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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
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7016—Disaccharides, e.g. lactose, lactulose
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
  • A61K36/258—Panax (ginseng)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/40—Cyclodextrins; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
  • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
  • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/08—Solutions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/04—Centrally acting analgesics, e.g. opioids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/02—Immunomodulators
  • A61P37/04—Immunostimulants
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/50—Improvements relating to the production of bulk chemicals
  • Y02P20/582—Recycling of unreacted starting or intermediate materials

Definitions

• the invention relates to a ginsenoside pharmaceutical composition and a preparation method thereof.
• Ginsenoside Rg3 is a tetracyclic triterpenoid saponin compound present in ginseng, having a molecular weight of 784. 13, which is further optically 20 (R) - ginsenoside Rg3 and 20 (s) - ginsenoside Rg3
• the isomer form exists, in which 20 (R)-ginsenoside Rg3 is chemically stable and insoluble in water, while 20 (s)-ginsenoside Rg3 is chemically unstable and soluble in water.
• Their structural formulas are:
• An object of the present invention is to provide a 20(R)-ginsenoside Rg3 pharmaceutical composition and preparation which is low in cost and easily absorbed by the human body, and a preparation method thereof and a medical use thereof.
• the main raw material (abbreviated as raw material) of the present invention is 2000-ginsenoside Rg3.
• the auxiliary materials (abbreviated as auxiliary materials) of the present invention are A and B, and the types A are deoxycholic acid (sodium), sodium decyl sulfonate (sodium sulfonate) and arginine; and the B is cyclodextrin, which includes : 1 cyclodextrin and its derivatives, such as polymerized cyclodextrin nanoparticles, polymerized cyclodextrin, branched cyclodextrin, 2 ⁇ -cyclodextrin and its derivatives, such as ⁇ -cyclodextrin, 2,6 - dimethyl- ⁇ -cyclodextrin, glucosyl- ⁇ -cyclodextrin, nano-based- ⁇ -cyclodextrin, sulfobutyl ether ⁇ -cyclodextrin,
• the weight of the raw materials and auxiliary materials of the present invention is as follows: 20(R)-ginsenoside Rg3: excipient A or B125 II 1: 1-300, 20 (R) - ginsenoside Rg3: excipient B34 II 1: 100-400.
• the clear liquid obtained by the above step (3) is in a vacuum degree 0. 01 ⁇ 0. 08MPa, temperature 80 ⁇ 100°C, recover the solvent under reduced pressure to 2/3 ⁇ near-dry volume of the original volume, add water to the original volume, dissolve and reduce the solvent to near dryness, then repeat the above operation. Then, finally add water for injection or purified water to dissolve, the aqueous solution is 20 (R) - ginsenoside Rg3 pharmaceutical composition solution, wherein 20 (R) - ginsenoside 13 ⁇ 43 and 4, B125 two kinds of excipients The composition of the solution containing the raw material 0.
• the powder of 20 (R)-ginsenoside Rg3 water-soluble pharmaceutical composition can be obtained by vacuum, spray or freeze-drying, and the drying method and drying conditions are as follows:
• Oral and external preparations a solution of 20 (R)-ginsenoside R g 3 obtained by reacting A and B excipients with a raw material, and drying to form a water-soluble ginsenoside Rg3 solid powder, and then with pharmacy
• the acceptable carrier can be formulated into various preparations by preparation process: such as granules, tablets (plain tablets, dispersible tablets, sustained release tablets, controlled release tablets, etc.), soft (hard) capsules, oral liquid, external use. Agent (patch, ointment, drops, aerosol).
• the solution of the solution is as follows: 1) Injectable activated carbon is evenly mixed. After incubating at 80 ° C for 30 minutes, the heat source was filtered through a 0.45 ⁇ m filter, and the solution was prepared by filtration through a 0.22 ⁇ m microporous membrane filter, or frozen before drying. Dry powder injection or sterile for injection Powder. 2) The solvent is recovered under reduced pressure and dried (vacuum, spray or freeze-dried) to form a stable, water-soluble ginsenoside Rg3 solid powder, which is reconstituted and then made into a lyophilized powder injection or a sterile powder for injection.
• the above 20 (R)-ginsenoside Rg3 medicinal solid and liquid composition and the pharmaceutical preparation thereof have the advantages of inhibiting tumor growth and metastasis, combining with radiotherapy and chemotherapy, increasing efficacy and attenuating, improving immune function, anti-fatigue, improving memory, and external use.
• the present invention has the following advantages over the prior art:
• the 20(R)-ginseng glucoside Rg3 composition solution prepared by the invention can be dried to obtain a powder completely dissolved in water and containing no residual organic solvent, thereby being able to meet the quality of the injection of the Pharmacopoeia of the People's Republic of China.
• the required freeze-dried powder injection can also be prepared into a variety of oral and topical pharmaceutical preparations.
• the 20 (R)-ginsenoside Rg3 composition prepared by the invention has a significantly higher bioavailability than the existing oral preparation (trade name: Shenyi capsule): the former can enter the animal 100% by injection. In the human blood, the absolute bioavailability is 100%, which is 20-50 times higher than the existing oral preparations; the latter also increases the bioavailability by more than 10 times compared with the existing oral preparations.
• the 20(R)-ginsenoside Rg3 prepared by the invention can form a composition solution with 100% of the auxiliary material, and can be dried to prepare a lyophilized powder injection, so that the utilization rate of 20 (R)-ginsenoside Rg3 raw material reaches 100%.
• the cost is significantly lower than the cost of the clathrate freeze-dried powder injection of the ingredient.
• the 20 (R)-ginsenoside Rg3 composition prepared by the invention can be used as an oral pharmaceutical preparation, and the biological utilization can be reduced by half, which can achieve the same or better therapeutic effect as the existing capsule, and the medical expenses of the tumor patient can be obtained. Significantly reduced.
• the 20 (R)-ginsenoside Rg3 composition injection prepared by the invention has a high concentration in the liver and stomach and intestine wall of rats and dogs, and has a good therapeutic effect on digestive tract tumors and metastasis.
• Figure 1 is a high performance liquid chromatographic chromatogram of 20 (R)-ginsenoside Rg3 standard.
• Figure 2 is a high performance liquid chromatogram of 20 (R)-ginsenoside 3 and sodium deoxycholate.
• Figure 3 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 standard.
• Figure 4 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 and sodium lauryl sulfate composition.
• Figure 5 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 standard.
• Figure 6 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 and 2,3,6-trihydroxypropyl- ⁇ -cyclodextrin compositions.
• Figure 7 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 standard.
• Figure 8 is a high performance liquid chromatogram of 20 (R)-ginsenoside Rg3 and ⁇ -cyclodextrin compositions.
• Figure 9 is a plasma drug concentration time curve after oral administration of 5. 6 g of Rg3 granules in 7 dogs.
• Figure 10 is a plasma drug concentration time curve after oral administration of 3 g of Rg3 Shenyi Capsule in 7 dogs.
• Figure 11 is a plasma drug concentration time curve after oral administration of Rg3 granules and Shenyi capsules in 7 dogs. detailed description
• the near-drying was carried out under reduced pressure on a rotary evaporator at a vacuum of 0.05 MPa and a temperature of 100 ° C. Distilled water was added to the original volume, and the solvent was dissolved and recovered to near dryness, and the above operation was repeated.
• the concentrate was dissolved in 2.5 liters of water for injection, and the obtained aqueous solution was 20 (R) - ginsenoside Rg3 water-soluble intermediate.
• the water-soluble intermediate contains ginsenoside Rg3 of 2 mg/ml as determined by a high performance liquid phase method, as shown in Figures 5 and 6.
• the above operation is repeated once again, and the concentrate is dissolved in 20 liters of water for injection, and the obtained aqueous solution is It is a water-soluble intermediate of 20 (R)-ginsenoside Rg3.
• the water-soluble intermediate contains ginsenoside Rg3 of 0.1 mg/ml, as shown in Figures 7 and 8.
• the temperature reaches 75 ° C, and can obtain 55 kg of water-soluble powder of 100 to 250 ⁇ m; or the above-mentioned dried water-soluble powder is re-dissolved, and then operated according to the freeze-drying method of Example 35, that is, lyophilized powder injection 10000 Branches (5 mg each) will be.
• Example 46 20 (R) - ginsenoside Rg3 composition granules in vivo to improve bioavailability test
• the concentration of the drug is 12 to 20 times higher than that of the 20 (R) ginsenoside Rg3 raw material, thereby indicating that the bioavailability of the Rg3 composition granule in the animal is significantly higher than that of the Rg3 raw material.
• the 20(R)-ginsenoside Rg3 composition granule obtained in Example 37 was orally administered to a Beagle dog, and its bioavailability was measured.
• the biological sample was measured by a liquid chromatography-tandem mass spectrometry using an API 4000 mass spectrometer.
• the plasma drug concentration time curve of 5.6 g ginsenoside Rg3 and ⁇ -cyclodextrin (1:200) pharmaceutical composition (containing Rg3 30 mg) was orally administered to 7 dogs, as shown in Figure 9. Seven dogs were orally administered with 3 ginseng.
• the plasma drug concentration time curve after one capsule (containing Rg3 30 mg, Rg3 10 mg/particle) is shown in Fig. 10.
• the average plasma drug concentration time curve of the two test groups is shown in Fig. 11. After oral administration of the pharmaceutical composition, the plasma drug concentration reached 6.8 ⁇ 1.8 n g /mL at a peak concentration of 2.3 ⁇ 0.9 h, the half-life was 6.0 ⁇ 0.9 h, and the area under the curve (AUCO-t) was 40.0 ⁇ . 15.7 ng*h/mL.
• Test drug ginsenoside Rg3 freeze-dried powder injection; batch number: 20030519, specifications: 5mg / support.
• the preparation method a precise amount of ginseng saponin Rg3 lyophilized powder injection or the corresponding adjuvant to the physiological saline to the desired concentration, the dosage volume of 0. 5ml / mouse.
• mice The source of nude mice was provided by the Experimental Animal Center of the Chinese Academy of Sciences of Shanghai, with the certificate number: SCXK 2003-0003 C 57 BL/6 and Kunming mice were provided by the experimental animal group of the hospital.
• the experimental animal use license number: SYXK (Shanghai ) 2004- 0015.
• mice were 6 weeks old, and the Kunming mice and C 57 BL/6 mice were 18-22 g.
• mice in each group were divided into 6 mice in each group, and 8-10 mice in each group.
• the negative control groups were each two groups.
• Dosage setting The dosage of ginsenoside Rg3 lyophilized powder injection is set to: 1.5mg/kg/d, 0.75 mg/kg/d, 0.375 mg/kg/d.
• Dosing regimen IV administration 2 times a day, human tumor model and cell model of vaccination ivX14bid, mouse tumor inoculation model ivXIObid regimen treatment.
• Test control give the corresponding auxiliary materials with the test group, the dosing regimen is the same as the test group; positive control: cyclophosphamide CTX 30mg/kg, MMC2 mg/kg and 5Fu30mg/kg intraperitoneal or intravenous administration once a day for seven consecutive days .
• Life extension rate Average survival days of the administration group / Average survival days of the control group X 100%
• the second-generation QGY tumor source was obtained under vigorous conditions under vigorous conditions, and prepared into a l-1 ⁇ 10 7 /ml cell suspension by homogenization method 1:6, and the homogenate was filtered through a 100-mesh stainless steel mesh for use.
• Nude mice were routinely sterilized, anesthetized in the mid-abdominal sacral process to open the skin and abdominal cavity, expose the liver, and inject 0.05 ml of cell suspension into the liver parenchyma with an imported 28 ga l / 2 ml syringe, close the abdominal cavity, suture the abdominal cavity and skin layer by layer .
• the nude mice were placed in a laminar flow rack, and the feed, litter, cages, and instruments in contact were used after autoclaving. The next day, according to the experimental design, the survival time of each group of animals was observed within 45 days, compared with the negative control group, and the life extension rate was statistically analyzed.
• Tumor inhibition rate% [(Control group average tumor weight-to-administered group mean tumor weight) I control group average tumor weight] X 100% 5.
• mice 80 C 57 BL / 6 mice 80, from the eye venous plexus of each rat blood, according to conventional slide leukocyte counting, measuring the number of leukocytes in each rat, 7500 ⁇ 300 select leukocytes / mm 3 in mice, randomized, 10 mice per group.
• the other groups were given the chemotherapy drug CTX 100 mg/kg ip X 2 .
• CTX 100 mg/kg ip X 2 .
• the number of white blood cells in each group was measured on the 0th day, and the white blood cell count of each group was measured every three days after the experiment, and the mean and standard deviation of the white blood cells of each group of mice in each phase were calculated until the positive.
• the white blood cells in the control group returned to normal numbers.
• the next day was randomized and administered according to the experimental design.
• the spleen of the mice was taken under aseptic conditions on the next day after the last administration, and a single spleen cell suspension was prepared with a 100 mesh sieve.
• the red blood cells were removed by hypotonicity, and the cell suspension was transferred. into culture flasks, 37 ° C5% C0 2 removal conditions after 1 hour incubation of adherent cells, viable cells were counted and the cell concentration adjusted to 3 X 10 6 cells / ml as effector cells.
• the target cells were cultured in vitro with L929, and cultured for 24 hours, and the cell concentration was adjusted to 1.5 ⁇ 10 5 cells/ml, and the ratio of the target cells was 20.1.
• 96-well culture plates were added to effector cells and target cells, and effector cells and target cell controls were added. After incubation at 37 ° C for 5% C0 2 for 4 hours, MTT staining solution was added, and after 2 hours of incubation, the digestive juice was added. The OD value of each well was measured daily, and the NK cytotoxic activity was calculated according to the formula.
• N cytotoxic activity % ⁇ [target cell control group 0D mean - (experimental group 0D mean - effector cell 0D mean)] / target cell control group 0D mean ⁇ X 100%
• mice in normal Kunming mice Male Kunming mice were randomly divided into groups and administered according to the experimental design. After the last administration, mice in each group were intraperitoneally injected with 0.5% hydrolyzed protein (1.5 ml/mouse), and 24 hours later, intraperitoneally injected with IX 10 6 chicken red blood cell suspension.
• the double antibody sandwich ELISA method was used to coat the mouse IL-2 monoclonal antibody on the ELISA plate.
• the IL-2 in the sample and the standard was combined with the monoclonal antibody, the free component was washed away, and biotinylation was added.
• An immune complex is formed and the free components are washed away. Add the developer, show blue, add stop solution to yellow. The OD value was measured at 450 nm, and the IL-2 concentration was directly proportional to the OD 45 () value, and the IL-2 concentration in the sample was determined by the plotted standard curve.
• Percentage of phagocytosis % (number of macrophages that phagocytose chicken red blood cells in 100 macrophages /100 macrophages)
• X I 00% phagocytic index total number of phagocytic chicken red blood cells in 100 macrophages /100 macrophages
• CTX 10x3 0. 89+0. 29** 56. 52 3. 2+0. 5** 82+8. 4** 2. 8 ⁇ 0. 3** 5FU 25x3 1. 08+0. 34** 41. 30 3. 9 ⁇ 0. 3** 90+13. 0 3. 1+0. 4 MTX 5x3 0. 27+0. 01** 85. 32 1. 6+0. 1** 51+1 0** 1. 8+0. 1** PDD 1x3 1. 09+0. 30** 40. 76 6. 0+0. 2 90+6. 0 3. 1+0. 2
• Control group Corresponding suspension poX lOqd 20. 90 ⁇ 5. 80 0. 34+0. 10
• Test animals 240 Kunming male mice, provided by the Experimental Animal Center of Sichuan University. (Animal Certificate No.: Chuan Shidong Pipe Quality No. 67)
• urea nitrogen and liver glycogen 30 minutes after the last gavage, the mice were placed in a swimming box (water depth 30cm, water temperature 30 ⁇ 0.5°C) for 90 minutes, and the blood of the eye was measured for serum urinary nitrogen. The content of the protein (diacetyl-hydrazine method), the liver was taken to determine the liver glycogen content (anthrone method).
• liver glycogen content in the high-dose group was significantly higher than that in the negative control group (P ⁇ 0.05).
• the serum urea-nitrogen content in the middle and high-dose mice was significantly lower than that in the negative group.
• this test (20 (R) ginsenoside Rg3 composition capsule) has an anti-fatigue effect.
• mice platform and water maze device are made by the College of Pharmacy of Jilin University, contact pressure regulator, manufactured by Zhongchuan Group Shanghai Zhenhua Regulator Factory.
• the mouse labyrinth has a starting zone, a multi-blind zigzag loop and a safety zone (one step).
• a starting zone a multi-blind zigzag loop and a safety zone (one step).
• the mice were returned to the starting area and induced to swim to the safe area.
• Each mouse was trained 10 times a day, each time 25 seconds apart, and arrived in the safe area within 30 seconds for correct response, and continuous training for 4 days. Record the correct number of responses for each group of animals, calculate the correct percentage of response and the average time to reach the safe zone.
• mice 72 healthy qualified mice were selected and weighed and randomly divided into 6 groups, 12 in each group.
• 20 (R) ginsenoside Rg3 composition particle dose component was 2. 16, 6. 48, 12. 96 mg / kg, positive control Yiheng granules 121.
• 65 mg / kg, blank control group and model group were given normal saline 0. 1 ml/10 g, once a day, for 10 consecutive days.
• the blank control group was intraperitoneally injected with the same volume of normal saline, and the model group, the Rg3 composition granule experimental group, and the Yiheng granule positive control group were intraperitoneally injected into the sputum.
• the results are shown in Table 4.
• the correct response rate of the model group mice was significantly lower than that of the normal control group.
• the 20 (R) ginsenoside Rg3 composition particles increased the percentage of correct response in mice dose-dependently from the second day of training, and the spatial discrimination of mice induced by scopolamine Obstacles have a significant improvement.
• mice 30 rats (provided by the Experimental Animal Center of Jilin University School of Pharmacy), weighing 250-300 grams, half male and half female, were randomly divided into three groups.
• the experimental group posted 20 (R) ginsenoside Rg3 combination (1 g dissolved in 1 ml of normal saline), the positive control group was coated with Yunnan Baiyao (1 g of white medicine dissolved in 1 ml of normal saline), and the negative control group was coated with normal saline, 1 Times/day.
• the rats to be tested were fed according to the component cages, awake after wounding for 0.5 hours, and the rats were touched with a disposable plastic rod for 10 hours to observe the two hind limb wounds for 2 hours (stimulation) 12 times)
• the wounds were healed for 3 days and 7 days, and the wound infection rate was recorded. Animals were sacrificed 7 days later to assess changes in body weight of each group of animals.
• the results of the wound were visually observed.
• the ginsenoside Rg3 composition group had dry wounds and no exudation, and the skin contraction was obvious.
• the Yunnan Baiyao group had a small amount of secretions and a slight contraction of the wound edge.
• the saline group had a large amount of wound secretion. The area of the wound is increased, and the wound has a purulent sputum. 7 days after injury, the ginsenoside Rg3 composition group had dry wounds and no infection. The wounds were basically filled with granulation, and the obvious neoplastic epithelium grew.
• the wound area of Yunnan Baiyao group was reduced, a small amount of exudation, only thin layer of granulation, no obvious new life. Epithelial growth; In the saline group, the wound pus 8 oozes more, the wound surface does not shrink significantly, and the ulcer surface is formed.
• the above results indicate that the ginsenoside Rg3 composition group is superior to the Yunnan white medicine and saline control group in the swelling, bacteriostatic and wound healing of the wound.

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• 2006
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• 2007
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