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WO2008140178A1 - Composition comprenant un extrait de ginseng traité pour prévenir et traiter l'obésité et utilisation de celle-ci - Google Patents

Composition comprenant un extrait de ginseng traité pour prévenir et traiter l'obésité et utilisation de celle-ci Download PDF

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Publication number
WO2008140178A1
WO2008140178A1 PCT/KR2008/001076 KR2008001076W WO2008140178A1 WO 2008140178 A1 WO2008140178 A1 WO 2008140178A1 KR 2008001076 W KR2008001076 W KR 2008001076W WO 2008140178 A1 WO2008140178 A1 WO 2008140178A1
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Prior art keywords
panax
extract
obesity
processed
ginseng
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English (en)
Inventor
Gwi Seo Hwang
Sung Jae Jung
Han Shin Lee
Hyun Young Kim
Bok Deuk Kim
Jeong Hill Park
Hyang Jin Lee
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Ginseng Science Inc
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Ginseng Science Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • the present invention relates to a pharmaceutical composition and functional health food comprising an extract of processed Panax genus plant as an active ingredient for preventing and treating obesity and the use thereof.
  • adipocyte cell is thought to be correlated with the occurrence of insulin resistance, in other words, the factors secreting from adipocyte cell or metabolic messenger are considered to inhibit the action of insulin within the liver and muscle.
  • TNF- ⁇ and leptin secreted from adipocyte cell are suggested as a factors of insulin resistance in obesity recently (Hotamisligil GS. et al., Tumor necrosis factor- ⁇ , a key component of the obesity-diabetes link, Diabetes, 43, pp.1271-1278, 1994; Cohen B., Novick D., Rubinstein M., Modulation of insulin activities by leptin, Science, 274. pp.1185-1188, 1996).
  • lipid is the major consumed component in the process of energy metabolism and both lipid synthesis and lipid degradation were increased.
  • the increase of lipid degradation and utilization of free fatty acid thereby are characteristic phenomena of obesity, in particular, abdominal obesity and showed close correlation between lipid volune and lipid oxidation, which are regarded as the main cause of increased free fatty acid and lipid oxidation in the serum.
  • the increase of lipid oxidation is observed in the early stage of obesity, even after fasting or glucose tolerance.
  • the deficiency of estrogen caused by decreased function of ovary has been primary factor of the obesity of menopausal women and estrogen inhibits the activity of lipoprotein lipase (LPL) in the adipocyte cell and inhibits the lipid accumulation (Hamosh M. et al., J. Clin. Invest.,55., pp.1132- 1135, 1975).
  • LPL lipoprotein lipase
  • the deficiency of estrogen increases the activity of lipoprotein lipase enzyme, which causes to accumulate the lipid in the adipocyte cell resulting in increased body weight.
  • lipid accumulation can be inhibited by administration of estradiol (E2) (Geary, N. et al. , J. Physiol. Regul. Intergr. Comp.
  • E2 induces the release of a hormone sensitive lipase (Palin S. L. et al, Metabolism, 52, pp.383-388, 2003) or increases the action of fatty acid ⁇ -oxidation of epinephrine, resulting in inhibiting lipid accumulation (Ackerman G.E. et al., Endocrinology.109. pp.2084-2088, 1981), to inhibit the adipocyte cell production from bone stromal cell (Heim M. et al., Endocrinology, 145, pp.848-859, 2004; Okazaki, R.
  • Araliaceae for example, Panax ginseng distributed or cultivated in far-eastern Asia region, Panax quinquefolia in America and Canada, Panax Notoginseng in China, Panax trifolia in eastern region of north America, Panax vietnamensis in Vietnam, Panax elegatior, Panax wangianus, Panax bipinratifidus and etc.
  • the most important ingredient in the plant belonged to Panax genus is dammarane saponin having 1-4 numbers of saccharides, particularly Korean ginseng comprises high amount of ginsenosides, such as ginsenoside RbI, Rb2, Rc, Rd, RgI, Re and etc. These saponins show various potency and pharmacological activities according to their structure.
  • ginsenosides are formed by the process that a part of sugar moiety in dammarane glycoside, i.e., ginsenosides RbI, Rb2, Rc and Rd, was cleaved and continuously subjected to dehydration reaction at the position of C- 20.
  • these new metabolites can be produced in the root, stem or leaf of any Panax genus plants such as Panax ginseng, Panax quinquefolia, Panax no- to ginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus and Panax bipinratifidus which contains dammarane glycoside through the processing method of Park et al. (Korean Patent Registration No. 192678 and US Patent No. 5776460).
  • Panax genus plants such as Panax ginseng, Panax quinquefolia, Panax no- to ginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus and Panax bipinratifidus which contains dammarane glycoside through the processing method
  • the inventors of the present invention have investigated an inhibiting effect of an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) over 1.0 against obesity through already well-known screening tests, i.e., the determination test on the change of body weight, the level of total cholesterol, LDL and triglyceride in blood using estrogen- deficient obesity rat model caused by ovariectomy and etc., and finally completed the present invention by confirming that the inventive extract reduces body weight, the level of total cholesterol, LDL and triglyceride within blood, increases the level of blood HDL as well as inhibits the lipid accunulation of Caenorhabditis elegans (C. elegans).
  • C. elegans Caenorhabditis elegans
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, as an active ingredient in an effective amount to treat and prevent obesity.
  • the present invention also provides a use of an extract of processed ginseng so as to make a ratio of gnsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, for the manufacture of pharmaceutical composition to treat and prevent obesity.
  • the present invention also provides a health functional food comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, for the prevention or alleviation of obesity.
  • a pharmaceutical composition comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, as an active ingredient in an effective amount to treat and prevent obesity.
  • the present invention to provide a pharmaceutical composition
  • a pharmaceutical composition comprising an extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O 0 C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, Ci-C 4 lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredient and pharmaceutically acceptable carrier, diluents or adjuvants to treat and prevent obesity.
  • the present invention provides a use of extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0 as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.
  • the present invention provides a use of extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O 0 C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C 1-C 4 lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.
  • It is an object of the present invention to provide a method of treating or preventing obesity in a mammal comprising administering an effective amount of an extractof processed ginseng so as to make a ratio of gmsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, together with a pharmaceutically acceptable carrier thereof to said mammal in need thereof.
  • It is an object of the present invention to provide a method of treating or preventing obesity in a mammal comprising administering an effective amount of an extractof processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O 0 C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C 1 -C 4 lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, together with a pharmaceutically acceptable carrier thereof to said mammal in need thereof.
  • extract of processed ginseng means "an extract of Panax genus plant", which specifically comprises the extract prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O 0 C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C r C 4 lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract of the present invention.
  • Panax genus disclosed herein comprises the root, stem, leaf of Panax ginseng, Panax quinquefolia, Panax notoginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus or Panax bipinratifidus.
  • the present invention for example, dried plant material of Panax genus was cut into small pieces and the piece was autoclaved at the temperature ranging from 70 to 15O 0 C, preferably 100 to 13O 0 C, for the period ranging from 2 to 6 hours, preferably 3 to 5 hours; and was mixed with 1 to 20-fold, preferably, 3 to 10-fold weight (kg) of water, C 1 -C 4 lower alcohol, such as methanol, ethanol, butanol or the mixtures thereof, preferably ethanol; was heated for the period ranging from 3 to 10 hours, preferably 3 to 6 hours, by reflux extraction with water, cold water extraction, ultra-sonication or conventional extraction, preferably by reflux extraction with water; the residue was filtered and then the filtrate was dried at the temperature ranging from 40 to 8O 0 C, preferably from 50 to 7O 0 C, to obtain inventive extract of processed ginseng.
  • C 1 -C 4 lower alcohol such as methanol, ethanol, butanol or the mixtures thereof, preferably
  • composition of the present invention has no toxicity and adverse effect therefore can be used with safe.
  • the present invention provides a pharmaceutical composition comprising the processed ginseng extract prepared by the above-described method as an active ingredient to prevent and treat obesity.
  • the inventive composition for treating and preventing obesity may comprise the above extract as from 0.01 to 50% by weight based on the total weight of the composition.
  • the inventive composition may additionally comprise conventional carrier, adjuvants or diluents in accordance with a using method well known in the art. It is preferable that said carrier is used as appropriate substance according to the usage and application method, but not limited. Appropriate diluents are listed in the written text of Remington's Pharmaceutical Science (Mack Publishing co, Easton PA).
  • composition according to the present invention can be provided as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calciun phosphate, calciun silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesiun stearate and mineral oil.
  • pharmaceutically acceptable carriers e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calciun phosphate, calciun
  • the formulations may additionally include fillers, anti- agglutinating agents, lubricating agents, wetting agents, flavoring agents, emulsifiers, preservatives and the like.
  • the compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a patient by employing any of the procedures well known in the art.
  • compositions of the present invention can be dissolved in oils, propylene glycol or other solvents that are commonly used to produce an injection.
  • suitable examples of the carriers include physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc., but are not limited to them.
  • R>r topical administration the extract of the present invention can be formulated in the form of ointments and creams.
  • compositions containing present composition may be prepared in any form, such as oral dosage form (powder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule), or topical preparation (cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like), or injectable preparation (solution, suspension, emulsion).
  • composition of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds.
  • the desirable dose of the inventive extract of the present composition varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to administer at the amount ranging from 0.0001 to 100 mg/kg, preferably 0.001 to 10 mg/kg by weight/ day of the inventive extract or compounds of the present invention. The dose may be administered in single or divided into several times per day. In terms of composition, the amount of inventive extract or compound should be present between 0.01 to 50% by weight, preferably 0.5 to 40% by weight based on the total weight of the composition.
  • composition of present invention can be administered to a subject animal such as mammals (rat, mouse, domestic animals or human) via various routes. All modes of administration are contemplated, for example, administration can be made orally, rectally or by intravenous, intramuscular, subcutaneous, intracutaneous, intrathecal, epidural or intracerebroventricular injection.
  • Theinventive extractof the present invention also can be used as a main component or additive and aiding agent in the preparation of various functional health food and health care food.
  • a functional health food comprisingextract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O 0 C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C r C 4 lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, for preventing or improving obesity.
  • a functional health food defined herein means "the functional food having enhanced functionality such as physical functionality or physiological functionality by adding the compound of the present invention to conventional food to prevent or improve obesity in human or mammal”.
  • a health care food defined herein means "the food containing the compound of the present invention showing no specific intended effect but general intended effect in a small amount of quantity as a form of additive or in a whole amount of quantity as a form of capsule, pill, tablet or etc".
  • a sitologically acceptable additive means "any substance the intended use which results or may reasonably be expected to result directly or indirectly in becoming a component or otherwise affecting the characteristics of any food” for example, thickening agent, maturing agent, bleaching agent, sequesterants, humectant, anti-caking agent, clarifying agents, curing agent, emulsifier, stabilizer, thickner, bases and acid, foaming agents, nutrients, coloring agent, flavoring agent, sweetner, preservative agent, antioxidant or etc., which shall be explained in detail as follows.
  • a substance is added to a food for a specific purpose, it is referred to as a direct additive and indirect food additives are those that become part of the food in trace amounts due to its packaging, storage or other handling.
  • Above described health foods can be contained in food, health beverage, dietary therapy etc, and may be used as a form of powder, granule, tablet, chewing tablet, capsule, beverage etc for preventing or improvingobesity.
  • above described extract can be added to food or beverage for prevention and improvement of obesity.
  • the amount of above described compound in food or beverage as a functional health food or health care food may generally range from about 0.01 to 100 w/w % of total weight of food for functional health food composition.
  • the preferable amount of the compound of the present invention in the functional health food, health care food or special nutrient food may be varied in accordance to the intended purpose of each food, it is preferably, in general, used as a additive in the amount of the extract of the present invention ranging from about 0.01 to 5% in food such as noodles and the like, from 40 to 100% in health care food on the ratio of 100% of the food composition.
  • the health beverage composition of present invention contains above described extract as an essential component in the indicated ratio
  • the other component can be various deodorant or natural carbohydrate etc such as conventional beverage.
  • natural carbohydrate are monosaccharide such as glucose, fructose and etc.; disaccharide such as maltose, sucrose and etc.; conventional sugar such as dextrin, cyclodextrin; and sugar alcohol such as xylitol, erythritol and etc.
  • natural deodorant such as taunatin, stevia extract such as levaudioside A, glycyrrhizin and etc., and synthetic deodorant such as saccharin, aspartam and etc.
  • the amount of above described natural carbohydrate is generally ranges from about 1 to 20 g, preferably 5 to 12 g in the ratio of 100 m# of present beverage composition.
  • the other components than aforementioned composition are various nutrients, vitamin, mineral or electrolyte, synthetic flavoring agent, coloring agent and improving agent in case of cheese, chocolate and etc., pectic acid and the salt thereof, alginic acid and the salt thereof, organic acid, protective colloidal adhesive, pH controlling agent, stabilizer, preservative, glycerin, alcohol, carbonizing agent used in carbonate beverage and etc.
  • the other component than aforementioned ones may be fruit juice for preparing natural fruit juice, fruit juice beverage and vegetable beverage, wherein the component can be used independently or in combination.
  • the ratio of the components is not so important but is generally range from about 0 to 20 w/w% per 100 w/w% present composition.
  • Examples of addable food comprising aforementioned extract therein are various food, beverage, gun, vitamin complex, health improving food and the like.
  • Inventive extract of the present invention have no toxicity and adverse effect therefore; they can be used with safe.
  • inventive extract of present invention showed potent anti-obesity activity through various experiments.
  • the inventive extract reduced body weight, the level of total cholesterol, LDL and triglyceride in blood, increased the level of blood HDL as well as inhibited the lipid accunulation of Caenorhabditis elegans (C. elegans). Therefore, it can be used as the therapeutics or health food for treating and preventing obesity without adverse action
  • Eg. 1 shows the change of rat body weight of each group according to the 6 weeks- treatment of SG
  • Eg. 2 shows the level of seran total cholesterol of each group according to the 6 weeks-treatment of SG;
  • Bg. 3 represents the level of serum triglyceride of each group according to the 6 weeks-treatment of SG;
  • Eg. 4 represents the level of serum blood high density lipoprotein (HDL) of each group according to the 6 weeks -treatment of SG;
  • Eg. 5 represents the level of serum low density lipoprotein (LDL) of each group according to the 6 weeks -treatment of SG;
  • Eg. 6 presents the inhibitory effect on the lipid droplet production in Caenorhabditis elegans (C. elegans) according to the 6 weeks-treatment of SG.
  • Experimental rat was anesthetized by intramuscular injection of ketamine (Yuhan, Korea) in the amount of 1 m ⁇ /kg, and then the abdominal fur was removed. The surgery region was sterilized with 70% ethanol and the skin, abdominal muscle and peritoneum were cut in about 1 cm. After exposing the ovary, ovariectomy was operated and the incised part was sutured. Sham operation, i.e., the peritoneum of the rat was cut and ovariectomy was not operated, in normal control group.
  • ketamine Yamahan, Korea
  • the experiment rats were classified into four groups, i.e., (1) normal group (NC group) consisting of 10 rats: the group which the sham operation was performed after incising peritoneun, (2) control group (OC group) consisting of 10 rats: the group not treated with drug after ovariectomy, (3) high-dose test group (SGH group) consisting of 8 rats: the group orally treated with SG in an amount of 200 mg/kg after ovariectomy, and (4) low-dose test group (SGL group) consisting of 8 rats: the group orally treated with SG in an amount of 100 mg/kg after ovariectomy.
  • NC group normal group
  • OC group control group
  • SGH group high-dose test group
  • SGL group low-dose test group
  • TC total cholesterol
  • HDL high density lipoprotein
  • TG triglyceride
  • LDL low density lipoprotein
  • the body weight of the rats after treating with extract for 6 weeks was observed as approximately 224.4 g in normal group (NC group), 276.8 g in control group (OC group), 263.1 g in high-dose test group (SGH group) and 259.3 g in low-dose test group (SGL group), respectively.
  • control group showed significant increased body weight comparing with normal group (NC group) while the test groups, i.e., high-dose test group (SGH group) and low-dose test group (SGL group) showed decreased body- weight comparing with the control group (OC group).
  • SGH group high-dose test group
  • SGL group low-dose test group
  • Triglyceride level [150] The level of serum triglyceride in control group (111.2+34.2 rrg/dl in OC group) was significantly increased comparing with that in normal group (69.2+7.5 mg/dl in NC group). The level of serum triglyceride in high-dose test group (SGH group) was significantly decreased to 97.6+16.3 rrg/dl ( See Table 4 and Eg. 3).
  • HDL-cholesterol level [155] The level of HDL-cholesterol in normal group (46.58+8.22 rrg/dl in NC group) and control group (37.75+5.44 rrg/dl in OC group) was decreased comparing with normal group (NC group).
  • LDL-cholesterol level [161] The level of serum LDL-cholesterol in control group (OC group) showed 17.8+7.02 rrg/dl and that in normal group (NC group) showed 17.8+7.02 mg/dl.
  • Caenorhabditis elegans (C. elegans) grown to L4 stage was placed to plate, one per plate and the groups were divided into control group and test sample group treated with 10 ⁇ g/md, of SG. On the next day, after eliminating the eel worm reached to PO generation among the test group, the plate was treated with Nile red solution and incubated for 3 days. After fixing the eelwormon each plate with sodium azide (NaN 3 ), the eelworm was photographed with fluorescence microscope (the length of WP: 628 nm, magnification at x400).
  • test sample group (C and D) showed decreased in the lipid droplet comparing with control group (A and B).
  • Powder preparation was prepared by mixing above components and filling sealed package.
  • Tablet preparation was prepared by mixing above components and entabletting.
  • Capsule preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method. [192]
  • Injection preparation was prepared by dissolving active component and then filling all the components in 2 ml ample and sterilizing by conventional injection preparation method.
  • Liquid medicine was prepared by dissolving the components to distilled water with a proper dose of lemon scent, mixing, adjusting to 100 ml with distilled water in brown bottle and sterilizing by conventional liquid medicine preparation method.
  • the inventive extract of processed Panax genus of the present invention reduced body weight, the level of serum total cholesterol, low density lipoprotein (LDL) and triglyceride, increased the level of serum high density lipoprotein (HDL) as well as inhibited the lipid accumulation of Caenorhabditis elegans (C. elegans). Therefore, it can be used as the therapeutics or health food for treating and preventing obesity without adverse action.
  • LDL low density lipoprotein
  • HDL high density lipoprotein
  • C. elegans Caenorhabditis elegans

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Abstract

La présente invention porte sur des compositions comprenant un extrait inventif du genre Panax traité de la présente invention et l'extrait inventif a réduit la masse corporelle, le taux de cholestérol total, de LDL et de triglycérides dans le sang, a augmenté le taux de HDL dans le sang et a également inhibé l'accumulation lipidique de Caenorhabditis elegans (C. elegans). Par conséquent, la composition peut être utilisée en tant que produit thérapeutique ou aliment diététique pour traiter et prévenir l'obésité sans action défavorable.
PCT/KR2008/001076 2007-05-09 2008-02-25 Composition comprenant un extrait de ginseng traité pour prévenir et traiter l'obésité et utilisation de celle-ci Ceased WO2008140178A1 (fr)

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KR10-2007-0044772 2007-05-09

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CN103076444A (zh) * 2013-01-04 2013-05-01 中国科学院东北地理与农业生态研究所 利用秀丽隐杆线虫鉴定白酒中塑化剂的方法
CN103432231A (zh) * 2013-08-30 2013-12-11 张松波 一种治疗产后缺乳的药物
WO2016124080A1 (fr) * 2015-02-06 2016-08-11 富力 20(r)-ginsenoside rg3 destiné à la préparation d'un médicament pour la prévention et/ou le traitement de l'obésité ou ses applications et médicament associé
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