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WO2012140894A1 - Composition pharmaceutique - Google Patents

Composition pharmaceutique Download PDF

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Publication number
WO2012140894A1
WO2012140894A1 PCT/JP2012/002540 JP2012002540W WO2012140894A1 WO 2012140894 A1 WO2012140894 A1 WO 2012140894A1 JP 2012002540 W JP2012002540 W JP 2012002540W WO 2012140894 A1 WO2012140894 A1 WO 2012140894A1
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WIPO (PCT)
Prior art keywords
tea leaves
tea
pharmaceutical composition
weeks
fermentation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2012/002540
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English (en)
Japanese (ja)
Inventor
志郎 馬渡
軍喜 船津
武彦 藤野
義治 野田
達朗 植木
園元　謙二
善藤　威史
健太郎 猪熊
崇 有吉
千賀 折居
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FUKUOKA SOY SAUCE BREWING COOPERATION
ICHIBAN FOODS CO Ltd
Kyushu University NUC
Institute of Rheological Function of Food Co Ltd
Inst of Rheological Function of Food Co Ltd
Original Assignee
FUKUOKA SOY SAUCE BREWING COOPERATION
ICHIBAN FOODS CO Ltd
Kyushu University NUC
Institute of Rheological Function of Food Co Ltd
Inst of Rheological Function of Food Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by FUKUOKA SOY SAUCE BREWING COOPERATION, ICHIBAN FOODS CO Ltd, Kyushu University NUC, Institute of Rheological Function of Food Co Ltd, Inst of Rheological Function of Food Co Ltd filed Critical FUKUOKA SOY SAUCE BREWING COOPERATION
Publication of WO2012140894A1 publication Critical patent/WO2012140894A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/181—Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin

Definitions

  • the present invention relates to a pharmaceutical composition containing a compound having a specific structure produced by fermentation of tea leaves using a bacterium belonging to the genus Aspergillus, particularly black koji, and obtained by extraction and purification.
  • the present invention relates to a pharmaceutical composition that is effective in suppressing blood sugar level elevation, reducing triglycerides, suppressing blood pressure elevation, improving cholesterol metabolism, improving liver and kidney function, improving brain function, and preventing and treating Alzheimer's disease. Belongs to the pharmaceutical preparation technology.
  • the characteristic components of tea are caffeine and a tannin-based substance catechin, and caffeine has an excitatory effect on humans, has a bitter taste, and also has a diuretic effect.
  • This catechin is the most abundant tea ingredient and is a tea astringent ingredient.
  • amino acids typified by theanine
  • vitamins typified by vitamin C
  • chlorophylls inorganic components such as potassium and calcium
  • fragrance components such as dimethyl sulfide, green leaf alcohol, and terpene alcohol are widely known. .
  • kelp fried tea and roasted green tea contain a large amount of nitrogen-containing compounds such as pyrazine and pyrrole
  • fermented tea is known to contain a large amount of terpene alcohol with floral aroma (published by Heibonsha: World Encyclopedia). ).
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2002-370994
  • black blood sugar that is, blood sugar obtained by hot water extraction from black tea that has been aged for a long time by a post-fermentation method using black koji mold or the like. It has been reported that value-inhibiting substances have been obtained.
  • Patent Document 2 JP-A-2005-341876 (Patent Document 2) reports that a tea having a maltase inhibitory effect can be obtained by adding koji mold or koji to tea leaves and fermenting them.
  • Patent Document 3 Japanese Patent Application Laid-Open No. 2007-238584
  • JP 2002-370994 A Japanese Patent Laying-Open No. 2005-341876 (Claims) JP 2007-238584 A (Claims) JP 2010-220489 A (Claims)
  • the inventors have identified the X component that was found to be produced by fermentation of tea leaves using Aspergillus spp. In the previous study (although it was previously estimated to be a gallic acid-derived compound), With regard to its effectiveness, in particular, the pharmacological properties were pursued more deeply, and studies were conducted in order to further utilize tea leaves, in particular, to effectively utilize the found X component.
  • the inventors identified an X component produced in tea leaves fermented with black koji, and found that this X component also has pharmacological properties that could not be found in the previous stage. Completed the invention.
  • the invention according to claim 1 of the present invention is A pharmaceutical composition comprising a compound represented by the following formula 1.
  • the invention according to claim 2 of the present invention is The pharmaceutical composition according to claim 1, wherein the compound is It is produced by fermentation of tea leaves using Aspergillus spp.
  • the invention according to claim 3 of the present invention is The pharmaceutical composition according to claim 2, wherein The fermentation is Aerobic fermentation is characterized in that the fermentation period is 3 to 10 days.
  • the invention according to claim 4 of the present invention is The pharmaceutical composition according to claim 2, wherein The tea leaves are It is characterized by being Nibancha.
  • the invention according to claim 5 of the present invention is It contains a compound represented by the following formula 1, and suppresses blood sugar level increase, neutral fat reduction, liver function improvement, blood pressure increase suppression, cholesterol metabolism improvement or kidney function improvement, brain function improvement, prevention and treatment of Alzheimer's disease It is used for the pharmaceutical composition characterized by the above-mentioned.
  • the pharmaceutical composition according to the present invention contains a compound having a specific structure represented by formula 1, thereby suppressing an increase in blood glucose level, a reduction in neutral fat, an improvement in liver function, an increase in blood pressure, an improvement in cholesterol metabolism, or a kidney. It is effective for improvement of function, improvement of brain function, prevention and treatment of Alzheimer's disease, not only can further use of tea leaves, but also enables chemical synthesis of this compound by elucidating the structure, It enables a wide range of pharmaceutical preparations in the pharmaceutical industry.
  • the compound in this invention can be used in a powder state or as acetic acid or water or an ethanol solution, it is effective and effective when used as a pharmaceutical agent in order to exhibit the above effects. It can be used in the future and is applied to health foods and has excellent effects.
  • FIG. 2 is a fractionation diagram of 4.5% acetic acid extract of fermented tea using a Bio-Gel column. It is a fractional drawing by the Bio-Gel column of the ethyl acetate extract from fermented tea acetic acid extract. It is a HPLC chart of 3 fractions of FIG.
  • FIG. 4 is a diagram of adsorption chromatography using a Sepdex LH column (2 ⁇ 27 cm) of fraction 5 in FIG. 4. 4 is an HPLC chart of the fraction containing the X component of fraction 5.
  • the specific compound represented by Formula 1 (hereinafter referred to as a specific compound) used in the present invention is a fermented tea (hereinafter referred to as a fermentation) obtained by fermentation of tea leaves using a conventionally known Aspergillus spp. It is produced by extraction and separation from fermented black tea, but its structure has been elucidated so that it can also be prepared by chemical synthesis.
  • tea leaves used as raw materials for obtaining this specific compound from fermented black tea include Gyokuro, Ichibancha, Nibancha, Sanbancha, and Akiyubancha.
  • the fermentation conditions for these tea leaves are generally the conditions for preparing fermented tea using black koji, such as raw black koji, temperature during fermentation (usually 30-45 ° C), moisture during fermentation (usually 25-35%), etc.
  • the target compound having a specific structure can be obtained.
  • the extraction of a specific compound from fermented black tea is also performed by a normal extraction method using dilute acetic acid, water, or hot water as an extraction medium.
  • the fermentation condition for maintaining the state in which the fermented black tea contains the specific compound is the most important condition.
  • Producing fermented black tea is said to take months if it is long. Also in Patent Document 2, it is preferably about 3 weeks (paragraph 0030), but as a period for satisfying the above conditions, a preferable fermentation period for this invention is 3 to 10 days. Moreover, aerobic fermentation is employ
  • the specific compound thus obtained can be orally administered to a patient as a drug dissolved or suspended in a diluent mixed with a pharmaceutically acceptable carrier.
  • the pharmaceutical composition of this invention comprises suitable additives, For example, lactose, sucrose, mannitol, corn starch, synthetic or natural gum, excipients such as crystalline cellulose, starch, cellulose derivatives, binders such as gum arabic, gelatin, polyvinylpyrrolidone, carboxymethylcellulose cellulose, Disintegrants such as sodium carboxymethyl cellulose, starch, corn starch, sodium alginate, lubricants such as talc, magnesium stearate, sodium stearate, fillers or dilutions such as calcium carbonate, sodium carbonate, calcium phosphate, sodium phosphate
  • a tablet, powder (powder), pill, granule or the like can be prepared by appropriately mixing with an agent. Moreover, it can also be set as a capsule using a hard or soft gelatin capsule.
  • the pharmaceutical composition of the present invention is dissolved in a generally used inert diluent such as purified water, and if necessary, this solution is infiltrated, emulsifier, dispersion aid, surfactant, sweetener.
  • a generally used inert diluent such as purified water
  • emulsifier such as glycerol
  • dispersion aid such as sodium bicarbonate
  • surfactant such as sodium bicarbonate
  • sweetener e.g., sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium
  • the dosage is determined by the dosage of the specific compound as the active ingredient.
  • the dose depends on the dosage form, the age of the patient, etc., but is in the range of 1 mg to 1,000 mg per day, and preferably 10 mg to 500 mg per day for an adult with a body weight of 50 kg.
  • the prepared seed meal was added so as to be 10 7 / g of Aspergillus niger (23 kg as the seed meal amount), and fermented at a set temperature of 35 ° C. for 6 days.
  • the temperature rise during fermentation was suppressed using an air cooling fan, and efforts were made to maintain the set temperature.
  • the fermented tea leaves were sterilized by steaming at 100 ° C and dried at 55 ° C to obtain fermented black tea.
  • Extraction / purification of specific compounds was carried out by the following procedure. First, 200 g of fermented black tea was used, extracted with 4.5% acetic acid as the extraction medium, and 72.6 g of extract (yield: 36.3%: hereinafter, black tea extraction) by concentration under reduced pressure and lyophilization. I got a thing).
  • FIG. 1 shows the results of HPLC analysis of this black tea extract
  • FIG. 2 shows the ultraviolet absorption spectrum of each peak. Peaks a to c in FIG. 1 are EGC, Caffeine, and EC, respectively, from the elution position and absorption spectrum, and peak d is the X component.
  • the supernatant obtained by adding methanol to the lyophilized fraction 5 and stirring and centrifuging was added to the Sephadex previously equilibrated with methanol.
  • the sample was applied to an LH column (2 ⁇ 27 cm) and developed with methanol.
  • the elution pattern is shown in FIG. 6, and the HPLC pattern of the fraction having absorption at 300 nm is shown in FIG.
  • the evaluation results of the functions relating to the pharmacological properties of the obtained X component are as follows. ⁇ Evaluation of antitoxic effect (in vivo experiment using STZ-induced rats)> In order to evaluate the antitoxic effect of the X component in an in vivo experiment, 7-week-old Wistar rats were obtained from KBT Oriental Co., Ltd., and were grouped into 5 groups as shown in Table 2 below after 1 week of preliminary breeding. . After pre-breeding, streptozotocin (STZ) was intraperitoneally administered to groups 2-5 to produce STZ-induced type 1 diabetes model rats. Among these groups, solid feed MF (produced by Oriental yeast) containing X component (black tea extract) was freely fed for 3 weeks until slaughter (12 weeks of age).
  • STZ streptozotocin
  • mice 1 and 2 only the solid feed MF was fed freely.
  • the administration samples of each group and their intake amounts are as shown in Table 2 below.
  • the compounding quantity of X component in this feed it set so that it might become 1 time, 4 times, and 7 times the intake (66 mg / day) in a human clinical test.
  • the rats are housed in a conventional breeding room (lighting time from 7:00 to 19:00) at a room temperature of 24 ⁇ 3 ° C. and a relative humidity of 55 ⁇ 15% throughout the pre-breeding period and experimental period, and the food intake and body weight are measured every week.
  • the blood glucose level was measured before and after the sample administration, and at the first and second weeks after the sample administration. Blood was collected from the heart at 12 weeks of age after sample administration for 3 weeks, and erythrocyte deformability measurement and blood biochemical tests (35 items such as cholesterol and blood glucose) were performed.
  • the blood glucose level of the diabetic control group increases significantly as the age of the week increases as compared to the normal group (group 1).
  • groups 3 and 5 to which the X component was administered showed significantly lower values than group 2 at the first week of STZ administration.
  • the increase in blood glucose level almost reached its peak at the second week of sample administration, and was significantly lower than that in Group 2. This suggests that the X component suppresses an increase in blood glucose level, although the time of suppression differs depending on the sample concentration.
  • alkaline phosphatase which is an index of liver function
  • group 1 the function of liver function is reduced by STZ administration.
  • the 4 groups administered with the X component showed a tendency to be lower than the 2 groups.
  • no significant difference / trend was observed in the other 3 and 5 groups, both showed lower values than the 2 groups. This suggested that the X component tends to suppress or improve the decrease in liver function.
  • groups 4 and 5 showed significantly lower values than group 2.
  • the X component suppresses the increase in neutral fat caused by STZ administration.
  • urea nitrogen which is an index of renal function
  • the group 3 showed a tendency toward a lower value compared to the group 2.
  • the urea nitrogen value became low as the sample concentration became high.
  • the X component may improve renal function in a concentration-dependent manner.
  • potassium and chlor which are indicators of renal function other than urea nitrogen, improve or tend to improve renal function in a concentration-dependent manner. Concentration-dependent results were seen for all three indicators of renal function.
  • mice are bred in a conventional room (lighting time from 7:00 to 19:00) with a room temperature of 24 ⁇ 3 ° C and a relative humidity of 55 ⁇ 15% throughout the pre-breeding period and experimental period, and food intake and body weight are measured every week. did.
  • the blood glucose level at the time of sacrifice was measured at 4 weeks, 5 weeks and 7 weeks after sample administration. After sample administration for 7 weeks (at 12 weeks of age), blood was collected from the heart and subjected to blood biochemical tests (34 items such as cholesterol and blood glucose).
  • KK-Ay mice develop hyperglycemia from 7 to 8 weeks of age. There is no significant difference between groups 1 and 2 after 4 weeks of sample administration (at 9 weeks of age), but 2 groups are significantly lower after 5 weeks of sample administration (at 10 weeks of age). It was. Thus, it was suggested that the X component significantly suppresses the increase in blood glucose level in the diabetes model mouse. In addition, since the effect in a model that genetically develops type 2 diabetes has been proved this time, prevention of diabetes in humans (blue boys) who have a predisposition to type 2 diabetes due to the X component is expected.
  • the compounding quantity of X component (black tea extract) in this feed it set so that it might become seven times the intake (66 mg / day) in a human clinical trial based on the result of a prior clinical trial.
  • the rats are housed in a conventional breeding room (lighting time from 7:00 to 19:00) at a room temperature of 24 ⁇ 3 ° C. and a relative humidity of 55 ⁇ 15% throughout the preliminary breeding period and the experimental period. It was measured.
  • the blood pressure was measured before the sample administration and at 1 week, 2 weeks, 3 weeks and 4 weeks (before sacrifice) after sample administration. Blood was collected from the abdominal aorta at the age of 13 weeks after sample administration for 4 weeks, and blood biochemical tests (34 items such as cholesterol and blood glucose) were performed.
  • the blood pressure was measured for a total of 5 systolic blood pressures (SBP) before the sample administration, 1 week, 2 weeks, 3 weeks and 4 weeks (before sacrifice) after sample administration.
  • SBP systolic blood pressures
  • the measurement was performed using a non-invasive blood pressure measuring device (Softlon Co., Ltd.).
  • the measurement was performed at least three times, and the average value of the three times was taken as the blood pressure of the individual, and the results are shown in FIG. Marks in the figure indicate that there is a significant difference / trend (#; p ⁇ 0.08, *; p ⁇ 0.05, **; p ⁇ 0.01).
  • FIGS. 19 to 21 show the results of CBC measurement (Sysmex) on the collected blood and the biochemical test performed on the obtained plasma (2000 rpm, 10 minutes, 25 ° C.). Marks in the figure indicate that there is a significant difference / trend (#; p ⁇ 0.08, *; p ⁇ 0.05, **; p ⁇ 0.01).
  • ALT which is an index of liver function
  • X component black tea extract
  • HDL-cho / T-cho 2 groups showed significantly higher values than 1 group. Therefore, it was suggested that black tea extract suppresses or improves the decrease in cholesterol metabolism.
  • the average body weight after 12 weeks of breeding is shown in FIG. 22, and the rate of weight change relative to the total intake is shown in FIG.
  • the sample containing the X component black tea extract
  • the X component black tea extract
  • the X component suppresses the weight gain of rats and is effective in preventing metabolic syndrome.
  • ⁇ Acute oral toxicity test ( Animal safety test)>
  • Animal safety test For the X component, an acute oral toxicity test using rats was requested from the Japan Food Analysis Center. The test group was administered with a sample at a dose of 150 mg / kg, and the control group was orally administered with water for injection as a solvent control to male and female rats once and observed for 14 days. As a result, no abnormalities or deaths were observed during the observation period. From this, it was considered that the LD50 value by single oral administration in the rat of the sample was 150 mg / kg or more in both sexes.
  • ⁇ Reversion mutation test> For the black tea extract containing the X component, a reverse mutation test was requested from the Japan Food Analysis Center.
  • the test method is Escherichia according to the attached “Genotoxicity Test Guidelines” in “Guidelines on Genotoxicity Tests of Drugs” (November 1, 1999, Pharmaceutical Examination No. 1604).
  • E. coli WP2uvrA and Salmonella typhimurium TA strain 4 were used.
  • the sample dose was 313-5000 ⁇ g / plate. As a result, an increase in the number of revertant colonies was not observed. From the above, it was concluded that the reverse mutagenicity of the specimen under the test conditions was negative.
  • the compound of the present invention specified by the above formula 1 suppresses an increase in blood glucose level, reduces neutral fat, improves liver function, suppresses an increase in blood pressure, improves cholesterol metabolism or kidney function, improves brain function, prevents Alzheimer's disease It is effective for treatment and not only enables further utilization of tea leaves, but also enables chemical synthesis of this compound by elucidating the structure.
  • the pharmaceutical composition containing the specific compound according to the present invention has excellent pharmacological properties
  • the specific compound can be supplied as a non-toxic solvent solution of powder or water, acetic acid or ethanol. It is highly likely to be widely used in the tea manufacturing industry and the pharmaceutical manufacturing industry where this specific compound can be supplied.

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Abstract

La présente invention concerne un composé produit dans des feuilles de thé par fermentation et non présent dans des feuilles de thé de matière première qui est obtenu par fermentation pendant 3 à 10 jours en utilisant du malt de riz noir et en utilisant en particulier un thé de deuxième récolte en tant que feuilles de thé, et utilisé en tant que substance active dans des médicaments pour supprimer l'élévation du taux de glycémie, abaisser les triglycérides, améliorer la fonction hépatique, supprimer l'élévation de la pression artérielle, améliorer le métabolisme du cholestérol, améliorer la fonction rénale, et similaire. En plus de pouvoir être obtenu à partir de feuilles de thé fermentées, le composé peut également être préparé par synthèse chimique, biosynthèse, et similaire, une fois que sa structure a été identifiée.
PCT/JP2012/002540 2011-04-12 2012-04-12 Composition pharmaceutique Ceased WO2012140894A1 (fr)

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JP2011088448A JP5794414B2 (ja) 2011-04-12 2011-04-12 医薬用組成物
JP2011-088448 2011-04-12

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108117559A (zh) * 2016-11-28 2018-06-05 勐海茶业有限责任公司 从发酵茶中分离泰德诺a和泰德诺b的混合物的方法
CN108117558A (zh) * 2016-11-28 2018-06-05 勐海茶业有限责任公司 从发酵茶中拆分泰德诺a和泰德诺b的方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015097511A (ja) * 2013-11-20 2015-05-28 株式会社 レオロジー機能食品研究所 ポリフェノール誘導体の製造方法、ポリフェノール誘導体を含有する飲食品および医薬品組成物
JP6727139B2 (ja) 2015-02-02 2020-07-22 マルコメ株式会社 ＰＰＡＲα活性化剤、医薬組成物、飲食品、食品添加物、サプリメント及びこれらの製造方法

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JP2008266311A (ja) * 2007-03-23 2008-11-06 Nagase Chemtex Corp アディポネクチン上昇剤
JP2010220489A (ja) * 2009-03-19 2010-10-07 Rheology Kino Shokuhin Kenkyusho:Kk 発酵茶および薬効性組成物
WO2011034218A1 (fr) * 2009-09-18 2011-03-24 株式会社Ｒｉｖｅｒｓｏｎ Extrait de thé fonctionnel ayant subi une fermentation microbienne et contenant un dérivé de polyphénol, et son procédé de production
WO2011034217A1 (fr) * 2009-09-18 2011-03-24 株式会社Ｒｉｖｅｒｓｏｎ Dérivé de polyphénol et son procédé de production

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