CN104546836B - One kind contains AZT and arginic pharmaceutical composition - Google Patents
One kind contains AZT and arginic pharmaceutical composition Download PDFInfo
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- CN104546836B CN104546836B CN201410796991.9A CN201410796991A CN104546836B CN 104546836 B CN104546836 B CN 104546836B CN 201410796991 A CN201410796991 A CN 201410796991A CN 104546836 B CN104546836 B CN 104546836B
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- azt
- arginine
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- injection
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 27
- 241000894006 Bacteria Species 0.000 claims abstract description 18
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 13
- 241000192125 Firmicutes Species 0.000 claims abstract description 4
- 229930064664 L-arginine Natural products 0.000 claims description 28
- 235000014852 L-arginine Nutrition 0.000 claims description 28
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 27
- 241000588724 Escherichia coli Species 0.000 claims description 4
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 4
- 241000191967 Staphylococcus aureus Species 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims 1
- 244000025254 Cannabis sativa Species 0.000 claims 1
- 239000004475 Arginine Substances 0.000 abstract description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 7
- 235000018977 lysine Nutrition 0.000 abstract 2
- 150000002669 lysines Chemical class 0.000 abstract 2
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 50
- 238000002347 injection Methods 0.000 description 24
- 239000007924 injection Substances 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 6
- 229960003644 aztreonam Drugs 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 235000009697 arginine Nutrition 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000007142 ring opening reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 150000003952 β-lactams Chemical class 0.000 description 4
- 244000063299 Bacillus subtilis Species 0.000 description 3
- 235000014469 Bacillus subtilis Nutrition 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 101710181936 Phosphate-binding protein PstS 3 Proteins 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- 102000006635 beta-lactamase Human genes 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- QGZCUOLOTMJILH-UHFFFAOYSA-N 2h-tetrazol-2-ium;bromide Chemical compound [Br-].C1=N[NH+]=NN1 QGZCUOLOTMJILH-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000019890 Amylum Nutrition 0.000 description 1
- 206010051093 Cardiopulmonary failure Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 101710146026 Peptidoglycan D,D-transpeptidase FtsI Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- -1 sorbefacient Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition, and in particular to a kind of antibacterial combination, wherein being made up of AZT, L arginine and L lysines, specifically, the weight ratio of AZT, L arginine and L lysines is 1：0.6‑0.9：0.3 0.6, described pharmaceutical composition has the effect of good resisting gram-positive bacteria and Gram-negative bacteria.
Description
Technical field
The present invention relates to antibacterial combination, and in particular to one kind contains AZT and arginic pharmaceutical composition.
Background technology
AZT is the beta-Lactam antibiotic of the monoamides ring class of Shi Guibao companies of U.S. exploitation, and being first is used to face
The monocyclic beta-Lactam antibiotic of bed, has good inhibitory activity to Gram-negative bacteria, with most of beta-lactams
Antibiotic is different, its not Induction of bacterial generation beta-lactamase, and have height to bacteriogenic most beta-lactamase
The stability of degree.AZT can run through the outer membranous wall of gram-negative aerobic bacteria, and to the (PBP- of PBP 3
3) there is high affinity, by acting on PBP-3, suppress the synthesis of bacteria cell wall, cause cell to dissolve and dead.Ammonia is bent
There is preferable resistance to enzymatic energy in south, when microorganism is insensitive to medicines such as penicillins, cephalosporins, aminoglycosides, should
Often can be effective with it.Therefore, AZT is largely used in clinic；Clinical effectiveness is good, curative effect affirmative.
AZT chemical name：[2S- [2a, 3b (Z)]] -2- [[[1- (2- amino -4- thiazolyls) -2- [(2- methyl -4- oxygen
Generation -1- sulfo group -3- azetidinyls) amino] -2- oxy ethylenes] amino] oxo] -2 Methylpropionic acid.No. CAS：
78110-38-0, molecular formula：Molecular formula：C13H17N5O8S2；Molecular weight：435.43.Its structure is as follows：
L-arginine plays important effect in aztreonam for injection, first, and it has increase AZT solubility
With dissolution velocity, regulation pH effect, if arginine is very few, the pH of solution is too low, and AZT dissolving is not clarified, arginine mistake
It is many, the pH rises of solution, excitant is larger during injection.Secondly, L-arginine has the effect for promoting AZT stable, L- essence ammonia
Acid can reduce the open loop impurity of AZT, AZT as other Beta-lactam medicines, its monoamides ring AZT with
Arginine mixing inequality or the also easy open loop in the case of wet, hot, form ring-opening aztreonam, ring-opening aztreonam is AZT
On the one hand a kind of major impurity, his presence reduces the content of medicine, and causing the potency of medicine reduces, and makes using AZT
Sterilization and fungistatic effect reduction, it is on the other hand, similar with other Beta-lactam medicines, after beta-lactam open loop, form activity
Target spot, easily occurs self-polymerization, forms high polymer (macromolecule impurity).High polymer or the miscellaneous sub content of macromolecule are directly affected
Anaphylactoid incidence, reduces ring-opening aztreonam impurity content, it is possible to control endogenous allergic reaction incidence.
1B is most important one kind in eight kinds of amino acid that are needed by human and itself can not synthesizing.It is long-term with
It is used as the complementary element of human nutrition, for diseases such as treatment albumen matter serious defect, cardiorespiratory failures, body can be adjusted
Intracellular metabolite balance, the absorption of increase protein, promotion upgrowth and development of children.
Chinese patent CN101579336A discloses a kind of injection being made up of beta crystal AZT and L-arginine, tool
Have the advantages that packed dose is accurate, well mixed, not stratified in production and transport, reduce the impurity of ring-opening aztreonam, still
Antibacterial effect needs further to improve.
Chinese patent CN101912356A discloses a kind of aztreonam/arginine medicinal composition micro-balloon injection, uses
Microballoon is protected to AZT, and ensures that arginine fully contacts AZT, promotes it to dissolve when in use, but clinical effect
Fruit is not obvious.
Chinese patent CN101951906A discloses the Inhaled aerosol of AZLI, for treating the strong of tuberculosis
Health Related Quality of Life symptom, but not disclosing it has the purposes of antibacterial.
The present inventor in research process it was unexpectedly found that, will be made up of AZT, L-arginine and 1B
Pharmaceutical composition antibacterial activity it is well more many than the pharmaceutical composition by AZT and L-arginine, so as to complete this hair
It is bright.
The content of the invention
It is an object of the present invention to provide a kind of pharmaceutical composition.
The invention provides a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is by AZT, L-arginine
With 1B composition.
Preferably, the weight ratio of AZT, L-arginine and 1B is 1 in pharmaceutical composition of the invention：0.6-
0.9：0.3-0.6.
It is highly preferred that the weight ratio of AZT, L-arginine and 1B is 1 in the pharmaceutical composition of the present invention：
0.7-0.8：0.4-0.5.
Most preferably, the weight ratio of AZT, L-arginine and 1B is 1 in pharmaceutical composition of the invention：
0.7：0.5.
The purposes of antibacterials is being prepared it is a further object to provide aforementioned pharmaceutical compositions.
Preferably, described bacterium is gram-positive bacteria and Gram-negative bacteria.
It is highly preferred that described bacterium is Escherichia coli, pseudomonas aeruginosa, bacillus subtilis and Staphylococcus aureus
Bacterium.
Pharmaceutical composition of the present invention can be prepared into various formulations according to conventional method pharmaceutically, with it is a kind of or
A variety of pharmaceutically acceptable auxiliary material mixing, are prepared into required formulation.The auxiliary material includes the conventional dilution of pharmaceutical field
Agent, excipient, filler, adhesive, wetting agent, sorbefacient, surfactant, lubricant, stabilizer etc., if necessary also
Flavouring agent, sweetener and pigment can be added, concretely starch, sodium carboxymethyl starch, microcrystalline cellulose, lactose, sucrose, poly- second
Alkene pyrrolidone, hydroxypropyl cellulose, amylum pregelatinisatum, superfine silica gel powder, magnesium stearate, PVPP or poly- second
One or more in glycol；Described pharmaceutical composition can be made oral including tablet, pulvis, granula or oral liquid
Preparation, or parenteral solution is made.
The invention provides the antibacterial combination being made up of AZT, L-arginine and 1B, inventor exists
In research process it was unexpectedly observed that with the market is existing is compared by AZT with the pharmaceutical composition of L-arginine, it is bent by ammonia
The antibacterial effect of the pharmaceutical composition in south, L-arginine and 1B composition, which has, significantly to be improved.
Embodiment
With reference to embodiment, the present invention is described in further detail, but the implementation of the present invention is not limited to this.
Method therefor is conventional method unless otherwise instructed in following embodiments.
Embodiment 1：AZT 100g, L-arginine 60g and 1B 30g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Embodiment 2：AZT 100g, L-arginine 70g and 1B 40g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Embodiment 3：AZT 100g, L-arginine 80g and 1B 50g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Embodiment 4：AZT 100g, L-arginine 90g and 1B 60g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Embodiment 5：AZT 100g, L-arginine 70g and 1B 50g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Embodiment 6：AZT 100g, L-arginine 80g and 1B 30g are taken, according to conventional injection preparation side
Method, is prepared into the injection that every bottle of 0.5g AZT is calculated.
Comparative example 1：AZT 100g, L-arginine 60g are taken, according to conventional injection preparation method, every bottle is prepared into
The injection that 0.5g AZTs are calculated.
Comparative example 2：AZT 100g, L-arginine 70g are taken, according to conventional injection preparation method, every bottle is prepared into
The injection that 0.5g AZTs are calculated.
Comparative example 3：AZT 100g, L-arginine 80g are taken, according to conventional injection preparation method, every bottle is prepared into
The injection that 0.5g AZTs are calculated.
Comparative example 4：AZT 100g, L-arginine 90g are taken, according to conventional injection preparation method, every bottle is prepared into
The injection that 0.5g AZTs are calculated.
Effect experiment：The experiment of external resisting gram-positive bacteria and Gram-negative bacteria
MIC of the pharmaceutical composition to bacterium is determined using mtt assay, MIC value (ug/ml) is calculated.
1. material
The reagent used：DMSO, MTT (trade name tetrazolium bromide), isopropanol, hydrochloric acid, it is AR,
Mueller-Hinton culture mediums, phosphate buffer (0.01mol/L, pH 7.4).
Strain：Escherichia coli, pseudomonas aeruginosa, bacillus subtilis and staphylococcus aureus give birth to by Southwestern University
Life science institute provides.
2 methods
The preparation of 2.1 culture mediums：Beef extract powder 4g, casein hydrolysate 16g, starch 1.2g are taken, 800mL distilled water is added
In, dissolving is boiled in heating, is dispensed, and 121 DEG C of autoclaving 15min are standby.
The culture of 2.2 test organisms：In desinfection chamber, Escherichia coli, pseudomonas aeruginosa, bacillus subtilis and golden yellow are taken
Four kinds of test strains of color staphylococcus, under alcolhol burner with transfer needle respectively on four kinds of test strain inclined-planes, scraping is a small amount of oblique
Face lawn, bacteria suspension is made with a certain amount of sterilized water, then takes a certain amount of be added to melt and be cooled to 50 DEG C or so of MH
In culture medium, shake up, pour at once in sterile petri dish, after being sealed after abundant condensation with plug, 18-24h is cultivated in 37 DEG C
It is standby.Bacterium solution 1mL is drawn, with MH culture mediums by 1: 1000 dilution, makes bacterial concentration about 105cfu/mL.
2.3 antibacterial experiment：Medicine to be measured is dissolved in DMSO and is configured to solution, then with doubling dilution by chemicals dilating
Into in finite concentration gradient and DMSO.100 μ L culture medium is separately added into sterilizing microtiter plate first, Article 2 is
Positive control, adds 100 μ L bacteria suspensions.90 μ L bacteria suspension and 10 μ L drug solution are added in remaining hole.Each medicine
Solution concentration is parallel 3 times.Bacteria name is indicated in microtiter plate bottom.The culture dish handled is cultivated into 24h in 37 DEG C, seen
Examine.
2.4MIC measure：After each microtiter plate can intuitively determine its MIC value, in each hole of plate
50 μ L phosphate buffers (0.01mol/L, pH 7.4) of middle addition, wherein including 2mg MTT/mL.Continue to be incubated at room temperature
4-5h.Material in hole is removed and added isopropanol that 100 μ L contain 5%1mol/L HCl to extract dyestuff.Continue in room
12h is educated in the lower tax of temperature, determines each hole light absorbs (OD values) in ELIASA, determines wavelength 550nm.Medicine pair is calculated according to each hole OD values
The MIC of bacterial growth.
MIC (MIC)：24h is incubated in certain circumstances, can suppress certain microorganism and occur what is rised appreciably
Lowest concentration of drug is MIC.According to the optical density (OD values) of measure, the standard for making bacterial growth inhibiting rate is bent
Line, tries to achieve its corresponding drug concentration on standard curve.The MIC measured is shown in Table 1.
The suppression MIC value (μ g/mL) of the pharmaceutical composition of the present invention of table 1 and comparative example to bacterium
Table 1 is test result indicates that the pharmaceutical composition being made up of AZT, L-arginine and 1B is for these four
The antibacterial effect of bacterium is provided with than the antibacterial effect of the current existing pharmaceutical composition being made up of AZT and L-arginine
It is obviously improved, achieves more preferable antibacterial effect.
Claims (6)
1. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is by AZT, L-arginine and 1B group
Into wherein the weight ratio of AZT, L-arginine and 1B is 1：0.6-0.9：0.3-0.6.
2. pharmaceutical composition according to claim 1, it is characterised in that the weight of AZT, L-arginine and 1B
Amount is than being 1：0.7-0.8：0.4-0.5.
3. pharmaceutical composition according to claim 1, it is characterised in that the weight of AZT, L-arginine and 1B
Amount is than being 1：0.7：0.5.
4. the pharmaceutical composition described in claim any one of 1-3 is preparing the purposes of antibacterials.
5. purposes according to claim 4, it is characterised in that described bacterium is gram-positive bacteria and Gram-negative
Bacterium.
6. purposes according to claim 4, it is characterised in that described bacterium is Escherichia coli, pseudomonas aeruginosa, withered grass
Bacillus and staphylococcus aureus.
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| CN201410796991.9A CN104546836B (en) | 2014-12-19 | 2014-12-19 | One kind contains AZT and arginic pharmaceutical composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410796991.9A CN104546836B (en) | 2014-12-19 | 2014-12-19 | One kind contains AZT and arginic pharmaceutical composition |
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| CN101773469B (en) * | 2010-02-05 | 2011-07-06 | 陶灵刚 | Aztreonam/arginine medicament composition suspension injection |
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