CN111467469A

CN111467469A - New clinical application of bupleurum tenue particles and antibiotics

Info

Publication number: CN111467469A
Application number: CN202010431646.0A
Authority: CN
Inventors: 刘宏; 江志强; 张俊华; 郑如文; 徐煜耀; 毕聪; 何逸禧; 杜海泳
Original assignee: Guangzhou Baiyunshan Guanghua Pharmacy Co ltd
Current assignee: Guangzhou Baiyunshan Guanghua Pharmacy Co ltd
Priority date: 2020-05-20
Filing date: 2020-05-20
Publication date: 2020-07-31

Abstract

The invention relates to a new clinical application of Xiaochaihu granules. Use of XIAOCHU LU or XIAOCHU LU combined with amikacin in preparing medicine for preventing and treating carbapenems-resistant Klebsiella pneumoniae infection is provided. The invention discovers that the bupleurum tenue particles can be combined with amikacin in antibiotics to improve the antibacterial effect on CRKP, have the sensitization effect and can be used as a natural antibiotic sensitizer. The bupleurum tenue particles and amikacin are used together to strengthen the clinical treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, and especially have good antibacterial effect and sensitization effect on bacterial pneumonia caused by CRKP.

Description

New clinical application of bupleurum tenue particles and antibiotics

Technical Field

The invention belongs to the field of Chinese patent medicines, and relates to a new application of a Chinese medicinal composition, namely small bupleurum particles combined with antibiotics.

Background

The Klebsiella Pneumoniae (KP) is a gram-negative bacillus, widely distributed in water and soil in the nature, is a common living bacterium in the nasopharynx and intestinal tract of human beings, is also a common conditional pathogen, can cause various infectious diseases such as human pneumonia, meningitis, urinary system infection, sepsis and the like, is one of important pathogenic bacteria of hospital infection, is one of Carbapenem-resistant Klebsiella Pneumoniae (Carbapen-resistant Klebsiella Pneumoniae, CRKP) can generate ultra-broad spectrum β -lactamase (ESB L s), ESB L is a plasmid-mediated β -lactamase capable of hydrolyzing oximino- β lactams and monoacylcycline antibiotics, can catalyze the hydrolysis of penicillin drugs, cephalosporins drugs and monocyclomides, can catalyze the hydrolysis of penicillin drugs, cefquinoxalinone drugs, aminoglycoside drugs and monobactams, can make the cefquinoxalinone drugs, antibiotic, cefalexin, and lactam drugs have strong antibiotic resistance, can be used for inhibiting the antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin, antibiotic, cefalexin.

The granule of bupleurum chinense is a pure Chinese medicinal preparation developed according to the famous formula of bupleurum chinense and bupleurum chinense decoction from the treatise on the exogenous febrile diseases of east Han medicine Shengzhang Zhongjing, is a main formula for treating cold, influenza, various variant influenza and other typhoid fever diseases, and is a granular Chinese patent medicine preparation prepared from seven medicinal ingredients of bupleurum chinense, scutellaria baicalensis, pinellia ternate (prepared from ginger), codonopsis pilosula, ginger, liquorice and Chinese date according to a formula of monarch, minister, assistant and guide. The bupleurum tenue particles have the purposes of strengthening healthy energy, eliminating evil and harmonizing yin and yang, can effectively improve the resistance and immunity of human bodies, and have obvious prevention and control curative effects on viruses such as cold, flu and the like. At present, there is no report that bupleurum tenue granules can treat carbapenem-resistant klebsiella pneumoniae infection, as to whether the bupleurum tenue granules can be combined with antibiotics to inhibit CRKP for clinical application, although the report mentions that the bupleurum tenue granules can be combined with antibiotics for use, how to use, mechanism and combination of the bupleurum tenue granules and the antibiotics can be really effective, which diseases are effective, and the current situation is not clear in view of the complexity of disease treatment.

Disclosure of Invention

One of the purposes of the invention is to provide a new clinical application of a traditional Chinese medicine composition, namely Xiaochaihu granules.

The invention develops new application of bupleurum tenue particles in clinical use, and the bupleurum tenue particles and antibiotics are jointly used for clinically treating CRKP infection, aiming at realizing the effects of delaying bacterial drug resistance and antibiotic cooperative sensitization.

The technical scheme for achieving the aim comprises the following steps.

The application of a traditional Chinese medicine composition in preparing a medicine for preventing and treating diseases caused by infection of carbapenems-resistant Klebsiella pneumoniae is characterized in that the traditional Chinese medicine composition comprises the following active components in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

The application of a traditional Chinese medicine composition and amikacin in preparing a medicine for preventing and treating diseases caused by infection of carbapenem-resistant Klebsiella pneumoniae is characterized in that the traditional Chinese medicine composition comprises the following active components in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

A combined medicine for preventing and/or treating diseases caused by infection of carbapenem-resistant Klebsiella pneumoniae comprises a traditional Chinese medicine composition and amikacin, wherein the traditional Chinese medicine composition and the antibiotic respectively form independent administration units or form a combined administration unit together; the traditional Chinese medicine composition comprises the following active ingredients in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

In some preferred embodiments, the carbapenem-resistant Klebsiella pneumoniae-induced disease can be various infectious diseases such as pneumonia, meningitis, urinary system inflammation, sepsis, skin inflammation and the like, and the disease caused by the carbapenem-resistant Klebsiella pneumoniae is pneumonia.

In some preferred embodiments, the active ingredients of the traditional Chinese medicine composition comprise the following components in parts by weight: 150 parts of radix bupleuri, 56 parts of scutellaria baicalensis, 56 parts of ginger processed pinellia, 56 parts of codonopsis pilosula, 56 parts of ginger, 56 parts of liquorice and 56 parts of Chinese dates.

In some preferred embodiments, the Chinese medicinal composition is bupleurum tenue particles.

The invention also provides application of the bupleurum tenue particles as a sensitizer of amikacin in preparing a medicine for preventing and treating pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

The inventor finds that the bupleurum tenue particles can be combined with Amikacin (AMK) to improve the antibacterial effect on CRKP in a plurality of antibiotics, can obviously improve the lung injury infected by CRKP, has sensitization effect, and can be used as a natural antibiotic sensitizer. The bupleurum tenue particles and Amikacin (AMK) are used together to strengthen the clinical treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, can obviously reduce the number of bacteria in the lung infected by CRKP, and particularly has good antibacterial effect and sensitization effect on bacterial pneumonia caused by CRKP.

Drawings

FIG. 1 is a bar graph of the lung wet-dry ratio of small bupleurum particles in combination with AMK, IPM, L VF, SCF in CRKP infected rats according to example 2 of the present invention.

FIG. 2 is a bar graph of lung index of CRKP-infected rats using the small bupleurum particles in combination with AMK, IPM, L VF, SCF in example 2 of the present invention.

FIG. 3 is a bar graph of the lung index inhibition rate of CRKP-infected rats when using the bupleurum tenue particles in combination with AMK, IPM, L VF and SCF according to example 2 of the present invention.

FIG. 4 is a bar graph of the bacterial counts of the use of the bupleurum tenue particles in combination with AMK, IPM, L VF, SCF in CRKP infected rats according to example 2 of the present invention.

Detailed Description

The following examples of the present invention are experimental methods without specifying specific conditions, generally according to conventional conditions, or according to conditions recommended by the manufacturer. The various chemicals used in the examples are commercially available.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

The terms "comprising" and "having" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, apparatus, product, or device that comprises a list of steps is not limited to only those steps or components listed, but may alternatively include other steps or components not listed, or inherent to such process, method, product, or device.

The "plurality" referred to in the present invention means two or more. "and/or" describes the association relationship of the associated objects, meaning that there may be three relationships, e.g., a and/or B, which may mean: a exists alone, A and B exist simultaneously, and B exists alone. The character "/" generally indicates that the former and latter associated objects are in an "or" relationship.

In order that the invention may be more fully understood, reference will now be made to the following description. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

The active ingredients of the bupleurum tenue granules of the invention are: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

The bupleurum tenue granules in the following embodiments are sold by Guangzhou Baiyunshan Guanghua pharmacy, and the active ingredients of the bupleurum tenue granules specifically comprise: 150g of radix bupleuri, 56g of radix scutellariae, 56g of ginger processed pinellia, 56g of radix codonopsitis, 56g of ginger, 56g of liquorice and 56g of Chinese date, and the preparation is granules. Since the adjuvant sucrose can cause false positive results in the antibacterial test, this study used bupleurum tenue granules (sugarless version) for the subsequent tests.

Example 1

Example 1 in vitro combination of Xiaochaihu granules with AMK, IPM, L VF and SCF for CRKP resistance study experiments were carried out by using a test tube double dilution method to determine the Minimum Inhibitory Concentration (MIC) of the medicinal solution of Xiaochaihu granules and four antibiotics on CRKP, and then a chessboard method is used to determine the MIC of each combination drug to study the sensitization effect of the solution of Xiaochaihu granules on AMK, IPM, L VF and SCF for CRKP resistance study.

1. Experimental materials:

1.1 test drugs: xiaochaihu granules (sugar-free, Guangzhou Baiyunshan Guanghua pharmaceutical GmbH).

1.2 control drugs Amikacin (AMK), Imipenem (IPM), levofloxacin (L VF), cefoperazone-Sulbactam (SCF).

1.3 Experimental strains:

the clinical isolated strain of carbapenem-resistant Klebsiella pneumoniae (CRKP, M1) and the standard strain of Klebsiella pneumoniae (ATCC700603) are provided by a clinical microbiology laboratory of the department of clinical laboratory of the department of clinical laboratory of medical laboratory of the university of Zhongshan.

2. The experimental method comprises the following steps:

2.1 grouping and preparation of drugs

Taking a bupleurum tenue particle sample, preparing a liquid medicine which is equivalent to 1000mg/m L of crude drug by using physiological saline under the aseptic operation condition, filtering impurities and bacteria by using a disposable aseptic 0.22 mu m microporous filter for standby, preparing a mother solution with the final concentration of 5120 mu g/m L by using AMK, IPM, L VF and SCF under the aseptic condition, and storing the mother solution in a refrigerator at 4 ℃ in a dark place for standby.

2.2 Small radix bupleuri particles with AMK, IPM, L VF, SCF alone for CRKP Minimum Inhibitory Concentration (MIC) determination

According to C L SI standard (ninth edition), test tube double dilution method is adopted for determination, see tables 1 and 2 for details, 11 sterile Fahrenheit tubes are taken, numbered 1-11, MH liquid culture medium 1.8m L or 1.6m L is added into the tube 1, 1m L is added into the tube 2-11 respectively, bupleurum particle liquid medicine 0.2m L or antibiotic 0.4m L is added into the tube 1, after uniform mixing, 1m L is added into the tube 2, the tube 9 is sequentially diluted to be removed, 1m L is sucked out and discarded as medicine-containing culture medium contrast, the tube 10 is broth aseptic growth contrast, the tube 11 is bacteria normal growth contrast tube, and the tubes except the

tubes

9 and 10 are inoculated with CRKP l.0 × 105CFU/m L, and are cultured for 24 hours at 35 ℃ and taken out, the growth condition of the bacteria is observed, and the lowest concentration of the antibacterial medicine without precipitation is the Minimum Inhibitory Concentration (MIC).

TABLE 1 test tube double dilution method for determining single dilution of granule liquid medicine of Bupleurum tenue

TABLE 2 test tube two-fold dilution method for determination of antibiotic dilution alone

2.3 Effect of Xiaochaihu granules on enhancing sensitivity to AMK, IPM, L VF and SCF to CRKP

Preparing a series of concentrations of liquid culture media containing medicaments, respectively carrying out a series of multiple dilution on granular liquid medicine of bupleurum tenue, AMK, IPM, L VF and SCF in MH broth culture media according to the MIC (table 3) of each medicament to CRKP, wherein the concentration of the granular liquid medicine of bupleurum tenue is 6 dilutions, the 6 dilutions of antibiotics are shown in table 4, keeping the concentration of each column of antibiotics unchanged, the concentration of the granular liquid medicine of bupleurum tenue in each row is inoculated into a 96-hole sterile culture plate, sequentially adding each bacterial suspension into each hole except a blank control, adjusting the concentration of the bacterial suspension to be l.0 × CFU/m L, sealing, slightly mixing, placing the mixture in an incubator at 37 ℃ for 24 hours, observing the degree of turbidity of the culture medium, finding out the concentration of the medicament with the maximum dilution degree of bupleurum tenue as the FIC of the bacteria to the test medicaments, calculating the partial FIC index to evaluate the mutual effect of the small particles and the FIC of the antibiotic combination antibiotic to show the optimal FIC of 0.5, and FIC to show the mutual effect of two medicaments, and calculating the FIC to show that the optimal FIC of two FIC 2 to show the antibiotic synergistic effect, wherein the FIC of the two FIC is as the following formula:

TABLE 3 Xiaochaihu granule liquid medicine, MIC for antibiotic alone (n ═ 6)

TABLE 4 chessboard dilution method for determining MIC of Xiaochaihu granule liquid medicine in combination with antibiotics

2.4 results of the experiment

The results show that the combination of the bupleurum tenue particles and the AMK shows obvious synergistic effect, no obvious interaction exists when the bupleurum tenue particles and the AMK are combined, and the IPM, L VF and SCF have no antagonism.

TABLE 5 MIC and FIC values for XIAOCHU granule and antibiotics (n is 6)

Example 2 Effect of bupleurum tenue particles in combination with AMK, IPM, L VF, SCF on rat CRKP infected pneumonia was investigated.

By adopting a CRKP infected pneumonia rat model to carry out experiments, the improvement effect of the combination of the bupleurum tenue particles and AMK, IPM, L VF and SCF on the pneumonia of the CRKP infected rat is inspected, and the sensitization effect of the bupleurum tenue particles on the CRKP resistance of antibiotics is discovered.

1.3 Experimental strains:

the clinical separated strain of carbapenem-resistant Klebsiella pneumoniae (CRKP, M1) is provided by clinical microbiology laboratory of department of clinical laboratory of institute of medical science of the affiliated first hospital of Zhongshan university, and the drug resistance of the strain is confirmed by the detection of the clinical microbiology laboratory of department of clinical laboratory of laboratory medical science of the affiliated first hospital of Zhongshan university.

1.4 test animals: SPF SD rat, male, with a body mass of 200-250 g, provided by Guangdong province medical laboratory animal center, with a quality certificate number SYXK (Guangdong) 2019-. The experiment is started one week after the experimental animals are adapted to the new environment, and an appropriate method is adopted to reduce the harm to the animals in the experimental process.

2. The experimental method comprises the following steps:

2.1 grouping and treatment of SD rats

220 SD rats are randomly divided into a blank control group, a model group, an AMK group (10 mg.kg < -1 > of clinical human equivalent dose), an IPM group (35 mg.kg < -1 > of clinical human equivalent dose), a L VF group (7 mg.kg < -1 > of clinical human equivalent dose), an SCF group (75 mg.kg < -1 > of clinical human equivalent dose), a small radix bupleuri particle group (5.4g/kg of clinical human equivalent dose), a small radix bupleuri particle, an AMK group, a small radix bupleuri particle, an IPM group, a small radix bupleuri particle, a L VF group, a small radix bupleuri particle and an SCF group in total 11 groups, wherein 20 rats in each group (10 are used for bacterial counting), after the rats are anesthetized by pentobarbital sodium, the blank control group is added with 1 × 109 CFU.m L-1 KP-M130 mu L slowly at the nose, the inoculation is carried out in 2 times, the upright position is kept for 20s, so as to ensure that the bacteria liquid enters the lung tissue blank control group, the blank control group is infected with physiological saline in equal amount for 4h, the same amount, the nasal drip, the blank control group and the corresponding gastric saline is added with the corresponding stomach saline for continuous infusion, and.

3 evaluation index

The effect of bupleurum tenue particles in combination with AMK, IPM, L VF and SCF on rat CRKP infected pneumonia is evaluated by lung wet-dry ratio, lung index inhibition rate and bacterial count.

3.1 Lung Wet-Dry ratio, Lung index and Lung index inhibition

On the 7 th day after infection, 10 rats in each group are killed by dissection, the rats are fasted without water supply for more than 12 hours before killing by dissection, the lungs of the rats are taken out after the axillary arteries are killed by bloodletting, the rats are placed in a culture dish containing 9 g/L physiological saline, surface blood is cleaned, surface water is sucked by absorbent paper and weighed, and the lungs are taken as the lung wet mass, the rats are marked and placed in a 65 ℃ oven to be dried to be constant weight, namely the lung dry mass, the lung wet-dry ratio, the lung index and the lung index inhibition rate are calculated according to the formula that the lung wet-dry ratio is lung wet mass (g)/dry lung mass (g), the lung index is lung mass (g)/weight (g) × 100%, the lung index inhibition rate is model control group average lung index-experimental group average lung index)/model control group average lung index × 100%, the data processing method is represented by average value +/-standard deviation, single-factor analysis is adopted for comparison between groups, and SPSS 22.0 software is adopted to process data, and the result table 6, figure 1, figure 2 and figure 3 are shown in the.

TABLE 6 Effect of bupleurum tenue granules in combination with AMK, IPM, L VF, SCF on CRKP-infected rat pulmonary wet-dry ratio, pulmonary index and pulmonary index inhibition (n ═ 10)

Note: compared with the blank control group, # P <0.05, # P < 0.01; p <0.05 compared to model control,

p < 0.01; the combination group has a bacterial count ^ P <0.05, ^ P <0.013.2, as compared with the group alone with the corresponding antibiotic

On the 7 th day after infection, the remaining 10 rats in each group were sacrificed, both lungs were harvested, PBS was washed 3 times, placed in a homogenizer and ground for 15min with 2m L PBS to make lung homogenate, the lung homogenate was diluted by 10 fold, 100u L was sequentially inoculated onto MH agar medium at each concentration, incubated at 37 ℃ for 24h, plates with colonies among 20-200 were selected for colony counting, data processing method, mean. + -. standard deviation was used for mean value, single factor analysis of variance was used for group comparison, SPSS 22.0 software was used for data processing, the results are shown in Table 7, FIG. 4, Table 7, small radix bupleuri granule in combination with SCF, AMK, L VF, IPM, bacterial count of CRKP infected rats (n ═ 10)

Numbering	Group of	Bacterial count (Bacterial count CFU 100. mu. L-1)
			1	Blank control group	—
2	Model set	18.0±2.41##
			3	AMK drug group	9.8±1.38**
4	IPM drug combinations	10.4±1.56**
			5	L VF drug group	11.1±1.41**
6	SCF drug combination	10.3±1.58**
			7	Granule group of Bupleurum tenue	13.9±1.35**
8	Xiaochaihu granules and AMK group	5.6±1.40**^^
			9	Xiaochaihu granules + IPM group	10.7±1.39**
10	Xiaochaihu granules + L VF group	10.6±1.31**
			11	Radix bupleuri granule + SCF group	9.7±1.60**

p < 0.01; the combination group has ^ P <0.05 and ^ P <0.014 compared with the corresponding antibiotic single group, experimental conclusion:

the results show that the combination of the bupleurum tenue particles and the IPM, L VF and SCF has no enhanced treatment effect and the effect is equivalent to the effect of the bupleurum tenue particles and the IPM, L VF and SCF when being used alone.

The results of the counting of the bacteria in the rat lung are fewer, which shows that the better the treatment effect of the medicine, as can be seen from table 7 and fig. 4, the combined use of the small bupleurum particles and AMK can obviously enhance the treatment effect and reduce the number of the bacteria in the lung, and is superior to the effect of the single use of the small bupleurum particles and AMK, the combined use of the small bupleurum particles, IPM, L VF and SCF has no obvious enhancement of the treatment effect, and the effect is equivalent to the effect of the single use of the small bupleurum particles, IPM, L VF and SCF.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed but not to be construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. The application of a traditional Chinese medicine composition in preparing a medicine for preventing and treating diseases caused by infection of carbapenems-resistant Klebsiella pneumoniae is characterized in that the traditional Chinese medicine composition comprises the following active components in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

2. The application of a traditional Chinese medicine composition and amikacin in preparing a medicine for preventing and treating diseases caused by infection of carbapenem-resistant Klebsiella pneumoniae is characterized in that the traditional Chinese medicine composition comprises the following active components in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

3. The use according to claim 2, wherein the disease is pneumonia.

4. The use of claim 2 or 3, wherein the active ingredients of the Chinese medicinal composition comprise, in parts by weight: 150 parts of radix bupleuri, 56 parts of scutellaria baicalensis, 56 parts of ginger processed pinellia, 56 parts of codonopsis pilosula, 56 parts of ginger, 56 parts of liquorice and 56 parts of Chinese dates.

5. The use of claim 2 or 3, wherein the dosage form of the Chinese medicinal composition is granules.

6. The combined medicine for preventing and/or treating diseases caused by infection of carbapenem-resistant Klebsiella pneumoniae comprises a traditional Chinese medicine composition and amikacin, wherein the traditional Chinese medicine composition and the amikacin form independent administration units respectively or form a combined administration unit together with the antibiotic; the traditional Chinese medicine composition comprises the following active ingredients in parts by weight: 150 plus or minus 5 parts of radix bupleuri, 56 plus or minus 5 parts of radix scutellariae, 56 plus or minus 3 parts of ginger processed pinellia, 56 plus or minus 3 parts of radix codonopsitis, 56 plus or minus 3 parts of ginger, 56 plus or minus 3 parts of liquorice and 56 plus or minus 3 parts of Chinese date.

7. The combination as claimed in claim 6, wherein the active ingredients of the Chinese medicinal composition comprise, in parts by weight: 150 parts of radix bupleuri, 56 parts of scutellaria baicalensis, 56 parts of ginger processed pinellia, 56 parts of codonopsis pilosula, 56 parts of ginger, 56 parts of liquorice and 56 parts of Chinese dates.

8. The combination as claimed in claim 6, wherein the Chinese medicinal composition is XIAOCHAIHU granule.

9. The bupleurum tenue particles are used as a sensitizer of amikacin in the preparation of drugs for preventing and treating diseases caused by carbapenem-resistant Klebsiella pneumoniae.

10. The use according to claim 9, wherein the disease is pneumonia.