US20090197964A1 - Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage - Google Patents

Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage Download PDF

Info

Publication number
US20090197964A1
US20090197964A1 US12/322,434 US32243409A US2009197964A1 US 20090197964 A1 US20090197964 A1 US 20090197964A1 US 32243409 A US32243409 A US 32243409A US 2009197964 A1 US2009197964 A1 US 2009197964A1
Authority
US
United States
Prior art keywords
subject
citrulline
nitric oxide
vasospasm
sah
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.)
Abandoned
Application number
US12/322,434
Other languages
English (en)
Inventor
Marshall L. Summar
Frederick E. Barr
Reid Carleton Thompson
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.)
Vanderbilt University
Original Assignee
Vanderbilt University
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 Vanderbilt University filed Critical Vanderbilt University
Priority to US12/322,434 priority Critical patent/US20090197964A1/en
Assigned to VANDERBILT UNIVERSITY reassignment VANDERBILT UNIVERSITY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: THOMPSON, REID, BARR, FREDERICK E., SUMMAR, MARSHALL L.
Publication of US20090197964A1 publication Critical patent/US20090197964A1/en
Priority to US13/331,678 priority patent/US9943494B2/en
Priority to US15/955,370 priority patent/US10500181B2/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61K31/185—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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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

Definitions

  • the presently disclosed subject matter relates to the treatment of Aneurysmal Subarachnoid Hemorrhage (SAH), complications associated with SAH (including vasospasm), and vasospasm associated with atherosclerosis, including but not limited to that associated with coronary arterial disease.
  • SAH Aneurysmal Subarachnoid Hemorrhage
  • complications associated with SAH including vasospasm
  • vasospasm associated with atherosclerosis
  • SAH Aneurysmal Subarachnoid Hemorrhage
  • SAH is a major concern throughout the world, with varying incidences of between about 1 and 96 incidents per 100,000 person/year (Batista da Costa Jr. et al. (2004) Arq Neuro - Psiquiatr (Sao Paulo) 62:245-249), with a worldwide incidence of about 10 per 100,000 person/year (Batista da Costa Jr. et al. (2004) Arq Neuro - Psiquiatr (Sao Paulo) 62:245-249). According to Suarez et al., SAH affects 21,000-33,000 people per year in the United States, and represents about 2-5% of all new strokes (Suarez et al. (2006) N Engl J Med 354:387-396).
  • an effective amount of a nitric oxide precursor is administered to a subject suffering from SAH and/or associated complications and/or at risk for suffering complications associated with SAH (e.g., vasospasm).
  • the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof.
  • the nitric oxide precursor, such as citrulline is administered orally.
  • the nitric oxide precursor, such as citrulline is administered intravenously.
  • the subject to be treated is a subject suffering from vasospasm.
  • the subject to be treated is a subject suffering from an acute condition associated with vasospasm.
  • the presently disclosed subject matter also provides methods and compositions for treating vasospasm.
  • the subject to be treated suffers from vasospasm associated with SAH.
  • the subject to be treated has suffered trauma that results in vasospasm (e.g., trauma that results in SAH).
  • the methods can comprise administering to a subject in need thereof an effective amount of a nitric oxide precursor.
  • the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof.
  • the subject to be treated is suffering from vasospasm associated with SAH.
  • the nitric oxide precursor, such as citrulline is administered orally.
  • the nitric oxide precursor, such as citrulline is administered intravenously.
  • FIG. 1 is a schematic of the urea cycle.
  • SAH Aneurysmal Subarachnoid Hemorrhage
  • the in vivo synthetic pathway for arginine commences with ornithine. Ornithine is combined with carbamyl phosphate to produce citrulline, which in turn is combined with aspartate, in the presence of adenosine triphosphate (ATP), to produce argininosuccinate. In the final step, fumarate is split from argininosuccinate, to produce arginine.
  • the degradative pathway for arginine is by the hydrolytic action of arginase, to produce ornithine and urea. These reactions form the urea cycle.
  • the urea cycle serves as the primary pathway for removing waste nitrogen produced by the metabolism of endogenous and exogenous proteins, and is shown schematically in FIG. 1 . In addition to its role in nitrogen clearance, the urea cycle is the body's intrinsic source of arginine which acts as a precursor of nitric oxide (NO), a potent vasodilator.
  • NO nitric oxide
  • SAH typically results from rupture of a cranial aneurysm which results in leakage of blood into compartments of the nervous system that contain cerebrospinal fluid.
  • Primary symptomology typically includes sudden onset of headache, which is usually very severe, nausea, vomiting, neck pain, photophobia, and loss of consciousness (Suarez et al. (2006) N Engl J Med 354:387-396), which is frequently associated with neurological deficits that become apparent on physical exam (Suarez et al. (2006) N Engl J Med 354:387-396).
  • Hydrocephalus (20%), rebleeding (7%), cerebral vasospasm (46%), seizures (30%), hyponatremia (28%), myocardial injury (35%), and pulmonary edema (23%) occur in a significant percentage of patients, even if the damage to the underlying vessel(s) is repaired. These events also frequently lead to additional secondary complications, including seizures, pulmonary edema, cardiac arrhythmias, electrolyte disturbances, and neuropsychological complications such as problems with memory, mood, and neuropsychological function.
  • FT angiography and/or cerebral angiography can locate an aneurysm, which is then repaired. If, however, the angiography is normal, CT angiography is typically repeated 1-3 weeks subsequent to initial presentation, optionally followed by brain, brain stem, and/or spinal cord imaging. In those cases where heat CT does not detect a subarachnoid hemorrhage, testing of cerebrospinal fluid obtained by lumbar puncture can also provide indicators of SAH, which then can be confirmed by angiography.
  • treatment generally includes securing of the aneurysm by neurosurgical clipping or endovascular coiling.
  • Treatment of associated symptoms including, but not limited to hypertension, hyperthermia, hyperglycemia, and ischemia are performed as needed.
  • a subject Given that complications associated with SAH typically develop over the course of several weeks, a subject generally remains hospitalized for extended periods in order to provide continuous monitoring of the subject's condition.
  • the presently disclosed subject matter provides methods for treating SAH and/or associated complications in a subject.
  • an effective amount of a nitric oxide precursor is administered to a subject suffering from SAH and/or associated complications and/or at risk for suffering complications associated with SAH. Representative examples of such complications are disclosed herein above.
  • the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof. See FIG. 1 .
  • the nitric oxide precursor is selected from the group including, but not limited to, citrulline, arginine, or combinations thereof.
  • the nitric oxide precursor, such as citrulline is administered orally.
  • the nitric oxide precursor, such as citrulline is administered intravenously.
  • the subject to be treated is a subject suffering from vasospasm. In some embodiments, the subject to be treated is a subject suffering from an acute condition associated with vasospasm. Representative examples of such conditions are disclosed herein above.
  • the subject suffering from a complication suffers from relative hypocitrullinemia.
  • relative hypocitrullinemia refers to a state in which the subject suffering from a complication has reduced plasma citrulline as compared to a subject not suffering from a complication.
  • the subject suffers from hypocitrullinemia.
  • the hypocitrullinemia is characterized by plasma citrulline levels of ⁇ 37 ⁇ mol/liter, in some embodiments, ⁇ 25 ⁇ mol/liter, in some embodiments, ⁇ 20 ⁇ mol/liter, in some embodiments, ⁇ 10 ⁇ mol/liter, in some embodiments, ⁇ 5 ⁇ mol/liter.
  • the presently disclosed subject matter also provides methods and compositions for treating vasospasm.
  • the subject to be treated suffers from vasospasm associated with SAH.
  • the subject to be treated has suffered trauma that results in vasospasm (e.g., trauma that results in SAH).
  • the vasospasm is associated with atherosclerosis in the subject.
  • the atherosclerosis is associated with coronary artery disease in the subject, with carotid arterial disease in the subject, with peripheral arterial disease in the subject, and combinations thereof.
  • the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof. See FIG. 1 .
  • the nitric oxide precursor is selected from the group including, but not limited to, citrulline, arginine, or combinations thereof.
  • the nitric oxide precursor, such as citrulline is administered orally.
  • the nitric oxide precursor, such as citrulline is administered intravenously.
  • the subject to be treated is a subject suffering from vasospasm.
  • the subject to be treated is a subject suffering from an acute condition associated with vasospasm (e.g. ischemia and/or angina in coronary arterial disease).
  • the subject suffering from a complication suffers from relative hypocitrullinemia.
  • relative hypocitrullinemia refers to a state in which the subject suffering from a complication has reduced plasma citrulline as compared to a subject not suffering from a complication.
  • the phrase “treating” refers to both intervention designed to ameliorate a condition in a subject (e.g., after initiation of a disease process or after an injury) as well as to interventions that are designed to prevent the condition from occurring in the subject.
  • the terms “treating” and grammatical variants thereof are intended to be interpreted broadly to encompass meanings that refer to reducing the severity of and/or to curing a condition, as well as meanings that refer to prophylaxis.
  • “treating” can refer to “preventing” to any degree, or otherwise enhancing the ability of the subject to resist the process of the condition, such as a subject at risk to suffer the condition.
  • the subject treated in the presently disclosed subject matter in its many embodiments is desirably a human subject, although it is to be understood that the principles of the presently disclosed subject matter indicate that the presently disclosed subject matter is effective with respect to all vertebrate species, including warm-blooded vertebrates such as mammals and birds, which are intended to be included in the term “subject”.
  • a mammal is understood to include any mammalian species in which treatment is desirable, such as but not limited to agricultural and domestic mammalian species.
  • mammals such as humans, as well as those mammals of importance due to being endangered (such as Siberian tigers), of economical importance (animals raised on farms for consumption by humans) and/or social importance (animals kept as pets or in zoos) to humans, for instance, carnivores other than humans (such as cats and dogs), swine (pigs, hogs, and wild boars), ruminants (such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels), and horses.
  • carnivores other than humans such as cats and dogs
  • swine pigs, hogs, and wild boars
  • ruminants such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels
  • domesticated fowl i.e., poultry, such as turkeys, chickens, ducks, geese, guinea fowl, and the like, as they are also of economical importance to humans.
  • livestock including, but not limited to, domesticated swine (pigs and hogs), ruminants, horses, poultry, and the like.
  • an effective dose of a composition of the presently disclosed subject matter is administered to a subject in need thereof.
  • An “effective amount” is an amount of a composition sufficient to produce a measurable response (e.g., a biologically or clinically relevant response in a subject being treated).
  • Actual dosage levels of active ingredients in the compositions of the presently disclosed subject matter can be varied so as to administer an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular subject.
  • the selected dosage level will depend upon the activity of the therapeutic composition, the route of administration, combination with other drugs or treatments, the severity of the condition being treated, and the condition and prior medical history of the subject being treated.
  • doses of compositions can be started at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved.
  • the potency of a composition can vary, and therefore an “effective amount” can vary.
  • the amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the subject to be treated and the particular mode of administration.
  • a formulation intended for administration to humans can contain from 0.5 mg to 5 g of active agent compounded with an appropriate and convenient amount of carrier material which may vary from about 5 to about 95 percent of the total composition.
  • the doses per person per administration are generally between 1 mg and 500 mg up to several times per day.
  • dosage unit forms will generally contain between from about 1 mg to about 500 mg of an active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, or 1000 mg.
  • the nitric oxide precursor is administered in some embodiments in a dose ranging from about 0.01 mg to about 1,000 mg, in some embodiments in a dose ranging from about 0.5 mg to about 500 mg, and in some embodiments in a dose ranging from about 1.0 mg to about 250 mg.
  • the nitric oxide precursor can also be administered in some embodiments in a dose ranging from about 100 mg to about 30,000 mg, and in some embodiments in a dose ranging from about 250 mg to about 1,000 mg.
  • a representative dose is 3.8 g/m2/day of arginine or citrulline (molar equivalents, MW L-citrulline 175.2, MW L-arginine 174.2).
  • Representative intravenous citrulline solutions can comprise a 100 mg/ml (10%) solution.
  • Representative intravenous citrulline dosages can comprise 200 mg/kg, 400 mg/kg, 600 mg/kg, and 800 mg/kg.
  • the dose can be decreased by an amount ranging from 50 mg/kg and 100 mg/kg to mitigate observed undesired effects on systemic blood pressure.
  • doses can be administered one or more times during a given period of time, such as a day.
  • a pharmaceutical composition comprises an amount of citrulline effective to raise plasma citrulline level to treat a complication as disclosed herein in a subject.
  • the level is determined by comparing plasma citrulline levels in a subject to be treated to that observed in a subject not suffering from the complication.
  • the amount of citrulline is effective to raise plasma citrulline level in a subject to at least 5 ⁇ mol/liter, optionally at least 10 ⁇ mol/liter, optionally at least 20 ⁇ mol/liter, optionally at least 25 ⁇ mol/liter, and optionally about 37 ⁇ mol/liter.
  • the presently disclosed subject matter provides pharmaceutical compositions comprising a nitric oxide precursor and a pharmaceutically acceptable carrier, such as a pharmaceutically acceptable carrier in humans. In some embodiments, the presently disclosed subject matter provides pharmaceutical compositions comprising citrulline or arginine in dosages as described above.
  • composition of the presently disclosed subject matter is typically administered orally or parenterally in dosage unit formulations containing standard nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles as desired.
  • parenteral as used herein includes intravenous, intra-muscular, intra-arterial injection, or infusion techniques.
  • Injectable preparations for example sterile injectable aqueous or oleaginous suspensions, are formulated according to the known art using suitable dispersing or wetting agents and suspending agents.
  • the sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic acceptable diluent or solvent, for example, as a solution in 1,3-butanediol.
  • Suitable vehicles and solvents that can be employed are water, Ringer's solution, and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any bland fixed oil can be employed including synthetic mono- or diglycerides.
  • fatty acids such as oleic acid find use in the preparation of injectables.
  • Exemplary carriers include neutral saline solutions buffered with phosphate, lactate, Tris, and the like.
  • doses can be administered to a subject several times during a relevant treatment period, including but not limited to 1, 2, 3, 4, 5, 6 or more dosages.
  • citrulline acting as a NO precursor can be a treatment for both SAH and coronary arterial disease through a similar mechanism of supporting vascular relaxation through restoring an adequate supply of citrulline which can act as a nitric oxide precursor amongst other actions.
  • Examples 1 and 2 present the results of assaying plasma levels of citrulline, ornithine, arginine, and nitric oxide in subjects with and without vasospasm. The samples were separated by 24 hours in time from collection. In Example 1, levels were assayed after early collection, and in Example 2, levels were assayed after late collection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Vascular Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US12/322,434 2008-01-31 2009-02-02 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage Abandoned US20090197964A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US12/322,434 US20090197964A1 (en) 2008-01-31 2009-02-02 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US13/331,678 US9943494B2 (en) 2008-01-31 2011-12-20 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US15/955,370 US10500181B2 (en) 2008-01-31 2018-04-17 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2517008P 2008-01-31 2008-01-31
US12/322,434 US20090197964A1 (en) 2008-01-31 2009-02-02 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/331,678 Continuation US9943494B2 (en) 2008-01-31 2011-12-20 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Publications (1)

Publication Number Publication Date
US20090197964A1 true US20090197964A1 (en) 2009-08-06

Family

ID=40932329

Family Applications (3)

Application Number Title Priority Date Filing Date
US12/322,434 Abandoned US20090197964A1 (en) 2008-01-31 2009-02-02 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US13/331,678 Active US9943494B2 (en) 2008-01-31 2011-12-20 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US15/955,370 Active US10500181B2 (en) 2008-01-31 2018-04-17 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Family Applications After (2)

Application Number Title Priority Date Filing Date
US13/331,678 Active US9943494B2 (en) 2008-01-31 2011-12-20 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US15/955,370 Active US10500181B2 (en) 2008-01-31 2018-04-17 Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Country Status (16)

Country Link
US (3) US20090197964A1 (fr)
EP (1) EP2240170B1 (fr)
JP (2) JP5623916B2 (fr)
KR (2) KR20100135728A (fr)
CN (2) CN102369006A (fr)
AU (2) AU2009212693B2 (fr)
BR (1) BRPI0906608A2 (fr)
CA (1) CA2715260C (fr)
DK (1) DK2240170T3 (fr)
ES (1) ES2732810T3 (fr)
HU (1) HUE045571T2 (fr)
PL (1) PL2240170T3 (fr)
PT (1) PT2240170T (fr)
RU (1) RU2528097C2 (fr)
SG (1) SG196863A1 (fr)
WO (1) WO2009099999A2 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040235953A1 (en) * 1999-06-01 2004-11-25 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US20090312423A1 (en) * 2008-01-31 2009-12-17 Vanderbilt University Therapeutic treatment for lung conditions
US8188147B2 (en) 1999-06-01 2012-05-29 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US8282967B2 (en) 2005-05-27 2012-10-09 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US8591876B2 (en) 2010-12-15 2013-11-26 Novan, Inc. Methods of decreasing sebum production in the skin
US8981139B2 (en) 2011-02-28 2015-03-17 The University Of North Carolina At Chapel Hill Tertiary S-nitrosothiol-modified nitric—oxide-releasing xerogels and methods of using the same
US9526738B2 (en) 2009-08-21 2016-12-27 Novan, Inc. Topical gels and methods of using the same
US9919072B2 (en) 2009-08-21 2018-03-20 Novan, Inc. Wound dressings, methods of using the same and methods of forming the same
US9943494B2 (en) 2008-01-31 2018-04-17 Vanderbilt University Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112017025768A2 (pt) 2015-06-29 2018-08-14 Univ Vanderbilt administração intravenosa de citrulina durante cirurgia
JP2022535927A (ja) 2019-06-05 2022-08-10 アスクレピオン ファーマシューティカルズ， エルエルシー シトルリンの合成および精製の改善された方法

Citations (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4196265A (en) * 1977-06-15 1980-04-01 The Wistar Institute Method of producing antibodies
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4554101A (en) * 1981-01-09 1985-11-19 New York Blood Center, Inc. Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) * 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4736866A (en) * 1984-06-22 1988-04-12 President And Fellows Of Harvard College Transgenic non-human mammals
US4769331A (en) * 1981-09-16 1988-09-06 University Patents, Inc. Recombinant methods and materials
US4965188A (en) * 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US4996236A (en) * 1988-06-22 1991-02-26 Takeda Chemical Industries, Ltd. Therapeutic composition for hepatic encephalopathy
US5162215A (en) * 1988-09-22 1992-11-10 Amgen Inc. Method of gene transfer into chickens and other avian species
US5217997A (en) * 1990-01-09 1993-06-08 Levere Richard D Use of l-arginine in the treatment of hypertension and other vascular disorders
US5279833A (en) * 1990-04-04 1994-01-18 Yale University Liposomal transfection of nucleic acids into animal cells
US5286739A (en) * 1991-09-27 1994-02-15 Board Of Regents, University Of Texas System Parenteral formulations for the inhibition of systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor
US5286634A (en) * 1989-09-28 1994-02-15 Stadler Joan K Synergistic method for host cell transformation
US5399346A (en) * 1989-06-14 1995-03-21 The United States Of America As Represented By The Department Of Health And Human Services Gene therapy
US5489742A (en) * 1990-10-23 1996-02-06 Board Of Regents, The University Of Texas System Transgenic rats and animal models of inflammatory disease
US5550316A (en) * 1991-01-02 1996-08-27 Fox Chase Cancer Center Transgenic animal model system for human cutaneous melanoma
US5550024A (en) * 1991-04-19 1996-08-27 Biotechnology Research & Development Corporation Genetic markers for pig litter size
US5573933A (en) * 1987-04-14 1996-11-12 Luminis Pty, Ltd. Transgenic pigs
US5614396A (en) * 1990-06-14 1997-03-25 Baylor College Of Medicine Methods for the genetic modification of endogenous genes in animal cells by homologous recombination
US5625125A (en) * 1994-08-09 1997-04-29 Dnx Biotherapeutics Phospholipase A2 expressing transgenic animals
US5641484A (en) * 1990-12-04 1997-06-24 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by adenoviral E1A and SV40 large T antigen
US5643567A (en) * 1990-12-04 1997-07-01 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by adenoviral E1A and SV40 large T antigen
US5646008A (en) * 1993-06-22 1997-07-08 The Regent Of The University Of Michigan Vertebrate apoptosis gene: compositions and methods
US5648061A (en) * 1995-05-24 1997-07-15 Thomas Jefferson University In vivo and in vitro model of cutaneous photoaging
US5651964A (en) * 1990-12-04 1997-07-29 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by the adenoviral EIA gene
US5741957A (en) * 1989-12-01 1998-04-21 Pharming B.V. Transgenic bovine
US5767160A (en) * 1994-10-05 1998-06-16 Notol, Inc. Method and formulation of stimulating nitric oxide synthesis
US5874471A (en) * 1997-02-27 1999-02-23 Waugh; William Howard Orthomolecular medical use of L-citrulline for vasoprotection, relaxative smooth muscle tone and cell protection
US5873359A (en) * 1990-12-05 1999-02-23 The General Hospital Corporation Methods and devices for treating pulmonary vasoconstriction and asthma
US5891459A (en) * 1993-06-11 1999-04-06 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US20010056068A1 (en) * 1998-03-04 2001-12-27 Kristof Chwalisz Method of treatment and prevention of nitric oxide deficiency-related disorders with citrulline and citrulline derivatives
US6343382B2 (en) * 1999-06-14 2002-02-05 Kevin Sciglia Hat
US6346382B1 (en) * 1999-06-01 2002-02-12 Vanderbilt University Human carbamyl phosphate synthetase I polymorphism and diagnostic methods related thereto
US6358536B1 (en) * 1997-10-15 2002-03-19 Thomas Jefferson University Nitric oxide donor compositions, methods, apparatus, and kits for preventing or alleviating vasoconstriction or vasospasm in a mammal
US20030134332A1 (en) * 2001-11-28 2003-07-17 Boykin Joseph V. Diagnosis of endothelial dysfunction by nitric oxide bioactivity index
US6689810B2 (en) * 2001-08-21 2004-02-10 Cellular Sciences, Inc. Method for treating pulmonary disease states in mammals by altering indigenous in vivo levels of nitric oxide
US20040235953A1 (en) * 1999-06-01 2004-11-25 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US20060194728A1 (en) * 2005-01-06 2006-08-31 Anthony Killian Surfactant treatment regimen
US20070026448A1 (en) * 2001-09-07 2007-02-01 Bristol-Myers Squibb Company Polynucleotide encoding a novel human G-protein coupled receptor, HBPRBMY39
US20070184554A1 (en) * 2005-12-01 2007-08-09 Nps Allelix Corp. Biomarker of improved intestinal function
US20090312423A1 (en) * 2008-01-31 2009-12-17 Vanderbilt University Therapeutic treatment for lung conditions

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA716628B (en) 1970-10-15 1972-06-28 Richardson Merrell Spa Composition and method for treatment of hepatic disease and mental fatigue
NL8102724A (nl) 1980-07-11 1982-02-01 Stamicarbon Werkwijze voor de bereiding van copolymeren van etheen met tenminste een ander 1-alkeen.
US5374651A (en) 1991-09-27 1994-12-20 Board Of Regents, The University Of Texas System Methods and compositions for the treatment of hypotension with arginine free essential and essential amino acids and arginine derivatives
US5334380A (en) 1991-09-27 1994-08-02 Board Of Regents, The University Of Texas System Anti-endotoxin, interleukin-1 receptor antagonist and anti-tumor necrosis factor antibody with arginine-free formulations for the treatment of hypotension
US5385940A (en) 1992-11-05 1995-01-31 The General Hospital Corporation Treatment of stroke with nitric-oxide releasing compounds
AU6232794A (en) 1993-01-29 1994-08-15 Brigham And Women's Hospital The use of nitric oxide-delivering compounds for the treatment or prevention of alcoholic liver injury
US6331543B1 (en) 1996-11-01 2001-12-18 Nitromed, Inc. Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use
US6028107A (en) * 1997-02-27 2000-02-22 Waugh; William Howard Orthomolecular medical use of L-citrulline for vasoprotection, relaxative smooth muscle tone and cell protection
US6796966B2 (en) 1997-10-15 2004-09-28 Jeffrey E. Thomas Apparatus, and kits for preventing of alleviating vasoconstriction or vasospasm in a mammal
US20020068365A1 (en) 1998-07-28 2002-06-06 Eric H. Kuhrts Controlled release nitric oxide producing agents
JP3506114B2 (ja) 2000-01-25 2004-03-15 株式会社ニコン モニタ装置及びこのモニタ装置を具えた研磨装置及び研磨方法
RU2202269C2 (ru) * 2001-02-14 2003-04-20 Жильвинас Закарявичюс Способ прогнозирования исхода хирургического лечения у больных среднего возраста в остром периоде внутричерепных кровоизлияний аневризматической природы
US6899140B2 (en) 2002-08-12 2005-05-31 Wellstream International Limited Flexible pipe and method of manufacturing same using metal reinforced tape
JP5623916B2 (ja) 2008-01-31 2014-11-12 バンダービルト・ユニバーシティＶａｎｄｅｒｂｉｌｔ Ｕｎｉｖｅｒｓｉｔｙ 動脈瘤性くも膜下出血及び血管痙攣に対する医薬組成物
US20090291066A1 (en) 2008-05-22 2009-11-26 Apostolos Pappas composition and method of treating facial skin defect

Patent Citations (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4196265A (en) * 1977-06-15 1980-04-01 The Wistar Institute Method of producing antibodies
US4458066A (en) * 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4554101A (en) * 1981-01-09 1985-11-19 New York Blood Center, Inc. Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity
US4769331A (en) * 1981-09-16 1988-09-06 University Patents, Inc. Recombinant methods and materials
US4736866B1 (en) * 1984-06-22 1988-04-12 Transgenic non-human mammals
US4736866A (en) * 1984-06-22 1988-04-12 President And Fellows Of Harvard College Transgenic non-human mammals
US4683202B1 (fr) * 1985-03-28 1990-11-27 Cetus Corp
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) * 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4683195B1 (fr) * 1986-01-30 1990-11-27 Cetus Corp
US4965188A (en) * 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US5573933A (en) * 1987-04-14 1996-11-12 Luminis Pty, Ltd. Transgenic pigs
US4996236A (en) * 1988-06-22 1991-02-26 Takeda Chemical Industries, Ltd. Therapeutic composition for hepatic encephalopathy
US5162215A (en) * 1988-09-22 1992-11-10 Amgen Inc. Method of gene transfer into chickens and other avian species
US5399346A (en) * 1989-06-14 1995-03-21 The United States Of America As Represented By The Department Of Health And Human Services Gene therapy
US5286634A (en) * 1989-09-28 1994-02-15 Stadler Joan K Synergistic method for host cell transformation
US5741957A (en) * 1989-12-01 1998-04-21 Pharming B.V. Transgenic bovine
US5217997A (en) * 1990-01-09 1993-06-08 Levere Richard D Use of l-arginine in the treatment of hypertension and other vascular disorders
US5279833A (en) * 1990-04-04 1994-01-18 Yale University Liposomal transfection of nucleic acids into animal cells
US5614396A (en) * 1990-06-14 1997-03-25 Baylor College Of Medicine Methods for the genetic modification of endogenous genes in animal cells by homologous recombination
US5489742A (en) * 1990-10-23 1996-02-06 Board Of Regents, The University Of Texas System Transgenic rats and animal models of inflammatory disease
US5643567A (en) * 1990-12-04 1997-07-01 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by adenoviral E1A and SV40 large T antigen
US5651964A (en) * 1990-12-04 1997-07-29 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by the adenoviral EIA gene
US5641484A (en) * 1990-12-04 1997-06-24 Board Of Regents, The University Of Texas System Methods for the suppression of neu mediated tumors by adenoviral E1A and SV40 large T antigen
US5873359A (en) * 1990-12-05 1999-02-23 The General Hospital Corporation Methods and devices for treating pulmonary vasoconstriction and asthma
US5550316A (en) * 1991-01-02 1996-08-27 Fox Chase Cancer Center Transgenic animal model system for human cutaneous melanoma
US5550024A (en) * 1991-04-19 1996-08-27 Biotechnology Research & Development Corporation Genetic markers for pig litter size
US5286739A (en) * 1991-09-27 1994-02-15 Board Of Regents, University Of Texas System Parenteral formulations for the inhibition of systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor
US20020013288A1 (en) * 1993-06-11 2002-01-31 Cooke John P. Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US5891459A (en) * 1993-06-11 1999-04-06 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US6337321B1 (en) * 1993-06-11 2002-01-08 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US6646006B2 (en) * 1993-06-11 2003-11-11 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US6642208B2 (en) * 1993-06-11 2003-11-04 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
US5646008A (en) * 1993-06-22 1997-07-08 The Regent Of The University Of Michigan Vertebrate apoptosis gene: compositions and methods
US5625125A (en) * 1994-08-09 1997-04-29 Dnx Biotherapeutics Phospholipase A2 expressing transgenic animals
US5767160A (en) * 1994-10-05 1998-06-16 Notol, Inc. Method and formulation of stimulating nitric oxide synthesis
US5648061A (en) * 1995-05-24 1997-07-15 Thomas Jefferson University In vivo and in vitro model of cutaneous photoaging
US5874471A (en) * 1997-02-27 1999-02-23 Waugh; William Howard Orthomolecular medical use of L-citrulline for vasoprotection, relaxative smooth muscle tone and cell protection
US6358536B1 (en) * 1997-10-15 2002-03-19 Thomas Jefferson University Nitric oxide donor compositions, methods, apparatus, and kits for preventing or alleviating vasoconstriction or vasospasm in a mammal
US20010056068A1 (en) * 1998-03-04 2001-12-27 Kristof Chwalisz Method of treatment and prevention of nitric oxide deficiency-related disorders with citrulline and citrulline derivatives
US6346382B1 (en) * 1999-06-01 2002-02-12 Vanderbilt University Human carbamyl phosphate synthetase I polymorphism and diagnostic methods related thereto
US6743823B1 (en) * 1999-06-01 2004-06-01 Vanderbilt University Therapeutic methods relating to human carbamyl phosphate synthetase I polymorphism
US20040235953A1 (en) * 1999-06-01 2004-11-25 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US6343382B2 (en) * 1999-06-14 2002-02-05 Kevin Sciglia Hat
US6689810B2 (en) * 2001-08-21 2004-02-10 Cellular Sciences, Inc. Method for treating pulmonary disease states in mammals by altering indigenous in vivo levels of nitric oxide
US20070026448A1 (en) * 2001-09-07 2007-02-01 Bristol-Myers Squibb Company Polynucleotide encoding a novel human G-protein coupled receptor, HBPRBMY39
US20030134332A1 (en) * 2001-11-28 2003-07-17 Boykin Joseph V. Diagnosis of endothelial dysfunction by nitric oxide bioactivity index
US20060194728A1 (en) * 2005-01-06 2006-08-31 Anthony Killian Surfactant treatment regimen
US20070184554A1 (en) * 2005-12-01 2007-08-09 Nps Allelix Corp. Biomarker of improved intestinal function
US20090312423A1 (en) * 2008-01-31 2009-12-17 Vanderbilt University Therapeutic treatment for lung conditions

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8536225B2 (en) 1999-06-01 2013-09-17 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US9486429B2 (en) 1999-06-01 2016-11-08 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US8188147B2 (en) 1999-06-01 2012-05-29 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US20040235953A1 (en) * 1999-06-01 2004-11-25 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US8956658B2 (en) 2005-05-27 2015-02-17 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US11691995B2 (en) 2005-05-27 2023-07-04 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US8282967B2 (en) 2005-05-27 2012-10-09 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US8962029B2 (en) 2005-05-27 2015-02-24 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US9403852B2 (en) 2005-05-27 2016-08-02 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US9403851B2 (en) 2005-05-27 2016-08-02 The University Of North Carolina At Chapel Hill Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
US10500181B2 (en) 2008-01-31 2019-12-10 Vanderbilt University Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US20090312423A1 (en) * 2008-01-31 2009-12-17 Vanderbilt University Therapeutic treatment for lung conditions
US9943494B2 (en) 2008-01-31 2018-04-17 Vanderbilt University Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
US9919072B2 (en) 2009-08-21 2018-03-20 Novan, Inc. Wound dressings, methods of using the same and methods of forming the same
US9737561B2 (en) 2009-08-21 2017-08-22 Novan, Inc. Topical gels and methods of using the same
US9526738B2 (en) 2009-08-21 2016-12-27 Novan, Inc. Topical gels and methods of using the same
US10376538B2 (en) 2009-08-21 2019-08-13 Novan, Inc. Topical gels and methods of using the same
US11583608B2 (en) 2009-08-21 2023-02-21 Novan, Inc. Wound dressings, methods of using the same and methods of forming the same
US8591876B2 (en) 2010-12-15 2013-11-26 Novan, Inc. Methods of decreasing sebum production in the skin
US9713652B2 (en) 2011-02-28 2017-07-25 The University Of North Carolina At Chapel Hill Nitric oxide-releasing S-nitrosothiol-modified silica particles and methods of making the same
US8981139B2 (en) 2011-02-28 2015-03-17 The University Of North Carolina At Chapel Hill Tertiary S-nitrosothiol-modified nitric—oxide-releasing xerogels and methods of using the same

Also Published As

Publication number Publication date
PT2240170T (pt) 2019-06-24
CN105106186A (zh) 2015-12-02
JP5623916B2 (ja) 2014-11-12
ES2732810T3 (es) 2019-11-26
RU2528097C2 (ru) 2014-09-10
EP2240170A2 (fr) 2010-10-20
JP2015017119A (ja) 2015-01-29
JP2011519821A (ja) 2011-07-14
EP2240170A4 (fr) 2014-10-29
HUE045571T2 (hu) 2020-01-28
AU2009212693A1 (en) 2009-08-13
CN102369006A (zh) 2012-03-07
CA2715260C (fr) 2017-07-04
CA2715260A1 (fr) 2009-08-13
AU2014204508A1 (en) 2014-08-07
KR20100135728A (ko) 2010-12-27
JP6042392B2 (ja) 2016-12-14
AU2009212693B2 (en) 2014-05-01
RU2010132580A (ru) 2012-03-10
US20180360787A1 (en) 2018-12-20
PL2240170T3 (pl) 2019-11-29
US20120088835A1 (en) 2012-04-12
BRPI0906608A2 (pt) 2015-07-14
US9943494B2 (en) 2018-04-17
EP2240170B1 (fr) 2019-05-22
KR101932831B1 (ko) 2018-12-27
AU2014204508B2 (en) 2016-07-14
WO2009099999A2 (fr) 2009-08-13
KR20170005497A (ko) 2017-01-13
US10500181B2 (en) 2019-12-10
SG196863A1 (en) 2014-02-13
DK2240170T3 (da) 2019-07-15
WO2009099999A3 (fr) 2013-11-28

Similar Documents

Publication Publication Date Title
US10500181B2 (en) Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage
Strzelczyk et al. Expanding the treatment landscape for Lennox-Gastaut syndrome: current and future strategies
Dewey Encephalopathies: disorders of the brain
Krueger et al. Current management of tuberous sclerosis complex
US11571397B2 (en) Compositions and methods for treating seizure-induced sudden death
US6596756B1 (en) Treatment of fibromyalgia
KR20190039227A (ko) 신경퇴행성 질병을 위한 치료제
JP2008519847A (ja) 運動障害の治療方法
AU2009212692B2 (en) Therapeutic treatment for lung conditions
EP1885379A2 (fr) Composes et procedes pour traiter des crises et des troubles paroxystiques
US20250188158A1 (en) Treatment of Parkinson's Disease
US20240358729A1 (en) Composition containing 2'-fl for ameliorating, preventing or treating diseases caused by reduction of dopamine
KR20190039226A (ko) 리소좀 축적 질환과 관련된 약제 조성물 및 용도
JP2025161861A (ja) うつ病の処置
MXPA00012808A (es) El uso de analogo de acido valproico para tratamiento y prevencion de migrana y enfermedad afectiva.
KR20200074170A (ko) 신경퇴행성 질병에 대한 치료제
Fotuhi et al. The effects of obesity on brain structure and size
Shinno et al. Successful treatment with levothyroxine for idiopathic hypersomnia patients with subclinical hypothyroidism
US7776913B2 (en) Carnitines for treating or preventing disorders caused by andropause
Warrit Perianesthesia analgesia, recovery efficacy, and financial impact of ultrasound-guided lumbar plexus and sciatic nerve analgesia in dogs undergoing tibial plateau leveling osteotomy
Gaspard et al. Alternative Therapies for Refractory Status Epilepticus
CHECK 2.81 Galantamine
BR112020007657B1 (pt) Uso de leucina, acetil-leucina ou um sal farmaceuticamente aceitável da mesma para tratamento da síndrome das pernas inquietas (rls)

Legal Events

Date Code Title Description
AS Assignment

Owner name: VANDERBILT UNIVERSITY, TENNESSEE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SUMMAR, MARSHALL L.;BARR, FREDERICK E.;THOMPSON, REID;REEL/FRAME:022333/0159;SIGNING DATES FROM 20090209 TO 20090210

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION