Claims
- 1. A method of preventing endotoxemia associated with pulmonary exposure to endotoxin in a subject, said method comprising administering to said subject an antiendotoxin compound having the formula: where R1 is selected from the group consisting of where each J, K, and Q, independently, is straight or branched C1 to C15 alkyl; L is O, NH, or CH2; M is O or NH; and G is NH, O, S, SO, or SO2; R2 is straight or branched C5 to C15 alkyl; R3 is selected from the group consisting of straight or branched C5 to C18 alkyl, where E is NH, O, S, SO, or SO2; each A, B, and D, independently, is straight or branched C1 to C15 alkyl; R4 is selected from the group consisting of straight or branched C4 to C20 alkyl, and where each U and V, independently, is straight or branched C2 to C15 alkyl, and W is hydrogen or straight or branched C1 to C5 alkyl; RA is R5 or R5—O—CH2—, R5 being selected from the group consisting of hydrogen, J′, —J′—OH, —J′—O—K′, —J′—O—K′—OH, and —J′—O—PO(OH)2, where each J′ and K′, independently, is straight or branched C1 to C5 alkyl; R6 is selected from the group consisting of hydroxy, halogen, C1 to C5 alkoxy, and C1 to C5 acyloxy; A1 and A2, independently, are selected from the group consisting of where Z is straight or branched C1 to C10 alkyl; or pharmaceutically acceptable salts thereof.
- 2. The method of claim 1, wherein said Lipid A analog has the structure:
- 3. The method of claim 1, wherein said antiendotoxin compound is administered by inhalation.
- 4. The method of claim 3, wherein said antiendotoxin compound is administered in an aerosolized formulation.
- 5. The method of claim 1, wherein 0.01-50 mg of said antiendotoxin compound is administered to said subject in a single dose.
- 6. The method of claim 5, wherein 0.05-25 mg of said antiendotoxin compound is administered to said subject in a single dose.
- 7. The method of claim 6, wherein 1-12 mg of said antiendotoxin compound is administered to said subject in a single dose.
- 8. A method of treating endotoxemia associated with pulmonary exposure to endotoxin in a subject, said method comprising administering to said subject an antiendotoxin compound having the formula: where R1 is selected from the group consisting of where each J, K, and Q, independently, is straight or branched C1 to C15 alkyl; L is O, NH, or CH2; M is O or NH; and G is NH, O, S, SO, or SO2; R2 is straight or branched C5 to C15 alkyl; R3 is selected from the group consisting of straight or branched C5 to C18 alkyl, where E is NH, O, S, SO, or SO2; each A, B, and D, independently, is straight or branched C1 to C15 alkyl; R4 is selected from the group consisting of straight or branched C4 to C20 alkyl, and where each U and V, independently, is straight or branched C2 to C15 alkyl, and W is hydrogen or straight or branched C1 to C5 alkyl; RA is R5 or R5—O—CH2—, R5 being selected from the group consisting of hydrogen, J′, —J′—OH, —J′—O—K′, —J′—O—K′—OH, and —J′—O—PO(OH)2, where each J′ and K′, independently, is straight or branched C1 to C5 alkyl; R6 is selected from the group consisting of hydroxy, halogen, C1 to C5 alkoxy, and C1 to C5 acyloxy; A1 and A2, independently, are selected from the group consisting of where Z is straight or branched C1 to C10 alkyl; or pharmaceutically acceptable salts thereof.
- 9. The method of claim 8, wherein said Lipid A analog has the structure:
- 10. The method of claim 8, wherein said antiendotoxin compound is administered by inhalation.
- 11. The method of claim 10, wherein said antiendotoxin compound is administered in an aerosolized formulation.
- 12. The method of claim 8, wherein 0.01-50 mg of said antiendotoxin compound is administered to said subject in a single dose.
- 13. The method of claim 12, wherein 0.05-25 mg of said antiendotoxin compound is administered to said subject in a single dose.
- 14. The method of claim 13, wherein 1-12 mg of said antiendotoxin compound is administered to said subject in a single dose.
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. Ser. No. 09/293,856, filed Apr. 2, 1999, (now U.S. Pat. No. 6,184,366) which is a continuation of U.S. Ser. No. 08/658,656, filed Jun. 5, 1996 (now U.S. Pat. No. 5,935,938), which is a continuation-in-part of U.S. Ser. No. 08/461,675, filed Jun. 5, 1995 (now U.S. Pat. No. 5,750,664).
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Continuations (1)
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Number |
Date |
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Parent |
08/658656 |
Jun 1996 |
US |
Child |
09/293856 |
|
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09/293856 |
Apr 1999 |
US |
Child |
09/449601 |
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US |
Parent |
08/461675 |
Jun 1995 |
US |
Child |
08/658656 |
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US |