FORMULATION AND METHOD FOR INCREASING ORAL BIOAVAILABILITY OF DRUGS

• US 20140348926A1
• Filed: 01/17/2013
• Published: 11/27/2014
• Est. Priority Date: 01/19/2012
• Status: Abandoned Application

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Hoffman, Amnon, Domb, Abraham J., Elgart, Anna, Cherniakov, Irina
• Application Number:
  US14/371,819
• Publication Number:
  US 20140348926A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 36/67 Piperaceae (Pepper family), e.g. Jamaican pepper or kava
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars

Abstract

The application discloses a formulation and method for increasing bioavailability of an orally administered drug.

Claims

1-48. -48. (canceled)

49. A composition for oral administration of at least one drug, said composition comprising:

a) a dispersible concentrate, wherein it is capable of forming, upon contact with an aqueous solution, particles of a size of less than about 500 nm, said dispersible concentrate comprising;

(i) at least one surfactant;

(ii) at least one solid component at room temperature; and

(iii) an amphiphilic solvent;

b) an amount of at least one piperine, piperine analog or isomer thereof, sufficient to increase the bioavailability of said composition.

50. The composition according to claim 49, further comprising at least one drug.

51. The composition according to claim 49, wherein the surfactant is a combination of at least one high HLB (hydrophilic/lipophilic balance) surfactant, having an HLB of at least about 8, with at least one surfactant being a low HLB surfactant having an HLB of less than about 5.

52. The composition according to claim 49, further comprising a phospholipid.

53. The composition according to claim 49, further comprising a fatty acid ester.

54. The composition according to claim 49, wherein said amphiphilic solvent is selected from the group consisting of lower alkyl esters of lactic acid, lower alkyl lactone esters and N-methylpyrrolidone.

55. The composition according to claim 49, wherein said piperine is obtained from Piper longum or Piper nigrum.

56. The composition according to claim 50, wherein said drug is a lipophilic compound or a mixture of at least two lipophilic compounds.

57. The composition according to claim 56, wherein the lipophilic compound is a cannabinoid, a derivative or a synthetic analog thereof, or a mixture of cannabinoids.

58. The composition according to claim 50, wherein the composition and at least one drug are formulated for administration in the same pharmaceutical formulation.

59. The composition according to claim 50, wherein the composition and drug are formulated for administration in different pharmaceutical formulations.

60. The composition according to claim 50, wherein said at least one drug is a cannabinoid, a derivative or a synthetic analog thereof, or a mixture of cannabinoids.

61. The composition according to claim 60, wherein said cannabinoid being selected from the group consisting of tetrahydrocannabinol, cannabidiol (CBD), cannabinol, cannabigerol, tetrahydrocannabivarin, cannabidivarin and cannabichromene.

62. A method for increasing the bioavailability of a drug in a mammal in need of said drug, the method comprising orally administering:

(1) said drug, and

(2) a composition according claim 49, wherein said at least one piperine, piperine analog or isomer thereof being present in said composition in an amount sufficient to provide a greater bioavailability of said drug than bioavailability of said drug in the absence of said at least one piperine, piperine analog or isomer thereof.

63. The method according to claim 62, wherein said composition being administered substantially simultaneously with the drug.

64. The method according to claim 62, wherein said composition and drug are sequentially administered.

65. The method according to claim 62, wherein the drug is administered in at least one dose within 24 hrs after administration of the dose of said composition.

66. The method according to claim 62, for treatment of at least one disease or disorder.

67. The method according to claim 62, wherein said at least one drug is a cannabinoid, a derivative or a synthetic analog thereof, or a mixture of cannabinoids.

68. The method according to claim 62, wherein said drug is a cannabinoid being selected from the group consisting of tetrahydrocannabinol, cannabidiol (CBD), cannabinol, cannabigerol, tetrahydrocannabivarin, cannabidivarin and cannabichromene.