Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome
First Claim
1. A method for preventing or reducing adult respiratory distress syndrome (ARDS) in a patient at risk of ARDS which comprises administering to said patient an effective amount of a dehydroepiandrosterone (DHEA) derivative having the general formulas I and II and their pharmaceutically acceptable salts whereinR1, R2, R3, R4, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R19 are independently H, —
- OH, halogen, C1-10 alkyl or C1-10 alkoxy;
R5 is H, —
OH, halogen, C1-10 alkyl, C1-10 alkoxy or OSO2R20;
R15 is (1) H, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is —
C(O)OR21 or (2) H, halogen, OH or C1-10 alkyl when R16 is H, halogen, OH or C1-10 alkyl or (3) H, halogen, C1-10 alkyl, C1-10 alkenyl, C1-10 alkynyl, formyl, C1-10 alkanoyl or epoxy when R16 is OH;
or R15 and R16 taken together are ═
O;
R17 and R18 are independently (1) H, —
OH, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is H, OH, halogen, C1-10 alkyl or —
C(O)OR21 or (2) H, (C1-10 alkyl)namino, (C1-10 alkyl)namino-C1-10 alkyl, C1-10 alkoxy, hydroxy-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, (halogen)m-C1-10 alkyl, C1-10 alkanoyl, formyl, C1-10 carbalkoxy or C1-10 alkanoyloxy when R15 and R16 taken together are ═
O;
or R17 and R18 taken together are ═
O or taken together with the carbon to which they are attached form a 3-6 member ring containing 0 or 1 oxygen atoms;
or R15 and R17 taken together with the carbons to which they are attached form an epoxide ring;
R20 is OH, pharmaceutically acceptable ester or pharmaceutically acceptable ether;
R21 is H, (halogen)m-C1-10 alkyl or C1-10 alkyl;
n is 0, 1 or 2; and
m is 1,2 or 3, with the provisos that(a) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14, R17 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 is H and R16 is OH;
(b) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 and R16 taken together are ═
O;
(c) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 and R16 taken together are ═
O; and
(d) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 is H and R16 is H, OH or halogen.
2 Assignments
0 Petitions
Accused Products
Abstract
The present invention is related to a method for preventing or reducing the effects of ischemia. The ischemia may be associated with injury or reperfusion injury, such as occurs as a result of infarctions, thermal injury (burns), surgical trauma, accidental trauma, hemorrhagic shock and the like. The invention is also related to methods for preventing or reducing bacterial translocation, adult respiratory distress syndrome, adherence of blood cells and platelets to endothelial cells and pulmonary hypertension. In accordance with the present invention, these conditions are prevented or reduced by administering a dehydroepiandrosterone (DHEA) derivative as defined herein.
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Citations
10 Claims
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1. A method for preventing or reducing adult respiratory distress syndrome (ARDS) in a patient at risk of ARDS which comprises administering to said patient an effective amount of a dehydroepiandrosterone (DHEA) derivative having the general formulas I and II and their pharmaceutically acceptable salts
wherein R1, R2, R3, R4, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R19 are independently H, — - OH, halogen, C1-10 alkyl or C1-10 alkoxy;
R5 is H, —
OH, halogen, C1-10 alkyl, C1-10 alkoxy or OSO2R20;
R15 is (1) H, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is —
C(O)OR21 or(2) H, halogen, OH or C1-10 alkyl when R16 is H, halogen, OH or C1-10 alkyl or (3) H, halogen, C1-10 alkyl, C1-10 alkenyl, C1-10 alkynyl, formyl, C1-10 alkanoyl or epoxy when R16 is OH;
orR15 and R16 taken together are ═
O;
R17 and R18 are independently (1) H, —
OH, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is H, OH, halogen, C1-10 alkyl or —
C(O)OR21 or(2) H, (C1-10 alkyl)namino, (C1-10 alkyl)namino-C1-10 alkyl, C1-10 alkoxy, hydroxy-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, (halogen)m-C1-10 alkyl, C1-10 alkanoyl, formyl, C1-10 carbalkoxy or C1-10 alkanoyloxy when R15 and R16 taken together are ═
O;
orR17 and R18 taken together are ═
O or taken together with the carbon to which they are attached form a 3-6 member ring containing 0 or 1 oxygen atoms;
orR15 and R17 taken together with the carbons to which they are attached form an epoxide ring;
R20 is OH, pharmaceutically acceptable ester or pharmaceutically acceptable ether;
R21 is H, (halogen)m-C1-10 alkyl or C1-10 alkyl;
n is 0, 1 or 2; and
m is 1,2 or 3, with the provisos that (a) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14, R17 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 is H and R16 is OH;
(b) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 and R16 taken together are ═
O;
(c) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 and R16 taken together are ═
O; and
(d) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 is H and R16 is H, OH or halogen. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
- OH, halogen, C1-10 alkyl or C1-10 alkoxy;
Specification