[go: up one dir, main page]

WO2016019313A1 - Composition et méthode de traitement du syndrome des jambes sans repos et des crampes aux jambes - Google Patents

Composition et méthode de traitement du syndrome des jambes sans repos et des crampes aux jambes Download PDF

Info

Publication number
WO2016019313A1
WO2016019313A1 PCT/US2015/043246 US2015043246W WO2016019313A1 WO 2016019313 A1 WO2016019313 A1 WO 2016019313A1 US 2015043246 W US2015043246 W US 2015043246W WO 2016019313 A1 WO2016019313 A1 WO 2016019313A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
administered
foregoing
rls
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.)
Ceased
Application number
PCT/US2015/043246
Other languages
English (en)
Inventor
Ki-Young SOHN
Yong-Hae HAN
Hye-Kyung Kim
Saeho Chong
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.)
Enzychem Lifesciences Corp
Original Assignee
Enzychem Lifesciences Corp
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 Enzychem Lifesciences Corp filed Critical Enzychem Lifesciences Corp
Publication of WO2016019313A1 publication Critical patent/WO2016019313A1/fr
Anticipated expiration legal-status Critical
Ceased 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • 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
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • 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
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps

Definitions

  • the present invention relates to a composition for treating restless legs syndrome and leg cramps, and more particularly to a composition or a health functional food for preventing or treating restless legs syndrome and leg cramps comprising monoacetyldiacylglycerol derivatives and a method for preventing or treating restless legs syndrome and leg cramps using the same.
  • Deer antler is one of the most widely used oriental medicines and is prepared by drying uncornified antler of a deer.
  • Deer antler has been claimed to have various medical effects, such as growth- and development-promoting effects, promoting hematopoietic function, treating nervous breakdown, treating cardiac insufficiency, improving the function of five viscera and six entrails, and so on (Donq-eui boqam, a classical medical literature in Korea).
  • deer antler has a tonic and nourishing effect, a powerful general systemic effect, a cardiac function improving effect, a fatigue recovery effect, the effect of enhancing systemic resistance to various diseases, and so on.
  • monoacetyldiacylglycerol components of the deer antler are effective in preventing or treating restless legs syndrome (RLS) and nocturnal leg cramps (NLC).
  • composition or a health functional food for preventing or treating restless legs syndrome and leg cramps and a method for preventing or treating restless legs syndrome and leg cramps using the same.
  • the present invention provides a composition or a health functional food for preventing or treating restless legs syndrome and leg cramps comprising monoacetyldiacylglycerol derivatives of the following
  • R1 and R2 are independently a fatty acid group of 14 to 22 carbon atoms.
  • the present invention provides a method for preventing or treating restless legs syndrome and leg cramps comprising a step of administering the composition or the health functional food to a subject.
  • composition of the present invention for treating restless legs syndrome (RLS) and leg cramps(NLC) includes monoacetyldiacylglycerol derivatives of the following Formula 1 ,
  • R1 and R2 are independently a fatty acid residue of 14 to 22 carbon atoms; for example, compounds of Formula 2 (PLAG):
  • the term "monoacetyldiacylglycerol derivatives means glycerol derivatives having one acetyl group and two acyl groups, and can be referred as “monoacetyldiacylglycerol (MADG)".
  • R1 and R2 are independently a fatty acid residue of 14 to 22 carbon atoms.
  • Fatty acid residue refers to the acyl moiety resulting from formation of an ester bond by reaction of a fatty acid and an alcohol.
  • Non-limiting examples of R1 and R2 thus include palmitoyl, oleoyl, linoleoyi, linolenoyl, stearoyi, myristoyl, arachidonoyl, and so on.
  • R1 and R2 include oleoyl/palmitoyl, palmitoyl/oleoyl, palmitoyl/linoleoyl, palmitoyl/linolenoyl, palmitoyl/arachidonoyl, palmitoyl/stearoyl, palmitoyl/palmitoyl, oleoyl/stearoyl, linoleoyl/palmitoyl,
  • the monoacetyldiacylglycerol derivatives of Formula 1 can be (R)-form, (S)-form or a racemic mixture, and may include their stereoisomers. Where the R1 and/or R2 substituents are unsaturated fatty acid residues, the double bond(s) may have the cis configutration.
  • the monoacetyldiacylglycerol derivatives is a compound of the following Formula 2.
  • the compound of Formula 2 is 1 -palmitoyl-2-linoleoyl-3-acetylglycerol, sometimes referred as "PLAG" in this specification.
  • R1 and R2 of the compound of Formula 2 are palmitoyl and linoleoyl, respectively.
  • PLAG of Formula 2 increases survivability ratio of animals in sepsis animal model experiment using cecal- ligation-puncture, and shows no-toxicity in GLP (Good Laboratory Practice) toxicity test.
  • GLP Good Laboratory Practice
  • the effect of monoacetyldiacylglycerol derivatives including PLAG on RLS and NLC is not known or disclosed in the prior arts.
  • the monoacetyldiacylglycerol derivatives can be separated or extracted from the natural deer antler or can be produced by conventional organic synthesis method(s).
  • Restless legs syndrome is a neurological sensorimotor disorder which is also known as Willis-Ekbom disease (WED).
  • WED Willis-Ekbom disease
  • RLS is characterized by an irresistible urge to move one's body to reduce uncomfortable sensations which commonly occurs on legs, but may occur on arms, torso, head, and so on. Moving the affected body part modulates the sensations, providing temporary relief.
  • RLS frequently occurs before sleep and disturbs sleep. In Korea, from the research for 5,000 adults of ages of 21 to 69, 5.4% of the adults have RLS.
  • causes of RLS are not yet explicitly identified, but it is presumed that RLS has some relation with an imbalance of dopamine system of a brain.
  • RLS can be classified into primary or idiopathic RLS and secondary RLS.
  • RLS may diagnosed by assessing the following symptoms identified by the International Restless Legs Syndrome Study Group, www.irlssg.org:
  • symptoms primary to another medical or a behavioral condition for example, myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping.
  • RLS The clinical significance of RLS is determined by whether the symptoms of RLS cause significant distress or impairment in social, occupational, educational, or other important areas of functioning by their impact on sleep, energy/vitality, daily activities, behavior, cognition, or mood.
  • medications useful for treating RLS include medications for Parkinson's disease which act on dopamine system and medications for sleep disturbance such as benzodiazepine.
  • Leg Cramps consist of a sudden, severe, and involuntary muscle contraction or over-shortening which occurs in the legs, especially in the calf, and may cause mild-to-excruciating pain. Leg Cramps generally cause sleep disturbance in night, and therefore is commonly known as Nocturnal Leg Cramps (NLC).
  • NLC causes of NLC are also not explicitly identified yet, but it is presumed that NLC has some relation with overwork, muscle fatigue, blood vessel disease, nerve disorder, pregnancy, and so on. Thus, NLC is commonly treated by physical treatment such as rest (relaxation) and stretching, or by medications such as muscle relaxants, magnesium supplements, calcium supplements, vitamin and so on.
  • the pharmaceutical composition for treating RLS and NLC of the present invention may consist of only or substantially pure monoacetyldiacylglycerol derivatives of Formula 1 , or may include active components (monoacetyldiacylglycerol derivatives of Formula 1 ) and conventional pharmaceutically acceptable carriers, excipients, or diluents.
  • the amount of monoacetyldiacylglycerol derivatives in the pharmaceutical composition can be widely varied without specific limitation, and is specifically 0.0001 to 100.0 weight%, preferably 0.001 to 50 weight%, more preferably 0.01 to 20 weight% with respect to the total amount of the composition.
  • the pharmaceutical composition may be formulated into solid, liquid, gel or suspension form for oral or non-oral administration, for example, tablet, bolus, powder, granule, capsule such as hard or soft gelatin capsule, emulsion, suspension, syrup, emulsifiable concentrate, sterilized aqueous solution, non-aqueous solution, freeze-dried formulation, suppository, and so on.
  • conventional excipients or diluents such as filler, bulking agent, binder, wetting agent, disintegrating agent, and surfactant can be used.
  • the solid formulation for oral administration includes tablet, bolus, powder, granule, capsule and so on, and the solid formulation can be prepared by mixing one or more of the active components and at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and so on. Besides the excipient, a lubricant such as
  • the liquid formulation for oral administration includes emulsion, suspension, syrup, and so on, and may include conventional diluents such as water and liquid paraffin or may include various excipients such as wetting agent, sweeting agent, flavoring agent, and preserving agent.
  • the formulation for non-oral administration includes sterilized aqueous solution, non-aqueous solution, freeze-dried formulation, suppository, and so on, and solvent for such solution may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and ester for syringe injection such as ethyl oleate.
  • Base materials of the suppository may include witepsol, macrogol, tween 61 , cacao butter, Laurin and glycerogelatine.
  • the disclosure provides a novel pharmaceutical unit dose drug product useful for preventing, improving or treating RLS and NLC, in the form of a soft gelatin capsule for oral administration containing 250-1000 mg, e.g., 500 mg, of PLAG drug substance, substantially free of other triglycerides, together with 0.1 - 3 mg, e.g.
  • a pharmaceutically acceptable tocopherol compound e.g., cc-tocopherol
  • an antioxidant e.g., for administration once or twice a day, at a daily dosage of 500 mg to 4,000 mg; for example 500 mg/day, administered as a single dose in the evening or 1000 mg/day administered as a divided dose 500 mg in the morning and 500 mg in the evening.
  • composition of the present invention can be administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount is used to refer to an amount that is sufficient to achieve a desired result in a medical treatment.
  • pharmaceutically effective amount can be determined in accordance with type, age and sex of a subject, severity and type of disease, activity of drug, sensitivity to drug, administration time, period and route, excretion rate, and so forth.
  • treatment includes mitigation, amelioration, delay or reduction symptoms, as well as complete elimination or prevention of symptoms, of RLS and NLC by administering the composition of the present invention.
  • the composition of the present invention can be administered alone or with other medicines sequentially or
  • the preferable amount of the composition of the present invention can be varied in accordance with the condition and weight of patient, severity of disease, formulation type of drug, administration route and period of drug.
  • An appropriate total amount of administration per 1 day can be determined by a physician, and is generally about 0.05 to 200 mg/kg. Extrapolating from in vivo experiments in animals and in vitro experiments in cells, the preferable total administration amount per day is determined to be 0.1 to 100 mg/kg for an adult human.
  • the total amount of 50 mg/kg can be administered once a day or can be administered in divided doses twice, three, or four times daily.
  • the composition of the present invention can be administered to any subject which requires the prevention or treatment of RLS and NLC.
  • the composition of the present invention can be administered to any subject which requires the prevention or treatment of RLS and NLC.
  • the composition of the present invention can be administered to any subject which requires the prevention or treatment of RLS and NLC.
  • the composition of the present invention can be administered to any subject which requires the prevention or treatment of RLS and
  • composition of the present invention can be administered to not only human but also non-human animal (specifically mammals) such as monkey, dog, cat, rabbit, guinea pig, rat, mouse, cow, sheep, pig, goat, and so on.
  • the composition of the present disclosure can be administered by conventional various methods, for example, by oral or rectum administration, or by intravenous, intramuscular, subcutaneous or cerebrovascular injection.
  • the disclosure also provides a health functional food for preventing, improving or treating RLS and NLC comprising monoacetyldiacylglycerol derivatives of Formula 1 as active component(s),
  • R1 and R2 are independently a fatty acid residue of 14 to 22 carbon atoms.
  • monoacetyldiacylglycerol derivatives of the present invention can be included in a health functional food.
  • the monoacetyldiacylglycerol derivatives, RLS and NLC are previously explained in detail.
  • the term “ improving” or “treating” means every change which reduces or advantageously changes RLS and NLC.
  • the composition of the present invention can be included alone or with other active component.
  • the amount of the compounds of the present invention in the health functional food can be determined in accordance with the intended use of the health functional food.
  • the composition of the present invention when preparing health functional food or beverage, can be included in the amount of less than 15 weight part, preferably less than 10 weight part, for example, 0.01 to 10 weight part, preferably 0.1 to 5 weight part with respect to 100 weight part of the food or beverage.
  • the amount of the composition can be reduced.
  • the active component does not cause any adverse effects, even at relatively high doses, the amount of the composition can be increased by more than the above mentioned amount.
  • the health functional food including the composition of the present invention can be any conventional food or beverage.
  • Specific examples of the food include meat, sausage, bread, chocolate, candy, snack, biscuit, pizza, Ramen, noodles, gum, ice cream, dairy product, soup, beverage, tea, drink, alcoholic drink, vitamin complex, and so on. If necessary, the food of the present invention can also include food for an animal.
  • the beverage may include conventional sweetener, flavoring agent, natural carbohydrate, and so on.
  • Examples of the natural carbohydrate include monosaccharide such as glucose and fructose, disaccharide such as maltose and sucrose, polysaccharide such as dextrin and cyclodextrin, and sugar alcohol such as xylitol, sorbitol, and erythritol.
  • the preferable amount of the natural carbohydrate can be about 0.01 to 0.04 g, more preferably about 0.02 to 0.03 g with respect to 100 ml of the beverage of the present invention.
  • Examples of the sweetener includes natural sweeteners such as Thaumatin and Stevia extract and artificial sweeteners such as saccharin and aspartame.
  • the health functional food of the present invention may further include various nutritional supplement, vitamin, electrolyte, flavoring agent, coloring agent, pectic acid and its salt, alginic acid and its salt, organic acid, protective colloid, thickener, pH adjuster, stabilizer, preservative, glycerin, alcohol, juice and so on.
  • the present invention provides a method for preventing or treating RLS and NLC comprising a step of administering the pharmaceutical composition or the health functional food comprising a compound of Formula 1 to a subject who is suspicious of having RLS and NLC.
  • a person at elevated risk of having RLS and NLC includes not only a person having RLS and NLC at the time of treatment but also a person who has had RLS or NLC in the past. Such a person may benefit from prophylactic administration of a compound of Formula 1 , e.g., PLAG.
  • the term "administering" means introducing the pharmaceutical composition of the present invention into the subject who is suspicious of having RLS and NLC by any means.
  • the administration route can be any route such as oral or non-oral route.
  • the disclosure thus provides, for example, a method (Method 1 ) for treatment (including prophylaxis) of restless leg syndrome and/or leg cramps, comprising administering an effective amount of a compound of Formula 1 :
  • R1 and R2 are independently a fatty acid group of 14 to 22 carbon atoms to a patient in need thereof.
  • R1 and R2 are independently a fatty acid group of 14 to 22 carbon atoms to a patient in need thereof.
  • R1 and R2 are independently selected from the group consisting of palmitoyl, oleoyl, linoleoyl, linolenoyl, stearoyl, myristoyl, and arachidonoyl.
  • monoacetyldiacylglycerol compounds e.g, wherein at least 95%, for example at least 99% of the total monoacetyldiacylglycerol compounds in the formulation are of Formula 2.
  • any foregoing method wherein the Compound of Formula 1 is administered in the form of a pharmaceutical composition which is a soft gelatin capsule containing the Compound of Formula 1 in combination or association with a pharmaceutically acceptable diluent or carrier, for example wherein the pharmaceutically acceptable diluent or carrier comprises an edible oil, e.g., a vegetable oil, for example olive oil.
  • a pharmaceutically acceptable diluent or carrier comprises an edible oil, e.g., a vegetable oil, for example olive oil.
  • Any foregoing method wherein the Compound of Formula 1 is administered in the form of a pharmaceutical composition comprising 0.0001 to 100.0 weight%, for example 50-95%, by weight of the composition.
  • the Compound of Formula 1 is a compound of Formula 2 administered in the form of a soft gelatin capsule containing 250mg of the Compound of Formula 2 in combination or association with approximately 50mg of a pharmaceutically acceptable diluent or carrier, for example an edible oil, e.g., a vegetable oil, e.g., olive oil.
  • a pharmaceutically acceptable diluent or carrier for example an edible oil, e.g., a vegetable oil, e.g., olive oil.
  • any foregoing method wherein the compound of formula 1 is a compound of Formula 2 (PLAG), administered in the form of a soft gelatin capsule for oral administration containing 500 mg of PLAG drug substance and 1 mg cc- tocopherol as an antioxidant, e.g., administered once or twice a day, at a total daily dosage of 500 mg to 4,000 mg, e.g., 500mg or 1000mg.
  • PLAG compound of Formula 2
  • a functional food for example as an additive or admixture to a food suitable for human consumption.
  • any foregoing method further comprising administration of one or more additional therapeutic agents, for example one or more agents selected from the group consisting of (i) dopaminergic drugs, for example a drug used to treat Parkinson's disease, e.g., ropinirole, rotigotine, carbodopa/levodopa, (ii) analgesic drugs, for example gabapentin, gabapentin enacarbil, codeine, oxycodone, oxycodone/acetaminophen, hydrocodone/acetaminophen, acetaminophen, naproxen, ibuprofen, or aspirin, and (iii) tranquilizing drugs, for example, benzodiazepines, for example, clonazepam, triazolam, eszopiclone, ramelteon, temazepam, zaleplon, and Zolpidem.
  • dopaminergic drugs for example a drug used to treat
  • Method 1 .17 wherein the additional therapeutic agent is an effective amount of an analgesic agent selected from selected from gabapentin or pregabalin. Any foregoing methods further comprising administration of an effective amount of one or more anticonvulsant agents, e.g., carbamazepine.
  • any foregoing method further comprising the administration of oral or parenteral iron supplements; for example, oral iron supplements, e.g., in an amount sufficient to increase the ferritin level in the patient's blood to at least 50 ⁇ g/L, e.g., at least 80 ⁇ g/L; for example administration of an orally available iron ion source, e.g., selected from ferrous gluconate, ferrous sulfate, ferrous fumarate, ferroglycine sulfate, heme iron polypeptide, carbonyl iron, and iron- dextran complex, e.g., in an amount to provide a daily dosage of 5mg - 10OOmg of elemental iron, e.g., up to 50-100 mg elemental iron three times daily for an iron deficient patient or 5 to 45 mg elemental iron daily for a patient not diagnosed with iron deficiency, for example 30-120 mg weekly.
  • oral iron supplements e.g., in an amount sufficient to increase the ferritin level
  • Any foregoing method further comprising administration of a therapeutic agent in addition to the compound of formula I, e.g., a therapeutic agent selected from the agents identified in any foregoing method, wherein the additional therapeutic agent is administered in an effective amount, e.g., in an amount which is effective in combination with the compound of Formula I but not effective in the absence of the compound of Formula 1 , e.g., in a synergistically effective amount.
  • a therapeutic agent in addition to the compound of formula I, e.g., a therapeutic agent selected from the agents identified in any foregoing method, wherein the additional therapeutic agent is administered in an effective amount, e.g., in an amount which is effective in combination with the compound of Formula I but not effective in the absence of the compound of Formula 1 , e.g., in a synergistically effective amount.
  • the disclosure additionally provides a pharmaceutical composition comprising a compound of Formula 1 , e.g., PLAG, for use in treating restless legs syndrome and/or nocturnal leg cramps, e.g., for use in any of Methods 1 , et. seq.
  • a pharmaceutical composition comprising a compound of Formula 1 , e.g., PLAG, for use in treating restless legs syndrome and/or nocturnal leg cramps, e.g., for use in any of Methods 1 , et. seq.
  • the disclosure additionally provides the use of a compound of Formula 1 , e.g., PLAG, in the manufacture of a medicament for treating restless legs syndrome and/or nocturnal leg cramps, e.g., for use in any of Methods 1 , et. seq.
  • a compound of Formula 1 e.g., PLAG
  • [0030] 1 Patients of RLS: A total 26 patients with idiopathic RLS between 20 to 80 years old (24 female patients and 2 male patients, Mean age: 55.6 + 6.97) were enrolled in this study during the period of November 2013 to March 2014. The diagnosis of primary RLS was made according to the essential criteria of the International Restless Legs Syndrome Study Group (IRLSSG). For enrollment in the study, patients were required to have a total score of at least 15 on the IRLSSG rating scale (IRLS) for satisfying moderate to severe disease.
  • IRLSSG International Restless Legs Syndrome Study Group
  • IRLS Korean version of the IRLS(K-IRLS) shown in Table 1 regarding their symptoms.
  • a score was evaluated in accordance with the criteria shown in Table 2.
  • the scores for the questions in Table 1 were summed to calculate IRLS total score. A reduction of at least 50% in the IRLS total score was considered clinically relevant; therefore, this threshold was used for the definition of responders (>50% reduction of IRLS total score) and non-responders ( ⁇ 50% reduction of the score).
  • the average number of NLC/day was 3.5 ⁇ 0.5 before medication of PLAG, but improved to 1 .87+0.88 after medication of PLAG.
  • the pain severity was 6.75 ⁇ 1 .06 before medication of PLAG, but improved to 3.5 ⁇ 1 .13 after medication of PLAG.
  • the sleep disturbance was 3.13 ⁇ 0.44 before
  • Example 3 Unit dosage formulation for use in treatment of RLS or NLC

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)
  • Pain & Pain Management (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des méthodes de traitement du syndrome des jambes sans repos et/ou des crampes aux jambes comprenant l'administration d'une quantité efficace d'un dérivé de monoacétyldiacylglycérol, par exemple le 1-palmitoyl-2-linoléoyl-3-acétylglycérol, conjointement avec des compositions destinées à être utilisées dans de tels procédés.
PCT/US2015/043246 2014-08-01 2015-07-31 Composition et méthode de traitement du syndrome des jambes sans repos et des crampes aux jambes Ceased WO2016019313A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462032354P 2014-08-01 2014-08-01
US62/032,354 2014-08-01

Publications (1)

Publication Number Publication Date
WO2016019313A1 true WO2016019313A1 (fr) 2016-02-04

Family

ID=55218376

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2015/043246 Ceased WO2016019313A1 (fr) 2014-08-01 2015-07-31 Composition et méthode de traitement du syndrome des jambes sans repos et des crampes aux jambes

Country Status (2)

Country Link
TW (1) TW201618767A (fr)
WO (1) WO2016019313A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019106632A1 (fr) * 2017-11-30 2019-06-06 Enzychem Lifesciences Corporation Compositions pour la prévention ou le traitement du syndrome d'irradiation aiguë

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090253923A1 (en) * 2005-07-20 2009-10-08 Enzychem Co., Ltd. Preparation of glycerol derivatives ad intermediates therefor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090253923A1 (en) * 2005-07-20 2009-10-08 Enzychem Co., Ltd. Preparation of glycerol derivatives ad intermediates therefor

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JIM, HSL ET AL.: "Sleep Disruption in Hematopoietic Cell Transplantation Recipients: Prevalence, Severity, and Clinical Management", BIOL BLOOD MARROW TRANSPLANT., vol. 20, 17 April 2014 (2014-04-17), pages 1465 - 1484, XP029051630, DOI: doi:10.1016/j.bbmt.2014.04.010 *
YANG, HO ET AL.: "Stimulatory Effects of Monoacetyldiglycerides on Hematopoiesis", BIOL. PHARM. BULL., vol. 27, no. 7, 2004, pages 1121 - 1125, XP002544791, DOI: doi:10.1248/bpb.27.1121 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019106632A1 (fr) * 2017-11-30 2019-06-06 Enzychem Lifesciences Corporation Compositions pour la prévention ou le traitement du syndrome d'irradiation aiguë
US11590096B2 (en) 2017-11-30 2023-02-28 Enzychem Lifesciences Corporation Compositions for prevention or treatment of acute radiation syndrome and other radiation exposure
US12076307B2 (en) 2017-11-30 2024-09-03 Enzychem Lifesciences Corporation Compositions for prevention or treatment of acute radiation syndrome and other radiation exposure

Also Published As

Publication number Publication date
TW201618767A (zh) 2016-06-01

Similar Documents

Publication Publication Date Title
KR102852384B1 (ko) 노화 방지제 및 노화 방지 방법
CN109222103B (zh) 增肌组合物和保健食品
TW200913988A (en) Anti-fatigue agent and oral composition each comprising andrographolide as active ingredient
KR20100094485A (ko) 아미노산 조성물을 함유하는 피로 방지제
JP2018536711A (ja) 粘膜炎の治療方法
KR20240050338A (ko) 생체활성 조성물 및 이의 사용 방법
KR20240004452A (ko) 1-메틸크산틴-기반 생체활성 조성물 및 이의 사용 방법
EP3115047B1 (fr) Agent prévenant la débilité
US11730713B2 (en) Composition for preventing or improving nociceptive pain
WO2011096413A1 (fr) Agent pour améliorer la motilité
WO2014069660A1 (fr) Agent facilitant l'écoulement du sang
US10653655B2 (en) Composition for preventing or improving peripheral neuropathy
JP6360172B2 (ja) チグリンアルデヒドを使用する組成物及び方法
CA2985564A1 (fr) Compositions comprenant du cinnamaldehyde et du zinc et procedes d'utilisation de ces compositions
EP3756475B1 (fr) Compositions comprenant de l'aldéhyde cinnamique et du zinc
JP6368368B2 (ja) ｐ−アニスアルデヒドを使用する組成物及び方法
EP3119385B1 (fr) Composition contenant du cinnamaldéhyde et du zinc pour améliorer la déglutition
WO2016019313A1 (fr) Composition et méthode de traitement du syndrome des jambes sans repos et des crampes aux jambes
JP6848962B2 (ja) 行動体力向上剤
KR102439576B1 (ko) 뇌기능 개선용 영양전달체 조성물
RU2698396C1 (ru) Фармацевтическая композиция для парентерального капельного введения
JP2016525133A (ja) クミンアルデヒドを使用する組成物及び方法
US20200261485A1 (en) Compositions comprising 3'-o-glucuronide epicatechin and methods of making and using such compositions
JP2020100591A (ja) 筋質向上剤
JP2006213628A (ja) 抗ストレス剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15827264

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15827264

Country of ref document: EP

Kind code of ref document: A1