WO2017190420A1 - 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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WO2017190420A1
WO2017190420A1 PCT/CN2016/089203 CN2016089203W WO2017190420A1 WO 2017190420 A1 WO2017190420 A1 WO 2017190420A1 CN 2016089203 W CN2016089203 W CN 2016089203W WO 2017190420 A1 WO2017190420 A1 WO 2017190420A1
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cancer
tumors
derivative monomer
lymphoma
leukemia
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Chinese (zh)
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余佩华
邓跃敏
钟牧源
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Shenzhen Enoch Phytomedicine Co Ltd
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Shenzhen Enoch Phytomedicine Co Ltd
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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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Definitions

  • the invention relates to the field of medicine, in particular to the use of a novel 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.
  • the fourth mode after surgery, radiotherapy and chemotherapy is the biological treatment of tumors, which mainly regulates the body's own biological response through the action of tumor host defense mechanisms or biological agents, thereby inhibiting or eliminating tumors; Too many toxic side effects, but 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.
  • Natural anticancer drugs play an important role in inhibiting or killing tumor cells, adjusting immune function, improving symptoms and characteristics, and reducing the side effects of radiotherapy and chemotherapy. As a result, new natural plant therapies will become the fifth mode after surgery, radiation therapy, chemotherapy and biological therapy.
  • 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.
  • mogroside II, III, IV, V, VI mogroside II, III, IV, V, VI
  • mogroside V-Mogroside V (1A) is 256-344 times sweeter than sucrose
  • Mogroside IV-Mogroside IV (1B) shown in Figure 1 has a sweetness of 126 times that of sucrose. Zero, has the effect of clearing away heat, moistening lungs, relieving cough, and relaxing bowel movements. It has preventive effects on obesity, constipation and diabetes.
  • Mogrosides are two C-glucosides consisting of four or less glucose units with a ⁇ -glycosidic bond and a sapogenin, Lo Hanol Mogrol (2) (as shown in Figure 2), C-3, C- 24 is linked, and the linkage between the side chain glucose 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 a novel mogroside derivative monomer (4), and the present invention further provides a novel use of a composition comprising the novel mogroside derivative monomer (4).
  • the novel mogroside derivative monomer (4) is different from the other highly oxidized decane-based tetracyclic triterpene compounds extracted and separated from most of the Cucurbitaceae plants.
  • the novel mogroside derivative monomer (4) is a low-oxidation cucurbit.
  • the first aspect of the invention provides the following structure
  • novel mogroside derivative monomer (4) is manifested in the use in the manufacture 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
  • Another use of the novel rohanol derivative monomer (4) is in the use of 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 novel mogroside derivative monomer (4), for use 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 novel mogroside derivative monomer (4) and optionally a pharmaceutically acceptable diluent, carrier, Forming agents, excipients or vehicles.
  • 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 novel mogroside derivative monomer (4), which provides a use of the composition comprising the above novel mogroside derivative monomer (4),
  • composition is a health supplement comprising a therapeutically and/or prophylactically effective amount of the novel mogroside derivative monomer (4) and an acceptable carrier in an optional health care product.
  • roorolol derivative monomer (3) as used herein means 3 ⁇ -hydroxy-25-dehydroxy-24-oxomogrol (3 ⁇ -hydroxy-25-Dehydroxy-24-oxomogrol) (structured as shown 3));
  • new romanol derivative monomer (4) as used herein means 3 ⁇ -hydroxy-22,24-diene-24,25-dehydroxy-rohansol (3 ⁇ -hydroxy-22, 24-diene-24, 25-dehydroxy-mogrol) (4) (Structural formula shown in Figure 4).
  • 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, optionally, together with one or more non-toxic pharmaceutically acceptable diluents, carriers, Pharmaceutical preparations of the compounds of the invention formulated together with 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 partial hydroxide, swelling Run Soil, 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 partial hydroxide, swelling Run Soil, 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 crystalline 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, Preservatives, excipients, etc.
  • 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 human and lower animal tissues without undue toxicity, irritation, allergies within the scope of sound medical judgment.
  • the reaction, etc. is commensurate with a reasonable effect/risk ratio and is effective for its intended use, and where possible, represents the zwitterionic form of the compound of the invention.
  • 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 novel mogroside derivative monomer (4) 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 prepared for treatment and/or prevention.
  • Drugs of different cancers and/or tumors, as well as health care products for immunomodulating and/or improving microcirculation and/or improving quality of life, are mainly applied to 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).
  • Fig. 4 is a schematic view showing the molecular structure of a novel mogroside derivative monomer (4).
  • Example 1 Preparation of mogroside derivative monomers (3) and (4) from 98% of the total saponins of Siraitia grosvenorum
  • 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.
  • Example 2 Preparation of mogroside derivative monomers (3) and (4) from 95% of the total saponins of Siraitia grosvenor
  • Luo Han Guo extract 95% of Luo Han Guo total saponin, containing 45% Luo Han Guo ⁇ V, purchased from Guilin Rhein Biotechnology Co., Ltd.
  • methanol solution methanol and water volume ratio of 3:2
  • the sulfuric acid was adjusted to a pH of 2.8), stirred and dissolved in a reaction vessel, and then heated to 120 ° C for 2 hours. After cooling to room temperature, the reaction solution was neutralized with a 1 M KOH lye to a pH of 7 at 90- Methanol was distilled off as much as possible at 95 ° C. The remaining concentrate was added to 200 mL of distilled water, stirred thoroughly, cooled, and allowed to stand.
  • the upper aqueous layer was separated and discarded to obtain a brown extract; 100 mL, 50 mL, 50 mL of ethyl acetate were used respectively.
  • the coffee extract was extracted 3 times, and after 3 times of extracting, the mixture was concentrated at 100-120 ° C with a rotary evaporator, and the ethyl acetate was completely evaporated to obtain a monomer containing the mogroside derivative (3) and rohanol.
  • the light brown solid of the monomer (4) was 15.5 g; the light brown solid was loaded onto a silica gel column with methanol, eluted with a gradient of acetonitrile:water (19:1), and the different effluent was collected in order, and concentrated to give A. (6.0g), B (5.2g) two components; first collected A (6 The .0g) component was separated by a silica gel column (chloroform: ethanol/60:5 elution) to obtain a mannose alcohol derivative monomer (3) 3.9 g (HPLC>99%); HPLC, 13 C-NMR, ESESI detection The result was identical to the compound (3) in Example 1.
  • Luo Han Guo extract 90% of Luo Han Guo total saponin, containing 40% Luo Han Guo ⁇ V, purchased from Guilin Rhein Biotechnology Co., Ltd.
  • n-propanol the ratio of n-propanol to water was 2:3.
  • the remaining concentrate was added to 200 mL of distilled water, stirred thoroughly, cooled, and allowed to stand. The upper aqueous layer was separated and discarded to obtain a brown extract; 100 mL, 50 mL, respectively. Extracting the brown extract with 50 mL of ethyl acetate 3 times, combining the extracts three times, concentrating at 100-120 ° C with a rotary evaporator, and evaporating the ethyl acetate completely to obtain a monomer containing rohanol derivative (3) And light brown solid of 14.1 g of the mogroside derivative monomer (4); the light brown solid was loaded onto a silica gel column with methanol/ethanol, and eluted with a gradient of acetonitrile:water (20:1).
  • Example 4 Preparation of mogroside derivative monomers (3) and (4) from an extract of 80% of total saponins of Siraitia grosvenorum
  • Luo Han Guo extract 80% of Luo Han Guo total saponin, containing 20% Luo Han Guo ⁇ V, purchased from Guilin Rhein Biotechnology Co., Ltd.
  • ethanol the volume ratio of ethanol to water is 1:1
  • the oxalic acid was adjusted to a pH of 2.6), dissolved in a reaction vessel, and then heated to 120 ° C for 2 hours. After cooling to room temperature, the reaction solution was neutralized to a pH of 1 M Na 2 CO 3 . 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.
  • Example 5 Monocrotool derivative monomer (4) inhibiting cell proliferation experiment
  • Test drug the mogroside derivative monomer prepared in Example 1 (4);
  • 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 by the mogroside derivative monomer (4) and the control drug Rg3.
  • Table 2 Experimental results of the effectiveness of the mogroside derivative monomer (4) and the control drugs paclitaxel and Rg3 inhibiting cell proliferation.
  • the independent-sample T-test was used to determine whether the difference between the mean of the drug group and the control group was statistically significant (P ⁇ 0.05 or P ⁇ 0.01).
  • the average IC50 of the mogroside derivative monomer (4) of the present invention in 24 cell lines was statistically significant when compared with the average IC50 of the control drug ginsenoside monomer Rg3 in 24 cell lines (P ⁇ 0.05). At the same time P ⁇ 0.01).
  • the average maximum percent inhibition of the mogroside derivative monomer (4) of the present invention in 24 cell lines is compared with the average highest percent inhibition of the control drug paclitaxel and the control drug ginsenoside monomer Rg3 in 24 cell lines. The difference was statistically significant (P ⁇ 0.05 and P ⁇ 0.01).
  • the cellulose-inhibiting activity of the mogroside derivative monomer (4) of the present invention in all 24 cell lines is higher than that of the similar control drug ginsenoside monomer Rg3 (the composition of the mogroside derivative monomer (4)) 50 is less than the IC 50 of the ginsenoside monomer Rg3.
  • the highest inhibition rate (effectiveness) of the romanol derivative monomer (4) of the present invention on all 24 tested cell lines is very close to 100%; and the reference drug paclitaxel and ginsenoside monomer Rg3 are measured 24 In the cell line, only about 100% inhibition rate was observed for the two cell lines. This indicates that the mogroin derivative monomer (4) 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 un monomère dérivé de mogrol (4) ayant une efficacité antitumorale à large spectre; le monomère est supérieur en termes d'activité et d'efficacité par rapport au médicament antitumoral/produit de santé Rg3 de structure similaire et disponible dans le commerce. En outre, il présente une plus grande efficacité que le médicament anticancéreux à large spectre paclitaxel, et peut être préparé en un médicament destiné à être utilisé dans le traitement et/ou la prévention de différents cancers et/ou tumeurs et en un produit de santé destiné à être utilisé dans l'immunomodulation et/ou l'amélioration de la microcirculation et/ou l'augmentation de la qualité de vie. Il trouve une application particulière dans le traitement de tumeurs malignes, et présente de larges perspectives d'application.
PCT/CN2016/089203 2016-05-06 2016-07-07 Utilisations de monomère dérivé de mogrol et composition correspondante Ceased WO2017190420A1 (fr)

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