CA3167551A1

CA3167551A1 - Use of pharmaceutical composition in preparing antibacterial drug

Info

Publication number: CA3167551A1
Application number: CA3167551A
Authority: CA
Inventors: Zhenhua Jia
Original assignee: Shijiazhuang Yiling Pharmaceutical Co Ltd
Current assignee: Shijiazhuang Yiling Pharmaceutical Co Ltd
Priority date: 2020-03-07
Filing date: 2021-03-02
Publication date: 2021-09-16
Also published as: CN113350440A; CN113350440B; ZA202208931B; WO2021179947A1

Abstract

A use of a pharmaceutical composition in preparing an antibacterial drug, the pharmaceutical composition being made from Ephedra sinica, gypsum, Forsythia, Scutellaria baicalensis, white mulberry root bark, fried bitter apricot kernel, radix peucedani, pinelliae rhizoma, chenpi, Bulbus Fritillariae thunbergii, greater burdock fruit, Flos Lonicerae japonicae, Rheum officinale, Chinese bellflower, and Glycyrrhiza uralensis, used to inhibit the Gram-positive bacteria Staphylococcus aureus, group A hemolytic streptococcus, group B hemolytic streptococcus, and Diplococcus pneumoniae, and the Gram-negative bacteria Escherichia coli and Shigella dysenteriae.

Description

USE OF PHARMACEUTICAL COMPOSITION IN PREPARING ANTIBACTERIAL
DRUG
[0001] This application claims the priority of Chinese Patent Application No.
202010153831.8, filed with the China National Intellectual Property Administration on March 7, 2020, and titled with "USE OF TRADITIONAL CHINESE MEDICINE COMPOSITION IN PREPARATION OF
ANTIBACTERIAL DRUG", which is hereby incorporated by reference in entirety.
FIELD

[0002] The present disclosure relates to the use of a pharmaceutical composition in the manufacture of antibacterial drugs, and belongs to the field of medicine.
BACKGROUND

[0003] Antibiotics refer to a class of secondary metabolic product, with anti-pathogen and other activities, from the life processes of microorganisms (including bacteria, fungi and actinomycetes) or higher animals and plants, and are chemical substances that can interfere with the developmental functions of other living cells. Commonly used antibiotics in clinics include extracts from microbial cultures and chemically synthesized or semi-synthetic compounds. The bacteriostatic or bactericidal effect of antibiotics mainly includes four major mechanisms, namely: inhibiting synthesis of bacterial cell wall, enhancing permeability of bacterial cell membrane, interfering with synthesis of bacterial protein, and inhibiting replication and transcription of bacterial nucleic acids.
Antibiotics play a major role in the treatment of many bacterial infectious diseases. However, misuse of antibiotics has caused more and more bacteria to develop drug resistance. The improper uses antibiotics, including the abuse (which may causes long course of treatment), arbitrary replacement, combination and blind use of antibiotics, have caused problem that many strains develop multi-drug resistance and extensive drug resistance.

[0004] Therefore, effective antibacterial drugs, especially for those with broad-spectrum antibacterial properties or capable of effectively improving drug resistance, are still desired.
- i -

[0005] The present disclosure is an improved invention based on the pharmaceutical composition disclosed in the patent CN101549060B, the contents of which are incorporated herein in its entirety.
The above-mentioned patent does not disclose that the pharmaceutical composition has antibacterial effect.
SUMMARY

[0006] The inventors unexpectedly found in the research that the pharmaceutical composition of this disclosure has excellent antibacterial effect, and the pharmaceutical composition is prepared from the following materials in parts by weight:
ephedrae herba 52-86, gypsum fibrosum 194-324, forsythiae fructus 194-324, scutellariae radix 78-130, mori cortex 194-324, armeniacae semen amarum 78-130, peucedani radix 78-130, pinelliae rhizoma 78-130, citri reticulatae pericarpium 78-130, fritillariae bulbus 78-130, arctii fructus 78-130, lonicerae japonicae flos 78-130, rhei radix et rhizoma 39-65, platycodonis radix 46-76, glycyrrhizae radix et rhizoma 39-65.

[0007] The pharmaceutical composition of this disclosure is preferably prepared from the following materials in parts by weight:
ephedrae herba 52, gypsum fibrosum 324, forsythiae fructus 194, scutellariae radix 78, mori cortex 194, armeniacae semen amarum 130, peucedani radix 78, pinelliae rhizoma 130, citri reticulatae pericarpium 78, fritillariae bulbus 78, arctii fructus 130, lonicerae japonicae flos 130, rhei radix et rhizoma 39, platycodonis radix 76, glycyrrhizae radix et rhizoma 65.

[0008] The pharmaceutical composition of this disclosure is also preferably prepared from the following materials in parts by weight:
ephedrae herba 86, gypsum fibrosum 194, forsythiae fructus 324, scutellariae radix 130, mori cortex 324, armeniacae semen amarum 78, peucedani radix 130, pinelliae rhizoma 78, citri reticulatae pericarpium 130, fritillariae bulbus 130, arctii fructus 78, lonicerae japonicae flos 78, rhei radix et rhizoma 65, platycodonis radix 46, glycyrrhizae radix et rhizoma 39.

[0009] The pharmaceutical composition of this disclosure is also preferably prepared from the following materials in parts by weight:
ephedrae herba 69, gypsum fibrosum 259, forsythiae fructus 259, scutellariae radix 104, mori cortex 259, armeniacae semen amarum 104, peucedani radix 104, pinelliae rhizoma 104, citri reticulatae pericarpium 104, fritillariae bulbus 104, arctii fructus 104, lonicerae japonicae flos 104, rhei radix et rhizoma 52, platycodonis radix 61;
glycyrrhizae radix et rhizoma 52.

[0010] The pharmaceutical composition of this disclosure is also preferably prepared from the following materials in parts by weight:

ephedrae herba 55, gypsum fibrosum 254, forsythiae fructus 318, scutellariae radix 107, mori cortex 203, armeniacae semen amarum 107, peucedani radix 82, pinelliae rhizoma 105, citri reticulatae pericarpium 84, fritillariae bulbus 125, arctii fructus 122, lonicerae japonicae flos 113, rhei radix et rhizoma 42, platycodonis radix 60, glycyrrhizae radix et rhizoma 50.

[0011] Preferably, in the pharmaceutical composition of this disclosure, the armeniacae semen amarum is stir-baked armeniacae semen amarum, the fritillariae bulbus is fritillariae thunbergii bulbus, the lonicerae japonicae flos is lonicerae flos, and the pinelliae rhizoma is pinelliae rhizoma praeparatum cum alumine.

[0012] The pharmaceutical composition of this disclosure has been proved by clinical experiments that it can effectively kill various bacteria with a remarkable effect.

[0013] The active ingredient of the pharmaceutical composition of this disclosure can be prepared by a method including:

[0014] step A. pulverizing fritillariae thunbergii bulbus weighed according to formula ratio into fine powder;

[0015] step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 40-70% ethanol in an amount of 8-10 times of the mixture for a first extraction under reflux for 1-4 h, adding 40-70% ethanol in an amount of 6-9 times of the mixture for a second extraction under reflux for 1-4 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.14-1.16 measured at 60 C while recovering ethanol;

[0016] step C. to a mixture of gypsum fibrosum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 9-11 times of the mixture for a first boiling for 1-4 h, adding water in an amount of 7-9 times of the mixture for a second boiling for 1-4 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.14-1.16 measured at 60 C, and combining with the clear paste obtained in the step B
to obtain a clear paste mixture; and

[0017] step D. mixing the fine powder obtained in the step A and the clear paste mixture obtained in the step C to obtain the active ingredients of the pharmaceutical composition.

[0018] The dosage form of the medicament of this disclosure can be in a form selected from the group consisting of capsule, tablet, powder, granule, oral liquid, pill, tincture, syrup, suppository, gel, spray and injection.

[0019] To obtain the above dosage forms, it is preferable to add a pharmaceutically acceptable adjuvant during the preparation of these dosage forms, including fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases and the like. The fillers include starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, and the like. The disintegrants include starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and the like. The lubricants include magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide and the like. The suspending agents include polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose and the like. The binders include starch syrup, polyvinylpyrrolidone, hydroxypropyl methylcellulose and the like. The sweeteners include sodium saccharin, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid and the like. The flavoring agents include sweeteners and various flavors. The preservatives include parabens, benzoic acid, sodium benzoate, sorbic acid and salts thereof, benzalkonium bromide, chlorhexidine acetate, eucalyptus oil and the like. The bases include PEG6000, PEG4000, insect wax and the like.

[0020] The tablet can be prepared by a process including:

[0021] step A. pulverizing fiitillaiiae bulbus weighed according to formula ratio into fine powder;

[0022] step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 40-70% ethanol in an amount of 8-10 times of the mixture for a first extraction under reflux for 1-4 h, adding 40-70% ethanol in an amount of 6-9 times of the mixture for a second extraction under reflux for 1-4 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.14-1.16 measured at 60 C while recovering ethanol;

[0023] step C. to a mixture of gypsum fibrosum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 9-11 times of the mixture for a first boiling for 1-4 h, adding water in an amount of 7-9 times of the mixture for a second boiling for 1-4 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.14-1.16 measured at 60 C, and combining with the clear paste obtained in the step B
to obtain a clear paste mixture;

[0024] step D. spray-drying the clear paste mixture obtained in the step C and collecting spray powder; and

[0025] step E. preparing the spray powder obtained in the step D and the fine powder obtained in the step A into soft material by using ethanol as binder, sieving, pelletizing, and tableting by conventional methods of pharmacy.

[0026] Preferably, the process for preparing the tablet includes:

[0027] step A. pulverizing fritillariae bulbus weighed according to formula ratio into fine powder;

[0028] step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 50% ethanol in an amount of 10 times of the mixture for a first extraction under reflux for 3 h, adding 50% ethanol in an amount of 6 times of the mixture for a second extraction under reflux for 3 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.15 measured at 60 C while recovering ethanol;

[0029] step C. to a mixture of gypsum fibrosum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 10 times of the mixture for a first boiling for 2 h, adding water in an amount of 7 times of the mixture for a first boiling for 2 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.15 measured at 60 C, and combining with the clear paste obtained in the step B to obtain a clear paste mixture;

[0030] step D. spray-drying the clear paste mixture obtained in the step C and collecting spray powder; and

[0031] step E. preparing the spray powder obtained in the step D and the fine powder obtained in the step A into soft material by using ethanol as binder, sieving, pelletizing, drying, granulating, mixing well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and tableting.

[0032] Other dosage forms of the medicament according to this disclosure can be prepared from the materials weighed in proportion by conventional preparation methods. For example, according to the preparation process described in Fan Biting's "Pharmaceuticals of Traditional Chinese Medicine" (Shanghai Science Press, December 1997 1st edition), pharmaceutically acceptable conventional dosage forms can be made.

[0033] Experiments have demonstrated that the pharmaceutical composition of this disclosure has significant bacteriostatic effect on a-hemolytic streptococcus, 13-hemolytic streptococcus, staphylococcus aureus and streptococcus pneumoniae.

[0034] In another aspect of this disclosure, a method of inhibiting or killing bacteria includes administering the pharmaceutical composition of this disclosure to a subject in need thereof In another aspect of this disclosure, a method of preventing bacterial infection or killing bacteria includes administering the pharmaceutical composition of this disclosure to a subject in need thereof. Preferably, the bacteria are gram-positive bacteria; and more preferably, the gram-positive bacteria are selected from the group consisting of staphylococcus aureus, a-hemolytic streptococcus, 13-hemolytic streptococcus and streptococcus pneumoniae. In another preferred aspect, the bacteria are gram-negative bacteria; and more preferably, the gram-negative bacteria are selected from the group consisting of escherichia coli and shigella dysenteriae.
BRIEF DESCRIPTION OF DRAWINGS

[0035] FIG. 1 shows the protective effect of the pharmaceutical composition of this disclosure on mice infected with staphylococcus aureus.
DETAILED DESCRIPTION

[0036] The following examples are intended to illustrate the preparation of the pharmaceutical compositions of this disclosure. It should be understood that they are intended to limit the scope of the present invention.
Examples Example 1

[0037] Formula:
ephedrae herba 52 g, gypsum fibrosum 324 g, forsythiae fructus 194 g, scutellariae radix 78 g, mori cortex 194 g, armeniacae semen amarum 130 g, peucedani radix 78 g, pinelliae rhizoma 130 g, citri reticulatae pericarpium 78 g, fi-itillariae thunbergii bulbus 78 g, arctii fructus 130 g, lonicerae flos 130 g, rhei radix et rhizoma 39 g, platycodonis radix 76 g, glycyrrhizae radix et rhizoma 65 g.

[0038] Preparation:

[0039] A. Fritillaiiae thunbergii bulbus was weighed according to the formula ratio and pulverized into fine powder.

[0040] B. Ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma were weighed according to the formula ratio. To the mixture, 50% ethanol was added in an amount of 10 times of the mixture for a first extraction under reflux for 3 h, and 50% ethanol was added in an amount of 6 times of the mixture for a second extraction under reflux for 3 h. The extracts were combined, and filtered. The filtrate was concentrated under reduced pressure into a clear paste with a relative density of 1.15 measured at 60 C, with ethanol being recovered.

[0041] C. Gypsum ustum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma were weighed according to the formula ratio. To the mixture, water was added in an amount of 10 times of the mixture for a first boiling for 2 h, and water was added in an amount of 7 times of the mixture for a first boiling for 2 h. The decoctions was combined, and filtered. The filtrate was concentrated into a clear paste with a relative density of 1.15 measured at 60 C. The clear paste was combined with the clear paste obtained in the step B to obtain a clear paste mixture.

[0042] D. The clear paste mixture obtained in the step C was spray-dried to collect spray powder.

[0043] E. The spray powder obtained in the step D and the fine powder obtained in the step A
were prepared into soft material using 80% ethanol as binder. The soft material was sieved, pelletized, dryed at 60 C, and granulated. The granules was mixed well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and prepared into tablets by conventional preparation methods.
Example 2

[0044] Formula:
ephedrae herba 86 g, gypsum fibrosum 194 g, forsythiae fructus 324 g, scutellariae radix 130 g, mori cortex 324 g, stir-baked armeniacae semen amarum 78 g, peucedani radix 130 g, pinelliae rhizoma 78 g, citri reticulatae pericarpium 130 g, fritillariae bulbus 130 g, arctii fructus 78 g, lonicerae flos 78 g, rhei radix et rhizoma 65 g, platycodonis radix 46 g, glycyrrhizae radix et rhizoma 39 g.

[0045] Preparation:

[0046] A. Fritillariae bulbus was weighed according to the formula ratio and pulverized into fine powder.

[0047] B. Ephedrae herba, forsythiae fructus, stir-baked armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma were weighed according to the formula ratio. To the mixture, 40% ethanol was added in an amount of 8 times of the mixture for a first extraction under reflux for 4 h, and 40% ethanol was added in an amount of 9 times of the mixture for a second extraction under reflux for 4 h. The extracts was combined and filtered. The filtrate was concentrated under reduced pressure into a clear paste with a relative density of 1.14 measured at 60 C, with ethanol being recovered.

[0048] C. Gypsum ustum, mori cortex, peucedani radix, citri reticulatae pericaTium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma were weighted according to the formula ratio. To the mixture, water was added in an amount of 9 times of the mixture for a first time boiling for 4 h, and water was added in an amount of 7 times of the mixture for a second boiling for 4 h. The decoctions were combined and filtered. The filtrate was concentrated into a clear paste with a relative density of 1.16 measured at 60 C. The clear paste was combined with the clear paste obtained in the step B to obtain a clear paste mixture.

[0049] D. The clear paste mixture obtained in the step C was spray-dried to collect spray powder.

[0050] E. The spray powder obtained in the step D and the fine powder obtained in the step A
were prepared into soft material using 80% ethanol as binder. The soft material was sieved, pelletized, dried at 60 C, and granulated. The granules was mixed well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and prepared into tablets by conventional preparation methods.
Example 3

[0051] Formula:
ephedrae herba 69 g, gypsum fibrosum 259 g, forsythiae fructus 259 g, scutellariae radix 104 g, mori cortex 259 g, stir-baked armeniacae semen amarum 104 g, peucedani radix 104 g, pinelliae rhizoma praeparatum cum alumine 104 g, citri reticulatae pericarpium 104 g, fiitillariae thunbergii bulbus 104 g, arctii fructus 104 g, lonicerae flos 104 g, rhei radix et rhizoma 52 g, platycodonis radix 61 g, glycyrrhizae radix et rhizoma 52 g.

[0052] Preparation:

[0053] A. Fritillaiiae thunbergii bulbus was weighed according to the formula ratio and pulverized into fine powder.

[0054] B. Ephedrae herba, forsythiae fructus, stir-baked armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma were weighed according to the formula ratio. To the mixture, 70% ethanol was added in an amount of 10 times of the mixture for a first extraction under reflux for 1 h, and 70% ethanol was added in an amount of 6 times of the mixture for a second extraction under reflux for 1 h. The extracts were combined and filtered. The filtrate was concentrated under reduced pressure into a clear paste with a relative density of 1.16 measured at 60 C, with ethanol being recovered.

[0055] C. Gypsum ustum, mori cortex, peucedani radix, citri reticulatae pericaTium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma were weighted according to the formula ratio. To the mixture, water was added in an amount of 11 times of the mixture for a first boiling for 1 h, and water was added in an amount of 7 times of the mixture for a second boiling for 1 h. The decoctions were combined and filtered. The filtrate was concentrated into a clear paste with a relative density of 1.14 measured at 60 C. The clear paste was combined with the clear paste obtained in the step B to obtain a clear paste mixture.

[0056] D. The clear paste mixture obtained in the step C was spray-dried to collect spray powder.

[0057] E. The spray powder obtained in the step D and the fine powder obtained in the step A
were prepared into soft material using 80% ethanol as binder. The soft material was sieved, pelletized, dried at 60 C, and granulated. The granules was mixed well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and prepared into tablets by conventional preparation methods.

Example 4:

[0058] Formula of materials:
ephedrae herba 55 g, gypsum fibrosum 254 g, forsythiae fructus 318 g, scutellariae radix 107 g, mori cortex 203 g, stir-baked armeniacae semen amarum 107 g, peucedani radix 82 g, pinelliae rhizoma 105 g, citri reticulatae pericarpium 84 g, fritillariae thunbergii bulbus 125 g, arctii fructus 122 g, lonicerae flos 113 g, rhei radix et rhizoma 42 g, platycodonis radix 60 g, glycyrrhizae radix et rhizoma 50 g.

[0059] Preparation:

[0060] A. Fritillariae thunbergii bulbus was weighed according to the formula ratio and pulverized into fine powder.

[0061] B. Ephedrae herba, forsythiae fructus, stir-baked armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma were weighed according to the formula ratio. To the mixture, 60% ethanol was added in an amount of 9 times of the mixture for a first time extraction under reflux for 2 h, and 60% ethanol was added in an amount of 7 times of the mixture for a second time extraction under reflux for 2 h. The extracts were combined and filtered. The filtrate was concentrated under reduced pressure into a clear paste with a relative density of 1.15 measured at 60 C, with ethanol being recovered.

[0062] C. Gypsum ustum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma were weighted according to the formula ratio. To the mixture, water was added in an amount of 10 times of the mixture for a first boiling for 2.5 h, and water was added in an amount of 7 times of the mixture for a second boiling for 2.5 h. Decoctions were combined and filtered. The filtrate was concentrated into a clear paste with a relative density of 1.14 measured at 60 C. The clear paste was combined with the clear paste obtained in the step B to obtain a clear paste mixture.

[0063] D. The clear paste mixture obtained in the step C was spray-dried to collect spray powder;
and

[0064] E. The spray powder obtained in the step D and the fine powder obtained in the step A
were prepared into soft material using 80% ethanol as binder. The soft material was sieved, pelletized, dried at 60 C, and granulated. The granules was mixed well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and prepared into tablets by conventional preparation methods.
Example 5:

[0065] Capsules were prepared by conventional methods from the following medical materials:
ephedrae herba 62 g, gypsum fibrosum 220 g, forsythiae fructus 256 g, scutellariae radix 90 g, mori cortex 300 g, armeniacae semen amarum 90 g, peucedani radix 90 g, pinelliae rhizoma 90 g, citri reticulatae pericamium 100 g, fritillariae bulbus 100 g, arctii fructus 100 g, lonicerae japonicae flos 100 g, rhei radix et rhizoma 50 g, platycodonis radix 66 g, and glycyrrhizae radix et rhizoma 50g.
Example 6:

[0066] Granules were prepared by conventional methods from the following medical materials:
ephedrae herba 68 g, gypsum fibrosum 215 g, forsythiae fructus 215 g, scutellariae radix 100 g, mori cortex 220 g, armeniacae semen amarum 90 g, peucedani radix 90 g, pinelliae rhizoma 90 g, citri reticulatae pericarpium 90 g, fritillariae bulbus 90 g, arctii fructus 90 g, lonicerae japonicae flos 90 g, rhei radix et rhizoma 50 g, platycodonis radix 50 g, and glycyrrhizae radix et rhizoma 50 g.
Example 7:

[0067] Injections were prepared by conventional methods from the following medical materials:
ephedrae herba 50 g, gypsum fibrosum 200 g, forsythiae fructus 300 g, scutellariae radix 100 g, mori cortex 250 g, armeniacae semen amarum 100 g, peucedani radix 100 g, pinelliae rhizoma 100 g, citri reticulatae pericarpium 100 g, fritillariae bulbus 100 g, arctii fructus 100 g, lonicerae japonicae flos 100 g, rhei radix et rhizoma 50 g, platycodonis radix 50 g, and glycyrrhizae radix et rhizoma 50 g.

Example 8:

[0068] Pills were prepared by conventional methods from the following medical materials:
ephedrae herba 60 g, gypsum fibrosum 200 g, forsythiae fructus 200 g, scutellariae radix 95 g, mori cortex 230 g, armeniacae semen amarum 95 g, peucedani radix 95 g, pinelliae rhizoma 95 g, citri reticulatae pericamium 95 g, fritillariae bulbus 95 g, arctii fructus 95 g, lonicerae japonicae flos 95 g, rhei radix et rhizoma 50 g, platycodonis radix 50 g, and glycyrrhizae radix et rhizoma 50 g.
Biological activity test examples:

[0069] In order to confirm that the pharmaceutical composition of this disclosure has antibacterial effects, the pharmaceutical composition prepared in Example 3 of this disclosure, that is, the granules after granulation but before being prepared into tablets in Step E of Example 3 (hereinafter referred to as the drug of this disclosure), was studied for pharmacology:

[0070] Study on the in vitro antibacterial effect of the pharmaceutical composition of this disclosure

[0071] Experimental Materials

[0072] 1. Drugs and reagents:

[0073] (1) The test drug was the pharmaceutical composition of this disclosure (prepared in Example 3), which was brown-yellow granules, and each gram of granules was equivalent to 4.095 g of crude drugs. The drug was administered orally at a daily dosage of 22 g of crude drugs/person, which was equivalent to 0.367 g of the pharmaceutical composition/kg of body weight based on 60 kg of human body weight.

[0074] (2) The positive control drug was Shuanghuanglian Oral Liquid, produced by Harbin Pharmaceutical Group Sanchine Pharmaceutical Co., Ltd., with the batch number of 07101243.

[0075] 2. Bacterial strains:

[0076] (1) Standard strains: staphylococcus aureus (no. 26112), a-hemolytic streptococcus (no.
32209), I3-hemolytic streptococcus (no. 32210), streptococcus pneumoniae (no.
31001), escherichia coli (no. 44155), staphylococcus epidermidis (no. 26487), micrococcus catarrhalis (no.
29103), pseudomonas aeruginosa (no. 10104), shigella dysenteriae (no. 51592), and salmonella typhi (no. 50071). They are all purchased from national institute for the Control of Pharmaceutical and Biological Products.

[0077] (2) Clinical strains: 5 strains each of staphylococcus aureus, a-hemolytic streptococcus, 13-hemolytic streptococcus and streptococcus pneumonia. The 20 strains of bacteria were clinically isolated from the Dongfang Hospital Affiliated to Beijing University of Traditional Chinese Medicine.

[0078] 3. Culture medium:

[0079] Broth medium and 2% agar broth medium were used for passage and test of staphylococcus aureus, escherichia coli, staphylococcus epidermidis, pseudomonas aeruginosa, shigella dysenteriae and salmonella typhi; 10% serum broth medium and 10%
serum agar broth medium were used for passage and test of a-hemolytic streptococcus, 0-hemolytic streptococcus and streptococcus pneumoniae.

[0080] Methods and Results

[0081] 1. Preparation of the pharmaceutical composition of this disclosure:

[0082] 4.88 g granules of the pharmaceutical composition of this disclosure was weighed and dissolved in 40 ml of physiological saline. The resultant was equivalent to 500 mg crude drug/ml.
After being sterilized under high pressure at 4 C and refrigerated for 5 days, the resultant was subjected to centrifugation at 5000 rpm for 20 min to collect the supernatant for in vitro experiments.

[0083] 2. Bacteriostatic effect of the pharmaceutical composition of this disclosure on standard strains (steel ring method):

[0084] Each standard strain used in the bacteriostatic test was passaged for two times with broth medium and serum broth medium respectively. Then, the 18-hour culture of each strain was diluted 10-2-fold with broth medium. 100 p.1 of the 10-2-fold diluted bacterial solution was added dropwise to a 2% agar broth plate and a 10% serum agar broth plate respectively, and spread evenly on the plate with a sterilized L-shaped glass rod. 5 sterile stainless steel rings (diameter 7 mm) were placed at certain intervals on the plate. Then sterile physiological saline (negative control) and the test drug solutions, namely the original solution of Shuanghuanglian, the original solution of the pharmaceutical composition of this disclosure (500 mg/ml), 1:1 dilution of the pharmaceutical composition of this disclosure (250mg/m1) and 1:2 dilution of the pharmaceutical composition of this disclosure (125 mg/ml), were added dropwise into each steel ring and cultured in an incubator at 37 C for 18 h, and then the diameter (mm) of the bacteriostatic ring was measured. According to the size of the bacteriostatic ring, the bacteriostatic effect of drugs was determined. The results are shown in Table 1 below.

[0085] Table 1 In vitro antibacterial effect of the pharmaceutical composition of this disclosure (diameter of bacteriostatic ring, mm) Pharmaceutical Pharmaceutical Pharmaceutical composition of composition of composition of Strain Control Shuanghuanglian this disclosure this disclosure this disclosure 500 mg/ml 250 mg/ml 125 mg/ml Pseudomonas aeruginosa 13-hemolytic 10.7 12.5 8.5 streptococcus Escherichia coli ¨ 9.4 9.5 ¨ ¨
Staphylococcus ¨ 12.2 13.7 9.3 ¨
epidermidis Staphylococcus ¨ 15.2 16.4 8.2 ¨
aureus Micrococcus ¨ 8.0 10.5 8.4 ¨
catanhalis Shigella ¨ 11.0 12.5 ¨
¨
dysenteriae Streptococcus ¨ 14.2 14.7 9.8 ¨
pneumoniae a-hemolytic ¨ 9.9 10.8 8.4 ¨
streptococcus Salmonella ¨ 12.1 ¨ ¨
¨
typhi Note: "¨" means no bacteriostatic ring

[0086] 2. In vitro inhibitory effect of the pharmaceutical composition of this disclosure against standard strains (test tube method):

[0087] The results of the above tests show that the pharmaceutical composition of this disclosure had a certain inhibitory effect against gram-positive bacteria. Therefore, four standard strains of gram-positive bacteria (streptococcus aureus, a-hemolytic streptococcus, 13-hemolytic streptococcus and streptococcus pneumoniae) and one strain of gram-negative bacteria (escherichia coli) were selected for this test.

[0088] (1) Drug dilution: 8 test tubes were numbered in sequence, and 4 ml of serum-containing broth medium was added by a pipette into each test tube except the first tube according to the aseptic operation procedure. To the first tube, instead of culture medium, 8 ml of the original solution of the pharmaceutical composition of this disclosure (500 mg/ml) was added. 4 ml of the solution in the first tube was transferred into the second tube and mixed well by shaking repeatedly.
Similarly, 4 ml of the solution in the second tube was transferred into the third tube and mixed well by shaking repeatedly. The above steps were repeated until the serial dilution was performed in the eighth tube. The titer of the drug dilutions were original solution, 1:1, 1:2, 1:4, 1:8, 1:16, 1:32 and 1:64, respectively, and the corresponding concentrations of the pharmaceutical composition of this disclosure were 500 mg/ml, 250 mg/ml, 125 mg/ml, 62.5 mg/ml, 31.3 mg/ml, 15.6 mg/ml, 7.8 mg/ml and 3.9 mg/ml. Shuanghuanglian Oral Liquid was diluted in the same way.

[0089] (2) Dilution of bacterial solution: 10 pi of the culture of streptococcus pneumoniae, a-hemolytic streptococcus, 13-hemolytic streptococcus, escherichia coli and staphylococcus aureus cultured for 18 h was diluted at 1:100 with 1 ml of broth medium.

[0090] (3) Test method: Into 40 test tubes, each tube was added with 1.8 ml of broth medium or serum-containing broth medium, followed by 0.2 ml of the pharmaceutical composition of this disclosure or Shuanghuanglian in different dilutions. The final concentrations of the pharmaceutical composition of this disclosure in each test tube were respectively 50 mg/ml, 25 mg/ml, 12.5 mg/ml, 6.25 mg/ml, 3.13 mg/ml, 1.56 mg/ml, 0.78 mg/ml and 0.39 mg/ml. Note that Shuanghuanglian Oral Liquid failed to be expressed by concentration because its concentration was not indicated. Bacterial inoculation: the diluted bacterial solutions of streptococcus pneumoniae, a-hemolytic streptococcus and 13-hemolytic streptococcus were added respectively in an amount of 20 pl to the serum-containing mediums, and the cultures of escherichia coli and staphylococcus aureus were added respectively in an amount of 10 pl to the serum-free mediums.
These bacteria were cultured at 37 C for 24 h to observe their growth. The lowest drug concentration that results in no bacterial growth was taken as the minimum inhibitory concentration (MIC) of the drug against the strain. 10 pl of culture, from each tube without visible bacterial growth, was transferred to sterile medium, and cultured at 37 C for 24 h to observe whether there was bacterial growth. No bacterial growth observed in a tube means that the concentration in the tube was the minimum bactericidal concentration (MBC) of the drug. The results are shown in Tables 2 and 3.

[0091] Table 2: Minimum inhibitory concentration of the pharmaceutical composition of this disclosure against standard strains in vitro (test tube method) Strains Pharmaceutical composition of this disclosure Shuanghuanglian Minimum inhibitory concentration (MIC) Drug dilution Drug dilution Escherichia coli ¨ ¨
¨
Staphylococcus aureus 12.5mg/m1 1:2 1:16 Streptococcus pneumoniae 6.25 mg/ml 1:4 1:16 a-hemolytic streptococcus 25 mg/ml 1:1 1:8 0-hemolytic streptococcus 12.5mg/m1 1:2 1:16 Table 3: Minimum bactericidal concentration of the pharmaceutical composition of this disclosure against standard strains in vitro (test tube method) Pharmaceutical composition of this disclosure Shuanghuanglian Strains Minimum bactericidal Drug dilution Drug dilution concentration (MBC) Escherichia coli ¨ ¨ ¨
Staphylococcus aureus 25mg/m1 1:1 1:32 Streptococcus pneumoniae 12.5mg/m1 1:2 1:32 a-hemolytic streptococcus 50mg/m1 Original solution 1:16 0-hemolytic streptococcus 25mg/m1 1:1 1:16

[0092] 3. In vitro inhibitory effect of the pharmaceutical composition of this disclosure against clinical strains (test tube method):

[0093] 20 strains of clinically isolated gram-positive bacteria (including 5 strains each of staphylococcus aureus, a-hemolytic streptococcus, 13-hemolytic streptococcus and Streptococcus pneumoniae) were selected for the study on the inhibitory effect of the pharmaceutical composition of this disclosure against the clinical strains. The test method was the same as above, and the results are shown in Tables 4 and 5.

[0094] Table 4: Bacteriostatic effect of the pharmaceutical composition of this disclosure on clinical strains (test tube method) Pharmaceutical composition of this disclosure Shuanghuanglian Strains Minimum inhibitory concentration Drug (MIC) dilution Drug dilution Staphylococcus aureus 12.5 mg/ml 1:2 1:32 Streptococcus 12.5 mg/m1 1:2 1:32 pneumoniae Original a-hemolytic streptococcus 50 mg/ml 1:16 solution I3-hemolytic streptococcus 12.5-25mg/m1 1:1-1:2 1:16-1:32 Table 5: Bactericidal effect of the pharmaceutical composition of this disclosure on clinical strains (test tube method) Pharmaceutical composition of this disclosure Shuanghuanglian Strains Minimum bactericidal concentration Drug dilution(MBC) Drug dilution Staphylococcus aureus 25 mg/ml 1:1 1:32 Streptococcus pneumoniae 25 mg/ml 1:1 1:32 a-hemolytic streptococcus ¨ ¨
1:16 I3-hemolytic streptococcus 50 mg/ml Original solution 1:16

[0095] Conclusions:

[0096] (1) The study on in vitro effect of the pharmaceutical composition of this disclosure against standard strains by using the steel ring method shows that the pharmaceutical composition of this disclosure had an in vitro inhibitory effect against the standard strains including staphylococcus aureus, a-hemolytic streptococcus, 13-hemolytic streptococcus, streptococcus pneumoniae, staphylococcus epidermidis, micrococcus catarrhalis, escherichia coli and shigella dysenteriae.

[0097] (2) The study on in vitro effect of the pharmaceutical composition of this disclosure against standard strains by using the test tube method shows that the pharmaceutical composition of this disclosure had a minimum inhibitory concentration of 25 mg/ml and a minimum bactericidal concentration of 50 mg/ml against a-hemolytic streptococcus, a minimum inhibitory concentration of 12.5 mg/ml and a minimum bactericidal concentration of 25 mg/ml against staphylococcus aureus or 13-hemolytic streptococcus, and a minimum inhibitory concentration of 6.25 mg/m1 and a minimum bactericidal concentration of 12.5 mg/ml against streptococcus pneumonia.

[0098] (3) The study on in vitro effect of the pharmaceutical composition of this disclosure against clinically isolated strains by the test tube method shows that the pharmaceutical composition of this disclosure had a minimum inhibitory concentration of 12.5 mg/ml and a minimum bactericidal concentration of 25 mg/ml against staphylococcus aureus or streptococcus pneumoniae, a minimum inhibitory concentration of 50 mg/ml against a-hemolytic streptococcus, and a minimum inhibitory concentration of 12.5-25 mg/ml and a minimum bactericidal concentration of 50 mg/ml against 13-hemolytic streptococcus.

[0099] It can be seen that the pharmaceutical composition of this disclosure had an effective in vitro antibacterial effect on gram-positive bacteria (a-hemolytic streptococcus, 13-hemolytic streptococcus, streptococcus pneumonia and staphylococcus aureus) common to respiratory tract infections.

[0100] II. Study on the in vivo antibacterial effect of the pharmaceutical composition of this disclosure

[0101] Experimental Materials

[0102] 1. Animals:

[0103] ICR mice, half male and half male, weighing 18-22 g, produced by Beijing Charles River Laboratory Animal Technology Co., Ltd., license number SCXK (Beijing 2005-2006).

[0104] 2. Drugs and reagents:

[0105] (1) The test drug was the pharmaceutical composition of this disclosure, which was the same as that in the study I on the in vitro antibacterial effect. The test drug was formulated with 0.5% CMC-Na to the required concentration before use.

[0106] (2) The positive control drug was Shuanghuanglian Oral Liquid, which was the same as that in the study I on the in vitro antibacterial effect.

[0107] (3) Gastrin was purchased from Beijing Yidelong Trading Company. 5 g of gastrin was ground in a mortar where 100 ml of physiological saline was added little by little, and then sterilized in an autoclaved at 10 pounds for 10 min.

[0108] 3. Strain:

[0109] Staphylococcus aureus (No. 26112) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products.

[0110] 4. Instruments:

[0111] UV-120-02 UV-Vis spectrophotometer was a product of Shimadzu, Japan, and 400R
high-speed refrigerated centrifuge was a product of Heraeus, Germany.

[0112] Methods and Results

[0113] 1. Preparation, injection and counting of staphylococcus aureus bacterial solution:

[0114] Staphylococcus aureus was subcultured once. The resulting bacterial culture cultured for 6 h was cultured with broth medium in a 37 C incubator for another 16 h and then centrifuged at 3000 rpm for 10 min to obtain precipitation. The precipitation was diluted with sterile physiological saline, and then placed in an UV-Vis spectrophotometer to compare the color at a wavelength of 640 nm, as the OD value of the bacterial solution was adjusted to 0.200. Part of the bacterial solution was taken out for counting the number of bacteria. The bacterial solution was centrifuged at 3000 rpm for 10 min to remove the supernatant and obtain bacteria which were then restored to the original volume with sterilized 5% gastrin. The resulting bacterial solution was intraperitoneally injected to each mouse at 0.4 ml which corresponded to about 1.6x108 bacteria.

[0115] 2. Animal grouping and treatment:

[0116] 92 ICR mice were randomly divided into 5 groups, namely, a control group (gavage of equal volume of 0.5% CMC-Na), a Shuanghuanglian group (gavage at 10 ml/kg which is equivalent to 10 times of the daily dosage for humans), and three pharmaceutical composition groups of this disclosure, administered by gavage, with doses of 1.9 g/kg (equivalent to 5 times of the daily dosage for humans), 3.7 g/kg (equivalent to 10 times of the daily dosage for humans), and 7.4 g/kg (equivalent to 20 times of the daily dosage for humans), respectively. The five groups were administered, 1 h before the injection of bacteria, at 0.4 m1/10 g of body weight, twice a day, for 3 days. Observation was performed continuously for a week, every 3 hours on the first day, and twice a day after that. The results show that the pharmaceutical composition of this disclosure at high and medium doses had a significant protective effect on mice infected with the lethal dose of staphylococcus aureus, and delayed the death time of the mice. Statistical analysis was performed using SPSS software for chi-square test. The results are shown in Tables 6, 7 and FIG. 1.

[0117] Table 6: In vivo effect of the pharmaceutical composition of this disclosure against staphylococcus aureus infection Number of mice surviving (after Dosage Number of administration) Groups (g/kg) animals 6h 9h 12h 24h 48h 96h 7days Control group ¨ 18 18 18 12 6 2 1 Shuanghuanglian group 1 Oml/kg 18 18 18 15 13 10 Pharmaceutical composition 7.4 19 19 19 18 18 12 9 group of this disclosure Pharmaceutical composition 3.7 19 19 19 17 16 10 8 group of this disclosure Pharmaceutical composition 1.9 18 group of this disclosure Table 7: In vivo protective effect of the pharmaceutical composition of this disclosure against staphylococcus aureus infection Number Average Dosage Number Number Mortality Groups of survival time (g/kg) of animals of deaths rate (%) survival (h) (x sd) Control group ¨ 18 1 17 94 37.3+39.0 Shuanghuanglian group 10m1/kg 18 9 9 50**
102.0+70.5 Pharmaceutical composition group of 7.4 19 9 10 53**
110.5+59.4 this disclosure Pharmaceutical composition group of 3.7 19 8 11 58**
98.5+64.3 this disclosure Pharmaceutical composition group of 1.9 18 5 13 72 72.7+15.4 this disclosure Note: *represents p<0.05, **represents p<0.01 compared with the control group.

[0118] Results and conclusions:

[0119] (1) The mortality rate of mice in the control group injected with staphylococcus aureus was 94% within 7 days.

[0120] (2) The mortality rate of mice orally administrated with Shuanghuanglian decreased to 50%, which had significant difference (p<0.01) compared with the control group, indicating that Shuanghuanglian had a significant in vivo protective effect on mice injected with staphylococcus aureus.

[0121] (3) The mortality rates of mice in the high and medium dose groups of the pharmaceutical composition of this disclosure decreased to 53% and 58%, respectively, which had significant difference (p<0.01) compared with the control group. Although the low dose group had no statistical difference, the mortality rate of mice appeared a decreasing trend, showing a dose-effect relationship in general. The results show that the pharmaceutical composition of this disclosure had a significant in vivo protective effect on mice injected with staphylococcus aureus, and can delay their death time.

Claims

1. Use of a pharmaceutical composition in the manufacture of an antibacterial medicament, wherein the pharmaceutical composition is prepared from the following materials in parts by weight:
ephedrae herba 52-86, gypsum fibrosum 194-324, forsythiae fructus 194-324, scutellariae radix 78-130, mori cortex 194-324, armeniacae semen amarum 78-130, peucedani radix 78-130, pinelliae rhizoma 78-130, citri reticulatae pericarpium 78-130, fritillariae bulbus 78-130, arctii fructus 78-130, lonicerae japonicae flos 78-130, rhei radix et rhizoma 39-65, platycodonis radix 46-76, glycyrrhizae radix et rhizoma 39-65.

2. The use according to claim 1, wherein the pharmaceutical composition is prepared from the following materials in parts by weight:
ephedrae herba 52, gypsum fibrosum 324, forsythiae fructus 194, scutellariae radix 78, mori cortex 194, armeniacae semen amarum 130, peucedani radix 78, pinelliae rhizoma 130, citri reticulatae pericarpium 78, fritillariae bulbus 78, arctii fructus 130, lonicerae japonicae flos 130, rhei radix et rhizoma 39, platycodonis radix 76, glycyrrhizae radix et rhizoma 65.

3. The use according to claim 1, wherein the pharmaceutical composition is prepared from the following materials in parts by weight:
ephedrae herba 86, gypsum fibrosum 194, forsythiae fructus 324, scutellariae radix 130, mori cortex 324, armeniacae semen amarum 78, peucedani radix 130, pinelliae rhizoma 78, citri reticulatae pericarpium 130, fritillariae bulbus 130, arctii fructus 78, lonicerae japonicae flos 78, rhei radix et rhizoma 65, platycodonis radix 46, glycyrrhizae radix et rhizoma 39.

4. The use according to claim 1, wherein the pharmaceutical composition is prepared from the following materials in parts by weight:
ephedrae herba 69, gypsum fibrosum 259, forsythiae fructus 259, scutellariae radix 104, mori cortex 259, armeniacae semen amarum 104, peucedani radix 104, pinelliae rhizoma 104, citri reticulatae pericarpium 104, fritillariae bulbus 104, arctii fructus 104, lonicerae japonicae flos 104, rhei radix et rhizoma 52, platycodonis radix 61;
glycyrrhizae radix et rhizoma 52.

5. The use according to claim 1, wherein the pharmaceutical composition is prepared from the following materials in parts by weight:

ephedrae herba 55, gypsum fibrosum 254, forsythiae fructus 318, scutellariae radix 107, mori cortex 203, armeniacae semen amarum 107, peucedani radix 82, pinelliae rhizoma 105, citri reticulatae pericarpium 84, fritillariae bulbus 125, arctii fructus 122, lonicerae japonicae flos 113, rhei radix et rhizoma 42, platycodonis radix 60, glycyrrhizae radix et rhizoma 50.

6. The use according to any one of claims 1-5, wherein the armeniacae semen amarum is stir-baked armeniacae semen amarum, the fritillariae bulbus is fritillariae thunbergii bulbus, the lonicerae japonicae flos is lonicerae flos, and the pinelliae rhizoma is pinelliae rhizoma praeparatum cum alumine.

7. The use according to any one of claims 1-6, wherein active ingredients of the pharmaceutical composition are prepared by:
step A. pulverizing fritillariae bulbus weighed according to formula ratio into fine powder;
step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 40-70% ethanol in an amount of 8-10 times of the mixture for a first extraction under reflux for 1-4 h, adding 40-70% ethanol in an amount of 6-9 times of the mixture for a second extraction under reflux for 1-4 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.14-1.16 measured at 60 C while recovering ethanol;
step C. to a mixture of gypsum fibrosurn, nlori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 9-11 times of the mixture for a first boiling for 1-4 h, adding water in an amount of 7-9 times of the mixture for a second boiling for 1-4 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.14-1.16 measured at 60 C, and combining with the clear paste obtained in the step B
to obtain a clear paste mixture; and step D. mixing the fine powder obtained in the step A and the clear paste mixture obtained in the step C to obtain the active ingredients of the pharmaceutical composition.

8. The use according to any one of claims 1-6, wherein the medicament is in a form selected from the group consisting of tablet, capsule, powder, granule, oral liquid, pill, tincture, syrup, suppository, gel, spray and injection.

9. The use according to claim 8, wherein the tablet is prepared by a process comprising:
step A. pulverizing fritillariae bulbus weighed according to formula ratio into fine powder;
step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 40-70% ethanol in an amount of 8-10 times of the mixture for a first extraction under reflux for 1-4 h, adding 40-70% ethanol in an amount of 6-9 times of the mixture for a second extraction under reflux for 1-4 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.14-1.16 measured at 60 C while recovering ethanol;
step C. to a mixture of gypsum fibrosum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 9-11 times of the mixture for a first boiling for 1-4 h, adding water in an amount of 7-9 times of the mixture for a second boiling for 1-4 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.14-1.16 measured at 60 C, and combining with the clear paste obtained in the step B

to obtain a clear paste mixture;
step D. spray-drying the clear paste mixture obtained in the step C and collecting spray powder;
and step E. preparing the spray powder obtained in the step D and the fine powder obtained in the step A into soft material by using ethanol as binder, sieving, pelletizing, and tableting.

10. The use according to claim 9, wherein the tablet is prepared by a process comprising:
step A. pulverizing fritillariae bulbus weighed according to formula ratio into fine powder;
step B. to a mixture of ephedrae herba, forsythiae fructus, armeniacae semen amarum, pinelliae rhizoma, arctii fructus, and rhei radix et rhizoma weighed according to formula ratio, adding 50% ethanol in an amount of 10 times of the mixture for a first extraction under reflux for 3 h, adding 50% ethanol in an amount of 6 times of the mixture for a second extraction under reflux for 3 h, combining extracts, filtering, and concentrating filtrate under reduced pressure into a clear paste with a relative density of 1.15 measured at 60 C while recovering ethanol;
step C. to a mixture of gypsum fibrosum, mori cortex, peucedani radix, citri reticulatae pericarpium, lonicerae japonicae flos, platycodonis radix, and glycyrrhizae radix et rhizoma weighted according to a formula ratio, adding water in an amount of 10 times of the mixture for a first boiling for 2 h, adding water in an amount of 7 times of the mixture for a first boiling for 2 h, combining decoctions, filtering, concentrating filtrate into a clear paste with a relative density of 1.15 measured at 60 C, and combining with the clear paste obtained in the step B to obtain a clear paste mixture;
step D. spray-drying the clear paste mixture obtained in the step C and collecting spray powder;
and step E. preparing the spray powder obtained in the step D and the fine powder obtained in the step A into soft material by using ethanol as binder, sieving, pelletizing, drying, granulating, mixing well with sodium carboxymethyl starch, microcrystalline cellulose and magnesium stearate, and tableting.

11. The use according to any one of claims 1-5, wherein the medicament is used for inhibiting infection caused by a gram-positive bacterium.

12. The use according to claim 11, wherein the gram-positive bacterium is selected from the group consisting of staphylococcus aureus, a-hemolytic streptococcus, 0-hemo1ytic streptococcus and streptococcus pneumoniae.

13. The use according to any one of claims 1-5, wherein the medicament is used for inhibiting infection caused by a gram-negative bacterium.

14. The use according to claim 13, wherein the gram-negative bacterium is selected from the group consisting of escherichia coli and shigella dysenteriae.