WO2003049687A2 - Compositions medicinales et methodes therapeutiques - Google Patents

Compositions medicinales et methodes therapeutiques Download PDF

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Publication number
WO2003049687A2
WO2003049687A2 PCT/US2002/038898 US0238898W WO03049687A2 WO 2003049687 A2 WO2003049687 A2 WO 2003049687A2 US 0238898 W US0238898 W US 0238898W WO 03049687 A2 WO03049687 A2 WO 03049687A2
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WO
WIPO (PCT)
Prior art keywords
therapeutic amount
composition
phenylalanine
leucine
therapeutic
Prior art date
Application number
PCT/US2002/038898
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English (en)
Other versions
WO2003049687A3 (fr
Inventor
Seymour Ehrenpreis
Lawrence Howard
Original Assignee
Weller Health, Inc.
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Publication date
Application filed by Weller Health, Inc. filed Critical Weller Health, Inc.
Priority to US10/497,631 priority Critical patent/US20040241256A1/en
Priority to AU2002359618A priority patent/AU2002359618A1/en
Publication of WO2003049687A2 publication Critical patent/WO2003049687A2/fr
Publication of WO2003049687A3 publication Critical patent/WO2003049687A3/fr
Priority to US11/479,216 priority patent/US20060252727A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A61K38/063—Glutathione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • 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
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/15—Pinaceae (Pine family), e.g. pine or cedar
    • 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
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • 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
    • A61K36/17—Gnetophyta, e.g. Ephedraceae (Mormon-tea family)
    • 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)
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • 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)
    • A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • 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)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • 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)
    • A61K36/74—Rubiaceae (Madder family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H

Definitions

  • the words “comprising,” “having,” and “including,” and other forms thereof, are intended to be equivalent in meaning and be open ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items.
  • the term “arthritis” means inflammation of the articular extremity of a bone resulting in erosion of the cartilage, loss of range of motion and pain.
  • Phenylalanine is now shown by the inventors to be a medication for various maladies, including high blood pressure and pain relief, including treating arthritis.
  • This amino acid includes D- phenylalanine (DPA) or D,L- phenylalanine (DLPA); the latter is a 50-50 mixture of the D and L forms of phenylalanine (DPA and LPA).
  • Phenylalanine is considered to be a dietary supplement; DLPA is sold over-the- counter.
  • DPA, but not LPA is an inhibitor of enzymes that inactivate the naturally occurring peptides — the enkephalins and other endorphins; this compound is termed an enkephalinase inhibitor.
  • DPA not LPA — the L form of phenylalanine-which is the active agent in providing relief in arthritis and other painful conditions.
  • levels of enkephalins in particular have been shown to increase in the central nervous system in mice.
  • various painful conditions are relieved.
  • DPA has been shown to have another activity, namely, as an anti-inflammatory agent.
  • analgesia plus anti-inflammatory activity suggest efficacy of DPA or DLPA in arthritis; data indicating that this is indeed the case as presented below.
  • DPA also lowers above normal blood pressure. This is in contradistinction to the conventional anti-hypertensive drugs that can significantly lower blood pressure even if it is normal.
  • DPA blood pressure-lowering effect of DPA is long-lasting in both animals and humans.
  • DPA may be administered as a once-a-day agent to achieve a blood-pressure lowering effect.
  • DPA appears to be unique among inhibitors of endorphin degradation since it was demonstrated that two other compounds with similar activities - thiorphan and actinonin - were essentially devoid of anti-hypertensive activities.
  • the causes of arthritis are not known, particularly osteoarthritis.
  • Rheumatoid arthritis appears to be an autoimmune disease.
  • Arthritis in animals and humans is attributed to the presence of excessive amounts of prostaglandins and other products of the arachidonic acid cascade, and proteolytic enzymes elaborated during the disease process, is treated by means of combinations of drugs and natural products which serve to prevent the accumulation of pathophysiological factors. Also, various painful conditions in animals and humans are treated by raising the levels of endorphins in the central nervous system through these same means.
  • a primary agent in all such combinations of drugs and natural products is phenylalanine, in doses sufficient to reverse, or prevent, the inflammation and pain of arthritis, or many other painful conditions.
  • the sequence of events that occur in an arthritic joint is as follows: If a pathophysiological event occurs, e.g.
  • arachidonic acid cascade is activated resulting in the generation of prostaglandins and leukotrienes; these substances promote inflammation and pain.
  • Cell membranes within the joint are damaged resulting in the release of proteolytic enzymes, which can erode the cartilage.
  • endorphins enkephalins, _ endorphin
  • DMARDs disease modifying anti-arthritic drugs
  • methotrexate cyclosporine
  • gold compounds gold compounds.
  • all of these drugs have a serious drawback in that they may cause serious, even fatal, adverse reactions.
  • these drugs are involved with many interactions with other drugs, such interactions at times being very deleterious, and requiring difficult adjustment of dosage for the interacting drugs. More recently, several nutraceuticals have been introduced with some success for arthritis treatment.
  • glucosamine GS
  • CSA chondroitin sulfate
  • cetyl myristoleate a naturally occurring compound that offers a new approach to treatment, namely, to slow down, or perhaps even reverse, the destruction of joint cartilage that is characteristic of arthritis. It should be noted that none of these newer agents have analgesic or anti-inflammatory activity.
  • the benefits of this invention include, but are not limited to, treating the following maladies: high blood pressure, osteoarthritis and rheumatoid arthritis, anxiety, depression, psychological disorders such as, for example, ADHD and ADD, OCD, stress, agorophobia, bulimia, anorexia, insomnia, lack of focus, craving including food, drug and alcohol addictions, fibromyalgia, and pain including (1) preventing or reversing the inflammation and chronic and acute pain of arthritis (2) reversing the destruction of cartilage that is present in arthritis, and (3) headache, toothaches, low back pain, musculoskeletal pain, pre-menstrual pain, pain due to sports injury, carpal tunnel injury, broken bones, post operative surgery, and dental pain.
  • compositions of this invention comprise: (1) a mixture of phenylalanine and the dietary food supplement identified below; (2) a mixture of leucine and the dietary food supplement identified below; (3) a mixture of hydrocinnamic acid and the dietary food supplement identified below; and (4) a mixture of and the dietary food supplement identified below and a blend of any two of the phenylalanine, leucine, and hydrocinnamic acid of these ingredients.
  • the phenylalanine, leucine, hydrocinnamic, or mixtures thereof may be present in an amount of from 5 to 95 weight percent and the dietary food supplement may be present in an amount of from 5 to 95 weight percent.
  • the phenylalanine may include as the major component the D -phenylalanine
  • the leucine may include as the major component the D-leucine.
  • the dietary food supplements consist of glucosamine, chondroitin sulfate, Cat's claw, Devil's claw, cetyl myristoleate, a mixture of a cetyl ester and cetyl myristoleate, coenzyme Q-10, fructose 1-6 diphosphate, glutathione (reduced), melatonin, Kava Kava extract, s-adenosylmethionine (SAMe), SAMe including as a major component the (SS)-(+)-SAMe, bromelain, a mixture of white willow bark powder and extract of salicin, either or both hydrolyzed and un-hydrolyzed Type II Collagen, methyl-sulfonyl-methane, hyaluronic acid, pine bark extract, Citrulline, L
  • SAMe compounds are well known pharmacologically active compositions that combat, for example, depression, arthritis, and liver diseases such as, for example, cirrhosis.
  • SAMe occurs as two diastereoisomers: (RS)-(+)-SAMe and (SS)- (+)-SAMe.
  • the (SS)-(+)-SAM-e diastereoisomer is the pharmacologically active diastereoisomer.
  • the SAMe includes as a major component the diastereoisomer (SS)-(+)-SAMe.
  • compositions of this invention may include a therapeutic amount of an anti-depressant medicinal substance such as, for example, fluoxitine, anti- depressants in the SSRI class, or tricyclic anti-depressants.
  • anti-depressant medicinal substances are typically prescription drugs that have adverse side effects. Reduce dosages of these drugs are employed in the compositions of this invention.
  • compositions of this invention are easily administered by the oral route.
  • oral administration via tablets (plain or enteric coated and/or time released), caplets (plain or enteric coated and /or time released), liquids, drinks (ready made or drinks by adding liquid), oral sprays and gels and soft gels (plain or enteric coated and /or time released).
  • the compositions of this invention may be administered by IV's, suppositories, creams, nasal sprays, inhalants, muscle /skeletal injections, added to foods, energy bars, etc., and patches.
  • These compositions may be given in dosages that are safe and provide therapeutic efficacy at such dosages. For example, even trace amounts may be beneficial such as, for example, as low as 1 microgram.
  • the dosage of the composition is from 1 to 400 grams per day, divided, preferably equally, into from 2 to 4 applications per day. In many instances, a dosage of 2-4 grams once a day is adequate.
  • the phenylalanine or leucine or hydrocinnamic acid (or mixtures of two or more) is mixed with Co-Q-10, or Citrulline, or L-Glutamine, or Glutathione, or L- Tryptophane, or mixtures thereof.
  • phenylalanine or leucine or hydrocinnamic acid is mixed with a therapeutic amount of an anti-hypertensive drug especially appropriate for this use. These compositions are especially useful when they include a dietary food supplement such as Co-Q-10.
  • anti-hypertensive drugs include blood vessel dilators such as diazoxide and diuretics such as a thiazide diuretic such as hydrochlorothiazide, a loop diuretic such as furosemide, a potassium-sparing diuretic such as triamterene, an adrenergic-beta-blocking agent a beta blocker such as propranolol, an angiotensin converting enzyme inhibitor such as lisinopril, an angiotensin II receptor, antagonist such as losartan, an alpha-b locker such as prazosin, a calcium channel blocker such as verapamil, a T-type calcium antagonist including for example 2 adrenergic agonist such as clonidine, an inhibitor of norepinephrine sythesis selected from the group consisting of methyl-p-tyrosine, diethyldithiocarbonate, inhibitors of dopamine-_-hydroxylase,
  • the phenylalanine or leucine or hydrocinnamic acid is mixed with Caffeine, Creatine, Ribose, Phosphates, Branch Chain Amino's, FDP, etc., strength and body building protein powders, Ephedra or Ephedrine, e. g., those found in herbs, Creatine, Glutamine, L-Carnitine, Androstene compounds or mixtures thereof.
  • the phenylalanine or leucine or hydrocinnamic acid is mixed with Gingko Biloba, Ginsing, St.
  • a therapeutic amount of the primary agent phenylalanine is blended with a therapeutic amount of one or more of the dietary food supplements set forth in Table 7.
  • one or more of the following: aspirin, acetaminophen, or a non-selective, non-steroid al, anti-inflammatory drug (NSAID), as well as COX 2 inhibitors (NSAID) is added to the blend of phenylalanine and dietary food supplement of the first embodiment.
  • One especially beneficiary composition is a blend of phenylalanine, acetaminophen, and therapeutic amount of glutathione.
  • One or more of the NSAIDs listed in Table 6 may be used.
  • D-phenylalanine is used in both embodiments.
  • the amount of D-phenylalanine administered is between approximately 10 and approximately 3000mg/day, and the amount of D,L- ⁇ henylalanine administered is between approximately 20 and approximately 6000mg/day. Administration may be in the form of a tablet or a capsule.
  • DPA/DLPA provides relief of pain, as do the NSAIDs.
  • the combination of NSAIDs with D-phenylalanine or D,L-phenylalanine has been shown to greatly enhance the analgesia provided by the NSAIDs alone.
  • the combination provides pain relief for those who fail to respond, or respond inadequately, to D-phenylalanine or D,L-phenylalanine alone or NSAIDs alone.
  • DPA/DLPA combined with the NSAIDs have potent anti-inflammatory activities.
  • DPA/DLPA is extremely safe as shown both in animal and human studies.
  • Glucosamine and chondroitin sulfate can promote regeneration of cartilage, which may be destroyed in arthritis.
  • the combinations discussed above provide the following advantages over using them individually: 1. Greater efficacy for relief of pain. 2 . Reduced drug toxicity, in particular by reducing the dosage of acetaminophen, aspirin and other NSAIDs. 3.
  • One aspect of the present invention is to use phenylalanine, leucine or hydrocinnamic acid, or combinations of these ingredients, to inhibit the enzymes that inactivate certain endorphins, thereby permitting these endorphins to accumulate in the central nervous system and the synovial fluid of joints. In so doing, these endorphins relieve the unwanted symptoms. For example, when treating arthritis, the pain and inflammation are reduced by providing analgesia for painful conditions.
  • compositions of this invention may include NSAIDs known to be effective in treating pain and inflammation, namely, aspirin, ibuprophen, etc., permitting the use of lower doses of each component to achieve the desired effect. As a result, adverse effects as well as drug-drug interactions are reduced.
  • Another aspect of the present invention is to use phenylalanine, leucine or hydrocinnamic acid, or combinations of these ingredients, at a dosage sufficient to relieve pain and inflammation of arthritis and the pain that accompanies such conditions as headache, low back pain, musculoskeletal pain, dental pain and pre- menstrual pain. All of the compounds and combinations described above can be offered as pharmaceutically accepted formulations using methods known to those of ordinary skill in the art.
  • formulations may only be administered by the oral route, whether solely or in combination.
  • the dosage of phenylalanine, leucine or hydrocinnamic acid, or combinations of these ingredients, or in combination with any of the other compounds, will depend on the severity of the arthritic, or other painful condition, as well as any existing or potential co-morbidity. It should be noted that the present invention has application for both human and veterinary use. Suggested oral dosages for humans are shown in Table 5. Formulations for human use will be in the form of tablets or capsules, normal and sustained release.
  • Table 1 Anti-inflammatory activity of DPA using the rat paw carrageenan method.
  • Table 2 Anti-inflammatory activity of DPA using the mouse writhing test.
  • Table 3 Analgesic activity of DPA using the mouse hot plate method. Combination of DPA with indomethacin and sulindac, two NSAIDs.
  • Table 5 Suggested dosage schedule for treating arthritis in humans using DPA or DLPA alone or in combination with various other compounds.
  • Table 6 List of NSAIDs, including COX 2 Inhibitors
  • Table 7 List of dietary food supplements combined with DPA
  • mice Male, albino, 22-25 grams.
  • DPA was injected subcutaneously or given by mouth at different times prior to PBQ.
  • the number of writhes were counted over a period of 20 minutes.
  • the effects of DPA were compared to that of similarly administered saline control. Results are shown in Table 2.
  • a drug that blocks writhing would be expected to have anti- inflammatory and hence anti-arthritic activity in humans.
  • the mouse hot plate is a generally recognized method for evaluating analgesic drugs that act on the endorphin system, e.g., morphine-like drugs and drugs that increase endorphin levels, e.g., DPA.
  • analgesic drugs that act on the endorphin system
  • drugs that increase endorphin levels e.g., DPA.
  • Such drugs are useful for treating many kinds of painful conditions including arthritis, headache, low back pain, musculoskeletal pain, pre-menstrual pain, and dental pain.
  • mice (6 albino mice per group, weighing between 22 and 25 grams) are individually placed on a hot plate at 55°C and a beaker is placed over the mouse. The time for the mouse to jump in an attempt to escape the painful condition is recorded.
  • An analgesic substance is one which increases the threshold to pain thereby permitting the mouse to remain on the hot plate for longer times.
  • the effect of the drug is compared to that of a saline control.
  • DPA at different doses was injected intraperitoneally into the mice 2 hours before they were placed on the hot plate, and jumping time determined over the next 1-2 hours. The effect of DPA was compared with that of an injection of saline.
  • the combination was injected at the same time.
  • the second drug consisted of indomethacin, diclofenac or acetaminophen. Each of these drugs is used for treating arthritis as well as many other painful conditions.
  • Table 3 Analgesic activity of DPA, DPA plus indomethacin, DPA plus diclofenac and DPA plus acetaminophen using the mouse hot plate method
  • Table 6 List of NSAIDs, including COX 2 Inhibitors

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Abstract

Les compositions de l'invention comprennent un mélange: 1) de phénylalanine et d'un complément alimentaire; 2) de leucine et d'un complément alimentaire; et 3) d'acide hydrocinnamique et d'un complément alimentaire. Les compositions de l'invention sont utilisées à des fins médicinales pour soulager diverses maladies.
PCT/US2002/038898 2001-12-06 2002-12-05 Compositions medicinales et methodes therapeutiques WO2003049687A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US10/497,631 US20040241256A1 (en) 2002-12-05 2002-12-05 Medicinal compositions & therapeutic methods
AU2002359618A AU2002359618A1 (en) 2001-12-06 2002-12-05 Medicinal compositions and therapeutic methods
US11/479,216 US20060252727A1 (en) 2001-12-06 2006-06-30 Medicinal compositions and therapeutic methods for treating arthritis and other painful conditions

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Cited By (13)

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WO2004039454A1 (fr) * 2002-10-30 2004-05-13 Asat Ag Applied Science & Technology Formulations contenant de la melatonine, du ginkgo biloba et de la biotine
WO2004110417A2 (fr) * 2003-06-12 2004-12-23 The Wwk Trust Compositions destinees a un traitement renforce de la depression
WO2005087207A1 (fr) * 2004-03-11 2005-09-22 Neurocure Ltd. Compositions et procedes pour traiter la depression et tout autre trouble affectif
WO2006062424A2 (fr) * 2004-11-08 2006-06-15 Sgp & Sons Ab Utilisation de 3-hydroxy-3-methylbutyrate seul ou combine a de l'alpha-cetoglutarate dans une croissance osseuse et une mineralisation physiologiques et dans une ostheochondropathie
WO2007055388A2 (fr) 2005-11-09 2007-05-18 Ajinomoto Co., Inc. Activateur du recepteur du calcium
US20110039928A1 (en) * 2009-08-13 2011-02-17 Golini Jeffrey M Cetylated fatty acid and alkali buffered creatine anti-inflammatory composition
US8173605B2 (en) 2005-11-09 2012-05-08 Ajinomoto Co., Inc. Kokumi-imparting agent
US8399417B2 (en) 2007-05-08 2013-03-19 Ajinomoto Co., Inc. Food
US8420144B2 (en) 2005-11-09 2013-04-16 Ajinomoto Co., Inc. Kokumi-imparting agent, method of using, and compositions containing same
US20130142894A1 (en) * 2011-11-16 2013-06-06 Bimini Llc Health supplement compositions for companion animals and methods of using the same
GB2510477A (en) * 2013-01-31 2014-08-06 Christopher Francis Bennett A formulation for use in the treatment of chronic fatigue syndrome
CN104306564A (zh) * 2014-10-31 2015-01-28 贵州黄平美娘冲民族服饰有限公司 一种治疗神经衰弱的药物组合物
JP2020172548A (ja) * 2020-07-28 2020-10-22 株式会社東洋新薬 関節機能改善組成物

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US8017645B2 (en) 2002-10-30 2011-09-13 Asat Ag Applied Science & Technology Melatonin daily dosage units
US8062648B2 (en) 2002-10-30 2011-11-22 Asat Ag Applied Science & Technology Formulations containing melatonin, ginkgo biloba, and biotin
WO2004039454A1 (fr) * 2002-10-30 2004-05-13 Asat Ag Applied Science & Technology Formulations contenant de la melatonine, du ginkgo biloba et de la biotine
WO2004110417A2 (fr) * 2003-06-12 2004-12-23 The Wwk Trust Compositions destinees a un traitement renforce de la depression
WO2004110417A3 (fr) * 2003-06-12 2005-03-24 Wwk Trust Compositions destinees a un traitement renforce de la depression
WO2005087207A1 (fr) * 2004-03-11 2005-09-22 Neurocure Ltd. Compositions et procedes pour traiter la depression et tout autre trouble affectif
WO2006062424A3 (fr) * 2004-11-08 2007-02-15 Sgp & Sons Ab Utilisation de 3-hydroxy-3-methylbutyrate seul ou combine a de l'alpha-cetoglutarate dans une croissance osseuse et une mineralisation physiologiques et dans une ostheochondropathie
WO2006062424A2 (fr) * 2004-11-08 2006-06-15 Sgp & Sons Ab Utilisation de 3-hydroxy-3-methylbutyrate seul ou combine a de l'alpha-cetoglutarate dans une croissance osseuse et une mineralisation physiologiques et dans une ostheochondropathie
US9395376B2 (en) 2005-11-09 2016-07-19 Ajinomoto Co., Inc. Kokumi-imparting agent
WO2007055388A3 (fr) * 2005-11-09 2007-09-27 Ajinomoto Kk Activateur du recepteur du calcium
US8106020B2 (en) 2005-11-09 2012-01-31 Ajinomoto Co., Inc. Calcium receptor activator
US8173605B2 (en) 2005-11-09 2012-05-08 Ajinomoto Co., Inc. Kokumi-imparting agent
WO2007055388A2 (fr) 2005-11-09 2007-05-18 Ajinomoto Co., Inc. Activateur du recepteur du calcium
US8420144B2 (en) 2005-11-09 2013-04-16 Ajinomoto Co., Inc. Kokumi-imparting agent, method of using, and compositions containing same
US8399417B2 (en) 2007-05-08 2013-03-19 Ajinomoto Co., Inc. Food
US20110039928A1 (en) * 2009-08-13 2011-02-17 Golini Jeffrey M Cetylated fatty acid and alkali buffered creatine anti-inflammatory composition
US20150011631A1 (en) * 2009-08-13 2015-01-08 Jeffrey M. Golini Cetylated fatty acid and alkali buffered creative anti-inflammatory composition
US9968581B2 (en) * 2009-08-13 2018-05-15 Jeffrey M. Golini Cetylated fatty acid and alkali buffered creatine anti-inflammatory composition
US20130142894A1 (en) * 2011-11-16 2013-06-06 Bimini Llc Health supplement compositions for companion animals and methods of using the same
GB2510477A (en) * 2013-01-31 2014-08-06 Christopher Francis Bennett A formulation for use in the treatment of chronic fatigue syndrome
GB2510477B (en) * 2013-01-31 2017-12-13 Francis Bennett Christopher Formulations for use in the treatment of chronic fatigue and associated conditions, etc
CN104306564A (zh) * 2014-10-31 2015-01-28 贵州黄平美娘冲民族服饰有限公司 一种治疗神经衰弱的药物组合物
JP2020172548A (ja) * 2020-07-28 2020-10-22 株式会社東洋新薬 関節機能改善組成物

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