WO2012050162A1 - Agent prolongateur de la durée de vie cellulaire, et activateur de la télomérase - Google Patents

Agent prolongateur de la durée de vie cellulaire, et activateur de la télomérase Download PDF

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Publication number
WO2012050162A1
WO2012050162A1 PCT/JP2011/073548 JP2011073548W WO2012050162A1 WO 2012050162 A1 WO2012050162 A1 WO 2012050162A1 JP 2011073548 W JP2011073548 W JP 2011073548W WO 2012050162 A1 WO2012050162 A1 WO 2012050162A1
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extract
cell
telomerase
aging
life extension
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PCT/JP2011/073548
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English (en)
Japanese (ja)
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健太朗 加治屋
伸幸 高倉
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株式会社資生堂
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • 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)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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

Definitions

  • the present invention provides a cell life extending agent, particularly a vascular endothelial cell life extending agent, and a telomerase activator comprising an extract derived from a plant belonging to the genus Cinnamomum, in particular, Cinnamomum cassia® Blume.
  • ⁇ Arterial blood ejected from the left ventricle passes through the aorta and is carried to the capillaries via the muscular arteries and arterioles.
  • the venous blood collected in the venule returns to the right atrium via the vena cava.
  • the blood that flows from the right atrium to the right ventricle is ejected to the lungs, and oxygen-containing blood is returned from the lungs to the left atrium and to the left ventricle.
  • the aorta and vena cava are exclusively functions as blood conduits, but the vena cava is thicker than the aorta and pools blood in preparation for anemia due to blood loss when arterial bleeding occurs. It has a function.
  • Non-patent Documents 1 and 2 tissue-specific self-replication of stem cells in organs / organs is performed in the vascular region (Non-patent Documents 1 and 2), that is, tissue maintenance is performed mainly in blood vessels. It shows that.
  • a blood vessel is covered with a single layer of endothelial cells, and vascular smooth muscle cells and pericytes collectively called wall cells mobilized on the outer side (basement membrane side) form a stable structure.
  • blood vessels carry oxygen, nutrients, and inflammatory cells as basic functions for life support, and are also involved in tissue formation itself. For this reason, when vascular endothelial cells reach the end of their lives, blood vessels degenerate and oxygen and nutrients do not reach the local area, but the vascular structure becomes brittle and causes an inflammatory reaction. The same applies to the skin, and not only does the supply of oxygen and nutrients spread throughout, but also causes an inflammatory skin reaction.
  • Non-patent Document 3 when oxygen and nutrients are deficient due to a decrease in blood flow resulting from degeneration of blood vessels, aging phenomena such as wrinkles due to a decrease in fibroblasts have been reported (Non-patent Document 3), and the blood vessel structure is brittle. It has been found that in mice, the inflammatory response is enhanced and the formation of wrinkles is promoted (Non-Patent Document 4). Furthermore, it is known that the number of capillaries decreases in photo-aged skin sites (Non-patent Document 5), and extending the life of vascular endothelial cells normalizes the skin condition, aging, and consequently It is thought that wrinkle formation can be prevented.
  • blood vessels have a function of maintaining tissue formation in relation to tissue stem cells, their failure, loss, and hyperproliferation cause various diseases.
  • so-called three major diseases such as cancer, myocardial infarction, and cerebral infarction increase with the aging and development of lifestyle-related diseases. Is observed. It has been elucidated that changes in environmental factors inside and outside blood vessels due to aging and lifestyle-related diseases cause stress on blood vessels and induce cellular senescence in vascular endothelial cells. It has been found to be deeply involved in the progress.
  • Non-patent Document 6 it is known that blood vessel rupture due to vascular aging results in functional deterioration of various organs such as renal disorder, osteoporosis, Alzheimer's disease, retinopathy, erectile dysfunction, and pulmonary dysfunction.
  • Non-patent Document 7 A telomere is present at the end of a chromosome that plays a central role in the genetic information of a cell, and is composed of a structure consisting of DNA having a characteristic repetitive sequence and various proteins. As the cell divides, this telomere becomes shorter, and when the telomere is shorter than a certain length, it is recognized as DNA damage and the activation of the DNA damage response pathway is the cause of loss of proliferative capacity due to cell aging (Non-Patent Document 8). In vascular endothelial cells, cell aging can be suppressed by overexpressing telomerase having a telomere prolonging effect (Non-patent Document 9), and it is understood that telomeres play an important role in cell aging.
  • telomere length induces cellular senescence, but various stresses have been found to induce cellular senescence of vascular endothelial cells.
  • the following pathological conditions and molecules are known as such cellular senescence factors.
  • Non-patent document 10 Angiotensin II related to hypertension
  • Non-patent document 11 Hyperglycemia
  • non-patent document 12 glycosylated protein
  • Smoking is thought to induce cellular aging through formation of oxidized LDL and DNA damage .
  • the above-mentioned pathological conditions and lifestyles described in 1) to 4) can all be arteriosclerosis risk factors, but such risk factors commonly increase oxidative stress and not only damage DNA.
  • Non-patent Document 14 It has also been reported to promote shortening of telomeres. Furthermore, it has been reported that when inflammatory cytokines such as interferon ⁇ and TNF ⁇ increase due to inflammation caused by vascular failure, aging of endothelial cells is promoted (Non-patent Document 15).
  • the causes of aging of vascular endothelial cells are not limited to the above, but generally, stress in the bloodstream caused by aging or lifestyle / lifestyle-related diseases and from outside the blood vessels is caused by vascular endothelial cells. Induces vascular abnormalities that underlie various diseases.
  • telomere activity in vascular endothelial cells in order to suppress vascular abnormalities due to aging of vascular endothelial cells related to the roots such as aging and lifestyle / lifestyle diseases .
  • Persistent telomere activity in vascular endothelial cells resists various stresses caused by aging and lifestyle / lifestyle-related diseases, suppresses vascular endothelial cell aging, and transports oxygen and nutrients to various organs
  • the anti-inflammatory action by infiltration of ordered inflammatory cells is promptly performed, and the tissue-specific stem cells that form the basis of tissue maintenance are maintained, thereby maintaining the organ.
  • a substance capable of maintaining telomere activity in vascular endothelial cells becomes possible by internal use, injection, and application, it can be an anti-aging agent that suppresses aging of an individual.
  • An object of the present invention is to provide a novel cell life extension agent, particularly a vascular endothelial cell life extension agent, and a telomerase activator.
  • the present inventor has found that an extract derived from a plant belonging to the genus Cinnamomum has an effect of activating telomerase based on experiments examined by using various herbal extracts, and has completed the present invention. .
  • this application includes the following inventions: (1) A cell life extension agent comprising an extract derived from a genus Nikkei. (2) The cell life extension agent according to (1), wherein the extract is derived from a siliceous plant. (3) The cell life extension agent according to (2), wherein the extract is derived from Keishi or Keihi. (4) The cell life extension agent according to any one of (1) to (3), wherein the extract is a water extract. (5) The cell life extension agent according to any one of (1) to (4), wherein the cell is a vascular endothelial cell. (6) Use of the cell life extension agent according to any one of (1) to (5) for delaying or stopping the progress of cell senescence or improving the cell aging state to prolong cell life.
  • a telomerase activator comprising an extract derived from a genus Nikkei.
  • FIG. 1 shows a comparison of telomerase activity in HUVEC with and without the addition of cinnamon extract.
  • Nikkei is a plant of the order Lauraceae and Lauraceae, and there are over 300 species, such as Cinnamomumnamcassia Blume, C. camphora, C. daphnoides (C. doederleinii), C. japonicum, Ogasawara jay (C. pseudo-pedunculatum), Nikkei (C. sieboldii), Shibaya bunkei kei Ceylon nicki (C. verum), Cinnamon (C. zeylanicum).
  • Cinnamomumnamcassia Blume C. camphora, C. daphnoides (C. doederleinii), C. japonicum, Ogasawara jay (C. pseudo-pedunculatum), Nikkei (C. sieboldii), Shibaya bunkei kei Ceylon nicki (C. verum), Cinnamon (C. zeylanicum).
  • Kei (Cinnamomum cassia Blume), in particular, a young branch of kei, Keishi or Keihi (cinnamon), as a cell life extension agent in the present invention, particularly a vascular endothelial cell life extension agent, and a telomerase activator Things are used.
  • An extract derived from keihi which is a bark of kei, is useful as an active ingredient of, for example, a hair restorer (Japanese Patent Laid-Open No. 10-265350), Tie2 (tyrosine kinase with Ig and EGF homology domain-2) phosphorylation activity
  • a hair restorer Japanese Patent Laid-Open No. 10-265350
  • Tie2 tyrosine kinase with Ig and EGF homology domain-2
  • phosphorylation activity Although it is known (Japanese Patent Laid-Open No. 2009-263358), it is not known at all that it has cell life
  • the said extract can be obtained by a conventional method, for example, after the plant used as the origin is immersed or heated and refluxed with normal temperature or a heating with an extraction solvent, it can filter and concentrate.
  • the extraction solvent can be arbitrarily used as long as it is a solvent that is usually used for extraction.
  • an aqueous solvent such as water, physiological saline, phosphate buffer, borate buffer, or an organic solvent such as ethanol, Alcohols such as propylene glycol, 1,3-butylene glycol and glycerin, hydrous alcohols, chloroform, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane and the like can be used alone or in combination.
  • water is used as the solvent.
  • the extract obtained by extraction with the above solvent can be used as it is or, for example, an extract concentrated by lyophilization or the like, and if necessary, an adsorbent method, for example, an ion exchange resin removed impurities, A polymer (eg, Amberlite XAD-2) adsorbed on a column, eluted with a desired solvent, and further concentrated can be used.
  • an adsorbent method for example, an ion exchange resin removed impurities, A polymer (eg, Amberlite XAD-2) adsorbed on a column, eluted with a desired solvent, and further concentrated can be used.
  • cell life extension is not particularly limited, but is caused by stress in the bloodstream and extravascular blood vessels caused by aging and lifestyle / lifestyle diseases. It refers to delaying or stopping the progression of cell senescence, or improving cell aging status and extending cell life.
  • the cell is not particularly limited, but is preferably a vascular epithelial cell.
  • telomerase activation refers to improving or promoting the activity of telomerase, and the activity can be examined by a known method (for example, Quantitative Telomerase Detection Kit; Allied Biotech). , Inc).
  • the cell life extension agent of the present invention in particular, the vascular endothelial cell life extension agent, and the telomerase activator can be used as various pharmaceuticals or cosmetics effective for prevention and improvement of various diseases caused by cell aging and aging.
  • various diseases and aging caused by cell aging include various inflammatory diseases, immune diseases, adult diseases, etc., such as various infectious diseases, rheumatoid arthritis, gout, hypertension, diabetes, arteriosclerosis, and high fat. Blood pressure, obesity, organ dysfunction and the like.
  • the cell life extension agent of the present invention in particular, the vascular endothelial cell life extension agent, and the telomerase activator can be used as a pharmaceutical or cosmetic effective for preventing or improving skin diseases and aging caused by cell aging.
  • skin diseases and aging caused by cell aging include rough skin, formation of wrinkles, coloring of spots, coloration of soil, formation of sagging, easy damage, and atrophy.
  • the present invention also provides a therapeutic or cosmetic method in which the cell life extension agent is applied to a site containing cells in need of the prevention or improvement in order to prevent or improve the disease or aging.
  • the cell life extension agent of the present invention in particular, the vascular endothelial cell life extension agent and the telomerase activator, can be appropriately determined in dosage, usage and dosage form according to the purpose of use.
  • the dosage form of the cell life extension agent of the present invention particularly the vascular endothelial cell life extension agent, and the telomerase activator may be oral, parenteral, external use and the like.
  • the dosage form include oral preparations such as tablets, powders, capsules, granules, extracts, and syrups, or parenteral preparations such as injections, drops, and suppositories, ointments, creams, emulsions, and lotions. And external preparations such as packs and bath preparations.
  • the compounding amount of the extract derived from the Nikkei plant that activates the telomerase in the cell life prolonging agent of the present invention in particular, the vascular endothelial cell life prolonging agent and the telomerase activator can be appropriately determined according to the use, but is generally inhibited.
  • the total amount of the agent it is 0.0001 to 20.0 mass%, preferably 0.0001 to 10.0 mass% as a dry product.
  • the vascular endothelial cell life extension agent and the telomerase activator in addition to the above-mentioned Nikkei plant-derived extract, for example, excipients used in normal foods and pharmaceuticals , Moisturizers, antiseptics, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, sour agents, seasonings, colorants, fragrances, etc., whitening agents, humectants, oily ingredients that are commonly used in cosmetics, etc. Ultraviolet absorbers, surfactants, thickeners, alcohols, powder components, colorants, aqueous components, water, various skin nutrients, and the like can be appropriately blended as necessary.
  • the cell life extension agent of the present invention particularly the vascular endothelial cell life extension agent, and the telomerase activator are used as a skin external preparation
  • auxiliary agents commonly used for the skin external preparation such as disodium edetate, trisodium edetate, etc.
  • Metal sequestering agents such as sodium, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extract, grabrizine, hot water extract of karin fruit,
  • Various crude drugs, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts, whitening agents such as vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid, glucose, fructose, mannose, sucrose, trehalose Sugars such as retinoin , Retinol, retinol acetate, may be appropriately blended well as vitamin A such as retinol palmitate.
  • a compounding quantity is the mass%.
  • Example 1 Preparation of Preparation Keishi Hot Water Extraction and Drying Residue 2 L of water was added to 400.7 g of Cinnamomum cassia Blume , followed by heat extraction for 3 hours and filtration. 2 L of water was added to the obtained residue, the same operation was repeated, and the heat extraction was further performed twice. The obtained filtrate was freeze-dried to obtain 39.7 g of a hot water extraction dry residue.
  • Keishi Extract HP-20 Column Treatment Charge 10 g of the hot water extract obtained above to a Diaion HP-20 (Mitsubishi Chemical) column and elute it with a water-containing ethanol system, and use the 50% ethanol elution fraction as the target elution fraction. Obtained.
  • Example 2 Evaluation of telomerase activity 1) Cultivation of vascular endothelial cells (HUVEC) EUV (registered trademark) -2 (Lonza) supplemented with 2% FBS using P10 cells after culturing HUVEC (Promocell) in a normal medium. ) And cultivated for 10 days in a 6-well plate with two types of medium: cinnamon extract V (lot number: 080919CE, Nippon Powdered Chemical Co., Ltd.) added at a final concentration of 0.01% and cinnamon free control. .
  • HUVEC vascular endothelial cells
  • EUV registered trademark
  • FBS fetal bovine serum
  • telomere activity In the test, Quantitative Telomerase Detection Kit (Allied Biotech, Inc) was used. The inside of the 6-well plate was washed twice with PBS, and 200 ⁇ l of 1 ⁇ Lysis Buffer was added. After standing on ice for 30 minutes, the cells were collected using a cell scraper. Centrifugation was performed at 12,000 g (MX-305, TOMY) for 5 minutes at 4 ° C. to obtain 160 ⁇ l of supernatant. They were stored at -80 ° C and used as samples.
  • Quantitative Telomerase Detection Kit Allied Biotech, Inc
  • telomerase activity In quantifying telomerase activity, Control Template TSR diluted with 1 ⁇ Lysis Buffer to 0.1 amol / ⁇ l, 0.02 amol / ⁇ l, 0.004 amol / ⁇ l, 0.0008 amol / ⁇ l was used. A telomerase reaction was carried out for 20 minutes in an incubator at 25 ° C., and Real-time PCR for detecting telomerase activity was performed according to the protocol (Roche Applied Science LightCycler 480 Instrument, Roche).

Abstract

La présente invention concerne : un nouvel agent prolongateur de la durée de vie cellulaire, en particulier un agent destiné à prolonger de la durée de vie d'une cellule endothéliale, qui comprend un extrait issu d'une plante appartenant au genre Cinnamonum ; et un activateur de la télomérase.
PCT/JP2011/073548 2010-10-15 2011-10-13 Agent prolongateur de la durée de vie cellulaire, et activateur de la télomérase WO2012050162A1 (fr)

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JP2010232664A JP2012087068A (ja) 2010-10-15 2010-10-15 細胞寿命延長剤及びテロメアーゼ活性剤
JP2010-232664 2010-10-15

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104758451A (zh) * 2015-04-28 2015-07-08 童长虹 一种治疗痛风的中药组合物

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Publication number Priority date Publication date Assignee Title
WO2002047699A1 (fr) * 2000-12-12 2002-06-20 Kaneka Corporation Compositions de prévention ou d'amélioration de syndromes multifactoriels
JP2005075812A (ja) * 2003-09-03 2005-03-24 Shiseido Co Ltd プラスミン特異的活性阻害剤
JP2006225297A (ja) * 2005-02-16 2006-08-31 Fancl Corp 肥満、高脂血症および動脈硬化性疾患の治療・予防剤
JP2007261996A (ja) * 2006-03-28 2007-10-11 Naris Cosmetics Co Ltd アクロレイン付加体形成阻害剤、及びそれを含有する皮膚外用剤及び飲食品
JP2009510053A (ja) * 2005-10-26 2009-03-12 コリア インスティチュート オブ オリエンタル メディシン 桂皮抽出物を有効成分として含む腸内菌叢改善及び免疫機能増進用組成物
JP2009263358A (ja) * 2008-03-31 2009-11-12 Shiseido Co Ltd 血管の成熟化、正常化又は安定化剤及びしわ防止・改善剤
JP2010083787A (ja) * 2008-09-30 2010-04-15 Kirin Holdings Co Ltd Ｃｂ１受容体アンタゴニストとしての桂皮アルデヒドおよび桂皮抽出物
JP2010518117A (ja) * 2007-02-09 2010-05-27 エフエイチジー・コーポレイション・ディ・ビー・エイ・インテグリティ・ニュートラスーティカルズ シンドロームｘ関連の危険因子を低減または除去する方法および材料

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002047699A1 (fr) * 2000-12-12 2002-06-20 Kaneka Corporation Compositions de prévention ou d'amélioration de syndromes multifactoriels
JP2005075812A (ja) * 2003-09-03 2005-03-24 Shiseido Co Ltd プラスミン特異的活性阻害剤
JP2006225297A (ja) * 2005-02-16 2006-08-31 Fancl Corp 肥満、高脂血症および動脈硬化性疾患の治療・予防剤
JP2009510053A (ja) * 2005-10-26 2009-03-12 コリア インスティチュート オブ オリエンタル メディシン 桂皮抽出物を有効成分として含む腸内菌叢改善及び免疫機能増進用組成物
JP2007261996A (ja) * 2006-03-28 2007-10-11 Naris Cosmetics Co Ltd アクロレイン付加体形成阻害剤、及びそれを含有する皮膚外用剤及び飲食品
JP2010518117A (ja) * 2007-02-09 2010-05-27 エフエイチジー・コーポレイション・ディ・ビー・エイ・インテグリティ・ニュートラスーティカルズ シンドロームｘ関連の危険因子を低減または除去する方法および材料
JP2009263358A (ja) * 2008-03-31 2009-11-12 Shiseido Co Ltd 血管の成熟化、正常化又は安定化剤及びしわ防止・改善剤
JP2010083787A (ja) * 2008-09-30 2010-04-15 Kirin Holdings Co Ltd Ｃｂ１受容体アンタゴニストとしての桂皮アルデヒドおよび桂皮抽出物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104758451A (zh) * 2015-04-28 2015-07-08 童长虹 一种治疗痛风的中药组合物

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