WO2017190419A1 - Utilisations de monomère dérivé de mogrol et composition correspondante - Google Patents

Utilisations de monomère dérivé de mogrol et composition correspondante Download PDF

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Publication number
WO2017190419A1
WO2017190419A1 PCT/CN2016/089199 CN2016089199W WO2017190419A1 WO 2017190419 A1 WO2017190419 A1 WO 2017190419A1 CN 2016089199 W CN2016089199 W CN 2016089199W WO 2017190419 A1 WO2017190419 A1 WO 2017190419A1
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Prior art keywords
cancer
tumors
lymphoma
derivative monomer
leukemia
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PCT/CN2016/089199
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English (en)
Chinese (zh)
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余佩华
邓跃敏
钟牧源
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深圳以诺生物制药有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention relates to the field of medicine, in particular to the use of a mogroside derivative monomer and a composition thereof.
  • Cancer is the second largest disease in the world that afflicts human life. Mortality is second only to cardiovascular and cerebrovascular diseases and is one of the most important causes of human death.
  • IARC International Agency for Research on Cancer
  • the latest edition of the World Cancer Report led by the International Agency for Research on Cancer (IARC), the official cancer organization of the WHO organization, predicts that global cancer cases will proliferate rapidly, from 14 million in 2012 to 19 million in 2025 will reach 24 million by 2035.
  • the report also showed that nearly half of the world's new cancer cases occurred in Asia in 2012, most of which were in China, and China's new cancer cases ranked first.
  • China China added 3.07 million cancer patients and caused about 2.2 million deaths, accounting for 21.9% and 26.8% of the global total, respectively.
  • the WHO's data is slightly lower than China's own statistics. According to the 2012 data released by the National Cancer Registry, about 3.5 million new cancer cases are reported each year in China, and about 2.5 million people die.
  • Tumor biotherapy is the fourth mode after surgery, radiotherapy and chemotherapy, mainly through the tumor host defense mechanism or the role of biological agents to regulate the body's own biological response, thereby inhibiting or eliminating tumors.
  • biological treatment does not have much toxic side effects, due to strict technical requirements and complicated processes, the price is high, and many cancer patients and their families are unbearable, affecting their popularity in the field of cancer treatment.
  • Mangosteen is a precious medicinal material belonging to the perennial vine of Cucurbitaceae. It is cool and sweet.
  • the non-sugar sweet saponin component of Luo Han Guo extract also known as Luo Han Guo total saponin, has been isolated and identified in the total saponin of Siraitia grosveni according to the number of saponin-linked glycosyl groups and the position of the saponin.
  • Mogrosides are two glucoside side chains consisting of four or fewer glucose units linked by a ⁇ -glycosidic bond to C-3 and C-24 of the sapogenin, Lo Hanol Mogrol (2) (as shown in Figure 2).
  • the linkage between the side chain glucoses is ⁇ -1,6 and ⁇ -l,2 glycosidic bonds.
  • mogroside can increase the utilization of glucose and fat and increase the sensitivity of insulin, but the active ingredients and mechanism of action of mogroside in hypoglycemic effect are not clear.
  • the highest content of mogroside V (1A) in Luo Han Guo was tested and found that it did not have AMPK.
  • the technical problem to be solved by the present invention is to provide a novel use of the mogroside derivative monomer (3), and the present invention further provides a novel use of the composition comprising the rohanol derivative monomer (3).
  • the mogroside derivative monomer (3) is different from the high oxidized decane-based tetracyclic triterpene compound directly extracted and separated in most other Cucurbitaceae plants, and the moultanol derivative monomer (3) provided by the present invention is low.
  • Oxidized cucurbitane tetracyclic triterpene compound, characterized in that -3, but not O is attached to C-3 and C-11, the degree of oxidation is greatly reduced, and it is currently impossible to directly extract and separate from plants, and is difficult to prepare. .
  • the first aspect of the invention provides the following structure
  • mogroside derivative monomer (3) is manifested in the use of a medicament for the treatment and/or prevention of tumors and/or cancer.
  • tumor and/or cancer is selected from the group consisting of:
  • Malignant tumors including bladder, breast, colon, kidney, liver, lung, head and neck cancer, esophageal cancer, gallbladder, ovarian, pancreatic, gastric, cervical, thyroid, prostate and skin cancer;
  • Hematopoietic tumors of the lymphatic system including leukemia, acute lymphoblastic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma , mantle cell lymphoma, myeloma, and Burkett's lymphoma;
  • Hematopoietic tumors of the myeloid system including acute and chronic myeloid leukemia, myelodysplastic syndrome, and promyelocytic leukemia;
  • Tumors of interstitial origin including fibrosarcoma and rhabdomyosarcoma;
  • Tumors of the central and peripheral nervous system including astrocytoma, fibrone, glioma, and schwannomas;
  • tumors include melanoma, seminoma, teratocarcinoma, osteosarcoma, exogenous pigmented neck tumor, thyroid follicular carcinoma, and Kaposi's sarcoma.
  • the second aspect of the present invention provides the following structure
  • mogroside derivative monomer (3) Another use of the mogroside derivative monomer (3) is manifested in the use in the preparation of a health supplement for immunomodulation and/or improved microcirculation and/or improved quality of life.
  • a third aspect of the present invention provides a use of the composition comprising the above-described mogroside derivative monomer (3), which is useful in the preparation of a medicament for the treatment and/or prevention of tumors and/or cancer;
  • the tumor and/or cancer is selected from the group consisting of:
  • Malignant tumors including bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer (including small cell lung cancer, non-small cell lung cancer), head and neck cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, stomach cancer, Cervical cancer, thyroid cancer, prostate cancer, and skin cancer (including squamous cell carcinoma);
  • Hematopoietic tumors of the lymphatic system including leukemia, acute lymphoblastic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma , mantle cell lymphoma, myeloma, and Burkett's lymphoma;
  • Hematopoietic tumors of the myeloid system including acute and chronic myeloid leukemia, myelodysplastic syndrome, and promyelocytic leukemia;
  • Tumors of interstitial origin including fibrosarcoma and rhabdomyosarcoma;
  • Tumors of the central and peripheral nervous system including astrocytoma, fibrone, glioma, and schwannomas;
  • tumors include melanoma, seminoma, teratocarcinoma, osteosarcoma, exogenous pigmented neck tumor, thyroid follicular carcinoma, and Kaposi's sarcoma.
  • the composition is a pharmaceutical formulation comprising a therapeutically and/or prophylactically effective amount of the mogroin derivative monomer (3) and optionally a pharmaceutically acceptable diluent, carrier, form Agent, excipient or vehicle.
  • the pharmaceutical preparation is in the form of an oral dosage form, an injection dosage form or a topical dosage form;
  • the oral dosage form comprises a tablet, a powder, a suspension, an emulsion, a capsule, a granule, a sugar-coated tablet, a pill, a liquid, an elixir, a syrup or a lemonade;
  • the injectable dosage form comprises a liquid, a suspension or a solution
  • the topical dosage form comprises an ointment, a solid, a suspension, a liquid, an elixir, a powder, a paste, a suppository, an aerosol, a poultice, a spread, a lotion, an enema or an emulsion.
  • a fourth aspect of the present invention provides another use of the composition comprising the above-described mogroside derivative monomer (3), which provides a use of the composition comprising the above-described mogroside derivative monomer (3),
  • composition is a nutraceutical comprising a therapeutically and/or prophylactically effective amount of the mogroside derivative monomer (3) and an acceptable carrier in an optional health care product.
  • mogroside derivative (3) as used herein means 3 ⁇ -hydroxy-25-dehydroxy-24-oxomogrol or its abbreviated name The mogroside derivative (3) (structure shown in Figure 3).
  • composition as used herein is intended to include a product comprising specified amounts of each of the specified ingredients, as well as any product that results, directly or indirectly, from the specified combination of the specified ingredients.
  • the topical dosage form includes an ointment, a solid, a suspension, a liquid, an elixir, a powder, a paste, a suppository, an aerosol, a poultice, a spread, a lotion, an enema or an emulsion.
  • the active compound is admixed under sterile conditions with apharmaceutically acceptable carrier and any of the required preservatives, buffers or propellants. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of the invention.
  • a therapeutically and/or prophylactically effective amount of a compound of the invention may be administered in pure form, or in the form of a pharmaceutically acceptable salt, ester or prodrug (in the presence of such forms) application.
  • the compound can be administered in a pharmaceutical composition comprising the compound of interest and one or more pharmaceutically acceptable excipients.
  • the phrase "therapeutically and/or prophylactically effective amount" of a compound of the invention refers to a sufficient amount of a compound to treat the disorder at a reasonable effect/risk ratio applicable to any medical treatment. It will be appreciated, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment.
  • the specific therapeutically and/or prophylactically effective dosage level for any particular patient will depend on a number of factors, including the disorder being treated and the severity of the disorder; the activity of the particular compound employed; Specific composition; age, weight, general health, sex and diet of the patient; time of administration, route of administration and excretion rate of the particular compound employed; duration of treatment; use in combination or concurrent use with the particular compound employed Drugs; and similar factors well known in the medical field.
  • the dosage of the compound be started from a level lower than that required to achieve the desired therapeutic effect, and the dosage is gradually increased until the desired effect is obtained.
  • the invention also provides pharmaceutical formulations comprising a compound of the invention, optionally formulated with one or more non-toxic pharmaceutically acceptable diluents, carriers, excipients, adjuvants or vehicles.
  • the pharmaceutical preparations may be specially formulated for oral administration in solid or liquid form for parenteral injection or for rectal administration.
  • composition of the present invention can be administered orally, rectally, parenterally, intra-, intravaginally, intraperitoneally, topically (e.g., by powder, ointment or drops), buccally to humans and other mammals, or as an oral spray. Or nasal spray.
  • parenteral refers to a mode of administration including intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, and intraarticular injections and infusions.
  • the invention provides a pharmaceutical composition comprising a component of the invention and a physiologically tolerable diluent.
  • the present invention includes one or more of the above compounds formulated in combination with one or more non-toxic physiologically tolerable or acceptable diluents, carriers, adjuvants or vehicles (collectively referred to herein as diluents)
  • diluents non-toxic physiologically tolerable or acceptable diluents, carriers, adjuvants or vehicles
  • compositions suitable for parenteral injection may include physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for the preparation of sterile injectable solutions or dispersions.
  • suitable aqueous or nonaqueous vehicles, diluents, solvents or vehicles include water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, etc.), vegetable oils (such as olive oil), injectable organic esters such as oleic acid. Ethyl esters and suitable mixtures thereof.
  • compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents.
  • adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents.
  • the action of microorganisms can be ensured by various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid and the like.
  • isotonic agents for example, sugars, sodium chloride, and the like.
  • Prolonged absorption of the injectable pharmaceutical form can be brought about through the use of materials which delay absorption, such as aluminum monostearate and gelatin.
  • Suspensions may contain suspending agents in addition to the active compound, such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite , agar and tragacanth or a mixture of these substances.
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite , agar and tragacanth or a mixture of these substances.
  • the rate of absorption of the drug depends on its rate of dissolution, which in turn may depend on crystal size and crystal form.
  • delayed absorption of a pharmaceutical form for parenteral administration is accomplished by dissolving or suspending the drug in an oil vehicle.
  • Injectable depot formulations are prepared by forming microencapsule matrices of the drug in a biodegradable polymer such as polylactide-polyglycolide. The rate of drug release can be controlled based on the ratio of drug to polymer and the nature of the particular polymer employed. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by embedding the drug in liposomes or microemulsions which are compatible with body tissues.
  • the injectable preparation can be sterilized, for example, by filtration with a bacteriophage or by incorporating a sterilizing agent in the form of a sterile solid composition which can be dissolved or dispersed in sterile water or other sterilized form before use. Injectable medium.
  • Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.
  • the active compound may be mixed with at least one inert pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or the following: a) filler or extender such as starch , lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and gum arabic; c) humectants such as glycerin; d) Decomposing agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarders such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) humectants such as whales Wax alcohol and glycerol monostearate;
  • Solid compositions of a similar type may be used as fillers in soft and hard capsules using such excipients as lactose and high molecular weight polyethylene glycols and the like.
  • the solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other materials known in the art of pharmaceutical preparations. These solid dosage forms may optionally contain opacifying agents and may be formulated such that they are only or preferentially released in a certain portion of the intestinal tract in a delayed manner. Examples of the embedding composition that can be used include high molecular substances and waxes. If appropriate, the active compounds may also be formulated in microencapsulated form with one or more of the above-mentioned excipients.
  • Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs.
  • the liquid dosage form may contain, in addition to the active compound, an inert diluent commonly used in the art, such as water or other solvents, solubilizers and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate.
  • the oral compositions may contain, in addition to inert diluents, excipients such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and flavoring agents.
  • compositions for rectal or vaginal administration are preferably suppositories.
  • Suppositories can be prepared by admixing a compound of the present invention with a suitable non- irritating excipient or carrier such as cocoa butter, polyethylene glycol or suppository wax, which are solid at room temperature but liquid at body temperature, thus Melting in the rectal cavity or vaginal cavity releases the active compound.
  • the compounds of the invention may also be administered in the form of liposomes.
  • liposomes are typically prepared using phospholipids or other lipid materials. Liposomes are formed from single or multiple layers of hydrated liquid crystal dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used.
  • the composition of the present invention in the form of a liposome may contain, in addition to the compound of the present invention, a stabilizer, a preservative, an excipient or the like.
  • Preferred lipids are natural and synthetic phospholipids and phosphatidylcholines (lecithins), which may be used alone or together. Methods of forming liposomes are well known in the art.
  • prodrug denotes a prodrug of a compound of the invention which is Suitable for use in contact with tissues of humans and lower animals without excessive toxicity, irritation, allergic reactions, etc., in proportion to the reasonable effect/risk ratio and effective for its intended use, where possible
  • the zwitterionic form of the compounds of the invention is also represented below.
  • Prodrugs of the invention can be rapidly converted in vivo to the parent compound of the above formula, for example by hydrolysis in blood.
  • the mogroside derivative monomer (3) of the present invention has antitumor activity for inhibiting proliferation of human tumor cells (23 kinds of tested cancer cells) and human umbilical vein endothelial cells, and can be made to treat and/or prevent different Cancer and/or tumor drugs, as well as health supplements for immunomodulating and/or improving microcirculation and/or improving quality of life, focus on the treatment of malignant tumors and have broad application prospects.
  • Fig. 1 is a schematic view showing the molecular structure of mogroside V(1A) and VI(1B).
  • Figure 2 is a schematic diagram showing the molecular structure of mogroside Mogrol (2).
  • Fig. 3 is a schematic view showing the molecular structure of the mogroside derivative monomer (3).
  • Luo Han Guo extract 98% of Luo Han Guo total saponin, containing 55% Luo Han Guo ⁇ V, purchased from Guilin Rhein Biotechnology Co., Ltd.
  • the hydrochloric acid was adjusted to a pH of 3.0), stirred and dissolved in a reaction vessel, and then heated to 120 ° C for 2 hours. After cooling to room temperature at 25 ° C, the reaction solution was neutralized with a 1 M NaOH lye to a pH of 7. Evaporate the ethanol as much as possible at 90-95 ° C. Add the remaining concentrate to 200 mL of distilled water, stir well, cool, and let stand.
  • Test drug the preparation of the mogroin derivative monomer (3) prepared in Example 1;
  • Control drug paclitaxel (SELLECK; Cat. #S1150); ginsenoside monomer Rg3 (purchased from Shanghai Yuanye Biotechnology Co., Ltd., product number B21059).
  • 24 cell lines (including 23 tumor cell lines and 1 human umbilical vein endothelial cell line) were used as experimental cell lines, and logarithmic growth phase cells (3 ⁇ 10 4 /mL to 2.5 ⁇ 10 5 /mL) were taken. 100 ⁇ L per well was seeded in a 96-well plate, and each cell line was plated with a 96-well plate; then, in addition to the control drug paclitaxel, 7 logarithmic decreasing concentrations were taken at a high concentration of 150 ⁇ M to a low concentration of 2 ⁇ M (two for each concentration) Double wells were added to the test drug solution and the control drug solution, respectively, 500 nL (test drug solution or control drug solution preparation: test drug or control drug dissolved in 0.5% DMSO solution, respectively).
  • Paclitaxel was added at a concentration ranging from a high concentration of 1 ⁇ M to a low concentration of 0.0014 ⁇ M. After test/control drug solution for 72 hours, use (Promega; Cat. #G7573) Luminescent cell viability assay to determine the percentage inhibition of proliferation of each cell of each cell in each cell line, and to plot the dose-effect relationship, and finally calculate the IC according to the curve in the figure 50 and the highest percent inhibition ( Emax ), as shown in Tables 1 and 2.
  • Table 1 Experimental results of inhibition of cell proliferation activity of the mogroside derivative monomer (3) and the control drug Rg3.
  • Table 2 Experimental results of the effectiveness of the mogroside derivative monomer (3) and the control drugs paclitaxel and Rg3 inhibiting cell proliferation.
  • Mangosteen alcohol derivative monomer 1 Mangosteen alcohol derivative monomer 1.
  • the present invention in average IC 24 Comparison of cell lines (3) in the average IC 24 of 50 cell lines with control drug monomer ginsenoside Rg3 50, presented a statistically significant difference ( P ⁇ 0.05 and P ⁇ 0.01).
  • the cellulite activity of the mogroside derivative monomer (3) of the present invention is higher than that of the similar control drug ginsenoside monomer Rg3 (the composition of the mogroside derivative monomer (3)) in all of the 24 cell lines tested. 50 is less than the IC 50 of the ginsenoside monomer Rg3.
  • the highest inhibition rate (effectiveness) of the romanol derivative monomer (3) of the present invention on all 24 tested cell lines is very close to 100%; and the reference drug paclitaxel and ginsenoside monomer Rg3 have been measured 24 In the cell line, only about 100% inhibition rate was observed for the two cell lines. This indicates that the mogroside derivative monomer (3) is significantly more effective than the control drug, and its high anticancer effectiveness is applicable to a plurality of cancer types.

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Abstract

L'invention concerne des utilisations d'un monomère dérivé de mogrol (3) dans la préparation d'un médicament destiné au traitement et/ou à la prévention de tumeurs et/ou de cancers et ses utilisations dans la préparation d'un produit de soins de santé pour l'immunomodulation, l'amélioration de la microcirculation et l'augmentation de la qualité de vie. Le monomère dérivé de mogrol (3) a un large spectre d'efficacité antitumorale et est principalement applicable dans le traitement de tumeurs malignes.
PCT/CN2016/089199 2016-05-06 2016-07-07 Utilisations de monomère dérivé de mogrol et composition correspondante WO2017190419A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108578702A (zh) * 2018-05-24 2018-09-28 深圳以诺生物制药有限公司 一种稀有人参皂苷的混合物及其应用

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105832748B (zh) * 2016-05-06 2019-06-07 深圳以诺生物制药有限公司 一种从罗汉果总皂苷中制备罗汉果醇衍生物的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1357003A (zh) * 1999-04-30 2002-07-03 亚其发展公司 类固醇衍生物
CN102526073A (zh) * 2012-01-06 2012-07-04 复旦大学 罗汉果醇h9在制备抗肿瘤药物中的应用
CN104042620A (zh) * 2013-03-12 2014-09-17 复旦大学 罗汉果醇在制备肿瘤多药耐药逆转剂中的用途

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101033244B (zh) * 2007-04-05 2010-05-19 上海交通大学 罗汉果醇的提纯制备方法
CN111920817A (zh) * 2013-09-26 2020-11-13 华安医学股份有限公司 活化ampk的化合物及其使用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1357003A (zh) * 1999-04-30 2002-07-03 亚其发展公司 类固醇衍生物
CN102526073A (zh) * 2012-01-06 2012-07-04 复旦大学 罗汉果醇h9在制备抗肿瘤药物中的应用
CN104042620A (zh) * 2013-03-12 2014-09-17 复旦大学 罗汉果醇在制备肿瘤多药耐药逆转剂中的用途

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Anticancer Effect of Sweetish Substances in Siraitia Grosvenorii", FOREIGN MEDICAL SCIENCES: TRADITIONAL CHINESE MEDICINE SECTION, vol. 25, no. 3, 31 December 2003 (2003-12-31), pages 174 *
CHEN, XUBING ET AL.: "Potential AMPK Activators of Cucurbitane Triterpenoids from Siraitia Grosvenorii Swingle", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 19, no. 19, 22 August 2011 (2011-08-22), pages 5776 - 5781, XP028294118 *
GAO, JIAQING: "Rare Anticancer Herbal-Siraitia Grosvenorii", BIOORGANIC & MEDICINAL CHEMISTRY, 31 December 1998 (1998-12-31), pages 27 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108578702A (zh) * 2018-05-24 2018-09-28 深圳以诺生物制药有限公司 一种稀有人参皂苷的混合物及其应用
CN108578702B (zh) * 2018-05-24 2022-11-29 深圳以诺生物制药有限公司 一种稀有人参皂苷的混合物及其应用

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