Enzymatic debridement therapy for abnormal cell proliferation

• US 8,754,045 B2
• Filed: 05/14/2007
• Issued: 06/17/2014
• Est. Priority Date: 05/12/2006
• Status: Active Grant

• Current Assignee: Alex Getahoun
• Original Assignee: James A. Livingston
• Inventors: Livingston, James A.
• Primary Examiner(s): Ha, Julie
• Application Number:
  US11/803,304
• Publication Number:
  US 20080044459A1
• Time in Patent Office: 2,591 Days
• Field of Search: 514/19.3, 514/19.4, 514/19.5, 514/19.6, 424/94.1, 424/94.64
• US Class Current: 514/19.3
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 38/45 Transferases (2)
• CPC Class Codes: A61K 38/482 Serine endopeptidases (3.4.21)
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: A61K 38/488 Aspartic endopeptidases (3.4.23), e.g. pepsin, chymosin, renin, cathepsin E
• CPC Class Codes: A61K 38/4886 Metalloendopeptidases (3.4.24), e.g. collagenase
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 15/38 containing enzymes
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B42D 15/045 Multi-part cards or sheets, i.e. combined with detachably mounted articles
• CPC Class Codes: C12Y 304/21004 Trypsin (3.4.21.4)
• CPC Class Codes: C12Y 304/21064 Peptidase K (3.4.21.64)
• CPC Class Codes: C12Y 304/22002 : Papain (3.4.22.2)
• CPC Class Codes: C12Y 304/22003 : Ficain (3.4.22.3)
• CPC Class Codes: C12Y 304/22032 : Stem bromelain (3.4.22.32)
• CPC Class Codes: C12Y 304/22033 : Fruit bromelain (3.4.22.33), i.e. juice bromelain

Abstract

Compositions and methods are provided to destroy internal cancerous lesions selectively by the administration of a combination of a debridement protease enzyme and a denaturant of cell structural proteins and or cell adhesion proteins.

Claims

1. A method of treating a cancer in a patient, comprising administering to a patient in need thereof a treatment effective amount of a composition consisting of one or more debridement enzymes and one or more denaturants, and a pharmaceutically acceptable carrier, wherein the cancer is a leukemia, ovarian, breast, colon, prostate, lung, renal, or CNS cancer.

2. The method of claim 1 wherein the debridement enzyme is selected from the group consisting of a plasma enzyme, a pancreatic enzyme, a cysteine protease, a serine protease, and a metallopeptidase.

3. The method of claim 1 wherein the debridement enzyme is selected from the group consisting of fibrinolysin, desoxyribonuclease, trypsin, chymotrypsin, krillase, bromelain, papain, ficin, subtilisins, proteinase K, collagenase, vibriolysin, thermolysin, streptokinase and streptodornase.

4. The method of claim 1 wherein the debridement enzyme is papain.

5. The method of claim 1 comprising administering the debridement enzyme in a dose in the range about 1×

10⁴ to 1×

10⁸ USP per gram.

6. The method of claim 1 comprising administering the debridement enzyme in a dose of about 1.1×

10⁶ USP per gram.

7. The method of claim 1 wherein the denaturant is selected from the group consisting of urea, lactic acid, citric acid, an aliphatic alcohol, β

-mercaptoethanol, a detergent, sodium dodecyl sulfate, formaldehyde, acetone, acetonitrile, dimethylsulfoxide, dimethylformamide, propylene carbonate, ethylene carbonate, a metal scavenger, crown ethers, a crown amine, a polyether, polyethyleneoxide, a polyamine, polyethyleneamine, cryptands, ethylenediarninetetraacetic acid or its salts, silver sulfadiazine, gentamicin, penicillin, a strong acid, hydrochloric acid, phosphoric acid, sulfuric acid, an acid with a pK_a less than about 4, a strong base, sodium hydroxide, potassium hydroxide, sodium carbonate, and a base with a pK_a greater than about 10.

8. The method of claim 1 wherein the denaturant is urea.

9. The method of claim 4 wherein the denaturant is urea.

10. The method of claim 1 wherein the denaturant is present in concentration range of about 0.1-40 weight percent.

11. The method of claim 1 wherein the denaturant is present in concentration range of about 10 weight percent to 50 weight percent.

12. The method of claim 1 wherein the denaturant is present in concentration range of about 5 weight percent to 20 weight percent.

13. The method of claim 1 wherein the denaturant is present in concentration range of about 1-5 weight percent.

14. The method of claim 1, wherein the enzyme retains at least 80% activity in the presence of the denaturant.

15. The method of claim 1, wherein the enzyme retains at least 90% activity in the presence of the denaturant.

16. The method of claim 1, wherein the enzyme retains at least 95% in the presence of the denaturant.