Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
1998-12-22
2001-08-07
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
C514S388000
Reexamination Certificate
active
06271217
ABSTRACT:
TECHNICAL FIELD
This invention is a method of inhibiting the growth of cancers and tumors in mammals, particularly in human and warm blooded animals. The method involves the sequential administration of chemotherapeutic agents which reduce the tumor size and a benzimidazole derivative, preferably carbendazim or 2-methoxycarbonylamino-benzimidazole, in either order.
BACKGROUND OF THE INVENTION
Cancers are a leading cause of death in animals and humans. The exact cause of cancer is not known, but links between certain activities such as smoking or exposure to carcinogens and the incidence of certain types of cancers and tumors has been shown by a number of researchers.
Many types of chemotherapeutic agents have been shown to be effective against cancers and tumor cells, but unfortunately, many of these agents also destroy normal cells. Despite advances in the field of cancer treatment the leading therapies to date are surgery, radiation and chemotherapy. Chemotherapeutic approaches are said to fight cancers that are metastasized or ones that are particularly aggressive. Such cytocidal or cytostatic agents work best on cancers with large growth factors, i.e., ones whose cells are rapidly dividing. The exact mechanism for the action of these chemotherapeutic agents are not always known. Moreover, while some chemotherapeutic agents reduce the tumor mass significantly after one treatment, they unfortunately cannot be administered again to the same patient when the tumor returns as is usually the case. Some can only be administered once in a lifetime, others require several months or years delay between treatments.
Clearly, the development of materials that would target tumor cells due to some unique specificity for them would be a breakthrough. Alternatively, materials that were cytotoxic to tumor cells while exerting mild effects on normal cells would be desirable. It has been found that the benzimidazoles are especially effective in suppressing the growth of the cancers and tumors. The use of these benzimidazoles in sequential combination with other chemotherapeutic agents which are effective in debulking the tumor is a novel method of treatment. The preferred method involves first debulking or reducing the mass of the tumor with a cytotoxic agent and then administering the benzimidazoles.
It is an object of this invention to provide an anti-cancer therapy comprising a administering a chemotherapeutic agent first to reduce the mass of the tumor and then administering a benzimidazole derivative as defined herein to maintain or destroy the cancer. The agents may also be administered with the benzimidazole first and then the chemotherapeutic agent.
The benzimidazole can be administered in conjunction with a potentiator.
These and other objects will become evident from the following detailed description of this inventions.
SUMMARY OF THE INVENTION
A method of treating cancer in mammals, and in particular, warm blooded animals and humans, comprising administering a chemotherapeutic agent which significantly reduces the mass of the tumor or cancer, and then administering a safe and effective amount of a benzimidazole selected from the group consisting of:
wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms; n is a positive integer of less than 4; Y is hydrogen, chlorine, nitro, methyl or ethyl; and R is hydrogen, or an alkyl group of from 1 to 8 carbon atoms or CONHR
3
and R
3
is alkyl of less than 7 carbons, preferably butyl or isobutyl, and R
2
is 4-thiazolyl, NHCOOR
1
, wherein R
1
is aliphatic hydrocarbon of less than 7 carbon atoms, and preferably an alkyl group of less than 7 carbon atoms is claimed.
Preferably the compositions are:
wherein R is hydrogen or CONHR
3
an d R
3
is alkyl of less than 7 carbons, preferably butyl or isobutyl or an alkyl of 1 through 8 carbon atoms and R
2
is selected from the group consisting of 4-thiazolyl, NHCOOR
1
, wherein R
1
is methyl, ethyl or isopropyl and the non-toxic, pharmaceutically acceptable acid addition salts with both organic and inorganic acids. The most preferred compounds are 2-(4-thiazolyl)benzimidazole, methyl (butylcarbamoyl)-2-benzimidazolecarbamate and 2-methoxycarbonylamino-benzimidazole and those wherein Y is chloro.
These compositions can be used to inhibit the growth of cancers and other tumors in humans or animals by administration of an effective amount either orally, rectally, topically or parenterally, intravenously or by injection into the tumor. Potentiators can also be used with this composition.
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Dabek Rose Ann
Goldberg Jerome D.
Miller Steven W.
The Procter & Gamble & Company
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