JPWO2015163294A1 - Porous material and porous sheet - Google Patents
Porous material and porous sheet Download PDFInfo
- Publication number
- JPWO2015163294A1 JPWO2015163294A1 JP2016514930A JP2016514930A JPWO2015163294A1 JP WO2015163294 A1 JPWO2015163294 A1 JP WO2015163294A1 JP 2016514930 A JP2016514930 A JP 2016514930A JP 2016514930 A JP2016514930 A JP 2016514930A JP WO2015163294 A1 JPWO2015163294 A1 JP WO2015163294A1
- Authority
- JP
- Japan
- Prior art keywords
- porous material
- silk fibroin
- porous
- containing compound
- hydroxyl group
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
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- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Cosmetics (AREA)
- Materials For Medical Uses (AREA)
Abstract
乾燥状態でも柔らかく、ハンドリング性及びスライス加工性に優れるフィブロイン多孔質体を用いた多孔質材料及び多孔質シートを提供する。フィブロイン多孔質体が、分子量が１，０００以下の水酸基含有化合物を２０〜７５質量％含むことを特徴とする多孔質材料である。Provided are a porous material and a porous sheet using a fibroin porous material that is soft even in a dry state and excellent in handling property and slicing property. The fibroin porous material is a porous material characterized by containing 20 to 75% by mass of a hydroxyl group-containing compound having a molecular weight of 1,000 or less.
Description
本発明は、フィブロイン多孔質体を用いて得られる多孔質材料及び多孔質シートに関するものである。 The present invention relates to a porous material and a porous sheet obtained using a fibroin porous material.
タンパク質、糖類等の生物由来物質を利用して作製可能である多孔質体は、癒着防止剤、創傷被覆材、薬剤徐放担体等の医療分野、微生物、細菌等の住処になる支持体として活用しうる浄水分野、細胞培養支持体（足場材料）、組織再生支持体等として活用しうる組織工学及び再生医療工学分野、エステティックサロン及び個人での使用による保湿等を目的とした化粧品・エステ分野、紙おむつ、生理用品等の生活日用品分野など、産業上幅広い分野で利用される。 Porous materials that can be produced using biological materials such as proteins and saccharides can be used as a support for medical fields such as anti-adhesive agents, wound dressings, and sustained-release carriers, and as a residence for microorganisms and bacteria. Water purification field, cell culture support (scaffolding material), tissue engineering and regenerative medical engineering fields that can be used as tissue regeneration support, cosmetic salons and cosmetics for the purpose of esthetic salon and personal use, It is used in a wide range of industries such as daily necessities such as disposable diapers and sanitary products.
上記のような幅広い分野に用いられる多孔質体を構成する材料として、セルロース、キチン等の糖類、コラーゲン、ケラチン、フィブロイン等のタンパク質群などの生体由来物質が知られている。これらの生体由来物質のうち、フィブロイン、とりわけシルクフィブロインは、原料の安定供給、価格の安定性から工業的に利用される。さらに、衣類用途以外に、手術用縫合糸として長く使用されてきた実績があり、近年、食品及び化粧品の添加物としても利用されている。シルクフィブロインは人体に対する安全性に優れる材料であるため、多孔質体を形成する材料としての使用が検討されている。
シルクフィブロイン多孔質体を作製する手法に関しては、いくつか報告がある。例えば、シルクフィブロイン水溶液を急速冷凍したのち結晶化溶媒に浸漬し、融解と結晶化を同時進行することによって得る方法（特許文献１）、シルクフィブロイン水溶液を冷凍した後に長時間凍結状態を維持することで多孔質体を作製する手法（特許文献２）、シルクフィブロイン水溶液に対して少量の水溶性有機溶媒を添加した後に、一定時間冷凍して融解することによってシルクフィブロイン多孔質体が得られる手法である（特許文献３）。Biological substances such as sugars such as cellulose and chitin, and protein groups such as collagen, keratin, and fibroin are known as materials constituting porous bodies used in a wide range of fields as described above. Of these bio-derived substances, fibroin, especially silk fibroin, is industrially used from the viewpoint of stable supply of raw materials and price stability. Furthermore, it has a track record of being used for a long time as a surgical suture, in addition to clothing applications, and has recently been used as an additive for foods and cosmetics. Since silk fibroin is a material excellent in safety to the human body, its use as a material for forming a porous body has been studied.
There are several reports on the technique for producing silk fibroin porous materials. For example, a method in which a silk fibroin aqueous solution is rapidly frozen and then immersed in a crystallization solvent and melted and crystallized at the same time (Patent Document 1). (Patent Document 2), a method of producing a porous material by adding a small amount of a water-soluble organic solvent to a silk fibroin aqueous solution, and then freezing and melting for a certain time to obtain a silk fibroin porous material. Yes (Patent Document 3).
上記の手法によって作製した多孔質体は水を含んだ湿潤状態では柔らかいものの、凍結乾燥等の乾燥により水を除去した乾燥状態では脆く、クラックが発生する等して加工性、及び外観に劣るという課題があった。 The porous body produced by the above method is soft in a wet state containing water, but is brittle in a dry state where water is removed by drying such as freeze-drying, and it is inferior in workability and appearance, such as generation of cracks. There was a problem.
ところで、上記の産業分野の中でも、生体親和性が高いというフィブロイン多孔質体の特性に着目し、特に、フィブロイン多孔質体の医療分野、組織工学及び再生医療工学分野での利用が検討されている。例えば、創傷被覆材は、創傷部に貼付することによる痛みの緩和、また該創傷部をぶつけた際の痛みを軽減するものとしてだけではなく、傷口等から滲み出してくる滲出液を吸収して創傷部に保持し、該滲出液に含まれる成分を積極的に活用することで、創傷を治癒させる湿潤療法に活用しうるものとして注目されている。
これらの用途に適用する場合、フィブロイン多孔質体には、上記の加工性、及び外観に加えて、滲出液等を吸収する吸水性、傷口等を保護するためのクッション性、伸縮に対する追随性も求められる。By the way, focusing on the characteristics of the fibroin porous material having high biocompatibility among the above-mentioned industrial fields, the use of the fibroin porous material in the medical field, tissue engineering and regenerative medical engineering field is being studied. . For example, wound dressings not only relieve pain caused by sticking to wounds, but also reduce pain when hitting the wounds, but also absorb exudate that exudes from wounds, etc. It has been attracting attention as being able to be used in wet therapy for healing a wound by holding it in a wound part and actively utilizing the components contained in the exudate.
When applied to these applications, the fibroin porous material has not only the above processability and appearance, but also water absorption to absorb exudate, etc., cushioning to protect wounds, etc. Desired.
本発明は、乾燥状態でも柔らかく、乾燥後の外観及びスライス加工性に優れ、かつ吸水性、弾力性及び追随性にも優れるフィブロイン多孔質体を用いた多孔質材料及び多孔質シートを提供することを課題とする。 The present invention provides a porous material and a porous sheet using a fibroin porous body that is soft even in a dry state, excellent in appearance after drying and slicing workability, and excellent in water absorption, elasticity, and followability. Is an issue.
本発明者は、前記課題を達成するために鋭意研究を重ねた結果、下記の発明により当該課題を解決できることを見出した。
［１］フィブロイン多孔質体が、分子量が１，０００以下の水酸基含有化合物を２０〜７５質量％含むことを特徴とする多孔質材料。
［２］前記水酸基含有化合物が、グリセリン、ポリグリセリン、ポリエチレングリコール、クエン酸トリエチル、乳酸、ポリビニルアルコール、プロピレングリコール、ブチレングリコール、アルコール、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、及びソルビタン脂肪酸エステルから選択される１種以上である［１］に記載の多孔質材料。
［３］前記水酸基含有化合物がグリセリンである［１］に記載の多孔質材料。
［４］［１］〜［３］のいずれかに記載の多孔質材料からなり、膜厚が０．１〜５０ｍｍである多孔質シート。As a result of intensive studies to achieve the above problems, the present inventor has found that the problems can be solved by the following invention.
[1] A porous material, wherein the fibroin porous material contains 20 to 75% by mass of a hydroxyl group-containing compound having a molecular weight of 1,000 or less.
[2] The hydroxyl group-containing compound is selected from glycerin, polyglycerin, polyethylene glycol, triethyl citrate, lactic acid, polyvinyl alcohol, propylene glycol, butylene glycol, alcohol, glycerin fatty acid ester, polyglycerin fatty acid ester, and sorbitan fatty acid ester. [1] The porous material according to [1].
[3] The porous material according to [1], wherein the hydroxyl group-containing compound is glycerin.
[4] A porous sheet made of the porous material according to any one of [1] to [3] and having a thickness of 0.1 to 50 mm.
本発明に係る多孔質材料及び多孔質シートは、乾燥状態でも柔らかく、乾燥後の外観及びスライス加工性に優れ、かつ吸水性、弾力性及び追随性にも優れる。 The porous material and porous sheet according to the present invention are soft even in a dry state, excellent in appearance after drying and slicing workability, and excellent in water absorption, elasticity, and followability.
〔多孔質材料〕
本発明に係る多孔質材料は、フィブロイン多孔質体が、分子量が１，０００以下の水酸基含有化合物を２０〜７５質量％含むことを特徴とするものである。すなわち、本発明の多孔質材料においては、フィブロイン多孔質体が上記水酸基含有化合物を保持している。[Porous material]
The porous material according to the present invention is characterized in that the fibroin porous body contains 20 to 75% by mass of a hydroxyl group-containing compound having a molecular weight of 1,000 or less. That is, in the porous material of the present invention, the fibroin porous body holds the hydroxyl group-containing compound.
上記水酸基含有化合物としては、１分子当り１つ以上の水酸基を有するものであればよく、１分子当り１〜１０の水酸基を有するものが好ましく、１分子当り１〜４の水酸基を有するものがより好ましい。
また、水酸基含有化合物の分子量は、１,０００以下であり、８００以下あることが好ましく、５００以下であることがより好ましい。水酸基含有化合物の分子量の下限は特に制限はないが、５０以上であることが好ましく、８０以上であることがより好ましい。The hydroxyl group-containing compound may be any compound having one or more hydroxyl groups per molecule, preferably having 1 to 10 hydroxyl groups per molecule, and more preferably having 1 to 4 hydroxyl groups per molecule. preferable.
Further, the molecular weight of the hydroxyl group-containing compound is 1,000 or less, preferably 800 or less, and more preferably 500 or less. The lower limit of the molecular weight of the hydroxyl group-containing compound is not particularly limited, but is preferably 50 or more, and more preferably 80 or more.
水酸基含有化合物の具体例としては、例えば、グリセリン、ポリグリセリン、ポリエチレングリコール、クエン酸トリエチル、乳酸、ポリビニルアルコール、プロピレングリコール、ブチレングリコール、アルコール、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル等が挙げられ、このうち１種又は２種以上を用いることができる。ハンドリング性、スライス加工性及び安全性の観点から、グリセリン、ポリエチレングリコール、クエン酸トリエチル、ポリグリセリン、乳酸、プロピレングリコール及びブチレングリコールが好ましい。これらの中でも、グリセリンは、肌を保湿する効果があるので、スキンケア材料、創傷被覆材等の肌に貼り付けて使用する用途において特に好ましい。 Specific examples of the hydroxyl group-containing compound include glycerin, polyglycerin, polyethylene glycol, triethyl citrate, lactic acid, polyvinyl alcohol, propylene glycol, butylene glycol, alcohol, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, and the like. Of these, one or more of them can be used. Glycerin, polyethylene glycol, triethyl citrate, polyglycerin, lactic acid, propylene glycol, and butylene glycol are preferred from the viewpoints of handling properties, slice processability, and safety. Among these, since glycerin has an effect of moisturizing the skin, it is particularly preferable in applications where the glycerin is used by being attached to the skin such as skin care materials and wound dressings.
本発明に係る多孔質材料、すなわち水酸基含有化合物を含むフィブロイン多孔質体中の水酸基含有化合物の含有量は、２０〜７５質量％であることを要する。また、水酸基含有化合物の含有量は、２５〜６０質量％であることがより好ましく、２５〜４５質量％であることがさらに好ましい。水酸基含有化合物の含有量が上記範囲内であると、柔軟性、加工性及びハンドリング性に優れる多孔質材料を得ることができる。より具体的には、２０質量％以上であると柔軟性に優れ、乾燥時に割れにくく、脆くなることがなく、スライス加工時に割れにくく、また優れたハンドリング性が得られる。一方、７５質量％以下であると柔軟性に優れ、凍結乾燥前後での収縮が小さく、多孔質材料の表面のタックが良好であり、スライス加工時にロールに巻きつきにくく、優れたハンドリング性が得られる。
また、本発明の多孔質材料は、上記範囲内において含有量を変化させることで、その硬さを調整することができる。水酸基含有化合物の含有量を多くするほど、多孔質材料は柔軟になる。Content of the hydroxyl-containing compound in the porous material which concerns on this invention, ie, the fibroin porous body containing a hydroxyl-containing compound, needs to be 20-75 mass%. Further, the content of the hydroxyl group-containing compound is more preferably 25 to 60% by mass, and further preferably 25 to 45% by mass. When the content of the hydroxyl group-containing compound is within the above range, a porous material excellent in flexibility, workability and handling properties can be obtained. More specifically, if it is 20% by mass or more, it is excellent in flexibility, hardly cracked during drying, does not become brittle, is not easily cracked during slicing, and provides excellent handling properties. On the other hand, when it is 75% by mass or less, it has excellent flexibility, small shrinkage before and after lyophilization, good surface tack of the porous material, hardly wraps around the roll during slicing, and has excellent handling properties. It is done.
Moreover, the hardness of the porous material of the present invention can be adjusted by changing the content within the above range. As the content of the hydroxyl group-containing compound is increased, the porous material becomes more flexible.
フィブロイン多孔質体の原料として用いられるフィブロインとしては、例えば、家蚕、野蚕、天蚕等の天然蚕、トランスジェニック蚕などから産生されるシルクフィブロイン等が挙げられる。本発明においては、乾燥状態でも柔らかく、乾燥後の外観、スライス加工性に優れる多孔質材料及び多孔質シートを得る観点から、シルクフィブロインを原料とすることが好ましい。 Examples of the fibroin used as a raw material for the fibroin porous material include silk fibroin produced from natural silkworms such as rabbits, wild silkworms, and tengu, and transgenic silkworms. In the present invention, it is preferable to use silk fibroin as a raw material from the viewpoint of obtaining a porous material and a porous sheet that are soft even in a dry state and excellent in appearance after drying and slice processability.
以下、フィブロインとして好ましいシルクフィブロインを例にとって説明する。シルクフィブロイン多孔質体は、シルクフィブロイン溶液から得られるが、水に溶解させる場合、シルクフィブロインは水に対する溶解性が悪く、直接水に溶解することは困難である。シルクフィブロイン水溶液を得る方法としては、公知のいかなる手法を用いてもよいが、高濃度の臭化リチウム水溶液にシルクフィブロインを溶解後、透析により脱塩し、シルクフィブロイン水溶液を得る方法が好適に挙げられる。また、水溶液中のシルクフィブロインの濃度調整の方法としては、風乾による濃縮を経る手法が簡便で好ましい。
シルクフィブロイン多孔質体は、その製造方法は問わないが、例えば、シルクフィブロイン水溶液を急速冷凍したのち結晶化溶媒に浸漬し、融解と結晶化を同時進行することによって得る方法（特許文献１）、シルクフィブロイン水溶液を冷凍した後に長時間凍結状態を維持することで多孔質体を作製する手法（特許文献２）、シルクフィブロイン水溶液に対して少量の水溶性液状有機物質を添加した後に、一定時間冷凍して融解することによって多孔質体を得る手法（特許文献３）が挙げられる。Hereinafter, a silk fibroin preferable as a fibroin will be described as an example. The silk fibroin porous material can be obtained from a silk fibroin solution, but when dissolved in water, silk fibroin has poor solubility in water and is difficult to dissolve directly in water. As a method for obtaining a silk fibroin aqueous solution, any known method may be used, but a method in which silk fibroin is dissolved in a high concentration lithium bromide aqueous solution and desalted by dialysis to obtain a silk fibroin aqueous solution is preferable. It is done. Further, as a method for adjusting the concentration of silk fibroin in an aqueous solution, a method through concentration by air drying is simple and preferable.
The method for producing the silk fibroin porous material is not limited, but, for example, a method of obtaining a silk fibroin aqueous solution by rapidly freezing a silk fibroin aqueous solution and then immersing it in a crystallization solvent and simultaneously proceeding with melting and crystallization (Patent Document 1), A method for producing a porous material by freezing a silk fibroin aqueous solution for a long time (Patent Document 2), and adding a small amount of a water-soluble liquid organic substance to a silk fibroin aqueous solution, and then freezing for a certain time. And a technique for obtaining a porous body by melting the composition (Patent Document 3).
また、シルクフィブロイン多孔質体は、シルクフィブロイン水溶液に特定の添加剤を加えて、該水溶液を凍結させ、次いで融解させることにより製造することが好ましい。
シルクフィブロイン多孔質体の製造において、シルクフィブロインの濃度は、シルクフィブロイン溶液中で１０〜４００ｇ／Ｌであることが好ましく、１５〜２００ｇ／Ｌであることがより好ましく、２０〜１２０ｇ／Ｌであることがさらに好ましい。この範囲内に設定することで、十分な強度を持ったシルクフィブロイン多孔質体を効率的に製造することができる。The silk fibroin porous material is preferably produced by adding a specific additive to a silk fibroin aqueous solution, freezing the aqueous solution, and then thawing it.
In the production of the silk fibroin porous body, the concentration of silk fibroin is preferably 10 to 400 g / L, more preferably 15 to 200 g / L, and more preferably 20 to 120 g / L in the silk fibroin solution. More preferably. By setting within this range, a silk fibroin porous body having sufficient strength can be efficiently produced.
前記添加剤としては、カルボン酸類、アミノ酸、及び水溶性液状有機物質等が好ましく挙げられる。また、シルクフィブロイン多孔質体の製造において用いられるカルボン酸類としては、ｐＫａが、５．０以下のものが好ましく、３．０〜５．０のものがより好ましく、３．５〜５．０のものがさらに好ましい。 Preferred examples of the additive include carboxylic acids, amino acids, and water-soluble liquid organic substances. Moreover, as carboxylic acid used in manufacture of a silk fibroin porous body, pKa is preferably 5.0 or less, more preferably 3.0 to 5.0, and 3.5 to 5.0. More preferred.
カルボン酸類としては、少なくとも分子中に一つのカルボキシ基を有する有機酸であれば特に制限はないが、例えば、モノカルボン酸、ジカルボン酸、トリカルボン酸等が挙げられる。カルボン酸類としては、カルボン酸類が好ましく、炭素数１〜６の脂肪族カルボン酸がより好ましく、炭素数２〜５の脂肪族カルボン酸がさらに好ましい。これらの脂肪族カルボン酸は飽和であってもよく、不飽和であってもよい。このようなカルボン酸として、具体的には、例えば、蟻酸、酢酸、プロピオン酸、酪酸、乳酸、アクリル酸、２−ブテン酸等のモノカルボン酸；シュウ酸、マロン酸、コハク酸、マレイン酸等のジカルボン酸などが好ましく挙げられる。これらは単独で、又は複数種を組み合わせて用いることができる。人体への安全性を考慮すると、酢酸、乳酸及びコハク酸がより好ましい。 The carboxylic acids are not particularly limited as long as they are organic acids having at least one carboxy group in the molecule, and examples thereof include monocarboxylic acids, dicarboxylic acids, and tricarboxylic acids. As carboxylic acids, carboxylic acids are preferable, aliphatic carboxylic acids having 1 to 6 carbon atoms are more preferable, and aliphatic carboxylic acids having 2 to 5 carbon atoms are more preferable. These aliphatic carboxylic acids may be saturated or unsaturated. Specific examples of such carboxylic acids include monocarboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, lactic acid, acrylic acid, and 2-butenoic acid; oxalic acid, malonic acid, succinic acid, maleic acid, and the like. Of these, dicarboxylic acids are preferred. These can be used alone or in combination of two or more. In view of safety to the human body, acetic acid, lactic acid and succinic acid are more preferable.
前記アミノ酸としては、特に制限はなく、例えば、バリン、ロイシン、イソロイシン、グリシン、アラニン、セリン、スレオニン、メチオニン等のモノアミノカルボン酸、アスパラギン酸、グルタミン酸等のモノアミノジカルボン酸（酸性アミノ酸）などの脂肪族アミノ酸；フェニルアラニン等の芳香族アミノ酸；ヒドロキシプロリン等の複素環を有するアミノ酸などが好ましく挙げられ、中でも形状の調整が容易な観点から酸性アミノ酸、及びヒドロキシプロリン、セリン、スレオニン等のオキシアミノ酸が好ましい。同様な観点で、酸性アミノ酸の中でもモノアミノカルボン酸がより好ましく、アスパラギン酸及びグルタミン酸が特に好ましく、オキシアミノ酸の中でもヒドロキシプロリンがより好ましい。これらのアミノ酸は、いずれか１種を単独で、あるいは２種以上組み合わせて使用することができる。
なお、アミノ酸には、Ｌ型とＤ型の光学異性体があるが、Ｌ型とＤ型を用いた場合に、得られる多孔質体に違いが見られないため、どちらのアミノ酸を用いてもよい。The amino acid is not particularly limited, and examples thereof include monoaminocarboxylic acids such as valine, leucine, isoleucine, glycine, alanine, serine, threonine, and methionine, and monoaminodicarboxylic acids (acidic amino acids) such as aspartic acid and glutamic acid. Preferred examples include aliphatic amino acids; aromatic amino acids such as phenylalanine; amino acids having a heterocyclic ring such as hydroxyproline, among which acidic amino acids and oxyamino acids such as hydroxyproline, serine, and threonine are preferred from the viewpoint of easy shape adjustment. preferable. From the same viewpoint, monoaminocarboxylic acid is more preferable among acidic amino acids, aspartic acid and glutamic acid are particularly preferable, and hydroxyproline is more preferable among oxyamino acids. These amino acids can be used alone or in combination of two or more.
Amino acids include L-type and D-type optical isomers, but when L-type and D-type are used, there is no difference in the resulting porous material. Good.
前記水溶性液状有機物質は、常温（２０℃）で液状であり、常温（２０℃）で水と混合した際に、分離せずに溶解、又は混和するものをいう。水溶性液状有機物質としては、例えば、メタノール、エタノール、イソプロパノール、ブタノール等のアルコール類；グリセリン、プロピレングリコール等の多価アルコール類；ジメチルスルホキシド（ＤＭＳＯ）、ジメチルホルムアミド（ＤＭＦ）、ピリジン、アセトン、アセトニトリルなどが好ましく挙げられる。これらは単独で、又は複数種を組み合わせて用いることができる。人体への安全性を考慮すると、エタノール、ジメチルスルホキシド、グリセリン及びアセトンが好ましく、エタノール及びグリセリンがより好ましい。 The water-soluble liquid organic substance is liquid at room temperature (20 ° C.) and is dissolved or mixed without separation when mixed with water at room temperature (20 ° C.). Examples of water-soluble liquid organic substances include alcohols such as methanol, ethanol, isopropanol, and butanol; polyhydric alcohols such as glycerin and propylene glycol; dimethyl sulfoxide (DMSO), dimethylformamide (DMF), pyridine, acetone, and acetonitrile. Etc. are preferred. These can be used alone or in combination of two or more. In consideration of safety to the human body, ethanol, dimethyl sulfoxide, glycerin and acetone are preferable, and ethanol and glycerin are more preferable.
シルクフィブロイン水溶液に添加剤を用いる場合の添加剤の含有量は、０．１〜１８体積％であることが好ましく、０．１〜５．０体積％であることがより好ましく、０．５〜４．０体積％であることがさらに好ましい。この範囲内に設定することで、十分な強度を持った多孔質体を製造することができる。
また、アミノ酸の含有量は、シルクフィブロインに対して、１〜５００質量％であることが好ましく、５〜５０質量％であることがより好ましく、１０〜３０質量％であることがさらに好ましい。When the additive is used in the silk fibroin aqueous solution, the content of the additive is preferably 0.1 to 18% by volume, more preferably 0.1 to 5.0% by volume, More preferably, it is 4.0 volume%. By setting within this range, a porous body having sufficient strength can be produced.
Moreover, it is preferable that content of an amino acid is 1-500 mass% with respect to silk fibroin, It is more preferable that it is 5-50 mass%, It is further more preferable that it is 10-30 mass%.
シルクフィブロイン水溶液の凍結は、シルクフィブロイン水溶液に添加剤を加えた溶液を容器に流し込み、該容器を液冷式の低温恒温槽中に入れることで行うことが好ましい。
凍結温度としては、添加剤を加えたシルクフィブロイン水溶液が凍結する温度であれば特に制限はないが、−５〜−４０℃程度が好ましく、−１０〜−３０℃程度がより好ましく、−１５〜−２５℃がさらに好ましい。凍結時間としては、添加剤を加えたシルクフィブロイン水溶液が十分に凍結し、かつ凍結状態を一定時間保持できるよう、２時間以上であることが好ましく、４時間以上であることがさらに好ましい。また、特に−１５〜−２５℃の温度条件下、１時間から１００時間保持して凍結することが好ましい。The freezing of the silk fibroin aqueous solution is preferably performed by pouring a solution obtained by adding an additive to the silk fibroin aqueous solution into a container and placing the container in a liquid-cooled low-temperature thermostat.
The freezing temperature is not particularly limited as long as the silk fibroin aqueous solution added with the additive is frozen, but is preferably about −5 to −40 ° C., more preferably about −10 to −30 ° C., and −15 to -25 ° C is more preferable. The freezing time is preferably 2 hours or longer, and more preferably 4 hours or longer so that the silk fibroin aqueous solution to which the additive is added can be sufficiently frozen and kept frozen. In particular, it is preferable to freeze by holding for 1 to 100 hours under a temperature condition of -15 to -25 ° C.
ここで、添加剤を加えたシルクフィブロイン水溶液を一気に凍結温度まで下げて凍結してもよいが、凍結の前に過冷却状態を経ることが、均一な構造のシルクフィブロイン多孔質体を得る上で好ましい。例えば、添加剤を加えたシルクフィブロイン水溶液を一旦、−５℃程度で２時間程度保持して、その後、凍結温度まで下げて凍結することで、均一な構造のシルクフィブロイン多孔質体を得ることができる。−５℃から凍結温度までにかける時間を調整することで、多孔質体の構造、強度をある程度制御することが可能である。 Here, the silk fibroin aqueous solution to which the additive has been added may be frozen at once to the freezing temperature. However, it is necessary to pass a supercooled state before freezing to obtain a silk fibroin porous body having a uniform structure. preferable. For example, a silk fibroin porous material having a uniform structure can be obtained by temporarily holding a silk fibroin aqueous solution to which an additive has been added at about −5 ° C. for about 2 hours and then freezing it to a freezing temperature. it can. The structure and strength of the porous body can be controlled to some extent by adjusting the time taken from −5 ° C. to the freezing temperature.
上記の手法でシルクフィブロイン水溶液を凍結させた後、次いで凍結した水分を融解することによって、シルクフィブロイン多孔質体が得られる。融解の方法としては、特に制限はなく、自然融解、恒温槽等での保管などの方法が好ましく挙げられる。 After the silk fibroin aqueous solution is frozen by the above method, the frozen water is then thawed to obtain a silk fibroin porous material. There is no restriction | limiting in particular as a melting method, Methods, such as natural melting and storage in a thermostat, etc. are mentioned preferably.
このようにして得られたシルクフィブロイン多孔質体には添加剤が含まれており、用途に応じて添加剤を除去する必要がある場合には、適当な方法でシルクフィブロイン多孔質体から添加剤を除去して用いることができる。例えば、シルクフィブロイン多孔質体を、純水中に浸漬して、添加剤を除去することが最も簡便な方法として挙げられる。 The silk fibroin porous material thus obtained contains an additive, and when it is necessary to remove the additive depending on the application, the additive is removed from the silk fibroin porous material by an appropriate method. Can be used. For example, the simplest method is to remove the additive by immersing the silk fibroin porous material in pure water.
シルクフィブロイン多孔質体は、スポンジ状の多孔質構造を有しており、通常このシルクフィブロイン多孔質体には凍結乾燥等により水除去を行わなければ水が含まれ、含水状態で柔らかい構造物である。また、シルクフィブロイン多孔質体を凍結乾燥することにより、シルクフィブロイン多孔質体の乾燥品を得ることができる。凍結乾燥は、水分を完全に昇華させずに乾燥を終えると、残った水分の表面張力の影響で空孔が潰れてしまうため、水分が完全に昇華するまで乾燥することが好ましい。例えば、温度条件として−５〜−８０℃程度であることが好ましい。 The silk fibroin porous body has a sponge-like porous structure. Normally, this silk fibroin porous body contains water unless it is removed by freeze-drying or the like. is there. In addition, a dried silk fibroin porous material can be obtained by freeze-drying the silk fibroin porous material. In freeze-drying, when the drying is completed without completely sublimating the water, the pores are crushed due to the effect of the surface tension of the remaining water. Therefore, it is preferable to dry until the water is completely sublimated. For example, the temperature condition is preferably about −5 to −80 ° C.
このシルクフィブロイン多孔質体は、シルクフィブロイン多孔質体作製時の容器を適宜選択することにより、フィルム状、シート状、ブロック状、管状、球状等、目的に応じた形状とすることができる。
容器としては、シルクフィブロイン溶液が流出しない形状及び形態のものであれば制限はなく、その素材としては、鉄、ステンレス、アルミニウム、金、銀、銅等の熱伝導率が高い素材を用いることが、凍結に要する工程時間を短縮できる観点から好ましい。また、型及び容器の壁の厚さは、その機能と凍結の際の膨張等による変形等を防止する観点から、０．５ｍｍ以上であることが好ましく、取り扱いが容易で、冷却効率的な観点から、より好ましくは１〜３ｍｍである。The silk fibroin porous material can be formed into a shape suitable for the purpose, such as a film shape, a sheet shape, a block shape, a tubular shape, a spherical shape, etc., by appropriately selecting a container for producing the silk fibroin porous material.
The container is not limited as long as the silk fibroin solution has a shape and shape that does not flow out, and as the material, a material having high thermal conductivity such as iron, stainless steel, aluminum, gold, silver, copper, or the like is used. From the viewpoint of reducing the process time required for freezing. In addition, the thickness of the mold and the wall of the container is preferably 0.5 mm or more from the viewpoint of its function and deformation due to expansion during freezing, etc., and is easy to handle and efficient in cooling. More preferably, the thickness is 1 to 3 mm.
ここで用いられる型及び容器は、シルクフィブロイン多孔質体の固着の予防を目的として、その内側のシルクフィブロイン溶液と接する内壁面に、離型層を設けることができる。
離型層としては、ポリテトラフルオロエチレン（ＰＴＦＥ）、テトラフルオロエチレン−ヘキサフルオロプロピレン共重合体（ＦＥＰ）、テトラフルオロエチレン−パーフルオロアルキルビニルエーテル共重合体（ＰＦＡ）等のフッ素樹脂からなるシート、ポリエチレンテレフタレート（ＰＥＴ）、ポリプロピレン（ＰＰ）等からなる離型処理されたシート、また、上記フッ素樹脂からなるコーティング層などが好ましく挙げられる。これらの離型層を用いた場合、シルクフィブロイン多孔質体の表面には細孔が少なく平滑なフィルム層が形成される。また、フィルム層を設けたくない場合は、ろ紙等といった表面が粗いシートを用いることで、フィルム層の大部分を剥離させることができる。離型層の採用については、例えば、化粧品及びエステ分野の用途において、揮発しやすい化粧成分を含有させて用いる場合で、該化粧成分の揮発を抑えてより長時間の化粧成分の効果を得ようとする場合は、フィルム層を有することが好ましいので、採用することが好ましい。このように、離型層は、フィルム層の要否に応じて、適宜選択すればよい。
また、離型層の厚さは、１０００μｍ以下であることが好ましく、５００μｍ以下であることがより好ましく、２００μｍ以下であることがさらに好ましい。離型層の厚さが上記範囲内であると、熱伝導を阻害しにくいため、凍結に要する工程時間を短縮することができる。The mold and container used here can be provided with a release layer on the inner wall surface in contact with the silk fibroin solution inside for the purpose of preventing the silk fibroin porous body from sticking.
As the release layer, a sheet made of a fluororesin such as polytetrafluoroethylene (PTFE), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA), Preferable examples include a release-treated sheet made of polyethylene terephthalate (PET), polypropylene (PP), and the like, and a coating layer made of the fluororesin. When these release layers are used, a smooth film layer with few pores is formed on the surface of the silk fibroin porous body. When it is not desired to provide a film layer, most of the film layer can be peeled off by using a sheet having a rough surface such as filter paper. Regarding the use of the release layer, for example, in the cosmetics and aesthetics applications, in the case of using a cosmetic component that is volatile, the volatilization of the cosmetic component will be suppressed, and a longer-lasting cosmetic component effect will be obtained. In this case, it is preferable to employ a film layer because it preferably has a film layer. Thus, what is necessary is just to select a mold release layer suitably according to the necessity of a film layer.
Further, the thickness of the release layer is preferably 1000 μm or less, more preferably 500 μm or less, and further preferably 200 μm or less. When the thickness of the release layer is within the above range, it is difficult to inhibit heat conduction, and therefore the process time required for freezing can be shortened.
このシルクフィブロイン多孔質体は、上記した融解する工程に次いで、切削加工、切断加工を施してもよい。シルクフィブロイン多孔質体をシート形状とする場合において、多孔質層のみからなる多孔質体とする場合には、容器の材質を選択するほかに、フィルム層を切除することで、表面構造を選択することができる。具体的には、例えば、テフロン（登録商標）シート等の離型層をその内壁面に設けたブロック状の型あるいは容器を用い、該型あるいは容器から取り出してから、側面の四面のフィルム層を取り除き、多孔質層の部分を切削あるいは切除する等して、多孔質層のみからなる多孔質体を得ることができる。また、一面のみにテフロン（登録商標）シート等の離型層をその内壁面に設け、その他の面の内壁面にろ紙を設けた型あるいは容器を用い、一面のみにフィルム層を有する多孔質体を得ることもできる。 This silk fibroin porous body may be subjected to a cutting process and a cutting process after the melting step described above. When making a silk fibroin porous body into a sheet shape, when making a porous body consisting only of a porous layer, in addition to selecting the material of the container, the surface structure is selected by cutting the film layer be able to. Specifically, for example, a block-shaped mold or container in which a release layer such as a Teflon (registered trademark) sheet is provided on the inner wall surface is taken out from the mold or container, and then the four side film layers are formed. The porous body which consists only of a porous layer can be obtained by removing and cutting or excising the part of a porous layer. Also, a porous body having a film layer only on one side using a mold or a container provided with a release layer such as a Teflon (registered trademark) sheet on the inner wall only on one side and a filter paper on the inner wall on the other side You can also get
シルクフィブロイン多孔質体に水酸基含有化合物を含有させる方法は特に限定されず、シルクフィブロイン多孔質体を製造する際に、シルクフィブロイン溶液に配合する方法、シルクフィブロイン多孔質体の作製後に、その全体が浸る程度の水酸基含有化合物を含む溶液に浸漬させる方法であってもよい。 The method of incorporating the hydroxyl group-containing compound into the silk fibroin porous body is not particularly limited. When producing the silk fibroin porous body, the method of blending it into the silk fibroin solution, after the production of the silk fibroin porous body, It may be a method of dipping in a solution containing a hydroxyl group-containing compound to the extent of dipping.
水酸基含有化合物を含む溶液中の、水酸基含有化合物の含有量は特に制限はなく、例えば０．５〜２０体積％であることが好ましく、１〜１０体積％であることがより好ましい。含有量が上記範囲内であると、シルクフィブロイン多孔質体中に水酸基含有化合物が十分に導入され、乾燥に適した水酸基含有化合物を含んだフィブロイン多孔質体が得られる。 There is no restriction | limiting in particular in content of the hydroxyl-containing compound in the solution containing a hydroxyl-containing compound, For example, it is preferable that it is 0.5-20 volume%, and it is more preferable that it is 1-10 volume%. When the content is within the above range, the hydroxyl group-containing compound is sufficiently introduced into the silk fibroin porous body, and a fibroin porous body containing a hydroxyl group-containing compound suitable for drying is obtained.
浸漬時間も特に制限はないが、シルクフィブロイン多孔質体内の水酸基含有化合物の濃度が均一になる時間であればよく、例えば、１〜４８時間であることが好ましく、１２〜３６時間であることがより好ましい。浸漬時間が上記範囲内であると、シルクフィブロイン多孔質体中に水酸基含有化合物が十分に導入され、またシルクフィブロイン多孔質体内における濃度のばらつきが生じることがなく、均一に水酸基含有化合物が含まれた、均質な多孔質材料が得られる。 The immersion time is not particularly limited as long as the concentration of the hydroxyl group-containing compound in the silk fibroin porous body is uniform. For example, it is preferably 1 to 48 hours, and preferably 12 to 36 hours. More preferred. When the immersion time is within the above range, the hydroxyl-containing compound is sufficiently introduced into the silk fibroin porous material, and there is no variation in concentration in the silk fibroin porous material, and the hydroxyl-containing compound is uniformly contained. In addition, a homogeneous porous material can be obtained.
このようにして得られる本発明の多孔質材料において、水酸基含有化合物は、該多孔質材料を構成するシルクフィブロイン多孔質体の細孔内、及び該多孔質体自体を構成するように多孔質体の構造内に存在することで、可塑効果、保湿効果及び吸水性が発現する。このような構成であることから、本発明の多孔質材料は、乾燥状態でも柔らかく及び乾燥後の外観及びスライス加工性に優れるものになっていると考えられる。 In the porous material of the present invention thus obtained, the hydroxyl group-containing compound is contained in the pores of the silk fibroin porous body constituting the porous material and the porous body so as to constitute the porous body itself. By existing in the structure, a plasticizing effect, a moisturizing effect and a water absorbing property are exhibited. Since it is such a structure, it is thought that the porous material of the present invention is soft even in a dry state and excellent in appearance and slicing workability after drying.
〔多孔質シート〕
本発明に係る多孔質シートは、上記多孔質材料からなり、その膜厚は、０．１〜５０ｍｍであり、０．２〜１０ｍｍであることが好ましく、０．５〜５ｍｍであることがより好ましい。
多孔質シートは、上記多孔質材料をスライスすることで容易に製造することができる。[Porous sheet]
The porous sheet which concerns on this invention consists of the said porous material, The film thickness is 0.1-50 mm, It is preferable that it is 0.2-10 mm, It is more preferable that it is 0.5-5 mm. preferable.
The porous sheet can be easily produced by slicing the porous material.
〔創傷被覆材〕
本発明の創傷被覆材は、上記の本発明の多孔質材料、又は多孔質シートを用いたものである。本発明の多孔質材料、多孔質シートは、乾燥状態でも柔らかく、乾燥後の外観及びスライス加工性に優れ、かつ吸水性、弾力性及び追随性にも優れている。そのため、本発明の創傷被覆材は、創傷部に貼付することによる痛みの緩和し、また該創傷部をぶつけた際の痛みを軽減するという特性、傷口等から滲み出してくる滲出液を吸収して創傷部に保持し、該滲出液に含まれる成分を積極的に活用し得る特性、腕、膝及び肘といった湾曲部位及び稼動部に用い得る特性に優れており、湿潤療法にも好適に用いることができ、また、加工性に優れ、所望のサイズに切り分けて使用することができるので、利便性にも優れたものとなる。[Wound dressing]
The wound dressing of the present invention uses the above porous material or porous sheet of the present invention. The porous material and porous sheet of the present invention are soft even in a dry state, excellent in appearance after drying and slicing workability, and excellent in water absorption, elasticity, and followability. Therefore, the wound dressing of the present invention absorbs exudate that exudes from the wound, etc., the characteristics of relieving pain caused by applying to the wound part, and reducing pain when hitting the wound part. It is excellent in the characteristics that can be held in the wound part and can be used positively for the components contained in the exudate, the curved part such as the arm, knee and elbow, and the working part, and is also suitable for wet therapy In addition, it is excellent in workability and can be used after being cut into a desired size, so that it is excellent in convenience.
本発明の創傷被覆材は、吸水性に優れた特性をいかし、薬剤を含ませることができる。薬剤を含ませることにより、本発明の創傷被覆材に創傷の治癒を促進する機能を付与することができる。薬剤を含ませる場合、例えば、殺菌剤、抗生物質、生理活性物質等の薬剤を、本発明の創傷被覆材に含浸もしくは塗布すればよい。これらの薬剤は１種または２種以上を組み合わせて使用することができる。 The wound dressing of the present invention can contain a drug by taking advantage of its excellent water absorption characteristics. By including a drug, the wound dressing of the present invention can be given a function of promoting wound healing. When the drug is included, for example, the wound dressing of the present invention may be impregnated or applied with a drug such as a bactericidal agent, an antibiotic or a physiologically active substance. These drugs can be used alone or in combination of two or more.
本発明の創傷被覆材は、多孔質材料、又は多孔質シートを、ドレッシングフィルム、包帯、粘着テープ等で固定する形態で用いることができる。
本発明の創傷被覆材は、乾燥状態でも柔らかいため、グリセリン、ポリビニルピロリドン、ポリビニルアルコール、ポリエチレングリコール等の保湿剤を含ませて用いることもできるが、そのまま用いることもできる。なお、保湿剤を含ませた状態の場合には、使用直前まで、水分量を保った状態で、乾燥を防ぐように、本発明の創傷被覆材を密閉状態にしておくことが好ましい。The wound dressing of the present invention can be used in a form in which a porous material or a porous sheet is fixed with a dressing film, a bandage, an adhesive tape or the like.
Since the wound dressing of the present invention is soft even in a dry state, it can be used by adding a humectant such as glycerin, polyvinyl pyrrolidone, polyvinyl alcohol, and polyethylene glycol, but can also be used as it is. In the case where a moisturizing agent is included, it is preferable to keep the wound dressing of the present invention in a hermetically sealed state so as to prevent drying in a state where the amount of moisture is maintained until just before use.
以下に、本発明を実施例によりさらに具体的に説明するが、本発明は、これらの実施例によってなんら限定されるものではない。 EXAMPLES The present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.
実施例１
（シルクフィブロイン溶液の調製）
シルクフィブロイン水溶液は、シルクフィブロイン粉末（「シルクパウダーＩＭ（商品名）」、ＫＢセーレン（株）製）を９Ｍ臭化リチウム水溶液に溶解し、遠心分離で不溶物を除去したのち、超純水に対して透析を繰り返すことによって得た。得られたシルクフィブロイン水溶液を透析チューブ中で風乾し濃縮した。この濃縮液に添加剤として酢酸を添加し、シルクフィブロイン濃度が３０ｇ／Ｌ、酢酸濃度が２体積％であるシルクフィブロイン溶液を調製した。Example 1
(Preparation of silk fibroin solution)
Silk fibroin aqueous solution is prepared by dissolving silk fibroin powder (“Silk Powder IM (trade name)”, KB Selen Co., Ltd.) in 9M lithium bromide aqueous solution, removing insoluble matter by centrifugation, and then adding ultrapure water. It was obtained by repeating dialysis against. The obtained silk fibroin aqueous solution was air-dried in a dialysis tube and concentrated. Acetic acid was added as an additive to the concentrated solution to prepare a silk fibroin solution having a silk fibroin concentration of 30 g / L and an acetic acid concentration of 2% by volume.
（シルクフィブロイン多孔質体の製造）
このシルクフィブロイン溶液をアルミ板で作製した型（内側サイズ；４００ｍｍ×３００ｍｍ×２０ｍｍ、６０ｍｍ×３０ｍｍ×１０ｍｍ、１００ｍｍ×１０ｍｍ×１０ｍｍ）に流し込み、予め−５℃に冷却しておいた液冷式低温恒温槽（（株）前川製作所製）に入れて−５℃で２時間静置した。冷媒としては、「ナイブラインＺ１（商品名）」（丸善石油化学（株）製）を用いた。
その後、−３℃／時間の速度で−２０℃まで冷却し、そのままの温度で５時間保持して凍結した。凍結した試料を自然解凍で室温に戻してから、型から取り出し、超純水に浸漬し、超純水を１日２回、３日間交換することによって、使用した酢酸を除去した。その後、凍結乾燥機（「ＦＤ−５５０Ｐ（型番）」、東京理化機械（株）製）を用いて３日間凍結乾燥し、内径６０ｍｍ×３０ｍｍ×１０ｍｍの型で作製したシルクフィブロイン多孔質体の乾燥質量を測定した。(Manufacture of silk fibroin porous material)
The silk fibroin solution was poured into a mold (inside size: 400 mm × 300 mm × 20 mm, 60 mm × 30 mm × 10 mm, 100 mm × 10 mm × 10 mm) made of an aluminum plate, and cooled at −5 ° C. in advance. It put into the thermostat (made by Maekawa Seisakusho) and left still at -5 degreeC for 2 hours. As the refrigerant, “Nibline Z1 (trade name)” (manufactured by Maruzen Petrochemical Co., Ltd.) was used.
Then, it cooled to -20 degreeC with the speed | rate of -3 degreeC / hour, and hold | maintained at the same temperature for 5 hours, and frozen. The frozen sample was returned to room temperature by natural thawing, then removed from the mold, immersed in ultrapure water, and the acetic acid used was removed by exchanging the ultrapure water twice a day for 3 days. Thereafter, the silk fibroin porous material was freeze-dried for 3 days using a freeze dryer (“FD-550P (model number)”, manufactured by Tokyo Rika Machinery Co., Ltd.) and dried with a mold having an inner diameter of 60 mm × 30 mm × 10 mm. The mass was measured.
（水酸基含有化合物の導入）
上記のようにして作製したシルクフィブロイン多孔質体の全体が浸る程度の５体積％グリセリン水溶液を用意し、２４時間静置した状態で浸漬させ、その後これを凍結乾燥して多孔質材料を得た。また、この凍結乾燥後の多孔質材料の乾燥質量を測定した。
多孔質材料中の水酸基含有化合物の含有量（質量％）は、多孔質材料に導入された水酸基含有化合物の質量を、水酸基含有化合物が導入された後の多孔質材料の乾燥質量で割ったものとし、以下の式で算出した。
（多孔質材料中の水酸基含有化合物の含有量（質量％））＝（（水酸基化合物導入後の多孔質材料の乾燥質量）−（水酸基含有化合物の未導入のシルクフィブロイン多孔質体の乾燥質量））／（水酸基含有化合物の導入後のシルクフィブロイン多孔質体の乾燥質量）×１００(Introduction of hydroxyl-containing compound)
A 5% by volume glycerin aqueous solution was prepared so that the entire silk fibroin porous material produced as described above was immersed, and was immersed for 24 hours, and then lyophilized to obtain a porous material. . Further, the dry mass of the porous material after lyophilization was measured.
The content (% by mass) of the hydroxyl group-containing compound in the porous material is obtained by dividing the mass of the hydroxyl group-containing compound introduced into the porous material by the dry mass of the porous material after the hydroxyl group-containing compound is introduced. And calculated by the following formula.
(Content of hydroxyl group-containing compound in porous material (% by mass)) = ((Dry mass of porous material after introduction of hydroxyl compound) − (Dry mass of silk fibroin porous material into which hydroxyl group-containing compound has not been introduced) ) / (Dry mass of silk fibroin porous material after introduction of hydroxyl group-containing compound) × 100
上述のようにして得た多孔質材料について、以下に示すようにして乾燥後の外観とスライス加工性とを評価した。評価結果を第１表に示す。
（乾燥後の外観）
乾燥後の多孔質材料の外観を観察し、目視で認識できる程度（幅０．３ｍｍ以上、長さ２ｍｍ以上）のクラックの有無と外観の状態を評価した。クラックの数が１つでもあれば「Ｃ」とし、クラックはないが多孔質材料に析出物等の外観異常がある場合は「Ｂ」とし、クラックも外観異常もないものは「Ａ」と判定した。
（スライス加工性）
乾燥後の多孔質材料を、スライス装置（（有）北島マシンナイフ製）を用いてスライス後の厚みが１ｍｍ程度になるようにスライスした。スライス時にシート、あるいは多孔質体が割れたものを「Ｂ」とし、割れがないものを「Ａ」と判定した。
（巻きつき性）
乾燥後の多孔質材料を、スライス装置（（有）北島マシンナイフ製）を用いてスライス後の厚みが１ｍｍ程度になるようにスライスした。３回スライスを行いスライス時にシートがロールに３回とも巻きついたものを「Ｃ」とし、１回又は２回巻きついたものを「Ｂ」、１回も巻きつかなかったものを「Ａ」と判定した。About the porous material obtained by making it above, the external appearance after drying and slicing workability were evaluated as shown below. The evaluation results are shown in Table 1.
(Appearance after drying)
The appearance of the porous material after drying was observed, and the presence or absence of cracks and the state of appearance to the extent that they could be recognized visually (width 0.3 mm or more, length 2 mm or more) were evaluated. If there is even one crack, it is “C”. If there is no crack but the porous material has an appearance abnormality such as precipitates, it is “B”. did.
(Slicing workability)
The porous material after drying was sliced using a slicing device (manufactured by Kitajima Machine Knife) so that the thickness after slicing was about 1 mm. When the sheet or the porous body was cracked at the time of slicing, it was determined as “B”, and when there was no crack, it was determined as “A”.
(Winding property)
The porous material after drying was sliced using a slicing device (manufactured by Kitajima Machine Knife) so that the thickness after slicing was about 1 mm. “C” means that the sheet is wound three times around the roll at the time of slicing, and “B” means that the sheet is wound once or twice, and “A” means that the sheet has not been wound once. It was determined.
実施例２〜２７及び比較例１〜６
実施例１において、水酸基含有化合物の種類、多孔質材料中の水酸基含有化合物の含有量を、第１表〜第４表に記載のものにかえた以外は、実施例１と同様にして多孔質材料を得た。また、乾燥後の外観、スライス加工性及び巻きつき性の評価結果も第１表〜第４表に示す。Examples 2-27 and Comparative Examples 1-6
In Example 1, the porous material was the same as in Example 1 except that the type of the hydroxyl group-containing compound and the content of the hydroxyl group-containing compound in the porous material were changed to those shown in Tables 1 to 4. Obtained material. Tables 1 to 4 also show evaluation results of the appearance after drying, slicing workability, and winding property.
実施例１〜２７の結果より、シルクフィブロイン多孔質体が分子量１，０００以下の水酸基含有化合物を含んでなる本発明の多孔質材料は、乾燥後の外観及びスライス加工性に優れていることが確認された。一方、比較例１〜７の結果より、水酸基を含まない化合物、水酸基を含むものの分子量が１，０００より高い化合物を含んでなる材料は、乾燥後にクラックが発生したり、外観の異常、スライス加工時に割れが生じることが確認された。 From the results of Examples 1 to 27, the porous material of the present invention, in which the silk fibroin porous material contains a hydroxyl group-containing compound having a molecular weight of 1,000 or less, is excellent in appearance after drying and slice processability. confirmed. On the other hand, from the results of Comparative Examples 1 to 7, a compound containing no hydroxyl group, a material comprising a hydroxyl group-containing compound having a molecular weight higher than 1,000 is cracked after drying, or has an abnormal appearance or slice processing. It was confirmed that cracking sometimes occurred.
実施例２８〜３５、並びに比較例７及び８
実施例１において、シルクフィブロイン水溶液の原料をシルクフィブロイン粉末から精練済み切繭（ながすな繭（株）製）とし、シルクフィブロイン水溶液をシルクフィブロインの濃度が４０ｇ／Ｌのものとし、水酸基含有化合物溶液中の該化合物の濃度を第５表に記載のものとし、アルミ板で作製した型のサイズを内径４００ｍｍ×３００ｍｍ×２０ｍｍのものにかえた以外は、実施例１と同様にして多孔質材料を得た。また、乾燥後の外観、スライス加工性及び巻きつき性の評価結果も第５表に示す。Examples 28-35 and Comparative Examples 7 and 8
In Example 1, the raw material of the silk fibroin aqueous solution was made from silk fibroin powder scoured slag (manufactured by Nagasuna Coffee Co., Ltd.), the silk fibroin aqueous solution had a silk fibroin concentration of 40 g / L, and the hydroxyl group-containing compound solution The porous material was prepared in the same manner as in Example 1 except that the concentration of the compound in the inside was changed to that shown in Table 5, and the size of the mold made of an aluminum plate was changed to that having an inner diameter of 400 mm × 300 mm × 20 mm. Obtained. Table 5 also shows the results of evaluation of the appearance after drying, slicing workability, and winding property.
＊１，ＧＬｙ：グリセリン
ＰＥＧ：ポリエチレングリコール
ＰＧＬ：ポリグリセリン
ＴＥＣ：クエン酸トリエチル
ＤＧＬ：デカグリセリンラウレート
ＳＬ：ソルビタンラウレート
ＤＭＳＯ：ジメチルスルホキシド
ＰＶＡ：ポリビニルアルコール
ＤＯＰ：フタル酸ジオクチル
ＯＩＬ：エポキシ化大豆油
＊２，ｖ：体積％、ｗ：質量％* 1, GLy: glycerin PEG: polyethylene glycol PGL: polyglycerin TEC: triethyl citrate DGL: decaglycerin laurate SL: sorbitan laurate DMSO: dimethyl sulfoxide PVA: polyvinyl alcohol DOP: dioctyl phthalate OIL: epoxidized soybean oil * 2, v: volume%, w: mass%
また、実施例２８、３０〜３２及び比較例１で得られた多孔質材料について、下記の方法に基づいて２５％圧縮応力を測定した。実施例２８の多孔質材料の圧縮応力は８０．１ｋＰａであり、実施例３０の多孔質材料の圧縮応力は５５．１ｋＰａであり、実施例３１の多孔質材料の圧縮応力は４６．８ｋＰａであり、実施例３２の多孔質材料の圧縮応力は４３．１ｋＰａであった。一方、比較例１の多孔質材料の圧縮応力は４３７．６ｋＰａであり、実施例の多孔質材料の圧縮応力よりも１０倍近く大きく、著しく柔軟性に劣っていることが確認された。
また、図１〜図６の写真より、実施例はクラックが発生していないが、比較例のものはクラックが入っていることが確認された。Moreover, about the porous material obtained by Example 28, 30-32, and the comparative example 1, 25% compressive stress was measured based on the following method. The compressive stress of the porous material of Example 28 is 80.1 kPa, the compressive stress of the porous material of Example 30 is 55.1 kPa, and the compressive stress of the porous material of Example 31 is 46.8 kPa. The compressive stress of the porous material of Example 32 was 43.1 kPa. On the other hand, the compressive stress of the porous material of Comparative Example 1 was 437.6 kPa, which was almost 10 times larger than the compressive stress of the porous material of the example, and was confirmed to be significantly inferior in flexibility.
Moreover, although the Example did not generate | occur | produce the crack from the photograph of FIGS. 1-6, it was confirmed that the thing of a comparative example has a crack.
（２５％圧縮応力の測定）
各実施例及び比較例で得られた材料について、万能試験機（「ＥＺ−（Ｎ）Ｓ（型番）」，（株）島津製作所製）を用い、ロードセルは５０Ｎ、治具として直径８ｍｍの円形の圧縮板を用いて、圧縮速度１ｍｍ／分、室温２２℃の条件下で、材料の厚さの２５％を圧縮板で押し込んだときのロードを測定し、以下の式により算出した値を２５％圧縮応力（ｋＰａ）とした。
２５％圧縮応力（ｋＰａ）＝材料の厚さの２５％を圧縮板で押し込んだときのロード／圧縮板の面積（ｍｍ２）×１０００(Measurement of 25% compressive stress)
For the materials obtained in each Example and Comparative Example, a universal testing machine (“EZ- (N) S (model number)”, manufactured by Shimadzu Corporation) was used, the load cell was 50 N, and the jig was a circle with a diameter of 8 mm. , The load when 25% of the thickness of the material was pushed by the compression plate under the conditions of a compression speed of 1 mm / min and a room temperature of 22 ° C. was measured, and a value calculated by the following equation was 25 % Compressive stress (kPa).
25% compressive stress (kPa) = Load / compression plate area (mm 2 ) × 1000 when 25% of the thickness of the material is pressed with the compression plate
実施例３６
実施例３１において、シルクフィブロイン溶液を流し込むアルミ板で作製した型のサイズを内径；５０ｍｍ×５０ｍｍ×３ｍｍとした以外は実施例３１と同様にして多孔質材料を作製した。得られた多孔質材料を用いて被覆材を作製し、クッション性試験を行った。結果を第６表に示す。
（被覆材の作製）
フィルムドレッシング材（オプサイトジェントルロール（製品番号：６６８０１１９７）、１０ｃｍ幅、Ｓｍｉｔｈ＆Ｎｅｐｈｅｗ ＫＫ製）をハサミで８ｃｍ角に切断した。得られた８ｃｍ角のフィルムドレッシング材の離型フィルム（ライナー）を剥離し、フィルムドレッシング材本体の粘着剤塗布面を露出させて、該粘着剤塗布面の中央部に上記の多孔質材料を貼り付けて、被覆材とした。得られた被覆材について、下記のクッション性試験でクッション性を評価した。その結果を第６表に示す。Example 36
In Example 31, a porous material was produced in the same manner as in Example 31 except that the size of the mold made of the aluminum plate into which the silk fibroin solution was poured was changed to an inner diameter of 50 mm × 50 mm × 3 mm. A covering material was prepared using the obtained porous material, and a cushioning property test was performed. The results are shown in Table 6.
(Preparation of coating material)
A film dressing material (opsite gentle roll (product number: 6801197), 10 cm width, manufactured by Smith & Nephew KK) was cut into 8 cm square with scissors. The release film (liner) of the obtained 8 cm square film dressing material is peeled off, the pressure-sensitive adhesive application surface of the film dressing material main body is exposed, and the porous material is pasted on the central portion of the pressure-sensitive adhesive application surface. In addition, a coating material was obtained. About the obtained coating | covering material, the cushioning property was evaluated by the following cushioning property test. The results are shown in Table 6.
比較例９、及び１０
浸漬するグリセリン水溶液の濃度を第６表に記載の値とした以外は実施例３６と同様にして多孔質材料を作製した。得られた多孔質材料を用いて実施例３６と同様の方法で被覆材を作製した。得られた被覆材について、下記のクッション性試験でクッション性を評価した。その結果を第６表に示す。Comparative Examples 9 and 10
A porous material was produced in the same manner as in Example 36 except that the concentration of the glycerol aqueous solution to be immersed was changed to the value shown in Table 6. A coating material was produced in the same manner as in Example 36 using the obtained porous material. About the obtained coating | covering material, the cushioning property was evaluated by the following cushioning property test. The results are shown in Table 6.
（クッション性試験）
被覆材を１０人の被験者（日本人男性５名、日本人女性５名）の肘部にヒジを曲げた状態で貼付し、該被覆材で覆われた部分を机に打ちつけた際のクッション性を下記の基準で評価した。
Ａ ：クッション性が高く、特に痛みが軽減されたと判断した被験者が、８人以上であった。
Ｂ ：クッション性が高く、特に痛みが軽減されたと判断した被験者が、４〜７人であった。
Ｃ ：クッション性が高く、特に痛みが軽減されたと判断した被験者が、３人未満であった。(Cushion test)
Cushioning properties when the covering material is applied to elbows of 10 subjects (5 Japanese men and 5 Japanese women) with elbows bent and the part covered with the covering material is struck against a desk Was evaluated according to the following criteria.
A: There were 8 or more subjects who judged that the cushioning properties were high and that pain was particularly reduced.
B: There were 4 to 7 subjects who judged that the cushioning property was high and that pain was particularly reduced.
C: There were less than 3 subjects who judged that the cushioning properties were high and that pain was particularly reduced.
＊１，ＧＬｙ：グリセリン
＊２，ｖ：体積％、ｗ：質量％
* 1, GLy: glycerin * 2, v: volume%, w: mass%
実施例３６及び比較例９、１０の結果から、本発明の多孔質材料を用いた創傷被覆材はクッション性に優れるため、創傷部に貼付することでぶつけた際の痛みを軽減する効果があることが分かった。これに対して比較例９、１０の被覆材は、乾燥シルクフィブロイン多孔質体部分が硬いため、クッション性に乏しく、創傷被覆材に適していないことが分かった。 From the results of Example 36 and Comparative Examples 9 and 10, since the wound dressing material using the porous material of the present invention is excellent in cushioning properties, there is an effect of reducing pain when applied to the wound part by applying to the wound part. I understood that. On the other hand, since the dry silk fibroin porous body part was hard, the covering materials of Comparative Examples 9 and 10 were poor in cushioning properties and were not suitable for wound dressings.
実施例３７及び比較例１１
実施例３６及び比較例９において、シルクフィブロイン溶液を流し込むアルミ板で作製した型のサイズを内径；５０ｍｍ×５０ｍｍ×１．０ｍｍとし、シルクフィブロインの濃度、浸漬させたグリセリン溶液の濃度を第７表に記載の濃度とした以外は実施例３６と同様にして多孔質材料を得た。次いで実施例３６と同様の方法で被覆材を作製し、各々実施例３７及び比較例１１の被覆材を得た。得られた被覆材を用いて下記のヒト腕部への貼付試験を行い、下記の基準で追随性の評価を行った。結果を第７表に示す。Example 37 and Comparative Example 11
In Example 36 and Comparative Example 9, the size of the mold made of the aluminum plate into which the silk fibroin solution was poured was set to an inner diameter; 50 mm × 50 mm × 1.0 mm, and the concentration of the silk fibroin and the concentration of the immersed glycerin solution are shown in Table 7. A porous material was obtained in the same manner as in Example 36 except that the concentration was described in the above. Subsequently, the coating material was produced by the method similar to Example 36, and the coating material of Example 37 and the comparative example 11 was obtained, respectively. Using the obtained coating material, the following test was performed on the human arm, and the following property was evaluated according to the following criteria. The results are shown in Table 7.
（ヒト腕部への貼付試験）
被覆材を１０人の被験者（日本人男性５名、日本人女性５名）の腕部に貼付した後に、ぴったりと密着する様に上から押さえた。次いで被覆材の様子を観察し、クッション性を下記の基準で評価した。
Ａ 貼付する際に腕部に沿って割れることなく密着させることができた。
Ｂ 貼付する際に割れてしまった。(Attachment test to human arm)
After the covering material was applied to the arms of 10 subjects (5 Japanese men and 5 Japanese women), it was pressed from above so as to be closely attached. Next, the state of the covering material was observed, and the cushioning property was evaluated according to the following criteria.
A: It was possible to adhere without cracking along the arm when applying.
B When it stuck, it broke.
＊１，ＧＬｙ：グリセリン
＊２，ｖ：体積％、ｗ：質量％
* 1, GLy: glycerin * 2, v: volume%, w: mass%
実施例３８、比較例１２
実施例３６において、シルクフィブロイン溶液を流し込むアルミ板で作製した型のサイズを内径；１００ｍｍ×１００ｍｍ×３．０ｍｍとし、シルクフィブロインの濃度、浸漬させたグリセリン溶液の濃度を第８表に記載の濃度とした以外は実施例３６と同様にして多孔質材料を得た。得られた多孔質材料を用いて、下記の吸水速度試験を行い、下記の基準で吸水性の評価を行った。結果を第８表に示す。Example 38, Comparative Example 12
In Example 36, the size of the mold made of the aluminum plate into which the silk fibroin solution was poured was set to an inner diameter; 100 mm × 100 mm × 3.0 mm. The concentration of silk fibroin and the concentration of the immersed glycerin solution were those shown in Table 8. A porous material was obtained in the same manner as in Example 36 except that. Using the obtained porous material, the following water absorption rate test was conducted, and the water absorption was evaluated according to the following criteria. The results are shown in Table 8.
実施例３９
実施例３８において、シルクフィブロイン溶液を流し込むアルミ板で作製した型のサイズを内径；１００ｍｍ×１００ｍｍ×６．０ｍｍとした以外は実施例３８と同様にして多孔質材料を作製した。得られた多孔質材料をスライス装置（（有）北島マシンナイフ製）を用いて、厚みが３．０ｍｍとなるようにスライスした。得られた多孔質材料は、おおよそ１００ｍｍ×１００ｍｍ×３．０ｍｍとなった。このスライス加工を施した多孔質材料について、下記の吸水速度試験を行った。結果を第８表に示す。Example 39
In Example 38, a porous material was prepared in the same manner as in Example 38 except that the size of the mold made of the aluminum plate into which the silk fibroin solution was poured was set to an inner diameter of 100 mm × 100 mm × 6.0 mm. The obtained porous material was sliced using a slicing device (manufactured by Kitajima Machine Knife) so as to have a thickness of 3.0 mm. The obtained porous material was approximately 100 mm × 100 mm × 3.0 mm. The porous material subjected to the slicing process was subjected to the following water absorption rate test. The results are shown in Table 8.
（吸水速度試験）
多孔質材料の１００ｍｍ×１００ｍｍの面の中心付近にプッシュボタン式液体用微量体積計を用いて超純水を１ｍＬ滴下し、吸収されるまでの時間を測定し、次式に従って吸水速度を算出した。測定は５回行いその平均値を示した。
吸水速度（μｌ／秒）＝純水滴下量（１０００μｌ）／吸水に要した時間（秒）(Water absorption rate test)
1 mL of ultrapure water was dropped in the vicinity of the center of the 100 mm × 100 mm surface of the porous material using a push button type liquid microvolume meter, the time until it was absorbed was measured, and the water absorption rate was calculated according to the following formula: . The measurement was performed 5 times and the average value was shown.
Water absorption rate (μl / second) = Pure water dripping amount (1000 μl) / Time required for water absorption (second)
＊１，ＧＬｙ：グリセリン
＊２，ｖ：体積％、ｗ：質量％
* 1, GLy: glycerin * 2, v: volume%, w: mass%
実施例３８及び３９の結果から、本発明の多孔質材料は吸水速度が速く、吸水性に優れるため、例えば創傷被覆材として用いた場合に、創傷部から出る滲出液を素早く吸収することができると考えられる。これに対して、酸基含有化合物を含有しない比較例１１の多孔質材料は、吸水速度が遅く吸水性が悪く、創傷被覆材への応用は難しいことが分かった。また、本発明の水酸基含有化合物を含有する多孔質材料は、スライス加工を施すことで、さらに吸水速度が向上することが分かった。型を用いて多孔質材料を作製する場合、その最表面には数μｍ〜１ｍｍ程度の厚さで細孔が相対的に少ない領域が存在することがあるが、本発明の多孔質材料はスライス加工に適しているため、該領域をスライスして除去し、吸水速度により優れた部分を無駄なく使用することが可能となる。 From the results of Examples 38 and 39, since the porous material of the present invention has a high water absorption rate and excellent water absorption, when used as a wound dressing, for example, it can quickly absorb exudate from the wound part. it is conceivable that. On the other hand, it was found that the porous material of Comparative Example 11 containing no acid group-containing compound had a slow water absorption rate and poor water absorption, and was difficult to apply to a wound dressing. Moreover, it turned out that the water absorption speed | rate improves further by giving the porous material containing the hydroxyl-containing compound of this invention to slice processing. When a porous material is produced using a mold, a region having a thickness of about several μm to 1 mm and relatively few pores may be present on the outermost surface, but the porous material of the present invention is sliced. Since it is suitable for processing, the region can be sliced and removed, and a portion superior in water absorption speed can be used without waste.
実施例４０
実施例３７と同様の操作で多孔質材料を作製し、下記の保水性試験を行った。その結果、保水率は１６８０％と大きく、多量の浸出液を吸収することができるため、特に創傷被覆材として有用であることが分かった。
（保水性試験）
多孔質材料を乾燥して得られた乾燥多孔質体を秤量後（この時の質量を乾燥質量とする）、超純水中に３０秒間浸漬した。次いで３０秒間空気中で保持し表面の水分を落として、再度秤量し（この時の質量を湿潤質量とする）、下式に従って保水率を算出した。
保水率％＝〔（湿潤質量（ｇ）−乾燥質量（ｇ））／乾燥質量（ｇ）〕×１００Example 40
A porous material was prepared in the same manner as in Example 37, and the following water retention test was performed. As a result, the water retention rate was as large as 1680%, and a large amount of leachate could be absorbed, which proved particularly useful as a wound dressing.
(Water retention test)
The dried porous material obtained by drying the porous material was weighed (the mass at this time was defined as the dry mass) and then immersed in ultrapure water for 30 seconds. Subsequently, it was kept in the air for 30 seconds, the surface moisture was dropped, weighed again (the mass at this time was defined as wet mass), and the water retention rate was calculated according to the following formula.
Water retention% = [(wet mass (g) −dry mass (g)) / dry mass (g)] × 100
本発明の多孔質材料は、癒着防止剤、創傷被覆材、薬剤徐放担体等の医療分野、微生物、細菌等の住処になる支持体として活用しうる浄水分野、細胞培養支持体（足場材料）、組織再生支持体等として活用しうる組織工学及び再生医療工学分野、エステティックサロン及び個人での使用による保湿等を目的とした化粧品・エステ分野、紙おむつ、生理用品等の生活日用品分野など、産業上幅広い分野で利用することができる。特に、癒着防止剤、創傷被覆材、薬剤徐放担体等の医療分野、細胞培養支持体（足場材料）、組織再生支持体等として活用しうる組織工学及び再生医療工学分野、化粧品及びエステ分野などに広く適用することができ、顔の形状に合わせたフェイスマスク及びアイマスクとしても極めて有用である。 The porous material of the present invention is a medical field such as an anti-adhesive agent, a wound dressing material, a drug sustained-release carrier, a water purification field that can be used as a support for living organisms such as microorganisms and bacteria, and a cell culture support (scaffold material). , Such as tissue engineering and regenerative medical engineering fields that can be used as tissue regeneration supports, cosmetics and esthetics for esthetic salons and personal use, and daily necessities such as disposable diapers and sanitary products. Can be used in a wide range of fields. In particular, medical fields such as anti-adhesion agents, wound dressings, sustained drug carriers, tissue engineering and regenerative medical engineering fields that can be used as cell culture supports (scaffolding materials), tissue regeneration supports, cosmetics and beauty treatment fields, etc. It is very useful as a face mask and an eye mask adapted to the shape of the face.
Claims (4)
The porous sheet which consists of a porous material in any one of Claims 1-3, and whose film thickness is 0.1-50 mm.
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| PCT/JP2015/062023 WO2015163294A1 (en) | 2014-04-21 | 2015-04-20 | Porous material and porous sheet |
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| CN106913900B (en) * | 2017-02-20 | 2020-07-10 | 苏州丝美特生物技术有限公司 | Silk fibroin hemostatic material and preparation method thereof |
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