Cochleates made with soy phosphatidylserine
Unpurified or low pure soy phosphatidylserine is used to make cochleates. The cochleates contain about 40-74% soy phosphatidylserine, a multivalent cation and a biological active. A preferred cochleate contains the antifungal agent amphotericin B.
1. A cochleate, comprising:
a soy-based phospholipid comprising 40% to 55% by weight soy phosphatidylserine,
a multivalent cation, and
a bioactive drug.
2. The cochleate of claim 1 , wherein the soy-based phospholipid is a mixture composed of at least soy phosphatidylserine and phosphatidic acid.
3. The cochleate of claim 1 , wherein the bioactive drug is at least one member selected from the group consisting of a protein, a small peptide, a polynucleotide, an aminoglycoside, an antiviral agent, an anesthetic, an antibiotic, an antifungal agent, an anticancer agent, an immunosuppressant, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, a tranquilizer, a nutritional supplement, an herbal product, a vitamin and a vasodilatory agent.
4. The cochleate of claim 3 , wherein the bioactive drug is at least one member selected from the group consisting of an aminoglycoside, amphotericin B, acyclovir, adriamycin, cabamazepine, curcumin, melphalan, nifedipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids, rapamycin, propanidid, propofol, alphadione, echinomycine, miconazole nitrate, teniposide, a taxane, paclitaxel, and taxotere.
5. The cochleate of claim 1 , wherein the multivalent cation is Ca ++ , Zn ++ , Ba ++ , or Mg ++ .
6. The cochleate of claim 1 , wherein the multivalent cation is Ca ++ .
7. The cochleate of claim 1 , wherein the bioactive drug is amphotericin B.
8. The cochleate of claim 1 , wherein the bioactive drug is curcumin.
9. The cochleate of claim 1 , wherein the bioactive drug is an aminoglycoside.
10. The cochleate of claim 1 , wherein the bioactive drug is amikacin.
11. The cochleate of claim 1 , wherein the cochleate further comprises bile salts.
12. The cochleate of claim 11 , wherein the weight ratio of soy-based phospholipid to the bile salts is between 20:1 and 0.5:1.
13. A method for administering a cochleate to a subject, the method comprising: administering the chochleate to the subject, wherein the cochleate comprises (i) a soy-based phospholipid that comprises 40% to 55% by weight soy phosphatidylserine, (ii) a multivalent cation, and (iii) a bioactive drug, wherein the cochleate is prepared by a process comprising the steps of:
(a) mixing a solution of the bioactive drug and the soy-based phospholipid to form a suspension of liposomes in an aqueous medium, wherein the liposomes comprise (i) a lipid bilayer comprising soy phosphatidylserine in an amount of 40% to 55% by weight of the lipid bilayer and (ii) the bioactive drug;
(b) adding a multivalent cation to the suspension of liposomes of (a) to form the cochleate; and
(c) collecting the cochleate.
14. The method of claim 13 , wherein in step (a), the aqueous medium containing the suspension of liposomes is buffered and has a pH of 6.5-7.5, and the solution of the bioactive drug is at pH 10 or higher prior to mixing with the soy-based phospholipid to form the suspension of liposomes.
15. The method of claim 14 , wherein the suspension of liposomes is buffered with phosphate.
16. The method of claim 13 , wherein the bioactive drug is at least one member selected from the group consisting of a protein, a small peptide, a polynucleotide, an antiviral agent, an anesthetic, an antibiotic, an antifungal agent, an anticancer agent, an immunosuppressant, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, a tranquilizer, a nutritional supplement, an herbal product, a vitamin and a vasodilatory agent.
17. The method of claim 16 , wherein the bioactive drug is at least one member selected from the group consisting of an aminoglycoside, amphotericin B, acyclovir, adriamycin, cabamazepine, curcumin, melphalan, nifedipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids, rapamycin, propanidid, propofol, alphadione, echinomycine, miconazole nitrate, teniposide, a taxane, paclitaxel, and taxotere.
18. The method of claim 13 , wherein the multivalent cation is Ca ++ , Zn ++ , Ba ++ , or Mg ++ .
19. The method of claim 18 , wherein the multivalent cation is Ca ++ .
20. The method of claim 13 , wherein the bioactive drug is amphotericin B.
21. The method of claim 13 , wherein the bioactive drug is curcumin.
22. The method of claim 13 , wherein the bioactive drug is amikacin.
23. The method of claim 13 , wherein the weight ratio of the lipid bilayer to the bioactive drug is from 3:1 to 20:1.
24. The method of claim 13 , wherein the process further comprises a step of adding bile salts to the suspension of liposomes of (a) before step (b) or adding bile salts to the cochleate after step (b), wherein the weight ratio of the lipid bilayer to the bile salts is between 20:1 and 0.5:1.
25. A method of administering a cochleate to a subject, the method comprising administering the cochleate to the subject, wherein the cochleate comprises (i) a soy-based phospholipid that comprises 40% to 55% by weight soy phosphatidylserine, (ii) a multivalent cation and (iii) a bioactive drug.
26. The method of claim 25 , wherein the bioactive drug is an anti-fungal agent and the method comprises administering to the subject an effective anti-fungal amount of the cochleate, wherein the cochleate comprises (i) the soy-based phospholipid that comprises 40% to 55% by weight soy phosphatidylserine, (ii) the multivalent cation and (iii) the anti-fungal agent.
27. The method of claim 26 , wherein the antifungal agent is amphotericin B.
28. The method of claim 25 , wherein the bioactive drug is an anti-bacterial agent and the method comprises administering to the subject an effective anti-bacterial amount of the cochleate, wherein the cochleate comprises (i) the soy-based phospholipid that comprises 40% to 55% by weight soy phosphatidylserine, (ii) the multivalent cation and (iii) the anti-bacterial agent.
29. The method of claim 28 , wherein the antibacterial agent is an aminoglycoside or amikacin.
30. The method of claim 25 , the bioactive drug is at least one member selected from the group consisting of a protein, a small peptide, a polynucleotide, an antiviral agent, an anesthetic, an antibiotic, an antifungal agent, an anticancer agent, an immunosuppressant, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, a tranquilizer, a nutritional supplement, an herbal product, a vitamin and a vasodilatory agent.
31. The method of claim 25 , wherein the bioactive drug is at least one member selected from the group consisting of an aminoglycoside, amphotericin B, acyclovir, adriamycin, cabamazepine, curcumin, melphalan, nifedipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids, rapamycin, propanidid, propofol, alphadione, echinomycine, miconazole nitrate, teniposide, a taxane, paclitaxel, and taxotere.
32. The method of claim 25 , wherein the multivalent cation is Ca ++ , Zn ++ , Ba ++ , or Mg ++ .
33. The method of claim 25 , wherein the multivalent cation is Ca ++ .
34. The cochleate of claim 1 , wherein the cochleate is a crystal cochleate.
35. The cochleate of claim 1 , wherein the cochleate is a geodate.
36. The method of claim 13 , wherein the cochleate is a crystal cochleate.
37. The method of claim 13 , wherein the cochleate is a geodate.
38. The method of claim 25 , wherein the cochleate is a crystal cochleate.
39. The method of claim 25 , wherein the cochleate is a geodate.