CN1301112C - Compound antimicrobial medicine containing N-acetophenetidin-D-chitosamine - Google Patents
Compound antimicrobial medicine containing N-acetophenetidin-D-chitosamine Download PDFInfo
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Abstract
The present invention discloses an application on the combination preparation of compound antibacterial drugs by N-acetyl-D-aminoglucose and antibiotics. A tenuous change that athogenic bacteria are converted into cryptic growth cells (CGC) is caused by the antibiotics in bacterial infection resisting treatment, and the pathogenic bacteria are promoted to form clusters, and physiological resisting drugs are generated. When drugs are used, CGC changes of normally residential flora in bodies are simultaneously caused, concurrent chronic diseases are generated after antibiotic treatment is carried out, the flora in bodies is in imbalance, and even dysfunction of intestinal tracts is caused and chronic function diseases are formed. When antibacterial treatment is carried out, the supply of the compound preparation of antibiotics and N-acetyl-D-aminoglucose can prevent bacterium CGC, and prevent complications after antibiotic drugs are used.
Description
Technical field
The present invention relates to the antibacterial application of N-acetyl-D-amino glucose and the acceptable salt of medicine thereof, relate to contain composite antibacterial drugs and the application of N-acetyl-D-amino glucose in the preparation composite antibacterial drugs that N-acetyl-D-amino glucose and various antibiotic are made specifically.
Background technology
Since the antibiotic invention, the infection that makes the mankind tackle pathogenic microorganism has had a strong weapon, and millions upon millions of people are away from the threat of infecting.But, As time goes on, for tackling bacterial resistance widely, the antibiotic kind is on the increase, consumption continues to increase, consequently producing little effect, and causing the variation of the multiple mode of antibacterial thus, comprising that antibacterial that the present invention proposes is dived to give birth to the new adaptation form that this antibacterial of body occurs in adverse environment controlling in bacterial resistance problem and the nosocomial infection problem.The variation of antibacterial causes normal flora to change conditioned pathogen into, causes flora disorder and nosocomial infection.Wherein the generation of the generation of the latent living body of antibacterial and field planting and irritable bowel syndrome and function of intestinal canal disorder is closely related, and this obtains proof in clinical investigation.
For a long time, antibacterial is considered to single celled biology, and each antibacterial carries out vital movement independently, and too many contact does not take place each other.But, studies show that in recent years, in fact the individual cells of antibacterial is different with colony's performance of antibacterial, particularly for the interaction of antibacterial and other biological, the effect that antibacterial produced be actually bacterial clump as a whole and the performance, its performance be similar to multicellular organism (Shapiro, J.A. " Bacteriaas multicellular organism. " Scientific American 1988,256:82-89).The inventor discovers that further under suitable condition of culture, antibacterial can generate the bacterium colony figure that is similar to ripple, shows vital movement phenomenon clocklike.This phenomenon is interesting for the life rule of understanding antibacterial, and the inventor etc. are with this phenomenon called after " biological ripple " (Xu Qiwang etc., the colony of growth of microorganism, cycle and ripple, Nature Journal, 1992,15 (3), 195-197), and this has been carried out studying (Liu Junkang etc., biological ripple Study on Theory, Chinese microecology magazine, 1994,6 (6), 40-46; Xu Qiwang etc., the non-equilibrium Mechanism Study of biological ripple, Northwest University's journal (natural science edition), 1997,27 (supplementary issues), 320-325).
The inventor etc. are in to biological ripple Study on Theory, discovery forms wavy bacterium colony, become the state that bacterial growth is vigorous and inhibition alternately exists, part in the bacterial growth inhibition, antibacterial is not divided, shape is very thin, extent of metabolism is low but mobility is strong, the inventor etc. be referred to as dive to give birth to body (CGC) (Deng Guohong, etc.The aperiodicity of surviving in the bacillus pyocyaneus water changes observes.Third Military Medical University's journal, 1997; 19 (3): 197-201).When further researching human body Pathophysiology, the discovery antibacterial is changed the living body (CGC) of diving in a large number in the environment of antibiotic substance is arranged, under the state of living body (CGC) of diving, bacterial antibiotic is extremely insensitive, also is difficult to it is killed (Deng Guohong even used a large amount of antibiotic.Antibacterials are dived to antibacterial and are given birth to the effect of body.The Nature is explored, and 1999; 18 (69): 67-68).In case and antibiotic disappears or concentration is reduced to the following level of MIC, the variation that antibacterial conforms takes place to change promptly fracture rapidly and form individual cells and be deposited in together accordingly, forms bacterium colony.Experimentation shows that antibiotic all can induce into CGC to Gram-positives such as colon bacillus, Bacillus proteus, Salmonella, dysentery bacterium or negative bacteria, in vivo test comprises that animal and human body all prove this effect and external consistent (Wang Zhenwei etc., dive and give birth to body spin property laboratory observation, Chinese public health, 2000,16 (5), 1-3; Liu, Junkang, et al, Turbulene under themicroscope, Journal of Biological Physics, 2000,00 (1), 1-7).
The antibacterial CGC that arrives involved in the present invention is regardless of formed all can the generation human body of which bacterioid and damages.Have been found that the very thin shape of form that antibacterial is taken place changes under the different ecological environment, change on poor metabolism, the toxicity on the physiology that very big difference (Guo Gang, Huang Chunji etc. are arranged when being in brood body to the damage of body and with a kind of antibacterial.Inductive very thin bacterium of antibiotic Sub-MICs and latent comparative study of giving birth to body.China's epidemiology magazine, 1996; 17 (3-C)).But this in the past difference does not attract much attention, antibacterial causes antibiotic consumption constantly to increase to the transformation of giving birth to body of diving, and effect reduces gradually, thus the probability that has increased mistaken diagnosis, disorderly offerd medicine, cause the state of an illness to increase the weight of even delay treatment opportunity, cause a large amount of adverse effectes.
Processes such as the inventor study for a long period of time, have proved that antibacterial CGC is human the contact due to the chemical substance, and the particularly antibiotic intestinal bacteria generation CGC that generally makes changes.Have been found that chronic diarrhea, chronic gastrointestinal dysfunction, particularly bigger irritable bowel syndrome (IBS) to the anthropogenic influence, all be since CGC directly or indirectly cause (Xu Qiwang. the antibacterial of irritable bowel syndrome dive to give birth to the body pathogenesis. science, 1998; 10:59-61).
The inventor etc. are in carrying out biological ripple theoretical research process, find that this fluctuation has its intrinsic regulatory mechanism, can utilize chemical substance that biological wave process is regulated, through separation and purification and evaluation, defining a kind of material is N-acetyl-D-amino glucose.Confirm to have the biological ripple effect that promotes fluctuation (Huang Hui etc., bacterium living beings ripple regulatory factor experimental analysis, Third Military Medical University's journal, 1999,21 (3), 178-180).
N-acetyl-D-amino glucose is a kind of known substance (2-acetylamino-2-deoxy-D-glucose; N-acetyl-D-(+)-glucosamine; GlcNAc; CAS No.7512-17-6).Structure is as follows:
N-acetyl-D-amino glucose has been disclosed and has been used for periodontitis (WO91/02539A1), inflammatory bowel disease (WO99/53929A1), keratopathy (JP10-287570A2), prostate hyperplasia (US5,116, treatment of diseases such as 615), the vaccine (WO97/18790A3) of preparation control infected by microbes, and the preparation (JP2-11505A2) etc. of improving looks (JP59-13708A2), have one's hair wash.In recent years on the basis that inventor etc. furthers investigate its short ripple effect, Chinese patent application (CN1156027 communique) as the new drug application of treatment IBS has also been proposed, and the therapeutic agent (number of patent application 01104884.0) that is used for the antibacterium field planting, but, thereby do not act on the report that antibacterial strengthens effects of antibiotics with it for the effect of antibacterial CGC due to the treatment antibiotic and the disease that causes thus report not still.
Summary of the invention
The inventor etc. are in the short ripple effect research of carrying out N-acetyl-D-amino glucose, be surprised to find that N-acetyl-D-amino glucose can prevent effectively antibacterial under antibiotic effect, change into dive ecological, thereby can significantly promote various antibiotic action effects, finish the present invention therefrom.
In other words, the present invention relates to the antibacterial application of N-acetyl-D-amino glucose and the acceptable salt of medicine thereof, specifically relate to contain composite antibacterial drugs and the application of N-acetyl-D-amino glucose in the preparation composite antibacterial drugs that N-acetyl-D-amino glucose and antibiotic are made.
The present invention relates to contain the application in the medicine of diseases such as the dysbacteriosis in preparation prevention or treatment irritable bowel syndrome, body of N-acetyl-D-amino glucose and antibiotic compositions, function of intestinal canal disorder.
The invention still further relates in addition by N-acetyl-D-amino glucose that gives the patient treatment effective dose and the antibiotic for the treatment of effective dose, thereby strengthen the method for antibiotic therapy effect, and by N-acetyl-D-amino glucose that gives the patient treatment effective dose and the antibiotic for the treatment of effective dose, the method for treatment treatable bacterial infection of antibiotic or disease that pathogenic propagation causes.
The invention still further relates to by N-acetyl-D-amino glucose that gives the patient treatment effective dose and the antibiotic for the treatment of effective dose, thus the method for diseases such as prevention or treatment irritable bowel syndrome, the interior dysbacteriosis of body, function of intestinal canal disorder.
The invention specific embodiment
Below be described in detail the present invention.
Of the present invention containing in N-acetyl-D-amino glucose and the antibiotic medicament/composition, N-acetyl-D-amino glucose structure is as follows:
Every physicochemical data of N-acetyl-D-amino glucose is as follows:
Molecular formula: C
8H
15NO
6
Molecular weight: 221.21 (accurate molecular weight 221.2096)
Fusing point: 201-204 ℃
N-acetyl-D-amino glucose can be various sources, and about its preparation, both at home and abroad chemosynthesis or semisynthesis of adopting also have directly to make from known method more.For example WO97/31121 is disclosed is equipped with N-acetyl-D-amino glucose from chitin polyase legal system, Japanese Patent Application Publication JP6-3273493 is disclosed a kind ofly to obtain N-acetyl-oligochitosan with chitin polysaccharide part acid hydrolysis, and then through enzyme handle the method for N-acetyl-D-amino glucose.
Of the present invention containing in N-acetyl-D-amino glucose and the antibiotic medicament/composition, N-acetyl-D-amino glucose can use its free alkali or the acceptable salt of medicine.The acceptable salt of medicine as N-acetyl-D-amino glucose, the hydrochlorate that for example can use N-acetyl-D-amino glucose and mineral acid to form, hydrobromate, borate, phosphate, sulfate, disulfate and hydrophosphate, the citrate that N-acetyl-D-amino glucose and organic acid form, benzoate, Ascorbate, Methylsulfate, the naphthalene esilate, picrate, fumarate, maleate, malonate, oxalates, succinate, acetate, tartrate, mesylate, toluene fulfonate, isethionate, alpha-ketoglutarate, α-glycerophosphate and Cori ester salt etc.Above-mentioned monomer or officinal salt all can use according to prepared person of known method or commercially available prod.
The present invention relates to contain in N-acetyl-D-amino glucose and antibiotic compositions, the medicine, antibiotic is meant and is applied to people or other mammals, can have the material of chemotherapy effect to microorganisms such as antibacterium, mycoplasma, chlamydia.Antibiotic described in the present invention can be fermentation, semi-synthetic or complete synthesis, and is unqualified to this.For example can be by producing the antibiotic that antibiotic microorganism (mycete, actinomycetes etc.) fermentation obtains, or the antibiotic that adopts the fermentation gained passes through structure of modification, parent nucleus is identical or similar semisynthetic antibiotics, or with the complete synthesis antibiotic of conventional antibiotic similar, comprise that also the various complete synthesis routines with antibacterial action also are considered as antibiotic chemotherapeutics such as carbostyril compound etc.
Antibiotic described in the present invention so long as act on antibacterial etc., can induce it to produce the ecology of diving, and just can use compositions/medicine of the present invention.
Among the present invention, operable antibiotic includes but not limited to:
Other beta-lactam antibiotic beyond aminoglycosides antibiotics, Penicillin antibiotics, cephalosporins, penicillin, the cephalosporins, chloromycetin series antibiotics, lincomycin series antibiotics, macrolide antibiotics, quinolones, tetracycline antibiotics etc., but be not limited thereto.
Aminoglycosides antibiotics of the present invention is the antibiotic that has the aminoglycoside structure in the molecule, that for example produce or be antibiotic such as basic semisynthetic streptomycin (II), kanamycin, amikacin with it by streptomycete, the gentamycin that micromonospora produces, sagamicin etc., but be not limited thereto.
Penicillin antibiotics of the present invention is meant the natural or semisynthetic antibiotic monomer that has penicillanic acid mother nucleus structure (III) in the molecule or its various officinal salts etc., for example: natural penicillin such as benzylpenicillin, penicillin V etc.; Semisynthetic penicillin such as ampicillin, carbenicillin, amoxicillin etc., but be not limited thereto.
Cephalosporins of the present invention is meant synthetic, the semi-synthetic or natural antibiotics that has Cephalosporanic acid (IV) or oxacephem (V) mother nucleus structure in the molecule, for example: Cefalexin, cefradine, cefaclor, cefuroxime, cefotaxime, latamoxef etc., but be not limited thereto.
Other beta-lactam antibiotic beyond penicillin of the present invention, the cephalosporins, be meant synthetic, the semi-synthetic or antibiotic that has beta-lactam ring structure (VI) but do not have penicillin, cephalosporin class formation, for example: Nocardicin, thiomycin, imipenum with carbapenem structure (VII); Sulbactam, its TZB, Sultamicillin (ampicillin-sulbactam) with sulfur penam structure (VIII); The clavulanic acid of oxapenam structure (IX) etc., but be not limited thereto.
Chloromycetin series antibiotics of the present invention is meant synthetic, the semi-synthetic or natural antibiotics or derivatives thereof that has with chloromycetin (X) similar structures, for example chloromycetin, chloramphenicol succinate, thiamphenicol etc., but be not limited thereto.
Lincomycin series antibiotics of the present invention, be meant for example have lincomycin (XI) or its analog, the isostructural antibiotic of derivant, for example, lincomycin, clindamycin etc., but be not limited thereto.
Macrolide antibiotics of the present invention is meant for example macrolide antibiotics and derivants such as salt, ester thereof such as erythromycin, spiramycin (XII), Roxithromycin, azithromycin, but is not limited thereto.
Quinolones described in the present invention belongs to the synthetic chemistry medicine, does not belong to antibiotic category, but for brevity, thinks also that from its drug effect it belongs to antibiotic herein, in the narration of this description this is not made any distinction between.Carbostyril compound comprises norfloxacin, ofloxacin, the ciprofloxacin of naphthyridines acids parent nucleus (XIII), the enoxacin of cinnolines carboxylic acids parent nucleus (XIV), and the pipemidic acid of Pyridopyrimidine carboxylic acids parent nucleus (XV) etc., but be not limited thereto.
Tetracyclines described in the present invention is meant the natural, semi-synthetic or synthetic antibiotic with perhydrophenanthrene basic framework by generations such as actinomycetes, for example tetracycline (XVI), chlortetracycline, oxytetracycline etc., but be not limited thereto.
Can be induced by antibiotic and produce the ecological antibacterial of diving, include but not limited to the intestinal gram negative bacilli, comprise pathogen and Chang Ju flora, anaerobic and facultative antibacterial etc.
Though do not intend sticking to any existing theory, N-acetyl-D-amino glucose and antibiotic and consider as follows among the present invention with the mechanism that can strengthen drug effect:
Antibiotic is that the reaction by antibacterial plays a role, and changes into when antibacterial and dives when giving birth to body, antibiotic is not reacted, and make antibiotic invalid; It is the bacterial reproduction volume morphing that N-acetyl-D-amino glucose can make the living body of diving reply, thereby makes it antibiotic sensitive, strengthens the antibiotic drug effect with this.
When N-acetyl-D-amino glucose and antibiotic use jointly in the compound preparation of the present invention, N-acetyl-D-amino glucose and antibiotic consumption and ratio are because of antibiotic different being not quite similar, specifically, because because N-acetyl-D-amino glucose has the antibiotic potentiation, so antibiotic consumption can adopt conventional amount used or be less than conventional amount used, for example reduce to conventional 50% even still less.N-acetyl-D-amino glucose itself is nontoxic, so its consumption is not particularly limited, and for example every day, consumption can be the scope of 100mg～10g.Specifically:
When N-acetyl-D-amino glucose and aminoglycosides antibiotics combination, both ratios can be N-acetyl-D-amino glucose: aminoglycosides antibiotics=1: 1.6～1: 5.As Compound Streptomycin, injection is used for quiet or intramuscular injection, and adult's consumption is 1g/ days.The compound recipe kanamycin, injection is used for intramuscular injection, and consumption is 300mg/ days, 8 hours/time.The compound gentamicin injection is used for intramuscular injection or quiet, and consumption is 90-300mg/ days, 8 hours/time.Above-described dosage is antibiotic, and is as follows.
When N-acetyl-D-amino glucose and macrolide antibiotics combination, ratio is a N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30.As the compound recipe spiramycin, be mixed in proportion powder and make capsule, oral, consumption is 2-3g/ days, 8 hours/time.
When N-acetyl-D-amino glucose and quinolones combination, ratio is a N-acetyl-D-amino glucose: quinolones=1: 2～1: 15.As, make compound norfloxacin, capsule, oral, consumption is 1200mg/ days, 8 hours/time; Compound ciprofloxacin, capsule, oral, consumption is 1200mg/ days, 8 hours/time, also can be made into injection, quiet, 200mg/ time, 1-2 time/day.
When N-acetyl-D-amino glucose and lincomycin series antibiotics combination, ratio is a N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10.For example, mixed-powder is made capsule, every day 0.6-1.8g; Also can be made into quiet of injection.
When N-acetyl-D-amino glucose and chloromycetin series antibiotics combination, ratio is a N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10.Mixed powder makes coated tablet or syrup, and is oral, 25-50mg/kg; Or be injection, intramuscular injection or quiet, 1-2g/ days, 2-4 time/day.
When N-acetyl-D-amino glucose and tetracycline antibiotics combination, ratio is a N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30.Make capsule or coated tablet, oral, 1-2g/ days; Also can make quiet of injection, 1-1.5g/ days
When N-acetyl-D-amino glucose and cephalosporins combination, ratio is a N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5.Mix to make injection as, N-acetyl-D-amino glucose with cefuroxime, be used for quiet or intramuscular injection, 1.5-6g/ days, 2 times/day; Mix to make injection with cefotaxime, be used for quiet or intramuscular injection, 2g/ days, 2 times/day.
When N-acetyl-D-amino glucose and penicillins combination, ratio is a N-acetyl-D-amino glucose: penicillins=1: 1～1: 30.As, mix to make capsule with ampicillin, oral, 50-100mg/kg/ days, make injection, intramuscular injection or quiet notes, 100-200mg/kg/ days; Make injection with Carbenicillin, intramuscular injection or quiet, 4-8g/ days, 4 times/day.
When N-acetyl-D-amino glucose and the combination of other beta-lactam antibiotic, ratio is a N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.As, make injection with cefoxitin, quiet notes or intramuscular injection, 8-10g/ days; Make compound recipe ampicillin-sulbactam injection, 1.5-6g/ days, 2-3 time/day, intramuscular injection or quiet notes.
Should illustrate, when N-acetyl-D-amino glucose and antibiotic are used in combination, as long as can realize purpose of the present invention, the two can be made compound preparation and use simultaneously, also can make preparation respectively, while or sequential use for example can give antibiotic earlier, take N-acetyl-D-amino glucose after a while again; Perhaps take N-acetyl-D-amino glucose conversely earlier, give antibiotic again, this is not added restriction.
Effect and the effects such as the disorder of prophylactic treatment intestinal microbial population, irritable bowel syndrome of following EXPERIMENTAL EXAMPLE proof N-acetyl-D-amino glucose of the present invention and antibiotic combination antagonism CGC.
Below used antibiotic be commercially available product, available from Third Military Medical University southwest hospital pharmacy.
Experimental example 1
The different proportion of aminoglycosides and N-acetyl-D-amino glucose is induced experiment to escherichia coli CGC in the compound antibacterial agent
Escherichia coli (No. 33310, Chengdu Biological Products Inst., Ministry of Public Health buys) are selected in this test for use; Antibiotic is got various concentration, and N-acetyl-D-amino glucose consumption carries out the grid method design from 10mg to 300mg.Carry out the plate coating respectively, medicine adopts the K-B method.At medicine inhibition zone edge picking colony, microscopically is observed.In each visual field, thalline length is more than 50 μ m, and quantity is being the CGC positive more than 5, with "+" expression; In each visual field, thalline length is in 50 μ m, and quantity is the CGC feminine gender at 0～4, with "-" expression.This moment, the ratio of two kinds of materials was " an effectively ratio ", and experimental result is added up in following table 1-1～table 1-9.
Table 1-1
Aminoglycosides antibiotics is selected kanamycin and gentamycin for use, and consumption all is that 50mg is to 500mg;
| Aminoglycosides (mg) formula (I) chemical compound (mg) | 50 | 100 | 150 | 200 | 300 | 400 | 500 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and aminoglycosides medicine is 1: 1.6～1: 5 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-2
Macrolide antibiotics is selected spiramycin for use, and consumption 300mg is to 1500mg
| Macrolide (mg) formula (I) chemical compound (mg) | 300 | 500 | 700 | 900 | 1100 | 1300 | 1500 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and Macrocyclolactone lactone kind medicine is 1: 5～1: 30 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-3
Quinolones is selected ciprofloxacin and norfloxacin for use, and consumption all is that 150mg is to 600mg;
| Quinolones (mg) formula (I) chemical compound (mg) | 150 | 200 | 300 | 400 | 500 | 550 | 600 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and quinolones is 1: 2～1: 15 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-4
Lincomycin series antibiotics is selected lincomycin for use, and consumption all is that 100mg is to 700mg
| Lincomycin (mg) formula (I) chemical compound (mg) | 100 | 200 | 300 | 400 | 500 | 600 | 700 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and lincomycin medicine is 1: 2.5～1: 10 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-5
The chloromycetin consumption is that 100mg is to 700mg
| Chloromycetin (mg) formula (I) chemical compound (mg) | 100 | 200 | 300 | 400 | 500 | 600 | 700 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and chloromycetin medicine is 1: 2.5～1: 10 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-6
Tetracyclines is selected tetracycline for use, and consumption is that 10mg is to 300mg
| Tetracyclines (mg) formula (I) chemical compound (mg) | 10 | 50 | 100 | 150 | 200 | 250 | 300 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and tetracycline medication is 1: 1～1: 30 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-7
Cephalosporins is selected cefuroxime and cefotaxime for use, and consumption all is that 50mg is to 800mg
| Cephalosporins (mg) formula (I) chemical compound (mg) | 50 | 100 | 200 | 300 | 450 | 650 | 800 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and cephalosporins medicine is 1: 2.6～1: 5 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-8
Penicillins is selected ampicillin and carbenicillin for use, and consumption all is that 10mg is to 300mg
| Beta-lactam (mg) formula (I) chemical compound (mg) | 10 | 50 | 100 | 150 | 200 | 250 | 300 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and Beta-lactam medicine is 1: 1～1: 30 in the compound antibacterial agent that stops escherichia coli CGC to form.
Table 1-9
Other beta-lactam is selected cefoxitin and ampicillin-sulbactam for use, and consumption all is that 500mg is to 2500mg
| Other beta-lactam (mg) formula (I) chemical compound (mg) | 500 | 800 | 1200 | 1500 | 1800 | 2000 | 2500 |
| 10 | - | + | + | + | + | + | + |
| 50 | - | - | + | + | + | + | + |
| 100 | - | - | - | + | + | + | + |
| 150 | - | - | - | - | + | + | + |
| 200 | - | - | - | - | - | + | + |
| 250 | - | - | - | - | - | - | + |
| 300 | - | - | - | - | - | - | - |
Conclusion: effective ratio of N-acetyl-D-amino glucose and other Beta-lactam medicine is 1: 8～1: 50 in the compound antibacterial agent that stops escherichia coli CGC to form.
Experimental example 2
The effect experiment that N-acetyl-D-amino glucose antibiotic compound preparation forms at external prevention antibacterial CGC
This test is carried out the plate coating respectively to Gram-negative amphimicrobe, gram-negative anaerobic bacteria, Gram-positive aerobe respectively external, experiment medicine and control drug are dissolved with the sterile water for injection of equal volume respectively, get 10 microlitres and prepare drug sensitive test paper, drug study adopts the K-B method, observe CGC formation and be suppressed situation, experimental result sees Table 2-1～2-9.
Table 2-1
The N-acetyl-D-amino glucose 100mg of experimental example 1 and the antibiotic kanamycin 300mg of aminoglycosides make compound injection, and control drug is the kanamycin of same dose.
| The bacterium name | Compound preparation | Kanamycin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| The negative anaerobism of gram-bacteria | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Above strain is identified to belonging to.
Conclusion: N-acetyl-D-amino glucose is compared with independent use aminoglycosides medicine with the compounded antibiotic preparation of aminoglycosides drug regimen, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-2
The N-acetyl-D-amino glucose of experimental example 1 and the antibiotic compound preparation of Macrolide (N-acetyl-D-amino glucose 100mg, spiramycin 900mg, powder mixes) control drug is spiramycin 900mg
| The bacterium name | Compound preparation | Spiramycin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| Removing from office blue oxygen Salmonella feminine gender detests | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use Macrocyclolactone lactone kind medicine with the compounded antibiotic preparation of Macrocyclolactone lactone kind medicine combination, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-3
The N-acetyl-D-amino glucose of experimental example 1 and the antibiotic compound preparation of quinolones (N-acetyl-D-amino glucose 100mg, norfloxacin 400mg mixes) control drug is the same dose norfloxacin
| The bacterium name | Compound preparation | Norfloxacin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| Removing from office blue oxygen Salmonella feminine gender detests | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use quinolones with the compounded antibiotic preparation of quinolones combination, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-4
The N-acetyl-D-amino glucose (100mg) of experimental example 1 is formed compound preparation with lincomycin (400mg), and control drug is lincomycin (400mg)
| The bacterium name | Compound preparation | Lincomycin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| The property leather is detested blue oxygen Salmonella the moon | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use lincomycin medicine with the compounded antibiotic preparation of lincomycin drug regimen, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-5
The N-acetyl-D-amino glucose (100mg) of experimental example 1 makes compound preparation with chloromycetin (400mg), and control drug is chloromycetin (400mg)
| The bacterium name | Compound preparation | Chloromycetin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| Removing from office blue oxygen Salmonella feminine gender detests | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use chloromycetin medicine with the compounded antibiotic preparation of chloromycetin drug regimen, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-6
The N-acetyl-D-amino glucose (50mg) of experimental example 1 is formed compound preparation with tetracycline (150mg), and control drug is tetracycline (150mg)
| The bacterium name | Compound preparation | Tetracycline | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| The property leather is detested blue oxygen Salmonella the moon | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The blue Xu Shi of oxygen sun lead fungi | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use tetracycline medication with the compounded antibiotic preparation of tetracycline medication combination, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-7
The N-acetyl-D-amino glucose of experimental example 1 and the antibiotic compound preparation of cephalosporins, (N-acetyl-D-amino glucose 100mg mixes with cefuroxime 300mg), control drug is cefuroxime 300mg
| The bacterium name | Compound preparation | Cefuroxime | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| Gram-negative anaerobic bacteria | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| Removing from office the blue oxygen Salmonella positive needs | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use cephalosporins medicine with the compounded antibiotic preparation of cephalosporins drug regimen, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-8
The N-acetyl-D-amino glucose of experimental example 1 and the antibiotic compound preparation of penicillins, (N-acetyl-D-amino glucose 150mg, ampicillin 150mg mixes composition) control drug is the ampicillin
| The bacterium name | Compound preparation | The ampicillin | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| Removing from office blue oxygen Salmonella feminine gender detests | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| The property leather need blue oxygen Salmonella sun | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with independent use Beta-lactam medicine with the compounded antibiotic preparation of Beta-lactam medicine combination, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Table 2-9
The N-acetyl-D-amino glucose of experimental example 1 and the antibiotic compound preparation of other beta-lactam (N-acetyl-D-amino glucose 100mg, ampicillin-sulbactam 1500mg mixes composition), control drug is ampicillin-sulbactam
| The bacterium name | Compound preparation | Ampicillin-sulbactam | |
| The Gram-negative amphimicrobe | Escherichia coli | - | + |
| Salmonella | - | + | |
| Shigella | - | + | |
| Klebsiella | - | + | |
| Bacillus proteus | - | + | |
| Citrobacter | - | + | |
| The negative anaerobism of gram-bacteria | Bacteroides fragilis | - | + |
| Bacteroides melanogenicus | - | + | |
| Clostridium difficile | - | + | |
| The nucleic acid bacillus | - | + | |
| Leather needs the blue oxygen Salmonella positive | Diphtheroid | - | + |
| Listeria spp | - | + | |
| Bacillus cereus | - | + | |
Conclusion: N-acetyl-D-amino glucose is compared with other Beta-lactam medicine of independent use with the compounded antibiotic preparation of other Beta-lactam medicine combination, can stop the common antibacterial of digestive tract to change CGC into effectively external.
Experimental example 3
The potency test that stops CGC to form in N-acetyl-D-amino glucose and the antibiotic compound antibiotic preparation body.
Select the Wistar rat for use, the effective ratio of laboratory observation N-acetyl-D-amino glucose and antibiotic is formed compound preparation, and (what provide in the following example is the medicine proportion of composing to the rat of infected mice Bacillus typhi and not infected rats in vivo test.Its dosage form is ditto described.The antibiotic that does not contain N-acetyl-D-amino glucose of getting equivalent in contrast.Every kilogram of dose of rat dosage behaviour consumption (as previously mentioned) multiply by 6.5 times.Experiment is taked random packet, 15 every group.
The intramuscular injection of dosage employing effective dose or oral continued for 1 week.Carry out 2 feces CGC every day and check, carried out in the 7th day intestinal mucosa CGC field planting detect determine with feces in the corresponding relation of CGC, feces has CGC and intestinal mucosa CGC field planting positive, otherwise negative.Method for expressing is that total zoopery number of elements is a denominator, and male number of animals is a molecule.The result is as follows:
Experimental example 3-1 aminoglycosides antibiotics
Medicine: N-acetyl-D-amino glucose (100mg)+kanamycin (200mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the aminoglycosides compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of kanamycin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and aminoglycosides compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-2 macrolide antibiotics
Medicine: N-acetyl-D-amino glucose (100mg)+spiramycin (900mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the Macrolide compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of spiramycin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and Macrolide compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-3 quinolones
Medicine: N-acetyl-D-amino glucose (100mg)+ciprofloxacin (500mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the quinolones compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of ciprofloxacin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and quinolones compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-4 lincomycin series antibiotics
Medicine: N-acetyl-D-amino glucose (100mg)+lincomycin (400mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the lincomycin compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of lincomycin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and lincomycin compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-5 chloromycetin series antibiotics
Medicine: N-acetyl-D-amino glucose (100mg)+chloromycetin (400mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the chloromycetin compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of chloromycetin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and chloromycetin compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-6 tetracycline antibiotics
Medicine: N-acetyl-D-amino glucose (150mg)+tetracycline (150mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the Tetracyclines compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of tetracycline and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and Tetracyclines compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-7 cephalosporins
Medicine: N-acetyl-D-amino glucose (100mg)+cefuroxime (300mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the cephalosporins compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of cefuroxime and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and cephalosporins compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 3-8 Penicillin antibiotics
Medicine: N-acetyl-D-amino glucose (100mg)+ampicillin (200mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and the beta-lactam compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of ampicillin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and beta-lactam compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Other beta-lactam of experimental example 3-9
Medicine: N-acetyl-D-amino glucose (100mg)+cefoxitin (150mg)
Conclusion: infected mice Bacillus typhi rat and not behind the infected rats N-acetyl-D-amino glucose that gives effective dose and other beta-lactam compounded antibiotic preparation in the feces positive rate of CGC and intestinal mucosa CGC be 0 (0/15), and only to the infected rats of cefoxitin and not infected rats CGC positive rate be 100% (15/15).CGC in the feces is positive to coincide with positive both results of intestinal mucosa CGC field planting.Show that N-acetyl-D-amino glucose and other beta-lactam compounded antibiotic preparation can stop the formation of CGC in animal body effectively.
Experimental example 4N-acetyl-D-amino glucose and antibiotic compound preparation cause the disorderly preventive effect laboratory observation of flora to antibacterial CGC
15 of rats are respectively organized in contrast, single respectively kanamycin, gentamycin, spiramycin, ciprofloxacin, norfloxacin, lincomycin, chloromycetin, tetracycline, cefuroxime, cefotaxime, ampicillin, carbenicillin, cefoxitin or the ampicillin-sulbactam of giving, all adopt effective dose, 2 times/day, continuous 15 days, detect the intestinal microbial population result; Each group of experiment gives respectively as the N-acetyl-D-amino glucose of experimental example 1 and effective compound preparation of kanamycin, gentamycin, spiramycin, ciprofloxacin, norfloxacin, lincomycin, chloromycetin, tetracycline, cefuroxime, cefotaxime, ampicillin, carbenicillin, cefoxitin or ampicillin-sulbactam, also successive administration is 15 days, detects intestinal microbial population.The result: contrast is respectively organized intestinal and is often occupied the strain class and be reduced to 5 kinds by 12 kinds of beginning, and change has taken place the ratio of Gram-positive bacillus and negative bacterium, the stool water content occurs and rises to 60% (symptom of diarrhea) by average 45%, and each organizes experiment and above-mentioned performance do not occur.Conclusion: dysbacteriosis does not appear in compound preparation, avoids dysbacteriosis to take place.
The effectively pre-bacteriological protection CGC of experimental example 5N-acetyl-D-amino glucose and antibiotic compound antibiotic preparation causes the effect experiment that irritable bowel syndrome (IBS) takes place.
Select 60 of rats, be divided into experimental group and matched group at random, every group each 30.Experimental group gives the N-acetyl-D-amino glucose and the antibiotic compound preparation of effective dose, and matched group gives the antibiotic of effective dose merely.Intramuscular injection, continuous 10 days, test group gave N-acetyl-D-amino glucose-aminoglycosides compounded antibiotic preparation, taked the effective dose successive administration 10 days, observed during the administration and the rat feces in 1 week of drug withdrawal, and whether the existence of affirmation CGC to be.Do not detect CGC yet in the rat feces after one week of drug withdrawal.Give the irritant test that IBS is induced in electricity irritation, Fructus Zanthoxyli water filling stomach, cold and constraint etc. on this basis, observe the incidence rate of two groups of IBS.
Experimental example 5-1 aminoglycosides
Medicine: N-acetyl-D-amino glucose+kanamycin, contrast: kanamycin
Result: occur a large amount of CGC in the control rats feces, after drug withdrawal-week, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and aminoglycosides compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-2 Macrolide
Medicine: N-acetyl-D-amino glucose+spiramycin, contrast: spiramycin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and Macrolide compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-3 quinolones
Medicine: N-acetyl-D-amino glucose+ciprofloxacin, contrast: ciprofloxacin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the administration group rat feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and quinolones compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-4 lincomycin class
Medicine: N-acetyl-D-amino glucose+lincomycin, contrast: lincomycin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and lincomycin compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-5 chloromycetin
Medicine: N-acetyl-D-amino glucose+chloromycetin, contrast: chloromycetin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and chloromycetin compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-6 Tetracyclines
Medicine: N-acetyl-D-amino glucose+tetracycline
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and Tetracyclines compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-7 cephalosporins
Medicine: N-acetyl-D-amino glucose+cefuroxime, contrast: cefuroxime
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and cephalosporins compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Experimental example 5-8 penicillins
Medicine: N-acetyl-D-amino glucose+ampicillin, contrast: ampicillin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and penicillins compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Other beta-lactam of experimental example 5-9
Medicine: N-acetyl-D-amino glucose+cefoxitin, contrast: cefoxitin
Result: occur a large amount of CGC in the control rats feces, after one week of drug withdrawal, still have CGC to exist in the rat feces, do not detect CGC in the rats in test groups feces.Electricity irritation, Fructus Zanthoxyli water are irritated stomach, cold and constraint etc. and are induced IBS incidence rate, administration group to be 0 (0/30), and matched group is respectively 33% (10/30), 33% (10/30), 33% (10/30).
Conclusion: N-acetyl-D-amino glucose and other beta-lactam compound preparation can effectively prevent antibacterial CGC and cause the irritable bowel syndrome generation.
Claims (6)
1. composite antibacterial drugs, contain N-acetyl-D-amino glucose or its officinal salt and antibiotic, wherein antibiotic is selected from other beta-lactam antibiotic outside aminoglycosides, Macrolide, Tetracyclines, quinolones, lincomycin class, chloromycetin, cephalosporins, penicillins, cephalosporins and the penicillins, and the two ratio is respectively N-acetyl-D-amino glucose according to class of antibiotic: aminoglycosides antibiotics=1: 1.6～1: 5; N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30; N-acetyl-D-amino glucose: quinolones=1: 2～1: 15; N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30; N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5; N-acetyl-D-amino glucose: penicillins=1: 1～1: 30; Or N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.
2. according to the medicine of claim 1, wherein said medicine is injection, capsule, tablet, powder or syrup.
3.N-acetyl-D-amino glucose or its officinal salt and the antibiotic application in the preparation composite antibacterial drugs, wherein antibiotic is selected from other beta-lactam antibiotic outside aminoglycosides, Macrolide, Tetracyclines, quinolones, lincomycin class, chloromycetin, cephalosporins, penicillins, cephalosporins and the penicillins, and the two ratio is respectively N-acetyl-D-amino glucose according to class of antibiotic: aminoglycosides antibiotics=1: 1.6～1: 5; N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30; N-acetyl-D-amino glucose: quinolones=1: 2～1: 15; N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30; N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5; N-acetyl-D-amino glucose: penicillins=1: 1～1: 30; Or N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.
4.N-acetyl-D-amino glucose or its officinal salt and antibiotic compositions are at preparation prevention or treatment irritable bowel syndrome, dysbacteriosis in the body, application in the medicine of function of intestinal canal disorders, wherein antibiotic is selected from aminoglycosides, Macrolide, Tetracyclines, quinolones, the lincomycin class, chloromycetin, cephalosporins, penicillins, other beta-lactam antibiotic outside cephalosporins and the penicillins, the two ratio is respectively N-acetyl-D-amino glucose according to class of antibiotic: aminoglycosides antibiotics=1: 1.6～1: 5; N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30; N-acetyl-D-amino glucose: quinolones=1: 2～1: 15; N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30; N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5; N-acetyl-D-amino glucose: penicillins=1: 1～1: 30; Or N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.
5.N-acetyl-D-amino glucose or its officinal salt have strengthened application in the medicine of antibiotic therapy effect in preparation, wherein antibiotic is selected from other beta-lactam antibiotic outside aminoglycosides, Macrolide, Tetracyclines, quinolones, lincomycin class, chloromycetin, cephalosporins, penicillins, cephalosporins and the penicillins, and the two ratio is respectively N-acetyl-D-amino glucose according to class of antibiotic: aminoglycosides antibiotics=1: 1.6～1: 5; N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30; N-acetyl-D-amino glucose: quinolones=1: 2～1: 15; N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30; N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5; N-acetyl-D-amino glucose: penicillins=1: 1～1: 30; Or N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.
6.N-acetyl-D-amino glucose or its officinal salt and the antibiotic application in the medicine of bacterial infection or disease that pathogenic propagation causes due to the latent ecology of the treatable antibacterial of preparation treatment antibiotic, wherein antibiotic is selected from aminoglycosides, Macrolide, Tetracyclines, quinolones, the lincomycin class, chloromycetin, cephalosporins, penicillins, other beta-lactam antibiotic outside cephalosporins and the penicillins, the two ratio is respectively N-acetyl-D-amino glucose according to class of antibiotic: aminoglycosides antibiotics=1: 1.6～1: 5; N-acetyl-D-amino glucose: macrolide antibiotics=1: 5～1: 30; N-acetyl-D-amino glucose: quinolones=1: 2～1: 15; N-acetyl-D-amino glucose: lincomycin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: chloromycetin series antibiotics=1: 2.5～1: 10; N-acetyl-D-amino glucose: tetracycline antibiotics=1: 1～1: 30; N-acetyl-D-amino glucose: cephalosporins=1: 2.6～1: 5; N-acetyl-D-amino glucose: penicillins=1: 1～1: 30; Or N-acetyl-D-amino glucose: other beta-lactam antibiotic=1: 8～1: 50.
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| EP1669077A4 (en) * | 2003-09-18 | 2007-10-03 | Univ Pla 3Rd Military Medical | Antibacterial compositions of n-acetyl-d-aminoglycosamine and antibiotics |
| CN104721176B (en) * | 2015-02-02 | 2018-07-10 | 中山大学 | Application of the α-ketoglutaric acid in terms of sensibility of bacteria on antibiotic is improved |
| CN107334782A (en) * | 2017-07-26 | 2017-11-10 | 吉林省始祖生物波医学研究院有限公司 | A kind of inhibiting bacteria and diminishing inflammation agent and its preparation method and application |
| CN111557946A (en) * | 2020-07-01 | 2020-08-21 | 上海玉曜生物医药科技有限公司 | New application of N-acetyl-D-glucosamine and related products |
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|---|---|---|---|---|
| US3660571A (en) * | 1968-03-28 | 1972-05-02 | Takeda Chemical Industries Ltd | Disease control composition for silkworms |
| JPH01132518A (en) * | 1987-11-18 | 1989-05-25 | Toyama Chem Co Ltd | Antibiotic composition |
| CN1156027A (en) * | 1996-12-27 | 1997-08-06 | 中国人民解放军第三军医大学 | Application of N-aceto-D-aminoglucose in medicinal preparation for curing intestinal diseases |
| WO1998006435A2 (en) * | 1996-08-14 | 1998-02-19 | Vanderbilt University | COMPOSITIONS OF ANTICHLAMYDIAL AGENTS FOR THE DIAGNOSIS AND MANAGEMENT OF INFECTION CAUSED BY $i(CHLAMYDIA) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3660571A (en) * | 1968-03-28 | 1972-05-02 | Takeda Chemical Industries Ltd | Disease control composition for silkworms |
| JPH01132518A (en) * | 1987-11-18 | 1989-05-25 | Toyama Chem Co Ltd | Antibiotic composition |
| WO1998006435A2 (en) * | 1996-08-14 | 1998-02-19 | Vanderbilt University | COMPOSITIONS OF ANTICHLAMYDIAL AGENTS FOR THE DIAGNOSIS AND MANAGEMENT OF INFECTION CAUSED BY $i(CHLAMYDIA) |
| CN1156027A (en) * | 1996-12-27 | 1997-08-06 | 中国人民解放军第三军医大学 | Application of N-aceto-D-aminoglucose in medicinal preparation for curing intestinal diseases |
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