Patent JPS5987113A successfully refreshed from Google Patents.
US4337760A
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US
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Method for the treatment of tumors with β-glucuronidase activity dependent pharmaceuticals
Assignee: CENTURY SCIENCE CORP 99 SOUNDVIEW DRIVE PORT WASHINGTON NEW YORK 11050 A CORP
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Filing: 1979-10-31
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Granted: 1982-07-06
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Expires: 1999-10-31
Abstract
Abstract Hyperacidified tumors having high beta -glucuronidase activity can be treated with glucuronides with aglycones toxic to the tumor cells with great safety toward the rest of the body by first administering an alkalinizing agent in an amount sufficient to maintain the pH level of non-tumor tissues at approximately 7.4 during the glucuronide treatment. This will cause inactivation of beta -glucuronidase activity in the rest of the body. When nitrile-containing aglycones are used sodium thiosulfate is also administered to avoid cyanide poisoning. Novel glucuronides are disclosed the aglycones of which exert a higher toxic effect in an acid environment or are water-soluble only in an alkaline environment. Such compounds have particular utility with the above process. By substituting radioisotopes into the aglycone, diagnosis and in situ radiation therapy may be accomplished. Bacterial cells having beta -glucuronidase activity may also be diagnosed and treated in accordance with the present invention. A urine test is disclosed to determine the amount of free glucuronic acid in the urine which is an indication of the presence of a tumor in the body having high beta -glucuronidase activity. Novel methods of synthesizing the glucuronide used in the present invention are also disclosed.
Inventors
- 👤 David Rubin
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 07:49
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0491; A61K31/00; A61K31/70; A61K31/7004; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/549; C; C07; C07H; C07H15/00; C07H15/18; C07H15/20; C07H15/203; C12; C12Q; C12Q1/00; C12Q1/34; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5091; A61K2123/00; C12Q2334/00; C12Q2334/40; G01N2333/00; G01N2333/90; G01N2333/914; G01N2333/924
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
138 words
In a process of selectively delivering the aglycone of a glucuronide compound to tumor cells having higher β-glucuronidase activity than that of the surrounding tissues by hyperacidifying the tumor cells and then administering to the patient a glucuronide compound, the aglycone of which is to be delivered to the tumor cells, whereby the β-glucuronidase activity of the hyperacidified tumor cells causes deconjugation of the glucuronide compound at the site of the tumor cells and release of the aglycone thereat, the improvement wherein the tumor selectivity of the process is improved and the risk of deconjugation of the glucuronide compound at the site of non-tumor tissues is diminished, comprising: administering to the patient an alkalinizing agent in an amount sufficient to maintain the pH level of the non-tumor tissues of the patient at approximately 7.4 during the glucuronide treatment.
Claim 2
Dependent Claim
138 words
In a process of selectively delivering the aglycone of a glucuronide compound to tumor cells having higher β-glucuronidase activity than that of the surrounding tissues by hyperacidifying the tumor cells and then administering to the patient a glucuronide compound, the aglycone of which is to be delivered to the tumor cells, whereby the β-glucuronidase activity of the hyperacidified tumor cells causes deconjugation of the glucuronide compound at the site of the tumor cells and release of the aglycone thereat, the improvement wherein the tumor selectivity of the process is improved and the risk of deconjugation of the glucuronide compound at the site of non-tumor tissues is diminished, comprising: administering to the patient an alkalinizing agent in an amount sufficient to maintain the pH level of the non-tumor tissues of the patient at approximately 7.4 during the glucuronide treatment.
Claim 3
Dependent Claim
52 words
Process in accordance with claim 1, wherein said compound is one in which the aglycone is toxic to tumor cells and exerts a higher toxic effect in an acid environment than in an alkaline environment or is water-soluble in an alkaline environment and water-insoluble or only poorly water-soluble in an acid environment.
Claim 4
Dependent Claim
39 words
Process in accordance with claim 2, wherein said glucuronide compound is selected from the group consisting of 2,4-dinitrophenol-β-D-glucuronic acid; 4-chloro-m-cresol-β-D-glucuronic acid; 4,6-dinitro-o-cresol-β-D-glucuronic acid; 4-chloro-3,5-xylanol-β-D-glucuronic acid; chlorothymol-β-D-glucuronic acid; 5-chloro-7-iodo-8-quinolinol-β-D-glucuronic acid; podophyllotoxin-β-D-glucuronic acid; 2-phenyl-6-chlorophenol-β-D-glucuronic acid; p-iodophenol β-D-glucuronic acid; and phenylsulfazole-β-D-glucuronic acid.
Claim 5
Dependent Claim
29 words
A process in accordance with claim 1, wherein said step of hyperacidifying the tumor cells comprises administering a hyperglycaemic agent in an amount sufficient to hyperacidify the tumor cells.
Claim 6
Dependent Claim
16 words
A process in accordance with claim 1, wherein said alkalinizing agent is administered orally or intravenously.
Claim 7
Dependent Claim
54 words
A process in accordance with claim 1, wherein said alkalinizing agent is administered prior to administration of said glucuronide compound, said glucuronide compound being administered after the pH of the urine of the patient is determined to be approximately 7.4 and wherein administration of said alkalinizing agent continues during administration of said glucuronide compound.
Claim 8
Dependent Claim
40 words
A process in accordance with claim 1 wherein the aglycone of said glucuranide compound is nitrile containing and further including the step of administering to the patient an amount of sodium thiosulfate sufficient to serve as antidote for cyanide poisoning.
Claim 9
Dependent Claim
57 words
A process in accordance with claim 1, further including the step of inducing hyperthermia at least at the site of the tumor being treated to an extent sufficient to substantially increase β-glucuronidase activity at the site without substantially affecting the overall health of the patient at least at the time of maximum glucuronide concentration at the tumor.
Claim 10
Dependent Claim
36 words
A process in accordance with claim 8, wherein said hyperthermia is induced locally at the tumor by administration of the glucuronide of a pyrogen, by microwave treatment or by passage of electrical current through the body.
Claim 11
Dependent Claim
24 words
A process in accordance with claim 1 further including the step of administering estrogen or testosterone substantially simultaneously with the administration of said glucuronide.
References Cited (Backward Citations)
US4106488A
Cited
US4181132A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-07-05 | 1986-01-04 | 1986-07-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-07-05 | 1990-01-04 | 1990-07-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-07-05 | 1994-01-04 | 1994-07-06 | $7700.00 | Window Closed / Lapsed |