WO-2026094406-A1 - COMPOSITE PARTICLE COMPRISING CRYSTALLINE ORGANIC COMPOUND AND METHOD FOR PRODUCING SAME

Abstract

Provided are composite particles each obtained by compositing, on a core particle, a crystalline organic compound in the form of fine particles. The composite particles each comprise: a core particle; and crystalline organic compound particles that are present on the surface of the core particle and that contain a crystalline organic compound. The specific surface area of the composite particles is 0.0015-60 m 2 /g.

Inventors

• KONDO KEITA

Assignees

• 学校法人 名城大学

Dates

Publication Date

20260507

Application Date

20250829

Priority Date

20241031

Claims (16)

1. It is a composite particle, Nuclear particles and, Crystalline organic compound particles containing a crystalline organic compound are present on the surface of the aforementioned core particle, Equipped with, A composite particle having a specific surface area of 0.0015 m² /g or more and 60 m² /g or less.
2. The composite particle according to claim 1, wherein the average particle size of the crystalline organic compound particles is 4.0 μm or less.
3. The composite particle according to claim 2, wherein the average particle size of the crystalline organic compound particles is 1.0 μm or less.
4. The composite particle according to claim 3, wherein the average particle diameter of the crystalline organic compound particles is 0.60 μm or less.
5. The composite particle according to claim 1, wherein the specific surface area of the composite particle is 0.075 m² /g or more and 30 m² /g or less.
6. The composite particle according to claim 1, wherein the specific surface area of the composite particle is 0.10 m² /g or more and 10 m² /g or less.
7. The composite particle according to claim 1, wherein the mass ratio of the core particle to the crystalline organic compound particle (core particle:crystalline organic compound particle) is 100:1 or more and 1:5 or less.
8. The composite particle according to claim 1, wherein the molecular weight of the crystalline organic compound is 200 or more and 1,300 or less.
9. The composite particle according to claim 1, wherein the molecular weight of the crystalline organic compound is 350 or more and 720 or less.
10. The composite particle according to any one of claims 1 to 9, wherein the crystalline organic compound particles are particles obtained by recrystallizing amorphous organic compound particles by storing them under certain conditions for a predetermined period of time.
11. The composite particle according to claim 10, wherein the crystalline organic compound particles are obtained by storing the amorphous organic compound particles for one hour or more.
12. The composite particle according to claim 10, wherein the crystalline organic compound particles are obtained by storing them at a temperature at least 10°C lower than the glass transition temperature of the amorphous organic compound particles.
13. The composite particle according to any one of claims 1 to 9, wherein the core particle is one or more selected from the group consisting of crystalline cellulose, hydroxypropyl cellulose, and methylcellulose.
14. The composite particle according to any one of claims 1 to 9, wherein the crystalline organic compound particles are bonded together to form a porous layer with interparticle gaps.
15. A pharmaceutical composition comprising the composite particles described in any one of claims 1 to 9 or the crystalline organic compound.
16. A method for producing composite particles, A first step involves mechanically stirring and mixing a core particle and a first crystalline organic compound particle to promote the pulverization and amorphousization of the crystalline organic compound particle, thereby producing a first composite particle having amorphous organic compound particles derived from the first crystalline organic compound particle on the surface of the core particle. A second step involves storing the first composite particles under certain conditions to recrystallize the amorphous organic compound particles, thereby producing a second composite particle having recrystallized organic compound particles on its surface. Equipped with, A manufacturing method comprising carrying out the first and second steps such that the specific surface area of the second composite particle is 0.0015 m² /g or more and 60 m² /g or less.

Description

Composite particles comprising crystalline organic compounds and method for producing the same (Cross-reference of related applications) This application claims priority based on Japanese Patent Application No. 2024-192291, filed on 31 October 2024, and the contents of said Japanese Patent Application are incorporated herein by reference as constituting a part of this Specification. This specification relates to composite particles comprising crystalline organic compounds and methods for producing the same. Reducing crystalline organic compounds used as active ingredients in pharmaceuticals into microparticles, such as nanoparticles, can be effective from the perspective of bioavailability. Generally, nanoparticle technology includes methods for dispersing crystals of the active ingredient in water and crushing them into balls (Patent Document 1), and methods for crystallizing a drug dissolved in an organic solvent into microparticles (Patent Document 2). However, all of these methods require a medium such as water or an organic solvent. Therefore, in addition to the problem of residual organic solvents, there are energy costs for removing the medium, the effect of heat during drying on the active ingredients, and the risk of inactivation due to particle aggregation. Furthermore, when using ball grinding, metal contamination may occur. Also, finely particulated crystalline organic compounds can sometimes be difficult to handle from a formulation perspective, as they tend to aggregate easily. This specification provides a technology for producing composite particles in which crystalline organic compounds are compounded as fine particles on a core particle. Furthermore, this specification provides a novel crystalline organic compound material suitable, for example, as a raw material for pharmaceuticals. The inventors have conducted various studies on the amorphous transformation of crystalline powders and have found that by mechanically stirring and mixing nucleation particles with crystalline organic compound particles smaller than the nucleation particles, the crystalline organic compound particles can be pulverized and amorphous through the action of the nucleation particles accompanying the mechanical action of stirring and mixing, thereby generating amorphous organic compound particles from the crystalline particles. Furthermore, these in-situ generated amorphous organic compound particles can be attached to and deposited on the nucleation particles. The inventors have found that by adjusting the degree of amorphousness of amorphous organic compound particles, it is possible to crystallize the amorphous organic compound particles into particles of a desired size when the composite particles are stored under certain conditions. Based on this finding, this specification provides the following means. Furthermore, the inventors have discovered that by deliberately promoting the recrystallization of amorphous organic compound particles on the core particles, composite particles having fine crystalline organic compound particles on their surface can be obtained. Based on this discovery, this specification further provides the following means relating to composite particles and methods for producing them. [1] A method for producing composite particles, A step of producing a first composite particle having amorphous organic compound particles derived from the crystalline organic compound particles on the surface of the core particle, by mechanically stirring and mixing core particles and crystalline organic compound particles to promote the pulverization and amorphousization of the crystalline organic compound particles, A step of storing the first composite particles under certain conditions to recrystallize the amorphous organic compound particles to produce a second composite particle having recrystallized organic compound particles on its surface, Equipped with, A method for producing the first composite particles, comprising the step of adjusting the degree of amorphousness of the amorphous organic compound particles so that the recrystallized organic compound particles are of a desired size. [2] The manufacturing method according to [1], wherein the nucleus particles include particles having an amorphous stabilizing effect. [3] The manufacturing method according to [1] or [2], wherein the step of producing the second composite particle is to store the first composite particle in the presence of water vapor. [4] The manufacturing method according to [1] or [2], wherein the step of producing the second composite particle is to store the first composite particle in the presence of an organic solvent vapor. [5] The method for producing organic solvents according to [4], wherein the organic solvent vapor comprises the vapor of one or more organic solvents selected from organic solvents having a boiling point of 80°C or lower. [6] The manufacturing method according to any one of [1] to [5], wherein the step of p