水結晶再生キトサンと、実施例３で得られた無水結晶再生キトサンとを、２．０％酢酸水溶液に０．５％の濃度で溶解してゲルを形成し、ゲル状態の保持時間を観察した。いずれも時間の経過とともにゲル状態から粘調状態となった後、完全に溶解したが、実施例１の無水結晶再生キトサンのゲルは、完全に溶解するまで約２週間であった。これに対し、実施例３の無水結晶再生キトサンのゲルは、完全に溶解するまで１ヶ月以上を要した。このことから、無水結晶再生キトサンのゲル寿命は、一般的なゲルに比べて短く、水熱処理時間等の処理条件を適宜調整することにより所望のゲル寿命の無水結晶再生キトサンを得ることができると考えられる。 Further, anhydrous crystal regenerated chitosan obtained by hydrothermal treatment at 180 ° C. in Example 1 and anhydrous crystal regenerated chitosan obtained in Example 3 were added at a concentration of 0.5% in a 2.0% acetic acid aqueous solution. Was dissolved to form a gel, and the retention time in the gel state was observed. In any case, the gel state changed from a gel state to a viscous state over time, and then completely dissolved. However, the anhydrous crystal regenerated chitosan gel of Example 1 was about 2 weeks until completely dissolved. In contrast, the anhydrous crystal regenerated chitosan gel of Example 3 required one month or more to completely dissolve. From this, the gel life of anhydrous crystal regenerated chitosan is shorter than that of a general gel, and it is possible to obtain anhydrous crystal regenerated chitosan having a desired gel life by appropriately adjusting treatment conditions such as hydrothermal treatment time. Conceivable.
本発明に係るキトサンゲルは、抗菌材料や医用材料、化粧品材料、食品添加材、分離材料、農業資材、シート材料、水処理材等の幅広い分野において利用可能である。 The chitosan gel according to the present invention can be used in a wide range of fields such as antibacterial materials, medical materials, cosmetic materials, food additives, separation materials, agricultural materials, sheet materials, and water treatment materials.
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|---|---|---|---|---|
| WO2006067987A1 (en) * | 2004-12-21 | 2006-06-29 | A School Corporation Kansai University | Neutral chitosan hydrogel and method for producing same |
| JP2019026763A (en) * | 2017-07-31 | 2019-02-21 | 甲陽ケミカル株式会社 | Composition for organic matter flocculation containing regenerated chitosan |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01215836A (en) * | 1988-02-24 | 1989-08-29 | Yaegaki Hakko Giken Kk | Chitosan gel composition and its production |
| JPH01304855A (en) * | 1988-06-03 | 1989-12-08 | Kanegafuchi Chem Ind Co Ltd | Fruit sauce and production thereof |
| JPH0233322A (en) * | 1988-02-08 | 1990-02-02 | E I Du Pont De Nemours & Co | Chitosan fiber having a high strength and its cloth |
| JPH03130043A (en) * | 1989-10-16 | 1991-06-03 | Snow Brand Milk Prod Co Ltd | Cottony gelatinized substance, pulpy jelly using the same as raw material and its production |
| JPH05207867A (en) * | 1991-12-27 | 1993-08-20 | Aron World:Kk | Production of chitosan solution, food treated with the same solution and food packing material |
| JPH06237712A (en) * | 1993-02-12 | 1994-08-30 | Aron World:Kk | Production of chitosan gel having decreased viscosity |
| JPH0790005A (en) * | 1993-09-24 | 1995-04-04 | Daiichi Seimo Kk | Production of water-soluble chitosan |
| JPH0790245A (en) * | 1993-09-24 | 1995-04-04 | Daiichi Seimo Kk | Composition gelable on heating |
| JPH0812965A (en) * | 1994-06-29 | 1996-01-16 | Matsugishi Kenkyusho:Kk | Preparation of chitosan cool storage material |
| JP2002010755A (en) * | 2000-06-29 | 2002-01-15 | Nichiro Corp | Gel-like chitosan formed product, food containing the same and method for modifying palate feeling of gel-like chitosan formed product |
-
2004
- 2004-08-03 JP JP2004226447A patent/JP5207015B2/en not_active Expired - Fee Related
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0233322A (en) * | 1988-02-08 | 1990-02-02 | E I Du Pont De Nemours & Co | Chitosan fiber having a high strength and its cloth |
| JPH01215836A (en) * | 1988-02-24 | 1989-08-29 | Yaegaki Hakko Giken Kk | Chitosan gel composition and its production |
| JPH01304855A (en) * | 1988-06-03 | 1989-12-08 | Kanegafuchi Chem Ind Co Ltd | Fruit sauce and production thereof |
| JPH03130043A (en) * | 1989-10-16 | 1991-06-03 | Snow Brand Milk Prod Co Ltd | Cottony gelatinized substance, pulpy jelly using the same as raw material and its production |
| JPH05207867A (en) * | 1991-12-27 | 1993-08-20 | Aron World:Kk | Production of chitosan solution, food treated with the same solution and food packing material |
| JPH06237712A (en) * | 1993-02-12 | 1994-08-30 | Aron World:Kk | Production of chitosan gel having decreased viscosity |
| JPH0790005A (en) * | 1993-09-24 | 1995-04-04 | Daiichi Seimo Kk | Production of water-soluble chitosan |
| JPH0790245A (en) * | 1993-09-24 | 1995-04-04 | Daiichi Seimo Kk | Composition gelable on heating |
| JPH0812965A (en) * | 1994-06-29 | 1996-01-16 | Matsugishi Kenkyusho:Kk | Preparation of chitosan cool storage material |
| JP2002010755A (en) * | 2000-06-29 | 2002-01-15 | Nichiro Corp | Gel-like chitosan formed product, food containing the same and method for modifying palate feeling of gel-like chitosan formed product |
Non-Patent Citations (2)
| Title |
|---|
| JPN6010072148; 繊維学会誌 Ｖｏｌ．５９ Ｎｏ．３, 2003, ｐ．１０４-１０９ * |
| JPN6011064420; キチン，キトサンハンドブック , 19950225, ｐ．３９８, 技報堂出版株式会社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067987A1 (en) * | 2004-12-21 | 2006-06-29 | A School Corporation Kansai University | Neutral chitosan hydrogel and method for producing same |
| JP2006176584A (en) * | 2004-12-21 | 2006-07-06 | Univ Kansai | Neutral chitosan hydrogel and its preparation method |
| JP2019026763A (en) * | 2017-07-31 | 2019-02-21 | 甲陽ケミカル株式会社 | Composition for organic matter flocculation containing regenerated chitosan |
| JP7071721B2 (en) | 2017-07-31 | 2022-05-19 | 甲陽ケミカル株式会社 | Composition for organic matter aggregation containing regenerated chitosan |
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