WO2012118236A1 - Corps moulé fibreux - Google Patents

Corps moulé fibreux Download PDF

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Publication number
WO2012118236A1
WO2012118236A1 PCT/JP2012/056211 JP2012056211W WO2012118236A1 WO 2012118236 A1 WO2012118236 A1 WO 2012118236A1 JP 2012056211 W JP2012056211 W JP 2012056211W WO 2012118236 A1 WO2012118236 A1 WO 2012118236A1
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WO
WIPO (PCT)
Prior art keywords
molded body
protein
fiber molded
fiber
solution
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PCT/JP2012/056211
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English (en)
Japanese (ja)
Inventor
本多　勧
真 佐竹
兼子　博章
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帝人株式会社
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Priority to JP2013502440A priority Critical patent/JP5698339B2/ja
Publication of WO2012118236A1 publication Critical patent/WO2012118236A1/fr

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    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4326—Condensation or reaction polymers
    • D04H1/435—Polyesters
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/88—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds
    • D01F6/92—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds of polyesters
    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning

Definitions

  • the present invention relates to a molded fiber comprising an aliphatic polyester, a protein, and phosphatidylethanolamine and / or polyoxyethylene sorbitan fatty acid esters.
  • Fibers produced by electrospinning have the advantage of being able to easily produce yarns with a smaller fiber diameter than conventional forming methods.
  • the surface area can be increased. Therefore, in recent years, fiber molded products obtained by electrospinning have been studied for application to cell culture carriers, scaffold materials for regenerative medicine, carriers for drug delivery systems, etc., and have been combined with drugs and proteins. Materials development is also underway.
  • synthetic polymers polyglycolic acid, polylactic acid, polycaprolactone, etc.
  • natural polymers collagen, gelatin, elastin, hyaluronic acid, alginic acid, chitosan, etc.
  • inorganic Materials hydroxyapatite, ⁇ -tricalcium phosphate
  • synthetic polymers molded articles obtained by processing aliphatic polyester into fibers have various applications such as sutures, bioabsorbable sheets, and carriers for drug delivery systems.
  • the drug and protein are water-soluble and cannot be dissolved in the polymer solution, so there is a limit to increasing the content, and the release behavior of the drug and protein has a problem that burst release occurs at an early stage. there were.
  • a method of 2) Y. Z. Zhang, X. et al. Wang, Y .; Feng, J .; Li, C.I. T.A. Lim, S .; Ramakrishna Biomacromolecules. , 7, 1049 (2006), it is described that burst release can be suppressed by producing nanofibers composed of core (bovine serum albumin) / shell (poly ⁇ -caprolactone).
  • nanofibers were prepared by electrospinning an emulsion consisting of a bovine serum albumin aqueous solution containing a nonionic surfactant and a poly (lactic acid-caprolactone) solution, and the release behavior was examined. What has been done is described and that the initial burst release was suppressed.
  • a fiber molded body made of an aliphatic polyester containing phosphatidylethanolamine and / or polyoxyethylene sorbitan fatty acid esters and a protein is not known.
  • the problem to be solved by the present invention is to provide a fiber molded body containing a protein, in which the initial burst release of the protein is suppressed and continuous sustained release property is imparted. It is also an object of the present invention to provide a fiber molded article made of fibers having excellent uniformity and having excellent self-supporting properties.
  • the inventors of the present invention have made extensive studies to solve the above problems, and as a result, have found that these problems can be solved by adding a specific surfactant.
  • the present invention is a fiber molded body comprising aliphatic polyester, protein, phosphatidylethanolamine and / or polyoxyethylene sorbitan fatty acid esters, and comprising fibers having an average fiber diameter of 0.05 to 50 ⁇ m.
  • the fiber molded product containing at least phosphatidylethanolamine contains the protein in the fiber, but does not exist on the fiber surface. As a result, the initial burst release of the protein is suppressed and continued. This is advantageous in that it has a sustained release property.
  • the fiber molded body containing at least polyoxyethylene sorbitan fatty acid esters has no bead-like fibers and a uniform fiber diameter, it is advantageous in that it has good self-supporting properties and excellent handling properties.
  • the bead-like fiber referred to here is a fiber having a fiber diameter portion smaller than 1 ⁇ 2 of the maximum fiber diameter in one fiber.
  • bead-like fibers do not exist means that, for example, when 100 fibers are randomly observed with an electron microscope, 90 or more are not bead-like fibers. If the bead-like fibers are present and the uniformity of the fiber molded body is lowered, the fiber molded body becomes fragile, which is not preferable.
  • FIG. 1 is an electron micrograph of the fiber molded body of the present invention produced in Example 9.
  • FIG. 2 is an electron micrograph of the fiber molded body produced in Comparative Example 5.
  • the fiber molded body refers to a three-dimensional molded body in which one or a plurality of obtained fibers are laminated and woven, knitted, or formed by other methods.
  • a specific form of the fiber molded body for example, a nonwoven fabric can be mentioned.
  • tubes, meshes and the like processed based thereon can be preferably used in the field of regenerative medicine, and are included in the fiber molded body.
  • the average fiber diameter of the fiber molded body of the present invention is 0.05 to 50 ⁇ m. An average fiber diameter of less than 0.05 ⁇ m is not preferable because the strength of the fiber molded body cannot be maintained. An average fiber diameter larger than 50 ⁇ m is not preferable because the specific surface area of the fiber is small.
  • the average fiber diameter is 0.2 to 30 ⁇ m.
  • a fiber diameter means the diameter of a fiber cross section.
  • the shape of the fiber cross section is not limited to a circle, and may be an ellipse or an irregular shape. With respect to the fiber diameter in this case, the average of the length in the major axis direction and the length in the minor axis direction of the ellipse is calculated as the fiber diameter. When the fiber cross section is neither circular nor elliptical, the fiber diameter is calculated by approximating a circle or ellipse.
  • the aliphatic polyester used in the present invention is preferably a bioabsorbable (also referred to as biodegradable) polymer.
  • bioabsorbable polymers examples include polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone, polyglycerol sebacic acid, polyhydroxyalkanoic acid, polybutylene succinate, and derivatives thereof. .
  • it is at least 1 sort (s) chosen from the group which consists of polyglycolic acid, polylactic acid, polycaprolactone, and those copolymers.
  • the most preferable are polylactic acid and a polylactic acid-glycolic acid copolymer. is there.
  • the copolymer of polylactic acid has few monomer components which provide elasticity.
  • the monomer component imparting such stretchability includes caprolactone monomer, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,2-butanediol, 1,4-butanediol, polycaprolactone diol, poly Examples thereof include soft components such as alkylene carbonate diol and polyethylene glycol unit. These soft components are preferably less than 50% by weight of the polymer. When there is more soft component than this, it becomes easy to lose self-supporting property, and it becomes a fiber molded body which is too soft and difficult to handle.
  • Monomers constituting the polymer in polylactic acid include L-lactic acid and D-lactic acid, but are not particularly limited.
  • the optical purity or molecular weight of the polymer there are no particular restrictions on the optical purity or molecular weight of the polymer, the composition ratio of the L-form and the D-form, and the arrangement, but a polymer having many L-forms is preferred.
  • a stereocomplex of poly L lactic acid and poly D lactic acid may be used.
  • the molecular weight of the aliphatic polyester used in the present invention is 1 ⁇ 10 3 to 5 ⁇ 10 6 , preferably 1 ⁇ 10 4 to 1 ⁇ 10 6 , more preferably 5 ⁇ 10 4 to 5 ⁇ 10 5 . is there.
  • the terminal structure of aliphatic polyester and the catalyst which polymerizes aliphatic polyester can be selected arbitrarily.
  • the fiber molded body of the present invention other polymers and other compounds may be used in combination as long as the purpose is not impaired.
  • polymer copolymerization polymer blending, compound mixing.
  • Such an aliphatic polyester is preferably highly pure, and in particular, it should have fewer residues such as additives, plasticizers, residual catalysts, residual monomers, and residual solvents used in molding and post-processing. preferable.
  • the fiber molded body of the present invention contains 0.1 to 100 parts by weight of protein with respect to 100 parts by weight of aliphatic polyester.
  • the protein content in the fiber molded body is reduced, and the effect based on the properties of the protein is not exhibited.
  • the protein content is more than 100 parts by weight, the durability of the fiber molded body itself is exceeded. Is not preferable.
  • the preferred content is 0.2 to 50 parts by weight, and more preferably 0.5 to 20 parts by weight.
  • the protein used in the present invention is not particularly limited. For example, enzymes such as asparaginase, catalase, and superoxide desmutase, hemoglobin, serum albumin, transport proteins such as low density lipoprotein, actin, and myosin are typical.
  • the protein used in the present invention may be derived from an animal or may be derived from a gene recombination technique. Human origin is more preferable if derived from animals. Moreover, the protein produced by the gene recombination technique may be a modified amino acid sequence.
  • the fiber molded body of the present invention contains 0.01 to 20 parts by weight of phosphatidylethanolamine and polyoxyethylene sorbitan fatty acid esters with respect to 100 parts by weight of aliphatic polyester (phosphatidylethanolamine or polyoxyethylene sorbitan). Including the case of containing only one of the fatty acid esters).
  • aliphatic polyester phosphatidylethanolamine or polyoxyethylene sorbitan
  • a protein is not included or a uniform fiber molded body cannot be stably obtained, and it is more than 20 parts by weight.
  • the durability of the fiber molded body itself is undesirably lowered.
  • a preferable content is 0.02 to 15 parts by weight, and more preferably 0.05 to 10 parts by weight.
  • the phosphatidylethanolamine used in the present invention may be extracted from animal tissue or artificially synthesized.
  • examples of such phosphatidylethanolamine include L- ⁇ -dimyristoyl phosphatidylethanolamine, L- ⁇ -dimyristoyl phosphatidylethanolamine, L- ⁇ -dilauroyl phosphatidylethanolamine, L- ⁇ -distearoyl phosphatidylethanolamine, L- ⁇ -dioleoylphosphatidylethanolamine, L- ⁇ -dilinoleoylphosphatidylethanolamine, L- ⁇ -dielcoyl phosphatidylethanolamine, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine Is mentioned.
  • polyoxyethylene sorbitan fatty acid esters used in the present invention examples include polyoxyethylene (20) sorbitan monolaurate (Tween (registered trademark, the same shall apply hereinafter) 20), polyoxyethylene (20) sorbitan monopalmitate (Tween 40). ), Polyoxyethylene (20) sorbitan monostearate (Tween 60), polyoxyethylene (20) sorbitan tristearate (Tween 65), polyoxyethylene (20) sorbitan monooleate (Tween 80), polyoxyethylene (20) Examples include sorbitan trioleate (Tween 85), polyoxyethylene (6) sorbitan tetraoleate, and polyoxyethylene (30) sorbitan tetraoleate.
  • one feature is that the protein is not present on the fiber surface of the fiber molded body.
  • X-ray photoelectron Spectroscopy abbreviated as XPS (X-ray Photoelectron Spectroscopy) or ESCA (Electron Spectroscopy for Chemical Analysis), Time-of-Flight Secondary Ion Mass Spectrometer (Time-of-flight second-Sensor) (TEM) or the like can be used.
  • XPS X-ray Photoelectron Spectroscopy
  • ESCA Electrodectron Spectroscopy for Chemical Analysis
  • TEM Time-of-Flight Secondary Ion Mass Spectrometer
  • TEM Time-of-flight second-Sensor
  • the nitrogen atom quantity N (at%) value derived from the protein is observed by ESCA measurement of the fiber molded body. That is, in the present invention, “the protein is encapsulated in the fiber but not on the fiber surface” means that the nitrogen atom quantity N (at%) value derived from the protein is measured by ESCA measurement of the fiber molded body of the present invention. That is not observed.
  • the “fibre-molded body surface” means a region to be measured by the analysis method, for example, a region from the outermost surface to 10 nm.
  • the fiber molded body of the present invention comprises long fibers.
  • the long fiber specifically refers to a fiber molded body that is formed without adding a step of cutting the fiber in the process from spinning to processing into a fiber molded body.
  • the electrospinning method, the spunbond method Although it can be formed by a melt blow method or the like, an electrospinning method is preferably used.
  • the electrospinning method is a method of obtaining a fiber molded body on an electrode by applying a high voltage to a solution in which a polymer is dissolved in a solvent.
  • the steps include a step of producing a solution by dissolving a polymer in a solvent, a step of applying a high voltage to the solution, a step of ejecting the solution, and evaporating the solvent from the ejected solution to form a fiber molded body.
  • the total thickness of the fiber molded body is not particularly limited, but is preferably 25 ⁇ m to 500 ⁇ m, more preferably 50 to 200 ⁇ m.
  • the spinning solution in the present invention is preferably an emulsion composed of an organic solvent solution of aliphatic polyester and an aqueous solution of protein.
  • the concentration of the aliphatic polyester in the organic solvent solution of the aliphatic polyester is preferably 1 to 30% by weight. If the concentration of the aliphatic polyester is lower than 1% by weight, it is difficult to form a fiber molded body, which is not preferable. Moreover, when higher than 30 weight%, the fiber diameter of the obtained fiber molded object becomes large and is unpreferable.
  • a more preferable concentration of the aliphatic polyester in the organic solvent solution is 2 to 20% by weight.
  • Such organic solvents may be used alone or in combination with a plurality of solvents.
  • the organic solvent used in the present invention is not particularly limited as long as it can dissolve an aliphatic polyester and can form an aqueous solution and an emulsion of protein and evaporate at the spinning stage to form fibers.
  • Examples include chloroform, 2-propanol, toluene, benzene, benzyl alcohol, dichloromethane, carbon tetrachloride, cyclohexane, cyclohexanone, trichloroethane, methyl ethyl ketone, ethyl acetate, or a mixed solvent of these organic solvents.
  • a solvent such as dimethylformamide, N, N-dimethylacetamide, acetonitrile, N-methyl-2-pyrrolidinone, N-methylmorpholine-N-oxide, 1,3-dioxolane may be contained. Among these, it is preferable to use dichloromethane from handling property and physical property.
  • the protein concentration in the aqueous protein solution used in the present invention is preferably 0.5 to 50% by weight.
  • the protein concentration is lower than 0.5% by weight, the protein content in the fiber molded body is lowered, and the effect based on the properties of the protein is not exhibited, which is not preferable.
  • a more preferable concentration of the protein in the aqueous solution is 1 to 40% by weight.
  • the aqueous solvent of the protein aqueous solution used in the present invention is not particularly limited as long as it can dissolve the protein and can form an emulsion with an organic solvent solution of an aliphatic polyester and evaporate at the spinning stage to form a fiber. Not.
  • physiological saline or various buffer solutions can be used.
  • a pharmaceutically acceptable protein stabilizer or additive may be added.
  • the phosphatidylethanolamine and polyoxyethylene sorbitan fatty acid esters used in the present invention may be added to and mixed with either an organic solvent solution of an aliphatic polyester or an aqueous solution of a protein, but in terms of forming a uniform solution, It is preferably dissolved in an organic solvent solution of an aliphatic polyester.
  • the mixing ratio of the aliphatic polyester organic solvent solution obtained above and the protein aqueous solution is not particularly limited as long as a stable emulsion is formed, but (protein aqueous solution) / (aliphatic polyester).
  • (Organic solvent solution) (volume ratio) is preferably 1/100 to 1/2, and more preferably 1/50 to 1/4. If (protein aqueous solution) / (aliphatic polyester organic solvent solution) (volume ratio) is less than 1/100, the protein content in the fiber molded product is lowered, and the effect based on the properties of the protein is not exhibited. If (protein aqueous solution) / (aliphatic polyester organic solvent solution) (volume ratio) is larger than 1/2, the emulsion becomes unstable, which is not preferable.
  • the emulsion solution is preferably a W / O emulsion solution.
  • a surfactant for forming a W / O emulsion a surfactant having an HLB value in the range of 3 to 8 is preferred.
  • O emulsions can be prepared, thereby obtaining uniform fiber shaped bodies.
  • a method for preparing an emulsion by mixing an organic solvent solution of an aliphatic polyester and an aqueous protein solution is not particularly limited, and ultrasonic waves and various stirring methods can be used.
  • the stirring method high-speed stirring such as a homogenizer, stirring methods such as an attritor and a ball mill can be used. Of these, a dispersion method using ultrasonic treatment is preferable.
  • an spinning solution by forming an emulsion with an organic solvent and an aqueous protein solution and then adding an aliphatic polyester.
  • a step of applying a high voltage to the emulsion spinning solution, a step of ejecting the emulsion spinning solution, and a step of evaporating the solvent from the ejected emulsion spinning solution to form a fiber molded body will be described.
  • an emulsion spinning solution comprising an organic solvent solution of an aliphatic polyester containing phosphatidylethanolamine and / or polyoxyethylene sorbitan fatty acid esters and an aqueous solution of protein is ejected, and the fiber molded body is ejected. Therefore, it is necessary to apply a high voltage to the emulsion spinning solution.
  • the method of applying a voltage is not particularly limited as long as the emulsion spinning solution is ejected to form a fiber molded body. However, the method of applying an voltage by inserting an electrode into the emulsion spinning solution, or the spinning solution ejection There is a method of applying a voltage to the nozzle.
  • an auxiliary electrode can be provided.
  • the value of the applied voltage is not particularly limited as long as the fiber molded body of the present invention is formed, but a range of 5 to 50 kV is usually preferable.
  • the applied voltage is lower than 5 kV, the spinning solution is not ejected and a fiber molded body is not formed, which is not preferable.
  • the applied voltage is higher than 50 kV, discharge is generated from the electrode toward the ground electrode, which is not preferable. More preferably, it is in the range of 10 to 30 kV.
  • the desired applied voltage may be generated by any known method.
  • the solvent used was volatilized immediately after the emulsion spinning solution consisting of an organic solvent solution of aliphatic polyester containing phosphatidylethanolamine and / or polyoxyethylene sorbitan fatty acid esters and an aqueous solution of protein was ejected.
  • a fiber molded body is formed. Ordinary spinning is performed at room temperature in the atmosphere, but when volatilization is insufficient, it can be performed under negative pressure or in a high-temperature atmosphere.
  • the spinning temperature depends on the evaporation behavior of the solvent and the viscosity of the spinning solution, but is usually in the range of 0 to 50 ° C.
  • the method for eliminating the charge of the fiber molded body is not particularly limited, but a preferable method is a method for eliminating the charge with an ionizer.
  • the ionizer is a device that can generate ions by a built-in ion generator and discharge the charges to the charged material to eliminate the charge of the charged material.
  • a preferable ion generator that constitutes an ionizer used in the method for producing a fiber molded body of the present invention an apparatus that generates ions by applying a high voltage to a built-in discharge needle can be given.
  • the step of accumulating the fiber molded body due to charge disappearance will be described.
  • the method for accumulating the fiber molded body by the loss of electric charge is not particularly limited, but a normal method includes a method for losing the electrostatic force of the fiber molded body due to the loss of electric charge and dropping and accumulating it by its own weight. Moreover, you may perform the method of attracting
  • the processing of laminating a cotton-like fiber structure on the surface of the fiber molded body of the present invention or forming a sandwich structure with the cotton-like structure sandwiched between the fiber molded bodies of the present invention is an object of the present invention.
  • coating treatment for imparting antithrombogenicity and surface coating with an antibody or a physiologically active substance can be optionally performed.
  • the coating method and treatment conditions at this time, and the chemicals used for the treatment can be arbitrarily selected within a range that does not damage the fiber structure and impair the purpose of the present invention.
  • a drug can be optionally contained inside the fiber of the fiber molded body of the present invention. In the case of molding by the electrospinning method, the drug used is not particularly limited as long as it is soluble in an organic solvent or an aqueous solution and does not impair the physiological activity by dissolution.
  • drugs may be tacrolimus or its analogs, statins, or taxane anticancer agents, protein preparations, nucleic acid drugs.
  • medical agent may be included and a metal, polysaccharide, a fatty acid, surfactant, and a volatile solvent tolerance microorganism may be sufficient.
  • Fluorescence microscope observation FITC-BSA (Albumin, Fluorescein isothiocyanate conjugate bovine) was used as a fluorescent label to confirm the dispersibility of the protein in the fiber molded body.
  • N (at%) value on fiber surface Detection was performed at a photoelectron take-off angle of 45 degrees using VG company ESCALAB 200 as the photoelectron spectrometer and MgK ⁇ ray (1253.6 eV) as the X-ray. 4).
  • Spinning uniformity A three-stage evaluation was performed regarding the extent of the spinning solution splashing from the spinning nozzle and the state in which the fiber assembly was deposited on the collector.
  • ⁇ Spattering liquid is widely scattered and fiber aggregates are uniformly deposited on the collector.
  • ⁇ Spinning liquid is scattered moderately and the fiber aggregates are uniformly deposited on the collector, but the deposition area is small. .
  • X Scattering of the spinning solution is narrow, and the fiber aggregate is not uniformly deposited on the collector. 5.
  • Spinning stability This means the stability of the tailor cone, and was evaluated according to the cleaning frequency in three stages.
  • ⁇ Needless cleaning of the spinning nozzle
  • ⁇ Moderate frequency of cleaning the spinning nozzle
  • ⁇ Needed to frequently clean the spinning nozzle
  • Self-supporting The handling property of the obtained fiber assembly was evaluated in two stages.
  • ⁇ Preparation of emulsion spinning solution The aqueous solution of the protein and the organic solvent solution of the aliphatic polyester is (protein aqueous solution) / (the organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (4 parts by weight of the protein with respect to 100 parts by weight of the polylactic acid) ) And mixing with sonication to form a uniform emulsion.
  • ⁇ Electrospinning> Using the emulsion spinning solution, spinning was performed by an electrospinning method at a humidity of 25% or less to obtain a sheet-like fiber molded body. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 15 kV, and the distance from the ejection nozzle to the flat plate was 20 cm.
  • the flat plate was used as a cathode during spinning.
  • the average fiber diameter of the obtained fiber molded body was 2.0 ⁇ m.
  • FITC-BSA was uniformly dispersed in the fiber molded body.
  • the number of carbon atoms C (at%) on the surface was 61.8
  • the number of oxygen atoms O (at%) was 38.2
  • the number of nitrogen atoms was N (at%) was 0, and the fiber surface No nitrogen atom number N (at%) was observed, and it was found that no protein was present on the fiber surface and it was encapsulated.
  • Example 1 A fiber molded body was prepared in the same manner as in Example 1 except that phosphatidylethanolamine dioleo oil (manufactured by NOF Corporation) was not included. The average diameter of the fiber molded body constituting the obtained fiber structure was 11.2 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • Example 2 Dissolve 3.3 parts by weight of L- ⁇ -dilauroylphosphatidylethanolamine (manufactured by NOF Corporation) and 100 parts by weight of polylactic acid (PL18, manufactured by Purac) so that the polylactic acid is 12% (w / v) in dichloromethane.
  • a fiber molded body was prepared in the same manner as in Example 1 except that a uniform solution was prepared.
  • the average fiber diameter of the obtained fiber molded body was 0.8 ⁇ m.
  • FITC-BSA was uniformly dispersed in the fiber molded body.
  • the surface composition analysis it was found that no protein was present on the fiber surface and it was encapsulated.
  • Example 3 Dissolve 3.3 parts by weight of L- ⁇ -diethylphosphatidylethanolamine (manufactured by NOF Corporation) and 100 parts by weight of polylactic acid (PL18, manufactured by Purac) so that the polylactic acid is 12% (w / v) in dichloromethane.
  • a fiber molded body was prepared in the same manner as in Example 1 except that a uniform solution was prepared. The average fiber diameter of the obtained fiber molded body was 1.1 ⁇ m.
  • FITC-BSA was uniformly dispersed in the fiber molded body.
  • the surface composition analysis it was found that no protein was present on the fiber surface and it was encapsulated.
  • ⁇ Preparation of protein solution Albumin (bovine serum-derived corn fraction V, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a phosphate buffer solution (manufactured by Invitrogen, 1X pH 7.4) so as to be 10 wt%, and FITC-BSA is used as a fluorescent label.
  • a phosphate buffer solution manufactured by Invitrogen, 1X pH 7.4
  • FITC-BSA is used as a fluorescent label.
  • the protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid).
  • Example 4 ⁇ Preparation of organic solvent solution of aliphatic polyester> 1 part by weight of polyoxyethylene (20) sorbitan trioleate (Tween 85) (manufactured by Wako Pure Chemical Industries, Ltd.) and 100 parts by weight of polylactic acid (PL18, manufactured by Purac) are mixed with dichloromethane so that the polylactic acid becomes 12% (w / v). To obtain a homogeneous solution.
  • ⁇ Preparation of protein solution Albumin (bovine serum-derived corn fraction V, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a phosphate buffer solution (manufactured by Invitrogen, 1X pH 7.4) so as to be 10 wt%, and FITC-BSA is used as a fluorescent label.
  • a phosphate buffer solution manufactured by Invitrogen, 1X pH 7.4
  • FITC-BSA is used as a fluorescent label.
  • the protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid).
  • Example 5 A fiber molded body was prepared in the same manner as in Example 4 except that the electrospinning conditions were changed to a voltage of 15 kV and a spinning solution flow rate of 1.6 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. No bead-like fibers were observed in the obtained fiber molded product, and the average fiber diameter was 2.7 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • Example 6 ⁇ Preparation of organic solvent solution of aliphatic polyester> 1 part by weight of polyoxyethylene (20) sorbitan monooleate (Tween 80) (manufactured by Tokyo Chemical Industry) and 100 parts by weight of polylactic acid (PL18, manufactured by Purac) are added to dichloromethane so that the polylactic acid becomes 12% (w / v). To obtain a homogeneous solution.
  • Example 7 A fiber molded body was prepared in the same manner as in Example 6 except that the electrospinning conditions were changed to a voltage of 12 kV and a spinning solution flow rate of 1.2 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. No bead-like fibers were observed in the obtained fiber molded product, and the average fiber diameter was 4.6 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • Example 8 A fiber molded body was prepared in the same manner as in Example 7, except that the electrospinning conditions were changed to a spinning solution flow rate of 3.0 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. No bead-like fibers were observed in the obtained fiber molded product, and the average fiber diameter was 6.8 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • Example 9 ⁇ Preparation of organic solvent solution of aliphatic polyester> 1 part by weight of polyoxyethylene (20) sorbitan monolaurate (Tween 20) (manufactured by MP Biomedicals Inc) and 100 parts by weight of polylactic acid (PL18, manufactured by Purac) are 12% (w / v) of polylactic acid in dichloromethane. To prepare a homogeneous solution.
  • ⁇ Preparation of protein solution Albumin (bovine serum-derived corn fraction V, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a phosphate buffer solution (manufactured by Invitrogen, 1X pH 7.4) so as to be 10 wt%, and FITC-BSA is used as a fluorescent label.
  • a phosphate buffer solution manufactured by Invitrogen, 1X pH 7.4
  • FITC-BSA is used as a fluorescent label.
  • the protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid).
  • Example 10 A fiber molded body was prepared in the same manner as in Example 9 except that the electrospinning conditions were changed to the spinning solution flow rate of 3.0 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. No bead-like fibers were observed in the obtained fiber molded product, and the average fiber diameter was 2.7 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • Example 11 A fiber molded body was prepared in the same manner as in Example 9 except that the electrospinning conditions were changed to a voltage of 12 kV and a spinning solution flow rate of 1.2 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. No bead-like fibers were observed in the obtained fiber molded product, and the average fiber diameter was 4.3 ⁇ m. As a result of the fluorescence microscope observation, it was confirmed that FITC-BSA was uniformly dispersed in the fiber molded body.
  • ⁇ Preparation of protein solution Albumin (bovine serum-derived corn fraction V, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a phosphate buffer solution (manufactured by Invitrogen, 1X pH 7.4) so as to be 10 wt%, and FITC-BSA is used as a fluorescent label.
  • a phosphate buffer solution manufactured by Invitrogen, 1X pH 7.4
  • FITC-BSA is used as a fluorescent label.
  • the protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid).
  • Comparative Example 4 A fiber molded body was prepared in the same manner as in Comparative Example 3 except that the electrospinning conditions were changed to a voltage of 15 kV and a spinning solution flow rate of 1.6 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. Many bead-like fibers were observed in the obtained fiber molded body.
  • ⁇ Preparation of emulsion spinning solution> The protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid). 4 parts by weight) was mixed and sonicated to form a uniform emulsion.
  • the inner diameter of the ejection nozzle was 0.8 mm, the voltage was 15 kV, the spinning solution flow rate was 1.6 mL / h, and the distance from the ejection nozzle to the flat plate was 20 cm.
  • the flat plate was used as a cathode during spinning.
  • the spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. Many bead-like fibers were observed in the obtained fiber molded body.
  • An electron micrograph is shown in FIG. [Comparative Example 6] A fiber molded body was prepared in the same manner as in Comparative Example 5 except that the electrospinning conditions were changed to 12 kV.
  • the spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1.
  • Comparative Example 8 A fiber molded body was prepared in the same manner as in Comparative Example 7, except that the electrospinning conditions were changed to a voltage of 15 kV and a spinning solution flow rate of 3.0 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. Many bead-like fibers were observed in the obtained fiber molded body.
  • ⁇ Preparation of protein solution Albumin (bovine serum-derived corn fraction V, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a phosphate buffer solution (manufactured by Invitrogen, 1X pH 7.4) so as to be 10 wt%, and FITC-BSA is used as a fluorescent label.
  • a phosphate buffer solution manufactured by Invitrogen, 1X pH 7.4
  • FITC-BSA is used as a fluorescent label.
  • the protein aqueous solution prepared above and the organic solvent solution of the aliphatic polyester are (protein aqueous solution) / (organic solvent solution of aliphatic polyester) (volume ratio) is 1/20 (the protein is contained in 100 parts by weight of polylactic acid).
  • Comparative Example 10 A fiber molded body was prepared in the same manner as in Comparative Example 9 except that the electrospinning conditions were changed to a voltage of 12 kV and a spinning solution flow rate of 1.2 mL / h. The spinning uniformity, spinning stability, and self-supporting properties are shown in Table 1. Many bead-like fibers were observed in the obtained fiber molded body.
  • the fiber molded body of the present invention is excellent in sustained release of protein, and is useful for pharmaceutical and medical supplies, especially for organ surface and wound site protection materials, DDS carriers, coating materials, sealing materials, artificial dura mater, adhesion prevention materials, etc. It is.

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  • Engineering & Computer Science (AREA)
  • Textile Engineering (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nonwoven Fabrics (AREA)
  • Artificial Filaments (AREA)

Abstract

L'invention concerne un corps moulé et fibreux qui est formé de fibres contenant un polyester aliphatique, une protéine, un phosphatidyl éthanol amine et/ou un ester d'acide gras de polyoxyéthylène sorbitane, et dont le diamètre moyen de fibre est de 0,05 à 50 µm. Ce corps moulé et fibreux est caractérisé en ce qu'il présente d'excellentes caractéristiques en termes d'uniformité et de support autonome et/ou en ce qu'il présente une libération continue et prolongée qui est obtenue par la suppression de la libération brusque, initiale, de la protéine.
PCT/JP2012/056211 2011-03-03 2012-03-05 Corps moulé fibreux WO2012118236A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107007889A (zh) * 2017-02-23 2017-08-04 中国科学院长春应用化学研究所 一种术后防粘连高分子薄膜及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001181924A (ja) * 1999-09-30 2001-07-03 Isotis Bv 生物活性剤を有するポリマー
JP2005290610A (ja) * 2004-03-31 2005-10-20 Akihiko Tanioka 多糖類のナノスケールの繊維および成形体
WO2006022430A1 (fr) * 2004-08-26 2006-03-02 Teijin Limited Structure fibreuse contenant un phospholipide
JP2008137967A (ja) * 2006-12-04 2008-06-19 Canon Inc 吐出用液体及び吐出方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001181924A (ja) * 1999-09-30 2001-07-03 Isotis Bv 生物活性剤を有するポリマー
JP2005290610A (ja) * 2004-03-31 2005-10-20 Akihiko Tanioka 多糖類のナノスケールの繊維および成形体
WO2006022430A1 (fr) * 2004-08-26 2006-03-02 Teijin Limited Structure fibreuse contenant un phospholipide
JP2008137967A (ja) * 2006-12-04 2008-06-19 Canon Inc 吐出用液体及び吐出方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107007889A (zh) * 2017-02-23 2017-08-04 中国科学院长春应用化学研究所 一种术后防粘连高分子薄膜及其制备方法
CN107007889B (zh) * 2017-02-23 2020-07-07 中国科学院长春应用化学研究所 一种术后防粘连高分子薄膜及其制备方法

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