# US 2016/0256566 A2 · Method for producing liposome encapsulating paclitaxel monoglycoside and/or docetaxel monoglycoside

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- Number: US 2016/0256566 A2
- Document ID: US20160256566A2
- Status: Published application
- Kind: A2
- Application number: 14/386,855
- Filed: 2013-03-22
- Published: 2016-09-08
- Earliest claimed: 2013-03-22
- Assignees: Ensuiko Sugar Refining Co., Ltd.; Hiroki HAMADA; Ichiro FUJIWARA; National University Corporation Okayama University
- Applicants: Ensuiko Sugar Refining Co., Ltd.; National University Corporation Okayama University
- Inventors: Hiroki HAMADA; Ichiro FUJIWARA; Masaharu SENO; Tomonari KASAI; Tsukasa SHIGEHIRO; Masaharu MURAKAMI; Katsuhiko MIKUNI
- Web page: https://patentgrep.com/patent/US20160256566A2

## CPC

- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/6913: {the liposome being modified on its surface by an antibody}
- A61P 35/00: Antineoplastic agents
- C07K 16/32: against translation products of oncogenes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

In order to reduce the side effects of paclitaxel derivatives having excellent anti-cancer effects, an attempt was made to produce a liposome encapsulating paclitaxel derivatives such as paclitaxel monoglycosides and docetaxel monoglycosides. However, the introduction efficiency of paclitaxel derivatives, etc., into a liposome was poor, and this technique was not developed to a practical level. The present invention provides a method for producing a liposome encapsulating a paclitaxel monoglycoside and/or a docetaxel monoglycoside, and having an antibody specifically recognizing a cancer cell, the method comprising a step of bringing a liposome encapsulating a polyoxyethylene ester derivative, a lower alcohol, and a buffer or water into contact with a solution in which a paclitaxel monoglycoside and/or a docetaxel monoglycoside is dissolved in an alkylene glycol-containing buffer or water.

## Claims

### Claim 1

A method for producing a liposome encapsulating a paclitaxel monoglycoside and/or a docetaxel monoglycoside, and having an antibody specifically recognizing a cancer cell,
the method comprising a step of bringing a liposome encapsulating a polyoxyethylene ester derivative, a lower alcohol, and a buffer or water into contact with a solution in which a paclitaxel monoglycoside and/or a docetaxel monoglycoside is dissolved in an alkylene glycol-containing buffer or water.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the glycoside is at least one member selected from the group consisting of glucoside, galactoside, mannoside, xyloside, fructoside, rhamnoside, arabinoside, alloside, altroside, idoside, N-acetylglucosaminide, N-acetylgalactosaminide, taloside, glucuronide, glucosaminide, galactosaminide, and fucoside.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the polyoxyethylene ester derivative is polyoxyethylene castor oil ester.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the liposome contains DPPC and cholesterol in a material quantity ratio of 3:0.5 to 3.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the contact time is 10 to 40 minutes.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the cancer cell is a breast cancer cell.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the antibody specifically binds to HER2 protein.

### Claim 8

A liposome formulation encapsulating a solution liquid of paclitaxel monoglycoside and/or docetaxel monoglycoside, and has an antibody specifically recognizing a cancer cell.

### Claim 9 (depends on 8)

The liposome formulation according to claim 8, wherein the solution liquid of paclitaxel monoglycoside and/or docetaxel monoglycoside is a solution liquid in which paclitaxel and/or docetaxel monoglycoside is dissolved in a mixed solvent containing a polyoxyethylene ester derivative, a lower alcohol, and a buffer or water.

### Claim 10 (depends on 8)

The liposome formulation according to claim 8, wherein the glycoside is at least one member selected from the group consisting of glucoside, galactoside, mannoside, xyloside, fructoside, rhamnoside, arabinoside, alloside, altroside, idoside, N-acetylglucosaminide, N-acetylgalactosaminide, taloside, glucuronide, glucosaminide, galactosaminide, and fucoside.

### Claim 11 (depends on 8)

The liposome formulation according to claim 8, wherein the polyoxyethylene ester derivative is polyoxyethylene castor oil ester.

### Claim 12 (depends on 8)

The liposome formulation according to claim 8, wherein the liposome contains DPPC and cholesterol in a weight ratio of 3:0.5 to 3.

### Claim 13 (depends on 8)

The liposome formulation according to claim 8, wherein the mol of the paclitaxel monoglycoside per mol of total lipids of the liposome is 1.0 to 15.0×10−2.

### Claim 14 (depends on 8)

The liposome formulation according to claim 8, wherein the cancer cell is a breast cancer cell.

### Claim 15 (depends on 8)

The liposome formulation according to claim 8, wherein the antibody specifically binds to HER2 protein.