WO2012143041A1 - Composition, son procédé de production et son utilisation - Google Patents

Composition, son procédé de production et son utilisation Download PDF

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Publication number
WO2012143041A1
WO2012143041A1 PCT/EP2011/056184 EP2011056184W WO2012143041A1 WO 2012143041 A1 WO2012143041 A1 WO 2012143041A1 EP 2011056184 W EP2011056184 W EP 2011056184W WO 2012143041 A1 WO2012143041 A1 WO 2012143041A1
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Prior art keywords
cancer
composition
magnesium
therapy
container
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Ceased
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PCT/EP2011/056184
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English (en)
Inventor
Taneaki Oikawa
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SOUND HOLDING AG
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SOUND HOLDING AG
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Priority to PCT/EP2011/056184 priority Critical patent/WO2012143041A1/fr
Publication of WO2012143041A1 publication Critical patent/WO2012143041A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • 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
    • A61K33/44—Elemental carbon, e.g. charcoal, carbon black
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B3/00—Hydrogen; Gaseous mixtures containing hydrogen; Separation of hydrogen from mixtures containing it; Purification of hydrogen; Reversible storage of hydrogen
    • C01B3/02—Production of hydrogen; Production of gaseous mixtures containing hydrogen
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B6/00—Hydrides of metals including fully or partially hydrided metals, alloys or intermetallic compounds ; Compounds containing at least one metal-hydrogen bond, e.g. (GeH3)2S, SiH GeH; Monoborane or diborane; Addition complexes thereof
    • C01B6/04—Hydrides of alkali metals, alkaline earth metals, beryllium or magnesium; Addition complexes thereof

Definitions

  • compositions may be used to treat e.g. cancer, pain, diabetes, osteoporosis and skin diseases such as dermatitis.
  • compositions emit hydrogen.
  • glia are nervous caretakers whose nurturing can go to far, see "New culprits in chronic pain", R. Douglas Fields, Neuroscience, Scientific American, Nov. 2009 page 30-37.
  • JP2002382862A Manufacture of a magnetic ceramic ball for water purifier is further disclosed in JP2002382862A. Said ball generates active hydrogen.
  • the process comprises mainly the following steps:
  • the spheres are reduction calcinated at 950° in a gas consisting of a mixture of N2 (nitrogen gas) and H2 (hydrogen gas) at a ratio of 90%: 10 % during 12 hours.
  • the drinking and eating of the minus hydrogen ions are said to be having an effect on overweight, prevention of cancer, in addition to an improvement of geriatric disorders, such as hypertension, high cholesterol, hyperlipemia and diabetes.
  • CaH2 is a metal hydride. It appears that the manufacturing process synthesizes the metal hydride by a direct reaction between the solid material and hydrogen gas. The reaction between the solid and gas can be written as follows:
  • eau de toilette is disclosed in WO2010/095279 which includes alkali reducing mineral ion water and process for its production.
  • coral is a limited material on earth.
  • embodiments of the present invention preferably seeks to mitigate, alleviate or eliminate one or more deficiencies, disadvantages or issues in the art, such as the above-identified, singly or in any combination by providing a pharmaceutical composition, method for its manufacture and use thereof according to the appended patent claims.
  • a hydrogen emitting composition for pharmaceutical use comprising a magnesium compound is provided.
  • a method for manufacturing a magnesium hydride set out in a preferred embodiment of the first aspect for use in a composition according to the first aspect comprising the following steps: a) providing magnesium oxide,
  • a magnesium hydride obtainable by the method according to the second aspect is provided.
  • a method for manufacturing a composition set out as a preferred embodiment of the first aspect comprising the following steps:
  • step f) filling the mix obtained in step e) into containers or into capsules, or tableting said mix into tablets, and optionally
  • the magnesium hydride in powder form is a magnesium hydride according to the third aspect, is provided.
  • step h) distributing the mix of step h) into a liquid, preferably water, whereby letting the suspension to rest, and optionally
  • the magnesium hydride in powder form is a magnesium hydride according to the third aspect, is provided.
  • a method for manufacturing a composition set out as a preferred embodiment of the first aspect comprising the following steps:
  • activated carbon preferably in powder form
  • step I) filling said mix of step I) into a perforated container, preferably in the form of a stick,
  • compositions according to the a preferred embodiment of the first aspect preferably in the form of sticks, in a weak acidic liquid, preferably vinegar, and p) inserting one of more of said washed compositions above in water and letting the water rest,
  • water obtainable by the method according the ninth aspect is provided.
  • composition according to a preferred embodiment of the first aspect for producing a hydrogen plasma water is provided.
  • step t) performing an oxidation calcination on the product of step t) at 720 °C and during about 8 hours
  • step v) performing a reduction calcination on the product of step u) at 650 °C and during about 6 hours under a gas atmosphere being a mix of N2 and H2, with ratio 90%: 10%, and w) milling the product of step v) and optionally, x) filling the milled product obtained in step w) into containers or into capsules, or tableting said milled product into tablets, and also optionally if the milled product obtained in step w) filled into capsules or tableted into tablets, packing said capsules or tablets in a container, is provided.
  • a minus hydrogen ion material obtainable by the method according the twelfth aspect is provided.
  • step z drying and forming the mix of step y) into (an) essentially spherical portion(s), aa) performing an oxidation calcination on the product of step z) at 720 °C and during about 8 hours,
  • step bb) performing a reduction calcination on the product of step aa) at 650 °C and during about
  • step bb 6 hours under a gas atmosphere being a mix of N2 and H2, with ratio 90%:10%, and cc) performing a magnetizing process on the product of step bb) and optionally, dd) filling the product obtained in step cc) into a container, is provided.
  • a magnetic ceramic ball obtainable by the method according the fourteenth aspect is provided.
  • composition according to the first aspect is used.
  • composition comprising magnesium for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • composition comprising a magnesium hydride according to the third aspect of the invention for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • liquid according to the sixth aspect of the invention for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • container according to the seventh aspect of the invention for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • water according to the tenth aspect of the invention for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • a magnetic ceramic ball according to the fifteenth aspect of the invention for use in treating an indication or in a therapy as set out in the sixteenth aspect of the invention is provided.
  • kits comprising a weak acidic liquid and a container according to the eighth aspect, preferably in the form of a stick, is provided.
  • mitochondria disease embraces any disease that impact the coordinated synthesis and regulation of energy metabolism. These diseases go by a variety of names. They may also be referred to as inherited respiratory chain diseases of the mitochondria as a way of underscoring the role of the mitochondria in oxygen consumption or respiration. Said disease may further be an orphan mitochondrial disease. A further example of such an orphan disease is Duchenne muscular dystrophy. Mitochondria may malfunction in a number of ways, but one reason may be a genetic error.
  • Inherited mitochondrial disease can arise from defects in genes located in either the nuclear or the mitochondrial genome.
  • Mitochondrial diseases may cause severe, often life-threatening disabilities. As the brain and the muscles consume disproportionate amount of energy and are afflicted early in the course of these diseases, said diseases are often referred to neuromuscular diseases. Mitochondrial diseases may also impair normal function of the heart, kidneys, liver, intestine and pancreas. Children and young adults with said diseases may be very sick, and succumb to progressive aging syndrome- in effect, accelerated aging.
  • a weak acidic liquid any acidic liquid which is edible.
  • One non-limiting example is acetic acid.
  • a preferred weak acidic liquid is vinegar.
  • the composition for pharmaceutical use according to the first aspect is a magnesium hydride or a magnesium metal.
  • the composition comprises a magnesium hydride and a minus hydrogen ion material, both preferably in powder form.
  • the composition comprises a magnesium metal and a minus hydrogen ion material, both preferably in powder form.
  • the composition comprises a magnesium hydride, a calcium hydride and a halogen chloride, preferably NaCI, all preferably in powder form.
  • the composition comprises a magnesium metal, preferably in powder form, magnetic ceramic balls and activated carbon, preferably in powder form.
  • the composition is in liquid form or in solid form.
  • the solid form is a capsule, tablet or a powder for suspending or immersing.
  • the tablet also comprises crystalline cellulose and sucrose fatty acid.
  • the powder for immersing is contained in a stick.
  • the liquid form is a filtered liquid or a suspension.
  • the composition also comprises CoQ10 or an analogue thereof.
  • CoQ10 is also known as Coenzyme Q10, ubiquinone, ubidecarenone or coenzyme Q, i.e.
  • said analogue i.e. CoQ10 analogue
  • said analogue is alpha-tocopherol quinone, tocotrienol quinone, tocotrienol hydroquinone or Idebenone.
  • Idebenone is also known as 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl- cyclohexa-2,5-diene-1 ,4-dione; sold under trade names Catena and Sovrima).
  • the composition may also comprise CoQ10, alpha-tocopherol quinone and Idebenone together or two of these at a time.
  • the composition also comprises a vitamin and/or an antioxidant besides CoQ10 or an analogue set out above.
  • the composition also comprises 4-(p-quinolyl)-2-hydroxybutanamide, 2-(3-hydroxy-3-methylbutyl)-6-(het)aryl-p-quinone or 2-(3- hydroxy-3-methylbutyl)-3-(het)aryl-p-quinone or a derivative thereof of said compounds.
  • the therapy is against cancer, wherein said cancer preferably is terminal cancer.
  • the therapy is against one or more tumors appearing on the surface of an animal or human body and/or inside of an animal or human body.
  • the tumor(s) appearing on the surface of an animal or human body is a melanoma or non-melanoma cancer.
  • the tumor(s) inside of an animal or human body is one or more of a retina blastoma cancer, pancreatic cancer, liver cancer, prostate cancer, ovarian cancer, gastric cancer, bile duct cancer, bladder cancer, colon cancer, epithelial cancer, breast cancer, oral cancer, nasal cancer, osteosarcomas, head cancer, neck cancer, brain cancer, peritoneal cancer, esophageal cancer, kidney cancer, lung cancer, cancer in the nerves, barretts esophagus, basal cell carcinoma, cervical cancer, esophagus cancer, gastrointestinal cancer, gynecology diseases, testicular cancer, rectal cancer and hpv warts.
  • a retina blastoma cancer pancreatic cancer, liver cancer, prostate cancer, ovarian cancer, gastric cancer, bile duct cancer, bladder cancer, colon cancer, epithelial cancer, breast cancer, oral cancer, nasal cancer, osteosarcomas, head cancer, neck cancer, brain cancer, peritoneal cancer,
  • the therapy is against pain.
  • the therapy is against a geriatric disorder.
  • the geriatric disorder is preferably one or more of hypertension, cholesterol, hyperlipemia and diabetes, most preferred hyperlipemia.
  • the therapy is against hyperlipemia.
  • the therapy is promoting hormonal secretion.
  • the dosage regime is 1 capsule or tablet a day.
  • said capsule or tablet is obtained from a method according to the fourth aspect or the twelfth aspect of the invention.
  • the dosage regime is two capsules before exercise.
  • said capsule or tablet is obtained from a method according to the fourth aspect or the twelfth aspect of the invention.
  • the indication is hair loss.
  • the indication is stress symptoms.
  • the indication is loss of sexual capacity.
  • the indication is an inflammation
  • the indication is a mitochondrial disease.
  • the mitochondrial disease is an orphan mitochondrial disease, preferably Duchenne muscular dystrophy or progressive aging syndrome.
  • the mitochondrial disease is associated with a point mutation of the DNA, preferably mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome), Kearns-Sayre Syndrome (KSS), primary progressive multiple sclerosis , Leber's hereditary optic neuropathy, dominant optic atrophy or Friedrich ' s ataxia.
  • MELAS syndrome mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
  • KSS Kearns-Sayre Syndrome
  • primary progressive multiple sclerosis preferably Leber's hereditary optic neuropathy, dominant optic atrophy or Friedrich ' s ataxia.
  • the mitochondrial disease is Huntington ' s disease, adult neurodegenerative disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease or pervasive developmental disorder such as autism.
  • the mitochondrial disease is blindness.
  • the therapy is against osteoporosis, arthritis or chronic anti-inflammatory diseases.
  • the therapy is against a skin disease selected from the group comprising serious atopic dermatitis, Congenital Epidermolysis Bullosa, psoriasis, eczema or inflammatory bowel disease, as like ulcerative colitis and haemorrhoids etc. and combinations thereof.
  • the dosage regime is four to six capsules a day in case of a skin disease as set out above.
  • said capsule is obtained from a method according to the fourth aspect or the twelfth aspect of the invention.
  • the therapy is against obesity.
  • the composition comprises a magnesium hydride or a magnesium metal, for use in treating an indication or in therapy as set out in the sixteenth aspect of the invention.
  • the magnesium hydride according to the third aspect may be used, the liquid according to the sixth aspect may be used, the container according to the eighth aspect may be used, the water according to the tenth aspect may be used, the minus hydrogen material according to the thirteenth aspect may be used or the magnetic ceramic ball according to the fifteenth aspect may be used.
  • compositions of the invention can also include conventional auxiliaries such as surface anaesthetics, sunscreens, flavours, scents, emollients or skin tone colourants and masks.
  • auxiliaries such as surface anaesthetics, sunscreens, flavours, scents, emollients or skin tone colourants and masks.
  • compositions of the present invention are as set out in the first aspect of the invention, the inclusion of other excipients in the composition may be useful.
  • excipients may be utilized with the composition in order to formulate the composition into tablets, capsules, suspensions, powders for suspension and the like.
  • Suitable surfactants include fatty acid and alkyl sulfonates; commercial surfactants such as benzethanium chloride (HYAMINE(R) 1622, available from Lonza, Inc., Fairlawn, N.J.); DOCUSATE SODIUM (available from Mallinckrodt Spec. Chem., St.
  • polyoxyethylene sorbitan fatty acid esters TWEEN(R), available from ICI Americas Inc., Wilmington, DE
  • LIPOSORB(R) P-20 available from Lipochem Inc., Patterson NJ
  • CAPMUL(R) POE-0 available from Abitec Corp., Janesville, Wl
  • natural surfactants such as sodium taurocholic acid, 1 -palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine, lecithin, and other phospholipids and mono- and diglycerides.
  • Such materials can advantageously be employed to increase the rate of dissolution by facilitating wetting, thereby increasing the maximum dissolved concentration, and also to inhibit crystallization or precipitation of drug by interacting with the dissolved drug by mechanisms such as complexation, formation of inclusion complexes, formation of micelles or adsorbing to the surface of solid drug.
  • These surfactants may comprise up to 5 wt% of the composition.
  • pH modifiers such as acids, bases, or buffers may also be beneficial, retarding or enhancing the rate of dissolution of the composition, or, alternatively, helping to improve the chemical stability of the composition.
  • compositions of this invention may be employed in the compositions of this invention, including those excipients well-known in the art (e.g., as described in Remington's).
  • excipients such as fillers, disintegrating agents, pigments, binders, lubricants, glidants, flavorants, and so forth may be used for customary purposes and in typical amounts without adversely affecting the properties of the compositions. These excipients may be utilized after the drug composition has been formed, in order to formulate the composition into tablets, capsules, suspensions, powders for suspension, and the like.
  • matrix materials, fillers, or diluents include lactose, mannitol, xylitol, dextrose, sucrose, sorbitol, compressible sugar, microcrystalline cellulose, powdered cellulose, starch, pregelatinized starch, dextrates, dextran, dextrin, dextrose, maltodextrin, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium carbonate, magnesium oxide, poloxamers such as polyethylene oxide, and hydroxypropyl methyl cellulose.
  • Examples of surface active agents include sodium lauryl sulfate and polysorbate 80.
  • drug complexing agents or solubilizers include the polyethylene glycols, caffeine, xanthene, gentisic acid and cylodextrins.
  • disintegrants examples include sodium starch glycolate, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, crospovidone (polyvinylpolypyrrolidone), methyl cellulose, microcrystalline cellulose, powdered cellulose, starch, pregelatinized starch, and sodium alginate.
  • tablet binders include acacia, alginic acid, carbomer, carboxymethyl cellulose sodium, dextrin, ethylcellulose, gelatin (also a preferred material for capsules obtainable from a method according to the fourth aspect or the twelfth aspect of the invention), guar gum, hydrogenatetd vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose (also a preferred material for capsules obtainable from a method according to the fourth aspect or the twelfth aspect of the invention), hydroxypropyl methyl cellulose, methyl cellulose, liquid glucose, maltodextrin, polymethacrylates, povidone, pregelatinized starch, sodium alginate, starch, sucrose, tragacanth, and zein.
  • acacia alginic acid, carbomer, carboxymethyl cellulose sodium, dextrin, ethylcellulose, gelatin (also a preferred material for capsules obtainable from a method according to the fourth aspect
  • lubricants include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, and zinc stearate.
  • glidants examples include silicon dioxide, talc and cornstarch.
  • compositions of this invention may be used in a wide variety of dosage forms for administration of drugs.
  • Exemplary dosage forms are powders or granules that may be taken orally either dry or reconstituted by addition of water to form a paste, slurry, suspension or solution; tablets; capsules; multiparticulates; and pills.
  • Various additives may be mixed, ground, or granulated with the compositions of this invention to form a material suitable for the above dosage forms.
  • the overall dosage form or powders (particles), granules or beads that make up the dosage form may have superior performance if coated with an enteric polymer to prevent or retard dissolution until the dosage form leaves the stomach.
  • enteric coating materials include
  • HPMCAS HPMCAS, HPMCP, CAP, CAT, carboxymethylethyl cellulose, carboxylic acid-functionalized
  • polymethacrylates and carboxylic acid-functionalized polyacrylates.
  • compositions of this invention may be administered in a controlled release dosage form.
  • the composition is incorporated into an erodible polymeric matrix device.
  • an erodible matrix is meant aqueous-erodible or water-swellable or aqueous-soluble in the sense of being either erodible or swellable or dissolvable in pure water or requiring the presence of an acid or base to ionize the polymeric matrix sufficiently to cause erosion or dissolution.
  • the erodible polymeric matrix When contacted with the aqueous environment of use, the erodible polymeric matrix imbibes water and forms an aqueous-swollen gel or "matrix" that entraps the composition. The aqueous-swollen matrix gradually erodes, swells, disintegrates or dissolves in the environment of use, thereby controlling the release of the drug mixture to the environment of use.
  • compositions of the present invention may be administered by or incorporated into a non-erodible matrix device.
  • the kit according to a twenty-third aspect of the invention may comprise the weak acidic liquid in a vial or bottle (preferably vinegar or acetic acid) and the container according to the eighth aspect in the form of a stick.
  • the bottle/vial together with stick may be comprised in a box. Said box may further contain several bottles/vials and sticks.
  • composition according to the first aspect of the invention is more nature friendly as set out earlier above, it has a better quality and is a cleaner product.
  • Figure 1 is a schematic drawing of the manufacture of the edible minus hydrogen powder
  • Figure 2 is a schematic drawing of the manufacture of the hydrogenated magnesium.
  • Figure 3 is a schematic drawing of the manufacture of the hydrogen balance capsule and tablet.
  • Figure 4 is a schematic drawing of the manufacture of the metal magnesium hydrogen ion capsule and tablet.
  • Figure 5 is a schematic drawing of the manufacture of the magnetic ceramic ball.
  • Figure 6 is a schematic drawing of the manufacture of the hydrogenated calcium powder for use when making hydrogen plasma water.
  • Figure 7 is a schematic drawing of the preparation of a hydrogen plasma water.
  • Figure 8 is a further schematic drawing of the preparation of a hydrogen plasma water.
  • Figure 9 is a schematic drawing of the preparation of a stick for providing a hydrogen plasma water.
  • Figure 10 is a schematic drawing of the method in example 10.
  • Figure 11 shows changes in triglyceride levels.
  • Figure 12 shows changes in LDL-cholesterol levels.
  • Figure 13 shows changes in HDL-cholesterol levels.
  • Figure 14 shows changes in ((TC-HDL)/HDL).
  • Figure 17 shows clinical examination.
  • FIG. 18 shows overview of hormones.
  • Figure 19 shows changes in estradiol.
  • FIG. 20 shows changes in ACTH.
  • Figure 21 shows changes in Cortisol.
  • Figure 22 shows changes in adrenaline.
  • Figure 23 shows changes in noradrenaline.
  • Figure 24 shows the material used in example 11.
  • Figure 25 shows analysis of hydrogen.
  • Figure 26 shows method of analysis of hydrogen.
  • Figure 27 shows changes in TG.
  • Figure 28 shows changes in TC (total cholesterol).
  • Figure 29 shows changes in fasting LDL cholesterol.
  • Figure 30 shows changes in fasting HDL cholesterol.
  • Figure 31 shows changes in ((TC-HDL)/HDL).
  • Figure 32 shows changes in HDL /HDL ratio.
  • Figure 33 shows changes in body weight.
  • Figure 34 and 35 show changes in fat.
  • Figure 36 shows method of analysis of hydrogen.
  • Figure 37 shows the case in example 12.
  • Figure 38 shows also the case in example 12.
  • Figure 39 shows also the case in example 13 - before treatment.
  • Figure 40 shows also the case in example 13 - after treatment.
  • Product name a food additives, corals uncalcined calcium
  • cover woven wire dryer only with a kitchen paper for the formed dumpling, and carry about 20 dumplings to one wire.
  • Drying times will be dried from a dryer operations commence for 18 hours or more on about the 1 day (overnight).
  • the capsule by which capsule filling was carried out sends pass box to a through packaging rooms.
  • control the quality so that temperature management may be performed (in particular summer) and deterioration of quality may not start.
  • SAMMAGU Kyowa herein after called SAMMAGU
  • the powder of about 1 kg was stuffed into one sagger container.
  • a milling process also has no materials after calcination because of a powder form.
  • the packed hydrogenated magnesium moves to a product preservation warehouse, and keep it.
  • the quality control so that temperature control may be performed (in particular summer) and deterioration of quality may not start.
  • the hydrogen balance powder or edible minus hydrogen ion powder and hydrogenated magnesium are dispatched to a contract processor, and then are making at there.
  • Example 4 manufacturing of magnesium metal combined with hydrogen ion balance; also reflected in Figure 4 Material
  • Edible minus hydrogen ion powder and metal magnesium are sent to the product room of the clean room A from a product preservation warehouse with pass box.
  • Example 5 manufacturing of magnetic ceramic balls; also reflected in Figure 5 (c.f.
  • Drying times will be dried from a dryer operations commence for 18 hours or more on about the 1 day (overnight).
  • Reduction calcination of ceramic balls does not use heating-proof containers, such as sagger container, in the furnace of a reduction calcination machine, but throws in directly the ceramic ball which carried out oxide calcination. - the color of the ceramic ball in this time - auburn.
  • the amount supplied to reduction furnace machine 1 set supplies 6kg or less to a standard. (A maximum of 6 to 7 kg)
  • the ceramic ball which carried out reduction calcinations is taken with magnetism irradiation, using a magnetization machine.
  • control the quality so that temperature management may be performed (in particular Summer) and deterioration of quality may not start.
  • Example 6 manufacturing of hydrogenated calcium; also reflected in Figure 6 (c.f.
  • a milling process also has no materials after calcination because of a powder form.
  • the packed calcium hydride moves to a product storage warehouse, and keep it.
  • control the quality so that temperature management may be performed (in particular summer) and deterioration of quality may not start.
  • Example 7 manufacturing of hydrogen plasma water; also reflected in Figure 7 -powder filtration good
  • Example 8 manufacturing of hydrogen plasma water using stick embodiment; also reflected in
  • the stick containing a magnetic ceramic ball (herein after the stick for hydrogen plasma waters®preparation) which possesses the reduction property is used (see example 5). Preparation cleaning
  • Example 9 manufacturing of stick embodiment used for hydrogen plasma water in example 8; also reflected in Figure 9
  • Activated carbon (for food manufacture processing water and drinking water)
  • Product name coconut activated carbon
  • Polyester mesh 25 mm x 140mm suture
  • the patients were diagnosed as hyperlipemic by medical diagnosis during 2006-2007. All patients then consumed minus hydrogen supplements and follow up tests were confirmed.
  • the blood samples performed all double checked. Starting by confirming the initial values from the medical test results, the test was subsequently performed double checks on each of the fasting blood tests done at 6 to 10 weeks and again at 14 to 20 weeks following the commencement of minus hydrogen supplement consumption.
  • test were checked for any significant data using a repetition variance analysis approach and compared results between groups with multiple comparisons.
  • Triglyceride levels went down significantly 2 months after diet guidance began. However, by 4 months there were no further reductions and normal triglyceride levels were not reached. After adding the hydrogen supplements these levels went down significantly with normal triglyceride levels being reached and maintained.
  • Hydrogen seemed to contribute to significant reductions in triglycerides and weight. Since there were also improvements in blood sugar A1 c among diabetic patients, hydrogen may have enabled greater energy metabolism, which is further supported by hydrogen's apparent synergistic effect with diet. (In fact, there were some cases where patient's blood sugar level, triglyceride level and weight increased among those who took only hydrogen supplements without diet.)
  • Estradiol is one of the female hormone, and also has a cells regeneration
  • a likelihood that the supplement has stimulated the gonadotrophic hormone of hypothalamus or the corpus luteum hormone (LH) of a hypophysis, and follicle- stimulating hormones (FSH) secretion can be considered.
  • Catecholamine is secreted from sympathetic nerves and adrenal medullas. Catecholamine
  • Noradrenaline went up intentionally by the woman.
  • estradiol went up intentionally by the woman.
  • Example 12 diabetes and hyperlipemia
  • Importance is attached to participation of the oxidization stress in various diseases. Activity is high, and specifically a hydroxyl radical has a short life, and since it is not qualitatively usual anti-oxidization enzyme or qualitatively / usual / of an anti-oxide eliminable, it is made high grade. It is reported that hydrogen gas eliminates a hydroxyl radical specifically in recent years.
  • Hydrogen gas was generated and it reached before and after a mean of 800 ppm. See figure 25-Hydrogen emission measurement. Objective
  • a Stat Mate III Program was employed; Factor repeated measures analysis of variance. It was authorized whether there is any their significance. It compared with a certain case each inter group by the multiple comparison.
  • figure 33 Height of 170cm / weight of 111kg
  • a generation of hydrogen gas was recognized for long time from hydrogen preservation object.
  • Discussion 1 A neutral fat value and body weight fell intentionally by hydrogen preservation objects ingestion.
  • Hydrogen is on a cellular level. Energy production and metabolisms are activated. Metabolic syndrome is also rivaled. Example 13 - serious atopic disease
  • the patient was a female infant and 4 years old. When the patient together with her parents had visited the clinic, the remainder of the patient life was estimated with one month by the physician in charge of the hospital.
  • the patient was a skin defect of terminal limb at birth.
  • the patient was diagnosed with congenital epidermolysis bullosa by DNA examination test.
  • the patient was constant malnutrition and constant state of anemia by reason of a frequent bleeding, fluid exudation and infection.

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Abstract

La présente invention concerne une composition, son procédé de production et son utilisation.
PCT/EP2011/056184 2011-04-18 2011-04-18 Composition, son procédé de production et son utilisation Ceased WO2012143041A1 (fr)

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US9750705B2 (en) 2012-08-31 2017-09-05 The Regents Of The University Of California Agents useful for treating obesity, diabetes and related disorders
CN110155942A (zh) * 2019-05-17 2019-08-23 上海镁源动力科技有限公司 一种基于氢化镁的缓释放氢制剂及其制备方法
CN113908172A (zh) * 2021-12-01 2022-01-11 河北医科大学 氢气、氢化珊瑚钙在制备治疗甲基苯丙胺所致高热和精神障碍的药物中的应用
CN114806725A (zh) * 2022-04-19 2022-07-29 青岛嘉乐宝环保用品有限公司 一种高效家用清洗剂及其制备方法
CN116076733A (zh) * 2022-10-10 2023-05-09 上海氢美健康科技有限公司 一种包含益生菌微胶囊和氢镁素的缓释组合物、制备方法及应用

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9750705B2 (en) 2012-08-31 2017-09-05 The Regents Of The University Of California Agents useful for treating obesity, diabetes and related disorders
CN110155942A (zh) * 2019-05-17 2019-08-23 上海镁源动力科技有限公司 一种基于氢化镁的缓释放氢制剂及其制备方法
CN113908172A (zh) * 2021-12-01 2022-01-11 河北医科大学 氢气、氢化珊瑚钙在制备治疗甲基苯丙胺所致高热和精神障碍的药物中的应用
CN114806725A (zh) * 2022-04-19 2022-07-29 青岛嘉乐宝环保用品有限公司 一种高效家用清洗剂及其制备方法
CN116076733A (zh) * 2022-10-10 2023-05-09 上海氢美健康科技有限公司 一种包含益生菌微胶囊和氢镁素的缓释组合物、制备方法及应用
CN116076733B (zh) * 2022-10-10 2024-04-02 上海氢美健康科技有限公司 一种包含益生菌微胶囊和氢镁素的缓释组合物、制备方法及应用

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