Thermogelling emulsions for sustained release of bioactive substances

• US 20040219175A1
• Filed: 12/31/2003
• Published: 11/04/2004
• Est. Priority Date: 12/31/2002
• Status: Abandoned Application

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: Lin, Xi-Zhang, Chang, Ken-Yuan, Kan, Pei, Hsieh, Ming-Fa
• Application Number:
  US10/748,192
• Publication Number:
  US 20040219175A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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

Abstract

The present invention relates to a temperature-sensitive thermogelling emulsion system for bioactive substances, consisting of a biodegradable temperature-sensitive aqueous phase polymer solution, and a pharmaceutically acceptable oil phase carrier, which embeds the bioactive substance. The oil phase carrier and the temperature-sensitive polymer solution are mixed mutually to produce the emulsion, and the emulsion is a liquid while the temperature is below the lower critical solution temperature (LCST) and reversibly transforms into a gel while the temperature is above said lower critical solution temperature. The emulsions are able to offer the controlled release without burst effect and afterward in a near zero order manner, as well as be non-invasively monitored post-implantation. The design of entrapment of the bioactive substances in the oily phase is also beneficial to preserve the bioactivity of the environment-sensitive substances.

Claims

1. A temperature-sensitive thermogelling emulsion delivery system, comprising:

a biodegradable temperature-sensitive aqueous phase polymer solution;

at least one bioactive substance, and

a pharmaceutically acceptable oil phase carrier, said oil carrier embeds said bioactive substance;

wherein

said oil phase carrier and said temperature-sensitive polymer solution are mixed mutually to form an emulsion, which is a liquid while at a temperature below a lower critical solution temperature (LCST) and transforms into a gel while the temperature of the emulsion is above said lower critical solution temperature (LCST).

2. The delivery system as claimed in claim 1, wherein said bioactive substance is embedded in said oil phase carrier by the means of dissolving, solid suspension or water/oil emulsification.

3. The delivery system as claimed in claim 1, wherein said temperature-sensitive polymer is selected from the group consisting of PEG-PLGA-PEG, PLGA-PEG-PLGA, PEG-PLGA and Poloxamor 407.

4. The delivery system as claimed in claim 3, wherein said PEG-PLGA-PEG is represented as formula (I):

5. The delivery system as claimed in claim 3, wherein said PEG-PLGA is represented as formula (II):

6. The delivery system as claimed in claim 3, wherein said Poloxamer 407 is represented below:

7. The delivery system as claimed in claim 1, wherein said physiologically accepted oil phase carrier is a fatty acid ester.

8. The delivery system as claimed in claim 7, wherein said physiologically accepted oil phase carrier is selected from the group consisting of lipiodol, medium chain triglyceride (MCT), soybean oil, sesame oil, castor oil, sunflower oil, mineral oil, vitamin E oil or a mixtire of them.

9. The delivery system as claimed in claim 1, wherein at least one bioactive substance is selected from the group consisting of chemical compound, protein, peptide, nucleic acid, polysaccharide, carbohydrate, lipid, glycoprotein and imaging agent.

10. The delivery system as claimed in claim 1, which is used for subcutaneous injection, intramuscular injection, intratumor injection or embolism agent.