CN107875154A - Composition containing Piperacillin, its pharmaceutical preparation and its application - Google Patents
Composition containing Piperacillin, its pharmaceutical preparation and its application Download PDFInfo
- Publication number
- CN107875154A CN107875154A CN201711415490.1A CN201711415490A CN107875154A CN 107875154 A CN107875154 A CN 107875154A CN 201711415490 A CN201711415490 A CN 201711415490A CN 107875154 A CN107875154 A CN 107875154A
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- China
- Prior art keywords
- sulbactam
- composition
- piperacillin
- pharmaceutical preparation
- ampicillin
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 45
- 229960002292 piperacillin Drugs 0.000 title claims abstract description 39
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 20
- IVBHGBMCVLDMKU-GXNBUGAJSA-N piperacillin Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 IVBHGBMCVLDMKU-GXNBUGAJSA-N 0.000 title claims abstract 6
- 229960005256 sulbactam Drugs 0.000 claims abstract description 32
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 claims abstract description 31
- 241000589291 Acinetobacter Species 0.000 claims abstract description 29
- 206010059866 Drug resistance Diseases 0.000 claims abstract description 13
- KMEGBUCIGMEPME-LQYKFRDPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(1r,4s)-3,3-dimethyl-2,2,6-trioxo-2$l^{6}-thiabicyclo[3.2.0]heptane-4-carboxylic acid Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)C2C(=O)C[C@H]21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 KMEGBUCIGMEPME-LQYKFRDPSA-N 0.000 claims abstract description 11
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 claims abstract description 10
- 229960004682 cefoperazone Drugs 0.000 claims abstract description 9
- 241000894006 Bacteria Species 0.000 claims description 17
- 239000007924 injection Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 239000000843 powder Substances 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 230000001524 infective effect Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 abstract description 13
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 description 33
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 17
- 229960000723 ampicillin Drugs 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 241000534944 Thia Species 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229960002260 meropenem Drugs 0.000 description 3
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical class CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- 108010040201 Polymyxins Proteins 0.000 description 2
- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 2
- 229960001931 ampicillin sodium Drugs 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 229940041153 polymyxins Drugs 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 229960002668 sodium chloride Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019254 sodium formate Nutrition 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 206010060976 Bacillus infection Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- NKZMPZCWBSWAOX-IBTYICNHSA-M Sulbactam sodium Chemical compound [Na+].O=S1(=O)C(C)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 NKZMPZCWBSWAOX-IBTYICNHSA-M 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000476 body water Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000030303 breathing problems Diseases 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- -1 cefoperazone Sulbactam compound Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 229960000614 sulbactam sodium Drugs 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 239000008215 water for injection 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
Landscapes
- 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)
Abstract
The invention provides a kind of composition containing Piperacillin, contain Piperacillin in said composition, also containing a certain proportion of ampicillin and Sulbactam.Present invention also offers its pharmaceutical preparation and application.The composition and pharmaceutical preparation of the present invention can significantly inhibit drug resistance Acinetobacter bauamnnii, and the Acinetobacter bauamnnii infection particularly to carbapenem antibiotic or to cefoperazone sulbactam resistance can play good therapeutic action, have significant clinical advantage.
Description
Technical field
The present invention relates to a kind of composition containing Piperacillin and its application.
Background technology
Acinetobacter bauamnnii is a kind of important pathogenic bacteria, can cause breathing, blood, abdominal cavity, nervous centralis, uropoiesis and skin
The infection of the systems such as skin soft tissue.Shown according to Chinese bacterial drug resistance monitoring (CHINET) 2016 annual report, Acinetobacter bauamnnii
It is accounting highest pathogen in respiratory tract specimens, prompts the bacterium that there is very important influence in breathing problem.Especially
For the urgent patient of long-term inpatients, pulmonary infection caused by Acinetobacter bauamnnii turns into the important cause of death.In addition,
All to be clinically separated in bacterium, the accounting of Acinetobacter bauamnnii is also up to 10.8%, is only second to Escherichia coli and Klebsiella Pneumoniae.
All the time, train southern class carbapenem antibiotics has preferably effect to Acinetobacter bauamnnii infection.But with
Widely use, multidrug resistant and extensive resistance occur, many Acinetobacter bauamnniis lack sensitiveness to training southern class.It is clinical
Upper other drug therapy selections also have polymyxins, cefoperazone sulbactam etc..But the stronger renal toxicity limitation of polymyxins
Its application, and cefoperazone sulbactam also increasingly highlights to the drug resistance problems of Acinetobacter bauamnnii.
According to CHINET report displays in 2010, Acinetobacter bauamnnii was 30% to the resistant rate of cefoperazone sulbactam, and
2016 annual reports show that this ratio has risen to 43%.Therefore, for more safely and effectively treating drug resistance Bao Man not
, urgent clinical demand be present in the medicine of dynamic bacillus infection.
The content of the invention
Present invention aim to address the drug resistance problems of Acinetobacter bauamnnii, particularly Acinetobacter bauamnnii to cephalo piperazine
The problem of ketone Sulbactam resistance.
The problem of resistance of bacterium is a complexity, the mechanism of resistance include bacterium and produce inaxtivation of drug enzyme, bacterium change
Drug target, the change of bacterial cell membrane permeability, overexpression of bacterium intracellular efflux pump etc..Piperacillin is clinical
Conventional penicillins antimicrobial.It is reported that Acinetobacter bauamnnii is also up to 70% to the resistant rate of Piperacillin
More than.But it is unexpectedly that inventor obtains a kind of composition containing Piperacillin and other components, the combination by research
Thing has extraordinary antibacterial action to Acinetobacter bauamnnii, it is achieved thereby that the purpose of the present invention.
The invention provides a kind of composition containing Piperacillin, also contain ampicillin and Shu Ba in the composition
Smooth, wherein the weight ratio of Piperacillin, ampicillin and Sulbactam is 200-400: 0.02-6: 100.
Preferably, in the present invention in composition, the weight ratio of Piperacillin, ampicillin and Sulbactam can be 200-
400: 0.02-3: 100, further preferably can be 200: 0.02-3: 100,300: 0.02-3: 100 or 400: 0.02-3:
100.Another preferred scheme is that the weight ratio of Piperacillin, ampicillin and Sulbactam in the present composition can be 200-
400: 0.04-6: 100, further preferably can be 200: 0.04-6: 100,300: 0.04-6: 100 or 400: 0.04-6:
100。
Preferably, composition of the invention is made up of Piperacillin, ampicillin and Sulbactam.
Present invention also offers a kind of pharmaceutical preparation, contain composition of the invention in the pharmaceutical preparation.
Preferably, described pharmaceutical preparation can be injection.It is further preferred that the injection can be dry powder shape
Formula or the solution form being configured to after being dissolved with solvent.Described dry powder form can be aseptic powder injection or freeze
Powder pin.Described solvent can be the Conventional solvents of suitable Clinical practice, such as D/W or sodium-chloride water solution etc..
The composition or pharmaceutical preparation of the present invention can be prepared by this area conventional method.
Present invention also offers a kind for the treatment of method of bacterial infective diseases, methods described is including the use of of the present invention
Composition or pharmaceutical preparation.Either, present invention also offers a kind of composition of the present invention or pharmaceutical preparation to control in preparation
Treat the application in terms of bacterial infective diseases.
Preferably, described bacterium is drug resistance Acinetobacter bauamnnii.
It is further preferred that described resistance refers to cefoperazone sulbactam resistance.
It should be noted that the title such as " Piperacillin ", " ampicillin " or " Sulbactam " in the present invention is a kind of system
Claim, i.e., Piperacillin, ampicillin or Sulbactam can refer to their free acid, salt, polymorph, hydrate or solvation
The different form such as thing.Such as common are Piperacillin acid ((2S, 5R, 6R) -3,3- dimethyl -6- [(R) -2- (4- ethyls -
2,3- dioxo -1- piperazines formamido groups) -2- phenylacetylaminos] -7- oxos -4- thia -1- azabicyclos [3.2.0] heptane -
2- formic acid), avocin ((2S, 5R, 6R) -3,3- dimethyl -6- [(R) -2- (4- ethyl -2,3- dioxo -1- piperazine first
Acylamino-) -2- phenylacetylaminos] -7- oxo -4- thia -1- azabicyclos [3.2.0] heptane -2- formic acid sodium salt), ammonia benzyl west
((2S, 5R, 6R) -3,3- dimethyl -6- [(R) -2- amino -2- phenylacetylaminos] -7- oxo -4- thia -1- azepines are double for woods acid
Ring [3.2.0] heptane -2- formic acid), ampicillin sodium ((2S, 5R, 6R) -3,3- dimethyl -6- [(R) -2- amino -2- phenylacetyls
Amino] -7- oxo -4- thia -1- azabicyclos [3.2.0] heptane -2- formic acid sodium salt), sulbactam ((2S, 5R) -3,3- bis-
Methyl -7- oxo -4- thia -1- azabicyclos [3.2.0] heptane -2- carboxylic acids -4,4- dioxide), sulbactam ((2S,
5R) -3,3- dimethyl -7- oxo -4- thia -1- azabicyclos [3.2.0] heptane -2- carboxylic acid sodiums -4,4- dioxide) etc..
Pharmaceutical preparation in the present invention refers to made according to certain formulation requirement, it is straightforward to provide to what is used using object
Medicine.The moisture or impurity of certain content can be contained in composition in the present invention.It can contain in the pharmaceutical preparation of the present invention
There is the auxiliary material of certain content.
Using a certain amount of Sulbactam and ampicillin to improve Bao Man not levers in the Piperacillin composition of the present invention
The drug resistance of bacterium.Although the preparation containing Sulbactam is also used for the treatment of Acinetobacter bauamnnii infection in the prior art, typically
It is considered Sulbactam role itself.And present invention firstly discovers that ampicillin a small amount of in composition is for anti-drug resistance
Acinetobacter bauamnnii serve unusual synergistic effect.Its mechanism is probably that ampicillin molecule passes through attack first
Drug-fast bacteria, increase permeability of cell membrane, add the probability and concentration of other drugs in the cell.
The composition and preparation of the present invention can be used for infectious disease caused by clinical treatment drug resistance Acinetobacter bauamnnii
Disease, particularly when Acinetobacter bauamnnii after the Drug-resistants such as cefoperazone sulbactam to still playing therapeutic effect, have aobvious
The technique effect and clinical advantage of work.
Embodiment
The present invention is further elaborated with embodiment below, but the technical scheme and skill being not intended to limit the invention
Art effect.
The preparation of the Piperacillin composition of embodiment 1
Take avocin (1000g in terms of Piperacillin acid), ampicillin sodium (0.1g in terms of the acid of ampicillin) and Sulbactam
Sodium (500g in terms of sulbactam), three kinds of materials are sufficiently mixed uniformly with single cone ribbon mixer, obtain a kind of composition.
Take a part of composition to be dispensed in aseptic condition, obtain the injection (aseptic powder injection) of dry powder form.Separately take a part of group
Compound 0.9% sodium-chloride water solution of 100 times of amounts (ml/g) dissolves, packing, obtains the parenteral solution of solution form.
The preparation of the Piperacillin composition of embodiment 2
Piperacillin acid 1000g, ampicillin acid 0.3g and sulbactam 500g are taken, with the aqueous solution containing 343g sodium acid carbonates
After dissolving, freeze, packing, obtain a kind of dry powder form injection (freeze-dried powder) containing composition.
The preparation of embodiment 3-6 Piperacillin compositions
Embodiment 3-6 operation is similar to Example 1, and the amount of Piperacillin and Sulbactam is same as Example 1, the difference is that each
The dosage of ampicillin gradually increases in embodiment, respectively 1g, 3g, 10g and 15g.
Comparative example 1-2
Comparative example 1-2 operation is similar to Example 1, and the amount of Piperacillin and Sulbactam is same as Example 1, the difference is that right
The dosage of ampicillin is respectively 60g and 200g in ratio 1-2.
Comparative example 3
The operation of comparative example 3 is similar to Example 1, and the dosage of Piperacillin and Sulbactam is same as Example 1, the difference is that not
Use ampicillin.
The preparation of embodiment 7-8 Piperacillin compositions
Embodiment 7-8 operation is similar to Example 1, the difference is that the dosage of Piperacillin is 1500g in two embodiments,
The dosage of Sulbactam is 500g, and the dosage of ampicillin is respectively 5g and 15g.
The preparation of the Piperacillin composition of embodiment 9
Avocin (1000g in terms of Piperacillin acid), ampicillin acid 0.1g and sulbactam are taken (in terms of sulbactam
250g), it is sufficiently mixed uniformly with Mixers with Multi-direction Movement, obtains a kind of composition.A part of composition is taken, is entered in aseptic condition
Row packing, obtains the injection of dry powder form.
The preparation of embodiment 10-14 Piperacillin compositions
Embodiment 10-14 operation is similar to Example 9, and the amount of Piperacillin and Sulbactam is same as Example 9.Unlike
The dosage of ampicillin gradually increases in each embodiment, respectively 0.2g, 0.7g, 3g, 5g and 15g.
Comparative example 4-5
Comparative example 4-5 operation is similar to Example 9, and the amount of Piperacillin and Sulbactam is same as Example 9.The difference is that right
The dosage of ampicillin is respectively 80g and 300g in ratio 4-5.
The different components of experimental example 1 cause the protective effect research that experimental animal infects to Acinetobacter bauamnnii
Test material：Test specimen is each composition, Meropenem, Sulbactam, cephalo in embodiment 1-14 and comparative example 1-5
Piperazine ketone Sulbactam.Experimental animal is ICR mouse.Test strain is ATCC19606 (Acinetobacter bauamnnii reference culture), CBP-R
(Carbapenem-resistant class Acinetobacter bauamnnii bacterial strain), CPZ/S-R (Acinetobacter bauamnnii of resistance to cefoperazone sulbactam bacterial strain), wherein
Standard bacteria comes from ATCC, and other bacterium come from and are clinically separated.
Grope test specimen dosage range：Test strain is diluted to 10 with 5% high activity dried yeast-1、10-2、10-3、
10-4The dilution bacterium solution of various concentrations, experimental animal is carried out that 0.5ml/ mouse are injected intraperitoneally respectively.Dead mouse is recorded after infection
Number, the minimum bacterium amount for causing mouse 100% dead are recorded as 1MLD.1MLD bacterium amount infecting mouses are prepared with 5% high activity dried yeast,
At once with 6 hours after, carry out trial test with the test specimen dosage of high, medium and low three various concentrations, mouse after record infection
Survival number, using this result as according to the dosage for carrying out designing animal protection test.Suitable dosage is maximum concentration group
More than 70% infection animal survival, the infection animal of least concentration group more than 70% are dead.
Animal protection test：Water, body weight 25-30g mouse are can't help in 18h fasting before taking experiment, male and female half and half, are randomly divided into
Several groups：(1) 19606 groups of ATCC, (2) CBP-R groups, (3) CPZ/S-R groups, every group of 5 test specimen concentration, every group 10 dynamic
Thing, and set 10 animals and make blank control group.The bacterium solution 0.5ml of 1MLD amounts is injected intraperitoneally per mouse, infection model is caused, in sense
The test specimen liquid 0.2ml/ mouse of various concentrations are subcutaneously injected in 0h and 6h respectively after dye, and blank control group gives isometric sterilizing
Water for injection.Continuous Observation 7 days, record the death condition of each group animal.Calculate each test specimen with Bliss methods 50% has
Imitate dosage (ED50)。ED50Smaller to show that fungistatic effect is better in test specimen body, the protective effect to experimental animal is better.
Result of the test：Different ED is represented with S, A, B, C, D50Rank.S：ED50≤20mg/kg；A：20mg/kg ＜ ED50
≤50mg/kg；B：50mg/kg ＜ ED50≤100mg/kg；C：100mg/kg ＜ ED50≤200mg/kg；D：ED50＞ 200mg/
kg.Table 1 lists the main result of this experiment.
Table 1：ED of the different components to Acinetobacter bauamnnii infection animal50Situation
In above-mentioned experiment, the Acinetobacter bauamnnii reference culture for not producing drug resistance, each test specimen can be effectively antibacterial.
Comparatively, the folk prescription drug effect of Meropenem or Sulbactam is advantageously.
For the Acinetobacter bauamnnii of drug resistance, the drug effect of Meropenem or Sulbactam folk prescription is decreased obviously, cefoperazone
Sulbactam compound fails to provide more preferable effect, and the Piperacillin composition of the present invention has obvious more preferable bacteriostasis,
Show powerful synergy.The amount of ampicillin influences this effect, and in the presence of a small amount of ampicillin, composition is to resistance to
The effect of medicine bacterium is preferable.
Above with general explanation, embodiment and experiment, the present invention is described in detail.The present invention's
On the basis of, those skilled in the art can to work reasonably modification or improve.Therefore, on the basis without departing from spirit of the present invention
Upper these modifications or improvements, belong to present disclosure.
Industrial applicibility
The present invention provides a kind of composition containing Piperacillin.Contain Piperacillin in composition of the present invention, also contain
A certain proportion of ampicillin and Sulbactam, wherein, the weight ratio of the Piperacillin, ampicillin and Sulbactam is 200-
400∶0.02-6∶100.Present invention also offers the pharmaceutical preparation comprising the composition and its application.Of the present invention group
Compound and pharmaceutical preparation can significantly inhibit drug resistance Acinetobacter bauamnnii, particularly to carbapenem antibiotic or to cephalo piperazine
Ketone Sulbactam resistance Acinetobacter bauamnnii infection can play good therapeutic action, there is significant clinical advantage, with compared with
Good economic value and application prospect.
Claims (10)
1. a kind of composition containing Piperacillin, ampicillin and Sulbactam are also contained in the composition, wherein piperazine draws west
The weight ratio of woods, ampicillin and Sulbactam is 200-400: 0.02-6: 100.
2. the weight ratio of composition according to claim 1, wherein Piperacillin, ampicillin and Sulbactam is 200-
400: 0.02-3: 100, or 200-400: 0.04-6: 100.
3. composition according to claim 1, said composition is made up of Piperacillin, ampicillin and Sulbactam.
4. a kind of pharmaceutical preparation, contain any described composition in claim 1-3.
5. pharmaceutical preparation according to claim 4, the pharmaceutical preparation is injection.
6. pharmaceutical preparation according to claim 5, the injection is the injection or solution form of dry powder form
Injection.
7. pharmaceutical preparation according to claim 6, the injection of the dry powder form is aseptic powder injection or freeze-dried powder.
8. a kind for the treatment of method of bacterial infective diseases, methods described is including the use of the composition or power described in claim 1-3
Profit requires the pharmaceutical preparation described in 4-7.
9. treatment method according to claim 8, described bacterium is drug resistance Acinetobacter bauamnnii.
10. treatment method according to claim 9, described resistance is to cefoperazone sulbactam resistance.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113382734A (en) * | 2019-03-05 | 2021-09-10 | 广州新创忆药物临床研究有限公司 | Composition for treating carbapenem antibiotic-resistant acinetobacter baumannii infection |
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| CN1850046A (en) * | 2006-06-01 | 2006-10-25 | 济南帅华医药科技有限公司 | Slow-release preparation containing beta-lactamase inhibitor and its use |
| CN111511368A (en) * | 2017-12-25 | 2020-08-07 | 湘北威尔曼制药股份有限公司 | Composition containing piperacillin, pharmaceutical preparation and application thereof |
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| CN1850046A (en) * | 2006-06-01 | 2006-10-25 | 济南帅华医药科技有限公司 | Slow-release preparation containing beta-lactamase inhibitor and its use |
| CN111511368A (en) * | 2017-12-25 | 2020-08-07 | 湘北威尔曼制药股份有限公司 | Composition containing piperacillin, pharmaceutical preparation and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113382734A (en) * | 2019-03-05 | 2021-09-10 | 广州新创忆药物临床研究有限公司 | Composition for treating carbapenem antibiotic-resistant acinetobacter baumannii infection |
| CN113382734B (en) * | 2019-03-05 | 2023-07-21 | 广州新创忆药物临床研究有限公司 | Composition for treating carbapenem-resistant antibiotic Acinetobacter baumannii infection |
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