CA2488230A1 - Inositol pyrophosphates, and methods of use thereof - Google Patents

Inositol pyrophosphates, and methods of use thereof Download PDF

Info

Publication number
CA2488230A1
CA2488230A1 CA002488230A CA2488230A CA2488230A1 CA 2488230 A1 CA2488230 A1 CA 2488230A1 CA 002488230 A CA002488230 A CA 002488230A CA 2488230 A CA2488230 A CA 2488230A CA 2488230 A1 CA2488230 A1 CA 2488230A1
Authority
CA
Canada
Prior art keywords
compound
instance
ihp
ammonium ions
internal pyrophosphate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002488230A
Other languages
French (fr)
Other versions
CA2488230C (en
Inventor
Yves Claude Nicolau
Jean Marie Lehn
Konstantina Fylaktakidou
Ruth Greferath
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NormOxys Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2488230A1 publication Critical patent/CA2488230A1/en
Application granted granted Critical
Publication of CA2488230C publication Critical patent/CA2488230C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • A61K31/6615—Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/18—Erythrocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/117—Esters of phosphoric acids with cycloaliphatic alcohols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C07F9/65746—Esters of oxyacids of phosphorus the molecule containing more than one cyclic phosphorus atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/207—Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0641—Erythrocytes

Abstract

The present invention comprises compounds, compositions thereof, and methods capable of delivering modified inositol hexaphosphate (IHP) comprising an internal pyrophosphate ring to the cytoplasm of mammalian cells. In certain embodiments, the present invention relates to compounds, compositions thereof, and methods that enhance the ability of mammalian red blood cells to deliver oxygen, by delivering IHP to the cytoplasm of the red blood cells.

Claims (92)

1. A composition, comprising a salt complex comprising an aliphatic ammonium cation, and an anionic ligand for an allosteric site of hemoglobin, wherein the anionic ligand comprises an internal pyrophosphate ring.
2. The composition of claim 1, wherein the anionic ligand comprises two internal pyrophosphate rings.
3. The composition of claim 2, wherein the anionic ligand comprises three internal pyrophosphate rings.
4. The composition of claim 1, wherein the anionic ligand is a phosphorylated inositol.
5. The composition of claim 1, wherein the anionic ligand is an inositol hexaphosphate.
6. The composition of claim 1, wherein the aliphatic ammonium canon is a lipophilic, water-soluble aliphatic ammonium cation.
7. The composition of claim 1, wherein the aliphatic ammonium cation is a monoalkyl, dialkyl, trialkyl or tetraalkyl ammonium moiety.
8. The composition of claim 1, wherein the aliphatic ammonium cation is an N,N-dimethyl-cyclohexylammonium cation.
9. The composition of claim 1, wherein the aliphatic ammonium cation is a monoalkyl ammonium cation.
10. The composition of claim 1, wherein the aliphatic ammonium cation is a primary ammonium cation.
11. A compound represented by structure I:
wherein:
C+ represents independently for each occurrence an aliphatic ammonium cation, an alkali metal cation, an alkaline earth cation, or other suitable metal canon;
and A represents an anionic ligand for a mammalian cellular receptor, wherein said anionic ligand comprises 1, 2, or 3 internal pyrophosphate rings; and n is an integer in the range of 1 to 10 inclusive.
12. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions.
13. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions.
14. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions.
15. The compound of claim 11, wherein an instance of C+ is N,N-dimethyl-cyclohexylammonium.
16. The compound of claim 11, wherein A is a ligand for the allosteric site of hemoglobin.
17. The compound of claim 11, wherein A is a phosphorylated inositol.
18. The compound of claim 11, wherein A is a phosphorylated inositol, wherein said phosphorylated inositol is a ligand for the allosteric site of hemoglobin.
19. The compound of claim 11, wherein A is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
20. The compound of claim 11, wherein A is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
21. The compound of claim 11, wherein A is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
22. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a ligand for the allosteric site of hemoglobin.
23. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a ligand for the allosteric site of hemoglobin comprising one internal pyrophosphate ring.
24. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a ligand for the allosteric site of hemoglobin comprising two internal pyrophosphate rings.
25. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;

and A n- is a ligand for the allosteric site of hemoglobin comprising three internal pyrophosphate rings.
26. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a phosphorylated inositol.
27. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a phosphorylated inositol comprising one internal pyrophosphate ring.
28. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a phosphorylated inositol comprising two internal pyrophosphate rings.
29. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is a phosphorylated inositol comprising three internal pyrophosphate rings.
30. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
31. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
32. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C1-C8 alkyl ammonium ions and C3-C10 cycloalkyl ammonium ions;
and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
33. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin.
34. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin comprising one internal pyrophosphate ring.
35. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin comprising two internal pyrophosphate rings.
36. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin comprising three internal pyrophosphate rings.
37. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a phosphorylated inositol.
38. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a phosphorylated inositol comprising one internal pyrophosphate ring.
39. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a phosphorylated inositol comprising two internal pyrophosphate rings.
40. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is a phosphorylated inositol comprising three internal pyrophosphate rings.
41. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is IHP.
42. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
43. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
44. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of C3-C10 cycloalkyl ammonium ions; and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
45. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin.
46. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin and comprises one internal pyrophosphate ring.
47. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin and comprises two internal pyrophosphate rings.
48. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a ligand for the allosteric site of hemoglobin and comprises three internal pyrophosphate rings.
49. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a phosphorylated inositol.
50. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a phosphorylated inositol and comprises one internal pyrophosphate ring.
51. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a phosphorylated inositol and comprises two internal pyrophosphate rings.
52. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is a phosphorylated inositol and comprises three internal pyrophosphate rings.
53. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is IHP.
54. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
55. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
56. The compound of claim 11, wherein an instance of C+ is selected from the group consisting of cyclohexyl ammonium ions; and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
57. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a ligand for the allosteric site of hemoglobin.
58. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a ligand for the allosteric site of hemoglobin, wherein said ligand for the allosteric site of hemoglobin comprises one internal pyrophosphate ring.
59. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a ligand for the allosteric site of hemoglobin, wherein said ligand for the allosteric site of hemoglobin comprises two internal pyrophosphate rings.
60. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a ligand for the allosteric site of hemoglobin, wherein said ligand for the allosteric site of hemoglobin comprises three internal pyrophosphate rings.
61. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a phosphorylated inositol, wherein said phosphorylated inositol is a ligand for the allosteric site of hemoglobin and comprises one internal pyrophosphate ring.
62. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a phosphorylated inositol, wherein said phosphorylated inositol is a ligand for the allosteric site of hemoglobin and comprises two internal pyrophosphate rings.
63. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is a phosphorylated inositol, wherein said phosphorylated inositol is a ligand for the allosteric site of hemoglobin and comprises three internal pyrophosphate rings.
64. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is IHP.
65. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
66. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
67. The compound of claim 11, wherein an instance of C+ is a sodium ion; and A
n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
68. The compound of claim 11, wherein an instance of C+ is a pyridinium ion, and A n- is IHP.
69. The compound of claim 11, wherein an instance of C+ is a pyridinium ion, and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
70. The compound of claim 11, wherein an instance of C+ is a pyridinium ion, and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
71. The compound of claim 11, wherein an instance of C+ is a pyridinium ion, and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
72. The compound of claim 11, wherein an instance of C+ is N,N
dimethylcyclohexylammonium, and A n- is IHP.
73. The compound of claim 11, wherein an instance of C+ is N,N
dimethylcyclohexylammonium, and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
74. The compound of claim 11, wherein an instance of C+ is N,N
dimethylcyclohexylammonium, and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
75. The compound of claim 11, wherein an instance of C+ is N,N
dimethylcyclohexylammonium, and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
76. The compound of claim 11, wherein an instance of C+ is cycloheptylammonium, and A n- is IHP.
77. The compound of claim 11, wherein an instance of C+ is cycloheptylammonium, and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
78. The compound of claim 11, wherein an instance of C+ is cycloheptylammonium, and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
79. The compound of claim 11, wherein an instance of C+ is cycloheptylammonium, and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
80. The compound of claim 11, wherein an instance of C+ is cyclooctylammonium, and A n- is IHP.
81. The compound of claim 11, wherein an instance of C+ is cyclooctylammonium, and A n- is IHP, wherein two phosphate groups of said IHP form an internal pyrophosphate ring.
82. The compound of claim 11, wherein an instance of C+ is cyclooctylammonium, and A n- is IHP, wherein 4 phosphate groups of said IHP form two internal pyrophosphate rings.
83. The compound of claim 11, wherein an instance of C+ is cyclooctylammonium, and A n- is IHP, wherein the 6 phosphate groups of said IHP form three internal pyrophosphate rings.
84. A pharmaceutical formulation, comprising a composition of claim 1 or a compound of claim 11; and a pharmaceutically acceptable excipient.
85. A method of enhancing oxygen delivery to a tissue or organ of a mammal, comprising the step of administering to a mammal a therapeutically effective amount of a composition of claim 1, a compound of claim 11, or a composition comprising hexasodium inositol tripyrophosphate.
86. The method of claim 85, wherein the composition is administered orally.
87. A method of enhancing oxygen delivery to a tissue or organ of a mammal, comprising the step of administering to a mammal red blood cells previously treated with a composition of claim 1, a compound of claim 11, or a composition comprising hexasodium inositol tripyrophosphate.
88. A method of treating a mammal afflicted with anemia, coronary infarction, pulmonary disease, congestive heart failure, diabetes, myocardial infarction, stroke, peripheral vascular disease, intermittent claudication, circulatory shock, hemorrhagic shock, chronic hypoxia, altitude sickness, arteriosclerosis, respiratory alkalemia, metabolic alkalosis, sickle cell anemia, reduced lung capacity, gangrene, anaerobic infections, carbon monoxide poisoning, nitric oxide poisoning, or cyanide poisoning, comprising the step of administering to said mammal a therapeutically effective amount of a composition of claim 1, a compound of claim 11, or a composition comprising hexasodium inositol tripyrophosphate.
89. The method of claim 88, wherein the composition is administered orally.
90. A method of treating a mammal afflicted with anemia, coronary infarction, pulmonary disease, congestive heart failure, diabetes, myocardial infarction, stroke, peripheral vascular disease, intermittent claudication, circulatory shock, hemorrhagic shock, chronic hypoxia, altitude sickness, arteriosclerosis, respiratory alkalemia, metabolic alkalosis, sickle cell anemia, reduced lung capacity, gangrene, anaerobic infections, carbon monoxide poisoning, nitric oxide poisoning, or cyanide poisoning, comprising the step of administering to said mammal red blood cells previously treated with a composition of claim 1, a compound of claim 11, or a composition comprising hexasodium inositol tripyrophosphate.
91. A method of improving the oxygen delivering capability of mammalian blood, comprising the step of adding to a volume of mammalian blood a composition of claim 1, a compound of claim 11, or a composition comprising hexasodium inositol tripyrophosphate.
92. A method of incorporating a therapeutically useful substance into mammalian red blood cells, comprising the step of treating a sample of mammalian red blood cells with a composition of claim 1, 2, or 3, or a compound of claim 12, or a composition comprising hexasodium inositol tripyrophosphate, wherein said compositions or compound comprise said therapeutically useful substance.
CA2488230A 2002-04-29 2003-04-29 Inositol pyrophosphates, and methods of use thereof Expired - Fee Related CA2488230C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US37638302P 2002-04-29 2002-04-29
US60/376,383 2002-04-29
US38885102P 2002-06-14 2002-06-14
US60/388,851 2002-06-14
US39574902P 2002-07-12 2002-07-12
US60/395,749 2002-07-12
US42457302P 2002-11-07 2002-11-07
US60/424,573 2002-11-07
PCT/US2003/013105 WO2003092700A1 (en) 2002-04-29 2003-04-29 Inositol pyrophosphates, and methods of use thereof

Publications (2)

Publication Number Publication Date
CA2488230A1 true CA2488230A1 (en) 2003-11-13
CA2488230C CA2488230C (en) 2013-04-09

Family

ID=29408059

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2488230A Expired - Fee Related CA2488230C (en) 2002-04-29 2003-04-29 Inositol pyrophosphates, and methods of use thereof

Country Status (5)

Country Link
US (7) US7084115B2 (en)
EP (1) EP1503768B1 (en)
AU (2) AU2003231157C1 (en)
CA (1) CA2488230C (en)
WO (1) WO2003092700A1 (en)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITRE20010042A1 (en) * 2001-04-24 2002-10-24 Corghi Spa LIFTING DEVICE FOR TIRE CHANGING MACHINES
FR2828206B1 (en) * 2001-08-03 2004-09-24 Centre Nat Rech Scient USE OF LYSYL OXIDASE INHIBITORS FOR CELL CULTURE AND TISSUE ENGINEERING
US20030232887A1 (en) * 2002-04-10 2003-12-18 Johnson Douglas Giles Preparation and use of a stable formulation of allosteric effector compounds
AU2003231157C1 (en) 2002-04-29 2009-02-26 Normoxys, Inc. Inositol pyrophosphates, and methods of use thereof
WO2005102305A2 (en) 2004-04-22 2005-11-03 Allos Therapeutics, Inc. Compositions of allosteric hemoglobin modifiers and methods of making the same
US8658203B2 (en) 2004-05-03 2014-02-25 Merrimack Pharmaceuticals, Inc. Liposomes useful for drug delivery to the brain
ES2616047T3 (en) * 2004-05-03 2017-06-09 Merrimack Pharmaceuticals, Inc. Liposomes useful for drug administration
US7745423B2 (en) * 2004-07-06 2010-06-29 NormOxys, Inc Calcium/sodium salt of inositol tripyrophosphate as an allosteric effector of hemoglobin
US20060106000A1 (en) * 2004-07-06 2006-05-18 Claude Nicolau Use of inositol-tripyrophosphate in treating tumors and diseases
US20060258626A1 (en) * 2004-07-06 2006-11-16 Claude Nicolau Use of inositol-tripyrophosphate in treating tumors and diseases
US20070135389A1 (en) * 2004-07-06 2007-06-14 Claude Nicolau Tumor eradication by inositol-tripyrophosphate
US20120003161A1 (en) * 2004-07-06 2012-01-05 Normoxys, Inc. Use of inositol-tripyrophosphate in treating tumors and diseases
CA2601641A1 (en) * 2005-03-18 2006-09-28 Oxyplus, Inc. Calcium salt of myo-inositol 1,6:2,3:4,5 tripyrophosphate as an allosteric effector of hemoglobin
EP2380588B1 (en) * 2005-12-12 2015-08-05 AC Immune S.A. Therapeutic vaccine
AU2006335318A1 (en) * 2006-01-06 2007-07-19 Oxyplus, Inc. Use of inositol-tripyrophosphate in treating tumors and diseases
UA96768C2 (en) * 2006-08-02 2011-12-12 Йоганес Гутенберг-Універсітет Майнц Medicament for lct poisoning
CN101686986A (en) * 2006-12-29 2010-03-31 诺尔姆奥克西斯公司 cyclitols and their derivatives and their therapeutic applications
CN101784193A (en) * 2007-05-01 2010-07-21 诺尔姆奥克西斯公司 erythropoietin complementation or replacement
US8986253B2 (en) 2008-01-25 2015-03-24 Tandem Diabetes Care, Inc. Two chamber pumps and related methods
AU2008356891A1 (en) * 2008-05-30 2009-12-03 Normoxys, Inc. Calcium/sodium salt of inositol tripyrophosphate as an allosteric effector of hemoglobin
US8408421B2 (en) 2008-09-16 2013-04-02 Tandem Diabetes Care, Inc. Flow regulating stopcocks and related methods
US8650937B2 (en) 2008-09-19 2014-02-18 Tandem Diabetes Care, Inc. Solute concentration measurement device and related methods
FR2944106B1 (en) * 2009-04-03 2012-09-28 Erytech Pharma METHOD OF DETERMINING INOSITOL HEXAPHOSPHATE (IHP).
RU2563127C2 (en) * 2009-07-07 2015-09-20 Нормоксис, Инк, Method for reducing multi-drug resistance with using inositol tripyrophosphate
CA2769030C (en) 2009-07-30 2016-05-10 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
US9180242B2 (en) 2012-05-17 2015-11-10 Tandem Diabetes Care, Inc. Methods and devices for multiple fluid transfer
US9555186B2 (en) 2012-06-05 2017-01-31 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
US9173998B2 (en) 2013-03-14 2015-11-03 Tandem Diabetes Care, Inc. System and method for detecting occlusions in an infusion pump
CA2907175C (en) * 2013-03-15 2022-11-08 M. Alphabet 3, L.L.C. Methods and compositions for enhancing oxygen levels in tissues
WO2015138916A1 (en) * 2014-03-14 2015-09-17 Yves Claude Nicolau Myo-inositol trispyrophoshate as an anti-diabetic agent
US20170021046A1 (en) * 2015-03-18 2017-01-26 Mojack Distributors, Llc Odor removal assembly
US10456360B2 (en) 2015-10-16 2019-10-29 Ipsen Biopharm Ltd. Stabilizing camptothecin pharmaceutical compositions
WO2018211474A1 (en) 2017-05-19 2018-11-22 Trudell Medical International Positive expiratory pressure device
USD903097S1 (en) 2018-05-18 2020-11-24 Trudell Medical International Mask
USD874064S1 (en) 2018-05-18 2020-01-28 Trudell Medical International Mask
USD893806S1 (en) 2018-11-09 2020-08-18 Trudell Medical Internationl Mask and shroud
CN109432410A (en) * 2018-12-19 2019-03-08 上海康孕企业管理合伙企业（有限合伙） Application of the ferroheme in the drug of prevention and/or improvement altitude sickness, Food and hygienical food
US10881781B1 (en) * 2020-04-29 2021-01-05 Orth Consulting, Llc Blood processing apparatus and method for detoxifying bacterial lipopolysaccharide
US11103628B1 (en) * 2020-04-29 2021-08-31 Orth Consulting, Llc Blood processing apparatus and method for detoxifying bacterial lipopolysaccharide

Family Cites Families (94)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US477134A (en) * 1892-06-14 Oyster-washing machine
JPS5858438B2 (en) 1976-03-08 1983-12-24 三井東圧化学株式会社 Cobalt-tin alloy plating bath
US4192869A (en) 1977-09-06 1980-03-11 Studiengesellschaft Kohle Mbh. Controlled improvement of the O2 release by intact erythrocytes with lipid vesicles
DE2740053A1 (en) 1977-09-06 1979-05-03 Klaus Prof Dr Med Gersonde USE OF ALLOSTERIC EFFECTORS WITH THE LIPID VESICLES WITH AN IRREVERSIBLE INCORPORATION FOR THE IMPROVED O DEEP 2 DISCHARGE OF THE HAEMOGLOBIN IN ERYTHROCYTES
JPS5828878B2 (en) * 1980-08-20 1983-06-18 三金工業株式会社 Cyclic pyrophosphate derivative
US4473496A (en) 1981-09-14 1984-09-25 The United States Of America As Represented By The Secretary Of The Army Intramolecularly crosslinked hemoglobin
FR2529463B1 (en) 1982-07-05 1986-01-10 Centre Nat Rech Scient METHOD AND DEVICE FOR THE ENCAPSULATION IN ERYTHROCYTES OF AT LEAST ONE BIOLOGICALLY ACTIVE SUBSTANCE, IN PARTICULAR ALLOSTERIC EFFECTORS OF HEMOGLOBIN AND ERYTHROCYTES OBTAINED THEREBY
US4473495A (en) 1983-07-28 1984-09-25 Northwestern University Albumin-solubilized hymenoptera venoms for vaccine use
US4478824A (en) 1983-08-08 1984-10-23 Franco Robert S Method for altering red blood cell function and survival
GB8328917D0 (en) * 1983-10-28 1983-11-30 Fisons Plc Blood substitute
US5015634A (en) 1986-04-16 1991-05-14 Perstorp Ab Method of treating tissue damage with inositol triphosphate
US5330979A (en) 1984-10-23 1994-07-19 Perstorp Ab Method of treating renal disorders with inositoltriphosphate
SE465951B (en) 1984-10-23 1991-11-25 Perstorp Ab ISOMER OF INOSITOL TRIPHOSPHATE PHARMACEUTICAL STATEMENTS FOR SALT FOR USE AS THERAPEUTIC OR PROPHYLACTIC AGENTS AND COMPOSITIONS THEREOF
US5023248A (en) 1984-10-23 1991-06-11 Perstorp Ab Method of treating diabetes with inositol triphosphate
US5545632A (en) 1984-10-23 1996-08-13 Perstorp Ab Method of treating retroviral disease
US5407924A (en) 1984-10-23 1995-04-18 Perstorp Ab Method of treating pain using inositol triphosphate
SE465305B (en) 1986-04-16 1991-08-26 Perstorp Ab USE OF INOSITOL PHOSPHATE FOR THE PREPARATION OF A MEDICINE
US4887995A (en) 1985-01-22 1989-12-19 University Of Pittsburgh Method of treating sickle cell anemia
WO1987005598A1 (en) 1986-03-11 1987-09-24 Mitsui Toatsu Chemicals, Incorporated Myoinositol derivatives and process for their preparation
US5292913A (en) * 1986-03-11 1994-03-08 Mitsui Toatsu Chemicals, Incorporated Myoinositol derivatives and preparation process thereof
US4751244A (en) 1986-04-04 1988-06-14 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4699926A (en) 1986-04-04 1987-10-13 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4731473A (en) 1986-04-04 1988-03-15 Merck & Co., Inc. Compounds useful in treating sickle cell anemia
US4731381A (en) 1986-04-04 1988-03-15 Merck & Co., Inc. Method of treating a person for sickle cell anemia
US5057507A (en) 1986-04-16 1991-10-15 Perstorp Ab Method of alleviating bone damage with inositoltriphosphate
US5135923A (en) 1986-04-16 1992-08-04 Perstorp Ab Method of treating cardiovascular diseases
US4952396A (en) 1986-11-19 1990-08-28 Linus Pauling Institute Of Science & Medicine Method of using phytic acid for inhibiting tumor growth
US5274161A (en) 1986-11-26 1993-12-28 Perstorp Ab Derivatives of cyclohexane
US4847082A (en) 1987-01-21 1989-07-11 Robert Sabin Method of treatment of Alzheimer's disease using phytic acid
EP0319577A4 (en) * 1987-04-24 1990-01-08 Nippon Kokan Kk High-speed rotational arc welding machine.
US4873355A (en) 1987-05-29 1989-10-10 E. I. Du Pont De Nemours And Company Process for regioselectively preparing phosphorylated inositols and other cyclitols
US4924023A (en) 1987-05-29 1990-05-08 E. I. Du Pont De Nemours And Company Phosphorylated inositols
US4931276A (en) * 1987-10-30 1990-06-05 Franco Robert S Method for introducing desired agents into red blood cells
JP2597618B2 (en) 1987-12-28 1997-04-09 三井東圧化学 株式会社 Optical splitting method
US5407926A (en) * 1987-12-29 1995-04-18 Alcon Laboratories, Inc. Ophthalmic composition
US4826675A (en) * 1988-02-17 1989-05-02 Colgate-Palmolive Company Anticalculus oral composition
US5043261A (en) 1989-04-10 1991-08-27 Cryopharm Corporation Lyophilized and reconstituted red blood cell and hemosome compositions
US5082833A (en) 1988-06-30 1992-01-21 Shamsuddin Abulkalam M Reduction of cell proliferation and enhancement of nk-cell activity
US4874690A (en) 1988-08-26 1989-10-17 Cryopharm Corporation Lyophilization of red blood cells
EP0392697A3 (en) 1989-04-12 1991-01-16 Petrolite Corporation Demulsifiers for resolving emulsions formed in the production of pharmaceuticals
EP0431197A4 (en) * 1989-06-28 1991-12-04 Mitsui Toatsu Chemicals Inc. Myoinositol derivative and method of production thereof, and phosphorylating agent and its use
US5151539A (en) * 1989-07-03 1992-09-29 Akzo America Inc. Formation of tetraarylpyrophosphate
US5091579A (en) * 1989-07-14 1992-02-25 Aristech Chemical Corporation Aniline catalyst
JPH04178394A (en) * 1989-09-22 1992-06-25 Mitsui Toatsu Chem Inc Inositol production and production thereof
JPH03115290A (en) * 1989-09-28 1991-05-16 Yokohama Rubber Co Ltd:The Synthesis of 1d-myoinositol-1-phosphoric acid
US5173426A (en) 1989-10-06 1992-12-22 Yale University DNAs encoding genetically engineered low oxygen affinity mutants of human hemoglobin
GB9001509D0 (en) * 1990-01-23 1990-03-21 Davy Mckee Poole An optical imaging device for guiding a robot
US5210263A (en) 1990-05-15 1993-05-11 University Of Pittsburgh Inositol phosphate analogs and methods for their use
WO1992020369A1 (en) 1991-05-14 1992-11-26 Dana Farber Cancer Institute Use of hemoglobin in a method for the treatment of tumors with chemotherapeutic agents
US5295944A (en) 1991-05-14 1994-03-22 Dana-Farber Cancer Institute Method for treating a tumor with ionizing radiation
JPH05210723A (en) 1991-12-10 1993-08-20 Nec Corp Command selecting system in interactive system
US5260472A (en) 1992-01-29 1993-11-09 The Board Of Governors For Higher Education State Of Rhode Island And Providence Plantations Efficient chemoenzymatic synthesis of D-myo-inositol 1,4,5-triphosphate, D-myo-inositol 1,3,4-triphosphate, and D-myo-inositol 1,3,4,5-tetraphosphate
US5296466A (en) 1992-02-19 1994-03-22 Board Of Regents, The University Of Texas System Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein
US5344393A (en) 1992-02-28 1994-09-06 Alliance Pharmaceutical Corp. Use of synthetic oxygen carriers to facilitate oxygen delivery
US5260287A (en) 1992-05-11 1993-11-09 Board Of Regents, The University Of Texas System Polyphosphorylated organic compounds: compositions useful in protecting biological tissues
US5691423A (en) 1992-08-24 1997-11-25 The United States Of America As Represented By The Department Of Health And Human Services Polysaccharide-bound nitric oxide-nucleophile adducts
AU680890B2 (en) 1993-03-23 1997-08-14 Cbr Laboratories, Inc. Method and apparatus for encapsulation of biologically-active substances in cells
US5866548A (en) 1993-04-09 1999-02-02 The Regents Of The University Of California Caged membrane-permeant inositol phosphates
EP0710115A1 (en) 1993-07-23 1996-05-08 PHARMACIA & UPJOHN COMPANY Method for administering hemoglobin
WO1995005830A1 (en) 1993-08-20 1995-03-02 The Regents Of The University Of California Polyanion anti-inflammatory agents
SE502989C2 (en) 1993-11-22 1996-03-04 Perstorp Ab Use of an inositol trisphosphate ester for drug preparation
SE503122C2 (en) 1993-11-22 1996-03-25 Perstorp Ab Use of an inositol trisphosphate ester for the treatment of inflammatory conditions
JPH08186151A (en) * 1994-12-29 1996-07-16 Sony Corp Semiconductor device and manufacture thereof
US5720921A (en) 1995-03-10 1998-02-24 Entremed, Inc. Flow electroporation chamber and method
US6074605A (en) 1995-03-10 2000-06-13 Entremed, Inc. Flow electroporation chamber and method
US5626884A (en) 1995-08-18 1997-05-06 Lockett; Curtis G. Treatment of sickle cell disease
US6949517B1 (en) 1996-06-24 2005-09-27 Matti Siren Method of treating inflammatory, tissue repair and infectious conditions
US5699926A (en) * 1996-08-13 1997-12-23 Ipl, Inc. Five-piece container with stabilizer tablet
US5977078A (en) 1996-09-20 1999-11-02 The Regents Of The Univesity Of California Inositol polyphosphate derivatives and methods of using same
US5880099A (en) 1996-09-20 1999-03-09 The Regents Of The University Of California Inositol polyphosphates and methods of using same
DE19649350A1 (en) * 1996-11-28 1998-06-04 Hoechst Ag Inositol glycans with an insulin-like effect
DE19649531A1 (en) * 1996-11-29 1998-06-04 Eastman Kodak Co Adjustable chute for X-ray sheet films
US6096916A (en) 1997-05-23 2000-08-01 Nutrimed Biotech Synthesis of D-3 phosphorylated phosphoinositides and analogues
JP4060913B2 (en) 1997-09-09 2008-03-12 株式会社岡村製作所 Chair back
US6187335B1 (en) 1997-12-31 2001-02-13 Orasomal Technologies, Inc. Polymerizable fatty acids, phospholipids and polymerized liposomes therefrom
JP2003507430A (en) * 1999-08-25 2003-02-25 ジーエムピー カンパニーズ，インコーポレーテッド Drugs that enhance oxygen transport in mammals
IL143305A0 (en) 1999-09-02 2002-04-21 Rice University Nitric oxide-producing hydrogel materials
AU7995600A (en) 1999-10-05 2001-05-10 Theramed, Inc. Compositions and methods for the incorporation of chemical substances into cells
DE50104611D1 (en) 2000-04-12 2004-12-30 Bitop Ag USE OF COMPATIBLE SOLUTES AS SUBSTANCES WITH RADICAL-CATCHING PROPERTIES
US7084126B1 (en) 2000-05-01 2006-08-01 Healthpartners Research Foundation Methods and compositions for enhancing cellular function through protection of tissue components
WO2002010177A1 (en) 2000-08-01 2002-02-07 Gmp Companies, Inc. Ammonium salts of inositol hexaphosphate and uses thereof
AU2001281071A1 (en) * 2000-08-01 2002-02-13 Gmp Companies, Inc. Ammonium salts of hemoglobin allosteric effectors, and uses thereof
JP2004518639A (en) 2000-11-21 2004-06-24 イノロジック， インコーポレイテッド Inositol derivatives for increasing chloride secretion and inhibiting inflammation
WO2002072788A2 (en) 2001-03-14 2002-09-19 Centocor, Inc. Chronic obstructive pulmonary disease-related immunglobulin derived proteins, compositions, methods and uses
EP1435969A4 (en) 2001-09-20 2006-08-16 Inologic Inc Method of modulating sodium ion absorption in epithelial cells
AU2003231157C1 (en) * 2002-04-29 2009-02-26 Normoxys, Inc. Inositol pyrophosphates, and methods of use thereof
WO2004002403A2 (en) * 2002-06-14 2004-01-08 Gmp Oxycell, Inc. Sterols bearing pendant allosteric effectors of hemoglobin, and uses thereof
AU2004225969A1 (en) 2003-03-27 2004-10-14 Inologic, Inc. Camphanylidene and phenylalkyl inositol polyphosphate compounds, compositions, and methods of their use
ES2232302B1 (en) 2003-11-07 2006-08-01 Universitat De Les Illes Balears MYO-INOSITOL HEXAFOSFATO FOR TOPICAL USE.
US20070135389A1 (en) 2004-07-06 2007-06-14 Claude Nicolau Tumor eradication by inositol-tripyrophosphate
US20060258626A1 (en) 2004-07-06 2006-11-16 Claude Nicolau Use of inositol-tripyrophosphate in treating tumors and diseases
US20060106000A1 (en) 2004-07-06 2006-05-18 Claude Nicolau Use of inositol-tripyrophosphate in treating tumors and diseases
CA2601641A1 (en) 2005-03-18 2006-09-28 Oxyplus, Inc. Calcium salt of myo-inositol 1,6:2,3:4,5 tripyrophosphate as an allosteric effector of hemoglobin
AU2006335318A1 (en) 2006-01-06 2007-07-19 Oxyplus, Inc. Use of inositol-tripyrophosphate in treating tumors and diseases

Also Published As

Publication number Publication date
US8178514B2 (en) 2012-05-15
EP1503768A4 (en) 2009-10-21
US7919481B2 (en) 2011-04-05
US20130059820A1 (en) 2013-03-07
CA2488230C (en) 2013-04-09
EP1503768B1 (en) 2015-10-28
AU2003231157A1 (en) 2003-11-17
US20070207986A1 (en) 2007-09-06
US7618954B2 (en) 2009-11-17
US20110281825A1 (en) 2011-11-17
AU2003231157B2 (en) 2008-10-09
US20060116358A1 (en) 2006-06-01
US7648970B2 (en) 2010-01-19
US20100256094A1 (en) 2010-10-07
AU2009200042A1 (en) 2009-02-05
US7084115B2 (en) 2006-08-01
AU2003231157C1 (en) 2009-02-26
US20040014642A1 (en) 2004-01-22
US9078908B2 (en) 2015-07-14
US20140170127A1 (en) 2014-06-19
EP1503768A1 (en) 2005-02-09
WO2003092700A1 (en) 2003-11-13

Similar Documents

Publication Publication Date Title
CA2488230A1 (en) Inositol pyrophosphates, and methods of use thereof
EP0861071B1 (en) Benzamidoxime prodrugs and use thereof for treating pneumonia
WO2002009723A3 (en) Ammonium salts of hemoglobin allosteric effectors, and uses thereof
JP2020100638A (en) Use of ferric citrate in treatment of chronic kidney disease patients
Juan et al. Hypophosphatemia in hospitalized patients
US9533049B2 (en) Method for preparing nanoparticles based on functional amphiphilic molecules or macromolecules, and the use thereof
US20020173494A1 (en) Ammonium salts of inositol hexaphosphate, and uses thereof
US11013711B2 (en) Fatty acid esters of hydroxy fatty acids (FAHFAs) for use in the treatment of type 1 diabetes
Tsuchiya et al. A Multicenter Phase II Study of Adjuvant Chemotherapy With Oral Fluoropyrimidine S-1 for Non–Small-Cell Lung Cancer: High Completion and Survival Rates
CA2145229A1 (en) Suppressory compositions against hepatic metastases of tumors
ZA200700134B (en) Antitumor effect fortifier, antitumor agent and method of therapy for cancer
US20110294732A1 (en) Erythropoletin complementation or replacement
Nathan et al. Curative effects of the antipiroplasms amicarbalide and imidocarb on Trypanosoma brucei infection in mice
Wieder et al. Pharmacokinetics and safety of ILX23-7553, a non-calcemic-vitamin D 3 analogue, in a phase I study of patients with advanced malignancies
Utz et al. Hamycin: chemotherapeutic studies in systemic mycoses of man
US20220062331A1 (en) Treating iron deficiency in subjects at risk of cardiovascular adverse events and iron for the management of atrial fibrillation
Frey et al. Pharmacokinetics of the soluble guanylate cyclase activator cinaciguat in individuals with hepatic impairment
Belchetz et al. Factitious hypercalcaemia.
CN102210694A (en) Oral amifostine preparation and preparation method thereof
WO2020249712A1 (en) Treating iron deficiency in subjects at risk of cardiovascular adverse events
Whitehead et al. A phase II trial of continuous-infusion recombinant interleukin-2 in patients with advanced renal cell carcinoma: a Southwest Oncology Group study
RU2197984C1 (en) Method for treating different forms of pulmonary tuberculosis, resistant to antitubercular chemotherapy, among them
Papac et al. Gamma heavy chain disease seen initially as gastric neoplasm
STEEN et al. Acute blastomycotic pneumonia: Report of a fatal case of short duration diagnosed by needle biopsy of lung
Vogelzang et al. Phase I and pharmacokinetic study of a new antineoplastic agent: pyrazine diazohydroxide (NSC 361456)

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20180430