WO2008050580A1 - Composition minérale pour la prévention ou le traitement d'une maladie diabétique - Google Patents

Composition minérale pour la prévention ou le traitement d'une maladie diabétique Download PDF

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WO2008050580A1
WO2008050580A1 PCT/JP2007/069002 JP2007069002W WO2008050580A1 WO 2008050580 A1 WO2008050580 A1 WO 2008050580A1 JP 2007069002 W JP2007069002 W JP 2007069002W WO 2008050580 A1 WO2008050580 A1 WO 2008050580A1
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Prior art keywords
aqueous solution
salt
diabetic
salt aqueous
arthritis
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PCT/JP2007/069002
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English (en)
Japanese (ja)
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Shigeo Kono
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Shigeo Kono
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Priority to JP2008540928A priority Critical patent/JP5323488B2/ja
Publication of WO2008050580A1 publication Critical patent/WO2008050580A1/fr

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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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P3/06—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

Definitions

  • the present invention relates to a mineral composition for the prevention and treatment of diabetic diseases or arthritis, and more specifically, a natural ion exchanger such as zeolite (mordenite) is brought into contact with an aqueous potassium salt solution, etc. Special salt obtained by elution by separation and separation of the eluate, etc.
  • Composition for preventing or treating diabetic disease or arthritis comprising as an active ingredient, a special salt sardecella, containing the special salt sardecella, It relates to functional foods or food materials that have an action for improvement.
  • Diabetes mellitus refers to abnormal metabolism of sugar, protein, or lipid resulting from impaired insulin secretion in the insulin-producing cells (/ 3 cells) of the spleen or insufficiency of insulin in the target cells.
  • Diseases type I diabetes
  • non-insulin-dependent diabetes mellitus type 2 diabetes
  • Insulin-dependent diabetes mellitus develops at a young age and cannot be treated without insulin injections.
  • Non-insulin dependent diabetes mellitus type 2 diabetes
  • Non-insulin dependent diabetes mellitus type 2 diabetes
  • a person who is born with a weak cellular power to produce insulin may be affected by obesity, lack of exercise, changes in hormone secretion, etc. If the supply is reduced and the required amount is not met, the patient will become sick. If you leave diabetes alone! /, Blood sugar levels will continue to be high, large and small blood vessels may become clogged, and it will become brittle, and various complications may occur in the organs throughout the body.
  • diabetic retinopathy diabetic nephropathy
  • diabetic neuropathy which are said to be dangerous complications, that is, three major complications.
  • sulphonium urea drugs that promote insulin secretion from the spleen, and the action of an enzyme that degrades disaccharides into monosaccharides ( ⁇ -darcosidase) in the small intestine are suppressed.
  • ⁇ -Dalcosidase inhibitor that improves blood sugar, fast-acting insulin secretagogue that increases insulin secretion from the viscera and effectively suppresses postprandial hyperglycemia, or recently promotes insulin secretion from the viscera
  • Insulin resistance-improving drugs thiazolidine-based preparations, etc.
  • they may be accompanied by various side effects depending on the administration or administration of these preparations. There is nothing.
  • Osteoarthritis an arthritis, is a joint disease with chronic arthritis. It is a disease that causes cartilage degeneration and proliferative changes in bone and cartilage due to degenerative degeneration of cartilage. Deformations of the joints, such as osteophytes at the epiphysis, are also observed. Osteoarthritis increases with age,
  • osteoarthritis centers Treatment of osteoarthritis centers on coping therapy that suppresses pain, and nonsteroidal anti-inflammatory analgesics, hyaluronic acid and steroids that are injected directly into the joint are used.
  • diabetic disease comprising as an effective component a mineral composition comprising minerals obtained by immersing a naturally-occurring ion exchanger in an aqueous potassium salt solution and separating the exudate from the exchanger.
  • a composition for preventing / treating arthritis has not been known.
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2002-332236
  • Patent Document 2 Japanese Patent Laid-Open No. 2003-246738
  • Patent Document 3 Japanese Patent Laid-Open No. 2001-226401
  • the object of the present invention is to prevent diabetic diseases or arthritis patients with few side effects, which can improve diabetic diseases such as hyperglycemia, diabetic hyperlipidemia, diabetic osteoporosis or arthritis.
  • the purpose is to provide therapeutic compositions, functional foods or food materials for the prevention and improvement of diabetic diseases or arthritis.
  • the present inventor has developed a special salt sardecera (hereinafter referred to as "special salt sardecera (a sodium salt)”) obtained by immersing a natural ion exchanger in a saline solution and separating the leachate from the exchanger.
  • special salt sardecera sodium salt
  • the natural ion exchanger is dipped in potassium salt aqueous solution in addition to salt, and the special salt Sardecella obtained in the same way is found to have an effect of promoting osteogenesis and preventing bone disease.
  • the present invention relates to (1) a natural ion exchanger, a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, ammonia water, an ammonium salt aqueous solution, an inorganic acid aqueous solution, an organic acid aqueous solution, seawater. , Salt lake water, or hot spring water, the components of the natural ion exchanger are eluted by ion exchange, and then the eluate is separated from the natural ion exchanger.
  • Zeolite is used as a natural ion exchanger as a composition for preventing or treating diabetic diseases or arthritis, characterized by comprising (1) The composition for preventing or treating diabetic disease or arthritis according to (1), or (3) The above described (1) or (2), wherein the diabetic disease is hyperglycemia A composition for the prevention / treatment of diabetic disease or arthritis, or (4) the diabetic disease or arthritis according to (1) or (2) above, wherein the diabetic disease is diabetic hyperlipidemia Composition for prevention or treatment of (2) or the composition for prevention / treatment of diabetic disease or arthritis according to (1) or (2) above, wherein the diabetic disease is diabetic osteoporosis Related to things.
  • the present invention also includes (6) a natural ion exchanger, a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, ammonia water, an ammonium salt aqueous solution, an inorganic acid aqueous solution, an organic acid aqueous solution, seawater , Salt lake water or hot spring water is contacted, the components of the natural ion exchanger are eluted by ion exchange, and the eluate is separated from the natural ion exchanger by the following!
  • the present invention provides (8) a naturally occurring ion exchanger, a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, ammonia water, ammonium salt water solution, inorganic acid aqueous solution, organic acid aqueous solution, Contact with seawater, salt lake water or hot spring water to elute the components of the natural ion exchanger by ion exchange, and then separate the eluate from the natural ion exchanger.
  • a method of using a food or food material to which salt saldecella has been added as a food or food material for the prevention or treatment of diabetic disease or arthritis (9) natural ion exchangers, sodium salt aqueous solution, strength rhodium salt Aqueous solution, calcium salt solution, magnesium salt solution, ammonia water, ammonium salt solution, inorganic acid solution, organic acid solution, seawater, salt lake A special salt Sardechiera obtained by contacting with hot spring water, eluting the components of the natural ion exchanger by ion exchange, and then separating the eluate from the natural ion exchanger.
  • the use of the special salt Sardecella as an active ingredient prevents or treats hyperglycemia, diabetic hyperlipidemia, diabetic osteoporosis or arthritis, etc. without side effects. It has a remarkable effect of being able to Can be provided in a food or a food material to provide a functional food or a food material that can improve the above symptoms.
  • the composition for prevention / treatment of diabetic disease or arthritis includes a naturally occurring ion exchanger, a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, ammonia water, an ammonium salt.
  • a naturally occurring ion exchanger a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, ammonia water, an ammonium salt.
  • An aqueous solution, an inorganic acid aqueous solution, an organic acid aqueous solution, seawater, salt lake water, or hot spring water are brought into contact with each other, and the content of the natural ion exchanger is eluted by ion exchange.
  • the composition for preventing or treating diabetic disease or arthritis is not particularly limited as long as it contains a special salt Sardecella obtained by separation from a naturally occurring ion exchanger as an active ingredient.
  • Concentration lowering action, blood fatty acid ester concentration lowering action, blood calcium concentration lowering action, etc., diabetic diseases are hyperglycemia, diabetes Hyperlipidemia, when a diabetic osteoporosis, etc., also has a particularly good these indications in contact! /, The force Rushiumu increasing effect at the metaphysis tissue of the joint portion.
  • the present invention provides a functional food or food material containing a special salt sardecella and having an action of improving diabetic disease or arthritis (that is, an indication that it is used for improving diabetic disease).
  • Functional foods or food materials) or foods or food materials added with special salt sardechiera as food or food materials for the prevention or treatment of diabetic diseases, or special salt sardechella Prevention or treatment of sexually transmitted diseases or arthritis Methods to use as a combination of foods or food materials for treatment, or the addition of a special salt Sardechera to foods or food materials Prevention or treatment of diabetic diseases or arthritis Foods or food materials for treatment
  • hyperglycemia, diabetic hyperlipidemia, diabetic osteoporosis and the like can be mentioned.
  • composition for the prevention and treatment of diabetic diseases comprising the special salt Sardecera of the present invention as an active ingredient is a blood glucose concentration lowering action in blood, a fatty acid ester concentration lowering action in blood, calcium in blood Concentration lowering action, blood inorganic phosphorus concentration increasing action, diaphyseal tissue and metaphyseal tissue calcium concentration increasing action, diaphyseal tissue and metaphyseal tissue DNA content increasing action, diaphysis Alkalis in tissues and metaphyseal tissues It has an effect of increasing phosphatase activity and has excellent efficacy against hyperglycemia, diabetic hyperlipidemia, diabetic osteoporosis and the like.
  • composition for the prevention and treatment of arthritis comprising the special salt sardecella of the present invention as an active ingredient does not change serum calcium and inorganic phosphorus, and increases the calcium concentration in the metaphyseal tissue. It has an effect of increasing al force phosphatase activity and DNA content in metaphyseal tissue, and has an excellent effect on bone tissue of arthritic patients.
  • the special salt Sardecera used in the present invention includes those obtained by the following production method.
  • natural ion exchangers sodium salt aqueous solution, potassium salt aqueous solution, calcium salt aqueous solution, magnesium salt aqueous solution, ammonia water, ammonium salt water solution, inorganic acid aqueous solution, organic acid aqueous solution, seawater, salt lake water, hot spring water It can be produced by contacting the heel, eluting the components contained in the natural ion exchanger by ion exchange, and then separating the eluate from the natural ion exchanger.
  • sodium salt aqueous solution examples include sodium chloride, trisodium citrate, sodium dalconate, sodium metaphosphate, sodium malate, sodium succinate, trisodium phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
  • an aqueous solution of sodium chloride can be suitably exemplified.
  • the potassium salt aqueous solution include a potassium salt aqueous solution in which sodium of the sodium salt is replaced with potassium.
  • a potassium chloride aqueous solution can be preferably exemplified.
  • calcium salt aqueous solution calcium chloride, calcium acetate and the like can be exemplified, and among these, calcium chloride can be preferably exemplified.
  • magnesium chloride, magnesium acetate, etc. can be illustrated as magnesium salt aqueous solution, Magnesium chloride can be illustrated suitably among these.
  • the aqueous ammonium salt solution include ammonium chloride and ammonium acetate, and among these, ammonium chloride can be preferably exemplified.
  • the inorganic acid aqueous solution include hydrochloric acid and nitric acid. Among these, hydrochloric acid is preferable. I can help.
  • organic acid aqueous solution examples include acetic acid and citrate, and among these, acetic acid can be preferably exemplified.
  • acetic acid can be preferably exemplified.
  • ammonia water or an aqueous ammonium solution a special salt sardecera can be produced by removing unnecessary components such as ammonium from the eluate.
  • Naturally-occurring ion exchanger examples include naturally occurring mordenite, calcite, fisheye, chabazite, gmelinite, soda zeolite, pyroxene, zeolitite, aragonite, riceite and other zeolites ( Zeolite), acid clay containing montmorillonite as a main component, bentonite and the like can be mentioned, but zeolite (mordenite) is preferable.
  • Zeolite is a hydrous silicate represented by the general formula WZO-sH 2 O.
  • a natural ion exchanger is brought into contact with an aqueous sodium salt solution, and the components contained in the natural ion exchanger are eluted by ion exchange.
  • a natural ion exchanger is preferably pulverized, and a sodium salt aqueous solution, a potassium salt aqueous solution, a calcium salt aqueous solution, a magnesium salt aqueous solution, an ammonia water, an ammonium salt aqueous solution, an inorganic acid aqueous solution, or an organic acid aqueous solution.
  • the ability to elute by an exchange reaction with Na + and K + ions can be specifically mentioned. In this case, heating can be performed at normal pressure or under pressure to promote elution.
  • the concentration of sodium salt (or potassium salt) in the aqueous solution of sodium salt (or potassium salt) during flow or immersion, and the exchanger and sodium salt (or potassium salt) The weight ratio with the aqueous solution depends on the composition of the exchanger used and the content ratio of sodium (or potassium) and other minerals in the target special salt, but the concentration of sodium salt (or potassium salt) is 0.5N to saturated solution is used, and if the concentration is low, the replacement rate is slow.
  • the ratio of the exchanger to the aqueous sodium salt (or strong sodium salt) solution is about 1: 1 to 1:10 by volume.
  • seawater or seawater concentrate including those from which the removed inorganic compound has been removed
  • Water lake water or salt lake water concentrate including those from which precipitated inorganic compounds have been removed
  • hot spring water can be used.
  • the method of elution by the flow method is preferable from the viewpoint of excellent elution efficiency compared with the method of elution by immersion.
  • the eluate is separated from the exchanger by a known method such as filtration or centrifugation to obtain a special salt salterella in the form of a solution. Further, if necessary, it is concentrated by a known method such as heat concentration in an open container or vacuum concentration in a sealed container, and is heated or normal pressure! Special salt Sardecella is obtained.
  • aqueous solution such as aqueous hydrochloric acid, aqueous acetic acid, aqueous ammonia, ammonium salt, or acetate
  • removal of hydrochloric acid and acetic acid may be performed under reduced pressure or drying under normal pressure. In order to completely remove ammonium ions or acetate ions, heat drying is preferred.
  • Minerals other than sodium in the special salt Sardecera (sodium salt) obtained by the above-described production method are calcium, magnesium, potassium, zinc, manganese, silicon, etc., and minerals other than sodium and sodium.
  • the ratio varies depending on the composition of the exchanger to be used, the concentration of the salt to be used, and the ratio to be used, but it can be easily obtained in a ratio of 100: 18 to 40 (molar ratio).
  • minerals other than potassium in the special salt Sardecera (potassium salt) are calcium, magnesium, sodium, zinc, manganese, silicon, etc., and the ratio of minerals other than potassium and potassium is the exchanger used. Depending on the composition, it is easy to obtain 100: 24-40 (molar ratio).
  • Sardecera hydrochloric acid, acetic acid, ammonium acetate, etc.
  • sodium and other minerals with a ratio of 100: 200 or more.
  • the diabetic disease refers to a state exhibiting symptoms of diseases such as type I and / or type II diabetes and various complications resulting from these diabetes, and as a diabetic disease, Hyperglycemia, diabetic hyperlipidemia, diabetic osteoporosis, symptoms of weight loss due to diabetes, changes in blood mineral concentration due to diabetes, complications such as neuropathy or retinopathy or kidney disorders The state which exhibited the symptom of this can be illustrated concretely.
  • the composition for preventing and treating diabetic diseases of the present invention comprises hyperglycemia, diabetic hyperlipidemia, Prevention of diabetic diseases such as diabetic osteoporosis 'Because it has an improving effect, preventive treatment of diabetic diseases by oral administration to diabetics or people with diabetes reserves' treatment method or added to food Therefore, it can be advantageously used as a functional food having an effect of preventing or improving diabetic disease or as a food material for a pharmacological composition.
  • arthritis refers to a state accompanied by redness, swelling, or pain that occurs when damage is applied to a part or when a foreign substance is present.
  • Representative arthritis can be exemplified by osteoarthritis, septic arthritis, tuberculosis arthritis, chronic rheumatism and the like.
  • the composition for preventing / treating arthritis according to the present invention has the ability to prevent / ameliorate osteoarthritis and the like, as well as the arthritis prevention / treatment method by oral administration to arthritic patients.
  • compositions containing the special salt sardecera (sodium salt) or the special salt sardecera (potassium salt) is used as a pharmaceutical product such as a composition for preventing or treating diabetic disease or arthritis, it is pharmaceutically acceptable.
  • a composition containing the special salt sardecera (sodium salt) or the special salt sardecera (potassium salt) is used as a pharmaceutical product such as a composition for preventing or treating diabetic disease or arthritis
  • it is pharmaceutically acceptable.
  • various formulation ingredients such as normal carriers, binders, stabilizers, excipients, diluents, pH buffers, disintegrants, solubilizers, solubilizers, isotonic agents S it can.
  • These prophylactic or therapeutic agents can be administered orally or parenterally.
  • the dose can be appropriately selected according to the purpose of prevention or treatment, the severity of diabetic disease or arthritis, the age of the patient, etc.For treatment in adults, Sardecera (sodium salt) or Sardecella ( Potassium salt (solid) 0 ⁇ ;!
  • “Essential elements of plants” 15 elements are C, 0, H, N, K, Ca, Mg, P, S, CI, Mo, Zn, Fe, Cu, Mn. There are more than 26, and “Necessary elements for humans” is more than 23 (more likely to increase if biotechnology research advances in the future), and C, 0, H, N, K, Ca, Mg, P, S, Cl, Na, F, Si, I, Mo, Zn, Fe, Cu, Mn, Ni, Se, Co, Cr. “Elements that may be essential or functional for humans” include Sr, V, Ge, B, Cd, Ba, Li, As, An, Sn, Pb, Br, and Al.
  • a type of food or food material having a function of preventing or treating diabetic disease or arthritis which is used for the prevention or treatment of diabetic disease or arthritis, with the addition of special salt sardecera or a composition containing special salt sardecera
  • special salt sardecera or a composition containing special salt sardecera Is not particularly limited, for example, mineral water, sports drinks, juice, milk, soy milk, liquor, coffee, tea, sencha, oolong tea and other beverages, yogurt, drink yogurt, pudding, cookies, bread, cake, jelly Baked confectionery such as rice crackers, Japanese confectionery such as sheep crab, bakery confectionery such as frozen confectionery, chewing gum, rice cakes such as udon and soba, and fish paste products such as force, maboko, ham and fish sausage , Miso, soy sauce, dressing, mayonnaise, sweeteners, dairy products such as cheese, butter, etc., tofu, konnyaku other Cite various dishes such as boiled fish, dump
  • Table 1 shows the composition of 1 kg of the special salt Sardecera (potassium salt).
  • Streptozotocin (hereinafter sometimes abbreviated as “STZ”) induces type I diabetes due to impaired insulin secretion when administered to rats.
  • STZ type I diabetes due to impaired insulin secretion when administered to rats.
  • Sardechiera potassium salt
  • Sardecera the effect of anti-diabetic disease by Sardechiera (potassium salt) (hereinafter sometimes simply referred to as Sardecera) was examined.
  • Streptozotocin (manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in a solution of 50 mM citrate ( ⁇ 4.5) in a 150 mM sodium chloride solution to prepare a 6 mg / ml solution, which is administered subcutaneously to rats. did.
  • Wistar male rats (5 weeks old; body weight 110 to 120 g) (obtained from Japan SLC (Hamamatsu)) were used.
  • Sardecera (potassium salt) powder in purified distilled water to prepare solutions with concentrations of 25 and 50 mg / ml, and use this solution once a day using a gastric tube 1 hour after administration of streptozotocin 14 It was orally administered continuously for days.
  • Rats were bled by cardiac puncture under light ether anesthesia 24 hours after the last dose, and the femur was removed.
  • Blood collected from the rat was allowed to stand at room temperature for 30 minutes and centrifuged at 3000 rpm for 5 minutes to obtain serum.
  • Concentrations of serum glucose and serum tridalycelide associated with diabetes in serum are measured using measurement kits (“Glucose Test 1 Koichi”, “Triglyceride 1 Test 1 Koichi” manufactured by Wako Pure Chemical Industries, Ltd.), and bone metabolism Also, the concentration of each of the strength and inorganic phosphorus related to the measurement was also measured using a measurement kit (“Power Lucium C-Test Koichi”, “P-Test Koichi” manufactured by Wako Pure Chemical Industries, Ltd.).
  • the femoral tissue removes muscular tissue and divides it into diaphysis (diaphysis; cortical bone with hard bone) and metaphysis (metaphysis; cancellous bone with soft bone) tissue.
  • Bone marrow was obtained by washing and removing bone marrow cells in a cold 0.25 M sucrose solution.
  • the amount of calcium that is a bone component in the diaphyseal and metaphyseal tissues, the expression level of alkaline phosphatase, the most important enzyme for promoting bone mineralization, and the amount of DNA as an indicator of the number of cells in the bone tissue Were measured by the following measuring methods. [0035] (Measurement of bone calcium)
  • the excised femur tissue piece was washed with 0.25 M sucrose solution and dried, and then the bone weight was measured. Thereafter, concentrated nitric acid was added to the tissue pieces to incinerate at 120 ° C. for 12 hours, and the amount of bone calcium was quantified using an atomic absorption spectrophotometer (“Perkin Elmer 1 303” manufactured by Perkin Elmer).
  • the excised femoral tissue pieces were washed with 0.25 M sucrose solution, crushed in 3 mL of 6.5 mM barbital buffer (PH7.4), and sonicated. This solution was centrifuged and the supernatant was measured as an enzyme solution according to the method of Walter and Schutt (in Method of Enzymatic Analysis, Vo 11-2, p856, Academic Press, New York, 1965).
  • the amount of DNA was quantified as an index of the number of cells in bone tissue.
  • the excised femoral tissue pieces were washed with a 0.25 M sucrose solution and the wet weight was measured. Then, it was pulverized in 4 mL of 0.1N NaOH and infiltrated at 4 ° C for 24 hours. This solution was centrifuged, and the supernatant was used as a sample for quantification according to the method of Ceri otti et al. (J. Biol. Chem., 241: 34-77, 1951).
  • results obtained are displayed as mean soil standard error, statistically processed by Student t test (t test), control group (using 6 rats) and Sardecera (using 6 rats in each treatment group) )
  • Significant difference test was performed by comparing the values obtained from the administration group, and a significant difference was found when the risk rate was 1% or less.
  • Example 4 25 and 50 mg / ml of a solution of Sardecella (potassium salt) powder in purified distilled water, 1 hour after administration of streptozotocin, a gastric sonde was used for 100 g of body weight per rat. Oml was orally administered once a day for 14 consecutive days. During this time, solid feed (oriental yeast, MF) and purified distilled water were freely consumed. Rats were sacrificed 24 hours after the last dose. In addition, the control was not administered with STZ and Sardecella (potassium salt).
  • Each value is expressed as the mean value standard error of the values obtained from 6 rats.
  • Kanolesum Inorganic phosphorus 10.8 ⁇ 0.10 S.8 ⁇ 0.34
  • Each value is expressed as the average soil standard error of the values obtained from 6 rats.
  • Each value is expressed as the average soil standard error of the values obtained from 6 rats.
  • the anti-diabetic effect of the aqueous solution of the special salt sardella (potassium salt) of the present invention was orally administered to diabetic rats once a day for 14 days as described above.
  • streptozotocin was administered to rats, the rats were induced to diabetic due to suppression of weight gain and marked increases in serum glucose and triglyceride concentrations.
  • bone components in the diaphysis (cortical bone) and metaphysis (cancellous bone) tissues of the femur of this diabetic rat were significantly reduced, and diabetic osteoporosis was revealed.
  • the test animals were Wistar male rats (body weight 100-; 1 10 g; 5 weeks old). During the experimental period, rats were given free access to purified distilled water and chow (oriental yeast MF; containing 1.1% calcium, 1.1% phosphorus, 57.4% carbohydrates).
  • the administration sample was prepared at 25.50 mg / ml by dissolving the entire Sardecella composition in purified distilled water. These sample solutions were orally administered at 1 ml per 100 g of rat body weight.
  • Mycobacterium butyricum (MB) was administered subcutaneously to produce arthritic rats. MB is a dead tuberculosis bacterium that is dissolved in liquid paraffin.
  • MB was administered subcutaneously at 50 ⁇ g / 0.1 ml / day 3 times every 3 days. Dissection was performed 18 days after the first dose.
  • the sample solution was orally administered to a joint inflammation rat using a stomach tube once a day for 18 days, and dissected under light ether anesthesia at 24 hours after the final administration. After blood collection, the femur was removed. did.
  • the femur except for the muscle composition, was washed and removed from the bone marrow and divided into a diaphysis (cortical bone) and a metaphysis (cancellous bone), and each was used to measure bone components.
  • the amount of calcium in bone tissue was colorimetrically determined by drying the bone tissue at 100 ° C for 5 hours, measuring the weight, and then digesting it in concentrated nitric acid 2.Oml at 100 ° C for 24 hours.
  • the alkaline phosphatase (bone mineralization promoting enzyme) activity in bone tissue was measured by the method described in the section “Measurement of alkaline phosphatase activity” in Example 3 above.
  • the amount of DNA as an index of the number of cells in the bone tissue was measured by the method described in the section “Quantification of DNA amount” in Example 3.
  • the blood was left at room temperature for 30 minutes and then centrifuged (3000 minutes for 5 minutes) to obtain serum.
  • the amounts of calcium, inorganic phosphorus and zinc as serum components were measured using a commercial kit. Obtained Statistical processing of the obtained data was performed using Student's t-test (t test).
  • Control group 1 75.0 ⁇ 5.1
  • Control group 10.8 ⁇ 0.10 8.8 ⁇ 0.34 Arthritic rats 10.8 F 0.29 8.5 Sat 0.43 Joint inflammation + Sardechera (25 mg / 100g) 10.6 ⁇ 0.1 1 8.5 ⁇ 0.37 Joint inflammation + Sardechera (50rr ig / 100g) 10.9 Sat 0.32 8.4 Soil 0.33 Each value is expressed as the mean and standard error of 6 runts. [0055] (Effects on bone tissue calcium content! /)
  • Table 7 shows the administration effect of the Sardecella composition on the bone tissue calcium content.
  • the calcium content in the diaphyseal tissue of the femoral tissue of joint inflammation rats was not significantly decreased compared to the control group, but the calcium content in the metaphyseal tissue was significantly decreased.
  • Oral administration of the monkey decherella composition (50 mg / 100 g body weight) significantly suppressed the decrease in the amount of calcium in the metaphyseal tissue of rats with joint inflammation.
  • Table 8 shows the effect of Sardecella on the alkaline phosphatase activity of the mineralization-promoting enzyme in the femoral tissue of rats with arthritic inflammation.
  • the alkaline phosphatase activity at the diaphysis was not significantly decreased in the arthritic rats as compared to the control group, but the alkaline phosphatase activity at the metaphysis was significantly decreased. This decrease was significantly improved by the administration of Sardecera (50 mg Zl00 g body weight).
  • Control group 1.491 ⁇ 0.105 1.284 Sat 0.075 Arthritic rats 1.432 ⁇ 0.13 F 0.484 Sat 0.027 * Arthritis + Sardechera (25 mg / 100 g) 1.345 Sat 0.164 0.697 Sat 0.138 Arthritis + Sardechera (50 mg / 100 g) 1. 288 ⁇ 0.124 1 ⁇ 14 soil 0.059 # Each value is shown as the mean and standard error of 6 rats.
  • the effect of Sardecella on the amount of DNA in femoral tissue of rats with arthritic inflammation was examined, and the results are shown in Table 9.
  • the amount of DNA in the diaphyseal and metaphyseal tissues was significantly decreased in rats with joint inflammation compared to the control group.
  • the decrease in DNA at the diaphysis was improved by administration of Sardecera (25 mg / l00 g body weight), and the decrease in the amount of DNA at the metaphysis was significantly improved by administration of Sardecera (50 mg / 100 g body weight).
  • Control group 2.65 ⁇ 0.047 3.60 Sat 0.222 arthritic rats 2.17 ⁇ 0.204 * 2.66 ⁇ 0.227 ** Joint inflammation + sardechera (25mg / 100 g ) 2.23 ⁇ 0.140 * 2.88 + 0.1 50 ** Joint inflammation + sardechera (50mg / 100g) 1.99 soil 0.10 * 3.57 soil 0.22 # Each value is expressed as the mean and standard error of 6 rats.

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Abstract

L'invention concerne un agent prophylactique ou thérapeutique pour une maladie diabétique lequel présente peu d'effets secondaires négatifs et un aliment fonctionnel ou une matière d'aliment pour la prévention ou l'amélioration d'une maladie diabétique, lesquels peuvent tous deux améliorer une maladie diabétique telle que l'hyperglycémie, l'hyperlipémie diabétique et l'ostéoporose diabétique. L'agent prophylactique ou thérapeutique ou l'aliment fonctionnel ou la matière d'aliment comprend, en tant qu'ingrédient actif, un sel spécial “Sal de Tierra” lequel peut être produit en mettant un échangeur d'ions naturel en contact avec une solution quelconque sélectionnée parmi une solution aqueuse de sel de sodium, une solution aqueuse de sel de potassium, une solution aqueuse de sel de calcium, une solution aqueuse de sel de magnésium, de l'ammoniaque en solution aqueuse, une solution aqueuse de sel d'ammonium, une solution aqueuse d'acide inorganique, une solution aqueuse d'acide organique, de l'eau de mer, une eau de lac salé et une eau de source chaude pour induire l'élution d'un composant contenu dans l'échangeur d'ions naturel hors de l'échangeur d'ions naturel par échange d'ions et en séparant ensuite l'éluat de l'échangeur d'ions naturel.
PCT/JP2007/069002 2006-10-27 2007-09-28 Composition minérale pour la prévention ou le traitement d'une maladie diabétique WO2008050580A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6219066A (ja) * 1985-07-17 1987-01-27 Shigeo Kono 特殊塩の製造方法
JP2006083161A (ja) * 2004-08-17 2006-03-30 Shigeo Kono 骨形成促進剤

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03293002A (ja) * 1990-04-10 1991-12-24 Kaoru Kawada ミネラル液及びその抽出方法
JP2006035047A (ja) * 2004-07-23 2006-02-09 Shimizu Corp バナジウム含有水の製造方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6219066A (ja) * 1985-07-17 1987-01-27 Shigeo Kono 特殊塩の製造方法
JP2006083161A (ja) * 2004-08-17 2006-03-30 Shigeo Kono 骨形成促進剤

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