CN105769891A - Low-polarity rare ginsenoside mixture and application thereof - Google Patents
Low-polarity rare ginsenoside mixture and application thereof Download PDFInfo
- Publication number
- CN105769891A CN105769891A CN201610223115.6A CN201610223115A CN105769891A CN 105769891 A CN105769891 A CN 105769891A CN 201610223115 A CN201610223115 A CN 201610223115A CN 105769891 A CN105769891 A CN 105769891A
- Authority
- CN
- China
- Prior art keywords
- low polarity
- cancer
- rare ginsenoside
- tumor
- polarity rare
- 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.)
- Granted
Links
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicine, and relates to application of a low-polarity rare ginsenoside mixture Rk2/Rh2 in preparation of medicine for treating and/or preventing tumors and/or cancers and health-care products for immune adjustment, microcirculation improvement and improvement of life quality. The invention further provides a composition of the low-polarity rare ginsenoside mixture Rk2/Rh2 and application thereof. The low-polarity rare ginsenoside mixture Rk2/Rh2 has the broad-spectrum high tumor resistance effectiveness, has the better activity and effectiveness compared with existing ginsenoside anti-tumor medicine/health-care products Rg3 and Rh2 and monomers Rk2 and Rh3 of the mixture on the market, can be prepared into the medicine used for treating and/or preventing different cancers and/or tumors and health-care products used for immune adjustment and/or microcirculation improvement and/or improvement of life quality, is emphatically applied to treating malignant tumors and has the wide application prospect.
Description
Technical field
The present invention relates to field of medicaments, be specifically related to low polarity rare ginsenoside mixture of class and application thereof.
Background technology
Cancer is the second-biggest-in-the-world disease torturing human life, and mortality rate is only second to cardiovascular and cerebrovascular disease, is one of the main factor of human death.By World Health Organization organize subordinate IARC of cancer mechanism of official (IARC) responsible latest edition " report of world's cancer " prediction, whole world cases of cancer will present rapidly breeds situation, by 14,000,000 people of 2012, fast 19,000,000 people increasing to 2025, were up to 24,000,000 people by 2035 year by year.Report also shows, within 2012, the newly-increased cases of cancer in the whole world has nearly half to occur in Asia, and wherein most is in China, and the newly-increased cases of cancer height of China ranks first.Within 2012, newly-increased 3,070,000 cancer patients of China also cause about 2,200,000 people dead, divide and account for the 21.9% and 26.8% of whole world total amount.The data of WHO are slightly below the statistics of China.2012 annual datas that whole nation tumor Register issues show, the annual newly-increased cases of cancer about 3,500,000 of China, there are about 2,500,000 people therefore dead.
The common method for the treatment of of cancer mainly has Three models now: operation, radiotherapy and Drug therapy, and which Therapeutic Method selected then depends on the position of tumor, grade malignancy, development degree and patient body state.In Three models, the Therapeutic Method of operation, the invasion of Chang Yinwei cancerous cell spreads to adjacent tissue or far-end shifts and limited efficiency；The Therapeutic Method of radiotherapy, then be limited to the injury that other normal structures internal are caused；The Therapeutic Method of medicine, for late period dispersivity and transitivity malignant tumor be most basic Therapeutic Method.In the decades in past, though the chemotherapy being conceived to direct killing tumor cell has obvious development and progress, become the backbone of tumor pharmacother, but the defect breeding solid tumor weak effect slowly, drug selectivity is little, toxicity is many and serious is become the important limiting factor in clinical treatment by this Therapeutic mode.Continue the Biotherapeutics that operation, the 4th kind of pattern after radiation and chemotherapy are tumors, it regulates the biologically of body self mainly by the effect of tumor host defense mechanism or biological preparation, thus suppressing or eliminating tumor；Although Biotherapeutics is too big toxic and side effects not, but owing to technology requires tight, complex process, therefore price is high, and numerous cancer patients and family members are difficult to bear, and affects its popularizing in field of cancer.
Owing to there is above-mentioned various restriction, the research and development of natural antitumor medicine achieve increasing concern.No matter natural anti-cancer drugs is at suppression or killing tumor cell, adjustment body's immunity, improves symptom and feature and alleviate on toxic and side effects of chemoradiotherapy, or in the conditioning after being ill of tumor, is respectively provided with important function.Thus, natural plants new therapy will become the 5th kind of pattern after operation, radiotherapy, chemotherapy and biotherapy.
Araliaceae (araliaceae) Panax (Panax) plant, such as Radix Ginseng (P.ginseng), Radix Panacis Quinquefolii (P.quenquefolinus), Radix Notoginseng (P.notoginseng), Rhizoma Panacis Japonici (P.uaponicus), cucurbitaceae genus gynostemma Herb Gynostemmae Pentaphylli (GynostemmaoentaphyllumThrunbMak) etc. is traditional medicinal plants that China is famous and precious, and its principle active component is dammarane type four-ring triterpenoid ginseng saponin series compound.The prototype ginsenoside having now been found that in Araliaceae has kind more than 60, called after R1, Ral, Ra2, Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rh1, F etc., all it is made up of glycoside unit and sugar, it is generally dissolved easily in water, its curative effect specifically includes that immunoloregulation function, improving micro_circulation effect, adjustment digestive function, hypermnesis and learning capacity, defying age, calms the nerves, but does not show obvious anti-tumor activity.
Low polarity rare ginsenoside content in former panax species is very micro-, exist only in wild ginseng, or in the Radix Ginseng that Radix Ginseng Rubra, black ginseng and cooked Radix Notoginseng etc. are concocted and Radix Notoginseng product, it is also only ten thousand/several, and it is insoluble in water, generally only it is dissolved in the low polar organic solvent such as ethanol or ethyl acetate, is referred to as low polarity rare ginsenoside, specifically includes that Rg3, Rh2, Rk1, Rg5, Rk2, Rh3, Rk3, Rh4 etc..Modern pharmacology research shows, low polarity rare ginsenoside has stronger anti-tumor activity, can grow by anticancer, bring out cancer cell-apoptosis, Selective depression tumor cell invasion and transfer, and make cancerous cell induction again be reversed into non-cancerous cells etc., therefore low polarity rare ginsenoside has high medical value and application prospect.
Tung et al. (Chem.Pharm.Bull.58 (8) 1111-1115 (2010)) once reported that too low polarity rare ginsenoside Rk2 or low polarity rare ginsenoside Rh3 had stronger active anticancer in acute human promyelocytic leukemia HL-60 cell line；At present, also low polarity rare ginsenoside is had to list as the main component in anticancer drugs or health product, such as low polarity rare ginsenoside-Rg3 (" Shenyi capsule ") and low polarity rare ginsenoside-Rh2 (" modern good fortune capsule ").But, existing low polarity rare ginsenoside monomer, for instance above-mentioned several ginsenosides do not embody absolute advantage yet in the active anticancer and effectiveness of its wide spectrum.
Summary of the invention
The technical problem to be solved in the present invention is to provide the low polarity rare ginsenoside mixture Rk2/Rh3 of a kind of anticancer effectiveness of height with wide spectrum, the invention provides the purposes of described low polarity rare ginsenoside mixture Rk2/Rh3, invention further provides the composition and use thereof including low polarity rare ginsenoside mixture Rk2/Rh3.
Low polarity rare ginsenoside mixture Rk2/Rh3 of the present invention is by being structured with formula
Low polarity rare ginsenoside monomer Rk2 and there is following structural
Low polarity rare ginsenoside monomer Rh3 mix, Rk2 and Rh3 belongs to isomers in chemical constitution.
The weight ratio of described low polarity ginsenoside monomer Rk2 and low polarity ginsenoside Rh 3 is 1～9:9～1, it is preferred to 1～5:5～1, more preferably 1～3:3～1.We find in an experiment: being combined in drug effect and create potentiation of two kinds of isomerss.
Described low polarity rare ginsenoside mixture Rk2/Rh3, in a purposes, shows the preparation purposes for treating and/or in the medicine of prophylaxis of tumours and/or cancer.
Wherein said tumor and/or cancer are selected from:
Malignant tumor, includes but not limited to bladder cancer, breast carcinoma, colon cancer, renal carcinoma, hepatocarcinoma, pulmonary carcinoma (including small cell lung cancer, nonsmall-cell lung cancer), head and neck cancer, the esophageal carcinoma, carcinoma of gallbladder, ovarian cancer, cancer of pancreas, gastric cancer, cervical cancer, thyroid carcinoma, carcinoma of prostate and skin carcinoma (including squamous cell carcinoma)；
Lymphoid hematopoetic tumor, includes but not limited to leukemia, acute lymphoblastic leukemia, Acute Lymphoblastic Leukemia, B-cell lymphom, T-cell lymphom, Huo Qijin lymphatic cancer, non-Huo Qijin lymphatic cancer, hairy cell lymphom, mantle cell lymphoma, myeloma and Burkett ' sShi lymphatic cancer；
The hematopoetic tumor of bone marrow system, includes but not limited to acute and chronic myelocytic leukemia, myelodysplastic syndrome and promyelocytic leukemia；
The tumor of the interstitial origin cause of formation, includes but not limited to fibrosarcoma and rhabdomyosarcoma；
The tumor of maincenter and peripheral nervous system, includes but not limited to astrocytoma, becomes neurofibroma, glioma and schwannoma；And
Other tumors, include but not limited to melanoma, spermocytoma, teratocarcinoma, osteosarcoma, exophytic pigment neck tumor, thyroid filter capsule cancer and Kaposi's sarcoma.
In another purposes of described low polarity rare ginsenoside mixture Rk2/Rh3, show prepare for immunomodulating, improve microcirculation, improve quality of life health product in purposes.
Present invention also offers a kind of compositions, including described low polarity rare ginsenoside mixture Rk2/Rh3.
Said composition is preferably pharmaceutical preparation, and it comprises treatment and/or prevents described low polarity rare ginsenoside mixture Rk2/Rh3 and optional pharmaceutically acceptable diluent, carrier, excipient, adjuvant or the vehicle of effective dose.
The dosage form of described pharmaceutical preparation is any in peroral dosage form, injection type or Topical application forms.
Described peroral dosage form includes but not limited to tablet, powder, suspension, emulsion, capsule, granule, coated tablet, pill, liquid, spirit, syrup or limonada.
Described injection type includes but not limited to water preparation, suspension or solution.
Described Topical application forms includes but not limited to ointment, solid, suspension, water preparation, spirit, powder, paste, suppository, aerosol, paste, liniment, lotion, enema or Emulsion.
In one purposes of described compositions, show the preparation purposes for treating and/or in the medicine of prophylaxis of tumours and/or cancer.
Wherein said tumor and/or cancer are selected from:
Malignant tumor, includes but not limited to bladder cancer, breast carcinoma, colon cancer, renal carcinoma, hepatocarcinoma, pulmonary carcinoma (including small cell lung cancer, nonsmall-cell lung cancer), head and neck cancer, the esophageal carcinoma, carcinoma of gallbladder, ovarian cancer, cancer of pancreas, gastric cancer, cervical cancer, thyroid carcinoma, carcinoma of prostate and skin carcinoma (including squamous cell carcinoma)；
Lymphoid hematopoetic tumor, includes but not limited to leukemia, acute lymphoblastic leukemia, Acute Lymphoblastic Leukemia, B-cell lymphom, T-cell lymphom, Huo Qijin lymphatic cancer, non-Huo Qijin lymphatic cancer, hairy cell lymphom, mantle cell lymphoma, myeloma and Burkett ' sShi lymphatic cancer；
The hematopoetic tumor of bone marrow system, includes but not limited to acute and chronic myelocytic leukemia, myelodysplastic syndrome and promyelocytic leukemia；
The tumor of the interstitial origin cause of formation, includes but not limited to fibrosarcoma and rhabdomyosarcoma；
The tumor of maincenter and peripheral nervous system, includes but not limited to astrocytoma, becomes neurofibroma, glioma and schwannoma；And
Other tumors, include but not limited to melanoma, spermocytoma, teratocarcinoma, osteosarcoma, exophytic pigment neck tumor, thyroid filter capsule cancer and Kaposi's sarcoma.
Described compositions is health product, and it comprises acceptable carrier in the described low polarity rare ginsenoside mixture Rk2/Rh3 and optional health product treating and/or preventing effective dose.
In another purposes of described compositions, show prepare for immunomodulating and/or improve microcirculation and/or improve quality of life health product in purposes.
The term that the present invention uses has defined below, unless otherwise described:
Term used herein " low polarity ", refers to for general ginsenosides, and Rg3, Rh2, Rk2, Rh3 etc. of content rareness are insoluble in water, are only dissolve in low polar organic solvent.
Term used herein " compositions " means to include comprising each product specifying composition of specified amount and any product directly or indirectly produced from each combination specifying composition of specified amount.Described Topical application forms includes ointment, solid, suspension, water preparation, spirit, powder, paste, suppository, aerosol, paste, liniment, lotion, enema or Emulsion..Aseptically by reactive compound and pharmaceutically acceptable carrier and any required preservative, buffer agent or propellants.Ophthalmic preparation, eye ointment, powder and solution are contemplated within the scope of the present invention.
When for above-mentioned treatment or other treatment, a kind of the compounds of this invention for the treatment of and/or prevention effective dose can be applied in a pure form, or with pharmaceutically acceptable salt, ester or prodrug forms (when there are these forms) application.Or, described compound can be administered with the pharmaceutical composition containing this purpose compound with one or more pharmaceutically acceptable excipient.The compounds of this invention of word " treatment and/or prevention effective dose " refers to the compound of the q.s with the reasonable effect/Hazard ratio treatment obstacle suitable in any therapeutic treatment.It is to be understood that total consumption per day of the compounds of this invention and compositions must be maked decision within the scope of reliable medical judgment by attending physician.Must determining according to many factors for any concrete patient, concrete treatment and/or prevention effective dose level, described factor includes the order of severity of obstacle and this obstacle treated；The activity of the particular compound adopted；The concrete compositions adopted；The age of patient, body weight, general health situation, sex and diet；The administration time of the particular compound adopted, route of administration and excretion rate；The treatment persistent period；With the particular compound combination use adopted or the medicine used simultaneously；And the known similar factor of medical field.Such as, the way of this area is, the dosage of compound, from the level being less than obtaining required therapeutic effect and require, is gradually increased dosage, until obtaining required effect.
The present invention also provides for comprising the pharmaceutical preparation of the compounds of this invention optionally formulated together with the acceptable diluent of one or more non-toxic pharmaceutical, carrier, excipient, adjuvant or vehicle.Described pharmaceutical preparation can become for oral administration with solid or liquid form, supply parental injection or for rectally by particular formulation especially.
The pharmaceutical composition of the present invention can by oral, rectum, parenteral, pond, intravaginal, intraperitoneal, locally (as by powder, ointment or drop), buccal gives the mankind and other mammals, or gives as oral spray or nasal mist.Term used herein " parenteral " refers to include intravenous, intramuscular, intraperitoneal, breastbone interior, the administering mode of subcutaneous and intra-articular injection and transfusion.
In yet another aspect, the present invention provides and comprises present component and the pharmaceutical composition of physiologically tolerable diluent.The present invention includes one or more above-claimed cpds, it is configured to compositions together with one or more nontoxic physiologically tolerable or acceptable diluent, carrier, adjuvant or vehicle (herein they being referred to as diluent), for parental injection, nasal delivery, with solid or liquid form oral administration, rectum or topical etc..
The compositions being suitable for parental injection can include physiologically acceptable sterile, aqueous or non-aqueous liquor, dispersant, suspensoid or Emulsion, and for reconstructing the sterile powders of sterile injectable solution agent or dispersant.Suitable moisture or nonaqueous carrier, diluent, solvent or vehicle example includes water, ethanol, polyhydric alcohol (propylene glycol, Polyethylene Glycol, glycerol etc.), vegetable oil (such as olive oil), injectable organic ester such as ethyl oleate and their suitable mixture.
These compositionss also can contain adjuvant, such as preservative, wetting agent, emulsifying agent and dispersant.By various antibacterial agents and antifungal, for instance parabens, chlorobutanol, phenol, sorbic acid etc., it can be ensured that prevent the effect of microorganism.It is also expected to include isotonic agent, for instance saccharide, sodium chloride etc..By using the material that can postpone to absorb, for instance aluminum monostearate and gelatin, the prolongation that can reach injectable drug form absorbs.
Suspensoid also can contain suspending agent in addition to the active compound, for instance the mixture etc. of ethoxylation i-octadecanol, polyoxyethylene sorbitol and polyoxyethylene sorbitan esters, microcrystalline Cellulose, inclined aluminium hydroxide, bentonite, agar and Tragacanth or these materials.
In some cases, for extending the effect of medicine, it is desirable to the absorption of the subcutaneously or intramuscularly injectable drug of slowing down.This can be realized by the liquid suspension of the crystal of use poorly water-soluble or amorphous substance.So, the infiltration rate of medicine depends on its dissolution velocity, and dissolution velocity can be depending on crystal size and crystal formation.Or, the delay of the medicament forms of parenteral absorb by by this medicine dissolution in or be suspended in oil vehicle and realize.
Injectable depot formulations form can be prepared by the microcapsule matrix of formation medicine in biodegradable polymer such as polylactide-polyglycolide (polylactide-polyglycolide).According to the character of the medicine ratio with polymer and the concrete polymer adopted, drug releasing rate can be controlled by.The example of other biological degradable polymer includes poe class (poly (orthoesters)) and polyanhydrides (poly (anhydrides)).Injectable depot formulations can be prepared in the liposome compatible with bodily tissue or microemulsion also by pharmaceutical pack being embedded in.
Injectable formulation can such as by filtering with bacteria filter or carrying out sterilizing by mixing the biocide of aseptic solid composite form, and described solid composite can be dissolved or dispersed in sterilized water or other sterile injectable medium before use.
Solid dosage forms for oral administration includes capsule, tablet, pill, powder and granule.In this type of solid dosage forms, reactive compound can mix with the pharmaceutically acceptable excipient of at least one inertia or carrier such as sodium citrate or dicalcium phosphate and/or following material: a) filler or extender such as starch, lactose, sucrose, glucose, mannitol and silicic acid；B) binding agent such as carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and Radix Acaciae senegalis；C) wetting agent such as glycerol；D) disintegrating agent such as agar, calcium carbonate, Rhizoma Solani tuber osi or tapioca, alginic acid, some silicate and sodium carbonate；E) solution retarding agents such as paraffin；F) accelerator such as quaternary ammonium compound is absorbed；G) wetting agent such as spermol and glyceryl monostearate；H) adsorbent such as Kaolin and bentonite and i) lubricant such as Pulvis Talci, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulphate and their mixture.When capsule, tablet and pill, described dosage form also can comprise buffer agent.
The solid composite of similar type uses excipients such as lactose and high molecular weight polyethylene glycol etc., it is possible to as the implant in soft capsule and hard capsule.
Tablet, dragee (dragees), capsule, pill can be prepared with the solid dosage forms of granule together with coating and shell material such as enteric coating material and field of medicine preparations other clothing materials known.These solid dosage formss can optionally contain opacifier, and its composition also can make its simply or preferentially at certain position of intestinal optionally with delayed mode release of active ingredients.The example of operable embedding composition includes polymer substance and wax class.If be suitable for, reactive compound also can be made into microencapsulated form with one or more above-mentioned excipient.
Liquid dosage form for oral administration includes pharmaceutically acceptable Emulsion, solution, suspensoid, syrup and elixir.Liquid dosage form is except also can contain inert diluent commonly used in the art containing active ingredient beyond the region of objective existence, such as water or other solvents, the fatty acid ester of solubilizing agent and emulsifying agent such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propylene glycol, 1,3 butylene glycol, dimethylformamide, oils (particularly Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Semen Maydis oil, germ oil, olive oil, Oleum Ricini and Oleum sesami), glycerol, tetrahydrofurfuryl alcohol (tetrahydrofurfurylalcohol), Polyethylene Glycol and sorbitan and their mixture.Orally administered composition also can comprise adjuvant except comprising inert diluent, for instance wetting agent, emulsifying and suspending agent, sweeting agent, correctives and flavouring agent.
Compositions for rectum or vagina administration is preferably suppository.Suppository can be prepared by being mixed with suitable non-irritating excipient or carrier such as cocoa butter, Polyethylene Glycol or suppository wax by the compounds of this invention, they are at room temperature solid, but it is then liquid under body temperature, therefore can melt in rectal cavity or vaginal canal and discharge reactive compound.
The compounds of this invention can also liposomal form administration.As it is known in the art, liposome prepares typically by phospholipid or other lipid materials.Liposome is formed by the single or multiple lift aquation liquid crystal being scattered in water-bearing media.On any nontoxic, physiology that can form liposome, acceptable and metabolizable lipid all can use.The present composition of liposomal form, except containing the compounds of this invention, also can contain stabilizer, preservative, excipient etc..Preferred lipid is phospholipid that is natural and that synthesize and phosphatidylcholine (lecithin), and they can use individually or together.The method forming liposome is well known in the art.
Term used herein " pharmaceutically acceptable prodrug " represents the prodrug of the compounds of this invention, it is suitable for occurring without excessive toxicity, stimulation, anaphylaxis etc. with the mankind and zootic contact tissue within the scope of reliable medical judgment, match with rational effect/Hazard ratio and its intended purpose is effective, also represent the zwitterionic form of the compounds of this invention in the conceived case.The prodrug of the present invention such as can be rapidly converted into the parent compound of above formula in vivo by being hydrolyzed in blood.
The low polarity rare ginsenoside mixture Rk2/Rh3 of the present invention has the anti-tumor activity of suppression human tumor cells (having surveyed tumor cell for 17 kinds) and cell proliferation of human umbilical vein, the experiment proved that because mixture synergism makes its wide spectrum high anti-cancer activity and effectiveness be better than low polarity rare ginsenoside monomer Rg3, Rh2, Rk2 and Rh3, treatment and/or the medicine of prevention various cancers and/or tumor can be made for, and be used for immunomodulating and/or improve microcirculation and/or improve the health product of quality of life, emphasis is applied to the treatment of malignant tumor, have broad application prospects.
Detailed description of the invention
Unless specifically indicated, term used herein has the general sense in art of the present invention.
Below with reference to specific embodiment, the present invention will be described, it is necessary to explanation, and these embodiments are merely illustrative, and are not considered as limiting the invention.Unreceipted concrete technology or condition in embodiment, technology or condition described by the document in this area or carry out according to product description.Agents useful for same or the unreceipted production firm person of instrument, be can pass through city available from conventional products.
Embodiment 1 low polarity rare ginsenoside mixture Rk2/Rh3 and preparation method thereof
Present embodiments providing a kind of low polarity rare ginsenoside mixture Rk2/Rh3, it is by being structured with formula
Low polarity rare ginsenoside monomer Rk2 and there is following structural
Low polarity rare ginsenoside monomer Rh3 mix with the ratio of weight ratio 1:3.
Concrete preparation method is as follows:
Weigh 2.59mg low polarity rare ginsenoside monomer Rk2 (to buy from Yuan Ye bio tech ltd, Shanghai, production code member is YY91303) and 7.76mg low polarity rare ginsenoside monomer Rh3 (from Yuan Ye bio tech ltd, Shanghai buy, production code member is YY90242), mix homogeneously, namely obtains low polarity rare ginsenoside mixture Rk2/Rh3.
Embodiment 2 low polarity rare ginsenoside mixture Rk2/Rh3 and preparation method thereof
The present embodiment and embodiment 1 are distinctive in that, it is the low polarity rare ginsenoside monomer Rh3 ratio mix homogeneously with weight ratio 5:1 of low polarity rare ginsenoside monomer Rk2 and the 1.73mg weighing 8.63mg, obtains low polarity rare ginsenoside mixture Rk2/Rh3.
Embodiment 3 low polarity rare ginsenoside mixture Rk2/Rh3 and preparation method thereof
The present embodiment and embodiment 1 are distinctive in that, be the low polarity rare ginsenoside monomer Rh3 of low polarity rare ginsenoside monomer Rk2 and the 9.32mg weighing 1.04mg with weight ratio 1:9 mix homogeneously, obtain low polarity rare ginsenoside mixture Rk2/Rh3.
The application of embodiment 4 low polarity rare ginsenoside mixture Rk2/Rh3
Experiment classification:
The low polarity rare ginsenoside mixture Rk2/Rh3 vitro inhibition multiclass tumor cell proliferation experiment of different mixing proportion
Laboratory sample:
Testing drug: the low polarity rare ginsenoside mixture Rk2/Rh3 that embodiment 1,2,3 prepares.
Control drug: low polarity rare ginsenoside monomer Rg3 (buys from Yuan Ye bio tech ltd, Shanghai, commodity article No. is B21059)；Low polarity rare ginsenoside monomer Rh2 (buys from Yuan Ye bio tech ltd, Shanghai, YY91267)；Low polarity rare ginsenoside monomer Rk2 (buys from Yuan Ye bio tech ltd, Shanghai, production code member is YY91303)；Low polarity rare ginsenoside monomer Rh3 (buys from Yuan Ye bio tech ltd, Shanghai, production code member is YY90242).
Experimental procedure:
With 18 kinds of cell lines (including 17 kinds of tumor cell lines and a kind of Human umbilical vein endothelial cells system) for experiment cell line, take the logarithm trophophase cell (3x104/ mL to 2.5x105/ mL), it is seeded in 96 orifice plates with every hole 100 μ L, each cell line is with 96 orifice plates；Then 7 logarithmic decrease concentration (each concentration sets two multiple holes) are taken with high concentration 150 μMs to low concentration 2 μMs, be separately added into testing drug solution and control drug solution (testing drug solution or control drug solution preparation: be respectively adopted testing drug or control drug be dissolved in 0.5% DMSO solution) 500nL, after after tested/control drug solution effects 72 hours, use (Promega；Cat.#G7573) luminescent cell viability examination method obtains each concentration of every kind of medicine in each cell line to this is the Proliferation Ability percentage rate of cell, and draws dose-effect relationship figure, finally according to curve measuring and calculating IC in figure50The highest inhibition percentage (Emax), as shown in Table 1 and Table 2.
Table 1: the low polarity rare ginsenoside mixture Rk2/Rh3 and control drug Rg3 of different mixing proportion, Rh2, Rk2 and Rh3 suppress cell-proliferation activity testing result
Table 2: the low polarity rare ginsenoside mixture Rk2/Rh3 and control drug Rg3 of different mixing proportion, Rh2, Rk2 and Rh3 suppress cell proliferation validation checking result
Note: the implication that the term that table 1, table 2 and context occur is expressed is as follows:
It is 1:3 that Rk2/Rh3 (1:3) represents the weight ratio of Rk2 and the Rh3 in low polarity rare ginsenoside mixture Rk2/Rh3, the low polarity rare ginsenoside mixture Rk2/Rh3 that namely embodiment 1 obtains.
It is 5:1 that Rk2/Rh3 (5:1) represents the weight ratio of Rk2 and the Rh3 in low polarity rare ginsenoside mixture Rk2/Rh3, the low polarity rare ginsenoside mixture Rk2/Rh3 that namely embodiment 2 obtains.
It is 1:9 that Rk2/Rh3 (1:9) represents the weight ratio of Rk2 and the Rh3 in low polarity rare ginsenoside mixture Rk2/Rh3, the low polarity rare ginsenoside mixture Rk2/Rh3 that namely embodiment 3 obtains.
SPSSStatistics software (supplier: IBMcorporation, software version: XLfit21) is used to provide statistical analysis.With whether the difference between cell mean every in repeated measure analysis of variance (RepeatedmeasureANOVA) detection table 1 to table 2 presents statistically significant (P < 0.05 or P < 0.01), then seek every class mean reason of discrepancies further with BonferroniTtests post hoc test.
Analyze result:
(1) table 1 shows, as the low polarity rare ginsenoside mixture Rk2/Rh3 of the different mixing proportion average IC in 18 cell line50Respectively with average IC in 18 cell line of control drug low polarity rare ginsenoside monomer Rg3, Rh2, Rk2 and Rh350Time relatively, difference between low polarity rare ginsenoside mixture Rk2/Rh3 (5:1) and all four control drug low polarity rare ginsenoside monomer Rg3, Rh2, Rk2 and Rh3 all presents statistically significant (P < 0.05 is P < 0.01 simultaneously), and also has notable difference (P < 0.05 is P < 0.01 simultaneously) between itself and low polarity rare ginsenoside mixture Rk2/Rh3 (1:3)；And low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) all has notable difference (P < 0.05 is P < 0.01 simultaneously) compared with the mixture of all four control drug and other two kinds of ratios (5:1 and 1:9)；Finally, the difference of low polarity rare ginsenoside mixture Rk2/Rh3 (1:9) and control drug low polarity rare ginsenoside monomer Rg3, Rh2, Rh3 and low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) presents statistically significant (Rk2/Rh3 (1:9) is than P < 0.05 P < 0.01 simultaneously of Rg3, Rh2, Rk2/Rh3 (1:3)；Rk2/Rh3 (1:9) is than the P < 0.05 of Rh3).Additionally, between control drug except the combination of Rk2 and Rh3 without significant difference (P>0.05) except, all the other compound modes all have notable difference (P<0.05 P<0.01) simultaneously.
(2) table 2 shows, when the low polarity rare ginsenoside mixture Rk2/Rh3 of the different mixing proportion the highest average inhibition percentage in 18 cell line compares with control drug low polarity rare ginsenoside monomer Rg3, Rh2, Rk2 and Rh3 the highest average inhibition percentage in 18 cell line respectively, the difference between low polarity rare ginsenoside mixture Rk2/Rh3 (5:1) and control drug low polarity rare ginsenoside monomer Rg3, Rk2 presents statistically significant, and (Rk2/Rh3 (5:1) is than P < 0.05 P < 0.01 simultaneously of Rg3；Rk2/Rh3 (5:1) is than the P < 0.05 of Rk2)；And low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) is except no significant difference between low polarity rare ginsenoside mixture Rk2/Rh3 (5:1) (P>0.05), with all the other four kinds of control drug, and the highest average inhibition percentage between low polarity rare ginsenoside mixture Rk2/Rh3 (1:9) all has notable difference, and (Rk2/Rh3 (1:3) is than P<the 0.05 simultaneously P<0.01 of Rg3；Rk2/Rh3 (1:3) is than the P < 0.05 of Rh2, Rk2, Rh3, Rk2/Rh3 (1:9))；Finally, the difference of low polarity rare ginsenoside mixture Rk2/Rh3 (1:9) and control drug low polarity rare ginsenoside monomer Rg3 and low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) also presents statistically significant (Rk2/Rh3 (1:9) is than P < 0.05 P < 0.01 simultaneously of Rg3；Rk2/Rh3 (1:9) is than the P < 0.05 of Rk2/Rh3 (1:3)).Additionally, control drug low polarity rare ginsenoside monomer Rg3 and its excess-three kind control drug all have notable difference (P < 0.05 is P < 0.01 simultaneously) when contrasting respectively；Without significant difference (P > 0.05) between its excess-three kind control drug.
Conclusion:
(1) the low polarity rare ginsenoside mixture Rk2/Rh3 of different proportion suppresses cell-proliferation activity and effectiveness monomer Rk2, Rh3 higher than similar low polarity rare ginsenoside monomer Rg3, Rh2 and this low polarity rare ginsenoside mixture all in various degree in all 18 kinds of surveyed cell lines, it was shown that two kinds of isomerss low polarity rare ginsenoside monomer Rk2, Rh3 are combined in drug effect and create potentiation.
(2) in all tested cell lines, when Rk2 and the Rh3 in low polarity rare ginsenoside mixture Rk2/Rh3 mixes with the ratio that weight ratio is 1:3, its activity is higher than other two kinds of mixed proportions (5:1 and 1:9), its effectiveness is higher than Rk2 and the Rh3 low polarity rare ginsenoside mixture Rk2/Rh3 mixed with the ratio that weight ratio is 1:9, therefore the ratio that weight ratio is 1:3 of Rk2 and the Rh3 in low polarity rare ginsenoside mixture Rk2/Rh3 is the optimal proportion of Rk2 and the Rh3 mixing in the low polarity rare ginsenoside mixture Rk2/Rh3 surveyed at present.
(3) in all tested cell lines, low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) has the highest suppression cell-proliferation activity (IC in fibrosarcoma cell system50=10.41 μMs)；Suppressing the cell line that cell-proliferation activity comes next is Human umbilical vein endothelial cells (IC50=13.78 μMs).
(4) low polarity rare ginsenoside mixture Rk2/Rh3 (1:3) is to the highest inhibition percentage (effectiveness) of all tested cell lines all closely 100%, it means that it has high anticancer effectiveness widely.And a kind of cell line is only had the suppression ratio of nearly 100% by similar control drug low polarity rare ginsenoside monomer Rg3；Though the effectiveness of monomer Rk2, Rh3 of similar control drug low polarity rare ginsenoside monomer Rh2 and this low polarity rare ginsenoside mixture is apparently higher than control drug low polarity rare ginsenoside monomer Rg3, but is all still below the effectiveness of low polarity rare ginsenoside mixture Rk2/Rh3 (1:3).
Claims (13)
1. one kind low polarity rare ginsenoside mixture, it is characterised in that it is mixed by low polarity rare ginsenoside monomer Rk2 and low polarity rare ginsenoside monomer Rh3.
2. low polarity rare ginsenoside mixture as claimed in claim 1, it is characterised in that described low polarity rare ginsenoside monomer Rk2 is structured with formula:
Described low polarity rare ginsenoside monomer Rh3 is structured with formula:
3. low polarity rare ginsenoside mixture according to claim 2, it is characterised in that the weight ratio of described low polarity rare ginsenoside monomer Rk2 and low polarity rare ginsenoside monomer Rh3 is 1:9～9:1.
4. low polarity rare ginsenoside mixture according to claim 3, it is characterised in that the weight ratio of described low polarity rare ginsenoside monomer Rk2 and low polarity rare ginsenoside monomer Rh3 is 1:5～5:1.
5. low polarity rare ginsenoside mixture according to claim 4, it is characterised in that the weight ratio of described low polarity rare ginsenoside monomer Rk2 and low polarity rare ginsenoside monomer Rh3 is 1:3～3:1.
6. the low polarity rare ginsenoside mixture according to any one of claim 1-5 is preparing the purposes for treating and/or in the medicine of prophylaxis of tumours and/or cancer.
7. purposes according to claim 6, it is characterized in that, described tumor and/or cancer are the one in malignant tumor, lymphoid hematopoetic tumor, the hematopoetic tumor of bone marrow system, the tumor of the interstitial origin cause of formation, maincenter and the tumor of peripheral nervous system, melanoma, spermocytoma, teratocarcinoma, osteosarcoma, exophytic pigment neck tumor, thyroid filter capsule cancer and Kaposi's sarcoma, wherein
Described malignant tumor is bladder cancer, breast carcinoma, colon cancer, renal carcinoma, hepatocarcinoma, pulmonary carcinoma, head and neck cancer, the esophageal carcinoma, carcinoma of gallbladder, ovarian cancer, cancer of pancreas, gastric cancer, cervical cancer, thyroid carcinoma, carcinoma of prostate or skin carcinoma；
Described lymphoid hematopoetic tumor is leukemia, acute lymphoblastic leukemia, Acute Lymphoblastic Leukemia, B-cell lymphom, T-cell lymphom, Huo Qijin lymphatic cancer, non-Huo Qijin lymphatic cancer, hairy cell lymphom, mantle cell lymphoma, myeloma or Burkett ' sShi lymphatic cancer；
The hematopoetic tumor of described bone marrow system is acute and chronic myelocytic leukemia, myelodysplastic syndrome or promyelocytic leukemia；
The tumor of the described interstitial origin cause of formation is fibrosarcoma or rhabdomyosarcoma；
Described maincenter is astrocytoma with the tumor of peripheral nervous system, becomes neurofibroma, glioma or schwannoma.
8. the low polarity rare ginsenoside mixture according to any one of claim 1-5 is used for immunomodulating in preparation, improves microcirculation and/or improves the purposes in the health product of quality of life.
9. a compositions, it is characterised in that include low polarity rare ginsenoside mixture according to any one of claim 1-5.
10. compositions according to claim 9, it is characterized in that, described compositions is pharmaceutical preparation, described pharmaceutical preparation comprises the low polarity rare ginsenoside mixture as according to any one of claim 1-5 and pharmaceutically acceptable diluent, carrier, excipient, adjuvant or the vehicle for the treatment of and/or prevention effective dose
The dosage form of described pharmaceutical preparation is peroral dosage form, injection type or Topical application forms；
Described peroral dosage form is tablet, powder, suspension, emulsion, capsule, granule, coated tablet, pill, liquid, spirit, syrup or limonada；
Described injection type includes water preparation, suspension or solution；
Described Topical application forms includes ointment, solid, suspension, water preparation, spirit, powder, paste, suppository, aerosol, paste, liniment, lotion, enema or Emulsion.
11. the compositions according to claim 9 or 10 is preparing the purposes for treating and/or in the medicine of prophylaxis of tumours and/or cancer；
Optional, described tumor and/or cancer are selected from:
Malignant tumor, including bladder cancer, breast carcinoma, colon cancer, renal carcinoma, hepatocarcinoma, pulmonary carcinoma, head and neck cancer, the esophageal carcinoma, carcinoma of gallbladder, ovarian cancer, cancer of pancreas, gastric cancer, cervical cancer, thyroid carcinoma, carcinoma of prostate and skin carcinoma；
Lymphoid hematopoetic tumor, including leukemia, acute lymphoblastic leukemia, Acute Lymphoblastic Leukemia, B-cell lymphom, T-cell lymphom, Huo Qijin lymphatic cancer, non-Huo Qijin lymphatic cancer, hairy cell lymphom, mantle cell lymphoma, myeloma and Burkett ' sShi lymphatic cancer；
The hematopoetic tumor of bone marrow system, including acute and chronic myelocytic leukemia, myelodysplastic syndrome and promyelocytic leukemia；
The tumor of the interstitial origin cause of formation, including fibrosarcoma and rhabdomyosarcoma；
The tumor of maincenter and peripheral nervous system, including astrocytoma, becomes neurofibroma, glioma and schwannoma；And
Other tumors, including melanoma, spermocytoma, teratocarcinoma, osteosarcoma, exophytic pigment neck tumor, thyroid filter capsule cancer and Kaposi's sarcoma.
12. the compositions according to claim 9, it is characterized in that, said composition is health product, its low polarity rare ginsenoside mixture as according to any one of claim 1-5 comprising treatment and/or prevention effective dose and acceptable carrier in optional health product.
13. the compositions according to claim 9 or 12 preparation for immunomodulating and/or improve microcirculation and/or improve quality of life health product in purposes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610223115.6A CN105769891B (en) | 2016-04-12 | 2016-04-12 | Low polarity rare ginsenoside mixture and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610223115.6A CN105769891B (en) | 2016-04-12 | 2016-04-12 | Low polarity rare ginsenoside mixture and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105769891A true CN105769891A (en) | 2016-07-20 |
| CN105769891B CN105769891B (en) | 2018-08-03 |
Family
ID=56395177
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610223115.6A Active CN105769891B (en) | 2016-04-12 | 2016-04-12 | Low polarity rare ginsenoside mixture and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105769891B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727638A (en) * | 2016-12-28 | 2017-05-31 | 吉林大学 | Application of the ginsenoside as heparanase inhibitors in anti-tumor medicine is prepared |
| CN107337704A (en) * | 2017-06-15 | 2017-11-10 | 吉林大学 | A kind of rare ginsenoside Rk2 and Rh3 separation method |
| CN108245525A (en) * | 2016-12-28 | 2018-07-06 | 吉林大学 | Ginsenoside inhibits application of the antagonist of albumen -2 in cancer in digestive system medicine is prepared as Protein Phosphatase 2A |
| CN108578702A (en) * | 2018-05-24 | 2018-09-28 | 深圳以诺生物制药有限公司 | A kind of mixture of rare ginsenoside and its application |
| CN109432150A (en) * | 2018-12-27 | 2019-03-08 | 吉林明心堂生物科技有限公司 | A kind of processing method of ginseng tablet |
| CN110237081A (en) * | 2018-03-08 | 2019-09-17 | 深圳以诺生物制药有限公司 | Low polarity rare ginsenoside mixture Δ (20-21) PPD/ Δ (20-22) PPD and application thereof |
| CN112236156A (en) * | 2018-05-25 | 2021-01-15 | 绿十字生命健康有限公司 | Composition for promoting muscle differentiation comprising processed ginseng extract |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030190378A1 (en) * | 2002-04-08 | 2003-10-09 | Ginseng Science Inc. | Extract of processed Panax genus plant, the preparation method thereof, and compositions containing the same |
| CN1465694A (en) * | 2002-06-20 | 2004-01-07 | 中国科学院大连化学物理研究所 | Aspergillus niger and method for preparing rare low polarity ginsenoside by alcoholysis of ginsenoside using same |
| CN101695513A (en) * | 2009-10-28 | 2010-04-21 | 上海永神生物科技有限公司 | Composition with anti-tumor effect and application thereof |
| CN102352402A (en) * | 2011-07-29 | 2012-02-15 | 金凤燮 | Method for preparing red ginseng saponins Rg3 group and Rh2 group mixed saponins |
| CN102973623A (en) * | 2012-12-20 | 2013-03-20 | 刘淑莹 | Separation method of ginseng rare saponins in ginseng fibrils |
-
2016
- 2016-04-12 CN CN201610223115.6A patent/CN105769891B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030190378A1 (en) * | 2002-04-08 | 2003-10-09 | Ginseng Science Inc. | Extract of processed Panax genus plant, the preparation method thereof, and compositions containing the same |
| CN1465694A (en) * | 2002-06-20 | 2004-01-07 | 中国科学院大连化学物理研究所 | Aspergillus niger and method for preparing rare low polarity ginsenoside by alcoholysis of ginsenoside using same |
| CN101695513A (en) * | 2009-10-28 | 2010-04-21 | 上海永神生物科技有限公司 | Composition with anti-tumor effect and application thereof |
| CN102352402A (en) * | 2011-07-29 | 2012-02-15 | 金凤燮 | Method for preparing red ginseng saponins Rg3 group and Rh2 group mixed saponins |
| CN102973623A (en) * | 2012-12-20 | 2013-03-20 | 刘淑莹 | Separation method of ginseng rare saponins in ginseng fibrils |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727638A (en) * | 2016-12-28 | 2017-05-31 | 吉林大学 | Application of the ginsenoside as heparanase inhibitors in anti-tumor medicine is prepared |
| CN108245525A (en) * | 2016-12-28 | 2018-07-06 | 吉林大学 | Ginsenoside inhibits application of the antagonist of albumen -2 in cancer in digestive system medicine is prepared as Protein Phosphatase 2A |
| CN107337704A (en) * | 2017-06-15 | 2017-11-10 | 吉林大学 | A kind of rare ginsenoside Rk2 and Rh3 separation method |
| CN107337704B (en) * | 2017-06-15 | 2019-05-31 | 吉林大学 | A kind of rare ginsenoside Rk2And Rh3Separation method |
| CN110237081A (en) * | 2018-03-08 | 2019-09-17 | 深圳以诺生物制药有限公司 | Low polarity rare ginsenoside mixture Δ (20-21) PPD/ Δ (20-22) PPD and application thereof |
| CN108578702A (en) * | 2018-05-24 | 2018-09-28 | 深圳以诺生物制药有限公司 | A kind of mixture of rare ginsenoside and its application |
| CN108578702B (en) * | 2018-05-24 | 2022-11-29 | 深圳以诺生物制药有限公司 | Mixture of rare ginsenoside and application thereof |
| CN112236156A (en) * | 2018-05-25 | 2021-01-15 | 绿十字生命健康有限公司 | Composition for promoting muscle differentiation comprising processed ginseng extract |
| CN109432150A (en) * | 2018-12-27 | 2019-03-08 | 吉林明心堂生物科技有限公司 | A kind of processing method of ginseng tablet |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105769891B (en) | 2018-08-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105769891A (en) | Low-polarity rare ginsenoside mixture and application thereof | |
| CN102302737B (en) | Traditional Chinese medicine composition for treating gastric cancer | |
| CN101495108A (en) | Composition for the treatment of resistant cancers comprising oridonin | |
| CN101780227B (en) | Traditional Chinese medicine composition for treating acute stroke and preparation method thereof | |
| CN102526427B (en) | Traditional Chinese medicinal composition for treating gastrointestinal diseases and quality inspection method | |
| CN101152165A (en) | Antineoplastic isoliquirtigenin tablet | |
| CN106668041A (en) | Application of rhizoma paridis saponin VI to preparation of anti-lung cancer drugs | |
| CN106083972B (en) | A kind of momordica grosvenori alcohol derivatives monomer | |
| CN106535939A (en) | Compositions comprising melatonin and flavonoids for use in the treatment of tumours resistant to chemotherapy | |
| CN101773532B (en) | Carpesium abrotanoides total terpene lactones extract | |
| CN103877508A (en) | Traditional Chinese medicine composition for treating metrocarcinoma | |
| CN105963307B (en) | A kind of purposes of momordica grosvenori alcohol derivatives monomer and combinations thereof | |
| CN106188205B (en) | A kind of purposes of momordica grosvenori alcohol derivatives monomer and combinations thereof | |
| CN107137416B (en) | A kind of pharmaceutical composition preventing and treating non-small cell lung cancer | |
| CN106163515A (en) | Anticancer and agents for relieving side effects | |
| CN102858359B (en) | Medicinal composition comprising alcohol-soluble and water-insoluble licorice extract, pharmaceutical preparation, pharmaceutical application, therapeutic method, and preparative method thereof | |
| CN100482266C (en) | Medical composite prepared by sarcandra and oldenlandia | |
| CN109731019B (en) | A composition with chemotherapy synergistic effect comprises components, preparation and application | |
| CN106668042A (en) | Application of Chonglou saponin VII to preparation of anti-lung-cancer medicament | |
| CN101259180B (en) | Shenshe composition and preparation thereof | |
| CN104688748A (en) | Pharmaceutical composition containing ursolic acid and cyclophosphamide | |
| CN105267793B (en) | A kind of new application of Chinese medicine composition | |
| CN104491721A (en) | Traditional Chinese medicine for treating spleen and kidney yang deficiency type cervical cancer and preparation method thereof | |
| CN100584352C (en) | Fructus Schisandrae Chinensis and extract thereof the purposes in preparation treatment tumor multi-medicine drug-resistant medicine | |
| CN101112504A (en) | Chinese medicine for curing cancer and the method for preparing the oral liquid thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |