Efficient microcapsule preparation and method of use

• US 5,238,714 A
• Filed: 10/02/1990
• Issued: 08/24/1993
• Est. Priority Date: 10/02/1990
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Yang, David, Wallace, Michael, Wallace, Sidney
• Primary Examiner(s): Stoll, Robert L.
• Assistant Examiner(s): COVERT, JOHN
• Application Number:
  US07/592,020
• Time in Patent Office: 1,057 Days
• Field of Search: 427/213.3, 427/213.36, 264/4.6
• US Class Current: 427/213.36
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 49/048 Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer
• CPC Class Codes: A61K 51/1251 micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: B01J 13/125 by evaporation of the solvent apparatus therefor B01J13/043
• CPC Class Codes: B01J 13/20 After-treatment of capsule walls, e.g. hardening

Abstract

The present invention relates to a method of preparing microcapsules suitable for encapsulation of therapeutic and diagnostic agents. The capsular coats are prepared from biodegradable polymers. In a particular aspect of the invention, surface charge of the polymeric material is altered by conjugation of an amino acid ester to the polymer, providing targeting to specific tissue cells. Encapsulation of hydrophilic radiodiagnostic agents in 1 μm capsules provides improved opacification. Encapsulation of cytotoxic agents in 100 μm capsules is useful in chemoembolization procedures.

Claims

1. A method of preparing amino-acid conjugated polymeric microcapsules capable of selective in vivo organ targeting, comprising the steps:

attaching an amino acid to poly-(D,L)-lactic acid to form a modified polymer;

combining water, organic solvent, an emulsifier and the modified polymer to form an emulsion;

agitating the mixture for a period of time sufficient to allow formation of microcapsules of about 0.5 to about 200 μ

m in size;

removing the organic solvent; and

collecting the microcapsules.

2. The method of claim 1 wherein the amino-acid conjugated polymeric microcapsule has a diameter of about 1-5 μ

m.

3. The method of claim 1 wherein the attached amino acid is tyrosine, tryptophan or methionine.

4. The method of claim 1 wherein the attached amino acid is phenylalanine.

5. The method of claim 1 wherein the amino acid conjugated polymeric microcapsule has a diameter of about 1-3 μ

m.

6. The method of claim 1 further comprising encapsulating a labeling agent.

7. The method of claim 6 wherein the labeling agent is meglumine diatrizoate.

8. The method of claim 1 further comprising encapsulating a therapeutic agent.

9. The method of claim 8 wherein the therapeutic agent is cisplatin, 5-fluorouracil or Tamoxifen.

10. The method of claim 8 wherein the therapeutic agent is a contrast agent.

11. The method of claim 1 wherein selective in vivo organ targeting is to the liver.

12. The method of claim 6 or 8 further comprising admixing the collected microcapsules with a pharmaceutical carrier suitable for intravascular administration.

13. The method of claim 1 wherein the organic solvent is acetone, ethylene chloride, chloroform, carbon tetrachloride or ethyl acetate.