CN1471920A - Compound antibacterial medicine containing N-acetyl-D-glucosamine - Google Patents

Abstract

The invention discloses an application of N-acetyl-D-glucosamine in preparing a compound antibacterial medicament by combining the N-acetyl-D-glucosamine with antibiotics. Antibiotics in the treatment of antibacterial infections cause the transformation of pathogenic bacteria into fibrillar Changes Called Synbiotics (CGCs) that promote colonization of pathogenic bacteria and produce physiological resistance. When the medicine is used, the change of CGC caused by the resident flora in the body can be caused, and the complicated chronic diseases after the antibiotic treatment can be caused, so that the dysbacteriosis in the body can be caused, and even the intestinal tract dysfunction can be caused to form the chronic functional diseases. The compound preparation of antibiotic and N-acetyl-D-glucosamine can prevent bacterial CGC formation and prevent complications after antibiotic administration.

Description

Compound antibacterial drugs containing N-acetyl-D-glucosamine

technical field

The present invention relates to the antibacterial use of N-acetyl-D-glucosamine and pharmaceutically acceptable salts thereof, in particular to compound antibacterial drugs containing N-acetyl-D-glucosamine and various antibiotics and N-acetyl -Application of D-glucosamine in the preparation of compound antibacterial drugs.

Background technique

Since the invention of antibiotics, human beings have a powerful weapon against the infection of pathogenic microorganisms, and millions of people are far away from the threat of infection. However, as time goes by, in order to deal with extensive bacterial resistance, the types of antibiotics continue to increase, and the amount of antibiotics is continuously increased. Bacteria vary in various ways, including the bacterial latent organism proposed by the present invention, which is a new adaptive form of bacteria that appears in an unfavorable environment. Bacterial variation leads to the transformation of normal flora into conditional pathogenic bacteria, causing flora disorder and nosocomial infection. Among them, the production and colonization of bacterial latent organisms are closely related to the occurrence of irritable bowel syndrome and intestinal dysfunction, which has been proved in clinical investigations.

For a long time, bacteria have been considered as single-celled organisms, and each bacteria carries out life activities independently without much contact with each other. However, research in recent years has shown that in fact individual cells of bacteria behave differently from colonies of bacteria, especially for the interaction of bacteria with other organisms, the effect produced by bacteria is actually the behavior of the bacterial colony as a whole , which behaves like multicellular organisms (Shapiro, J.A. "Bacteria as multicellular organism." Scientific American 1988, 256:82-89). The inventors have further studied and found that under suitable culture conditions, bacteria will form colony patterns similar to waves, showing regular life activities. This phenomenon is interesting for understanding the law of life of bacteria, and the inventors name this phenomenon "biological wave" (Xu Qiwang etc., group, cycle and wave of microbial growth, Nature Magazine, 1992, 15( 3), 195-197), and studied it (Liu Junkang et al., Research on Biological Wave Theory, Chinese Journal of Microecology, 1994, 6(6), 40-46; Xu Qiwang et al., Non-equilibrium of biological wave Mechanism Research, Journal of Northwest University (Natural Science Edition), 1997, 27 (Supplement), 320-325).

In the study of the biological wave theory, the present inventors found that the wavy colonies are formed in a state where the bacterial growth is vigorous and inhibited alternately. In the part where the bacterial growth is inhibited, the bacteria do not divide, the shape is slender, and the degree of metabolism is low. Mobility is strong, and the inventor etc. call it latent organism (CGC) 〔Deng Guohong, etc. Observation of aperiodic changes in the survival of Pseudomonas aeruginosa in water. Journal of the Third Military Medical University, 1997; 19(3): 197-201]. In the further study of human pathophysiology, it was found that bacteria transformed into latent organisms (CGC) in large quantities in the environment with antibacterial substances. It is difficult to kill him [Deng Guohong. The effect of antimicrobial agents on bacterial latent organisms. Nature Exploration, 1999;18(69):67-68]. Once the antibiotic disappears or the concentration drops below the MIC level, the bacteria adapt to the change of the environment, and when corresponding changes occur, they quickly break down and individual cells accumulate together to form colonies. Experimental studies have shown that antibiotics can induce CGCs on Gram-positive or negative bacteria such as Escherichia coli, Proteus, Salmonella, and Shigella. In vivo experiments including animals and humans have proved that this effect is consistent with that in vitro (Wang Zhenwei et al., Experimental observation of spin in latent organisms, China Public Health, 2000, 16(5), 1-3; Liu, Junkang, et al, Turbulene under the microscope, Journal of Biological Physics, 2000, 00(1), 1-7) .

The bacterial CGC involved in the present invention can cause damage to the human body regardless of the type of bacteria formed. It has been found that bacteria in different ecological environments have slight changes in morphology, low metabolism and changes in toxicity, and the damage to the body is very different from that of the same bacteria when they are in propagules (Guo Gang, Huang Chunji, etc. A comparative study of cellulite and latent organisms induced by antibiotic Sub-MICs. Chinese Journal of Epidemiology, 1996; 17(3-C)). However, this difference has not attracted people's attention in the past. The transformation of bacteria into latent organisms has led to an increase in the amount of antibiotics used, but the effect has gradually decreased, which has increased the possibility of misdiagnosis and random administration of drugs, leading to aggravation of the disease and even delays in treatment. cause a large number of adverse drug reactions.

After long-term research, the inventors of the present invention have proved that bacterial CGC is caused by human exposure to chemical substances, especially the widespread use of antibiotics can cause CGC changes in intestinal bacteria. It has been found that chronic diarrhea, chronic gastrointestinal dysfunction, especially irritable bowel syndrome (IBS), which has a greater impact on humans, are all caused directly or indirectly by CGC (Xu Qiwang. Bacterial latent organisms in irritable bowel syndrome Pathogenesis. Science, 1998;10:59-61).

In the process of carrying out biological wave theory research, the present inventors found that this fluctuation has its internal regulation mechanism, and chemical substances can be used to regulate the biological fluctuation process. After separation, purification and identification, a substance was determined to be N-acetyl- D-glucosamine. It is confirmed that there is a biological wave effect that promotes fluctuations (Huang Hui et al., Experimental Analysis of Regulatory Factors of Bacterial Biowaves, Journal of Third Military Medical University, 1999, 21(3), 178-180).

N-acetyl-D-glucosamine is a known substance (2-acetylamino-2-deoxy-D-glucoSe; N-acetyl-D-(+)-glucosamine; GlcNAc; CAS No.7512-17-6) . The structure is as follows:

N-acetyl-D-glucosamine has been disclosed for periodontitis (WO91/02539A1), inflammatory bowel disease (WO99/53929A1), corneal disease (JP10-287570A2), prostatic hypertrophy (US5,116,615) and other diseases Treatment, preparation of vaccines for the prevention and treatment of microbial infections (WO97/18790A3), beauty treatment (JP59-13708A2), shampoo preparations (JP2-11505A2), etc. In recent years, on the basis of in-depth research on its wave-promoting effect, the inventors have also proposed a Chinese patent application (No. CN1156027 communique) as a new drug application for the treatment of IBS, and a therapeutic agent for anti-bacterial colonization (patent application No. 01104884.0), but there is no report on the effect of treating bacterial CGC caused by antibiotics and the diseases caused by it, and there is no report that it acts on bacteria to enhance the effect of antibiotics.

Contents of the invention

When the present inventors were conducting research on the wave-promoting effect of N-acetyl-D-glucosamine, they unexpectedly found that N-acetyl-D-glucosamine can effectively prevent bacteria from transforming into latent ecology under the action of antibiotics, thereby enabling The effects of various antibiotics are remarkably improved, thereby completing the present invention.

That is to say, the present invention relates to the antibacterial use of N-acetyl-D-glucosamine and pharmaceutically acceptable salts thereof, specifically to compound antibacterial drugs containing N-acetyl-D-glucosamine and antibiotics and N- Application of acetyl-D-glucosamine in the preparation of compound antibacterial drugs.

The invention relates to the application of the composition containing N-acetyl-D-glucosamine and antibiotics in the preparation of medicines for preventing or treating diseases such as irritable bowel syndrome, flora imbalance in the body, intestinal dysfunction and the like.

In addition, the present invention also relates to a method for enhancing the therapeutic effect of antibiotics by administering to a patient a therapeutically effective amount of N-acetyl-D-glucosamine and a therapeutically effective amount of antibiotics, and by administering to a patient a therapeutically effective amount of N-acetyl-D-glucosamine Glucose and a therapeutically effective amount of an antibiotic, a method of treating a bacterial infection or disease caused by pathogenic proliferation that is treatable by an antibiotic.

The present invention also relates to a method for preventing or treating diseases such as irritable bowel syndrome, dysbiosis in vivo, and intestinal dysfunction by administering therapeutically effective doses of N-acetyl-D-glucosamine and therapeutically effective doses of antibiotics to patients.

Specific Embodiments of the Invention

The present invention will be described in detail below.

In the medicine/composition containing N-acetyl-D-glucosamine and antibiotics of the present invention, the structure of N-acetyl-D-glucosamine is as follows:

The physical and chemical data of N-acetyl-D-glucosamine are as follows:

Molecular formula: C ₈ H ₁₅ NO ₆

Molecular weight: 221.21 (exact molecular weight 221.2096)

Melting point: 201-204°C

N-acetyl-D-glucosamine can be obtained from various sources. For its preparation, chemical synthesis or semi-synthesis methods are mostly used at home and abroad, and some are directly obtained from known methods. For example, WO97/31121 discloses the enzymatic preparation of N-acetyl-D-glucosamine from chitin polysaccharides, and Japanese Patent Application Publication JP6-3273493 discloses a partial acid hydrolysis of chitin polysaccharides to obtain N-acetyl-chitooligosaccharides, and then A method for obtaining N-acetyl-D-glucosamine by enzymatic treatment.

In the medicine/composition containing N-acetyl-D-glucosamine and antibiotics of the present invention, N-acetyl-D-glucosamine can be used as its free base or pharmaceutically acceptable salt. As pharmaceutically acceptable salts of N-acetyl-D-glucosamine, for example, hydrochloride, hydrobromide, borate, phosphate, and sulfate formed of N-acetyl-D-glucosamine and inorganic acids can be used. , bisulfate and hydrogen phosphate, citrate, benzoate, ascorbate, methylsulfate, naphthaleneethanesulfonate, picrate, rich Maleate, maleate, malonate, oxalate, succinate, acetate, tartrate, mesylate, tosylate, isethionate, alpha-ketoglutadiene salt, α-glycerophosphate and glucose-1-phosphate, etc. The above-mentioned monomers or pharmaceutically acceptable salts can be prepared according to known methods or commercially available.

The present invention relates to a composition and medicine containing N-acetyl-D-glucosamine and antibiotics. Antibiotics refer to substances that can be applied to humans or other mammals and have chemotherapeutic effects against microorganisms such as bacteria, mycoplasma, and chlamydia. The antibiotics described in the present invention can be fermented, semi-synthetic or fully synthetic, which is not limited. For example, it can be an antibiotic obtained by fermentation of antibiotic-producing microorganisms (mold, actinomycetes, etc.), or a semi-synthetic antibiotic with the same or similar mother nucleus after structural modification of the antibiotic obtained by fermentation, or a structure similar to conventional antibiotics Totally synthetic antibiotics also include various fully synthetic chemotherapeutic drugs that have antibacterial effects and are conventionally regarded as antibiotics, such as quinolones.

As long as the antibiotics described in the present invention act on bacteria and the like and can induce latent ecology, the composition/drug of the present invention can be used.

In the present invention, antibiotics that can be used include but are not limited to:

Aminoglycoside antibiotics, penicillin antibiotics, cephalosporin antibiotics, penicillins, β-lactam antibiotics other than cephalosporins, chloramphenicol antibiotics, lincomycin antibiotics, macrolides Antibiotics, quinolones, tetracyclines, etc., but not limited thereto.

Aminoglycoside antibiotics of the present invention are antibiotics with aminoglycoside structure in the molecule, such as streptomycin (II), kanamycin, amikacin produced by Streptomyces or semi-synthesized on the basis of it Antibiotics such as Amycin, gentamicin and sagamycin produced by Micromonospora, but not limited thereto.

The penicillin antibiotics described in the present invention refer to the natural or semi-synthetic antibiotic monomers or various pharmaceutically acceptable salts thereof with the penicillanic acid core structure (III) in the molecule, for example: natural penicillins such as penicillin G, Penicillin V, etc.; semi-synthetic penicillins such as ampicillin, carbenicillin, amoxicillin, etc., but not limited thereto. (X=H, OCH ₃ )

Z＝S(IV)，(X＝H，OCH₃)＝O(V)The cephalosporin antibiotics of the present invention refers to the synthetic, semi-synthetic or natural antibiotic with cephalosporin (IV) or oxycephem (V) nucleus structure in the molecule, for example: ceftrixin, cefradine, cefaclor , Cefuroxime, Cefotaxime, Latamoxef, etc., but not limited thereto.

Z=S(IV), (X=H, OCH ₃ )=O(V)

Other β-lactam antibiotics other than penicillins and cephalosporins in the present invention refer to synthetic, semi-synthetic or Antibiotics, for example: nocardycin, thiamycin with carbapenem structure (VII), imipenem; sulbactam, tazobactam, sultacillin with thiopenem structure (VIII) ( ampicillin-sulbactam); clavulanic acid of the oxypenicillane structure (IX), etc., but not limited thereto.

The chloramphenicol antibiotics of the present invention refer to synthetic, semi-synthetic or natural antibiotics or derivatives thereof with a structure similar to chloramphenicol (X), such as chloramphenicol, succinylchloramphenicol, thiamphenicol etc., but not limited to this.

The lincomycin class antibiotics described in the present invention refer to, for example, antibiotics with structures such as lincomycin (XI) or its analogs and derivatives, such as lincomycin, clincomycin, etc., but Not limited to this.

The macrolide antibiotics of the present invention refer to derivatives such as macrolide antibiotics such as erythromycin, spiramycin (XII), roxithromycin, azithromycin, and salts and esters thereof , but not limited to this.

The quinolones described in the present invention belong to synthetic chemotherapeutic drugs and do not belong to the category of antibiotics, but for the sake of brevity herein, they are also considered to belong to antibiotics from the perspective of their drug effects, and no distinction is made to this in the narration of this specification. Quinolones include norfloxacin, ofloxacin, ciprofloxacin of the nalidixic acid core (XIII), enoxacin of the cinnoline carboxylic acid core (XIV), pyridopyrimidine carboxylic acid Pipemidic acid and the like of the nucleus (XV), but not limited thereto. X=C, Z=C(XIII)C, N(XIV)N, N(XV)

The tetracyclines described in the present invention refer to natural, semi-synthetic or synthetic antibiotics with phenanthrene basic skeletons produced by actinomycetes, such as tetracycline (XVI), aureomycin, oxytetracycline, etc., but not limited to this.

Bacteria that can be induced by antibiotics to produce latent ecology include but are not limited to intestinal Gram-negative bacilli, including pathogenic bacteria and resident flora, anaerobic and facultative bacteria, etc.

Although not intending to be bound by any existing theory, the mechanism by which N-acetyl-D-glucosamine can be used in combination with antibiotics in the present invention to enhance the drug effect is considered as follows:

Antibiotics play a role through the reaction of bacteria. When bacteria transform into latent organisms, they do not respond to antibiotics and make antibiotics ineffective; N-acetyl-D-glucosamine can make latent organisms return to the form of bacterial propagules, thereby making the antibiotics ineffective. It is sensitive to antibiotics, so as to enhance the efficacy of antibiotics.

When N-acetyl-D-glucosamine and antibiotics are used together in the compound preparation of the present invention, the dosage and ratio of N-acetyl-D-glucosamine and antibiotics are different due to different antibiotics. Specifically, because N- Acetyl-D-glucosamine has a synergistic effect on antibiotics, so the dosage of antibiotics can be conventional or less than conventional, for example, reduced to 50% or even less than conventional. N-acetyl-D-glucosamine itself is non-toxic, so its dosage is not particularly limited, for example, the daily dosage can range from 100 mg to 10 g. Specifically:

When N-acetyl-D-glucosamine and aminoglycoside antibiotics are combined, the ratio of the two can be N-acetyl-D-glucosamine:aminoglycoside antibiotics=1:1.6˜1:5. Such as compound streptomycin, injection, for intravenous drip or intramuscular injection, the dosage for adults is 1g/day. Compound kanamycin, injection, for intramuscular injection, the dosage is 300mg/day, 8 hours/time. Compound gentamicin injection, for intramuscular injection or intravenous infusion, the dosage is 90-300mg/day, 8 hours/time. The doses mentioned above are for antibiotics, the same below.

When N-acetyl-D-glucosamine is combined with macrolide antibiotics, the ratio is N-acetyl-D-glucosamine:macrolide antibiotics=1:5˜1:30. Such as compound spiramycin, mixed powder in proportion to make capsules, orally, the dosage is 2-3g/day, 8 hours/time.

When N-acetyl-D-glucosamine and quinolones are combined, the ratio is N-acetyl-D-glucosamine:quinolones=1:2 to 1:15. For example, make compound norfloxacin, capsules, orally, the dosage is 1200mg/day, 8 hours/time; Injection, intravenous drip, 200mg/time, 1-2 times/day.

When N-acetyl-D-glucosamine and lincomycin antibiotics are combined, the ratio is N-acetyl-D-glucosamine: lincomycin antibiotics=1:2.5～1:10. For example, mix powder to make capsules, 0.6-1.8g per day; it can also be made into injections for intravenous infusion.

When N-acetyl-D-glucosamine is combined with chloramphenicol antibiotics, the ratio is N-acetyl-D-glucosamine:chloramphenicol antibiotics=1:2.5˜1:10. Mixed powder, made into sugar-coated tablets or syrup, orally, 25-50mg/kg; or injection, intramuscular injection or intravenous drip, 1-2g/day, 2-4 times/day.

When N-acetyl-D-glucosamine is combined with tetracycline antibiotics, the ratio is N-acetyl-D-glucosamine:tetracycline antibiotics=1:1-1:30. Made into capsules or sugar-coated tablets, taken orally, 1-2g/day; also made into injections, 1-1.5g/day

When N-acetyl-D-glucosamine is combined with cephalosporin antibiotics, the ratio is N-acetyl-D-glucosamine: cephalosporin antibiotics=1:2.6～1:5. For example, N-acetyl-D-glucosamine is mixed with cefuroxime to make injections for intravenous infusion or intramuscular injection, 1.5-6g/day, twice a day; mixed with cefotaxime to make injections for intravenous infusion or intramuscular injection Intramuscular injection, 2g/day, 2 times/day.

When N-acetyl-D-glucosamine is combined with penicillins, the ratio is N-acetyl-D-glucosamine:penicillins=1:1-1:30. For example, mixed with ampicillin to make capsules, taken orally, 50-100mg/kg/day, made into injections, intramuscularly or intravenously, 100-200mg/kg/day; made into injections with carbenicillin, intramuscularly or intravenously, 4 -8g/day, 4 times/day.

When N-acetyl-D-glucosamine is combined with other β-lactam antibiotics, the ratio is N-acetyl-D-glucosamine: other β-lactam antibiotics=1:8～1:50. For example, make injection with cefoxitin, intravenous or intramuscular injection, 8-10g/day; make compound ampicillin-sulbactam injection, 1.5-6g/day, 2-3 times/day, intramuscular or intravenous injection .

It should be noted that when N-acetyl-D-glucosamine is used in combination with antibiotics, as long as the purpose of the present invention can be achieved, the two can be made into compound preparations and used at the same time, or can be made into preparations separately, and used simultaneously or sequentially, for example There is no limit to giving antibiotics first and N-acetyl-D-glucosamine later or vice versa.

The following experimental examples demonstrate the combination of N-acetyl-D-glucosamine and antibiotics of the present invention against CGC, prevention and treatment of intestinal flora disorder, irritable bowel syndrome and other effects.

The following antibiotics were all commercially available and purchased from the Pharmacy of Southwest Hospital of Third Military Medical University.

Experimental example 1

Effects of Different Proportions of Aminoglycosides and N-Acetyl-D-Glucosamine in Compound Antibacterial Agents on Escherichia coli CGC Induction Experiment

Escherichia coli (No. 33310, purchased by the Chengdu Institute of Biological Products, Ministry of Health) was used in this experiment; various concentrations of antibiotics were used, and the dosage of N-acetyl-D-glucosamine was from 10 mg to 300 mg for grid design. The plates were coated separately, and the drug was applied by the K-B method. Colonies were picked at the edge of the drug inhibition zone and observed under a microscope. In each field of view, the length of bacteria is more than 50 μm, and the number is more than 5, which is CGC-positive, which is indicated by "+"; "-"express. At this time, the ratio of the two substances is the "effective ratio", and the experimental results are summarized in Table 1-1 to Table 1-9 below.

Table 1-1

Aminoglycoside antibiotics are selected from kanamycin and gentamicin, and the dosage is 50mg to 500mg; Aminoglycosides (mg) Formula (I) compound (mg) 50 100 150 200 300 400 500 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to aminoglycosides in the compound antibacterial agent for preventing the formation of Escherichia coli CGC is 1:1.6～1:5.

Table 1-2

Spiramycin is selected as the macrolide antibiotic, and the dosage is 300mg to 1500mg Macrolides (mg) Formula (I) compound (mg) 300 500 700 900 1100 1300 1500 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to macrolides in the compound antibacterial agent for preventing the formation of Escherichia coli CGC is 1:5-1:30.

Table 1-3

Ciprofloxacin and norfloxacin are selected as quinolones, and the dosage is 150mg to 600mg; Quinolones (mg) Formula (I) compound (mg) 150 200 300 400 500 550 600 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to quinolones in the compound antibacterial agent for preventing the formation of CGC of Escherichia coli is 1:2～1:15.

Table 1-4

Lincomycin antibiotics are selected from lincomycin, and the dosage is 100mg to 700mg Lincomycin (mg) compound of formula (I) (mg) 100 200 300 400 500 600 700 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to lincomycin in the compound antibacterial agent preventing the formation of E. coli CGC is 1:2.5～1:10.

Table 1-5

The dosage of chloramphenicol is 100mg to 700mg Chloramphenicol (mg) Formula (I) compound (mg) 100 200 300 400 500 600 700 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to chloramphenicol in the compound antibacterial agent for preventing the formation of CGC of Escherichia coli is 1:2.5～1:10.

Table 1-6

Tetracyclines choose tetracycline, the dosage is 10mg to 300mg Tetracyclines (mg) Formula (I) compound (mg) 10 50 100 150 200 250 300 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to tetracyclines in the compound antibacterial agent for preventing the formation of CGC in Escherichia coli is 1:1-1:30.

Table 1-7

The cephalosporins are selected from cefuroxime and cefotaxime, and the dosage is 50mg to 800mg Cephalosporins (mg) Formula (I) compound (mg) 50 100 200 300 450 650 800 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to cephalosporins in the compound antibacterial agent preventing the formation of E. coli CGC is 1:2.6～1:5.

Table 1-8

Ampicillin and carbenicillin are selected as penicillins, and the dosage is 10mg to 300mg β-lactams (mg) Formula (I) compound (mg) 10 50 100 150 200 250 300 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine to β-lactam drugs in the compound antibacterial agent for preventing the formation of Escherichia coli CGC is 1:1～1:30.

Table 1-9

For other β-lactams, choose cefoxitin and ampicillin-sulbactam, the dosage is 500mg to 2500mg Other β-lactams (mg) Formula (I) compound (mg) 500 800 1200 1500 1800 2000 2500 10 - + + + + + + 50 - - + + + + + 100 - - - + + + + 150 - - - - + + + 200 - - - - - + + 250 - - - - - - + 300 - - - - - - -

Conclusion: The effective ratio of N-acetyl-D-glucosamine and other β-lactam drugs in the compound antibacterial agent for preventing the formation of Escherichia coli CGC is 1:8～1:50.

Experimental example 2

Efficacy of N-acetyl-D-glucosamine antibiotic compound preparation in preventing bacterial CGC formation in vitro

In this test, Gram-negative facultative bacteria, Gram-negative anaerobic bacteria, and Gram-positive aerobic bacteria were respectively coated on plates in vitro, and the experimental drug and the control drug were dissolved in the same volume of sterile water for injection. , take 10 microliters to prepare drug-sensitive discs, and use the K-B method for drug experiments to observe the inhibition of CGC formation. The experimental results are shown in Tables 2-1 to 2-9.

table 2-1

100 mg of N-acetyl-D-glucosamine in Experimental Example 1 and 300 mg of aminoglycoside antibacterial kanamycin were used to make a compound prescription, and the control drug was kanamycin of the same dose. Bacteria name compound Kanamycin Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anaerobic Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

The above strains were identified as genus.

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine and aminoglycosides can effectively prevent common bacteria in digestive tract from transforming into CGC in vitro, compared with aminoglycosides alone.

Table 2-2

The N-acetyl-D-glucosamine and macrolide antibacterial compound preparation of Experimental Example 1 (N-acetyl-D-glucosamine 100mg, spiramycin 900mg, powder mixing) control drug is spiramycin 900mg Bacteria name compound Spiramycin Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anorexia Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine combined with macrolides can effectively prevent common bacteria in digestive tract from transforming into CGC in vitro compared with macrolides alone.

Table 2-3

The N-acetyl-D-glucosamine of experimental example 1 and quinolone antibacterial compound preparation (N-acetyl-D-glucosamine 100mg, norfloxacin 400mg are mixed) control drug is the same dosage norfloxacin Bacteria name compound Norfloxacin Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anorexia Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: Compared with quinolones alone, the compound antibacterial preparation of N-acetyl-D-glucosamine and quinolones can effectively prevent the conversion of common bacteria in the digestive tract to CGC in vitro.

Table 2-4

The N-acetyl-D-glucosamine (100mg) and lincomycin (400mg) of Experimental Example 1 form a compound preparation, and the contrast drug is lincomycin (400mg) Bacteria name compound Lincomycin Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Sexual grammyia pussy Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: Compared with lincomycin alone, the compound antibacterial preparation of N-acetyl-D-glucosamine and lincomycin can effectively prevent common bacteria in the digestive tract from transforming into CGC in vitro.

Table 2-5

The N-acetyl-D-glucosamine (100mg) of experimental example 1 and chloramphenicol (400mg) make compound preparation, contrast medicine is chloramphenicol (400mg) Bacteria name compound Chloramphenicol Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anorexia Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine and chloramphenicol can effectively prevent common bacteria in digestive tract from transforming into CGC in vitro compared with chloramphenicol alone.

Table 2-6

The N-acetyl-D-glucosamine (50mg) of experimental example 1 and tetracycline (150mg) form compound preparation, contrast drug is tetracycline (150mg) Bacteria name compound tetracycline Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Sexual grammyia pussy Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Oxygenin diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine combined with tetracyclines can effectively prevent common bacteria in digestive tract from transforming into CGC in vitro compared with tetracyclines alone.

Table 2-7

The N-acetyl-D-glucosamine and cephalosporin antibacterial compound preparation of Experimental Example 1, (N-acetyl-D-glucosamine 100mg mixes with cefuroxime 300mg), and the control drug is cefuroxime 300mg Bacteria name compound Cefuroxime Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anaerobic bacteria Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Gram-positive bacteria diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine combined with cephalosporins can effectively prevent common bacteria in digestive tract from transforming into CGC in vitro compared with cephalosporins alone.

Table 2-8

The N-acetyl-D-glucosamine and penicillins antibacterial compound preparation of Experimental Example 1, (N-acetyl-D-glucosamine 150mg, ampicillin 150mg mixed composition) control drug is ampicillin Bacteria name compound Ampicillin Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anorexia Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Sexual Gramma Positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine and β-lactam drugs can effectively prevent common bacteria in the digestive tract from transforming into CGC in vitro compared with β-lactam drugs alone.

Table 2-9

The N-acetyl-D-glucosamine of Experimental Example 1 and other β-lactam antibacterial compound preparations (N-acetyl-D-glucosamine 100mg, ampicillin-sulbactam 1500mg mixed composition), the control drug is ampicillin- Sulbactam Bacteria name compound ampicillin-sulbactam Gram-negative facultative bacteria Escherichia coli - + salmonella - + Shigella - + Klebsiella - + Proteus - + Citrobacter - + Gram-negative anaerobic Bacteroides fragilis - + Bacteroides melanogenes - + Clostridium difficile - + nucleobacterium - + Grammobacterium positive diphtheria-like bacteria - + Listeria - + Bacillus cereus - +

Conclusion: The compound antibacterial preparation of N-acetyl-D-glucosamine combined with other β-lactam drugs can effectively prevent the conversion of common bacteria in the digestive tract to CGC in vitro compared with other β-lactam drugs alone. .

Experimental example 3

Efficacy test of N-acetyl-D-glucosamine and antibiotic compound antibacterial preparation in preventing CGC formation in vivo.

Select Wistar rats, experimental observation N-acetyl-D-glucosamine and antibiotic effective ratio form the compound preparation to in vivo test on rats infected with Salmonella typhimurium and uninfected rats (provided in the following example is the composition ratio of the drug. Its Dosage form is the same as previously described. The antibiotic that does not contain N-acetyl-D-glucosamine of equal amount is taken as contrast. The dosage for rats is multiplied by 6.5 times per kilogram of drug dosage of human consumption (as mentioned above). Experiment is taken at random Divide into groups, 15 in each group.

The dosage is administered by intramuscular injection or oral administration at an effective dose, and lasts for 1 week. The fecal CGC examination was performed twice a day, and the intestinal mucosal CGC colonization test was performed on the seventh day to determine the corresponding relationship with the CGC in the feces. The presence of CGC in the feces and intestinal mucosal CGC colonization was positive, otherwise it was negative. The expression method is that the total number of animal experiments is the denominator, and the number of positive animals is the numerator. The result is as follows:

Experimental example 3-1 aminoglycoside antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + kanamycin (200mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC in rats infected with Salmonella typhimurium and uninfected rats was given an effective dose of N-acetyl-D-glucosamine and aminoglycoside compound antibacterial preparations was 0 (0/15 ), while the positive rate of CGC in both the infected rats given kanamycin and the uninfected rats was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and aminoglycoside can effectively prevent the formation of CGC in animals.

Experimental example 3-2 macrolide antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + spiramycin (900mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC was 0(0/ 15), while the positive rate of CGC in both infected rats and uninfected rats given only spiramycin was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and macrolides can effectively prevent the formation of CGC in animals.

Experimental example 3-3 quinolones

Drug: N-acetyl-D-glucosamine (100mg) + ciprofloxacin (500mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosal CGC in rats infected with Salmonella typhimurium and uninfected rats was 0 (0/15), The positive rate of CGC in both infected rats and uninfected rats given only ciprofloxacin was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and quinolones can effectively prevent the formation of CGC in animals.

Experimental example 3-4 lincomycin antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + lincomycin (400mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC in rats infected with Salmonella typhimurium and uninfected rats was given an effective dose of N-acetyl-D-glucosamine and lincomycin compound antibacterial preparation was 0 (0/15 ), while the positive rate of CGC in both infected rats and uninfected rats given only lincomycin was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and lincomycin can effectively prevent the formation of CGC in animals.

Experimental example 3-5 chloramphenicol antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + chloramphenicol (400mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC in rats infected with Salmonella typhimurium and uninfected rats was given an effective dose of N-acetyl-D-glucosamine and chloramphenicol compound antibacterial preparations was 0 (0/15 ), while the positive rate of CGC in both the infected rats given chloramphenicol and the uninfected rats were 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and chloramphenicol can effectively prevent the formation of CGC in animals.

Experimental Example 3-6 Tetracycline Antibiotics

Drug: N-acetyl-D-glucosamine (150mg) + tetracycline (150mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosal CGC in rats infected with Salmonella typhimurium and uninfected rats was 0 (0/15), The positive rate of CGC in the infected rats and uninfected rats only given tetracycline was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and tetracyclines can effectively prevent the formation of CGC in animals.

Experimental example 3-7 cephalosporin antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + cefuroxime (300mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC in rats infected with Salmonella typhimurium and uninfected rats was given an effective dose of N-acetyl-D-glucosamine and cephalosporin compound antibacterial preparations was 0 (0/15 ), while the positive rate of CGC in both the infected rats given cefuroxime and the uninfected rats was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and cephalosporins can effectively prevent the formation of CGC in animals.

Experimental example 3-8 penicillin antibiotics

Drug: N-acetyl-D-glucosamine (100mg) + ampicillin (200mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC was 0(0/ 15), while the positive rates of CGC in both the infected rats given ampicillin and the uninfected rats were 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that the compound antibacterial preparation of N-acetyl-D-glucosamine and β-lactam can effectively prevent the formation of CGC in animals.

Experimental Example 3-9 Other β-lactams

Drug: N-acetyl-D-glucosamine (100mg) + cefoxitin (150mg)

Conclusion: The positive rate of CGC in feces and intestinal mucosa CGC in rats infected with Salmonella typhimurium and uninfected rats given effective doses of N-acetyl-D-glucosamine and other β-lactam compound antibacterial preparations was 0 (0 /15), while the positive rate of CGC in both infected rats and uninfected rats given only cefoxitin was 100% (15/15). The positive results of CGC in feces were consistent with the positive results of CGC colonization in intestinal mucosa. It shows that N-acetyl-D-glucosamine and other β-lactam compound antibacterial preparations can effectively prevent the formation of CGC in animals.

EXPERIMENTAL EXAMPLE 4 Experimental observation on the preventive effect of N-acetyl-D-glucosamine and antibiotic compound preparation on the bacterial flora disorder caused by bacterial CGC

15 rats in each control group were given single administration of kanamycin, gentamicin, spiramycin, ciprofloxacin, norfloxacin, lincomycin, chloramphenicol, tetracycline, cefuroxime, Cefotaxime, ampicillin, carbenicillin, cefoxitin or ampicillin-sulbactam, all used effective doses, 2 times/day, for 15 consecutive days, to detect the results of intestinal flora; N-acetyl-D-glucosamine in Example 1 and kanamycin, gentamicin, spiramycin, ciprofloxacin, norfloxacin, lincomycin, chloramphenicol, tetracycline, cefuroxime , cefotaxime, ampicillin, carbenicillin, cefoxitin, or an effective compound preparation of ampicillin-sulbactam was administered continuously for 15 days to detect intestinal flora. Results: The types of resident bacteria in the intestinal tract of each control group were reduced from 12 to 5, the ratio of Gram-positive bacilli to negative bacteria changed, and the water content of stool increased from an average of 45% to 60% (diarrhea symptoms ), the above-mentioned performances did not appear in each group of the experiment. Conclusion: The compound preparation does not appear flora imbalance, and avoids the occurrence of flora disorder.

Experimental example 5 Efficacy experiment of N-acetyl-D-glucosamine and antibiotic compound antibacterial preparation effectively preventing the occurrence of irritable bowel syndrome (IBS) caused by bacterial CGC.

60 rats were selected and randomly divided into experimental group and control group, with 30 rats in each group. The experimental group was given effective dose of N-acetyl-D-glucosamine and antibiotic compound preparation, and the control group was given effective dose of antibiotic alone. Intramuscular injection, for 10 consecutive days, the test group was given N-acetyl-D-glucosamine-aminoglycoside compound antibacterial preparations, and an effective dose was taken for 10 consecutive days, and the feces of rats were observed during the administration and within 1 week of drug withdrawal. , to confirm the presence or absence of CGC. CGC was not detected in the feces of rats one week after drug withdrawal. On this basis, electrical stimulation, gavage of Sichuan pepper water, cold and restraint were given to induce IBS stimulation tests, and the incidence of IBS in the two groups was observed.

Experimental Example 5-1 Aminoglycosides

Drug: N-acetyl-D-glucosamine + Kanamycin, Control: Kanamycin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and aminoglycosides can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-2 Macrolides

Drug: N-acetyl-D-glucosamine + spiramycin, control: spiramycin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and macrolides can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental example 5-3 quinolones

Drug: N-acetyl-D-glucosamine + ciprofloxacin, control: ciprofloxacin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the treatment group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and quinolones can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-4 Lincomycins

Drug: N-acetyl-D-glucosamine + lincomycin, control: lincomycin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and lincomycin can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-5 Chloramphenicols

Drug: N-acetyl-D-glucosamine + chloramphenicol, control: chloramphenicol

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and chloramphenicol can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-6 Tetracyclines

Drug: N-acetyl-D-glucosamine + tetracycline

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and tetracyclines can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-7 Cephalosporins

Drug: N-acetyl-D-glucosamine + cefuroxime, control: cefuroxime

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and cephalosporins can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-8 Penicillins

Drug: N-acetyl-D-glucosamine + ampicillin, control: ampicillin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: The compound preparation of N-acetyl-D-glucosamine and penicillins can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Experimental Example 5-9 Other β-lactams

Drug: N-acetyl-D-glucosamine + cefoxitin, control: cefoxitin

Results: A large number of CGCs appeared in the feces of the rats in the control group. One week after drug withdrawal, CGCs still existed in the feces of the rats, and no CGC was detected in the feces of the rats in the test group. The incidence of IBS induced by electrical stimulation, Sichuan pepper water gavage, cold and restraint, etc., was 0 (0/30) in the treatment group, 33% (10/30), 33% (10/30), and 33% (10/30) in the control group, respectively. 33% (10/30).

Conclusion: N-acetyl-D-glucosamine and other β-lactam compound preparations can effectively prevent the occurrence of irritable bowel syndrome caused by bacterial CGC.

Claims (10)

1. A compound antibacterial drug made from N-acetyl-D-glucosamine and antibiotics. 2. The medicine according to claim 1, wherein N-acetyl-D-glucosamine is its free base or pharmaceutically acceptable salt, and the antibiotic is selected from the group consisting of aminoglycosides, macrolides, tetracyclines, quinolones, linco Mycins, chloramphenicols, cephalosporins, penicillins, other β-lactam antibiotics. 3. The application according to claim 1, wherein the medicine is an injection, tablet, capsule and other mixed preparations. 4. Application of N-acetyl-D-glucosamine in the preparation of compound antibacterial drugs. 5. according to the application of claim 4, wherein N-acetyl-D-glucosamine is its free base or pharmaceutically acceptable salt, antibiotic is selected from aminoglycosides, macrolides, tetracyclines, quinolones, linco Mycins, chloramphenicols, cephalosporins, penicillins, other β-lactam antibiotics. 6. The application of the composition of N-acetyl-D-glucosamine and antibiotics in the preparation of medicines for preventing or treating diseases such as irritable bowel syndrome, dysbiosis in vivo, and intestinal dysfunction. 7. according to the application of claim 6, wherein N-acetyl-D-glucosamine is its free base or pharmaceutically acceptable salt, antibiotic is selected from aminoglycosides, macrolides, tetracyclines, quinolones, linco Mycins, chloramphenicols, cephalosporins, penicillins, other β-lactam antibiotics. 8. A method of enhancing the therapeutic effect of an antibiotic by administering to a patient a therapeutically effective amount of N-acetyl-D-glucosamine and a therapeutically effective amount of the antibiotic. 9. The method according to claim 8, wherein N-acetyl-D-glucosamine is its free base or a pharmaceutically acceptable salt, and the antibiotic is selected from the group consisting of aminoglycosides, macrolides, tetracyclines, quinolones, lincosamine Mycins, chloramphenicols, cephalosporins, penicillins, other β-lactam antibiotics. 10. A method for treating antibiotic-treatable bacterial infections or diseases caused by pathogenic proliferation by administering to a patient a therapeutically effective amount of N-acetyl-D-glucosamine and a therapeutically effective amount of antibiotics.