Medical composition and medical kit

• US 9,642,938 B2
• Filed: 06/26/2009
• Issued: 05/09/2017
• Est. Priority Date: 06/27/2008
• Status: Active Grant

• Current Assignee: National Cerebral And Cardiovascular Center, Osaka City University
• Original Assignee: Japan Health Sciences Foundation, Osaka City University
• Inventors: Fukumoto, Shinya, Nishizawa, Yoshiki, Okada, Masahiro, Koyama, Hidenori, Furuzono, Tsutomu
• Primary Examiner(s): Chen, Shin Lin
• Application Number:
  US13/000,838
• Publication Number:
  US 20110104292A1
• Time in Patent Office: 2,874 Days
• Field of Search: 424 7808, 424 931, 424490
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 27/32 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body

Abstract

In order to provide (i) a medical composition that has a strong angiogenic effect, has low invasiveness to a body of a patient, and is easy to administer to a living subject and (ii) a medical kit using a medical composition, the medical composition includes: a carrier in a particle form, the carrier having (a) a support made from a bioabsorbable polymer and (b) a surface layer made from hydroxyapatite and provided on the support; and cells provided on a surface of the carrier.

Claims

1. A medical composition for injection, the composition comprising:

a carrier in particle form, the carrier having (i) a support made from a bioabsorbable polymer particle and (ii) a surface layer made from hydroxyapatite nanocrystal particles, which have diameters of 25 nm to 500 nm, and provided on the support, wherein the particle diameter of the carrier is not less than 10 μ

m and not greater than 200 μ

m; and

a sufficient number of cells, which are effective to generate new blood vessels in a living subject, said cells being adhered directly onto the surface layer of the carrier by adhesive ability of said cells by mixing said carrier and said cells in such a manner that the number, per carrier, of said cells to be mixed is less than or equal to 1×

10¹⁰;

wherein the composition does not contain gelatin,

wherein the ratio by weight of said carrier to said cells is from 1/10 to 10/1, and

wherein said cells are myelomonocytic cells.

2. The medical composition according to claim 1, wherein the carrier has a porous structure.

3. The medical composition according to claim 1, wherein the bioabsorbable polymer is at least one selected from the group consisting of:

polylactic acid, polyglycolic acid, polyethylene glycol, propylene glycol, polyhydroxybutylate, polycarbonate, polyamide, cellulose, chitin, chitosan, starch, polyglutamic acid, polydioxanone, cyanoacrylate polymers, polycaprolactone, synthetic polypeptides, hyaluronic acid, polymalic acid, poly butylene succinate, and copolymers of any combination thereof.

4. The medical composition according to claim 1, further comprising angiogenesis cytokine provided on the surface of the carrier.

5. The medical composition according to claim 4, wherein the angiogenesis cytokine is at least one selected from the group consisting of:

acidic fibroblast growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, platelet-induced growth factor, tumor necrosis factor, epidermal growth factor, angiopoietin, interleukin, hemangiopoietin, sonic hedgehog, transforming growth factor-beta, granulocyte-colony stimulating factor, macrophage-colony stimulating factor, stem cell factor, erythropoietin, thrombopoietin, and FMS-like tyrosine kinase ligand.

6. A medical kit, comprising:

a medical composition recited in claim 1; and

an injector for administering the medical composition to a living subject.

7. The medical composition according to claim 1, wherein fusion bonding between each hydroxyapatite nanocrystal particles is prevented.

8. A method of producing a medical composition, which does not contain gelatin, the method comprising mixing a carrier in particle form and a sufficient number of cells in such a manner that the number, per carrier, of said cells to be mixed is less than or equal to 1×

10¹⁰, the carrier having (i) a support made from a bioabsorbable polymer particle and (ii) a surface layer made from hydroxyapatite nanocrystal particles, which have diameters of 25 nm to 500 nm, and provided on the support;

wherein the particle diameter of the carrier is not less than 10 μ

m and not greater than 200 μ

m, and wherein the ratio by weight of said carrier to said cells is from 1/10 to 10/1 and said cells are myelomonocytic cells;

such that said sufficient number of cells, which are effective to generate new blood vessels in a living subject, are caused to adhere directly onto the surface layer of said carrier by adhesive ability of the cells.