Biodegradable polymeric drug delivery system with adjuvant activity

• US 4,863,735 A
• Filed: 10/02/1986
• Issued: 09/05/1989
• Est. Priority Date: 02/19/1985
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Fox, James G., Niemi, Steven M., Langer, Robert S., Kohn, Joachim B.
• Primary Examiner(s): Moskowitz, Margaret
• Assistant Examiner(s): Draper, Garnette D.
• Application Number:
  US06/914,380
• Time in Patent Office: 1,069 Days
• Field of Search: 424/422, 424/426, 424/457, 424/458, 424/460-461, 424/218, 424/223, 424/88, 424/78, 424/89, 424/92, 514/885, 514/953, 604/891, 604/892, 604/894, 525/54.1
• US Class Current: 424/422
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: C08G 69/10 Alpha-amino-carboxylic acids polysuccinimides C08G73/1092

Abstract

An antigen delivery system utilizing a biodegradable polymer with good mechanical properties in combination with a material stimulating the immune system. The material having adjuvant activity may be polymer degradation products or an adjuvant which is contained within or bound to the polymer. In one embodiment, the polymer is formed from tyrosine dipeptides. Poly(CTTH-iminocarbonate) is a preferred tyrosine dipeptide polymer for constructing implantable delivery systems for antigenic material. The polymer is not an adjuvant in itself but degrades into products which stimulate the immune system. The tyrosine dipeptide can also be used as a conventional adjuvant. The advantages of the system are that a polymer can be used to form a biodegradable integral structure which is useful as both an implantable source of an antigen or other biologically active compound and as a control means for the rate of release of the biologically active compound, wherein the result is sustained, relatively constant delivery of antigen with simultaneous stimulation of the immune response.

Claims

1. An implantable, polymeric device for delivery of biologically active compounds, said device comprising at least one biologically active compound and a biodegradable, tyrosine dipeptide polymer said polymer degrading to form a product having adjuvant activity for said biologically active compound.

2. The device of claim 1 further comprising an additional material having adjuvant activity for said biologically active compound, said additional material being chemically bound to the tyrosine dipeptide polymer forming the device.

3. The device of claim 1 wherein the tyrosine dipeptide polymer having adjuvant activity is a degradation product of the biodegradable polymer forming the device.

4. The device of claim 1 wherein said tyrosine dipeptide polymer is selected from the group consisting of poly(CTTH-iminocarbonate) and poly(CTTE-iminocarbonate).

5. The device of claim 1 wherein said polymers are chemically structured to degrade over a specific period of time.

6. The device of claim 1 wherein said tyrosine dipeptide polymer encapsulates the biologically active compound.

7. The device of claim 1 wherein the biologically active compound is dispersed within the tyrosine dipeptide polymer.

8. The device of claim 1 wherein said biologically active compound is selected from the group consisting of antigens, immunomodulators, drugs, inorganic compounds, nucleic acids, lipids and saccharides.

9. The device of claim 1 wherein the tyrosine dipeptide polymer further encapsulates a material having adjuvant activity for said biologically active compound, said material being selected from the group consisting of complete Freund'"'"'s adjuvant, muramyl acid, and tyrosine and tyrosine derivatives.

10. A biodegradable device for the controlled release of at least one biologically active compound, said device comprising a tyrosine dipeptide polymer and at least one biologically active compound, which device, when implanted into a host, controllably releases the biologically active compound while simultaneously degrading to form a compound having adjuvant activity for the controllably released, biologically active compound.

11. A biodegradable device as in claim 10 further containing therein an additional material having adjuvant activity.

12. A biodegradable device as in claim 11 wherein said additional material is selected from the group consisting of Freund'"'"'s adjuvant, muramyl acid, tyrosine and tyrosine derivatives.