JP2005080927A - Production method of medical porous body - Google Patents

Production method of medical porous body Download PDF

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JP2005080927A
JP2005080927A JP2003317258A JP2003317258A JP2005080927A JP 2005080927 A JP2005080927 A JP 2005080927A JP 2003317258 A JP2003317258 A JP 2003317258A JP 2003317258 A JP2003317258 A JP 2003317258A JP 2005080927 A JP2005080927 A JP 2005080927A
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porous body
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Hideki Tadokoro
英記 田所
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JMS Co Ltd
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JMS Co Ltd
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a production method of a medical porous body which is made of a high polymer without using a freeze-drying apparatus. <P>SOLUTION: This production method is that a high polymer solution is produced by dissolving the high polymer which is a material for the medical porous body in a solvent. The high polymer solution is mixed with a material to form holes and poured in a mold with a desired shape to be frozen in a freezing chamber so that a frozen body of the high polymer solution is obtained. Afterwards, an extraction solvent in which the high polymer in the frozen body is hardly or not soluble, and the solvent and the material to form the holes are soluble is used to extract the solvent from the frozen body. Finally, the extraction solvent which is included in the porous body is removed by drying. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明は、細胞増殖や生体内埋設に用いる医療用多孔質体を製造する方法に関し、特に、その製造コストを抑制する技術に関するものである。   The present invention relates to a method for producing a medical porous body used for cell growth and in vivo implantation, and particularly relates to a technique for suppressing the production cost.

近年、医療分野や再生医工学の分野においては、組織再生の足場材料として高分子からなる医療用の多孔質体が用いられている。この多孔質体は、組織の導入により細胞の分化誘導や組織形成に用いられるほか、構造的に表面積が大きいことから徐放薬剤の担体としても用いられる。
このような多孔質体の製造方法としては、特許文献1〜4に見られるように高分子溶液を凍結した後真空減圧下にて溶媒を揮発させる凍結乾燥法や、特許文献5に見られるように造孔材を含有させた固形物から造孔材を抽出させる造孔材抽出法を用いることが一般的である。
In recent years, in the medical field and the field of regenerative medical engineering, a medical porous body made of a polymer has been used as a scaffold material for tissue regeneration. This porous body is used for induction of cell differentiation and tissue formation by introduction of tissue, and also as a carrier for sustained release drugs because of its structurally large surface area.
As a method for producing such a porous body, as shown in Patent Documents 1 to 4, a freeze-drying method in which a polymer solution is frozen and then the solvent is volatilized under vacuum and reduced pressure, as shown in Patent Documents 5 and 4 It is common to use a pore former extraction method in which a pore former is extracted from a solid containing a pore former.

凍結乾燥法は、上記のように低温かつ高真空下において処理されるので、材料となる高分子の化学的劣化を抑制しながら多孔質体を製造することができるものの、高価な凍結乾燥装置を必要とするため、イニシャルコストやランニングコストが高いというデメリットがある。さらに、多孔質体における孔径を制御するためには、凍結温度や凍結体の有形成分濃度を複雑に組み合わせて最適化する必要があり、所望の孔径を得ることは非常に難しい。   Since the freeze-drying method is processed at a low temperature and under a high vacuum as described above, it is possible to produce a porous body while suppressing chemical deterioration of the polymer as a material, but an expensive freeze-drying apparatus is used. Since it is necessary, there is a demerit that initial cost and running cost are high. Furthermore, in order to control the pore diameter in the porous body, it is necessary to optimize by combining the freezing temperature and the concentration of the component of the frozen body in a complicated manner, and it is very difficult to obtain a desired pore diameter.

他方、造孔材抽出法は、使用する造孔材の径を選択することにより比較的容易に所望の孔径を得ることができるものの、造孔材の添加量を多くして多孔度の高いものを得ようとする場合、表面から遠い位置にある造孔材は抽出液が届きにくく抽出されずに残存する可能性がある。
このように造孔材が残存することを抑制するため、真空乾燥によって昇華する造孔材を用い、凍結乾燥法によりその造孔材を昇華させる技術が開示されている(特許文献6参照)。
特開平05−43734号公報 特開平09−99051号公報 特開平11−319066号公報 特開平2000−329761号公報 特公平7−4420号公報 特開平2002−146084号公報
On the other hand, the pore former extraction method can obtain a desired pore diameter relatively easily by selecting the diameter of the pore former to be used, but has a high porosity by increasing the amount of pore former added. When trying to obtain, the pore former located at a position far from the surface is difficult to reach the extract and may remain without being extracted.
In order to prevent the pore former from remaining in this way, a technique has been disclosed in which a pore former that sublimates by vacuum drying is used and the pore former is sublimated by a freeze drying method (see Patent Document 6).
JP 05-43734 A JP 09-99051 A JP 11-319066 A Japanese Patent Laid-Open No. 2000-329761 Japanese Patent Publication No. 7-4420 Japanese Patent Application Laid-Open No. 2002-146084

しかしながら、上記造孔材を昇華させる技術においては、依然として高価な高真空装置や低温トラップなどを備える凍結乾燥装置を用いる必要があり、多孔質体を製造する際においては、そのイニシャルコストが上昇するとともに高真空に保持するためのランニングコストもかさみ、多孔質体の製造コストが高くなるという問題がある。
本発明は、上記課題に鑑み、凍結乾燥装置を用いることなく医療用の多孔質体を製造することができる医療用多孔質体の製造方法を提供することを目的とする。
However, in the technique for sublimating the pore former, it is still necessary to use an expensive high vacuum apparatus or a freeze-drying apparatus equipped with a low temperature trap or the like, and the initial cost increases when producing a porous body. In addition, there is a problem that the running cost for maintaining a high vacuum is increased, and the manufacturing cost of the porous body is increased.
An object of this invention is to provide the manufacturing method of the medical porous body which can manufacture a medical porous body, without using a freeze-drying apparatus in view of the said subject.

上記課題を解決するために、本発明に係る医療用多孔質体の製造方法は、高分子からなる医療用多孔質体の製造方法であって、高分子を溶媒に溶解させた溶液と造孔材との混合溶液を凍結させて凍結体を作製し、高分子が難溶または不溶でありかつ前記溶媒および造孔材が可溶である抽出溶媒を用いて凍結体から溶媒および造孔材を抽出することを特徴とする。   In order to solve the above problems, a method for producing a medical porous body according to the present invention is a method for producing a medical porous body comprising a polymer, wherein the polymer is dissolved in a solvent and pores Freezing the mixed solution with the material to prepare a frozen body, and using the extraction solvent in which the polymer is hardly soluble or insoluble and the solvent and the pore former are soluble, the solvent and the pore former are removed from the frozen body. It is characterized by extracting.

ここで、上記凍結体は、高分子と溶媒とが相分離した複相構造をなすので、抽出によって溶媒が取り除かれた部分にも孔が形成される。
溶媒および造孔材の抽出は、凍結体の形が崩壊することを抑制するため、溶媒の凝固点近傍で行うことが望ましい。
なお、混合溶液に対し、さらに徐放薬剤を添加して凍結させるようにすれば、薬剤を多孔質体の製造時において担持させることができ、多孔質体の製造後に薬剤を外部から浸透させる方法と比べて多孔質体内部にまで薬剤を含侵させることができる。
Here, since the frozen body has a multiphase structure in which the polymer and the solvent are phase-separated, pores are also formed in the portion where the solvent is removed by extraction.
The extraction of the solvent and the pore former is preferably performed in the vicinity of the freezing point of the solvent in order to prevent the frozen body from collapsing.
In addition, if a sustained-release drug is further added to the mixed solution and frozen, the drug can be supported during the production of the porous body, and the drug is permeated from the outside after the production of the porous body. Compared with, the drug can be impregnated into the porous body.

具体的には、高分子として熱可塑性高分子を用いることができる。
また、その熱可塑性高分子としては、ウレタン系樹脂、塩化ビニル系樹脂、アクリル系樹脂、スチレン系樹脂、ポリエステル類、ポリビニルアルコール、ポリアクリル酸、ポリアルギン酸からなる群から選択された高分子を用いることができる。
具体的に、テトラヒドロフラン、メチルエーテルケトン、アセトン、ジメチルサルフォキサイド、ジオキサンからなる群から選択された溶媒を用いることができる。
Specifically, a thermoplastic polymer can be used as the polymer.
As the thermoplastic polymer, a polymer selected from the group consisting of urethane resins, vinyl chloride resins, acrylic resins, styrene resins, polyesters, polyvinyl alcohol, polyacrylic acid, and polyalginic acid is used. be able to.
Specifically, a solvent selected from the group consisting of tetrahydrofuran, methyl ether ketone, acetone, dimethyl sulfoxide, and dioxane can be used.

また、抽出溶媒としては、水系溶媒が用いられ、水、塩酸、硝酸の群から選択された抽出溶媒を用いることができる。
また、造孔材としては、水溶性材料が用いられ、塩化ナトリウム、炭酸カルシウム、酸化マグネシウムの群から選択された造孔材を用いることができる。
As the extraction solvent, an aqueous solvent is used, and an extraction solvent selected from the group of water, hydrochloric acid, and nitric acid can be used.
As the pore former, a water-soluble material is used, and a pore former selected from the group of sodium chloride, calcium carbonate, and magnesium oxide can be used.

従来、溶媒および造孔材を除去するために凍結乾燥装置を用いて除去していたが、本発明は、それらを除去するために高分子が難溶または不溶でありかつ溶媒および造孔材が可溶である抽出溶媒を用いて抽出を行っている。このような抽出溶媒を用いることにより、特許文献6に記載された造孔材を昇華させる技術と同様、凍結体から溶媒を除去するとともに造孔材を除去することができる。また、この溶媒および造孔材の抽出された部分が孔として形成されるため、造孔材抽出法に比べて造孔材の使用量を減らすことができ、高い多孔度の多孔質体を形成する場合においても造孔材が残存しにくい。さらに、高価な凍結乾燥装置を用いなくても溶媒と造孔材を除去できるため、医療用多孔質体を製造する際の装置にかかるイニシャルコストおよびランニングコストを抑制することが可能となる。そして、多孔質体が形成された後においては、残存する抽出溶媒を自然乾燥などさせることにより除去することができる。   Conventionally, the solvent and the pore former were removed using a freeze-drying apparatus. However, in the present invention, the polymer is hardly soluble or insoluble and the solvent and the pore former are not removed. Extraction is performed using a soluble extraction solvent. By using such an extraction solvent, the solvent can be removed from the frozen body and the pore former can be removed as in the technique for sublimating the pore former described in Patent Document 6. In addition, since the extracted part of the solvent and the pore former is formed as pores, the amount of pore former used can be reduced compared to the pore former extraction method, and a highly porous body is formed. Even in this case, it is difficult for the pore former to remain. Furthermore, since the solvent and the pore former can be removed without using an expensive freeze-drying apparatus, it is possible to suppress the initial cost and the running cost of the apparatus for producing a medical porous body. After the porous body is formed, the remaining extraction solvent can be removed by natural drying or the like.

以下、本発明に係る医療用多孔質体(以下、「多孔質体」という。)およびその製造方法の一実施の形態について説明する。
まず、多孔質体の材料に使用する高分子について説明する。
本発明に係る多孔質体を構成する高分子は、例えば、熱可塑性の高分子であり、溶媒に可溶なものであれば特に制限されることなく用いることができる。例えば、熱可塑性高分子としては、熱可塑性ウレタン系樹脂、塩化ビニル系樹脂、アクリル系樹脂、スチレン系樹脂、ポリエステル類、およびポリビニルアルコールやポリアクリル酸、ポリアルギン酸等の水溶性高分子を使用することができる。また、これらの高分子を複数ブレンドしたものや共重合体を用いることもできる。好ましくは、生体吸収性および強度に優れた分子量が10万〜30万の乳酸−εカプロラクトン共重合体を用いることができる。
Hereinafter, a medical porous body according to the present invention (hereinafter referred to as “porous body”) and a method for producing the same will be described.
First, the polymer used for the porous material will be described.
The polymer constituting the porous body according to the present invention is, for example, a thermoplastic polymer and can be used without particular limitation as long as it is soluble in a solvent. For example, as the thermoplastic polymer, thermoplastic urethane resin, vinyl chloride resin, acrylic resin, styrene resin, polyester, and water-soluble polymer such as polyvinyl alcohol, polyacrylic acid, polyalginic acid, etc. are used. be able to. Moreover, what blended two or more of these polymers and a copolymer can also be used. Preferably, a lactic acid-ε caprolactone copolymer having a molecular weight of 100,000 to 300,000 excellent in bioabsorbability and strength can be used.

ここで、熱可塑性ポリウレタン系樹脂や塩化ビニル系樹脂といった生体吸収性を示さない高分子は、生体の外部に貼付する薬剤担体に用いることが望ましい。一方、生体吸収性を示す高分子である、ポリエステル類に属するポリ乳酸やポリグリコール酸、ポリリンゴ酸、ポリカプロラクトン、およびこれらの共重合体などは、生体内に埋植可能な組織再生用のスキャホールドとして用いることが望ましい。   Here, it is desirable to use a polymer that does not exhibit bioabsorbability, such as a thermoplastic polyurethane-based resin or a vinyl chloride-based resin, as a drug carrier to be attached to the outside of the living body. On the other hand, polylactic acid, polyglycolic acid, polymalic acid, polycaprolactone, and copolymers thereof belonging to polyester, which are bioabsorbable polymers, can be implanted in the living body for tissue regeneration. It is desirable to use it as a hold.

図1は、多孔質体の製造過程における高分子の状態を示す模式図である。
図1(a)に示すように、容器3において上記高分子を溶媒に溶解させた高分子溶液1と造孔材2とを混合した混合溶液を作製し、この溶液を有底筒状の型4に流し込む。ここで、型4の形状は筒状に限定されるものではなく、所望の多孔質体の形状にあわせたものを使用することができる。
FIG. 1 is a schematic view showing a state of a polymer in the production process of a porous body.
As shown in FIG. 1A, a mixed solution in which a polymer solution 1 in which the polymer is dissolved in a solvent and a pore former 2 are mixed in a container 3 is prepared, and this solution is used as a bottomed cylindrical mold. Pour into 4. Here, the shape of the mold 4 is not limited to a cylindrical shape, and a shape matching the shape of a desired porous body can be used.

混合溶液に使用する溶媒としては、多孔質体を構成する高分子を溶解させることができ、かつ添加する造孔材2が不溶または難溶であるとともに、冷凍庫の温度において凝固するものが好ましい。
例えば、テトラヒドロフラン(THF)、メチルエーテルケトン(MEK)、アセトン、ジメチルスルフォキサイド(DMSO)、ジオキサンなどの有機溶媒あるいはこれらの混合物を用いることができる。特に、ジオキサンは、一般家庭において使用されている冷凍庫の温度(−20℃)程度において凝固するため、特殊な冷凍庫が不要でありイニシャルコストを下げ、多孔質体のコストを下げることができるため好ましい。
The solvent used for the mixed solution is preferably a solvent that can dissolve the polymer constituting the porous body, and that the pore former 2 to be added is insoluble or hardly soluble, and solidifies at the temperature of the freezer.
For example, an organic solvent such as tetrahydrofuran (THF), methyl ether ketone (MEK), acetone, dimethyl sulfoxide (DMSO), dioxane, or a mixture thereof can be used. In particular, dioxane is preferable because it solidifies at about the temperature of a freezer (-20 ° C.) used in general households, so that a special freezer is unnecessary, the initial cost can be reduced, and the cost of the porous body can be reduced. .

造孔材2としては、有機物あるいは無機物等種々のものを使用することができる。高分子を溶解する溶媒と、造孔材2を抽出する抽出溶媒との組み合わせを考慮すると、好ましくは、水溶性材料である無機塩類の造孔材が好ましい。例えば、塩化ナトリウム、炭酸カルシウム、酸化マグネシウムなどが挙げられるが、溶媒に不溶かつ抽出溶媒に可溶なものであればよく、これらの混合物でもよい。造孔材2の粒子径および添加量は、所望する多孔質体の孔径や多孔度に合わせて選択すればよく、高分子溶液に対して質量比2倍以上添加することが好ましい。なお、医療用に用いる場合、多孔質体の多孔度としては、80〜98%が適していると考えられる。   As the pore former 2, various materials such as an organic material or an inorganic material can be used. In consideration of the combination of the solvent for dissolving the polymer and the extraction solvent for extracting the pore former 2, an inorganic salt pore former that is a water-soluble material is preferred. For example, sodium chloride, calcium carbonate, magnesium oxide and the like can be mentioned as long as they are insoluble in a solvent and soluble in an extraction solvent, or a mixture thereof. What is necessary is just to select the particle diameter and addition amount of the pore making material 2 according to the desired pore diameter and porosity of the porous body, and it is preferable to add the mass ratio to the polymer solution by 2 times or more. In addition, when using for medical use, it is thought that 80 to 98% is suitable as the porosity of a porous body.

次に、図1(b)に示すように、この混合溶液が流し込まれた型4を冷凍庫にて凍結させて凍結体5を作製する。
次に、図1(c)に示すように型4から取り出すことにより高分子溶液の凍結体5を得る。ここで、凍結体5においては、その凍結を行うことによって図1(c)の拡大図に示すように高分子11と溶媒12とが相分離した複相構造をなしていると考えられる。
Next, as shown in FIG.1 (b), the type | mold 4 into which this mixed solution was poured is frozen in a freezer, and the frozen body 5 is produced.
Next, as shown in FIG.1 (c), the frozen body 5 of a polymer solution is obtained by taking out from the type | mold 4. As shown in FIG. Here, it is considered that the frozen body 5 has a multiphase structure in which the polymer 11 and the solvent 12 are phase-separated as shown in the enlarged view of FIG.

次に、図1(d)に示すように、抽出容器6に注入された抽出溶媒20に対し、凍結体5を凍結させた状態にて浸漬させる。
ここで、抽出溶媒20は、高分子11が難溶または不溶であり、かつ溶媒12および造孔材2と相溶性のあるものが用いられる。そのため、この浸漬により抽出溶媒20と相溶性のある造孔材2と溶媒12とが抽出溶媒20に溶解・抽出される一方、高分子11は、抽出溶媒に対してほとんど溶けないため、そのまま残存することになる。
Next, as shown in FIG. 1 (d), the frozen body 5 is immersed in the extraction solvent 20 injected into the extraction container 6 in a frozen state.
Here, as the extraction solvent 20, a solvent in which the polymer 11 is hardly soluble or insoluble and compatible with the solvent 12 and the pore former 2 is used. Therefore, by this immersion, the pore former 2 and the solvent 12 compatible with the extraction solvent 20 are dissolved / extracted in the extraction solvent 20, while the polymer 11 is hardly dissolved in the extraction solvent, so that it remains as it is. Will do.

この抽出においては、凍結した高分子溶液の形状が崩れない温度、すなわち溶媒12の凝固点近傍(例えば、上記冷凍庫内にて−20℃)に管理した状態において抽出溶媒に浸漬する必要がある。ここで、抽出溶媒20としては、溶媒、造孔材との関係から水系溶媒が好ましく、水や、塩酸、硝酸などの酸あるいはこれらの混合物を用いることができる。
この抽出によって、図1(d)に示すように高分子11は析出する一方、溶媒12と造孔材2とが抽出溶媒20と溶け合って置換されるので、抽出により形成される高分子11からなる多孔質体には抽出溶媒20が含侵された状態となる。
In this extraction, it is necessary to immerse in the extraction solvent at a temperature at which the shape of the frozen polymer solution does not collapse, that is, in the vicinity of the freezing point of the solvent 12 (for example, −20 ° C. in the freezer). Here, the extraction solvent 20 is preferably an aqueous solvent in view of the relationship between the solvent and the pore former, and water, an acid such as hydrochloric acid or nitric acid, or a mixture thereof can be used.
By this extraction, the polymer 11 is precipitated as shown in FIG. 1 (d), while the solvent 12 and the pore former 2 are dissolved and replaced with the extraction solvent 20, so that the polymer 11 formed by the extraction can be used. The resulting porous body is impregnated with the extraction solvent 20.

最後に、その多孔質体を抽出容器6から取り出して自然乾燥を行い、含侵された抽出溶媒20を蒸発させることによって多孔質体を得ることができる。
このような方法によれば、抽出溶媒にて溶媒と造孔材とを取り除くことができるので、高価な凍結乾燥装置を用いて溶媒や造孔材を除去する必要がない。
したがって、多孔質体製造時におけるイニシャルコストやランニングコストを低減することができ、多孔質体の製造コストを下げることができる。
Finally, the porous body can be obtained by taking out the porous body from the extraction container 6 and performing natural drying to evaporate the impregnated extraction solvent 20.
According to such a method, since the solvent and the pore former can be removed with the extraction solvent, it is not necessary to remove the solvent and the pore former using an expensive freeze-drying apparatus.
Therefore, the initial cost and running cost at the time of manufacturing the porous body can be reduced, and the manufacturing cost of the porous body can be reduced.

さらに、本発明に係る多孔質体の製造方法によれば、得られた多孔質体は、外表面に近い部分が緻密になり内部が粗となるいわゆるスキン−コア構造が見られなくなる。したがって、多孔質体は、全体的に均一な多孔度を有する構造となり、足場材料などに適用する場合にはスキン−コア構造を有するものよりも適したものとなる。また、造孔材が内部に残されることはない。
(実施例1)
以下、本発明に係る製造方法を用いて、生体吸収性高分子であるL乳酸−εカプロラクトン共重合体の多孔質体を製造する方法について説明する。
Furthermore, according to the method for producing a porous body according to the present invention, the obtained porous body does not show a so-called skin-core structure in which a portion close to the outer surface becomes dense and the inside becomes rough. Therefore, the porous body has a structure having a uniform porosity as a whole, and is more suitable than that having a skin-core structure when applied to a scaffold material or the like. Further, the pore former is not left inside.
(Example 1)
Hereinafter, a method for producing a porous body of L-lactic acid-ε caprolactone copolymer, which is a bioabsorbable polymer, using the production method according to the present invention will be described.

(1)組成比50:50のL乳酸−εカプロラクトン共重合体(以下、P(LA50/CL50)という。)を溶媒である1,4−ジオキサンに溶解し、8質量%の溶液を調整した。
(2)次に、そのP(LA50/CL50)溶液50mLに粒径100μmのNaClを100g添加し、混合溶液を得た。
(1) An L-lactic acid-ε caprolactone copolymer (hereinafter referred to as P (LA50 / CL50)) having a composition ratio of 50:50 was dissolved in 1,4-dioxane as a solvent to prepare an 8 mass% solution. .
(2) Next, 100 g of NaCl having a particle size of 100 μm was added to 50 mL of the P (LA50 / CL50) solution to obtain a mixed solution.

(3)次に、そのP(LA50/CL50)溶液を内径20mmのチューブ状鋳型に静かに流し込み、家庭用フリーザー(温度−20℃)にて12時間凍結させた。
(4)その後、凍結したP(LA50/CL50)溶液を鋳型から取り出し、20mmφ×80mmの円柱状の凍結体を得た。
(5)この円柱状の凍結体を、抽出溶媒である−4℃に冷却した水1L中に浸漬させ、当該水を攪拌させながら24時間放置することによって、1,4−ジオキサン溶媒と造孔材であるNaClを同時に抽出した。ここで、水は、P(LA50/CL50)に難溶または不溶であり、かつ1,4−ジオキサンおよびNaClに可溶である。また水については、その抽出効率を向上させるため、抽出開始から6時間後、12時間後、18時間後に新しいものと交換した。
(3) Next, the P (LA50 / CL50) solution was gently poured into a tubular mold having an inner diameter of 20 mm and frozen in a home freezer (temperature −20 ° C.) for 12 hours.
(4) Thereafter, the frozen P (LA50 / CL50) solution was taken out of the mold, and a 20 mmφ × 80 mm cylindrical frozen body was obtained.
(5) This cylindrical frozen body is immersed in 1 L of water cooled to −4 ° C., which is an extraction solvent, and allowed to stand for 24 hours while stirring the water. The material NaCl was extracted at the same time. Here, water is hardly soluble or insoluble in P (LA50 / CL50) and soluble in 1,4-dioxane and NaCl. Moreover, about water, in order to improve the extraction efficiency, it replaced | exchanged for the new thing 6 hours, 12 hours, and 18 hours after the start of extraction.

(6)その後、得られたP(LA50/CL50)を24時間真空乾燥することによって多孔質体を得た。
このようにして得られた多孔質体は、走査型電子顕微鏡を用いて観察することにより、図2に示すように、連続した気泡を有するとともに、スキン−コア構造が存在せず、表皮部分と内部との孔径(2μm〜500μm)および多孔度(80%〜98%)が略等しいものであることが確認された。また、造孔材であるNaClの残存も見られず、抽出溶媒による抽出が完全に行われていることが確認された。このような多孔度を有する多孔質体は、組織再生用のスキャホールドの用途に適していると考えられる。
(6) Thereafter, the obtained P (LA50 / CL50) was vacuum-dried for 24 hours to obtain a porous body.
The porous body thus obtained is observed using a scanning electron microscope, and as shown in FIG. 2, the porous body has continuous bubbles and does not have a skin-core structure. It was confirmed that the pore diameter (2 μm to 500 μm) and the porosity (80% to 98%) with the inside were substantially equal. Further, no residual NaCl, which is a pore-forming material, was observed, and it was confirmed that extraction with an extraction solvent was completely performed. It is considered that a porous body having such a porosity is suitable for a scaffold for tissue regeneration.

なお、上記実施の形態においては、高分子を溶媒に溶解させて凍結させていたが、凍結前に徐放薬剤を混合するようにしてもよい。このようにすれば、薬剤を多孔質体の製造時において担持させることができ、多孔質体の製造後に薬剤を外部から浸透させる方法と比べて多孔質体内部にまで薬剤を含侵させることができる。   In the above embodiment, the polymer is dissolved in a solvent and frozen, but a sustained-release drug may be mixed before freezing. In this way, the drug can be supported during the production of the porous body, and the drug can be impregnated into the porous body as compared with the method in which the drug penetrates from the outside after the production of the porous body. it can.

本発明に係る医療用多孔質体の製造方法は、特にコストの安さが求められる医療用多孔質体に有効である。   The method for producing a medical porous body according to the present invention is particularly effective for a medical porous body for which low cost is required.

本発明に係る医療用多孔質体の製造過程における高分子の状態を示す模式図である。It is a schematic diagram which shows the state of the polymer in the manufacture process of the medical porous body which concerns on this invention. 本発明に係る医療用多孔質体の走査型電子顕微鏡写真である。It is a scanning electron micrograph of the medical porous body which concerns on this invention.

符号の説明Explanation of symbols

1 高分子溶液
2 造孔材
3 容器
4 型
5 凍結体
6 抽出容器
11 高分子
12 溶媒
20 抽出溶媒
DESCRIPTION OF SYMBOLS 1 Polymer solution 2 Porous material 3 Container 4 Type 5 Frozen body 6 Extraction container 11 Polymer 12 Solvent 20 Extraction solvent

Claims (11)

高分子からなる医療用多孔質体の製造方法であって、
高分子を溶媒に溶解させた溶液と造孔材との混合溶液を凍結させて凍結体を作製し、前記高分子が難溶または不溶でありかつ前記溶媒および造孔材が可溶である抽出溶媒を用いて前記凍結体から前記溶媒および前記造孔材を抽出する
ことを特徴とする医療用多孔質体の製造方法。
A method for producing a porous medical material made of a polymer,
A frozen solution is prepared by freezing a mixed solution of a solution in which a polymer is dissolved in a solvent and a pore former, and the polymer is hardly soluble or insoluble and the solvent and the pore former are soluble. The method for producing a porous body for medical use, wherein the solvent and the pore former are extracted from the frozen body using a solvent.
前記凍結体は、高分子と溶媒とが相分離した複相構造をなしていることを特徴とする請求項1に記載の医療用多孔質の製造方法。   The method for producing a porous medical material according to claim 1, wherein the frozen body has a multiphase structure in which a polymer and a solvent are phase-separated. 前記溶媒および造孔材の抽出は、溶媒の凝固点近傍で行うことを特徴とする請求項1または2に記載の医療用多孔質体の製造方法。   The method for producing a medical porous body according to claim 1 or 2, wherein the extraction of the solvent and the pore former is performed near the freezing point of the solvent. 前記混合溶液に対し、さらに徐放薬剤を添加して凍結させることを特徴とする請求項1〜3のいずれかに記載の医療用多孔質体の製造方法。   The method for producing a porous body for medical use according to any one of claims 1 to 3, further comprising adding a sustained-release drug and freezing the mixed solution. 前記高分子は、熱可塑性高分子であることを特徴とする請求項1〜4のいずれかに記載の医療用多孔質体の製造方法。   The method for producing a medical porous body according to any one of claims 1 to 4, wherein the polymer is a thermoplastic polymer. 前記熱可塑性高分子は、ウレタン系樹脂、塩化ビニル系樹脂、アクリル系樹脂、スチレン系樹脂、ポリエステル類、ポリビニルアルコール、ポリアクリル酸、ポリアルギン酸からなる群から選択された高分子であることを特徴とする請求項5に記載の医療用多孔質体の製造方法。   The thermoplastic polymer is a polymer selected from the group consisting of urethane resins, vinyl chloride resins, acrylic resins, styrene resins, polyesters, polyvinyl alcohol, polyacrylic acid, and polyalginic acid. The method for producing a medical porous body according to claim 5. 前記溶媒は、テトラヒドロフラン、メチルエーテルケトン、アセトン、ジメチルサルフォキサイド、ジオキサンからなる群から選択された溶媒であることを特徴とする請求項1〜6のいずれかに記載の医療用多孔質体の製造方法。   The medical porous body according to any one of claims 1 to 6, wherein the solvent is a solvent selected from the group consisting of tetrahydrofuran, methyl ether ketone, acetone, dimethyl sulfoxide, and dioxane. Manufacturing method. 前記抽出溶媒は、水系溶媒であることを特徴とする請求項1〜7のいずれかに記載の医療用多孔質体の製造方法。   The method for producing a medical porous body according to any one of claims 1 to 7, wherein the extraction solvent is an aqueous solvent. 前記水系溶媒は、水、塩酸、硝酸の群から選択された溶媒であることを特徴とする請求項8に記載の医療用多孔質体の製造方法。   The method for producing a medical porous body according to claim 8, wherein the aqueous solvent is a solvent selected from the group of water, hydrochloric acid, and nitric acid. 前記造孔材は、水溶性材料から構成されていることを特徴とする請求項1〜9のいずれかに記載の医療用多孔質体の製造方法。   The said porous material is comprised from the water-soluble material, The manufacturing method of the medical porous body in any one of Claims 1-9 characterized by the above-mentioned. 前記水溶性材料は、塩化ナトリウム、炭酸カルシウム、酸化マグネシウムの群から選択された材料であることを特徴とする請求項10に記載の医療用多孔質体の製造方法。   The method for producing a medical porous body according to claim 10, wherein the water-soluble material is a material selected from the group consisting of sodium chloride, calcium carbonate, and magnesium oxide.
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JPS61252261A (en) * 1985-05-01 1986-11-10 Bio Materiaru Yunibaasu:Kk Porous transparent polyvinyl alcohol gel and production thereof
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JPH01131257A (en) * 1987-11-16 1989-05-24 Oji Paper Co Ltd Production of microcellular molded body of high polymer
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