Biodegradable particle and method for producing the same

Abstract

The present invention aims to provide a biodegradable particle capable of being molded without an aggregation or cohesion of the particles, capable of being carried or injected without clogging by an aggregation in a micro diameter tube such as of a catheter, needle or syringe mainly used in pharmaceutical and medical applications of which inner diameter is smaller than the particle size or in a blood vessel and capable of being smoothly degraded in a specified period of time so that degraded component can finally be absorbed or discharged in vitro. As means for solving the problem, the present invention provides a biodegradable particle characterized in that a compressive modulus of the particle in water saturated state is 10 MPa or less.

Description

TECHNICAL FIELD[0001]The present invention relates to a biodegradable spherical particle which can be carried through tubes having a micro diameter smaller than the particle size, such as of catheter, needle or injector which are pharmaceutical and medical devices.BACKGROUND ART[0002]In medical field, safety of therapy or minimum invasive therapy which is light in patient's pain has become important. Along with that, techniques for designing or synthesizing safer materials or techniques for administration in vivo have been developed. One of them is technique of therapy or administration of drug through a tube of small inner diameter. By being the inner diameter of the tube small, it became unnecessary to incise patient's body, and a pain accompanied by inserting the tube into body was also greatly reduced. Therapy by catheter is a marked example of that. Another one is a technology relating to a biodegradable or bioabsorbable material which is not left in the body. A sewing thread o...

AI Technical Summary

Benefits of technology

[0051]According to the present invention, as explained in the following, it is possible to provide a particle capable of not clogging by an aggregation in a micro diameter tube of devices such as a catheter, needle or syringe mainly used in pharmaceutical and medical applications or in a blood vessel and capable of recovering to original shape after passing the tube, and furthermore, not depending on indwelled site or indwelled environment, capable of being smoothly degraded after passing a specified period of time so that degraded component can finally be absorbed or discharged in vitro.BEST EMBODIMENT FOR CARRYING OUT THE INVENTION

[0052]The biodegradable particle of the present invention is a particle degradable by a chemical decomposition represented by hydrolysis or by an enzyme produced by a cell or a microorganism. Mainly, a hydrolyzable one is preferable. As starting materials used for the biodegradable particle, it is not especially limited, but may be any one of a natural polymers or an artificially synthesized polymers, and polyesters, polyethers, polyacid anhydrides, polypeptides, poly(α-cyanoacrylate)s polyacrylamides, poly(ortho esters), polyphosphazenes, polyamino acids, biodegradable polyurethanes, polycarbonates, polyiminocarbonates, nucleic acids, polysaccharides or the like are mentioned, and as concrete representative examples, gelatin, chitin, chitosan, dextran, gum ababic, alginic acid, starch, polylactic acid (hereafter, referred to as PLA), polyglycolic acid (hereafter, referred to as PGA), polylactic acid glycolic acid copolymer (hereafter, referred to as PLGA), hydroxy terminal poly(ε-caprolactone)-polyether, polycaprolactone, n-butyl cyanoacrylate, copolymer consisting of the above-mentioned polymer, etc., are mentioned.

[0053]As the first embodiment of the biodegradable particle of the present invention, since it is preferable that a material having an elasticity capable of passing through a micro diameter tube smaller than the particle size and capable of keeping a necessary strength in catheter tube or in blood vessel, etc., it is good that a compressive modulus in water saturated state is 10 MPa or less, to be 0.5 MPa or more and 10 MPa or less is preferable, to be 5 MPa or less is more preferable and to be 3 MPa or less is still more preferable. The water saturated state mentioned here means a state in which water content becomes constant for a material immersed in pure water of ordinary temperature. Whereas, to be constant in water content means, for a specified material, to be within 3% in weight change in several hours. A material having a compressive modulus exceeding 10 MPa in water saturated state is hard and not suitable as a material which is administrated by such as a microcatheter having a smaller tube than the particle diameter of the biodegradable particle.

[0054]The modulus characteristics are, for example, can be evaluated as follows.[Measuring Condition]

[0055]Compression tester: MCT-W500; Shimadzu Corp. (or, may be an instrument by which same result in same condition can be obtained.)

[0060]Based on a stress-strain curve obtained by this way, compressive modulus was determined by using the following equation.Compressive modulus(unit:MPa)=(δ2−δ1) / (ε2−ε1)

Problems solved by technology

However, there are following problems in the microparticle carrier consisting of polymer particle or the embolization material.

(2) In a tube of pharmaceutical and medical application devices such as catheter, needle or syringe, it may aggregate or its viscosity may increase to clog the tube.

In particular, the clogging frequently occurs when a particle smaller than inner diameter of the catheter is passed through.

(3) It may not be able to be carried to a desired site since it aggregates or its viscosity increases in a normal blood vessel on the way to an affected region.

(4) In case where it is used as an embolization material, since its material quality is hard and does not fit to cross-sectional shape of a blood vessel, although it may decrease blood flow, it may not be able to perfectly embolize.

(6) Since particle diameter is not appropriate, it may not be able to be indwelled at a desired site.

(7) In particular, in case of a particle which is smaller than inner diameter of the catheter, after passing through the catheter, since it is carried to an affected region in a crushed condition without recovering to its original shape, it may embolize at a farther site than desired.

However, in this technique, it was impossible to control softness and necessary strength for molding of the substrate polymer, and there were problems in at least one of the above-mentioned (1) to (5).

However, in this case, too, it was impossible to control softness and necessary strength for molding of the substrate polymer, and there were problems in at least one of the above-mentioned (1) to (5) and (7).