Patent US5541232A successfully refreshed from Google Patents.
US5541232A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Treatment of multidrug resistant diseases
Assignee: Abeona Therapeutics Inc
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Filing: 1994-06-23
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Granted: 1996-07-30
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Expires: 2014-06-23
Abstract
Abstract A method and composition for treating multidrug resistance in a mammal, in which the composition includes NDGA or an analog of NDGA in accordance with the following formula: ##STR1## wherein R 1 and R 2 are independently H, lower alkyl or lower acyl; R 3 , R 4 , R 5 , and R 6 are independently H or lower alkyl; R 7 , R 8 and R 9 are independently H, hydroxy, lower alkoxy or lower acyloxy; and R 10 , R 11 , R 12 and R 13 are independently H or lower alkyl, in a pharmaceutically acceptable vehicle. The method is particularly suitable for administering an antineoplastic agent, and the composition includes the combination of NDGA, or an analog with such an antineoplastic agent.
Inventors
- 👤 Stephen Howell
- 👤 Atul Khandwala
- 👤 Om P. Sachdey
- 👤 Charles G. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 18:32
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/045; A61K31/05; A61K31/075; A61K31/085; A61K31/09; A61K31/21; A61K31/215; A61K31/22; A61K31/33; A61K31/395; A61K31/435; A61K31/47; A61K31/475; A61K33/00; A61K33/24; A61K33/243
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
143 words
A pharmaceutical composition for the prevention or treatment of multidrug resistance in cancer cells of a patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, comprising a compound of the formula or a pharmaceutically acceptable salt therof: ##STR3## wherein R 1 and R 2 are independently H, lower alkyl or lower acyl; R 3 , R 4 , R 5 and R 6 are independently H or lower alkyl; R 7 , R 8 and R 9 are independently H, hydroxy, lower alkoxy or lower acyloxy; and R 10 , R 11 , R 12 and R 13 are independently H or lower alkyl, and an antineoplastic agent other than the compound, to which antineoplastic agent the cancer cells of the patient are susceptible to multidrug resistance or have developed multidrug resistance, in a pharmaceutically acceptable vehicle.
Claim 2
Dependent Claim
143 words
A pharmaceutical composition for the prevention or treatment of multidrug resistance in cancer cells of a patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, comprising a compound of the formula or a pharmaceutically acceptable salt therof: ##STR3## wherein R 1 and R 2 are independently H, lower alkyl or lower acyl; R 3 , R 4 , R 5 and R 6 are independently H or lower alkyl; R 7 , R 8 and R 9 are independently H, hydroxy, lower alkoxy or lower acyloxy; and R 10 , R 11 , R 12 and R 13 are independently H or lower alkyl, and an antineoplastic agent other than the compound, to which antineoplastic agent the cancer cells of the patient are susceptible to multidrug resistance or have developed multidrug resistance, in a pharmaceutically acceptable vehicle.
Claim 3
Dependent Claim
26 words
The pharmaceutical composition of claim 1 wherein said lower alkyl is C 1 -C 6 alkyl and said lower acyl is C 1 -C 6 acyl.
Claim 4
Dependent Claim
40 words
The pharmaceutical composition of claim 1 wherein said compound is selected from the group consisting of: d-, 1-racemic mixture of d- and 1-, meso-isomers of 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dihydroxyphenyl)butane; 1,4-bis(3,4-dimethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-diethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropoxyphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxyphenyl)-4-(3',4',5'-trihydroxyphenyl)butane; 1,4-bis(3,4-diacetoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropionyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dibutyroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-divaleroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipivaloyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dineopentylcarboxylphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxphenyl)-4-phenylbutane and 1-(3,4-dihydroxyphenyl-4-(2,5-dihydroxyphenyl)butane.
Claim 5
Dependent Claim
10 words
The pharmaceutical composition of claim 1 in a solid form.
Claim 6
Dependent Claim
10 words
The pharmaceutical composition of claim 1 in a liquid form.
Claim 7
Dependent Claim
10 words
The pharmaceutical composition of claim 1 in an injectable form.
Claim 8
Dependent Claim
9 words
The pharmaceutical composition of claim 1 for topical administration.
Claim 9
Dependent Claim
69 words
A composition for treating multidrug resistance in cancer cells of patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, which comprises a catecholic butane of the formula of claim 1 or a pharmaceutically acceptable salt thereof, an antineoplastic compound to which the cells are susceptible to developing multidrug resistance or to which the cells have developed multidrug resisitance, and a biologically acceptable carrier.
Claim 10
Dependent Claim
18 words
The composition of claim 8 wherein the catecholic butane is selected from the group defined in claim 3.
Claim 11
Dependent Claim
36 words
The composition of claim 9 wherein the catecholic butane is selected from the group selected from the following: NDGA; d,l NDGA; NDGA tetracetate; NDGA tetrapropionate; 1,4-bis(3'-methoxy-4'-hydroxyphenyl butane; 1,4 -bis(3'-methoxy-4'-hydroxyphenyl)-2,3-dimethyl butane; 1-(3',4'-dihydroxyphenyl)-4-(2',3',4'-trihydroxphenyl)-butane; 1-(3',4'-dihydroxyphenyl)-4(3',4',5'-trihydroxyphenyl)-butane; 1-(3',4'-dihydroxyphenyl)-4-(2',5'-dihydroxyphenyl)-butane; and 1-(3',4'-dihydroxyphenyl)-4-phenyl butane.
Claim 12
Dependent Claim
11 words
The composition of claim 10 wherein the catecholic butane is NDGA.
Claim 13
Dependent Claim
26 words
The composition of claim 11 wherein the antineoplastic compound is selected from the group consisting of a vinca alkaloid, an antibiotic or a platinum coordination complex.
Claim 14
Dependent Claim
11 words
The composition of claim 12 wherein the antineoplastic compound is vinblastine.
Claim 15
Dependent Claim
10 words
The composition of claim 12 wherein said antibiotic is doxorubicin.
Claim 16
Dependent Claim
12 words
The composition of claim 12 wherein said platinum coordination complex is cisplatin.
Claim 17
Dependent Claim
20 words
The composition of claim 12 wherein the catecholic butane is NDGA and the antineoplastic compound is vinblastine, doxorubicin or cisplatin.
Claim 18
Independent Claim
153 words
A method for preventing or inhibiting multidrug resistance in cancer cells of a patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, comprising the administration to said patient of a pharmaceutical composition comprising a compound of the formula or a pharmaceutically acceptable salt thereof: ##STR4## wherein R 1 and R 2 are independently H, lower alkyl or lower acyl; R 3 , R 4 , R 5 and R 6 are independently H or lower alkyl; R 7 , R 8 and R 9 are independently H, hydroxy, lower alkoxy or lower acyloxy; and R 10 , R 11 , R 12 and R 13 are independently H or lower alkyl, in a pharmaceutically acceptable vehicle, which composition is administered in combination with an antineoplastic or cytotoxic agent to which the cells are susceptible to developing multidrug resistance or to which the cells have developed multidrug resistance.
Claim 19
Independent Claim
153 words
A method for preventing or inhibiting multidrug resistance in cancer cells of a patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, comprising the administration to said patient of a pharmaceutical composition comprising a compound of the formula or a pharmaceutically acceptable salt thereof: ##STR4## wherein R 1 and R 2 are independently H, lower alkyl or lower acyl; R 3 , R 4 , R 5 and R 6 are independently H or lower alkyl; R 7 , R 8 and R 9 are independently H, hydroxy, lower alkoxy or lower acyloxy; and R 10 , R 11 , R 12 and R 13 are independently H or lower alkyl, in a pharmaceutically acceptable vehicle, which composition is administered in combination with an antineoplastic or cytotoxic agent to which the cells are susceptible to developing multidrug resistance or to which the cells have developed multidrug resistance.
Claim 20
Dependent Claim
25 words
The method of claim 17 wherein said lower alkyl is C 1 -C 6 alkyl and said lower acyl is C 1 -C 6 acyl.
Claim 21
Dependent Claim
39 words
The method of claim 17 wherein said compound is selected from the group consisting of: d-,1-racemic mixture of d- and 1-, meso-isomers of 1,4-bis(3,4 -dihydroxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dihydroxyphenyl)butane; 1,4-bis(3,4-dimethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-diethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropoxyphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxyphenyl)-4-(3',4',5'-trihydroxyphenyl)butane; 1,4-bis(3,4-diacetoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropionyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dibutyroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-divaleroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipivaloyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dineopentylcarboxylphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxyphenyl)-4-phenylbutane and 1-(3,4-dihydroxyphenyl-4-(2,5-dihydroxyphenyl)butane.
Claim 22
Dependent Claim
117 words
The method of claim 17 wherein said multidrug resistance treatment is in conjunction with the treatment of mammalian tumors and malignancies selected from the group comprising: head and neck cancer, lung cancer, mesothelioma cancer, mediastinum cancer, esophagus cancer, stomach cancer, pancreas cancer, hepatobiliary system cancer, small intestine cancer, colon cancer, rectum cancer, anus cancer, kidney cancer, ureter cancer, bladder cancer, prostate cancer, urethra cancer, penis cancer, testis cancer, cancer of gynecological organs, ovarian cancer, breast cancer, endocrine system cancer, skin cancer, central nervous system cancer, soft tissue sarcoma, bone sarcoma, cutaneous melanomas, intraocular melanoma, childhood leukemias and lymphomas, Hodgkin's disease, lymphomas of lymphocytic lymphoma, cutaneous lymphoma, acute and chronic leukemia, plasma cell neoplasm and cancers in AIDS.
Claim 23
Dependent Claim
13 words
The method of claim 17 wherein said composition is in a solid form.
Claim 24
Dependent Claim
13 words
The method of claim 17 wherein said composition is in a liquid form.
Claim 25
Dependent Claim
13 words
The method of claim 17 wherein said composition is in an injectable form.
Claim 26
Dependent Claim
12 words
The method of claim 17 wherein said composition is for topical administration.
Claim 27
Dependent Claim
18 words
The method of claim 15 wherein said composition for topical administration is in the form of an emollient.
Claim 28
Dependent Claim
18 words
The method of claim 15 wherein said composition for topical administration is in the form of a cream.
Claim 29
Dependent Claim
18 words
The method of claim 15 wherein said composition for topical administration is in the form of an ointment.
Claim 30
Dependent Claim
19 words
The method of claim 15 wherein said composition for topical administration is in the form of a liposomal preparation.
Claim 31
Dependent Claim
19 words
The method of claim 15 wherein said composition for topical administration is in the form of a membrane patch.
Claim 32
Dependent Claim
38 words
A method for treating multidrug resistance in solid tumor cells of a patient, which cells are susceptible to multidrug resistance or which cells have become multidrug resistant, which comprises administering to the patient the composition of claim 8.
Claim 33
Dependent Claim
14 words
The method of claim 30 wherein the catecholic butane is defined in claim 10.
Claim 34
Dependent Claim
32 words
The method of claim 31 wherein the antineoplastic compound is selected from the group consisting of a vinca alkaloid, an antibiotic or a platinum coordination complex and the catecholic butane is NDGA.
Claim 35
Dependent Claim
14 words
The method of claim 32 wherein the antineoplastic compound is vinblastine, doxorubicin or cisplatin.
Claim 36
Dependent Claim
23 words
The method of claim 33 wherein the administration of the composition increases the apparent initial uptake and accumuation of vinblastine in the cells.
Claim 37
Dependent Claim
24 words
The method of claim 34 wherein the administration of the composition does not promote the apparent rate of efflux of vinblastine from the cells.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-07-30 | 2000-01-29 | 2000-07-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-07-30 | 2004-01-29 | 2004-07-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-07-30 | 2008-01-29 | 2008-07-30 | $7700.00 | Window Closed / Lapsed |