Microencapsulated genetically engineered microorganisms for clinical application

• US 6,217,859 B1
• Filed: 07/22/1998
• Issued: 04/17/2001
• Est. Priority Date: 01/23/1996
• Status: Expired due to Fees

• Current Assignee: McGill University
• Original Assignee: McGill University
• Inventors: Prakash, Satya, Chang, Thomas M. S.
• Primary Examiner(s): Hauda, Karen M.
• Assistant Examiner(s): SCHNIZER, RICHARD A
• Application Number:
  US09/117,099
• Time in Patent Office: 1,000 Days
• Field of Search: 264/5-14, 424/450, 424/451, 424/490, 435/177
• US Class Current: 424/93.2
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 9/80 acting on amide bonds in linear amides (3.5.1)

Abstract

The present invention relates to a composition for oral administration to a patient for removal of undesired chemicals or amino acids caused by disease. The composition comprises an entrapped or encapsulated microorganism capable of removing the undesired chemicals or amino acids. The composition may comprise a pharmaceutically acceptable carrier for oral administration to the patient.

Claims

1. A method of reducing the concentration of ammonia or urea, or both ammonia and urea, in a mammal comprising orally administering genetically engineered bacteria Escherichia coli DH5 which comprise the urease gene from Klebsiella aerogens, wherein said bacteria are entrapped or microencapsulated in alginate-poly-L-lysine-alginate microcapsules, and are further contained in a pharmaceutically acceptable carrier, wherein the administration of said genetically engineered bacteria results in the removal of said ammonia or urea, or ammonia and urea, from said mammal.

2. The method of claim 1 wherein said microorganism is microencapsulated using any microcapsule material which can retain the microorganism and which allows urea and ammonia to enter the microcapsules.

3. The method of claim 1 wherein said microorganism is entrapped within a carrier using any entrapment material which can retain the microorganism and which allows urea and ammonia to enter the microcapsules.

4. The method of claim 1, wherein said ammonia or urea is caused by a disease.

5. The method of claim 4, wherein said disease is a kidney-failure-causing disease.

6. The method of claim 4, wherein said disease is a liver-failure-causing disease.

7. The method of claim 4, wherein said disease is hyperammonemia with an elevated ammonia level.

8. The method of claim 2 wherein said microorganism is microencapsulated using any material selected from the group consisting of nylon, silicon rubber, nylon-polyethylenimine, polylactic acid, polyglycolic acid, chitosan alginate, cellulosesulphate-poly(dimethyldiallyl)ammonium chloride, hydroxy-ethyl methacrylate-methyl methacrylate, chitosan-carboxymethyl-cellulose, and alginate-polylysine-alginate.

9. A method of reducing the concentration of urea in a mammal comprising orally administering genetically engineered bacteria Escherichia coli DH5 which comprise the urease gene from Klebsiella aerogens in a pharmaceutically acceptable carrier, wherein the administration of said genetically engineered bacteria results in the removal of said urea from said mammal.