Apatite-coated solid composition

• US 6,344,209 B1
• Filed: 10/20/1999
• Issued: 02/05/2002
• Est. Priority Date: 04/24/1997
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Saito, Kazuhiro, Hoshino, Tetsuo
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/403,414
• Time in Patent Office: 839 Days
• Field of Search: 424/426, 424/501, 424/457, 424/462, 424/463, 424/486, 424/489, 514/963, 514/772.3
• US Class Current: 424/426
• CPC Class Codes: A61F 2310/00796 Coating or prosthesis-covering structure made of a phosphorus-containing compound, e.g. hydroxy(l)apatite
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/501 Inorganic compounds
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/32 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

An apatite-coated solid composition which contains a biodegradable polymer and an apatite-coated solid composition which contains a biodegradable polymer and a medicinal substance have properties of sustained release and of osteoconductive activity.

Claims

1. A solid composition comprising a medicinal substance and an apatite-coated biodegradable polymer selected from the group consisting of polylactic acid, polyglycolic acid, a co-polymer of polylactic acid and polyglycolic acid, or a block polymer selected from polylactic acid, polyglycolic acid and polyethyleneglycol.

2. A solid composition according to claim 1, which comprises a sustained release preparation.

3. A solid composition according to claim 1, wherein the medicinal substance is hardly soluble in water.

4. A solid composition according to claim 1, wherein the medicinal substance is a medicine for treatment of bone diseases, an antibiotic, an anti-inflammatory agent or an anti-tumor agent.

5. A solid composition according to claim 1, wherein the apatite is a crystalline mineral substance which has (1) at least one cation selected from the group consisting of Na⁺, K⁺, H⁺, Ca²⁺, Sr²⁺, Ba²⁺, Pb²⁺, Zn²⁺, Cd²⁺, Mg²⁺, Fe²⁺, Mn²⁺, Ra²⁺, Al³⁺, Y³⁺, Ce³⁺, Nd³⁺, La³⁺ and Dy³⁺, and (2) at least one anion selected from the group consisting of SO₄²⁻

, CO₃²⁻

, HPO₄²⁻

, PO₃F²⁻

, PO₄³⁻

, AsO₄³⁻

, VO₄³⁻

, BO₃³⁻

, CrO₄³⁻

, SiO₄³⁻

, GeO₄³⁻

, (CO₃F)³⁻

and BO₄⁵⁻

.

6. A solid composition according to claim 1, wherein the apatite is hydroxyapatite.

7. A solid composition according to claim 1, wherein the apatite is phosphate apatite.

8. A solid composition according to claim 1, which is a microcapsule preparation.

9. A solid composition according to claim 1, wherein the apatite layer has a honeycomb structure.

10. A solid composition according to claim 1, wherein the apatite layer is about 1 nm to 50 μ

m.

11. The composition of claim 1 which is an injectable composition.

12. The composition of claim 1 wherein the polymer composition is a microcapsule preparation.

13. A method for producing an apatite-coated solid composition comprising a medicinal substance and a biodegradable polymer, which method comprises subjecting a substrate of a solid composition comprising a medicinal substance and a biodegradable polymer to immersion in an aqueous ion solution which is capable of forming an apatite.

14. A method according to claim 13, wherein the aquous ion solution is an aqueous solution which comprises at least one of Na⁺, K⁺, Mg⁺, Ca⁺, Cl⁻

, CO₃²⁻

;

PO₄³⁻

or SO₄²⁻

.

15. A method according to claim 13, wherein the temperature at the immersion is about 10 to 150°

C.