Drug Carrier

• US 20090136443A1
• Filed: 03/10/2006
• Published: 05/28/2009
• Est. Priority Date: 03/16/2005
• Status: Active Grant

• Current Assignee: JCR Pharmaceuticals Co., Ltd., Waseda University (Waseda University Educational Association)
• Original Assignee: Oxgenix Company Limited, Waseda University (Waseda University Educational Association)
• Inventors: Kanazawa, Hideo, Okamura, Yosuke, Hisamoto, Shuji, Kubota, Kohei, Takeoka, Shinji, Obata, Yosuke
• Granted Patent: US 8,647,613 B2
• Time in Patent Office: Days
• US Class Current: 424/78.270
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543

Abstract

The present invention has an object of providing a drug carrier capable of controlling in vivo pharmacokinetics. The present invention is directed to a drug carrier comprising a molecular assembly having a drug incorporated therein, and the above object can be achieved by a part of the amphiphilic molecules included in the molecular assembly being released from the molecular assembly by an external environmental change. The present invention utilizes a phenomenon that the hydrophilic-hydrophobic balance of the amphiphilic molecules is shifted toward hydrophilicity by an external environmental change and thus the amphiphilic molecules are freed from the molecular assembly.

Claims

1. A drug carrier comprising a molecular assembly having a drug incorporated therein, wherein in vivo pharmacokinetics are controlled by a part of amphiphilic molecules included in the molecular assembly being released from the molecular assembly by an external environmental change.

2. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules are represented by:

(drug)-(binding site A)-(hydrophilic part)-(binding site B)-(hydrophobic part) . . . 1 or

(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site C)-(drug) . . . 2

wherein, the binding site A is a site for binding the hydrophilic part and the drug, the binding site B is a site for binding the hydrophilic part and the hydrophobic part, and the binding site C is a site for binding the hydrophobic part and the drug.

3. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules are represented by:

(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part) . . . 3 or

(recognition site)-(binding site E)-(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part) . . . 4

wherein, the binding site B is a site for binding the hydrophilic part and the hydrophobic part, the binding site D is a site for binding the hydrophilic polymer and the hydrophilic part, and the binding site E is a site for binding the recognition site and the hydrophilic polymer; and

the in vivo pharmacokinetics are controlled by the amphiphilic molecules being released.

4. The drug carrier according to claim 1, wherein:

an amphiphilic molecule 5 represented by;

(recognition site)-(binding site E)-(hydrophilic part)-(binding site B)-(hydrophobic part) . . . 5

wherein, the binding site B is a site for binding the hydrophilic part and the hydrophobic part, and the binding site E is a site for binding the recognition site and the hydrophilic part is incorporated in the molecular assembly;

an amphiphilic molecule 3 represented by;

(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part) . . . 3

wherein, the binding site B is a site for binding the hydrophilic part and the hydrophobic part, and the binding site D is a site for binding the hydrophilic polymer and the hydrophilic part is introduced to the molecular assembly and in the state of inhibiting recognition of the amphiphilic molecule 5; and

the in vivo pharmacokinetics are controlled by the amphiphilic molecule 3 being released and thus the recognizing ability of the amphiphilic molecule 5 being appeared.

5. The drug carrier according to any one of claims 1 through 4, wherein the hydrophobic part of the releasable amphiphilic molecules includes 2 or greater and 18 or less hydrocarbon chains.

6. The drug carrier according to claim 5, wherein the binding site B of the releasable amphiphilic molecules includes an oligosaccharide chain, an oligopeptide chain, a polyester chain, a vinyl-based oligomer or a dendron structure.

7. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules are represented by:

(drug)-(binding site A)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part) . . . 6 or

(drug)-(binding site A)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part)-(binding site A)-(drug) . . . 7

wherein, the binding site A is a site for binding the drug and the hydrophilic part, and the binding site B is a site for binding the hydrophilic part and the hydrophobic part.

8. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules are represented by:

(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part) . . . 8,

(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part)-(binding site D)-(hydrophilic polymer) . . . 9,

(recognition site)-(binding site E)-(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part)-(binding site D)-(hydrophilic polymer) . . . 10, or

(recognition site)-(binding site E)-(hydrophilic polymer)-(binding site D)-(hydrophilic part)-(binding site B)-(hydrophobic part)-(binding site B)-(hydrophilic part)-(binding site D)-(hydrophilic polymer)-(binding site E)-(recognition site) . . . 11,

wherein, the binding site B is a site for binding the hydrophilic part and the hydrophobic part, the binding site D is a site for binding the hydrophilic polymer and the hydrophilic part, and the binding site E is a site for binding the recognition site and the hydrophilic polymer, and the in vivo pharmacokinetics are controlled by the amphiphilic molecules being released.

9. The drug carrier according to claim 1, wherein the hydrophilic part or the hydrophilic polymer of the releasable amphiphilic molecules includes polyethylene glycol.

10. The drug carrier according to claim 1, wherein the amphiphilic molecules are released from the molecular assembly by a dispersion of the molecular assembly being diluted.

11. The drug carrier according to claim 1, wherein the amphiphilic molecules are released from the molecular assembly by a temperature change.

12. The drug carrier according to claim 1, wherein the amphiphilic molecules are released from the molecular assembly by a concentration change of at least one selected from the group consisting of proton, alkaline metal ion and alkaline-earth metal ion.

13. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules include at least one type of bond selected from the group consisting of an ester bond, an amide bond, a urethane bond and a Schiff base in a site for binding the hydrophilic part and the hydrophobic part or in the hydrophobic part, and the amphiphilic molecules are released from the molecular assembly by hydrolysis of such a bond.

14. The drug carrier according to claim 1, wherein the releasable amphiphilic molecules include a disulfide bond in a site for binding the hydrophilic part and the hydrophobic part or in the hydrophobic part, and the amphiphilic molecules are released from the molecular assembly by reduction of the disulfide bond.

15. The drug carrier according to claim 1, wherein the drug incorporated in the molecular assembly is released by partial or entire destruction of a structure of the molecular assembly occurring due to the release of the amphiphilic molecules.

16. The drug carrier according to claim 1, wherein the molecular assembly has a structure of a vesicle.

17. The drug carrier according to claim 16, wherein the drug retained in an aqueous phase of the vesicle is released by partial or entire destruction of the structure of the vesicle occurring due to the release of the amphiphilic molecules.