Methods and compositions for preventing, reducing, or eliminating toxicity caused by acetaminophen (APAP)

Abstract

The present invention provides methods and compositions for preventing, reducing, or eliminating the toxicity caused by acetaminophen (APAP). [Solution] A method for preventing, reducing, reducing or eradicating toxicity caused by acetaminophen (APAP) or its derivatives, comprising administering a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, to a subject in need of it in an amount effective to prevent, reduce or eradicate toxicity caused by APAP. The toxicity caused by APAP is nephrotoxicity and / or hepatotoxicity.

Claims

1. A method for preventing, reducing, mitigating, or eliminating toxicity caused by acetaminophen (APAP) or its derivatives, Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG 8000, Span A method comprising administering a compound selected from the group consisting of 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof, to a subject in need of it in an amount effective to prevent, reduce, or eliminate toxicity caused by APAP.

2. A method for preventing, reducing, mitigating, or eliminating toxicity caused by acetaminophen (APAP) or its derivatives, A method comprising administering a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol, and any combination thereof, to a subject in need in an amount effective to prevent, reduce, or eliminate toxicity caused by APAP.

3. The method according to claim 1 or 2, wherein the toxicity is nephrotoxicity and / or hepatotoxicity.

4. The method according to claim 2, wherein the first compound comprises a combination of Eudragit S100, Pluronic F68, and naringenin.

5. The method according to claim 2, further comprising administering to a subject a second compound selected from the group consisting of mannitol, sucralose, luteolin, and any combination thereof.

6. The first and second compounds administered to the subjects are as follows: (i) A combination of Eudragit S100 and sucralose; (ii) A combination of Pluronic F68 and sucralose; (iii) combination of Eudragit S100 and mannitol; (iv) Pluronic F68 and mannitol combination; (v) A combination of Eudragit S100, sucralose, and luteolin; (vi) combinations of kaempferol, mannitol and sucralose; and (v) combination of naringenin, mannitol, and sucralose; The method according to claim 5, which is a combination selected from the group consisting of the following.

7. The use of a compound for the manufacture of an agent (e.g., an antidote) for preventing, reducing, or eliminating the toxicity caused by acetaminophen (APAP) or its derivatives (e.g., as an acetaminophen toxicity inhibitor or preventative agent), The compound is Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG Use of a substance selected from the group consisting of PEG-8000, Span 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, provideon K30, PEG-2000, and any combination thereof.

8. The use of a first compound for the manufacture of an agent (e.g., an antidote) for preventing, reducing, or eliminating the toxicity caused by acetaminophen (APAP) or its derivatives (e.g., as an acetaminophen toxicity inhibitor or blocker), The first compound is selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol, and any combination thereof.

9. The use according to claim 7 or 8, wherein the toxicity is nephrotoxicity and / or hepatotoxicity.

10. The use according to claim 8, wherein the first compound comprises a combination of Eudragit S100, Pluronic F68, and naringenin.

11. The use according to claim 8, wherein the first compound is administered together with a second compound selected from the group consisting of mannitol, sucralose, luteolin, and any combination thereof.

12. The first compound and the second compound are as follows: (i) A combination of Eudragit S100 and sucralose; (ii) A combination of Pluronic F68 and sucralose; (iii) combination of Eudragit S100 and mannitol; (iv) Pluronic F68 and mannitol combination; (v) A combination of Eudragit S100, sucralose, and luteolin; (vi) combinations of kaempferol, mannitol and sucralose; and (v) combination of naringenin, mannitol, and sucralose; The use according to claim 11, which is a combination selected from the group consisting of the following.

13. A composition for preventing, reducing, or eliminating toxicity caused by acetaminophen (APAP) or its derivatives (for example, as an acetaminophen toxicity inhibitor or blocker), Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG 8000, Span A composition comprising compounds selected from the group consisting of 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof.

14. A composition for use in preventing, reducing, or eliminating toxicity caused by acetaminophen (APAP) or its derivatives (for example, as an acetaminophen toxicity inhibitor or preventative agent), A composition comprising a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol, and any combination thereof.

15. The composition according to claim 13 or 14, wherein the toxicity is nephrotoxic and / or hepatotoxic.

16. The composition according to claim 14, wherein the first compound comprises a combination of Eudragit S100, Pluronic F68, and Naringenin.

17. The composition according to claim 14, further comprising a second compound selected from the group consisting of mannitol, sucralose, luteolin, and any combination thereof.

18. The first compound and the second compound are as follows: (i) A combination of Eudragit S100 and sucralose; (ii) A combination of Pluronic F68 and sucralose; (iii) combination of Eudragit S100 and mannitol; (iv) Pluronic F68 and mannitol combination; (v) A combination of Eudragit S100, sucralose, and luteolin; (vi) combinations of kaempferol, mannitol and sucralose; and (v) combination of naringenin, mannitol, and sucralose; The composition according to claim 17, which is a combination selected from the group consisting of the following.

19. A method for preventing, reducing, mitigating, or eliminating nephrotoxicity caused by acetaminophen (APAP) or its derivatives, Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG 8000, Span A method comprising administering a compound selected from the group consisting of 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof, to a subject in need of it in an amount effective to prevent, reduce, or eliminate toxicity caused by APAP.

20. A method for preventing, reducing, mitigating, or eliminating nephrotoxicity caused by acetaminophen (APAP) or its derivatives, A method comprising administering to a subject in need of it, in an amount effective to prevent, reduce or eliminate toxicity caused by APAP, a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, and / or a second compound selected from the group consisting of mannitol, sucralose, luteolin and any combination thereof.

21. The method according to claim 20, wherein the first compound comprises a combination of Eudragit S100, Pluronic F68, and naringenin.

22. The method according to claim 20, wherein the second compound comprises mannitol and sucralose.

23. The method according to claim 20, wherein a combination of the first compound and the second compound is administered to a subject.

24. The first compound and the second compound are as follows: (i) A combination of Eudragit S100 and sucralose; (ii) A combination of Pluronic F68 and sucralose; (iii) combination of Eudragit S100 and mannitol; (iv) Pluronic F68 and mannitol combination; (v) A combination of Eudragit S100, sucralose, and luteolin; (vi) combinations of kaempferol, mannitol and sucralose; and (v) combination of naringenin, mannitol, and sucralose; The method according to claim 23, which is a combination selected from the group consisting of the following.

25. Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij Use of compounds selected from the group consisting of 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG 8000, Span 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof.

26. The use of a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, and / or a second compound selected from the group consisting of Mannitol, Sucralose, Luteolin and any combination thereof, for the manufacture of a drug (e.g., an antidote) for preventing, reducing or eradicating nephrotoxicity caused by acetaminophen (APAP) or its derivatives (e.g., as an acetaminophen toxicity inhibitor or prophylactic agent).

27. A composition for use in preventing, reducing, or eliminating nephrotoxicity caused by acetaminophen (APAP) or its derivatives (for example, as an acetaminophen toxicity inhibitor or prophylaxis), Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween 40, PEG 400, PEG 4000, PEG 8000, Span A composition comprising compounds selected from the group consisting of 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof.

28. A composition for use in preventing, reducing, or eliminating nephrotoxicity caused by acetaminophen (APAP) or its derivatives, A composition comprising a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, and / or a second compound selected from the group consisting of mannitol, sucralose, luteolin and any combination thereof.

29. To treat conditions treatable by APAP, in amounts effective to prevent, reduce or eliminate toxicity caused by APAP, the following ingredients are used: Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofor RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofor EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween A method of administering a therapeutically effective amount of APAP or a derivative thereof to a subject in need, in combination with a compound selected from the group consisting of PEG 40, PEG 400, PEG 4000, PEG 8000, Span 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, provideon K30, PEG 2000, and any combination thereof.

30. A method of administering a therapeutically effective amount of APAP or a derivative thereof to a subject in need, in combination with a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, and / or a second compound selected from the group consisting of mannitol, sucralose, luteolin and any combination thereof, in an amount effective to prevent, reduce or eliminate the toxicity caused by APAP, for the purpose of treating a condition treatable by APAP.

31. A therapeutically effective dose of APAP, and an effective amount to prevent, reduce or eliminate the toxicity caused by APAP, containing: Eudragit S100, Pluronic F68, Naringenin, Kaempferol, Mannitol, Sucralose, Luteolin, Menthol, Polyethylene glycol sorbitan monolaurate (Tween 20), Microcrystalline cellulose, Brij 35, Saccharin, Cremofol RH40, Crospovidone, Sodium starch glycolate, Eudragit S100, Croscarmellose sodium, Low-substituted hydroxypropyl cellulose, Pregelatinized starch, Dextrate NF hydrate, Citric acid, Cremofol EL, Aerosil 200, Myrj 52, Sorbic acid, Lemon oil, Hydroxypropyl cellulose, Sorbitol, Acesulfame potassium, Hydroxypropyl methylcellulose, Lactose monohydrate, Maltodextrin, Brij 58, Brij 76, Tween 80, Tween A combination comprising compounds selected from the group consisting of PEG 40, PEG 400, PEG 4000, PEG 8000, Span 60, sodium benzoate, hydroxyethyl methylcellulose, methylcellulose, Span 80, sodium cyclamate, glyceryl behenate, oxide red, glycerin monostearate, copovidone K28, starch acetate, magnesium stearate, sodium lauryl sulfate, providedon K30, PEG 2000, and any combination thereof.

32. A combination comprising a therapeutically effective dose of APAP, and a first compound selected from the group consisting of Eudragit S100, Pluronic F68, Naringenin, Kaempferol and any combination thereof, in an amount effective to prevent, reduce or eliminate the toxicity caused by APAP, and / or a second compound selected from the group consisting of mannitol, sucralose, luteolin and any combination thereof.

33. The method according to claim 29 or 30, or the combination according to claim 31 or 32, wherein APAP is administered in a higher dose than the usual dose.

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