AP897A - Use of gaseous nitric oxide for the manufacturing of a therapeutic gas for the treatment of hemoglobinopathy. - Google Patents

Use of gaseous nitric oxide for the manufacturing of a therapeutic gas for the treatment of hemoglobinopathy. Download PDF

Info

Publication number: AP897A
Authority: AP; ARIPO
Prior art keywords: patient; therapeutic gas; oxygen; ppm; hemoglobin
Prior art date: 1996-04-05

Application number

APAP/P/1998/001358A

Other languages

English (en)

Other versions

AP9801358A0 (en

Inventor

Alvin C Head

Warren M Zapol

Original Assignee

Massachusetts Gen Hospital

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.)

1996-04-05

Filing date

1997-04-03

Publication date

2000-11-17

1997-04-03 Application filed by Massachusetts Gen Hospital filed Critical Massachusetts Gen Hospital

1998-12-31 Publication of AP9801358A0 publication Critical patent/AP9801358A0/xx

2000-11-17 Application granted granted Critical

2000-11-17 Publication of AP897A publication Critical patent/AP897A/en

Links

MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title claims abstract description 424
230000001225 therapeutic effect Effects 0.000 title claims abstract description 83
208000034737 hemoglobinopathy Diseases 0.000 title claims abstract description 41
238000004519 manufacturing process Methods 0.000 title claims abstract 7
238000011282 treatment Methods 0.000 title claims description 34
239000007789 gas Substances 0.000 claims abstract description 105
210000003743 erythrocyte Anatomy 0.000 claims abstract description 78
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 75
239000001301 oxygen Substances 0.000 claims abstract description 75
229910052760 oxygen Inorganic materials 0.000 claims abstract description 75
108010054147 Hemoglobins Proteins 0.000 claims abstract description 62
102000001554 Hemoglobins Human genes 0.000 claims abstract description 62
150000001875 compounds Chemical class 0.000 claims abstract description 29
230000002829 reductive effect Effects 0.000 claims abstract description 16
239000003814 drug Substances 0.000 claims abstract 5
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 44
229910002091 carbon monoxide Inorganic materials 0.000 claims description 44
210000004369 blood Anatomy 0.000 claims description 37
239000008280 blood Substances 0.000 claims description 37
208000007056 sickle cell anemia Diseases 0.000 claims description 35
210000004027 cell Anatomy 0.000 claims description 32
230000007423 decrease Effects 0.000 claims description 17
206010040642 Sickle cell anaemia with crisis Diseases 0.000 claims description 12
238000001356 surgical procedure Methods 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
208000000859 Sickle cell trait Diseases 0.000 claims description 6
101000886863 Phacoides pectinatus Hemoglobin-1 Proteins 0.000 claims description 5
101000886862 Phreagena soyoae Globin-1 Proteins 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
108010047389 hemoglobin D Proteins 0.000 claims description 5
108010009903 hemoglobin Kansas Proteins 0.000 claims description 5
238000011065 in-situ storage Methods 0.000 claims description 5
239000012528 membrane Substances 0.000 claims description 5
108091005904 Hemoglobin subunit beta Proteins 0.000 claims description 4
229940100563 gas for inhalation Drugs 0.000 claims description 4
238000002347 injection Methods 0.000 claims description 4
239000007924 injection Substances 0.000 claims description 4
230000009935 nitrosation Effects 0.000 claims description 4
238000007034 nitrosation reaction Methods 0.000 claims description 4
WTLKTXIHIHFSGU-UHFFFAOYSA-N 2-nitrosoguanidine Chemical compound NC(N)=NN=O WTLKTXIHIHFSGU-UHFFFAOYSA-N 0.000 claims description 3
102100021519 Hemoglobin subunit beta Human genes 0.000 claims description 3
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 claims description 3
YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 claims description 3
229960003711 glyceryl trinitrate Drugs 0.000 claims description 3
238000001361 intraarterial administration Methods 0.000 claims description 3
238000010253 intravenous injection Methods 0.000 claims description 3
229960002460 nitroprusside Drugs 0.000 claims description 3
241000208125 Nicotiana Species 0.000 claims description 2
235000002637 Nicotiana tabacum Nutrition 0.000 claims description 2
239000002516 radical scavenger Substances 0.000 claims description 2
239000000779 smoke Substances 0.000 claims description 2
108700028369 Alleles Proteins 0.000 claims 1
238000000034 method Methods 0.000 description 25
238000002474 experimental method Methods 0.000 description 17
230000029058 respiratory gaseous exchange Effects 0.000 description 17
230000003247 decreasing effect Effects 0.000 description 13
230000009467 reduction Effects 0.000 description 13
108010061951 Methemoglobin Proteins 0.000 description 12
208000018337 inherited hemoglobinopathy Diseases 0.000 description 12
230000000694 effects Effects 0.000 description 11
238000002560 therapeutic procedure Methods 0.000 description 10
230000008859 change Effects 0.000 description 9
238000000338 in vitro Methods 0.000 description 9
108010044267 Abnormal Hemoglobins Proteins 0.000 description 8
108010064719 Oxyhemoglobins Proteins 0.000 description 7
239000000203 mixture Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
206010021143 Hypoxia Diseases 0.000 description 5
235000013922 glutamic acid Nutrition 0.000 description 5
239000004220 glutamic acid Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000036407 pain Effects 0.000 description 5
230000036961 partial effect Effects 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 4
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
-1 amino acid glutamate Chemical class 0.000 description 4
230000008901 benefit Effects 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
230000001146 hypoxic effect Effects 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
239000011261 inert gas Substances 0.000 description 4
239000002245 particle Substances 0.000 description 4
238000006116 polymerization reaction Methods 0.000 description 4
102100040141 Aminopeptidase O Human genes 0.000 description 3
108050008333 Aminopeptidase O Proteins 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
208000002903 Thalassemia Diseases 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
201000010099 disease Diseases 0.000 description 3
238000010494 dissociation reaction Methods 0.000 description 3
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210000004072 lung Anatomy 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000000241 respiratory effect Effects 0.000 description 3
210000002345 respiratory system Anatomy 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000000243 solution Substances 0.000 description 3
210000000952 spleen Anatomy 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
238000009120 supportive therapy Methods 0.000 description 3
OMDHRFLPMCNHCN-REOHCLBHSA-N (2r)-2-amino-3-nitrosulfanylpropanoic acid Chemical compound OC(=O)[C@@H](N)CS[N+]([O-])=O OMDHRFLPMCNHCN-REOHCLBHSA-N 0.000 description 2
XOHUEYCVLUUEJJ-UHFFFAOYSA-N 2,3-Bisphosphoglyceric acid Chemical compound OP(=O)(O)OC(C(=O)O)COP(O)(O)=O XOHUEYCVLUUEJJ-UHFFFAOYSA-N 0.000 description 2
XOHUEYCVLUUEJJ-UHFFFAOYSA-I 2,3-Diphosphoglycerate Chemical compound [O-]P(=O)([O-])OC(C(=O)[O-])COP([O-])([O-])=O XOHUEYCVLUUEJJ-UHFFFAOYSA-I 0.000 description 2
108010044495 Fetal Hemoglobin Proteins 0.000 description 2
206010061216 Infarction Diseases 0.000 description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
206010028851 Necrosis Diseases 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
208000007502 anemia Diseases 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
208000005980 beta thalassemia Diseases 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
230000036770 blood supply Effects 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
230000008021 deposition Effects 0.000 description 2
239000001307 helium Substances 0.000 description 2
229910052734 helium Inorganic materials 0.000 description 2
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
238000005534 hematocrit Methods 0.000 description 2
230000007574 infarction Effects 0.000 description 2
230000003993 interaction Effects 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
229940127554 medical product Drugs 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
230000035772 mutation Effects 0.000 description 2
230000017074 necrotic cell death Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
238000002106 pulse oximetry Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000002000 scavenging effect Effects 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
239000004474 valine Substances 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
MNNBCKASUFBXCO-RXMQYKEDSA-N (2r)-2-acetamido-3-methyl-3-sulfanylbutanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)C(C)(C)S MNNBCKASUFBXCO-RXMQYKEDSA-N 0.000 description 1
INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
229920006384 Airco Polymers 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
208000034502 Haemoglobin C disease Diseases 0.000 description 1
206010018910 Haemolysis Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
108090000862 Ion Channels Proteins 0.000 description 1
102000004310 Ion Channels Human genes 0.000 description 1
206010023126 Jaundice Diseases 0.000 description 1
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
208000019693 Lung disease Diseases 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
ZPGKBYMJBZKMAM-UHFFFAOYSA-I calcium;potassium;barium(2+);pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[K+].[Ca+2].[Ba+2] ZPGKBYMJBZKMAM-UHFFFAOYSA-I 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
230000002612 cardiopulmonary effect Effects 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
230000008260 defense mechanism Effects 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000005183 environmental health Effects 0.000 description 1
230000001667 episodic effect Effects 0.000 description 1
239000012530 fluid Substances 0.000 description 1
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
238000002695 general anesthesia Methods 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
125000000291 glutamic acid group Chemical class N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
125000000404 glutamine group Chemical class N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
108010073937 hemoglobin Arab Proteins 0.000 description 1
230000008588 hemolysis Effects 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
125000001165 hydrophobic group Chemical group 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
208000005135 methemoglobinemia Diseases 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
MDKQJOKKKZNQDG-UHFFFAOYSA-N n,n'-dimethylhexane-1,6-diamine Chemical compound CNCCCCCCNC MDKQJOKKKZNQDG-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000002840 nitric oxide donor Substances 0.000 description 1
FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical class CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
238000011369 optimal treatment Methods 0.000 description 1
230000008816 organ damage Effects 0.000 description 1
238000002496 oximetry Methods 0.000 description 1
238000002640 oxygen therapy Methods 0.000 description 1
238000006213 oxygenation reaction Methods 0.000 description 1
238000007427 paired t-test Methods 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
230000007425 progressive decline Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
208000002815 pulmonary hypertension Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HUAUNKAZQWMVFY-UHFFFAOYSA-M sodium;oxocalcium;hydroxide Chemical compound [OH-].[Na+].[Ca]=O HUAUNKAZQWMVFY-UHFFFAOYSA-M 0.000 description 1
230000003068 static effect Effects 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
125000000341 threoninyl group Chemical class [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
230000019432 tissue death Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
238000012762 unpaired Student’s t-test Methods 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- 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
- A61K31/13—Amines
- A61K31/131—Amines acyclic
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/295—Iron group metal compounds
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Emergency Medicine (AREA)
Inorganic Chemistry (AREA)
Organic Chemistry (AREA)
Hematology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

APAP/P/1998/001358A 1996-04-05 1997-04-03 Use of gaseous nitric oxide for the manufacturing of a therapeutic gas for the treatment of hemoglobinopathy. AP897A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US1488696P	1996-04-05	1996-04-05
PCT/US1997/005633 WO1997037644A1 (en)	1996-04-05	1997-04-03	Treatment of a hemoglobinopathy

Publications (2)

Publication Number	Publication Date
AP9801358A0 AP9801358A0 (en)	1998-12-31
AP897A true AP897A (en)	2000-11-17

Family

ID=21768361

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1998/001358A AP897A (en)	1996-04-05	1997-04-03	Use of gaseous nitric oxide for the manufacturing of a therapeutic gas for the treatment of hemoglobinopathy.

Country Status (15)

Country	Link
US (1)	US5885621A (es)
EP (1)	EP0914103B1 (es)
JP (1)	JP2000510448A (es)
CN (1)	CN1208053C (es)
AP (1)	AP897A (es)
AT (1)	ATE331505T1 (es)
AU (1)	AU720686B2 (es)
BR (1)	BR9708601A (es)
CA (1)	CA2251530C (es)
DE (1)	DE69736230T2 (es)
DK (1)	DK0914103T3 (es)
ES (1)	ES2267141T3 (es)
OA (1)	OA10893A (es)
PT (1)	PT914103E (es)
WO (1)	WO1997037644A1 (es)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6063407A (en) *	1995-02-16	2000-05-16	The General Hospital Corporation	Treatment of vascular thrombosis and restenosis with inhaled nitric oxide
US6627738B2 (en)	1995-09-15	2003-09-30	Duke University	No-modified hemoglobins and uses therefor
US6197745B1 (en)	1995-09-15	2001-03-06	Duke University	Methods for producing nitrosated hemoglobins and therapeutic uses therefor
US6911427B1 (en)	1995-09-15	2005-06-28	Duke University	No-modified hemoglobins and uses therefore
US8128963B2 (en) *	1996-09-27	2012-03-06	The Trustees Of Columbia University In The City Of New York	Methods for treating ischemic disorders using carbon monoxide
US6656452B1 (en)	1997-10-21	2003-12-02	The General Hospital Corporation	Use of inhaled NO as anti-inflammatory agent
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Also Published As

Publication number	Publication date
OA10893A (en)	2001-10-11
CN1208053C (zh)	2005-06-29
EP0914103A1 (en)	1999-05-12
ATE331505T1 (de)	2006-07-15
AP9801358A0 (en)	1998-12-31
CA2251530C (en)	2002-11-19
CA2251530A1 (en)	1997-10-16
DK0914103T3 (da)	2006-10-23
EP0914103A4 (en)	2003-09-03
DE69736230D1 (de)	2006-08-10
EP0914103B1 (en)	2006-06-28
JP2000510448A (ja)	2000-08-15
US5885621A (en)	1999-03-23
AU720686B2 (en)	2000-06-08
CN1227485A (zh)	1999-09-01
ES2267141T3 (es)	2007-03-01
PT914103E (pt)	2006-09-29
AU2440397A (en)	1997-10-29
WO1997037644A1 (en)	1997-10-16
DE69736230T2 (de)	2007-05-31
BR9708601A (pt)	1999-08-03

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