WO2008122102A1 - Composition à base de mélatonine améliorant le sommeil - Google Patents

Composition à base de mélatonine améliorant le sommeil Download PDF

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Publication number
WO2008122102A1
WO2008122102A1 PCT/CA2007/000578 CA2007000578W WO2008122102A1 WO 2008122102 A1 WO2008122102 A1 WO 2008122102A1 CA 2007000578 W CA2007000578 W CA 2007000578W WO 2008122102 A1 WO2008122102 A1 WO 2008122102A1
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WO
WIPO (PCT)
Prior art keywords
melatonin
release
sleep
extract
effective amount
Prior art date
Application number
PCT/CA2007/000578
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English (en)
Inventor
Marvin Heuer
Ken Clement
Shan Chaudhuri
Megan Thomas
Original Assignee
Iomedix Development International Srl
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.)
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Publication date
Application filed by Iomedix Development International Srl filed Critical Iomedix Development International Srl
Priority to PCT/CA2007/000578 priority Critical patent/WO2008122102A1/fr
Publication of WO2008122102A1 publication Critical patent/WO2008122102A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics

Definitions

  • the present invention is directed towards supplemental compositions containing melatonin and methods for improving sleep and relaxation in an individual.
  • the regulation of sleep in humans is governed by three processes - each influenced by hormonal and environmental factors: a daily sleep- wake cycle influenced by a circadian rhythm (24 hour cycle) tied to light-dark cycles.
  • the need for sleep is a biological drive similar to thirst or hunger.
  • insomnia is estimated to affect a significant portion of the population every year and is associated with health problems and concomitant economic loss to society (Stoller MK. Economic effects of insomnia. Clin Ther. 1994 Sep-Oct;16(5):873-97 Abstract). It is clear that the impairment of sleep is detrimental to one's health. In humans, mild sleep deprivation results in indications of impaired immune system function (Irwin M, McClintick J, Costlow C, Fortner M, White J, Gillin JC. Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J. 1996 Apr;10(5):643-53.). Prolonged sleep deprivation is even known to result in death. It has been determined by many that an individual can survive longer without food than one can without sleep; thus indicating the importance of sleep.
  • a supplemental composition comprising an effective amount of melatonin, an effective amount of an extract of lavender and an effective amount of an extract of Ferula to improve sleep and relaxation in an individual.
  • the composition may be provided in a multi-compartmentalized capsule-based form to facilitate a controlled and sustained release of specific active ingredients in a specific sequence of release.
  • the present invention is directed towards compositions and methods to improve sleep and relaxation.
  • the composition comprises melatonin, lavender flower powder and Ferula.
  • the composition comprises melatonin, lavender flower powder and Ferula in a multi- compartmentalized dosage form comprised of a plurality individual capsule-based compartments wherein each of the capsule-based compartments contains specific ingredients to a provide specific and controlled release of specific active ingredients in a predetermined sequence to facilitate the quality of sleep and relaxation in a mammal.
  • the composition comprises melatonin, lavender flower powder and Ferula in a multi- compartmentalized dosage form comprised of a plurality of beadlets contained in a capsule dosage from wherein each of the beadlets contains specific ingredients to a provide specific and controlled release of specific active ingredients in a predetermined sequence to facilitate the quality of sleep and relaxation in a mammal.
  • improvements in sleep may be both of a quantitative nature, e.g. increased length of sleep, decreased time of sleep onset, and of a qualitative nature e.g. deeper, more restful undisturbed and following an ideal pattern through the four known stages of sleep. It is further understood that improvements in sleep may also be both direct and indirect. For example, sleep will be directly improved by the administration of a substance which is known to reduce time to sleep onset. Sleep may be indirectly improved, for example, by the administration of a substance which is known to result in feelings of relaxation and calmness.
  • unmodified-release' format is understood to be defined as pertaining to the dissolution and bioavailability profile of an ingested dietary ingredient wherein no additional modifications, be it chemical or physical, have been made to the ingredient with the specific intent to alter the dissolution or bioavailability profile from that of ingredient in a naturally occurring form. It is also understood that unmodified-release is, essentially, immediate-release of active ingredients. This is further understood to be traditional- or conventional-release format where no slow-, delayed- or extended-release effect is incorporated.
  • controlled-release' format is understood to be defined as a formulation of active ingredients and appropriate excipients in a specific format to facilitate a controlled- or non-immediate-release of active ingredients.
  • the components of a controlled-release format may have been subjected to additional modifications, be it chemical or physical, with the specific intent to alter the dissolution or bioavailability profile from that of ingredient in a naturally occurring form.
  • the term 'slow-release' format is understood to be defined as a controlled-release format wherein the release of active ingredients are delayed for a period of time or gradually released over an extended period of time. This is accomplished through the use of specific excipients and may include structural features designed to facilitate controlled-release. It is further understood that a slow- release format releases active ingredients at a rate slower than immediate-release.
  • delayed-release' format is understood to be defined essentially as a controlled-release format wherein the components of the delayed-release format have undergone specific modifications, be it physical or chemical, to facilitate the release of active ingredients at a specific time after ingestion. It is further understood that delayed-release formats, release active ingredients at a period of time later than unmodified release.
  • the term 'quick-release' format is understood to be defined essentially as 'unmodified-release', as defined above. However, the term 'quick-release' may further include components having modifications, chemical or physical, to enhance the rate of dissolution or bioavailability of active ingredients.
  • Melatonin is a hormone produced by the pineal gland and is derived from the amino acid tryptophan. While possibly being involved in multiple biological processes, melatonin has largely been studied for its involvement in sleep regulation (Karasek M, Winczyk K. Melatonin in humans. J Physiol Pharmacol. 2006 Nov;57 Suppl 5:19-39) with respect to the circadian rhythm cycle of an individual. Levels of melatonin cycle in the body based on lighting conditions - i.e. low melatonin levels during the day, higher levels at night. Typically, melatonin levels peak in the middle of the night and diminish thereafter.
  • the composition includes melatonin to improve sleep onset and sleep quality.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.1000 g of melatonin.
  • said melatonin is provided in three distinct formats wherein each of said formats provided is designed to have different rate of release.
  • a first dosage format comprises from about 0.0001 g to about 0.005 g of melatonin in a quick-release format. About 0.0030 g of melatonin in said first dosage format is preferably provided in a serving.
  • a second dosage format of melatonin comprising a slow- release technology in the present invention comprises from about 0.0001 g to about 0.005 g of melatonin. About 0.0020 g of melatonin in said second dosage format is preferably provided in a serving.
  • a third dosage format of said melatonin of the present invention comprises from about 0.0010 g to about 0.0100g of melatonin in an unmodified release format. The preferred dosage of said third format comprises about 0.0050 g of melatonin.
  • Oil from the lavender plant is commonly used in aromatherapy for relaxation.
  • the mild sedative effects of lavender have been demonstrated in animals and humans (Lis-Balchin M, Hart S. Studies on the mode of action of the essential oil of lavender (Lavandula angustifolia P. Miller). Phytother Res. 1999 Sep;13(6):540-2).
  • Transdermal absorption of the main constituent of lavender oil, linalool has been shown to reduce blood pressure and skin temperature in humans, evidencing a relaxing effect (Heuberger E, Redhammer S, Buchbauer G. Transdermal absorption of (-)-linalool induces autonomic deactivation but has no impact on ratings of well-being in humans. Neuropsychopharmacology. 2004 Oct;29(10):1925-32).
  • the composition includes lavender flower powder to promote a feeling of relaxation.
  • a serving of the supplemental composition includes from about 0.0010 g to about 0.0100 g of lavender flower powder.
  • the preferred dosage of lavender flower powder in the present invention comprises about 0.0050 g. per serving.
  • Ferula is a genus of herbaceous perennial plant that has scented flowers and is native to the Mediterranean region east to central Asia, mostly growing in arid climates. Ferula extracts have demonstrated relaxant effects (Fatehi M, Farifteh F, Fatehi-Hassanabad Z. Antispasmodic and hypotensive effects of Ferula asafoetida gum extract. J Ethnopharmacol. 2004 Apr;91(2-3):321-4 Abstract).
  • the composition includes Ferula to reduce anxiety.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Ferula.
  • the preferred dosage of Ferula in the present invention comprises about 0.0010 g per serving.
  • Nyctanthes arbortirstis and it is sometimes called the tree of grief because the flowers lose their brightness during daytime.
  • Nyctanthes extracts have been shown to have tranquilizing effects (Saxena RS, Gupta B, Lata S. Tranquilizing, antihistaminic and purgative activity of Nyctanthes arbor tristis leaf extract. J Ethnopharmacol. 2002 Aug;81(3):321-5 Abstract).
  • the composition includes Nyctanthes to promote feelings of tranquility.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Nyctanthes.
  • the preferred dosage of Nyctanthes in the present invention comprises about 0.0010 g per serving.
  • Passion flower has been used traditionally for relaxation and as a sleep-aid and treatment for anxiety.
  • Specific flavonoids contained in Passion flower have been shown to have sedative properties.
  • Passion flower extract has been noted to reduce anxiety and induce sleep in mice (Soulimani R, Younos C, Jarmouni S, Bousta D, Misslin R, Mortier F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997 Jun;57(l):l l-20 Abstract).
  • the composition includes an extract of Passion flower to promote feelings of relaxation and calmness and to induce sleep.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of an extract of Passion flower.
  • the preferred dosage of an extract of Passion flower in the present invention comprises about 0.002 g per serving.
  • the composition includes Elettaria cardamom to promote feelings of relaxation.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Elettaria cardamom.
  • the preferred dosage of Elettaria cardamom in the present invention comprises about 0.0010 g per serving.
  • Lactium® is a hydrolyzed milk peptide that has been used in stress management in adult females, and has demonstrated a protective effect on sleep during periods of mild chronic stress in mice (http://www.lactium.com/). The action is likely mediated via binding of this specific peptide, having the amino acid sequence of 91 Typ-Leu-Gly-Tyr-Leu-Glu-Gln-Leu-Leu-Arg 100 in a benzodiazepine-like fashion (Lecouvev M, Frochot C, Miclo L, Orlewski P, Driou A, Linden G, Gaillard JL, Marraud M, Cung MT, Vanderesse R.
  • the neurotransmitter GABA is the primary inhibitory neurotransmitter and one of its effects is to induce sleep. Signaling through the GABA-receptor changes the electrochemical gradient of the neuron, leading to activity inhibition.
  • Benzodiazepines are thought to act via interaction with the GABA receptor; thus enhancing the inhibitory effects of GABA. As such, benzodiazepines are a widely used class of drugs primarily used as tranquilizers, muscle-relaxants, hypnotics or sedatives.
  • the composition includes Lactium® to promote feelings of relaxation and to induce sleep.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Lactium®.
  • the preferred dosage of Lactium® in the present invention comprises about 0.0010 g per serving.
  • Theanine also known as ⁇ -glutamethylethylamide and N-ethyl-L- glutamine, is an amino acid found in green tea. It is however distinct from the polyphenols and catechins which are typically associated with the beneficial effects of green tea. While catechins are generally associated with antioxidant activities, theanine is associated with anti-stress. In hypertensive rats, theanine lowers blood pressure (Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N. Reduction effect of theanine on blood pressure and brain 5- hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1995
  • the composition includes theanine to reduce stress.
  • a serving of the supplemental composition includes from about 0.010 g to about 0.100 g of theanine.
  • the preferred dosage of theanine in the present invention comprises about 0.052 g per serving.
  • the composition includes Gardenia gummifera to promote feelings of relaxation.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Gardenia gummifera
  • the preferred dosage of Gardenia gummifera in the present invention comprises about 0.0010 g per serving.
  • Marjoram is an herb commonly used in aromatherapy and is known for its soothing effects and is additionally purported to relieve anxiety.
  • the composition includes Marjoram to reduce anxiety and promote feelings of relaxation.
  • a serving of the supplemental composition includes from about 0.0001 g to about 0.0050 g of Marjoram.
  • the preferred dosage of Marjoram in the present invention comprises about 0.0010 g per serving.
  • the present invention may additionally further comprise between from about 0.0001 g and about 0.0050 g of sweet violet per serving.
  • the preferred dosage of Sweet violet in the present invention comprises about 0.0010 g per serving.
  • the present invention may additionally further comprise between from about 0.000001 g and about 0.00001 g of Vitamin B12 per serving.
  • the preferred dosage of Vitamin B12 in the present invention comprises about 0.000006 g per serving.
  • the composition is comprised of melatonin, lavender flower extract and Ferula extract.
  • the composition is comprised of melatonin, lavender flower extract, Ferula and one or more of the following: Passion flower extract, Nyctanthes, Elettaria cardamom, Lactium®, Theanine, Gardenia gummifera and ' Marjoram.
  • various embodiments of the present invention comprise
  • the individual components of the present invention in all of its embodiments will act to advantageously improve sleep by the combined and synergistic effects of directly promoting sleep onset and maintenance and indirectly by promoting feelings conducive to sleep such as relaxation and calmness.
  • the various time- release formats and specific dosages thereof of specific ingredient comprising the compositions disclosed herein contribute to an effective dosing regime over the duration of an individual's night sleep.
  • the respective amounts of said ingredients in the various time-release formats are herein understood by the inventors provide an effective about of said ingredient at points during one's sleep when they are in need thereof.
  • the supplemental composition may be consumed in any form.
  • the dosage form of the nutritional supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel.
  • the preferred dosage form of the present invention is that of a dietary gel.
  • release formats may be achieved through the use of specific excipients and specific combinations of excipients. Furthermore, it is known that a single oral solid dosage format may be produced that provides combinations of release formats. Such formats may be described as having multi-phasic release properties. Furthermore, each specific release format contained in such a multi-phasic release format may be physically separated into distinct compartments.
  • Such multi-phasic, multi-compartment formats may contain a homogeneous mixture of ingredients separated into distinct compartments, each with a distinct release format, to achieve a complex controlled-release of all ingredients contained in the multi-phasic, multi-compartment format.
  • such multi-phasic, multi-compartment formats may contain specific different ingredients in different compartments, each with a distinct release format, to achieve a complex controlled-release of specific ingredients at distinct times.
  • the specific ingredients of specific compartments may be in a particular form e.g. solid, powder, liquid, gel, beadlet, as dictated by the nature of the specific ingredients or by the desired release format.
  • the present invention may be provided in a multi-phasic, multi-compartment format that facilitates the specific release of particular ingredients in such a way that the desired beneficial effect is achieved.
  • specific components of the present invention directed at promoting the onset of sleep may be contained in a specific compartment of a multi-phasic, multi-compartment format for immediate- or quick-release to quickly encourage sleep in an individual.
  • Other specific components of the present invention directed at promoting the maintenance of sleep may be contained in a specific different compartment of a multi-phasic, multi-compartment format for slow- or delayed-release to encourage the maintenance of sleep in an individual.
  • the specific ingredients of the various embodiments of the present invention may be made bioavailable at a specific predetermined time-frame to maximize beneficial effects based on mechanism of action or intended use for .improving sleep and relaxation in an individual.
  • the supplemental composition may be provided in a dietary gel format.
  • the dietary gel is comprised of ingredients wherein like ingredient may be in various time-release formats; a quick-release format, a slow-release format and unmodified release format.
  • each time-release format will provide unique release characteristics such that a predetermined amount of a specific ingredient is available within an individual following ingestion at given time points.
  • a controlled release of the composition can be achieved to maintain effective amounts specific ingredients at time points wherein said ingredients would provide the most effective benefit to improve the quality sleep in an individual.
  • the dosage form of the supplemental composition may be provided in accordance with customary processing techniques for herbal and nutritional supplements in any of the forms mentioned above.
  • the supplemental composition set forth in the example embodiment herein may contain any appropriate number and type of excipients, as is well known in the art.
  • a method for improving the onset of sleep and improvement of sleep quality is provided.
  • the present nutritional composition or those similarly envisioned by one of skill in the art, may be utilized in methods to improve the quality of sleep in an individual.
  • a nutritional supplement to help promote quality sleep for use immediately prior to bedtime contains the following:
  • a nutritional supplement to help promote quality sleep for use immediately prior to bedtime contains the following:
  • Nyctanthes about 0.0020 g of Passion flower extract, about 0.0010 g of Elettaria cardamom, about 0.0010 g of Lactium®, about 0.0520 g of Theanine, about 0.0010 g of Gardenia gummifera, about 0.0010 g of Marjoram, about 0.0010 g of Sweet violet, and about 0.000006 g of Vitamin B12. Extensions and Alternatives

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  • Health & Medical Sciences (AREA)
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Abstract

Méthode d'amélioration du sommeil chez un individu qui consiste à administrer une composition contenant de la mélatonine, de l'extrait de fleur de lavande et de l'extrait de Ferula. Cette composition peut se présenter sous une forme solide en couche assurant une libération contrôlée et soutenue d'ingrédients spécifiques.
PCT/CA2007/000578 2007-04-05 2007-04-05 Composition à base de mélatonine améliorant le sommeil WO2008122102A1 (fr)

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PCT/CA2007/000578 WO2008122102A1 (fr) 2007-04-05 2007-04-05 Composition à base de mélatonine améliorant le sommeil

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Application Number Priority Date Filing Date Title
PCT/CA2007/000578 WO2008122102A1 (fr) 2007-04-05 2007-04-05 Composition à base de mélatonine améliorant le sommeil

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20110332A1 (it) * 2011-03-03 2012-09-04 Ambros Pharma S R L Formulazioni contenenti melatonina a rilascio pulsatile o sequenziale e procedimento per la loro preparazione

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994007487A1 (fr) * 1992-10-01 1994-04-14 Massachusetts Institute Of Technology Utilisation de la melatonine pour induire le sommeil
WO2003015690A2 (fr) * 2001-08-14 2003-02-27 Neurim Pharmaceuticals (1991) Ltd. Methode de traitement de l'insomnie primaire
CA2561616A1 (fr) * 2004-04-06 2005-10-20 Taiyokagaku Co., Ltd. Composition d'amelioration du sommeil

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994007487A1 (fr) * 1992-10-01 1994-04-14 Massachusetts Institute Of Technology Utilisation de la melatonine pour induire le sommeil
WO2003015690A2 (fr) * 2001-08-14 2003-02-27 Neurim Pharmaceuticals (1991) Ltd. Methode de traitement de l'insomnie primaire
CA2561616A1 (fr) * 2004-04-06 2005-10-20 Taiyokagaku Co., Ltd. Composition d'amelioration du sommeil

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Iovate Health Sciences Sleep MD, EZ-Swallow Caplets", 2006, Retrieved from the Internet <URL:http://www.walgreens.com/store/products.jsp?CATID=304747&navAction=jump&navCount=1&skuid=sku2949067&id=prod2950234#> *
FATEHI M. ET AL.: "Antispasmodic and hypotensive effects of Ferula asafoetida gum extract", vol. 91, 2004, pages 321 - 324 *
GUILLEMAIN J. ET AL.: "Effects neurodepresseurs de l'huile essentielle de Lavandula angustifolia Mill", ANNALES PHARMACEUTIQUES FRANCAISES, vol. 47, 1989, pages 337 - 343, XP009058907 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20110332A1 (it) * 2011-03-03 2012-09-04 Ambros Pharma S R L Formulazioni contenenti melatonina a rilascio pulsatile o sequenziale e procedimento per la loro preparazione

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