Dehydrated hydrogel inclusion complex of a bioactive agent with flowable drug delivery system

Patent metadata

Field	Value
Publication number	US-9486531-B2
Application number	US-99595609-A
Country	US
Kind code	B2
Filing date	Jun 3, 2009
Priority date	Jun 3, 2008
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The invention provides a controlled release biodegradable polymer formulation adapted for administering bioactive agents such as therapeutic proteins to a patient through implantation of a bolus that forms a depot within the patient's body tissues. The formulation includes a dehydrated inclusion complex of the bioactive agent within a hydrogel, wherein the hydrogel can comprise a polymerized polyalkyleneglycolyl diacrylate, and, optionally, polyalkyleneglycolyl monoacrylates, including methacrylates. Alternatively, the hydrogel can comprise hyaluronic acid, chitosan, agarose, polyvinylacetate, polyvinylpyrrolide, or polyvinylalcohol nanoparticles. The bioactive agent can be a macromolecular material, such as a protein. A method of forming the inventive formulation is also provided, as well as a method for using the formulation in the treatment of a malcondition in a patient in need thereof.

First claim

What is claimed is:

1. A formulation comprising a dehydrated inclusion complex dispersed in a solution;
wherein the dehydrated inclusion complex comprises a protein stabilized within a hydrogel;
wherein the hydrogel comprises a polymerized polyethyleneglycolyl dimethacrylate having a molecular weight from about 500 Daltons to about 10,000 Daltons, and
wherein the solution consists of:
(i) a poly(lactide-glycolide) copolymer, and
(ii) N-methylpyrrolidone, dimethylacetamide, dimethylformamide, dimethylsulfoxide, a polyethyleneglycol, or a combination of two or more thereof.

2. The formulation of claim 1 , wherein the polyalkyleneglycol diacrylate has a molecular weight of about 750 Daltons to about 2,000 Daltons.

3. The formulation of claim 1 , wherein the protein is a monoclonal antibody.

4. The formulation of claim 1 , wherein the protein is insulin, human growth hormone, cetuximab, or bevacizumab.

5. The formulation of claim 1 , wherein the hydrogel particles are present in a concentration of about 5 wt % to about 50 wt %.

6. A formulation comprising:
(i) a dehydrated inclusion complex comprising a protein stabilized within a hydrogel; wherein the hydrogel comprises a polyalkyleneglycol diacrylate;
(ii) a biodegradable polymer consisting of a poly(lactide-glycolide) copolymer; and
(iii) N-methylpyrrolidone, dimethylacetamide, dimethylformamide, dimethylsulfoxide, a polyethyleneglycol, or a combination of two or more thereof.

7. The formulation of claim 6 , wherein the polyalkyleneglycol diacrylate has a molecular weight of about 500 Daltons to about 10,000 Daltons.

8. The formulation of claim 6 , wherein the polyalkyleneglycol diacrylate is a polyalkyleneglycolyl dimethacrylate.

9. The formulation of claim 6 , wherein the polyalkyleneglycolyl diacrylate is a polyethyleneglycolyl dimethacrylate.

10. The formulation of claim 6 , wherein the protein is insulin, human growth hormone, cetuximab, or bevacizumab.

11. The formulation of claim 6 , wherein the protein is a monoclonal antibody.

Assignees

• Dadey Eric
• Watkins Andrew (Drew)
• Indivior Uk Ltd

Inventors

• Dadey Eric
• Watkins Andrew (Drew)

Classifications

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title