Liposomal antineoplaston therapies with markedly improved antineoplastic activity

• US 6,013,278 A
• Filed: 05/14/1997
• Issued: 01/11/2000
• Est. Priority Date: 05/14/1996
• Status: Expired due to Fees

• Current Assignee: Burzynski Research Institute, Inc.
• Original Assignee: Burzynski Research Institute, Inc.
• Inventors: Burzynski, Stanislaw R., Byra, Anna, Waldbillig, Robert J.
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/856,133
• Time in Patent Office: 972 Days
• Field of Search: 424/450, 514/299, 514/557, 514/646
• US Class Current: 424/450
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/45 having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A second generation of antineoplaston therapies with markedly improved antineoplastic activity is disclosed. Among others, members of the antineoplaston family include phenylacetate (PN), 3-phenylacetyl-amino-2, 6, piperidinedione (CN), and hydrolysis derivatives of CN: phenylacetylglutamine (PG) and isophenylacetylglutamine (Iso-PG). In part, these increases in antineoplastic activity result from large increases in the transport of antineoplaston compositions into cells. Importantly and unexpectedly these increases in antineoplastic activity also result from the capacity of the drug delivery system to direct antineoplaston compounds intracellular trafficking to intracellular binding sites influencing cell viability and proliferation. Liposomal formulations of antineoplaston compositions increase in vitro antineoplastic activity by a factor of 750 to 1500 as compared to administration of antineoplaston compounds given without liposomal formulations. In addition, these liposomal formulations enhanced cellular uptake of antineoplaston compounds from 30 to more that 80 fold. Liposomal formulations were also found to increase intracellular levels of the antineoplaston CN (3-phenylacetyl-amino-2,6, piperidinedione) by directing CN to intracellular binding sites that influence cell viability and proliferation and block its hydrolysis. Under conditions where free CN has no antineoplastic activity, liposomally formulated CN can produce essentially complete and relatively long-lasting blockade of cell growth. Cell growth was found to be restored as intracellular levels of bound CN decrease to undetectable levels.

Claims

1. A pharmaceutical composition comprising lipids in a liposomal formulation and an antineoplaston agent within the liposomal formulation, wherein the antineoplaston agent comprises 3-phenylacetylamino-2,6, piperidinedione wherein the molar ratio of antineoplaston agent to lipid is between 1:

0.1 to 1;

100.

2. A pharmaceutical composition comprising lipids in a liposomal formulation and an antineoplaston agent within the liposomal formulation, wherein the antineoplaston agent comprises phenylacetate and phenylacetylglutamine wherein the molar ratio of antineoplaston agent to lipid is between 1:

0.1 to 1;

100.

3. The pharmaceutical composition according to claim 2, wherein the phenylacetylglutamine is L-phenylacetylglutamine.

4. The pharmaceutical composition according to claim 2, wherein the molar ratio of phenylacetate to phenylacetylglutamine is 8 to 1.

7. A method of treating malignant neoplastic disease, comprising administering to the patient a pharmaceutical composition according to any one of claims 3 to 8.

5. A pharmaceutical composition comprising lipids in a liposomal formulation and an antineoplaston agent within the liposomal formulation, wherein the antineoplaston agent comprises phenylacetylglutamine and isophenylacetylglutamine wherein the molar ratio of antineoplaston agent to lipid is between 1:

0.1 to 1;

100.

6. The pharmaceutical composition according to claim 5, wherein the molar ratio of phenylacetylglutamine to iso-phenylacetylglutamine is 4 to 1.