Patent US4622218A successfully refreshed from Google Patents.
US4622218A
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US
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Testicular-specific drug delivery
Assignee: University of Florida
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Filing: 1983-03-15
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Granted: 1986-11-11
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Expires: 2003-03-15
Abstract
Abstract Testicularly acting drug species are site-specifically/sustainedly delivered to the testes by administering to a male in need of such treatment a pharmacologically effective amount of the target drug species [D] tethered to a reduced, blood-testis barrier penetrating lipoidal form [D--DHC] of a dihydropyridine⃡pyridinium salt type redox carrier, e.g. 1,4-dihydrotrigonelline. Oxidation of the dihydropyridine carrier moiety in vivo to the ionic pyridinium salt type drug/carrier entity [D--QC] + prevents elimination thereof from the testes, while elimination from the general circulation is accelerated, resulting in significant and prolongedly sustained testicular-specific drug activity, whether ascribable to the cleavage of the [D--QC] + entity and sustained release of the drug [D] in the testes and/or to [D--QC] + itself.
Inventors
- 👤 Nicholas S. Bodor
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 14:48
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/79; C07D213/80; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/559; C07D209/00; C07D209/02; C07D209/04; C07D209/30; C07D209/32; C07D211/00; C07D211/04; C07D211/80; C07D211/84; C07D211/90; C07D213/81; C07D213/82; C07D401/00; C07D401/02; C07D401/12; C07J; C07J43/00; C07J43/003; C07K; C07K14/00; C07K14/435; C07K14/665; C07K14/70; A61K38/00
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
116 words
A method for site-specifically and sustainedly delivery a testicularly acting drug species to the testes, comprising administering to a male mammal in need of such treatment a quantity of a compound having the formula [D--DHC] (I) or a non-toxic pharmaceutically acceptable salt thereof, wherein [D] is testicularly acting drug species and [DHC] is the reduced, biooxidizable, lipoidal form of a dihydropyridine⃡pyridinium salt redox carrier, said redox carrier facilitating the transport of said testicularly acting drug species across the blood-testis barrier and delivering said testicularly acting drug species to the testes in a site-specific and sustained manner, said quantity being sufficient to deliver a testicularly, pharmacologically effective amount of said testicularly acting drug species to the testes.
Claim 2
Independent Claim
116 words
A method for site-specifically and sustainedly delivery a testicularly acting drug species to the testes, comprising administering to a male mammal in need of such treatment a quantity of a compound having the formula [D--DHC] (I) or a non-toxic pharmaceutically acceptable salt thereof, wherein [D] is testicularly acting drug species and [DHC] is the reduced, biooxidizable, lipoidal form of a dihydropyridine⃡pyridinium salt redox carrier, said redox carrier facilitating the transport of said testicularly acting drug species across the blood-testis barrier and delivering said testicularly acting drug species to the testes in a site-specific and sustained manner, said quantity being sufficient to deliver a testicularly, pharmacologically effective amount of said testicularly acting drug species to the testes.
Claim 3
Dependent Claim
116 words
A method as defined by claim 1 for site-specifically and sustainedly delivering an androgenic drug species to the testes, comprising administering to a male mammal in need of such treatment a quantity of a compound having the formula [D--DHC] (I) or a non-toxic pharmaceutically acceptable salt thereof, wherein [D] is an androgenic drug species and [DHC] is the reduced, biooxidizable, lipoidal form of a dihydropyridine⃡pyridinium salt redox carrier, said redox carrier facilitating the transport of said androgenic drug species across the blood-testis barrier and delivering said androgenic drug species to the testes in a site-specific and sustained manner, said quantity being sufficient to deliver an androgenically effective amount of said androgenic drug species to the testes.
Claim 4
Dependent Claim
45 words
A method as defined by claim 1, wherein [D] is a testicularly acting drug species and [DHC] is the reduced, biooxidizable, blood-testis barrier penetrating, lipoidal form of a dihydropyridine⃡pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR21## then [D] cannot be testosterone.
Claim 5
Dependent Claim
14 words
A method as defined by claim 1, wherein [D] is a testicularly acting antibacterial.
Claim 6
Dependent Claim
15 words
A method as defined by claim 1, wherein [D] is a testicularly acting antiviral agent.
Claim 7
Dependent Claim
14 words
A method as defined by claim 1, wherein [D] is a testicularly acting analgesic.
Claim 8
Dependent Claim
17 words
A method as defined by claim 1, wherein [D] is a testicularly acting antitumor or anticancer agent.
Claim 9
Dependent Claim
15 words
A method as defined by claim 1, wherein [D] is a testicularly acting hormonal agent.
Claim 10
Dependent Claim
13 words
A method as defined by claim 7, wherein [D] is a nitrogen mustard.
Claim 11
Dependent Claim
11 words
A method as defined by claim 9, wherein [D] is chlorambucil.
Claim 12
Dependent Claim
11 words
A method as defined by claim 9, wherein [D] is melphalan.
Claim 13
Dependent Claim
14 words
A method as defined by claim 7, wherein [D] is a folic acid antagonist.
Claim 14
Dependent Claim
11 words
A method as defined by claim 12, wherein [D] is methotrexate.
Claim 15
Dependent Claim
14 words
A method as defined by claim 7, wherein [D] is a platinum coordination complex.
Claim 16
Dependent Claim
13 words
A method as defined by claim 14, wherein [D] is a cisplatin analogue.
Claim 17
Dependent Claim
14 words
A method as defined by claim 7, wherein [D] is an antibiotic anticancer agent.
Claim 18
Dependent Claim
11 words
A method as defined by claim 16, wherein [D] is dactinomycin.
Claim 19
Dependent Claim
14 words
A method as defined by claim 7, wherein [D] is a hormonal anticancer agent.
Claim 20
Dependent Claim
15 words
A method as defined by claim 8, wherein [D] is a pituitary or nonpituitary gonadotropin.
Claim 21
Dependent Claim
13 words
A method as defined by claim 8, wherein [D] is a glucocorticoid steroid.
Claim 22
Dependent Claim
11 words
A method as defined by claim 8, wherein [D] is testosterone.
Claim 23
Dependent Claim
11 words
A method as defined by claim 8, wherein [D] is methyltestosterone.
Claim 24
Dependent Claim
12 words
A method as defined by claim 8, wherein [D] is an antiandrogen.
Claim 25
Dependent Claim
18 words
A method as defined by claim 3, wherein [DHC] comprises the reduced form of a nicotinic acid derivative.
Claim 26
Dependent Claim
16 words
A method as defined by claim 3, wherein [DHC] comprises the reduced form of a trigonelline.
Claim 27
Dependent Claim
16 words
A method as defined by claim 3, wherein [DHC] comprises the reduced form of an isoquinoline.
Claim 28
Dependent Claim
17 words
The method as defined by claim 3, wherein [DHC] comprises the reduced form of a pyridinium alcohol.
Claim 29
Dependent Claim
63 words
A method as defined by claim 3, wherein [DHC] is ##STR22## wherein the ##STR23## substituents in formulae (i), (ii) and (iii) each can be in the 2-, 3- or 4- position on the ring, R 1 is C 1 -C 7 alkyl or C 7 -C 10 aralkyl and R 3 is (CH 2 ) n wherein n is 1, 2 or 3.
Claim 30
Dependent Claim
11 words
A method as defined by claim 28, wherein [DHC] is ##STR24##
Claim 31
Dependent Claim
22 words
A method as defined in claim 3, wherein [D] is chlorambucil, melphalan, methotrexate, a cisplatin analogue, dactinomycin, testosterone or a testosterone analogue.
Claim 32
Dependent Claim
63 words
A method as defined by claim 2 wherein [DHC] is ##STR25## wherein the ##STR26## substitutents in formulae (i), (ii) and (iii) each can be in the 2-, 3- or 4- position on the ring, R 1 is C 1 -C 7 alkyl or C 7 -C 10 aralkyl and R 3 is (CH 2 ) n wherein n is 1, 2 or 3.
Claim 33
Dependent Claim
11 words
A method as defined in claim 2 wherein [DHC] is ##STR27##
Claim 34
Dependent Claim
25 words
A method as defined by claim 2 wherein [D] is the residue of testosterone or of methyl testosterone, said residue having the formula ##STR28## respectively.
Claim 35
Dependent Claim
25 words
A method as defined by claim 31 wherein [D] is the residue of testosterone or of methyl testosterone, siad residue having the formula ##STR29## respectively.
Claim 36
Dependent Claim
25 words
A method as defined by claim 32 wherein [D] is the residue of testosterone or of methyl testosterone, said residue having the formula ##STR30## respectively.
Claim 37
Dependent Claim
58 words
A method as defined by claim 35 for site-specifically and sustainedly delivering testosterone to the testes, comprising administering to a male mammal in need of such treatment a quantity of a compound of the formula ##STR31## or a non-toxic pharmaceutically acceptable salt thereof, said quantity being sufficient to deliver an androgenically effective amount of testosterone to the testes.
Claim 38
Dependent Claim
13 words
A method as defined by claim 36 wherein the compound administered is 17β-[(1,4-dihydro-1-methyl-3-pyridinylcarhonyl)oxy]androst-4-en-3-one
References Cited (Backward Citations)
US4479932A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-11-10 | 1990-05-12 | 1990-11-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-11-10 | 1994-05-12 | 1994-11-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-11-10 | 1998-05-12 | 1998-11-11 | $7700.00 | Window Closed / Lapsed |