Composition containing nanoparticles containing water-soluble basic drug encpsulated therein

• US 20060269613A1
• Filed: 09/06/2004
• Published: 11/30/2006
• Est. Priority Date: 09/04/2003
• Status: Abandoned Application

• Current Assignee: NanoCarrier Co., Ltd.
• Original Assignee: NanoCarrier Co., Ltd.
• Inventors: Saito, Hiroyuki, Higashi, Sohei, Ogawa, Yasuaki, Tsuchiya, Chieko, Nagasaki, Shoko
• Application Number:
  US10/570,819
• Publication Number:
  US 20060269613A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/24 of the sex hormones

Abstract

A drug and a biodegradable polymer having at least one carboxyl group are encapsulated into nanoparticle which is formed by a block copolymer having a hydrophilic segment and a hydrophobic segment. This invention thus provides a drug-encapsulated nanoparticle which shows an increased in vivo drug-stability.

Claims

1. A composition containing drug-encapsulated nanoparticles each of which comprises three components of a) water-soluble and basic drug, b) a biodegradable polymer having at least one carboxyl group in a molecule, and c) a block copolymer having a hydrophilic segment and a hydrophobic segment.

2. A composition according to claim 1 wherein the water-soluble and basic drug is polypeptide.

3. A composition according to claim 1 wherein the water-soluble and basic drug is a water-soluble camptothecin derivative.

4. A composition according to claim 1 wherein the biodegradable polymer having carboxyl group is poly(lactic acid) or poly(lactic-coglycolic acid).

5. A composition according to claim 1 wherein the block copolymer comprises hydrophilic segment selected from the group consisting of poly(ethyleneoxide), poly(vinylalcohol), poly(vinylpyrrolidone), poly(N,N-dimethylacrylamide) and dextran, and hydrophobic segment selected from the group consisting of poly(β

-alkylaspartate), poly(β

-alkylaspartate-coaspartic acid), poly(β

-aralkylaspartate), poly(β

-aralkylaspartate-coaspartic acid), poly(γ

-alkylglutamate), poly(γ

-alkylglutamate-coglutamic acid), poly(γ

-aralkylglutamate), poly(γ

-alkylaspartamide), poly(γ

-alkylaspartamide-coaspartic acid), poly(β

-aralkylaspartamide), poly(β

-aralkylaspartamide-coaspartic acid), poly(γ

-alkylglutamide), poly(γ

-alkylglutamide-coglutamic acid), poly(γ

-aralkylglutamide), poly(γ

-aralkylglutamide-coglutamic acid), poly(lactide), poly(lactide-coglycolide), poly(ε

-caprolactone), poly(δ

-valerolactone) and poly(γ

-butyrolactone), and is capable of forming polymer micelle in an aqueous medium.

6. A composition according to claim 5 wherein the block copolymer has formula (I) or (II) as follows:

wherein R₁ and R₃ independently denote a hydrogen atom or a lower alkyl group which is either substituted by a fimctional group which may be protected or unsubstituted;

R₂ denotes a hydrogen atom, a saturated or unsaturated C₁-C₂₉ aliphatic carbonyl group or an aryl carbonyl group;

R₄ denotes a hydroxyl group, a saturated or unsaturated C₁-C₃₀ aliphatic oxy group or an aryl-lower alkyloxy group;

R₅ denotes a benzyl group, an alkylbenzyl group or an allyl group;

L₁ and L₂ independently denote a linker;

n denotes an integer of 10 to 2500; and

x and y are the same or different, and each denote an integer such that the total of x and y is 10 to 300, provided that x;

y falls in the range of 2-0;

8-10, and that, when x is not zero, the recurring units of x are each present at random.

7. A composition according to claim 6 wherein L₁ is selected from the group consisting of —

NH—

, —

O—

, —

CO—

, —

CH₂—

, —

O-Z-S-Z-, —

O-Z-NH— and

—

OCO-Z-NH—

(Z independently denotes a C₁-C₄ alkylene group), and L₂ is selected from the group consisting of —

OCO-Z-CO—

, —

NHCO-Z-CO— and

—

O-Z-NH—

(Z independently denotes a C₁-C₄ alkylene group).

8. A composition according to claim 1 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

9. A composition according to claim 2 wherein the block copolymer comprises hydrophilic segment selected from the group consisting of poly(ethyleneoxide), poly(vinylalcohol), poly(vinylpyrrolidone), poly(N,N-dimethylacrylamide) and dextran, and hydrophobic segment selected from the group consisting of poly(β

-alkylaspartate), poly(β

-alkylaspartate-coaspartic acid), poly(β

-aralkylaspartate), poly(β

-aralkylaspartate-coaspartic acid), poly(γ

-alkylglutamate), poly(γ

-alkylglutamate-coglutamic acid), poly(γ

-aralkylglutamate), poly(β

-alkylaspartamide), poly(β

-alkylaspartamide-coaspartic acid), poly(β

-aralkylaspartamide), poly(β

-aralkylaspartamide-coaspartic acid), poly(γ

-alkylglutamide), poly(γ

-alkylglutamide-coglutamic acid), poly(γ

-aralkylglutamide), poly(γ

-aralkylglutamide-coglutamic acid), poly(lactide), poly(lactide-coglycolide), poly(ε

-caprolactone), poly(δ

-valerolactone) and poly(γ

-butyrolactone), and is capable of forming polymer micelle in an aqueous medium.

10. A composition according to claim 3 wherein the block copolymer comprises hydrophilic segment selected from the group consisting of poly(ethyleneoxide), poly(vinylalcohol), poly(vinylpyrrolidone), poly(N,N-dimethylacrylamide) and dextran, and hydrophobic segment selected from the group consisting of poly(β

-alkylaspartate), poly(β

-alkylaspartate-coaspartic acid), poly(β

-aralkylaspartate), poly(β

-aralkylaspartate-coaspartic acid), poly(γ

-alkylglutamate), poly(γ

-alkylglutamate-coglutamic acid), poly(γ

-aralkylglutamate), poly(β

-alkylaspartamide), poly(β

-alkylaspartamide-coaspartic acid), poly(β

-aralkylaspartamide), poly(β

-aralkylaspartamide-coaspartic acid), poly(γ

-alkylglutamide), poly(γ

-alkylglutamide-coglutamic acid), poly(γ

-aralkylglutamide), poly(γ

-aralkylglutamide-coglutamic acid), poly(lactide), poly(lactide-coglycolide), poly(ε

-caprolactone), poly(δ

-valerolactone) and poly(γ

-butyrolactone), and is capable of forming polymer micelle in an aqueous medium.

11. A composition according to claim 4 wherein the block copolymer comprises hydrophilic segment selected from the group consisting of poly(ethyleneoxide), poly(vinylalcohol), poly(vinylpyrrolidone), poly(N,N-dimethylacrylamide) and dextran, and hydrophobic segment selected from the group consisting of poly(β

-alkylaspartate), poly(β

-alkylaspartate-coaspartic acid), poly(β

-aralkylaspartate), poly(β

-aralkylaspartate-coaspartic acid), poly(γ

-alkylglutamate), poly(γ

-alkylglutamate-coglutamic acid), poly(γ

-aralkylglutamate), poly(β

-alkylaspartamide), poly(β

-alkylaspartamide-coaspartic acid), poly(β

-aralkylaspartamide), poly(β

-aralkylaspartamide-coaspartic acid), poly(γ

-alkylglutamide), poly(γ

-alkylglutamide-coglutamic acid), poly(γ

-aralkylglutamide), poly(γ

-aralkylglutamide-coglutamic acid), poly(lactide), poly(lactide-coglycolide), poly(ε

-caprolactone), poly(δ

-valerolactone) and poly(γ

-butyrolactone), and is capable of forming polymer micelle in an aqueous medium.

12. A composition according to claim 2 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

13. A composition according to claim 3 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

14. A composition according to claim 4 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

15. A composition according to claim 5 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

16. A composition according to claim 6 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).

17. A composition according to claim 7 wherein a mixture of the drug a) and the biodegradable polymer b) is encapsulated into nanoparticle formed by the block copolymer c).