WO2006007758A1 - Traditional chinese medicine composition for treating acute and chronic nasosinusitis and preparation thereof - Google Patents

Traditional chinese medicine composition for treating acute and chronic nasosinusitis and preparation thereof Download PDF

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Publication number
WO2006007758A1
WO2006007758A1 PCT/CN2004/000824 CN2004000824W WO2006007758A1 WO 2006007758 A1 WO2006007758 A1 WO 2006007758A1 CN 2004000824 W CN2004000824 W CN 2004000824W WO 2006007758 A1 WO2006007758 A1 WO 2006007758A1
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weight
parts
chinese medicine
traditional chinese
medicine composition
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PCT/CN2004/000824
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French (fr)
Chinese (zh)
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Zhiquan Zhao
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Zhiquan Zhao
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236Ligusticum (licorice-root)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/17Gnetophyta, e.g. Ephedraceae (Mormon-tea family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534Mentha (mint)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/57Magnoliaceae (Magnolia family)
    • A61K36/575Magnolia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/63Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A61K36/634Forsythia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants

Definitions

  • the present invention relates to a traditional Chinese medicine composition, and more particularly to a traditional Chinese medicine composition for treating acute and chronic nasal apes and a preparation method thereof.
  • Another object of the present invention is to provide a method of preparing the traditional Chinese medicine composition for treating acute and chronic nasal apes.
  • the traditional Chinese medicine composition of the invention is guided by the theory of traditional Chinese medicine, combined with the modern medical knowledge of acute and chronic rhinitis and the latest progress of the treatment of acute and chronic nasal abdomen by Chinese medicine, through clinical observation, screening effective drugs, and developing acute and chronic treatment A new formula for the nose.
  • Xanthium, Xinyishantong is a medicinal herb, white peony, ephedra, peppermint help Xinyi, Xanthium evade exogenous evil, Xuantong lung gas, Lizhi analgesic as a drug, Sakamoto, Astragalus, Forsythia, Wild chrysanthemum, trichosanthin, raw land, salvia, and medlar are adjuvants, and licorice is used to make medicines.
  • Xanthium, sexual Xin, bitter temperature, into the lungs, this medicine is both windy, and can solve the symptoms, hurricane and pain.
  • Xinyi Sexual Xin Wen, into the lungs, stomach, this product hurricane and cold, can rise to the head, the two drugs used to evacuate the evil, Xuantong nose, dampness and pain relief. Supplemented with ephedra and phlegm to promote the lungs, help its all-night force.
  • Mint, light and clear, and sexual ascension help Xinyi Xingzi to evacuate the wind and heat, and the leader.
  • the nose is the lungs, and the lungs are suitable for the nose.
  • the above three herbs are used to help the lungs and evacuate the evil spirits. At the same time, it also directly treats headaches, nasal congestion and sneezing. Astragalus, forsythia, and wild chrysanthemum clear away heat and detoxification, so that the evils of wind and heat can be solved from the surface, and the sputum of headache and headache is treated by Sakamoto. Tianhua powder, Shengdi nourishing yin and moistening, cooling blood and fluid, to the dryness of the sinister hot medicine. Hey, wet the tori. Salvia, blood circulation. All kinds of medicines are combined to strengthen the work of sputum discharge; licorice is used to reconcile various medicines.
  • the traditional Chinese medicine composition of the invention is made of the following raw materials
  • the raw material for preparing the traditional Chinese medicine composition of the present invention further includes the following raw materials: wild chrysanthemum 20-40 parts by weight, top pollen 20-40 parts by weight, rehmannia 30-60 parts by weight
  • the drug substance for preparing the traditional Chinese medicine composition of the present invention further comprises 5-15 parts by weight of licorice, that is:
  • the raw material medicine for preparing the traditional Chinese medicine composition of the present invention is preferably
  • the Xanthium sibiricum in each of the above-mentioned raw material drug compositions is preferably fried.
  • the method of preparing the traditional Chinese medicine composition of the present invention is:
  • the preparation of the traditional Chinese medicine composition of the present invention is carried out in accordance with the formulation of each of the above-mentioned raw material medicinal materials.
  • dosage form such as pills, tablets, granules, oral solutions, capsules, ointments, emulsions, and traditional Chinese medicine films.
  • dosage form is preferably a granule.
  • Conventional excipients used in the preparation of the traditional Chinese medicine composition of the present invention include flavoring agents, dispersing agents, binders, thickeners, lubricants, diluents, disintegrating agents, preservatives and the like.
  • the traditional Chinese medicine composition of the invention has remarkable effects in treating acute and chronic nasal acupoints, has the characteristics of good purulent sputum effect and quick effect, and can act on various links of inflammatory reaction, thereby reducing symptoms of inflammatory reaction and causing inflammation
  • the reaction subsides and has a good anti-inflammatory effect on acute and chronic inflammation; it has different degrees of antibacterial activity against common pathogenic bacteria causing acute and chronic rhinitis and sinusitis; 'For non-specific immune function and specific immune function, Certain promotion.
  • composition of the present invention will be further described in detail below in conjunction with the examples and pharmacodynamic tests.
  • the traditional Chinese medicine composition has swelling of rat ankle caused by carrageenan, increased capillary permeability caused by histamine and serotonin, and leukocyte migration and ratification caused by sodium carboxymethyl cellulose.
  • the subcutaneous cotton granuloma hyperplasia has obvious inhibitory effect. This suggests that the composition acts on multiple parts of the inflammatory response, thereby reducing the symptoms of the inflammatory response and allowing the inflammatory response to resolve. It has good anti-inflammatory effects on acute and chronic inflammation.
  • In vitro bacteriostatic test A total of 106 clinical isolates were selected, among which most strains were resistant to common antibacterial drugs penicillin and streptomycin, and 3 standard strains. The in vitro antibacterial effect of the traditional Chinese medicine composition of the present invention was studied.
  • the drug has different degrees of antibacterial activity against common pathogenic bacteria causing acute and chronic rhinitis and sinusitis, such as Staphylococcus aureus, hemolytic streptococcus, Pseudomonas aeruginosa, Proteus, and Klebsiella.
  • the traditional Chinese medicine composition of the invention has obvious promoting effect on the non-specific immune function-mononuclear macrophage phagocytosis function of mice, and improves the colloidal clearance speed of blood in mice; in the delayed allergic reaction, the traditional Chinese medicine combination of the invention
  • the substance can also increase the degree of swelling of the ear shell after sensitization by DNFB, improve the susceptibility of the normal body to hypersensitivity, and improve its cellular immune function: In the immune organ, the weight of the spleen is increased.
  • humoral immunity hemolysin production in mice with immunocompromised effects induced by cyclophosphamide has a certain effect.
  • the traditional Chinese medicine composition of the present invention has a certain promoting effect on non-specific immune function and specific immune function, including cellular immunity and humoral immunity.
  • In vitro bacteriostatic test of the traditional Chinese medicine composition of the present invention against bud-free anaerobic a total of 24 representative anaerobic bacteria were selected, and the anti-anaerobic activity of the traditional Chinese medicine composition of the present invention was measured, and the nitrous oxide was measured. Azole was used as a positive control.
  • the test results show that the traditional Chinese medicine composition of the present invention has three kinds of sporeless cells. Anaerobic bacteria have a certain inhibitory effect, but its antibacterial activity is much lower than the control drug metronidazole.
  • Prophylactic administration that is, administration 3 days before infection, has a certain protective effect on mice infected with Staphylococcus aureus at a higher dose, and ED 5Q is 14.4 g/Kg. This result is consistent with the results of having anti-S. aureus action in vitro.
  • the sample of the traditional Chinese medicine composition of the present invention was subjected to the following experiment using the clearing paste of Example 10, and the crude drug concentration was 3 g/ml, and the concentrations used below were all expressed as crude drugs.
  • Instrument 72 type spectrophotometer, ordinary optical microscope.
  • Wistar rats weighing 150-190 (173 ⁇ 12) g, male and female, were randomly divided into 5 groups, 10 in each group, respectively, distilled water group, chlorpheniramine group and high, medium and low doses of the samples of the present invention.
  • Group, the drug volume was 10 ml / kg, once a day, for 3 consecutive days.
  • One hour after the last administration the four parts of the back were shaved, respectively, by intradermal injection of 0.1% histamine and 0.1% 5-HT 0.1 ml (two points) to form a hillock, and then immediately injected into the femoral vein 1%.
  • Sapphire blue 4ml/kg.
  • MH M U ller-Hinton
  • MH M U ller-Hinton
  • Streptococcus was inoculated on a chocolate agar plate.
  • strains choose to treat the disease with the drug
  • a total of 109 pathogenic bacteria and some standard strains S. aureus ATCC25925, Escherichia coli ATCC25922, Pseudomonas aeruginosa MCC27853 were isolated from clinical isolates.
  • strains of Staphylococcus aureus There were 21 strains of Staphylococcus aureus, 19 strains of Staphylococcus epidermidis, 3 strains of hemolytic streptococcus, 22 strains of Escherichia coli, 16 strains of Pseudomonas aeruginosa, 15 strains of Proteus, and 13 strains of Klebsiella.
  • the tested strains were identified by the Department of Microbiology, Tongji Medical University and the Laboratory of the Department of Laboratory Medicine, Union Hospital.
  • test bacteria were inoculated separately into the broth and cultured at 37 ° C for 6-8 hours.
  • the sterile cotton swabs were evenly spread on the surface of the agar and cultured at 37 ° C.
  • the size of the inhibition zone was measured after 16-18 h. Judging according to the unified antibiotic drug susceptibility test criteria.
  • test bacteria were inoculated separately into the broth, cultured at 37 ° C for 16-18 h (E. coli and P. aeruginosa culture for 8 h), and then diluted with sterile broth into 1:1000 bacteria solution for use. 2ml of Biyuanjingqing cream with different concentrations (6g/ml, 3g/ml, 1.5g/ml-0.009375 g/ml) was added to 18ml MH medium, shake well and then inverted.
  • the final concentration of the drug in the medium was 0.6g/ml 0.3g/ml 0.15g/ml administrated with the medium, not inoculated).
  • Bacteria) and the test strains were compared to the plate (the medium contained no drug).
  • the experimental bacteria were inoculated with an inoculation loop, and the drug concentration, the bacterial species and the strain number were indicated on the bottom of the plate, and the results were observed after incubating in a 37 °C incubator for 24 hours.
  • MIC is the lowest drug concentration that inhibits bacterial growth.
  • Results The results of the paper-based drug susceptibility test are shown in Table 5. 92% of the clinical pathogens collected in this experiment were sensitive to norfloxacin, all Staphylococcus aureus and 73% of Staphylococcus epidermidis were resistant to penicillin, and 44% of Gram-negative bacilli were resistant to streptomycin.
  • the in vitro antibacterial activity of the traditional Chinese medicine composition of the present invention is shown in Table 6.
  • the traditional Chinese medicine composition of the present invention has different degrees of bacteriostatic action on the test strain, and the MIC 5Q of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Proteus and Klebsiella pneumoniae 0.02812, 0.02344, 0.18, 0.09, 0.206>0.6 g/ml; MIC 90 is 0.0375 0.0625 0.42 0.14 >0.6 >0.6 g/ml, respectively, and the MIC range for hemolytic streptococcus is 0.075-0.6 g/ml.
  • the drug control in this experiment did not show bacterial growth, and the test strains grew well, indicating that the drug itself does not contain live bacteria, and the culture conditions meet the test requirements.
  • the traditional Chinese medicine composition of the present invention is a traditional Chinese medicine compound preparation, and has the functions of clearing away heat and detoxifying.
  • a total of 106 clinical isolates (including most of the strains resistant to the commonly used antibacterial drugs penicillin and streptomycin) and 3 standard strains were selected, and the in vitro antibacterial effect of the traditional Chinese medicine composition of the present invention was tested.
  • the drug has various degrees of bacteriostatic action on common pathogenic bacteria causing acute and chronic rhinitis and sinusitis, such as Staphylococcus aureus, hemolytic streptococcus, Pseudomonas aeruginosa, Proteus, and Klebsiella. Results of paper-based drug susceptibility test of clinical isolates against three antimicrobial agents
  • S number of sensitive strains
  • M number of moderately sensitive strains
  • R %: number of resistant strains (percentage of resistant Zhu).
  • mice of 20_24g male and female, were randomly divided into 5 groups, namely distilled water group, Yunzhi polysaccharide positive control group, high, medium and low dose groups of the present invention, each group was 10ml/kg.
  • Shake well in 2 ml of 0.1% sodium carbonate solution measure the optical density at 680 mm wavelength with a 751 ultraviolet spectrophotometer, and calculate the clearance index K value according to the following formula.
  • K (logOD 2 -logOD 10 )/ (t 10 -t 2 ) OD 2 and OD 1Q represent the optical density of the blood samples measured in 2 and 10 minutes, respectively, and t 10 and t 2 represent the measurement time, after the blood collection is completed, small Rats were sacrificed by cervical dislocation, and the liver and spleen weights were weighed separately. Then, the phagocytic index a value was calculated according to the following formula:
  • the K value and the a value of each group were expressed by XSD, and the F test was performed to compare the significance of each group.
  • mice On the sixth day of administration, 1% DNFB solution ⁇ was evenly spread on both sides of the right auricle for attack, and the left ear was used as a control. After 24 hours of attack, the mice were sacrificed by whitening the neck, and the left and right ear shells were cut out. The ear piece with a diameter of 3 mm was removed with a puncher, and the weight of the two ears was the degree of ear swelling. At the same time, the spleen of each mouse was taken out. Weighed with the thymus, weighing spleen (mg) and thymus weight (mg) per 10 g of mice, respectively:
  • Spleen index spleen weight (mg) / body weight (g) X 10
  • Thymus index thymus weight (mg) / body weight (g) X 10
  • the ear shell swelling degree, spleen index and thymus index were tested by F test, and the differences of each group were judged to be significant.
  • the swelling degree of the ear shell of the Tripterygium wilfordii group was 0.49 ⁇ 0.24, which was significantly lower than that of the distilled water group 1.24 ⁇ 0.47. It is consistent with the results reported in the literature that the Tripterygium wilfordii inhibits the delayed allergic reaction, while the traditional Chinese medicine composition of the present invention is in the middle and the middle.
  • the ear shell swelling degree of the low-dose group and the Yunzhi polysaccharide-administered group were 1.83 ⁇ 0.38, 1.66 + 0.38, 2.51, respectively. Both ⁇ 0.36 and 2.31 ⁇ 0.35 were significantly higher than the distilled water group, and the lower dose group was more effective (see Table 8).
  • Cyclophosphamide is a product of Shanghai Twelve Pharmaceutical Factory. The approval number is: Huwei Medicine Zhunzi (1981) No. 0364 (12).
  • SRBC preservation solution glucose 2.05g, sodium chloride 0. 42g, sodium citrate 0.8g, citric acid 0.05g, distilled water 100ml, dissolved and mixed filter, sterilized under 8 pounds pressure for 10 minutes, at 4 ° C saves the spare.
  • Duchen solution (used for the determination of hemoglobin): sodium hydrogencarbonate 1.0 g, high iron cyanide steel, 0.2 g, potassium cyanide 0.05 g plus distilled water 1000 ml.
  • SRBC Under aseptic conditions, take blood from the jugular vein of healthy adult sheep, shake the blood into a triangular beaker with glass beads for 10 minutes to remove fibrin, add 2 times the amount of preservation solution, put 4 °C refrigerator spare, temporarily washed with physiological saline 3 times, 2000 rpm, 10 minutes, to accumulate red blood cells, and then diluted to the required concentration.
  • the eyeballs were removed from the eyelids of the mice, the serum was separated, the serum was diluted 800 times, and the diluted serum 1 ml, 5% SRBC 0.5 ml, 10% complement lml, and 3 ml of Dud solution were added to the test tube in turn, and shaken. After 10 minutes, the absorbance was recorded at a wavelength of 540 nm, and 5% 0.25 ml of SRBC and 4 ml of turbid liquid were added. The absorbance value was recorded. This value is the value of the luminosity of the half hemolysis of the SRBC used in the experiment. The half of the hemolysis value of the sample is calculated by the following formula.
  • Half of the hemolysis value (HC 5G ) absorbance value of the sample X dilution factor
  • Test drug test drug: The sample clearing paste of the embodiment 10 of the present invention contains 3 g of crude drug per ml. Prepare 5000mg/ml with distilled water, sterilize with steam at 100 ° C for 30 min, and dilute with time. Positive control drug: metronidazole, Wuhan Binhu Pharmaceutical Co., Ltd., batch number 960541, formulated into 320ug/ml.
  • test strains and the test strains are isolates of clinical case specimens in Wuhan, including 20 strains of Bacteroides fragilis and 2 strains of Bacillus gingivalis, a total of 3 strains of 24 strains.
  • the tested strains were identified by the bacteria room of the Department of Microbiology, Tongji Medical University.
  • the standard strain (Bacteroides fragilis 5524) was purchased from Beijing Biopharmaceutical Inspection Institute. All strains were lyophilized at -30 ° C, diluted with sterile physiological saline, inoculated in anaerobic separation medium, anaerobic cultured at 37 ° C for 48 h, and then picked up a single colony to be inoculated into anaerobic basal medium. Analyze culture at 37 ° C for 24 h, adjust the bacterial solution to 10 6 cfo / ml. 3. Medium, anaerobic medium, purchased from Shanghai Medical Institute.
  • Test method agar plate dilution method, 5000 mg/ml of the traditional Chinese medicine composition of the present invention and 320 ug/ml metronidazole 2 ml were separately diluted, and the minimum concentrations were 39 mg/ml and 0.3 ug/ml, respectively.
  • the drug concentration, the bacterial species and the strain number were indicated on the bottom of the plate, and the results were observed after 37 hours of anaerobic conditions.
  • the MIC is the lowest drug concentration that inhibits the growth of bacteria.
  • Drug, test drug The clearing paste of the embodiment 10 of the present invention is a sample, a brown liquid, and contains 3 g of crude drug per ml. Mix with different concentrations (0.3, 0.6, 0.9, 1.2, 1.5 g/ml) in distilled water and mix as needed.
  • Control drug Ciprofloxacin lactate injection (200mg/100ml), produced by Guangzhou Qiaoguang Pharmaceutical Factory, batch number 95091502, formulated into 0.3mg/ml with sterile physiological saline.
  • the bacteria used to infect animals are clinically isolated Staphylococcus aureus, which is identified by the bacteria laboratory of the Department of Clinical Laboratory of Tongji Hospital affiliated to Tongji Medical University.
  • Test animals Kunming mice, weighing 18-22 g, male and female, fasting water supply 18 h before the test.
  • the test animals were provided by the Medical Laboratory Animal Center of Tongji Medical University. 5, test methods, according to animal weight, gender stratification random group, each group of 10, a total of 7 groups, namely distilled water negative control, ciprofloxacin (3mg / kg / time) positive control, 5 groups of different doses of this
  • the traditional Chinese medicine composition group of the invention (3, 6, 9, 12, 15 g/Kg/day).
  • the infected animals were intraperitoneally injected with the prepared bacterial solution, 0.5 ml per mouse.
  • the traditional Chinese medicine composition of the present invention is intragastrically administered once every day before infection and 4 days after infection, and ciprofloxacin is intravenously injected immediately after infection and 6 hours after infection, and the negative control group is given equal volume of distilled water, and the administration capacity is 0.1 ml/10 g.
  • the observation time was 7 days, and the number of deaths of each group of mice was recorded, and ED 5 () of the traditional Chinese medicine composition of the present invention was calculated according to the Bliss method.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • the above fourteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 675ml of water to extract the volatile oil.
  • the distilled aqueous solution and the dregs are collected separately; the other ten herbs are added with water 3800ml to cook for 1. 5 hours, hot filtered
  • the filtered dregs are combined with the above dregs, and then boiled 4500 ml of water for 3 times, each time for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, the pharmacy is added through a conventional procedure. Acceptable excipients are made into capsules.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • the above fourteen flavors, Xinyi, Mint, Sakamoto, wild chrysanthemum four herbs add 1200ml of water to extract volatile oil, the distilled aqueous solution and dregs are separately collected; the other ten herbs add water 5000ml decoction for 2 hours, hot filtered; The above two kinds of dregs are combined, and then boiled with 6000 ml of water twice, each time for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable form is added through a conventional procedure. The agent is made into a soft capsule.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • Xanthium is better for frying.
  • the above eight flavors, Xinyi, Mint, and Sakamoto three kinds of medicines add 400ml of water to extract volatile oil, and the distilled aqueous solution and dregs are collected separately; the other five herbs add water 3000ml to cook for 1.5 hours, hot filtered; The slag is combined, and then decocted with water 3500 ml, once every 0.5 hours, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable excipient is added through a conventional procedure.
  • the auxiliary material is made into a soft capsule.
  • Xanthium is better for frying.
  • the above thirteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 800ml of water to extract volatile oil.
  • the distilled aqueous solution and dregs are collected separately; the other nine herbs are boiled in 4000ml for 2 hours, and hot filtered; The above two kinds of dregs are combined, and then boiled twice with water 4000 ml, one hour each time, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable shape is added through a conventional procedure.
  • the agent is made into a soft capsule.

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Abstract

The invention relates to a Traditional Chinese Medicine composition for treating acute and chronic nasosinusitis and preparation thereof. The Traditional Chinese Medicine composition is made from the starting materials comprising Flos Magnoliae Liliflorae, Fructus Xanthü, Herba Ephedrae, Radix Angelicae Dahuricae, Herba Menthae, Rhizoma ligustici, Fructus Forsythiae and like and is the form of various clinically acceptable dosage forms, such as granule, tablet, solution for oral administration or like. The Traditional Chinese Medicine composition has good benefits in treating acute and chronic nasosinusitis.

Description

一种治疗急慢性鼻渊的中药组合物及其制备方法 发明领域  Traditional Chinese medicine composition for treating acute and chronic nasal aquegia and preparation method thereof
本发明涉及一种中药组合物,尤其涉及用于治疗急、慢性鼻渊的中药组合物及其制 备方法。 背景技术  The present invention relates to a traditional Chinese medicine composition, and more particularly to a traditional Chinese medicine composition for treating acute and chronic nasal apes and a preparation method thereof. Background technique
现代医学认为, 急慢性鼻窦炎的病因主要是人体抵抗力降低,鼻道内和外在的病毒 及细菌乘隙侵入, 造成鼻腔炎症。 急慢性鼻渊是我国常 '见病和多发病, 据文献报道, 各 地鼻病发生率波动在 10.7-44.5%之间, 尤其在南方各地, 气候潮湿, 发病率甚高, 其中 76%是发生在 30岁以下,从 40-50岁间有 6.4%, 50岁以后仅有 1%或 2%,该病病程长, 易反复, 常因伴有头痛、 头晕、 记忆力减退等症状, 给患者带来不利影响。 发明内容  Modern medicine believes that the cause of acute and chronic sinusitis is mainly the reduction of human body's resistance, and the invasion of viruses and bacteria in the nasal passages and external organs, causing nasal inflammation. Acute and chronic nasal abdomen is often seen and frequently afflicted in China. According to the literature, the incidence of nasal diseases varies from 10.7 to 44.5%, especially in the south. The climate is humid and the incidence is very high, 76% of which occur. Under the age of 30, 6.4% from 40-50 years old, only 1% or 2% after 50 years old, the disease is long, easy to repeat, often accompanied by headache, dizziness, memory loss and other symptoms, bring patients with To adversely affect. Summary of the invention
本发明的一个目的在于提供一种新的治疗急慢性鼻渊的中药组合物。  It is an object of the present invention to provide a novel Chinese medicinal composition for the treatment of acute and chronic nasal apes.
本发明的另一个目的在于提供一种制备所述治疗急慢性鼻渊的中药组合物的方法。 本发明的中药组合物是以中医药理论为指导,结合现代医学对于急慢性鼻炎的认识 以及中医药治疗急慢性鼻渊的最新进展, 通过临床观察, 筛选有效药物, 研制而成的治 疗急慢性鼻渊的新配方。本方中苍耳子、辛夷善通鼻窍为君药, 白芷、 麻黄、 薄荷助辛 夷、 苍耳子疏散外邪、 宣通肺气、 利窍止痛为臣药, 蕖本、 黄芩、 连翘、 野菊花、 天花 粉、 生地、 丹参、 茯苓为佐药, 甘草调和诸药为使药。 苍耳子, 性辛、 苦温, 入肺经, 此药既散风通窍, 又能解表、 祛风止痛。 辛夷, 性辛温, 入肺、 胃经, 本品祛风散寒, 能上行头面, 二药合用起到疏散外邪、 宣通鼻窍、 祛湿止痛之功。 辅以麻黄辛散宣肺, 助其通窍之力。 白芷, 性辛温, 入肺、 胃经, 为治疗鼻渊头痛的要药, 又辅君药加强其 祛风宣肺、 通窍止痛的作用。 薄荷, 轻清扬散, 性升浮, 则助辛夷苍耳子疏散风热, 利 头目。鼻为肺窍,肺气宜则鼻窍自通,故辅以上三味药, 以助宣通肺气,疏散外邪之功, 同时, 也对头痛、 鼻塞、 喷嚏等兼证起直接治疗作用。 黄芩、 连翘、 野菊花清热解毒, 使风热之邪得以从表解, 藁本上行头目治疗头痛、 头痛之合并症。天花粉、 生地滋阴润 燥、凉血生津, 以制方中辛热药之燥性。茯苓, 祛湿托里。丹参, 活血化瘀。诸药配合, 加强通窍排脓之功; 甘草调和诸药, 为使药。 本发明的中药组合物由以下原料药材所制成 Another object of the present invention is to provide a method of preparing the traditional Chinese medicine composition for treating acute and chronic nasal apes. The traditional Chinese medicine composition of the invention is guided by the theory of traditional Chinese medicine, combined with the modern medical knowledge of acute and chronic rhinitis and the latest progress of the treatment of acute and chronic nasal abdomen by Chinese medicine, through clinical observation, screening effective drugs, and developing acute and chronic treatment A new formula for the nose. In this party, Xanthium, Xinyishantong is a medicinal herb, white peony, ephedra, peppermint help Xinyi, Xanthium evade exogenous evil, Xuantong lung gas, Lizhi analgesic as a drug, Sakamoto, Astragalus, Forsythia, Wild chrysanthemum, trichosanthin, raw land, salvia, and medlar are adjuvants, and licorice is used to make medicines. Xanthium, Sexual Xin, bitter temperature, into the lungs, this medicine is both windy, and can solve the symptoms, hurricane and pain. Xinyi, Sexual Xin Wen, into the lungs, stomach, this product hurricane and cold, can rise to the head, the two drugs used to evacuate the evil, Xuantong nose, dampness and pain relief. Supplemented with ephedra and phlegm to promote the lungs, help its all-night force. White peony, Sexual Xin Wen, into the lungs, stomach, for the treatment of nasal headache, and auxiliary drugs to strengthen its role in phlegm and blood stasis, Tongqiao analgesic. Mint, light and clear, and sexual ascension, help Xinyi Xingzi to evacuate the wind and heat, and the leader. The nose is the lungs, and the lungs are suitable for the nose. Therefore, the above three herbs are used to help the lungs and evacuate the evil spirits. At the same time, it also directly treats headaches, nasal congestion and sneezing. Astragalus, forsythia, and wild chrysanthemum clear away heat and detoxification, so that the evils of wind and heat can be solved from the surface, and the sputum of headache and headache is treated by Sakamoto. Tianhua powder, Shengdi nourishing yin and moistening, cooling blood and fluid, to the dryness of the sinister hot medicine. Hey, wet the tori. Salvia, blood circulation. All kinds of medicines are combined to strengthen the work of sputum discharge; licorice is used to reconcile various medicines. The traditional Chinese medicine composition of the invention is made of the following raw materials
辛夷 10-30重量份 苍耳子 30-90重量份 麻黄 20-60重量份  Xinyi 10-30 parts by weight Xanthium 30-90 parts by weight Ephedra 20-60 parts by weight
白芷 30-90重量份 薄荷 10-30重量份 藁本 5-15重量份  White 芷 30-90 parts by weight Mint 10-30 parts by weight 藁 5-15 parts by weight
黄芩 20-40重量份 连翘 20-40重量份  Astragalus 20-40 parts by weight Forsythia 20-40 parts by weight
除上述原料药材外, 制备本发明的中药组合物的原料药材还进一步包括下述原料 野菊花 20-40重量份 天花粉 20-40重量份 地黄 30-60重量份  In addition to the above-mentioned raw materials, the raw material for preparing the traditional Chinese medicine composition of the present invention further includes the following raw materials: wild chrysanthemum 20-40 parts by weight, top pollen 20-40 parts by weight, rehmannia 30-60 parts by weight
丹参 20-40重量份 茯苓 40-120重量份  Salvia 20-40 parts by weight 茯苓 40-120 parts by weight
制备本发明的中药组合物的原料药再进一步包括甘草 5-15重量份, 即为:  The drug substance for preparing the traditional Chinese medicine composition of the present invention further comprises 5-15 parts by weight of licorice, that is:
辛夷 10-30重量份 苍耳子 30-90重量份 麻黄 20-60重量份  Xinyi 10-30 parts by weight Xanthium 30-90 parts by weight Ephedra 20-60 parts by weight
白芷 30-90重量份 薄荷 10-30重量份 藁本 5-15重量份  White 芷 30-90 parts by weight Mint 10-30 parts by weight 藁 5-15 parts by weight
黄芩 20-40重量份 连翘 20-40重量份  Astragalus 20-40 parts by weight Forsythia 20-40 parts by weight
天花粉 20-40重量份 地黄 30-60重量份  Trichosanthin 20-40 parts by weight Rehmannia 30-60 parts by weight
茯苓 40-120重量份 甘草 5-15重量份  茯苓 40-120 parts by weight licorice 5-15 parts by weight
制备本发明的中药组合物的原料药材优选为  The raw material medicine for preparing the traditional Chinese medicine composition of the present invention is preferably
辛夷 15-25重量份 苍耳子 50-70重量份 麻黄 30-50重量份  Xinyi 15-25 parts by weight Xanthium 50-70 parts by weight Ephedra 30-50 parts by weight
白正 50-70重量份 薄荷 15-35重量份 藁本 8-18重量份  White 正 50-70 parts by weight Mint 15-35 parts by weight 藁本 8-18 parts by weight
黄芩 30-50重量份 连翘 30-50重量份 野菊花 30-50重量份  Astragalus 30-50 parts by weight Forsythia 30-50 parts by weight Wild chrysanthemum 30-50 parts by weight
天花粉 30-50重量份 地黄 50-70重量份 丹参 30-50重量份  Trichosanthin 30-50 parts by weight Rehmannia 50-70 parts by weight Salvia 30-50 parts by weight
茯苓 70-90重量份 甘草 8-15重量份,  茯苓 70-90 parts by weight licorice 8-15 parts by weight,
最佳为:  The best is:
辛夷 20重量份 苍耳子 60重量份 麻黄 40重量份  Xinyi 20 parts by weight Xanthium 60 parts by weight Ephedra 40 parts by weight
白芷 60重量份 薄荷 20重量份 藁本 10重量份  White peony 60 parts by weight mint 20 parts by weight 藁 10 parts by weight
黄芩 40重量份 连翘 40重量份 野菊花 40重量份  Astragalus 40 parts by weight Forsythia 40 parts by weight Wild chrysanthemum 40 parts by weight
' 天花粉 40重量份 地黄 60重量份 丹参 40重量份  'Tianhua powder 40 parts by weight Rehmannia 60 parts by weight Salvia 40 parts by weight
茯苓 80重量份 甘草 10重量份  茯苓 80 parts by weight Licorice 10 parts by weight
上述各原料药组成中的苍耳子以炒为佳。  The Xanthium sibiricum in each of the above-mentioned raw material drug compositions is preferably fried.
制备本发明的中药组合物的方法为:  The method of preparing the traditional Chinese medicine composition of the present invention is:
按照上述各原料药材的配方进行本发明中药组合物的制备。 在辛夷、 薄荷、 藁本、 野菊花四味药中加入 5- 10倍水(w/v)以提取挥发油, 蒸馏后的水溶液及药渣分别另器 收集; 其余原料药加 5- 15倍水(w/v)煎煮 1-3小时, 趁热过滤, 滤液备用, 过滤后的 药渣与上述药渣合并, 再加 5-15倍水 (w/v)煎煮 1-3次, 每次 0. 5-1. 5小时, 过滤, 合并所有滤液和上述辛夷等蒸馏后的水溶液,浓缩成清膏;然后加入药学上可接受的辅 料, 以常规工艺制成临床上可接受的剂型, 如丸剂、 片剂、 颗粒剂、 口服液、 胶囊剂、 膏剂、 乳剂和中药膜剂等。 其中所述剂型以颗粒剂为较佳。 The preparation of the traditional Chinese medicine composition of the present invention is carried out in accordance with the formulation of each of the above-mentioned raw material medicinal materials. Add 5-10 times water (w/v) to the four herbs of Magnolia, Mint, Sakamoto and Wild Chrysanthemum to extract the volatile oil, and distill the aqueous solution and dregs respectively. Collect the remaining APIs and add 5-15 times water (w/v) for 1-3 hours, filter while hot, drain the filtrate, and mix the filtered slag with the above slag, add 5-15 times water (w /v) decocting 1-3 times, each time 0. 5-1. 5 hours, filtration, combining all the filtrate and the above-mentioned distilled aqueous solution, and concentrating into a clear paste; then adding pharmaceutically acceptable excipients, Conventional processes are used to prepare clinically acceptable dosage forms such as pills, tablets, granules, oral solutions, capsules, ointments, emulsions, and traditional Chinese medicine films. Wherein the dosage form is preferably a granule.
制备本发明的中药组合物所使用的常规辅料包括调味剂、分散剂、粘合剂、增稠剂、 润滑剂、 稀释剂、 崩解剂、 防腐剂等。  Conventional excipients used in the preparation of the traditional Chinese medicine composition of the present invention include flavoring agents, dispersing agents, binders, thickeners, lubricants, diluents, disintegrating agents, preservatives and the like.
本发明的中药组合物在治疗急慢性鼻渊中有显著的效果,具有收脓涕效果好、见效 快的特点, 它可作用于炎症反应的多个环节, 从而减轻炎症反应的症状, 使炎症反应消 退,对急慢性炎症均有良好的抗炎作用;对引起急慢性鼻炎及鼻窦炎的常见致病菌有不 同程度的抑菌作用; '对非特异免疫功能及特异性免疫功能, 都有一定的促进作用。 具体实施方式  The traditional Chinese medicine composition of the invention has remarkable effects in treating acute and chronic nasal acupoints, has the characteristics of good purulent sputum effect and quick effect, and can act on various links of inflammatory reaction, thereby reducing symptoms of inflammatory reaction and causing inflammation The reaction subsides and has a good anti-inflammatory effect on acute and chronic inflammation; it has different degrees of antibacterial activity against common pathogenic bacteria causing acute and chronic rhinitis and sinusitis; 'For non-specific immune function and specific immune function, Certain promotion. detailed description
下面结合实施例与药效试验对本发明的药物组合物作进一步的详细说明。  The pharmaceutical composition of the present invention will be further described in detail below in conjunction with the examples and pharmacodynamic tests.
本中药组合物对角叉菜胶所致的大鼠足跖肿胀, 对组胺和 5—羟色胺所致的毛细血 管通透性增加,羧甲基纤维素钠引起的大鼠白细胞游走以及大鼠皮下棉球肉芽肿增生均 有明显抑制作用。提示该组合物作用于炎症反应的多个环节,从而降低炎症反应的症状, 使炎症反应消退。对急、慢性炎症均有良好的抗炎作用。体外抑菌试验选择 7种临床分 离菌株共 106株 (其中多数菌株对常用抗菌药物青霉素和链霉素耐药)及 3株标准菌株, 对本发明的中药组合物进行了体外抗菌作用的实验研究,结果表明该药对引起急、慢性 鼻炎及鼻窦炎的常见致病菌,如金黄色葡萄球菌、溶血性链球菌、绿脓杆菌、变形杆菌、 肺炎杆菌等均有不同程度的抑菌作用。本发明的中药组合物对小鼠非特异免疫功能一单 核巨噬细胞吞噬功能具有明显的促进作用,提高小鼠对血中胶体廓清速度;在迟发性变 态反应中, 本发明的中药组合物也都能增加 DNFB致敏后的耳壳肿胀度, 提高正常机 体对超敏反应的感受力, 提高其细胞免疫功能: 在免疫器官方面, 对脾脏重量有增加趋 势。在体液免疫方面,对环磷酰胺所致免疫功能低下小鼠溶血素生成都具有一定提高作 用。 以上研究初步表明, 本发明的中药组合物对非特异免疫功能及特异性免疫功能, 包 括细胞免疫,体液免疫都具有一定的促进作用。本发明的中药组合物对无芽胞厌氧的体 外抑菌试验: 选择有代表性的各种厌氧菌共 24株, 测定了本发明的中药组合物的体外 抗厌氧活性,并以甲硝唑作阳性对照。试验结果表明本发明的中药组合物对 3种无芽胞 厌氧菌均有一定的抑制作用, 但其抑菌活性远低于对照药甲硝唑。体内抗菌试验: 采用 预防性给药, 即感染前 3天给药,在较高剂量时对金色葡萄球菌所致小鼠感染有一定的 保护作用, ED5Q为 14.4g/Kg。 这一结果与其在体外具有抗金葡萄球菌作用的结果是一 致的。 The traditional Chinese medicine composition has swelling of rat ankle caused by carrageenan, increased capillary permeability caused by histamine and serotonin, and leukocyte migration and ratification caused by sodium carboxymethyl cellulose. The subcutaneous cotton granuloma hyperplasia has obvious inhibitory effect. This suggests that the composition acts on multiple parts of the inflammatory response, thereby reducing the symptoms of the inflammatory response and allowing the inflammatory response to resolve. It has good anti-inflammatory effects on acute and chronic inflammation. In vitro bacteriostatic test: A total of 106 clinical isolates were selected, among which most strains were resistant to common antibacterial drugs penicillin and streptomycin, and 3 standard strains. The in vitro antibacterial effect of the traditional Chinese medicine composition of the present invention was studied. The results showed that the drug has different degrees of antibacterial activity against common pathogenic bacteria causing acute and chronic rhinitis and sinusitis, such as Staphylococcus aureus, hemolytic streptococcus, Pseudomonas aeruginosa, Proteus, and Klebsiella. The traditional Chinese medicine composition of the invention has obvious promoting effect on the non-specific immune function-mononuclear macrophage phagocytosis function of mice, and improves the colloidal clearance speed of blood in mice; in the delayed allergic reaction, the traditional Chinese medicine combination of the invention The substance can also increase the degree of swelling of the ear shell after sensitization by DNFB, improve the susceptibility of the normal body to hypersensitivity, and improve its cellular immune function: In the immune organ, the weight of the spleen is increased. In terms of humoral immunity, hemolysin production in mice with immunocompromised effects induced by cyclophosphamide has a certain effect. The above studies have initially shown that the traditional Chinese medicine composition of the present invention has a certain promoting effect on non-specific immune function and specific immune function, including cellular immunity and humoral immunity. In vitro bacteriostatic test of the traditional Chinese medicine composition of the present invention against bud-free anaerobic: a total of 24 representative anaerobic bacteria were selected, and the anti-anaerobic activity of the traditional Chinese medicine composition of the present invention was measured, and the nitrous oxide was measured. Azole was used as a positive control. The test results show that the traditional Chinese medicine composition of the present invention has three kinds of sporeless cells. Anaerobic bacteria have a certain inhibitory effect, but its antibacterial activity is much lower than the control drug metronidazole. In vivo antibacterial test: Prophylactic administration, that is, administration 3 days before infection, has a certain protective effect on mice infected with Staphylococcus aureus at a higher dose, and ED 5Q is 14.4 g/Kg. This result is consistent with the results of having anti-S. aureus action in vitro.
药效试验:  Pharmacodynamic test:
1、抗炎作用  1, anti-inflammatory effect
一、 实验材料及统计方法  I. Experimental materials and statistical methods
1 、 药物: 以实施例 10中的清膏为本发明中药组合物的样品进行下述实验, 其生 药浓度为 3g/ml, 以下所用浓度均以生药表示。分别取 3g/ml的本发明样品 40ml、 20ml、 10ml, 加蒸馏水至 100ml配成 120%、 60%、 30%的混悬液备用, 用时混匀; 地塞米松 片 (合肥制药厂, 批号 890572), 用蒸馏水配成 0.125g/ml的溶液备用; 阿斯匹林片 (济南 第三制药厂, 批号 9105812— 5), 用乙醇溶解, 配成 2%的溶液备用; 扑尔敏片 (山东德 州制药厂, 批号 920401); 用蒸馏水配成 1 %的溶液备用。  1. Drug: The sample of the traditional Chinese medicine composition of the present invention was subjected to the following experiment using the clearing paste of Example 10, and the crude drug concentration was 3 g/ml, and the concentrations used below were all expressed as crude drugs. Take 3g/ml of the sample of the invention 40ml, 20ml, 10ml respectively, add distilled water to 100ml to prepare 120%, 60%, 30% suspension for use, mix with time; dexamethasone tablets (Hefei Pharmaceutical Factory, batch number 890572 ), using distilled water to prepare a solution of 0.125g / ml; Aspirin tablets (Jinan Third Pharmaceutical Factory, batch number 9105812-12), dissolved in ethanol, formulated into 2% solution for use; chlorpheniramine tablets (Shandong Dezhou Pharmaceutical Factory, batch number 920401); Prepare 1% solution in distilled water for use.
2、 试剂: 角叉菜胶 (Nacala Tesqe , Inc Japan); 5—羟色胺(Koch— Light Lab.Ltd.England); 组胺 (上海生化所); 羟甲基纤维素钠 (上海赛璐珞厂)。  2. Reagents: Carrageenan (Nacala Tesqe, Inc Japan); serotonin (Koch-Light Lab. Ltd. England); Histamine (Shanghai Institute of Biochemistry); Sodium hydroxymethylcellulose (Shanghai Celluloid Plant).
3、 动物: Wistar大鼠, 同济医科大学实验动物中心提供。  3. Animals: Wistar rats, provided by the Experimental Animal Center of Tongji Medical University.
4、 仪器: 72型分光光度计, 普通光学显微镜。  4. Instrument: 72 type spectrophotometer, ordinary optical microscope.
5、 统计方法: 所有数据均用均数标准表示, 各均数间差异用方差分析进行差异显 著性检验。 显著性界限为 p<0.05。  5. Statistical methods: All data were expressed by means of the mean standard. Differences between the mean were analyzed by variance analysis for significance test. The significance limit was p < 0.05.
二、 方法与结果  Second, methods and results
1、 对大鼠足跖肿胀的影响: Wistar大鼠 50只, 体重 120—160(157± 12)g, 雌雄各 半, 随机分成 5组, 每组 10只, 设蒸馏水组、 阿斯匹林组和本发明样品高、 中、 低剂 量组, 分别给予每日灌胃一次, 连续 3天, 末次给药后 1小时, 每鼠右后足跖皮下注射 1 %角叉莱胶 0.1ml,给药前和后 1、 2、 3、 4、 5和 6小时分别测定固定位置的足跖体积 (毛 细管放大测量法), 二者之差即肿胀度。 结果表明阿斯匹林在上述各时间点对足跖肿胀 均有显著抑制作用。 高剂量组在致炎后 2、 3、 4、 5和 6小时时间点有明显抑制作用, 中、 低剂量组在 4、 5小时时间点有抑制作用, 见表 1。 本发明中药组合物对大鼠足跖肿胀的影响 (X土 SD) 1. Effects on paw swelling in rats: 50 Wistar rats weighing 120-160 (157±12) g, male and female, randomly divided into 5 groups, 10 in each group, with distilled water and aspirin. The group and the high, middle and low dose groups of the sample of the present invention were administered once a day for 3 consecutive days, and 1 hour after the last administration, 0.1 ml of 1% carrageenan was injected subcutaneously into the right hind paw of each mouse. The ankle volume (fixed capillary measurement) at a fixed position was measured before, after, and after 1, 2, 3, 4, 5, and 6 hours, respectively, and the difference between the two was the degree of swelling. The results showed that aspirin significantly inhibited the swelling of the athlete's foot at each of the above time points. The high-dose group showed significant inhibition at 2, 3, 4, 5, and 6 hours after inflammation, and the middle and low-dose groups had inhibitory effects at 4 and 5 hours, as shown in Table 1. Effect of Chinese Herbal Medicine Composition on Swelling of Rat Foot (X Soil SD)
Figure imgf000006_0001
Figure imgf000006_0001
与蒸馏水比较 ** p<0.01  Compared with distilled water ** p<0.01
2、 对血管通透性的影响: 2. Effects on vascular permeability:
Wistar大鼠 50只, 体重 150— 190(173 ± 12)g, 雌雄各半, 随机分成 5组, 每组 10 只,分别设蒸馏水组、扑尔敏组和本发明样品高、中、低剂量组,给药容量均为 10ml/kg, 每日灌胃一次, 连续 3天。末次给药后 1小时后在背部已剃毛的四个部位, 分别皮内注 射 0.1 %组胺和 0.1 %5—HT 0.1ml (各二点)形成小丘,然后立即股静脉注射 1 %伊纹氏蓝 4ml/kg。 5分钟后断头处死; 剥开背部皮肤, 将着色的皮肤剪下, 切碎, 放人 5ml生理 盐水一丙酮溶液 (3 :7)内浸泡 24小时, 离心 (3000rpm 20min), 取上清液, 在 610nm波 长处比色 (72型分光光度计)。结果表明扑尔敏、本发明样品的高、 中剂量能明显抑制组 胺和 5— HT引起的血管通透性增高, 见表 2。 表 2、 本发明的中药组合物对血管通透性的影响 (x士 SD) 50 Wistar rats, weighing 150-190 (173 ± 12) g, male and female, were randomly divided into 5 groups, 10 in each group, respectively, distilled water group, chlorpheniramine group and high, medium and low doses of the samples of the present invention. Group, the drug volume was 10 ml / kg, once a day, for 3 consecutive days. One hour after the last administration, the four parts of the back were shaved, respectively, by intradermal injection of 0.1% histamine and 0.1% 5-HT 0.1 ml (two points) to form a hillock, and then immediately injected into the femoral vein 1%. Sapphire blue 4ml/kg. After 5 minutes, the head was killed; the back skin was peeled off, the colored skin was cut, chopped, and soaked in 5 ml of physiological saline-acetone solution (3:7) for 24 hours, centrifuged (3000 rpm for 20 minutes), and the supernatant was taken. , colorimetric at 610 nm wavelength (type 72 spectrophotometer). The results showed that the high and medium doses of chlorpheniramine and the samples of the present invention significantly inhibited the increase of vascular permeability caused by histamine and 5-HT, as shown in Table 2. Table 2. Effect of the traditional Chinese medicine composition of the present invention on vascular permeability (x, SD)
Figure imgf000007_0001
Figure imgf000007_0001
与蒸馏水组比较 *p<0.05 **P<0.01  Compared with distilled water group *p<0.05 **P<0.01
3、 对白细胞游走反应的影响:  3. Effects on leukocyte migration response:
雄性 Wistar大鼠 50只, 体重 130— 180(153 ± 13)g。 随机分成 5组, 每组 10只, 分 别设蒸馏水组、 地塞米松组和本发明样品高、 中、 低剂量组。 给药容量均为 10ml/kg, 每日灌胃一次, 连续三天。 致炎前一天在背部肩胛间区皮下注射 5ml空气, 形成气囊。 末次给药后 1小时,抽囊内注入 1.5、 3和 7.5小时从囊内吸取液体 0.1ml作白细胞计数。 结果表明地塞米松和高剂量组本发明的中药组合物明显抑制白细胞游走反应, 见表 3。  There were 50 male Wistar rats weighing 130-180 (153 ± 13) g. They were randomly divided into 5 groups of 10, each of which was divided into a distilled water group, a dexamethasone group, and a high, medium, and low dose group of the present invention. The drug delivery capacity was 10 ml/kg, and it was administered once a day for three consecutive days. On the day before the inflammation, 5 ml of air was injected subcutaneously into the dorsal interscapular region to form a balloon. One hour after the last administration, 0.1 ml of the liquid was aspirated from the capsule for 1.5, 3, and 7.5 hours in the sac. The results showed that the dexamethasone and the high dose group of the traditional Chinese medicine composition of the present invention significantly inhibited the leukocyte migration reaction, as shown in Table 3.
表 3、 本发明的中药组合物对大鼠白细胞游走反应的影响 (x±SD)  Table 3. Effect of traditional Chinese medicine composition of the present invention on leukocyte migration response in rats (x±SD)
Figure imgf000007_0002
Figure imgf000007_0002
与蒸馏水组比较 *ρ<0.01 4、 对大鼠皮下棉球肉芽肿增生的影响- 雄性 Wistar大鼠 50只, 体重 120— 160(142 ± 12)g, 随机分成 5组, 每组 10只, 分 别设蒸镏水组, 地塞米松组和本发明样品高、 中、低剂量组。 浅麻醉无菌条件下, 将棉 球 (29— 31mg)植入两侧腹股沟。 术前三天给药, 每日灌胃十次, 连续 10天。 给药结束 后断头处死动物, 剥出棉球肉芽肿, 9CTC烤箱内干燥, 1小时后称重。 结果表明地塞米 松和高、 中剂量本发明中药组合物明显抑制皮下棉球肉芽肿增生, 抑制率分别为 24.8 %、 20.0%和 13.3 % , 见表 4。 Compared with distilled water group *ρ<0.01 4. Effects on the proliferation of subcutaneous cotton granuloma in rats - 50 male Wistar rats weighing 120-160 (142 ± 12) g were randomly divided into 5 groups, 10 in each group, respectively, with steamed water group, ground The dexamethasone group and the high, medium and low dose groups of the inventive samples. Under light anesthesia, cotton balls (29 - 31 mg) were implanted into the bilateral groin. Three days before the operation, 10 times a day, for 10 consecutive days. After the end of the administration, the animals were killed by decapitation, the cotton granuloma was peeled off, dried in a 9 CTC oven, and weighed after 1 hour. The results showed that the dexamethasone and the high and medium doses of the traditional Chinese medicine composition of the present invention significantly inhibited the proliferation of subcutaneous cotton granuloma, and the inhibition rates were 24.8%, 20.0% and 13.3%, respectively, as shown in Table 4.
表 4、 本发明的中药组合物对大鼠棉球肉芽肿的影响 (X士 SD)  Table 4. Effect of the traditional Chinese medicine composition of the present invention on rat cotton granuloma (X Shi SD)
Figure imgf000008_0001
Figure imgf000008_0001
与蒸镏水组比较 *p<0.05 **p<0.01  Compared with steamed water group *p<0.05 **p<0.01
结论:该项研究对本发明的中药组合物在四种大鼠动物模型上进行了实验。其剂量 由人用量折算而来。 人用每日剂量 30— 45g(10— 15g, Tid)相当于生药 16.8— 25.2g, 按 公斤体重计为 0.34-0.50g/kg/日, 实验结果表明, 本发明的中药组合物对角叉菜胶所致 的大鼠足跖肿胀, 对组胺和 5—羟色胺所致的毛细血管通透性增加, 羧甲基纤维至少钠 引起的大鼠白细胞游走以及大鼠皮下棉球肉芽肿增生均有明显抑制作用。提示本发明的 中药组合物对炎症反应的多个环节都有作用,从而降低炎症反应的症状,使炎症反应消 退。 对急、 慢性炎症均有良好的抗炎作用。  Conclusion: This study tested the traditional Chinese medicine composition of the present invention on four rat animal models. The dose is converted from human consumption. The daily dose of 30-45 g (10-15 g, Tid) is equivalent to 16.- 25.2 g of crude drug, and 0.34-0.50 g/kg/day is calculated according to the weight of the kilogram. The experimental results show that the traditional Chinese medicine composition of the present invention has a diagonal fork. Rat foot spasm caused by vegetable gum, increased capillary permeability due to histamine and serotonin, rat white blood cell migration caused by sodium carboxymethyl fiber and rat subcutaneous cotton granuloma hyperplasia Both have significant inhibitory effects. It is suggested that the traditional Chinese medicine composition of the present invention has an effect on various steps of the inflammatory reaction, thereby reducing the symptoms of the inflammatory reaction and causing the inflammatory reaction to regress. It has a good anti-inflammatory effect on acute and chronic inflammation.
II.体外抑菌作用 II. In vitro bacteriostasis
一、实验材料: 1、样品: 以实施例 10中的清膏为例进行下述实验, 每毫升含生药 3g。 配制方法同前, 以蒸气 100°C, 30min灭菌备用。 2、 药敏纸片: 青霉素 G, (10IU/ 片), 批号 931211 : 链霉素 (10IU/片), 批号 931127: 诺氟沙星 (lOug/片)。 以上药敏纸片 均由北京天坛药物生物技术幵发部生产。 3、 培养基: MH(MUller— Hinton)培养基, 每 100中含牛肉膏 3g, 蛋白胨 17.5g, 可溶性淀粉 1.5g, 琼脂 17g, PH 7.4经高压灭菌 (115 V , 30分钟后)备用。链球菌接种于巧克力琼脂平板。 4、菌种: 选用与该药主治疾病有 关的临床分离所得致病菌及部分标准菌株 (金黄色葡萄球菌 ATCC25925 , 大肠杆菌 ATCC25922, 绿脓杆菌 MCC27853)共 109株。 其中金黄色葡萄球菌 21株, 表皮葡萄 球菌 19株, 溶血性链球菌 3株, 大肠杆菌 22株, 绿脓杆菌 16株, 变形杆菌 15株, 肺 炎杆菌 13株。受试菌株经同济医科大学微生物学教研室和协和医院检验科细菌室鉴定。 1. Experimental materials: 1. Sample: The following experiment was carried out by taking the clear paste in Example 10 as an example, and 3 g of crude drug per ml was contained. The preparation method was the same as before, and it was sterilized by steam at 100 ° C for 30 minutes. 2. Drug sensitive paper: Penicillin G, (10 IU/tablet), Lot 931211: Streptomycin (10 IU/tablet), Lot 931127: Norfloxacin (lOug/tablet). The above susceptibility papers are produced by Beijing Tiantan Pharmaceutical Biotechnology Development Department. 3. Medium: MH (M U ller-Hinton) medium containing 3g of beef extract per 100 grams, peptone 17.5g, soluble starch 1.5g, agar 17g, pH 7.4 autoclaved (115 V, 30 minutes later) spare. Streptococcus was inoculated on a chocolate agar plate. 4, strains: choose to treat the disease with the drug A total of 109 pathogenic bacteria and some standard strains (S. aureus ATCC25925, Escherichia coli ATCC25922, Pseudomonas aeruginosa MCC27853) were isolated from clinical isolates. There were 21 strains of Staphylococcus aureus, 19 strains of Staphylococcus epidermidis, 3 strains of hemolytic streptococcus, 22 strains of Escherichia coli, 16 strains of Pseudomonas aeruginosa, 15 strains of Proteus, and 13 strains of Klebsiella. The tested strains were identified by the Department of Microbiology, Tongji Medical University and the Laboratory of the Department of Laboratory Medicine, Union Hospital.
二、 方法和结果:  Second, methods and results:
1、 纸片法药敏试验, 将测试菌分别接种于肉汤中, 置 37°C培养 6— 8h, 用无菌棉 拭子蘸取菌液均匀涂布于琼脂表面, 置 37°C培养 16— 18h后测量抑菌圈大小。 按照统 一规定的抗菌药物药敏试验判断标准进行判断。  1. Paper-based drug susceptibility test. The test bacteria were inoculated separately into the broth and cultured at 37 ° C for 6-8 hours. The sterile cotton swabs were evenly spread on the surface of the agar and cultured at 37 ° C. The size of the inhibition zone was measured after 16-18 h. Judging according to the unified antibiotic drug susceptibility test criteria.
2、 MIC测定, 将测试菌分别接种于肉汤中, 置 37°C培养 16— 18h(大肠杆菌和绿脓 杆菌培养 8h)后, 用无菌肉汤稀释成 1:1000的菌液备用。采用平皿内药液稀释法, 取不 同浓度 (6g/ml, 3g/ml, 1.5g/ml-0.009375 g/ml)的鼻渊净清膏 2ml分别加入 18ml MH培 养基中, 摇匀后倒人无菌平皿内, 使培养基内药物终浓度分别为 0.6g/ml 0.3g/ml 0.15g/ml……, 0.009375g/ml), 同时设药物对照平皿 (仅药物与培养基混合,不接种细菌) 和受试菌株对照平皿 (培养基内不含药物)。 待琼脂凝固后, 用接种环划线接种各实验菌 液,. 并于平皿底部标明药物浓度和细菌种类及菌株编号, 置 37°C培养箱培养 24h后观 察结果。 MIC为抑制细菌生长的最低药物浓度。  2. MIC measurement, the test bacteria were inoculated separately into the broth, cultured at 37 ° C for 16-18 h (E. coli and P. aeruginosa culture for 8 h), and then diluted with sterile broth into 1:1000 bacteria solution for use. 2ml of Biyuanjingqing cream with different concentrations (6g/ml, 3g/ml, 1.5g/ml-0.009375 g/ml) was added to 18ml MH medium, shake well and then inverted. In a sterile dish, the final concentration of the drug in the medium was 0.6g/ml 0.3g/ml 0.15g/ml......, 0.009375g/ml), and the drug control plate was set up (only the drug was mixed with the medium, not inoculated). Bacteria) and the test strains were compared to the plate (the medium contained no drug). After the agar was coagulated, the experimental bacteria were inoculated with an inoculation loop, and the drug concentration, the bacterial species and the strain number were indicated on the bottom of the plate, and the results were observed after incubating in a 37 °C incubator for 24 hours. MIC is the lowest drug concentration that inhibits bacterial growth.
3、 结果: 纸片法药敏试验结果见表 5。 本试验所收集的临床致病菌 92%的菌株对 诺氟沙星敏感, 所有金黄色葡萄球菌和 73%表皮葡萄球菌对青霉素耐药, 44%革兰氏 阴性杆菌对链霉素耐药。 本发明的中药组合物的体外抗菌活性见表 6。 由表 6可见, 本 发明的中药组合物对受试菌株具有不同程度的抑菌作用,对金黄色葡萄球菌、表皮葡萄 球菌、大肠杆菌、绿脓杆菌、变形杆菌、肺炎杆菌的 MIC5Q的分别为 0.02812、 0.02344、 0.18、 0.09、 0.206>0.6 g/ml; MIC90分别为 0.0375 0.0625 0.42 0.14 >0.6 >0.6g/ml, 对溶血性链球菌的 MIC范围为 0.075— 0.6g/ml。本试验所设药物对照平服均未见细菌生 长, 受试菌株对照生长良好, 表明药物本身不含有活菌, 培养条件符合试验要求。 3. Results: The results of the paper-based drug susceptibility test are shown in Table 5. 92% of the clinical pathogens collected in this experiment were sensitive to norfloxacin, all Staphylococcus aureus and 73% of Staphylococcus epidermidis were resistant to penicillin, and 44% of Gram-negative bacilli were resistant to streptomycin. The in vitro antibacterial activity of the traditional Chinese medicine composition of the present invention is shown in Table 6. It can be seen from Table 6 that the traditional Chinese medicine composition of the present invention has different degrees of bacteriostatic action on the test strain, and the MIC 5Q of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Proteus and Klebsiella pneumoniae 0.02812, 0.02344, 0.18, 0.09, 0.206>0.6 g/ml; MIC 90 is 0.0375 0.0625 0.42 0.14 >0.6 >0.6 g/ml, respectively, and the MIC range for hemolytic streptococcus is 0.075-0.6 g/ml. The drug control in this experiment did not show bacterial growth, and the test strains grew well, indicating that the drug itself does not contain live bacteria, and the culture conditions meet the test requirements.
三、结论: 本发明的中药组合物是中药复方制剂, 具有清热解毒等作用。本试验选 择 7种临床分离菌株共 106株 (其中多数菌株对常用抗菌药物青霉素和链霉素耐药)及 3 株标准菌株,对本发明的中药组合物进行了体外抗菌作用的实验研究,结果表明该药对 引起急、慢性鼻炎及鼻窦炎的常见致病菌, 如金黄色葡萄球菌、溶血性链球菌、绿脓杆 菌、 变形杆菌、 肺炎杆菌等均有不同程度的抑菌作用。 临床分离株对 3种抗菌药物的纸片法药敏试验结果 III. Conclusion: The traditional Chinese medicine composition of the present invention is a traditional Chinese medicine compound preparation, and has the functions of clearing away heat and detoxifying. In this experiment, a total of 106 clinical isolates (including most of the strains resistant to the commonly used antibacterial drugs penicillin and streptomycin) and 3 standard strains were selected, and the in vitro antibacterial effect of the traditional Chinese medicine composition of the present invention was tested. The drug has various degrees of bacteriostatic action on common pathogenic bacteria causing acute and chronic rhinitis and sinusitis, such as Staphylococcus aureus, hemolytic streptococcus, Pseudomonas aeruginosa, Proteus, and Klebsiella. Results of paper-based drug susceptibility test of clinical isolates against three antimicrobial agents
Figure imgf000010_0001
Figure imgf000010_0001
S: 敏感菌株数, M: 中度敏感菌株数, R ( % ): 耐药菌株数 (耐药朱百分比)。  S: number of sensitive strains, M: number of moderately sensitive strains, R (%): number of resistant strains (percentage of resistant Zhu).
表 6本发明中药组合物对 109株细菌的 MIC测定  Table 6 MIC determination of 109 strains of bacteria of the traditional Chinese medicine composition of the present invention
细菌 株 药物浓度(g/ml) MIC50 MICx, MIC范围 数 0.009375 0.01875 0.0375 0.075 0.15 0.3 0.6 >0.6 Fine strain drug concentration (g/ml) MIC 50 MICx, MIC range: 0.009375 0.01875 0.0375 0.075 0.15 0.3 0.6 >0.6
金黄色 21 1 18 2 0.02812 0.0375 0.01875-0. 葡萄球 075 菌 Golden yellow 21 1 18 2 0.02812 0.0375 0.01875-0. Grape ball 075
表皮葡 19 5 3 6 5 0.02344 0.0625 0.009375-0 萄球菌 .075 溶血性 3 1 2 0.075-0.6 链球菌 Epidermal Portuguese 19 5 3 6 5 0.02344 0.0625 0.009375-0 Staphylococcus .075 Hemolysis 3 1 2 0.075-0.6 Streptococcus
大肠杆 22 10 6 6 0.18 0.42 0.15-0.6 菌 Large intestine rod 22 10 6 6 0.18 0.42 0.15-0.6 bacteria
绿脓杆 16 6 9 1 0.09 0.14 0.075-0.6 菌 Green pus 16 6 9 1 0.09 0.14 0.075-0.6 bacteria
变形杆 15 4 2 3 4 2 0.206 >0.6 0.009375-> 菌 0.6 肝炎杆 13 3 10 >0.6 >0.6 0.6->0.6Deformation rod 15 4 2 3 4 2 0.206 >0.6 0.009375-> bacteria 0.6 hepatitis rod 13 3 10 >0.6 >0.6 0.6->0.6
II m.对免疫功能的作用 II m. Effect on immune function
一、 本发明的中药组合物对小鼠碳粒廓清的影响:  1. Effect of the traditional Chinese medicine composition of the present invention on the clearance of carbon particles in mice:
1、 材料: 样品: 以实施例 10中的清膏为例进行下述实验, 每毫升含生药 3g, 配 制方法同前; 云芝多糖胶囊系南京老山制药厂产品, 批准文号: 苏卫药准字 (87)3612— 1号;规格是 0.5克 /粒,用去离子水稀释成 10%浓度混悬液,供试验使用,使用时振摇; 印度墨汁系英国 Winsor&Newton产品; 751分光光度计, 上海分析仪器厂产品; 动物: 昆明种小鼠, 由同济医科大学动物实验中心提供;  1. Material: Sample: Take the cleaning paste in Example 10 as an example, the following experiment is carried out, containing 3g of crude drug per ml, the preparation method is the same as before; Yunzhi polysaccharide capsule is the product of Nanjing Laoshan Pharmaceutical Factory, approval number: Su Wei Pharmacopoeia (87) 3612-1; the specification is 0.5 g / granule, diluted with deionized water to a 10% concentration suspension for experimental use, shaken during use; Indian ink is British Winsor & Newton products; 751 spectrophotometry , Shanghai Analytical Instrument Factory; Animals: Kunming mice, provided by the Animal Experimental Center of Tongji Medical University;
2、 方法: 取 20_24g健康小鼠 50只, 雌雄各半, 随机分成 5组,即蒸馏水组、 云 芝多糖阳性对照组、 本发明样品高、 中、 低剂量组, 各组均按 10ml/kg体重口服灌胃给 药, 每日一次, 连续 7天, 第 7天给药后每鼠尾静脉注射印度墨汁 10ml/kg体重, 于 2、 10分钟后分别从眼眶静脉取血 0.03ml, 加到 0.1 %碳酸钠溶液 2ml中摇匀, 用 751紫外 光分光度计在 680mm波长处测定光密度,按下列公式计算廓清指数 K值。 K=(logOD2 -logOD10)/ (t10-t2)OD2和 OD1Q分别代表 2、 10分钟所测血样的光密度, t10和 t2代表测 定时间, 取血完毕后, 小鼠颈椎脱曰处死, 分别称取肝、 脾重量, 然后根据下列公式计 算吞噬指数 a值: ' 2. Methods: 50 healthy mice of 20_24g, male and female, were randomly divided into 5 groups, namely distilled water group, Yunzhi polysaccharide positive control group, high, medium and low dose groups of the present invention, each group was 10ml/kg. Oral administration of body weight, once daily for 7 days, after the 7th day of administration, 10 ml/kg body weight of Indian ink was injected into the tail vein of rats, and 0.03 ml of blood was taken from the orbital veins after 2 and 10 minutes. Shake well in 2 ml of 0.1% sodium carbonate solution, measure the optical density at 680 mm wavelength with a 751 ultraviolet spectrophotometer, and calculate the clearance index K value according to the following formula. K=(logOD 2 -logOD 10 )/ (t 10 -t 2 ) OD 2 and OD 1Q represent the optical density of the blood samples measured in 2 and 10 minutes, respectively, and t 10 and t 2 represent the measurement time, after the blood collection is completed, small Rats were sacrificed by cervical dislocation, and the liver and spleen weights were weighed separately. Then, the phagocytic index a value was calculated according to the following formula:
a= (体重 /脾肝重 )X 3 a= (weight/spleen liver weight) X 3
各组的 K值和 a值均以 XSD表示, 进行 F检验, 比较各组差异显著性。  The K value and the a value of each group were expressed by XSD, and the F test was performed to compare the significance of each group.
3、 实验结果: 蒸馏水组廓清指数 K值和吞噬指数 a值分别是 5.2± 1.7(KX 1000, XSD下同)和 2.75 ±0.5(x士 sD下同), 而云芝多糖组分别是 13.75 ±5.7和 3.7±9.50, 两 者具有显著性差异 (p<0.01)。 证实此方法是可靠的, 与文献报道一致[1()], 云芝多糖能增 加小鼠吞噬功能, 本发明的中药组合物高、中、低剂量组廓清指数和吞噬指数与蒸馏水 组比较都具有显著差异 (p<0.05), 与云芝多糖比较, 除低剂量组有显著差异外 (p<0.05), 高、 中剂量则无显著差异 (p〉0.05), 这表明在较高剂量时, 本发明的中药组合物具有与 云芝多糖类似的增加小鼠吞噬功能的作用,本发明的中药组合物各个剂量组廓清指数与 剂量间有一定相关性, 剂量增大, 吞噬活性增强, 高低剂量相比较, 具有显著性差异 (p<0.05), 吞噬指数各个剂量组之间则无显著差异 (p>0.05), 以上结果表明; 本发明的 中药组合物可增加单核巨噬细胞系统对血中胶体碳的廓清速度,提高其吞噬功能,见表 7。 7、 本发明的中药组合物对小鼠碳粒廓清功能的影响 (XSD) 3. Experimental results: The K value and the phagocytic index a of the distilled water group were 5.2 ± 1.7 (KX 1000, XSD the same) and 2.75 ± 0.5 (x sD), while the Yunzhi polysaccharide group was 13.75 ±. 5.7 and 3.7 ± 9.50, there was a significant difference between the two (p < 0.01). This method was confirmed to be reliable. Consistent with the literature report [1()] , Yunzhi polysaccharide can increase the phagocytic function of mice. The high-, medium-, and low-dose groups of the traditional Chinese medicine composition of the present invention have a clearing index and a phagocytic index compared with the distilled water group. There was a significant difference (p<0.05), compared with Yunzhi polysaccharide, except for the significant difference in the low-dose group (p<0.05), there was no significant difference between the high and middle doses (p>0.05), indicating that at higher doses The traditional Chinese medicine composition of the invention has the effect of increasing the phagocytic function of the mouse similar to the Yunzhi polysaccharide, and the dosage index of the traditional Chinese medicine composition of the invention has a certain correlation with the dose, the dose is increased, the phagocytic activity is enhanced, and the height is low. There was a significant difference (p<0.05) between the doses, and there was no significant difference between the phagocytic index groups (p>0.05). The above results indicate that the traditional Chinese medicine composition of the present invention can increase the mononuclear macrophage system. The clearance speed of colloidal carbon in the blood increases its phagocytic function, as shown in Table 7. 7. Effect of the traditional Chinese medicine composition of the present invention on the carbon particle clearance function of mice (XSD)
Figure imgf000012_0001
Figure imgf000012_0001
与蒸馏水组比较, *p<0.05, **p<0.01 ; 与云芝多糖组比较, #p<0.05;  *p<0.05, **p<0.01 compared with distilled water group; #p<0.05 compared with Yunzhi polysaccharide group;
与本发明的中药组合物低剂量组比较 @p<0.05  Compared with the low dose group of the traditional Chinese medicine composition of the present invention @p<0.05
二、 本发明的中药组合物对迟发性变态反应的影响  Second, the effect of the traditional Chinese medicine composition of the invention on delayed allergic reaction
(一)、材料: 1、本发明的中药组合物样品, 云芝多糖胶囊同前, 按同法配成试验 所需浓度。 2、 雷公藤片, 系湖北省黄石市制药厂产品, 批准文号: 鄂卫药准字 (89)240 号, 用去离子水稀释成 0.0033 %混悬液供实验使用, 使用时振摇。 3、 2, 4一二硝氟苯 (D PB)系上海金山化工厂产品, 用丙酮麻油溶液配制成 1 %DNFB。 4、 动物: 昆明种 小鼠, 同济医科大学动物实验中心提供  (1) Materials: 1. The sample of the traditional Chinese medicine composition of the present invention, the Yunzhi polysaccharide capsule is the same as before, and the required concentration is tested according to the same method. 2. Tripterygium wilfordii Hook. is a product of Huangshi City Pharmaceutical Factory in Hubei Province. Approval number: E. Pharmacopoeia (89) No. 240, diluted with deionized water to 0.0033% suspension for experimental use, shaken during use. 3, 2, 4 dinitrofluorobenzene (D PB) is a product of Shanghai Jinshan Chemical Plant, formulated with acetone sesame oil solution to make 1% DNFB. 4. Animals: Kunming mice, provided by the Animal Experimental Center of Tongji Medical University
(二)、方法:取 18— 22g健康小鼠 60只,雌雄各半随机分成 6组, 即蒸馏水空白 对照组, 云芝多糖对照组, 雷公藤对照组, 本发明的中药组合物高、 中、低剂量组, 按 口服灌胃'给药, 每日一次, 连续 7天, 在第一天给药的同时, 各鼠腹部去毛, 范围约为 3 X 3CM2, 用 1 %D FB丙酮麻油溶液 50ul均匀涂抹皮肤表面致敏, 第二天再强化致敏 一次,给药第 6天,将 1 %DNFB溶液 ΙΟιιΙ均匀涂抹右耳廓两面进行攻击,左耳作对照。 攻击 24小时后, 颈部脱白处死小鼠, 剪下左右耳壳, 用打孔器取下直径 3mm的耳片, 称重, 两耳片重量之差为耳肿胀度, 同时取出各鼠脾脏和胸腺称重, 分别以每 10g小鼠 的脾重 (mg)和胸腺重 (mg)的, 即: (B), Method: Take 18-22g healthy mice 60, male and female are randomly divided into 6 groups, namely distilled water blank control group, Yunzhi polysaccharide control group, Tripterygium wilfordii control group, Chinese medicine composition of the present invention high, medium , low-dose group, according to oral gavage 'dosing, once a day, for 7 consecutive days, while the first day of administration, each mouse abdomen hair removal, the range is about 3 X 3CM 2 , with 1% D FB acetone 50 ul of sesame oil solution was evenly applied to the skin surface for sensitization. The sensitization was strengthened once the next day. On the sixth day of administration, 1% DNFB solution ΙΟιιΙ was evenly spread on both sides of the right auricle for attack, and the left ear was used as a control. After 24 hours of attack, the mice were sacrificed by whitening the neck, and the left and right ear shells were cut out. The ear piece with a diameter of 3 mm was removed with a puncher, and the weight of the two ears was the degree of ear swelling. At the same time, the spleen of each mouse was taken out. Weighed with the thymus, weighing spleen (mg) and thymus weight (mg) per 10 g of mice, respectively:
脾指数 =脾重 (mg)/体重 (g) X 10  Spleen index = spleen weight (mg) / body weight (g) X 10
胸腺指数=胸腺重重 (mg)/体重 (g)X 10  Thymus index = thymus weight (mg) / body weight (g) X 10
将耳壳肿胀度, 脾指数、 胸腺指数进行 F检验, 判断各组差异显著性。  The ear shell swelling degree, spleen index and thymus index were tested by F test, and the differences of each group were judged to be significant.
(三)、 结果  (three), results
雷公藤组其耳壳肿胀度是 0.49±0.24, 较蒸馏水组 1.24±0.47有较明显地下降, 与 文献报道雷公藤抑制迟发性变态反应结果完全一致, 而本发明的中药组合物髙、 中、低 三种剂量给药组和云芝多糖给药组其耳壳肿胀度分别是 1.83 ±0.38 , 1.66 + 0.38, 2.51 ±0.36和 2.31 ±0.35, 均较蒸馏水组有明显增加, 低剂量组作用更强 (见表 8)。 对脾脏 指数有一定的提高作用, 但无显著意义, 中高剂量对胸腺指数有降低作用, 低剂量对其 无影响,通过本实验揭示本发明的中药组合物能增强小鼠致敏反应,参与机体的免疫功 能的调节作用。 The swelling degree of the ear shell of the Tripterygium wilfordii group was 0.49±0.24, which was significantly lower than that of the distilled water group 1.24±0.47. It is consistent with the results reported in the literature that the Tripterygium wilfordii inhibits the delayed allergic reaction, while the traditional Chinese medicine composition of the present invention is in the middle and the middle. The ear shell swelling degree of the low-dose group and the Yunzhi polysaccharide-administered group were 1.83 ± 0.38, 1.66 + 0.38, 2.51, respectively. Both ±0.36 and 2.31 ±0.35 were significantly higher than the distilled water group, and the lower dose group was more effective (see Table 8). It has a certain effect on the spleen index, but it has no significant effect. The medium and high dose has a lowering effect on the thymus index, and the low dose has no effect on it. This experiment reveals that the traditional Chinese medicine composition of the invention can enhance the sensitization reaction of the mouse and participate in the body. The regulatory role of immune function.
表 8本发明的中药组合物对小鼠耳壳肿胀、 脾指数和胸腺指数的影响 (X土 SD)  Table 8 Effect of traditional Chinese medicine composition of the present invention on ear shell swelling, spleen index and thymus index of mice (X soil SD)
Figure imgf000013_0001
Figure imgf000013_0001
与蒸馏水组比较, *ρ<0.05, **ρ<0.01 ;  Compared with the distilled water group, *ρ<0.05, **ρ<0.01;
三、本发明的中药组合物对环磷酰胺所致小鼠免疫功能低下血清溶血素生成的影响 (一)、 材料:  The effect of the traditional Chinese medicine composition of the invention on the production of serum hemolysin caused by cyclophosphamide in mice with low immune function (1), material:
1、 本发明中药组合物、 雷公藤、 云芝多糖胶囊同前实验。  1. The traditional Chinese medicine composition, tripterygium wilfordii, and Yunzhi polysaccharide capsule of the present invention are the same as the previous experiment.
2、环磷酰胺系上海十二制药厂产品,批准文号:沪卫药准字 (1981)第 0364号一(十二)。 2. Cyclophosphamide is a product of Shanghai Twelve Pharmaceutical Factory. The approval number is: Huwei Medicine Zhunzi (1981) No. 0364 (12).
3、 SRBC保存液 (Alsever)葡萄糖 2.05g, 氯化钠 0. 42g, 柠檬酸钠 0.8g, 柠檬酸 0.05g, 蒸馏水 100ml, 溶解混合过滤, 在 8磅压力下灭菌 10分钟, 在 4°C保存备用。 3, SRBC preservation solution (Alsever) glucose 2.05g, sodium chloride 0. 42g, sodium citrate 0.8g, citric acid 0.05g, distilled water 100ml, dissolved and mixed filter, sterilized under 8 pounds pressure for 10 minutes, at 4 ° C saves the spare.
4、 都氏溶液 (用测定血红蛋白使用): 碳酸氢钠 1.0 g, 高铁氰化钢, 0.2 g, 氰化钾 0.05g 加蒸馏水 1000ml。  4. Duchen solution (used for the determination of hemoglobin): sodium hydrogencarbonate 1.0 g, high iron cyanide steel, 0.2 g, potassium cyanide 0.05 g plus distilled water 1000 ml.
5、 补体: 取新鲜豚鼠 (3只)混合血清经 SRBC (以 10:1)的体积比例 (于 4°C吸收 30分钟, 震荡离心 (2000rpm, 10分钟)取上清液, 用蒸馏水按 1:10将血清稀释备用。  5, Complement: Take fresh guinea pig (3) mixed serum by SRBC (in 10:1) volume ratio (absorbed at 4 ° C for 30 minutes, shake the centrifugation (2000 rpm, 10 minutes) to take the supernatant, press 1 with distilled water : 10 Serve the serum for later use.
6、 SRBC: 在无菌条件下, 从健康成年绵羊颈静脉取血, 将血液放入有玻璃珠的三角烧 杯中轻摇 10分钟以除去纤维蛋白, 加入 2倍量的保存液, 放入 4°C冰箱备用, 临时用 生理盐水洗涤 3次, 经 2000rpm, 10分钟, 得压积红细胞, 再按所需浓度稀释。  6. SRBC: Under aseptic conditions, take blood from the jugular vein of healthy adult sheep, shake the blood into a triangular beaker with glass beads for 10 minutes to remove fibrin, add 2 times the amount of preservation solution, put 4 °C refrigerator spare, temporarily washed with physiological saline 3 times, 2000 rpm, 10 minutes, to accumulate red blood cells, and then diluted to the required concentration.
7、 昆明种小鼠: 由同济医科大学动物实验中心提供。  7. Kunming mice: provided by the Animal Experimental Center of Tongji Medical University.
(二)、方法:取健康小鼠 60只, 体重在 20-24g,雌雄各半随机分成 6组, 即蒸馏 水组, 环磷酰胺组, 环磷酰胺加云芝多糖组, 环磷酰胺加本发明的中药组合物高、 中、 低剂量组。 给药前先给各鼠 (除蒸馏水组外)环磷酰胺按 110mg/kg皮下注射造成免疫功 能低下的病理模型, 然后连续口服给药 7天, 在给药第二天每鼠腹腔注射致敏。第八天 从小鼠眼眶摘除眼球取血, 分离血清, 将血清稀释 800倍, 在试管内依次加入经稀释的 血清 lml, 5%SRBC0.5ml, 10%补体 lml,加都氏液 3ml,摇匀后放置 10分钟,在 540nm 波长处比色记录吸光度, 另外取 5 %SRBC0.25ml, 加都氏液 4ml, 记录其吸光度值, 此值即为实验所用 SRBC半数溶血时的肖光度值, 最后按下式计算样品的半数溶血值。 (B), Method: Take 60 healthy mice, weighing 20-24g, male and female are randomly divided into 6 groups, namely distilled water group, cyclophosphamide group, cyclophosphamide plus Yunzhi polysaccharide group, cyclophosphamide plus this Inventive traditional Chinese medicine composition high, medium, Low dose group. Before administration, each mouse (except the distilled water group) was injected subcutaneously with cyclophosphamide at 110 mg/kg to cause a pathological model with low immune function, and then orally administered for 7 days continuously, and sensitized per mouse intraperitoneally on the second day after administration. . On the eighth day, the eyeballs were removed from the eyelids of the mice, the serum was separated, the serum was diluted 800 times, and the diluted serum 1 ml, 5% SRBC 0.5 ml, 10% complement lml, and 3 ml of Dud solution were added to the test tube in turn, and shaken. After 10 minutes, the absorbance was recorded at a wavelength of 540 nm, and 5% 0.25 ml of SRBC and 4 ml of turbid liquid were added. The absorbance value was recorded. This value is the value of the luminosity of the half hemolysis of the SRBC used in the experiment. The half of the hemolysis value of the sample is calculated by the following formula.
半数溶血值 (HC5G)= 样品的吸光度值 X稀释倍数 Half of the hemolysis value (HC 5G ) = absorbance value of the sample X dilution factor
SRBC半数溶血时吸光度值  Absorbance value of half of hemolysis in SRBC
(三)、结果:环磷酰胺组半数溶血值 (HC5Q)325.4166.10(XSD)明显地低于蒸馏水组 464.8615.85, 其差异有显著性 (P<0.01), 通过给环磷酰胺造成体液免疫功能低下, 在给 予环磷酰胺同时, 给予本发明的中药组合物, 都能提高半数溶血值, 其高、 中、低剂量 组 HC50值分别是 427.94 ±33.63, 396.9675.66和 397.29±71.32, 与单用环磷酰胺组比 较, 差异都具有显著性 (PO.05或 P<0.01), 云芝多糖组作用非常明显, 其 HC5Q值与环 磷酰胺组比较明显提高 (PO.01), 在本发明的中药组合物各组中, 高剂量组作用最强, 见表 9。 (III) Results: The half hemolysis value (HC 5Q ) of the cyclophosphamide group (HC 5Q ) was significantly lower than that of the distilled water group of 464.81.85.85. The difference was significant (P<0.01), which was caused by the cyclophosphamide. The humoral immune function is low. When the cyclophosphamide is administered, the traditional Chinese medicine composition of the present invention can increase the half hemolysis value, and the HC 50 values of the high, medium and low dose groups are 427.94 ± 33.63, 396.9675.66 and 397.29 ±, respectively. 71.32, compared with the cyclophosphamide group alone, the difference was significant (PO.05 or P<0.01), the effect of the Yunzhi polysaccharide group was very obvious, and its HC 5Q value was significantly higher than that of the cyclophosphamide group (PO.01). In the various groups of the traditional Chinese medicine compositions of the present invention, the high dose group has the strongest effect, as shown in Table 9.
表 9. 本发明的中药组合物对免疫功能低下小鼠血清溶血素生产的影响 (X±SD) Table 9. Effect of the traditional Chinese medicine composition of the present invention on serum hemolysin production in immunocompromised mice ( X ± SD)
Figure imgf000014_0001
Figure imgf000014_0001
^与蒸馏水组比较 PO.01 ;  ^Compared with distilled water group PO.01;
*与环磷酰胺比较 ΡΟ.05; **与环磷酰胺组比较 Ρ<0.01。 本发明的中药组合物对免疫功能药效学结论:实验结果表明,三种剂量本发明的中 药组合物对小鼠非特异免疫功能一单核巨噬细胞吞噬功能都具有明显的促进作用,提高 小鼠对血中胶体廓清速度, 高剂量组较低剂量组作用更为明显; 在迟发性变态反应中, 三种剂量本发明的中药组合物也都能增加 DNFB致敏后的耳壳肿胀度, 提高正常机体 对超敏反应的感受力, 提高其细胞免疫功能, 其中以低剂量组作用更强: 在免疫器官方 面, 对脾脏重量有增加趋势; 在体液免疫方面, 三种剂量本发明样品对环磷酰胺所致免 疫功能低下小鼠溶血素生成都具有一定提高作用。 *Compared with cyclophosphamide ΡΟ.05; **Compared with cyclophosphamide group Ρ<0.01. Pharmacodynamics conclusions of the traditional Chinese medicine composition of the present invention on immune function: The experimental results show that the three doses of the traditional Chinese medicine composition of the present invention have obvious promoting effects on the non-specific immune function-mononuclear macrophage phagocytosis of mice, and improve The mice were more effective in the clearance of colloids in the blood, and the lower doses in the high dose group. In the delayed allergic reaction, the three doses of the traditional Chinese medicine composition of the present invention also increased the swelling of the ear shell after sensitization by DNFB. Degree, improve the normal body's susceptibility to hypersensitivity, improve its cellular immune function, which is stronger in the low dose group: in the immune organs, the spleen weight has an increasing trend; in the body fluid immunity, three doses of the invention The sample has a certain effect on the hemolysin production in immunosuppressed mice induced by cyclophosphamide.
以上研究初步表明,本发明的中药组合物对非特异免疫功能及特异性免疫功能,包 括细胞免疫, 体液免疫都具有一定的促进作用。  The above studies have initially shown that the traditional Chinese medicine composition of the present invention has a certain promoting effect on non-specific immune function and specific immune function, including cellular immunity and humoral immunity.
IV.对无芽胞厌氧的体外抑菌试验  IV. In vitro bacteriostatic test for bud-free anaerobic
―、材料和方法: 1、试验药品, 试验药: 本发明实施例 10的样品清膏, 每毫升含 生药 3g。 用蒸馏水配制 5000mg/ml, 以蒸气 100°C, 30min灭菌备用, 用时稀释。 阳性 对照药: 甲硝唑, 武汉滨湖制药广生产, 批号 960541, 配制成 320ug/ml。  ―, materials and methods: 1. Test drug, test drug: The sample clearing paste of the embodiment 10 of the present invention contains 3 g of crude drug per ml. Prepare 5000mg/ml with distilled water, sterilize with steam at 100 ° C for 30 min, and dilute with time. Positive control drug: metronidazole, Wuhan Binhu Pharmaceutical Co., Ltd., batch number 960541, formulated into 320ug/ml.
2、 试验菌株, 试验用菌株均为武汉地区临床病例标本的分离株, 其中脆弱类杆菌 20株, 齿龈类杆菌 2株, 共计 3种 24株。 受试菌株经同济医科大学微生物学教研室细 菌室鉴定。标准菌株 (脆弱类杆菌 5524)购于北京生物药品检验所。所有菌株均冻干存于 -30°C, 使用时用无菌生理盐水稀释, 接种于厌氧分离培养基, 37°C厌氧培养 48h, 再挑 取单个菌落接种于厌氧菌基础培养基, 37°C厌氧培养 24h, 调整菌液至 106cfo/ml。 3、 培养基, 厌氧培养基, 购于上海医工所。 2. The test strains and the test strains are isolates of clinical case specimens in Wuhan, including 20 strains of Bacteroides fragilis and 2 strains of Bacillus gingivalis, a total of 3 strains of 24 strains. The tested strains were identified by the bacteria room of the Department of Microbiology, Tongji Medical University. The standard strain (Bacteroides fragilis 5524) was purchased from Beijing Biopharmaceutical Inspection Institute. All strains were lyophilized at -30 ° C, diluted with sterile physiological saline, inoculated in anaerobic separation medium, anaerobic cultured at 37 ° C for 48 h, and then picked up a single colony to be inoculated into anaerobic basal medium. Analyze culture at 37 ° C for 24 h, adjust the bacterial solution to 10 6 cfo / ml. 3. Medium, anaerobic medium, purchased from Shanghai Medical Institute.
4、 试验方法, 琼脂平板稀释法, 取 5000mg/ml的本发明的中药组合物和 320ug/ml 甲硝唑 2ml分别作对倍稀释, 最小浓度分别为 39mg/ml和 0.3ug/ml。 分别取两种药物 各种浓度药液 2ml加入 18ml厌氧琼脂培养基中, 摇匀后分别倒人无菌平皿内。 待琼脂 凝固后, 用接种环划线接种各实验菌液, 同时接种不含药物的平皿, 于平皿底部标明药 物浓度和细菌种类及菌株编号, 37Ό厌氧条件下培养 48h后观察结果。 MIC为抑制细 菌生长的最低药物浓度。  4. Test method, agar plate dilution method, 5000 mg/ml of the traditional Chinese medicine composition of the present invention and 320 ug/ml metronidazole 2 ml were separately diluted, and the minimum concentrations were 39 mg/ml and 0.3 ug/ml, respectively. Take 2ml of each drug and add 2ml of various concentrations of the drug solution to 18ml anaerobic agar medium, shake it and pour it into the sterile plate. After the agar was coagulated, each experimental bacterial solution was inoculated with an inoculation loop, and a plate containing no drug was inoculated. The drug concentration, the bacterial species and the strain number were indicated on the bottom of the plate, and the results were observed after 37 hours of anaerobic conditions. The MIC is the lowest drug concentration that inhibits the growth of bacteria.
二、 结果: 本发明的中药组合物和甲硝唑对 24株无芽胞厌氧菌的最小抑菌浓度见 表 10。 表 10本发明的中药组合物和皿硝唑对 24株厌氧菌的体外抑菌作用 2. Results: The minimum inhibitory concentration of the traditional Chinese medicine composition of the present invention and metronidazole against 24 strains of non-spore anaerobic bacteria is shown in Table 10. Table 10 In vitro antibacterial activity of the traditional Chinese medicine composition of the present invention and the nitrated azole on 24 strains of anaerobic bacteria
Figure imgf000016_0001
讨论: 本试验选择有代表性的各种厌氧菌共 24株, 测定了本发明的中药组合物的 体外抗厌氧活性,并以甲硝唑做阳性对照。试验结果表明本发明的中药组合物对 3种无 芽厌氧菌均有一定的抑制作用, 但其抑菌活性远低于对照药甲硝唑。
Figure imgf000016_0001
Discussion: In this experiment, a total of 24 representative anaerobic bacteria were selected, and the anti-anaerobic activity of the traditional Chinese medicine composition of the present invention was measured, and metronidazole was used as a positive control. The test results show that the traditional Chinese medicine composition of the invention has certain inhibitory effects on three kinds of bud-free anaerobic bacteria, but its antibacterial activity is much lower than that of the control drug metronidazole.
V.体内抗菌试验  V. In vivo antibacterial test
一、 材料和方法: 1、药品,试验药: 本发明实施例 10的清膏为样品, 棕色液体, 每 ml含生药 3g。 用蒸馏水配成不同浓度 (0.3、 0.6、 0.9、 1.2、 1.5g/ml)的混悬液, 用时 混匀。 对照药: 乳酸环丙沙星注射液 (200mg/100ml), 广州侨光制药厂生产, 批号 95091502, 用无菌生理盐水配制成 0.3mg/ml。  1. Materials and methods: 1. Drug, test drug: The clearing paste of the embodiment 10 of the present invention is a sample, a brown liquid, and contains 3 g of crude drug per ml. Mix with different concentrations (0.3, 0.6, 0.9, 1.2, 1.5 g/ml) in distilled water and mix as needed. Control drug: Ciprofloxacin lactate injection (200mg/100ml), produced by Guangzhou Qiaoguang Pharmaceutical Factory, batch number 95091502, formulated into 0.3mg/ml with sterile physiological saline.
2、 试验菌株,  2. Test strains,
用于感染动物的细菌为临床分离的金黄色葡萄球菌,经同济医科大学附属同济医院 检验科细菌室鉴定。  The bacteria used to infect animals are clinically isolated Staphylococcus aureus, which is identified by the bacteria laboratory of the Department of Clinical Laboratory of Tongji Hospital affiliated to Tongji Medical University.
3. 菌液制备, 试验前一日, 取 5个菌落移种于 5ml肉汤试管, 37°C培养 18h后作 为原菌液。 原菌液用生理盐水适当稀释, 取稀释后的菌液 lml加 5 %胃膜素 9ml, 制成 均匀混悬液。根据 MLD预试验结果最终用 5 %胃膜素制成感染动物用菌液。 MLD为最 小 100%致死病菌 (Minimall00% lethal dose of bacteria)。 本试验选用 80%—90% 小鼠死亡的细菌量感染动物。  3. Preparation of bacterial solution. On the day before the test, 5 colonies were transplanted into 5 ml broth test tubes, and cultured at 37 ° C for 18 hours as the original bacterial solution. The original bacterial solution was appropriately diluted with physiological saline, and 1 ml of the diluted bacterial solution was added to 5 ml of 5% gastric gas to prepare a uniform suspension. According to the results of the MLD pretest, the bacterial liquid for the infected animal was finally made with 5% of the gastric membrane. MLD is the minimum 100% lethal dose of bacteria (Minimall00% lethal dose of bacteria). In this experiment, animals were infected with 80%-90% of the dead mice.
4. 试验动物, 昆明种小鼠, 体重 18— 22g, 雌雄各半, 试验前 18h禁食供水。 试 验动物由同济医科大学医学实验动物中心提供。 5、试验方法, 按动物体重, 性别分层随机分组, 每组 10只, 共分 7组, 即蒸馏水 阴性对照,环丙沙星 (3mg/kg/次)阳性对照, 5组不同剂量的本发明的中药组合物组 (3、 6、 9、 12、 15g/Kg/日)。 用准备好的菌液采用腹腔注射感染动物, 每只小鼠 0.5ml。 本发明 的中药组合物于感染前 3天及感染后 4天每天灌胃一次,环丙沙星于感染后即刻及感染 后 6h各静脉注射一次, 阴性对照组给予等容量蒸馏水, 给药容量为 0.1ml/10g。观察时 间 7天, .记录各组小鼠死亡数, 按 Bliss法计算本发明的中药组合物的 ED5()4. Test animals, Kunming mice, weighing 18-22 g, male and female, fasting water supply 18 h before the test. The test animals were provided by the Medical Laboratory Animal Center of Tongji Medical University. 5, test methods, according to animal weight, gender stratification random group, each group of 10, a total of 7 groups, namely distilled water negative control, ciprofloxacin (3mg / kg / time) positive control, 5 groups of different doses of this The traditional Chinese medicine composition group of the invention (3, 6, 9, 12, 15 g/Kg/day). The infected animals were intraperitoneally injected with the prepared bacterial solution, 0.5 ml per mouse. The traditional Chinese medicine composition of the present invention is intragastrically administered once every day before infection and 4 days after infection, and ciprofloxacin is intravenously injected immediately after infection and 6 hours after infection, and the negative control group is given equal volume of distilled water, and the administration capacity is 0.1 ml/10 g. The observation time was 7 days, and the number of deaths of each group of mice was recorded, and ED 5 () of the traditional Chinese medicine composition of the present invention was calculated according to the Bliss method.
二、 结果  Second, the results
小鼠感染金黄色葡萄球菌后, 本发明的中药组合物及对照组小鼠死亡数见表 11, 本发明的中药组合物的 ED5Q与 95 %可信限分别为 14.4g/kg和 9.1〜22.8g/Kg。 表 11 本发明的中药组合物金黄色葡萄球菌感染小鼠的体内保护试验 After the mice were infected with S. aureus, the death rate of the traditional Chinese medicine composition of the present invention and the control group was shown in Table 11. The ED 5Q and 95% confidence limits of the traditional Chinese medicine composition of the present invention were 14.4 g/kg and 9.1, respectively. 22.8 g / Kg. Table 11 In vivo protection test of the traditional Chinese medicine composition of the present invention against Staphylococcus aureus-infected mice
Figure imgf000017_0001
讨论: 由于中药抗菌作用较弱, 难以在体内达到有效抗菌浓度, 且中药常可能通过 调动非特异抗感染能力而起效, 故正式试验时感染菌量应低于 MLD, 以选取 80-90%小 鼠死亡的细菌量感染动物,并且研究中药体内抗菌作用时常采用预防性给药。本试验蒸 馏水组和环丙沙星对照组小鼠死亡率分别为 90%和 0%, 说明所选用的感染菌量是适当 的。 试验药本发明的中药组合物采用预防性给药, 即感染前 3天给药。 研究结果表明, 本品在较高剂量时对金黄色葡萄球菌所致小鼠感染有一定的保护作用, ED5o为 14.4g/kg。 这一结果与其在体外具有抗金葡萄球菌作用的结果是一致的。 以下为本发明中药组合物的制备实施例:
Figure imgf000017_0001
Discussion: Due to the weak antibacterial effect of traditional Chinese medicine, it is difficult to achieve effective antibacterial concentration in the body, and traditional Chinese medicine may often work by mobilizing non-specific anti-infective ability. Therefore, the amount of infectious bacteria should be lower than MLD in formal test, so 80-90% should be selected. The amount of bacteria that died in mice infects animals, and the in vivo antibacterial action of Chinese medicines is often used for prophylactic administration. The mortality of the distilled water group and the ciprofloxacin control group in this test were 90% and 0%, respectively, indicating that the selected amount of infectious bacteria was appropriate. Test Drug The Chinese medicinal composition of the present invention is administered by prophylactic administration, i.e., 3 days before infection. The results showed that this product had a certain protective effect on mice infected with Staphylococcus aureus at a higher dose, and the ED 5 o was 14.4 g/kg. This result is consistent with the results of having anti-S. aureus action in vitro. The following are examples of preparation of the traditional Chinese medicine composition of the present invention:
实施例 1 :  Example 1
辛夷 10g 苍耳子 30g 麻黄 20g 白 芷 30g 薄 荷 10g 藁本 5g 黄 芩 20g 连翘 20g 野菊花 20g 天花粉 20g  Xinyi 10g Xanthium 30g Ephedra 20g White 芷 30g Thin Lotus 10g 藁本 5g 黄 芩 20g Forsythia 20g Wild Chrysanthemum 20g Trichosanthin 20g
地黄 30g 丹参 20g 茯苓 40g 甘草 5g  Rehmannia 30g Salvia 20g 茯苓 40g Licorice 5g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 450ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 2000ml煎煮 2小时, 趁热过滤; 过滤后 的药渣与上述药渣合并, 再加水 2800ml煎煮 1次, 每次 0. 5小时, 过滤, 合并滤液与 上述辛夷等蒸镏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形 剂辅料制成软胶囊。 实施例 2:  The above fourteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 450ml of water to extract volatile oil. The distilled aqueous solution and dregs are collected separately; the other ten herbs are added with water 2000ml for 2 hours, hot filtered; After the dregs are combined with the above-mentioned dregs, and then boiled in 2800 ml of water for 1 time, each time 0.5 hours, filtered, and the combined filtrate and the above-mentioned steamed aqueous solution of Xinyi and the like are concentrated to form a clear paste; finally, the pharmacy is added through a conventional procedure. The acceptable excipients are made into soft capsules. Example 2:
辛夷 10g 苍耳子 30g 麻黄 60g 白 芷 30g 薄 荷 10g 藁本 5g 黄 芩 20g 连翘 20g 野菊花 20g 天花粉 20g  Xinyi 10g Xanthium 30g Ephedra 60g White 芷 30g Thin Lotus 10g 藁本 5g 黄 芩 20g Forsythia 20g Wild Chrysanthemum 20g Trichosanthin 20g
地黄 30g 丹参 20g 茯苓 40g 甘草 5g  Rehmannia 30g Salvia 20g 茯苓 40g Licorice 5g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 230ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 2000ml煎煮 3小时, 趁热过滤; 过滤后 的药渣与上述药渣合并, 再加水 1600ml煎煮两次, 每次 50分钟, 过滤, 合并滤液与上 述辛夷等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂 辅料制成软胶囊。 实施例 3:  The above fourteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 230ml of water to extract volatile oil. The distilled aqueous solution and dregs are collected separately; the other ten herbs are added with water 2000ml for 3 hours, hot filtered; After the dregs are combined with the above dregs, and then decocted with water 1600ml twice, each time for 50 minutes, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, the pharmaceutically acceptable step is added through a conventional procedure. The excipients are made into soft capsules. Example 3:
辛夷 30g 苍耳子 90g 麻黄 20g 白 芷 90g 薄 荷 30g  Xinyi 30g Xanthium 90g Ephedra 20g White 芷 90g Thin Lotus 30g
藁本 15g 黄 芩 40g 连翘 40g 野菊花 40g 天花粉 40g  Sakamoto 15g yellow 芩 40g forsythia 40g wild chrysanthemum 40g trichosanthin 40g
地黄 60g 丹参 40g 茯苓 120g 甘草 15g  Rehmannia 60g Salvia 40g 茯苓 120g Licorice 15g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 600ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 2800ml煎煮 2. 5小时, 趁热过滤; 过滤 后的药渣与上述药渣合并, 再加水 3500ml煎煮两次, 每次 1. 5小时, 过滤, 合并滤液 与上述辛夷等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋 形剂辅料制成软胶囊。 实施例 4: The above fourteen flavors, Xinyi, Mint, Sakamoto, Wild Chrysanthemum, four flavors of water and 600ml of water to extract volatile oil, the aqueous solution and the dregs after distillation are separately collected; other ten herbs add water 2800ml decoction 2. 5 hours, hot filtered ; Filter After the dregs are combined with the above-mentioned dregs, and then boiled in 3500 ml of water twice, each time for 1.5 hours, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, the pharmacy is added through a conventional procedure. Acceptable excipients are made into soft capsules. Example 4:
辛夷 10g 苍耳子 30g 麻黄 20g 白 芷 30g 薄 荷 10g 藁本 5g 黄 芩 40g 连翘 20g 野菊花 20g 天花粉 20g 地黄 30g 丹 参 20g 茯苓 40g 甘 草 5g  Xinyi 10g Xanthium 30g Ephedra 20g White 芷 30g Thin Lotus 10g 藁本 5g Yellow 芩 40g Forsythia 20g Wild Chrysanthemum 20g Trichosanthin 20g Rehmannia 30g Danshen 20g 茯苓 40g Licorice 5g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、薄荷、 藁本、野菊花四味药加水 675ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 3800ml煎煮 1. 5小时, 趁热过滤; 过滤 后的药渣与上述药渣合并, 再加水 4500ml煎煮 3次, 每次 1小时, 过滤, 合并滤液与 上述辛夷等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形 剂辅料制成胶囊。 实施例 5:  The above fourteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 675ml of water to extract the volatile oil. The distilled aqueous solution and the dregs are collected separately; the other ten herbs are added with water 3800ml to cook for 1. 5 hours, hot filtered The filtered dregs are combined with the above dregs, and then boiled 4500 ml of water for 3 times, each time for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, the pharmacy is added through a conventional procedure. Acceptable excipients are made into capsules. Example 5
辛夷 30g 苍耳子 90g 麻黄 60g 白 芷 90g 薄 荷 30g 藁本 15g 黄 芩 20g 连翘 40g 野菊花 40g 天花粉 40g 地黄 60g 丹 参 40g 茯苓 120g 甘 草 15g  Xinyi 30g Xanthium 90g Ephedra 60g White 芷 90g Thin 30g 藁15g Yellow 芩 20g Forsythia 40g Wild chrysanthemum 40g Trichosanthin 40g Rehmannia 60g Danshen 40g 茯苓 120g Licorice 15g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、 野菊花四味药加水 1725ml提取挥发油, 蒸馏后 的水溶液及药渣分别另器收集; 其他十味药加水 7575ml煎煮 2小时, 趁热过滤; 将上 述两种药渣合并, 再加水 9300ml煎煮 3次, 每次 1. 5小时, 过滤, 合并滤液与上述辛 夷等蒸镏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料 制成胶囊。 实施例 6:  The above fourteen flavors, Xinyi, Mint, Sakamoto, wild chrysanthemum four herbs add water 1725ml to extract volatile oil, distilled aqueous solution and dregs separately collected; other ten herbs add water 7575ml decoction for 2 hours, hot filtered; The above two kinds of dregs are combined, and then boiled in water at 9,300 ml for 3 times, each time for 1.5 hours, filtered, and the combined filtrate and the above-mentioned steamed aqueous solution of Xinyi and the like are concentrated to form a clear paste; finally, the pharmaceutically acceptable step is added through a conventional procedure. The excipients are made into capsules. Example 6:
辛夷 15g 苍耳子 50g 麻黄 30g 白 ϊ£ 50g 薄 荷 15g 藁本 8g 黄 苓 30g 连翘 30g 野菊花 30g 天花粉 30g 地黄 50g 丹 参 30g 茯苓 70g 甘 草 8g 其中, 苍耳子以炒为佳。 Xinyi 15g Xanthium 50g Ephedra 30g White peony £50g Mint 15g Sakamoto 8g Astragalus 30g Forsythia 30g Wild chrysanthemum 30g Trichosanthin 30g Rehmannia 50g Salvia 30g 茯苓70g Licorice 8g Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 600ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 3600ml煎煮 1小时, 趁热过滤; 将上述 两种药渣合并, 再加水 4200ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷等 蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料制成 片剂。 实施例 7:  The above fourteen flavors, Xinyi, Mint, Sakamoto, wild chrysanthemum four flavors of water plus 600ml extract volatile oil, distilled aqueous solution and dregs separately collected; other ten flavors add water 3600ml boiling for 1 hour, hot filtered; The above two kinds of dregs are combined, and then boiled in 4200 ml of water twice, each time for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable form is added through a conventional procedure. The adjuvant is made into a tablet. Example 7
辛夷 15g 苍耳子 50g 麻黄 30g 白 芷 50g 薄 荷 15g 藁本 8g 黄 芩 50g 连翘 30g 野菊花 30g 天花粉 30g 地黄 50g 丹 参 30g 茯苓 70g 甘 草 8g  Xinyi 15g Xanthium 50g Ephedra 30g White 芷 50g Thin Lotus 15g Sakamoto 8g Yellow 芩 50g Forsythia 30g Wild Chrysanthemum 30g Trichosanthin 30g Rehmannia 50g Danshen 30g 茯苓 70g Licorice 8g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 500ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 3800ml煎煮 1. 5小时, 趁热过滤; 将上 述两种药渣合并, 再加水 4500ml煎煮两次, 每次 1. 5小时, 过滤, 合并滤液与上述辛 夷等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料 制成片剂。 实施例 8:  The above fourteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 500ml of water to extract the volatile oil, and the distilled aqueous solution and the dregs are collected separately; the other ten herbs are added with water 3800ml to cook for 1. 5 hours, hot filtered The above two kinds of dregs are combined, and then boiled in 4,500 ml of water twice, each time for 1.5 hours, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, the pharmacy is added through a conventional procedure. The excipient excipients received were made into tablets. Example 8
辛夷 25g 苍耳子 70g 麻黄 50g 白 芷 70g 薄 荷 35g 藁本 18g 黄 芩 50g 连翘 50g 野菊花 50g 天花粉 50g 地黄 70g 丹 参 50g 茯苓 90g 甘 草 15g  Xinyi 25g Xanthium sinensis 70g Ephedra 50g White 芷 70g Thin Lotus 35g 藁本 18g 黄 芩 50g Forsythia 50g Wild Chrysanthemum 50g Trichosanthin 50g Rehmannia 70g Danshen 50g 茯苓 90g Licorice 15g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、 野菊花四味药加水 1200ml提取挥发油, 蒸馏后 的水溶液及药渣分别另器收集; 其他十味药加水 5600ml煎煮 3小时, 趁热过滤; 将上 述两种药渣合并, 再加水 5400ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷 等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料制 成软胶囊。 实施例 9: The above fourteen flavors, Xinyi, Mint, Sakamoto, wild chrysanthemum four herbs add 1200ml of water to extract volatile oil, the distilled aqueous solution and dregs are separately collected; the other ten herbs add water 5600ml to cook for 3 hours, hot filtered; The above two kinds of dregs are combined, and further boiled in 5400 ml of water for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable form is added through a conventional procedure. The agent is made into a soft capsule. Example 9
辛夷 25g 苍耳子 70g 麻黄 50g 白 芷 70g 薄 荷 35g 藁本 18g 黄 芩 30g 连翘 50g 野菊花 50g 天花粉 50g 地黄 70g 丹 参 50g 茯苓 90g 甘 草 15g  Xinyi 25g Xanthium sinensis 70g Ephedra 50g White 芷 70g Thin Lotus 35g 藁本 18g 黄 芩 30g Forsythia 50g Wild chrysanthemum 50g Trichosanthin 50g Rehmannia 70g Danshen 50g 茯苓 90g Licorice 15g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、 野菊花四味药加水 1200ml提取挥发油, 蒸馏后 的水溶液及药渣分别另器收集; 其他十味药加水 5000ml煎煮 2小时, 趁热过滤; 将上 述两种药渣合并, 再加水 6000ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷 等蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料制 成软胶囊。 实施例 10:  The above fourteen flavors, Xinyi, Mint, Sakamoto, wild chrysanthemum four herbs add 1200ml of water to extract volatile oil, the distilled aqueous solution and dregs are separately collected; the other ten herbs add water 5000ml decoction for 2 hours, hot filtered; The above two kinds of dregs are combined, and then boiled with 6000 ml of water twice, each time for 1 hour, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable form is added through a conventional procedure. The agent is made into a soft capsule. Example 10
辛夷 20g 苍耳子 60g 麻黄 40g 白 芷 60g 薄 荷 20g 藁本 10g 黄 芩 40g 连翘 40g 野菊花 40g 天花粉 40g 地黄 60g 丹 参 40g 茯苓 80g 甘 草 10 g  Xinyi 20g Xanthium 60g Ephedra 40g White 芷 60g Thin Lotus 20g Sakamoto 10g Yellow 芩 40g Forsythia 40g Wild Chrysanthemum 40g Trichosanthin 40g Rehmannia 60g Danshen 40g 茯苓 80g Licorice 10 g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十四味, 辛夷、 薄荷、 藁本、野菊花四味药加水 900ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他十味药加水 5200ml煎煮 1. 5小时, 趁热过滤; 将上 述两种药渣合并, 再加水 6200ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷 等蒸馏后的水溶液, 浓缩至 60°C相对密度 1. 35-1. 40的清膏; 与辅料混合制粒, 千燥 整粒,制成 200粒,喷挥发油,密闭 24小时,即得颗粒剂。每粒 0. 3克,相当原料 2. 8g, 开水冲服, 一日 3次, 一次 10- 15g, 每袋装 10g。  The above fourteen flavors, Xinyi, Mint, Sakamoto, Wild Chrysanthemum, four flavors of water and 900ml of water to extract volatile oil, the aqueous solution and the dregs after distillation are separately collected; the other ten herbs add water 5200ml to cook 1. 5 hours, hot filtered The singularity of the above-mentioned two medicinal slags, and then adding the water to 6200ml, simmering, and sifting, and sifting to a concentration of 1.35-1. Clear paste; mixed with auxiliary materials, granules, dried and granulated, made into 200 capsules, sprayed with volatile oil, sealed for 24 hours, that is, granules. Each tablet is 0.3 g, which is quite raw material 2. 8 g, boiled in water, 3 times a day, 10-15 g once, 10 g per bag.
实施例 11 :  Example 11:
辛夷 20g 苍耳子 60g 麻黄 40g 白芷 60g  Xinyi 20g Xanthium 60g Ephedra 40g White Pelican 60g
薄荷 20g 藁 本 10g 黄芩 40g 连翘 40g  Mint 20g 藁 Ben 10g Astragalus 40g Forsythia 40g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上八味, 辛夷、 薄荷、藁本三味药加水 450ml提取挥发油, 蒸馏后的水溶液及药 渣分别另器收集; 其他五味药加水 2400ml煎煮 2小时, 趁热过滤; 将上述两种药渣合 并, 再加水 3000ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷等蒸馏后的水 溶液, 浓缩成清膏; 最后经过常规工序加入药学上可接受的赋形剂辅料制成软胶囊。 实施例 12: The above eight flavors, Xinyi, Mint, and Sakamoto three kinds of medicines add 450ml of water to extract volatile oil, and the distilled aqueous solution and dregs are collected separately; the other five herbs are boiled in water 2400ml for 2 hours, hot filtered; the above two kinds of dregs are combined Add 3,000ml of water to boil twice, each time for 1 hour, filter, combine the filtrate with the above distilled water solution, and concentrate to a clear paste. Finally, add pharmaceutically acceptable excipients to make soft capsules through routine procedures. . Example 12
辛夷 10g 苍耳子 30g 麻黄 60g 白芷 30g  Xinyi 10g Xanthium 30g Ephedra 60g White Pelican 30g
薄荷 10g 藁 本 5g 黄芩 20g 连翘 20g  Mint 10g 藁 this 5g jaundice 20g forsythia 20g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上八味, 辛夷、薄荷、藁本三味药加水 300ml提取挥发油, 蒸馏后的水溶液及药 渣分别另器收集; 其他五味药加水 1500ml煎煮 1小时, 趁热过滤; 将上述商种药渣合 并, 再加水 2000ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷等蒸馏后的水 溶液, 浓缩成清膏; 最后经过常规工序加入药学上可接受的赋形剂辅料制成软胶囊。 实施例 13- 辛夷 30g 苍耳子 90g 麻黄 20g 白芷 90g The above eight flavors, Xinyi, Mint, Sakamoto three herbs add water 300ml to extract volatile oil, the distilled aqueous solution and dregs are separately collected; the other five herbs add water 1500ml boiling for 1 hour, hot filtered; combine the above-mentioned commercial dregs Add boiling water 2000ml twice, each time for 1 hour, filter, combine the filtrate with the above distilled water solution, and concentrate to a clear paste; finally add pharmaceutically acceptable excipients to make soft capsules through routine procedures. . Example 13 - Xinyi 30g Xanthium 90g Ephedra 20g White Pelican 90 g
薄荷 10g 藁 本 5g 黄芩 40g 连翘 40g  Mint 10g 藁 this 5g jaundice 40g forsythia 40g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上八味, 辛夷、薄荷、藁本三味药加水 400ml提取挥发油, 蒸馏后的水溶液及药 渣分别另器收集; 其他五味药加水 3000ml煎煮 1. 5小时, 趁热过滤; 将上述两种药渣 合并, 再加水 3500ml煎煮 1次, .每次 0. 5小时, 过滤, 合并滤液与上述辛夷等蒸馏后 的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料制成软胶囊。 实施例 7:  The above eight flavors, Xinyi, Mint, and Sakamoto three kinds of medicines add 400ml of water to extract volatile oil, and the distilled aqueous solution and dregs are collected separately; the other five herbs add water 3000ml to cook for 1.5 hours, hot filtered; The slag is combined, and then decocted with water 3500 ml, once every 0.5 hours, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable excipient is added through a conventional procedure. The auxiliary material is made into a soft capsule. Example 7
辛夷 20g 苍耳子 60g 麻黄 40g 白 芷 60g 薄 荷 20g  Xinyi 20g Xanthium 60g Ephedra 40g White 芷 60g Thin Lotus 20g
藁本 10g 黄 芩 40g 连翘 40g 野菊花 40g 天花粉 40g  Sakamoto 10g yellow 芩 40g forsythia 40g wild chrysanthemum 40g trichosanthin 40g
地黄 60g 丹 参 40g 茯苓 80g Rehmannia 60g Danshen 40g 茯苓 80g
其中, 苍耳子以炒为佳。  Among them, Xanthium is better for frying.
以上十三味, 辛夷、 薄荷、 藁本、野菊花四味药加水 800ml提取挥发油, 蒸馏后的 水溶液及药渣分别另器收集; 其他九味药加水 4000ml煎煮 2小时, 趁热过滤; 将上述 两种药渣合并, 再加水 4000ml煎煮两次, 每次 1小时, 过滤, 合并滤液与上述辛夷等 蒸馏后的水溶液,浓缩成清膏;最后经过常规工序加入药学上可接受的赋形剂辅料制成 软胶囊。  The above thirteen flavors, Xinyi, Mint, Sakamoto, and wild chrysanthemums are added with 800ml of water to extract volatile oil. The distilled aqueous solution and dregs are collected separately; the other nine herbs are boiled in 4000ml for 2 hours, and hot filtered; The above two kinds of dregs are combined, and then boiled twice with water 4000 ml, one hour each time, filtered, and the combined filtrate and the above-mentioned distilled aqueous solution are concentrated to form a clear paste; finally, a pharmaceutically acceptable shape is added through a conventional procedure. The agent is made into a soft capsule.

Claims

权利要求 Rights request
1. 一种治疗急慢性鼻渊的中药组合物, 其特征在于, 所述组合物是由以下原料药 材制备而成:  A traditional Chinese medicine composition for treating acute and chronic nasal apes, characterized in that the composition is prepared from the following raw materials:
辛夷 10-30重量份 苍耳子 30-90重量份 麻黄 20-60重量份  Xinyi 10-30 parts by weight Xanthium 30-90 parts by weight Ephedra 20-60 parts by weight
白芷 30-90重量份 薄荷 10-30重量份 藁本 5-15重量份  White 芷 30-90 parts by weight Mint 10-30 parts by weight 藁 5-15 parts by weight
黄芩 20-40重量份 连翘 20-40重量份  Astragalus 20-40 parts by weight Forsythia 20-40 parts by weight
2.如权利要求 1所述的中药组合物, 其特征在于, 所述原料药材进一步包括: 野菊花 20-40重量份 天花粉 20-40重量份 地黄 30-60重量份'  The traditional Chinese medicine composition according to claim 1, wherein the raw material medicinal material further comprises: wild chrysanthemum 20-40 parts by weight, trichosanthin 20-40 parts by weight, rehmannia 30-60 parts by weight
丹参 20-40重量份 茯苓 40-120重量份  Salvia 20-40 parts by weight 茯苓 40-120 parts by weight
3. 如权利要求 2所述的中药组合物, 其特征在于, 所述原料药材还包括甘草 5-15  3. The traditional Chinese medicine composition according to claim 2, wherein the raw material medicine further comprises licorice 5-15
4.如权利要求 3所述的中药组合物, 其特征在于, 所述原料药材为: The traditional Chinese medicine composition according to claim 3, wherein the raw material medicine is:
辛夷 15-25重量份 苍耳子 50-70重量份 麻黄 30-50重量份  Xinyi 15-25 parts by weight Xanthium 50-70 parts by weight Ephedra 30-50 parts by weight
白芷 50-70重量份 薄荷 15-35重量份 藁本 8-18重量份  White 芷 50-70 parts by weight Mint 15-35 parts by weight 藁 Ben 8-18 parts by weight
黄芩 30-50重量份 连翘 30-50重量份 野菊花 30-50重量份  Astragalus 30-50 parts by weight Forsythia 30-50 parts by weight Wild chrysanthemum 30-50 parts by weight
丹参 30-50重量份  Salvia miltiorrhiza 30-50 parts by weight
茯苓 70-90重量份 甘草 8-15 重量份  茯苓 70-90 parts by weight licorice 8-15 parts by weight
5.如权利要求 4所述的药物组合物, 其特征在于, 所述原料药材为:  The pharmaceutical composition according to claim 4, wherein the raw material medicine is:
辛夷 20重量份 苍耳子 60重量份 麻黄 40重量份  Xinyi 20 parts by weight Xanthium 60 parts by weight Ephedra 40 parts by weight
白芷 60重量份 薄荷 20重量份 藁本 10重量份  White peony 60 parts by weight mint 20 parts by weight 藁 10 parts by weight
黄芩 40重量份 连翘 40重量份 野菊花 40重量份  Astragalus 40 parts by weight Forsythia 40 parts by weight Wild chrysanthemum 40 parts by weight
天花粉 40重量份 地黄 60重量份 . 丹参 40重量份  40 parts by weight of Tianhua powder 60 parts by weight of Dihuang. 40 parts by weight of Salvia miltiorrhiza
茯苓 80重量份 甘草 10重量份  茯苓 80 parts by weight Licorice 10 parts by weight
6. 如权利要求 1、 2、 3、 4或 5所述的中药组合物, 其特征在于, 苍耳子是炒苍耳 子'  6. The traditional Chinese medicine composition according to claim 1, 2, 3, 4 or 5, wherein the Xanthium is a fried scorpion
7. 一种制备权利要求 1至 6中任意一种中药组合物的方法, 其特征在于, 所述方 法为: 在辛夷、 薄荷、 藁本、 野菊花四味药中加入 5-10倍水(w/v) 以提取挥发油, 蒸 馏后的水溶液及药渣分别另器收集;其余原料药组分加 5-15倍水(w/v)煎煮 1-3小时, 趁热过滤, 滤液备用, 过滤后的药渣与上述药渣合并, 再加 5-15倍水 (w/v) 煎煮 1-3 次, 每次 0.5-1.5小时, 过滤, 合并所有滤液和上述辛夷等蒸馏后的水溶液, 浓缩成清 膏; 然后加入药学上可接受的辅料, 以常规工艺制成临床上可接受的剂型. A method for preparing a traditional Chinese medicine composition according to any one of claims 1 to 6, wherein the method comprises: adding 5-10 times of water to the four flavors of Magnolia, Mint, Sakamoto and Wild Chrysanthemum ( w/v) to extract volatile oil, the distilled aqueous solution and dregs are separately collected; the remaining raw material components are added 5-15 times water (w/v) for 1-3 hours, filtered while hot, and the filtrate is reserved. The filtered dregs are combined with the above-mentioned dregs, and then added 5-15 times of water (w/v) for 1-3 times, 0.5-1.5 hours each time, filtered, and all the filtrates and the above-mentioned distilled aqueous solution are combined. , concentrated into clear 1. A pharmaceutically acceptable excipient is then added to form a clinically acceptable dosage form by conventional techniques.
8. 如权利要求 1至 5中任意一种中药组合物, 其特征在于, 该中药组合物的存在 形式是任何一种临床上所能接受的剂型。  8. A traditional Chinese medicine composition according to any one of claims 1 to 5, characterized in that the traditional Chinese medicine composition is present in any clinically acceptable dosage form.
9. 如权利要求 6所述的中药组合物, 其特征在于, 该中药组合物的存在形式是任 何一种临床上所能接受的剂型。  9. The traditional Chinese medicine composition according to claim 6, wherein the traditional Chinese medicine composition is present in any clinically acceptable dosage form.
10. 如权利要求 8或 9所述的中药物组合物, 其特征在于, 所述剂型为颗粒剂。  The pharmaceutical composition according to claim 8 or 9, wherein the dosage form is a granule.
PCT/CN2004/000824 2004-07-16 2004-07-16 Traditional chinese medicine composition for treating acute and chronic nasosinusitis and preparation thereof WO2006007758A1 (en)

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CN102614259A (en) * 2011-06-03 2012-08-01 宋协勘 Chinese medicine for treating chronic suppurative nasosinusitis
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CN104189703A (en) * 2014-07-30 2014-12-10 严中明 Traditional Chinese medicine composition for treating kidney-vitality deficiency type running nose
CN104258318A (en) * 2014-07-30 2015-01-07 严中明 Traditional Chinese medicine composition for treating lung qi deficiency and cold type rhinorrhea disease
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CN102274335A (en) * 2011-05-09 2011-12-14 杨兴周 Chinese herbal medicine nasal drops for one-time radical treatment of rhinitis and nasosinusitis
CN102614259A (en) * 2011-06-03 2012-08-01 宋协勘 Chinese medicine for treating chronic suppurative nasosinusitis
CN102697894A (en) * 2012-06-04 2012-10-03 韦相炎 Medicinal composition for treating nasal cavity inflammatory disease and preparation method thereof
CN102697894B (en) * 2012-06-04 2014-04-30 韦相炎 Medicinal composition for treating nasal cavity inflammatory disease and preparation method thereof
CN103223019A (en) * 2013-04-04 2013-07-31 施怀杰 Traditional Chinese medicine for treating rhinitis
CN103142709A (en) * 2013-04-07 2013-06-12 步新源 Medicament for treating cold
CN104189703A (en) * 2014-07-30 2014-12-10 严中明 Traditional Chinese medicine composition for treating kidney-vitality deficiency type running nose
CN104258318A (en) * 2014-07-30 2015-01-07 严中明 Traditional Chinese medicine composition for treating lung qi deficiency and cold type rhinorrhea disease
CN104337919A (en) * 2014-10-15 2015-02-11 四川金堂海纳生物医药技术研究所 Internal medicine for treating nasosinusitis and preparation method thereof
CN107684586A (en) * 2017-08-27 2018-02-13 钟启义 A kind of Chinese medicine for treating chronic frontal sinusitis
CN107496505A (en) * 2017-09-30 2017-12-22 廖会吉 It is a kind of to treat rhinitis, nasosinusitis, the medicine and preparation method thereof of nasal polyp enlargement

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