CN106265574A - A kind of method of the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease - Google Patents
A kind of method of the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease Download PDFInfo
- Publication number
- CN106265574A CN106265574A CN201610858325.2A CN201610858325A CN106265574A CN 106265574 A CN106265574 A CN 106265574A CN 201610858325 A CN201610858325 A CN 201610858325A CN 106265574 A CN106265574 A CN 106265574A
- Authority
- CN
- China
- Prior art keywords
- pivoxil hydrochloride
- cefetamet pivoxil
- weight portion
- weight
- infectious disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A kind of method that the invention discloses medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease, belongs to pharmaceutical technology field.It prepares pharmaceutical composition with Cefetamet Pivoxil Hydrochloride, amylum pregelatinisatum, microcrystalline Cellulose 102, carboxymethylstach sodium, hydroxypropylcellulose, Glyceryl Behenate, magnesium stearate for raw material.Finding through test, tablet prepared by this Cefetamet Pivoxil Hydrochloride crystal compound compared with the prior art, not only has relatively low high molecular polymer content, and good stability, and the content of high molecular polymer increases seldom along with the prolongation of period of storage；Meanwhile, said composition has more significantly antibacterial activity to streptococcus pneumoniae, hemophilus influenza, and enterococcus, staphylococcus is also had stronger antibacterial activity.
Description
The application is the joyful Pharmaceutical Technology Co., Ltd of Chinese of applicant Yantai City, the application for a patent for invention of Zhao Kongbo proposition
(invention entitled: a kind of medicine Cefetamet Pivoxil Hydrochloride compositions treating sensitive organism infectious disease, Application No.:
2015102460574, filing date: on May 15th, 2015) divisional application.
Technical field
The invention belongs to pharmaceutical technology field, relate to a kind of medicine hydrochloric acid cephalo preparing treatment sensitive organism infectious disease
The method of his U.S. ester compositions.
Background technology
Cefetamet Pivoxil Hydrochloride is third generation broad-spectrum cephalosporin class antibiotic.It is hydrolyzed to the most rapidly after Kou Fu
The cefetamet having antibacterial activity plays bactericidal action.Cefetamet Pivoxil Hydrochloride is to Streptococcus (except streptococcus faecalis), pneumonia
The gram positive bacterias such as coccus, and escherichia coli, Klebsiella, hemophilus influenza, Diplococcus gonorrhoeae are had the strongest antibacterial work
Property, resisting of especially low to cephalosporin sensitivity Serratia, indole-positive Bacillus proteus, Enterobacter and citric acid Pseudomonas
Bacterium activity is substantially.Stable to bacteriogenic β-lactamase.Cefetamet Pivoxil Hydrochloride is former to Pseudomonas, mycoplasma, clothing
Body, enterococcus and drug resistance staphylococcus are invalid.
But, owing to its basic structure is the same with antibiotic in the semisynthetic beta-lactam of many listed, hydrochloric acid head
Spore he also can form high molecular polymer by U.S. ester, also can cause type Ⅰ hypersensitivity reaction in Clinical practice, patient is endangered pole
Greatly.Prior art improves its stability mostly in terms of improving content, reduction impurity etc..
Research prove, cause beta-lactam antibiotic type Ⅰ hypersensitivity reaction anaphylactogen be with its present in high score
Sub-polymer content is relevant.Reduce high molecular polymer content present in Cefetamet Pivoxil Hydrochloride crude drug, improve stability,
Make its can ensure in long term storage the content of its high molecular polymer existed relatively low be reduce anaphylactic shock anti-
The effective way that should occur.Therefore, it is necessary to provide a kind of hydrochloric acid cephalo that high molecular polymer content is low, performance is more superior
His U.S. ester compounds.
Summary of the invention
The goal of the invention of the present invention is to provide a kind of cefetamet pivoxil hydrochloride tablets agent compositions.
In order to complete the purpose of the present invention, the technical scheme of employing is:
The present invention relates to a kind of medicine Cefetamet Pivoxil Hydrochloride compositions treating sensitive organism infectious disease, wherein said group
Compound is sweet by Cefetamet Pivoxil Hydrochloride, amylum pregelatinisatum, microcrystalline Cellulose 102, carboxymethylstach sodium, hydroxypropylcellulose, behenic acid
Grease, magnesium stearate are made；Described Cefetamet Pivoxil Hydrochloride is crystal, uses the X-ray powder that Cu-K alpha ray measurement obtains
End diffraction pattern is as shown in Figure 1.
First optimal technical scheme of the present invention is: in parts by weight, described compositions is by the hydrochloric acid of 1.0-1.5 weight portion
Ro-15-8075, the amylum pregelatinisatum of 0.5-1.5 weight portion, the microcrystalline Cellulose 102 of 1.0-1.5 weight portion, 0.3-0.4 weight
The carboxymethylstach sodium of part, the hydroxypropylcellulose of 0.1-0.3 weight portion, the Glyceryl Behenate of 0.05-0.15 weight portion, 0.04-
The magnesium stearate of 0.06 weight portion is made.
Second optimal technical scheme of the present invention is: in parts by weight, and described compositions is by the hydrochloric acid head of 1.25 weight portions
His U.S. ester of spore, the amylum pregelatinisatum of 1.0 weight portions, the carboxymethylstarch of microcrystalline Cellulose 102,0.35 weight portion of 1.25 weight portions
Sodium, the hydroxypropylcellulose of 0.2 weight portion, the Glyceryl Behenate of 0.1 weight portion, the magnesium stearate of 0.05 weight portion are made.
3rd optimal technical scheme of the present invention is: the preparation method of described compositions comprises the following steps:
1) supplementary material processes: with vibration screen-dividing machine by amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose, carboxymethylstarch
Sodium, Cefetamet Pivoxil Hydrochloride sieve；
2) weigh: weigh all supplementary materials according to prescription；
3) mixing: join in mixer by load weighted supplementary material, arranges motor rotation frequency, opens mixer and mixes 25 points
Clock；
4) selecting high speed tablet press tabletting, regulation pressure makes slice, thin piece energy molding and hardness be not more than 1% at 4-9kgf, friability；
5) packaging.
4th optimal technical scheme of the present invention is: amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropyl in described step 1)
Cellulose crosses 60 mesh sieves, and carboxymethylstach sodium crosses 120 mesh sieves, and Cefetamet Pivoxil Hydrochloride crosses 80 mesh sieves.
5th optimal technical scheme of the present invention is: arranging motor rotation frequency in described step 3) is 200r/min.
The preparation method of the Cefetamet Pivoxil Hydrochloride crystal in the present composition comprises the following steps:
Take Cefetamet Pivoxil Hydrochloride crude drug, add ether and the ethanol composition of 8 times that volume is Cefetamet Pivoxil Hydrochloride weight
Mixed solution, wherein the volume ratio of ether and ethanol is 4:2.5, is heated to 30-35 DEG C；Cefetamet Pivoxil Hydrochloride crude drug is molten
After Qing, add activated carbon decolorizing, filter；Temperature 35-40 DEG C is heated and kept to filtrate, and to drip volume be Cefetamet Pivoxil Hydrochloride
Dimethylformamide and the volume ratio of acetone mixed solvent, dimethylformamide and acetone that weight is 6 times are 2:1；Drip and finish, stirring
Cooling, described stirring cooling is to be cooled to 20-25 DEG C by 1.5-3.5 DEG C/min speed under rotating speed is 50-75rmp stirring, then
Under rotating speed 30-45rmp stirs, it is cooled to 5-10 DEG C by 0.5-1 DEG C/min speed, stands 5 hours, filter, washing, it is dried
To white crystalline powder.
The polymorphism of solid chemical is the natural phenomena that a kind of universal material exists, and this phenomenon refers to one
Can there is 2 kinds or two or more crystal form state in solid chemical, be also called the polymorphic state of material, the polymorphic of material
State is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, but its physics and chemistry
Matter is probably different.For " allomorphism medicine " that physicochemical property is different, different preventing and treating can also be shown clinically
The curative effect of disease, directly affects application and the clinical effectiveness of medicine.
Owing to the basic structure of Cefetamet Pivoxil Hydrochloride is with antibiotic one in the semisynthetic beta-lactam of many listed
Sample, also can cause type Ⅰ hypersensitivity reaction in Clinical practice, very harmful to patient.Research proves, causes beta-lactam
The anaphylactogen of antibiotic type Ⅰ hypersensitivity reaction be with its present in high molecular polymer content relevant.But prior art is big
How in terms of improving content, reduction impurity etc., to improve its stability, high molecular polymer content therein is not suggested that and appoints
What improves.
The present inventor has obtained a kind of Cefetamet Pivoxil Hydrochloride novel crystal forms being different from prior art through substantial amounts of test
Structure, and by test, show that this novel crystal forms structure not only has relatively low high molecular polymer content, and during along with storage
Between its high molecular polymer content of prolongation increase seldom.
Meanwhile, the present inventor passes through In vitro Bactericidal Experiments, surprisingly finds, Cefetamet Pivoxil Hydrochloride provided by the present invention
Compound has a more significantly antibacterial activity to streptococcus pneumoniae, hemophilus influenza, and to the hydrochloric acid cephalo of prior art report he
U.S. ester also has stronger antibacterial activity without enterococcus, the staphylococcus of antibacterial activity.
Compared with prior art, present invention have the advantage that
(1) cefetamet pivoxil hydrochloride compound provided by the present invention is crystal compound, is that one is different from prior art
The cefetamet pivoxil hydrochloride compound of report, finds through test, this Cefetamet Pivoxil Hydrochloride crystal compound relatively prior art
Cefetamet pivoxil hydrochloride compound compare, not only there is relatively low high molecular polymer content, and along with period of storage
Extend its high molecular polymer content to increase seldom；
(2) cefetamet pivoxil hydrochloride compound provided by the present invention has more significantly resisting to streptococcus pneumoniae, hemophilus influenza
Bacterium activity, and the Cefetamet Pivoxil Hydrochloride of prior art report is also had stronger without enterococcus, the staphylococcus of antibacterial activity
Antibacterial activity.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction spectrum of the Cefetamet Pivoxil Hydrochloride crystal of the embodiment of the present invention 1 preparation.
Detailed description of the invention
Below by specific embodiment, the summary of the invention of the present invention is described in further detail, but the most therefore limits
Determine present disclosure.
Embodiment 1: the preparation of Cefetamet Pivoxil Hydrochloride crystal
Take Cefetamet Pivoxil Hydrochloride crude drug, add ether and the ethanol composition of 8 times that volume is Cefetamet Pivoxil Hydrochloride weight
Mixed solution, wherein the volume ratio of ether and ethanol is 4:2.5, is heated to 30-35 DEG C；Cefetamet Pivoxil Hydrochloride crude drug is molten
After Qing, add activated carbon decolorizing, filter；Temperature 35-40 DEG C is heated and kept to filtrate, and to drip volume be Cefetamet Pivoxil Hydrochloride
Dimethylformamide and the volume ratio of acetone mixed solvent, dimethylformamide and acetone that weight is 6 times are 2:1；Drip and finish, stirring
Cooling, described stirring cooling is to be cooled to 20-25 DEG C by 1.5-3.5 DEG C/min speed under rotating speed is 50-75rmp stirring, then
Under rotating speed 30-45rmp stirs, it is cooled to 5-10 DEG C by 0.5-1 DEG C/min speed, stands 5 hours, filter, washing, it is dried
To white crystalline powder.
The X-ray powder diagram that the Cefetamet Pivoxil Hydrochloride crystal use Cu-K alpha ray measurement prepared obtains is such as
Shown in Fig. 1, its purity of high-performance liquid chromatogram determination is 99.99%.
Embodiment 2: the preparation of cefetamet pivoxil hydrochloride tablets, step is as follows:
Prescription: in parts by weight
Preparation method:
1) supplementary material processes: with vibration screen-dividing machine, amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose are crossed 60 mesh sieves, carboxylic
First Starch Sodium crosses 120 mesh sieves, and Cefetamet Pivoxil Hydrochloride crosses 80 mesh sieves；
2) weigh: weigh all supplementary materials according to prescription；
3) mixing: join in mixer by load weighted supplementary material, arranges motor rotation frequency 200r/min, opens mixer
Mix 25 minutes；
4) selecting high speed tablet press tabletting, regulation pressure makes slice, thin piece energy molding and hardness be not more than 1% at 4-9kgf, friability；
5) packaging.
Embodiment 3: the preparation of cefetamet pivoxil hydrochloride tablets, step is as follows:
Prescription: in parts by weight
Preparation method:
1) supplementary material processes: with vibration screen-dividing machine, amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose are crossed 60 mesh sieves, carboxylic
First Starch Sodium crosses 120 mesh sieves, and Cefetamet Pivoxil Hydrochloride crosses 80 mesh sieves；
2) weigh: weigh all supplementary materials according to prescription；
3) mixing: join in mixer by load weighted supplementary material, arranges motor rotation frequency 200r/min, opens mixer
Mix 25 minutes；
4) selecting high speed tablet press tabletting, regulation pressure makes slice, thin piece energy molding and hardness be not more than 1% at 4-9kgf, friability；
5) packaging.
Embodiment 4: the preparation of cefetamet pivoxil hydrochloride tablets, step is as follows:
Prescription: in parts by weight
Preparation method:
1) supplementary material processes: with vibration screen-dividing machine, amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose are crossed 60 mesh sieves, carboxylic
First Starch Sodium crosses 120 mesh sieves, and Cefetamet Pivoxil Hydrochloride crosses 80 mesh sieves；
2) weigh: weigh all supplementary materials according to prescription；
3) mixing: join in mixer by load weighted supplementary material, arranges motor rotation frequency 200r/min, opens mixer
Mix 25 minutes；
4) selecting high speed tablet press tabletting, regulation pressure makes slice, thin piece energy molding and hardness be not more than 1% at 4-9kgf, friability；
5) packaging.
Test example 1: high molecular polymer comparision contents is tested
(1) accelerated test
By following each sample temperature 40 DEG C, place 6 months under the conditions of relative humidity 75%, respectively at the 1st, 2,3, June takes
Sample, according to " HPLC method measure in Cefetamet Pivoxil Hydrochloride have related substance and polymer " [king builds, and wangdan is red, Hong Liya.
HPLC method measures has related substance and a polymer (J) in Cefetamet Pivoxil Hydrochloride, pharmaceutical analysis magazine, and 2015, (2)] measure
The content of polymer in each sample, and with 0 day results contrast.Result of the test is shown in Table 1:
Trial target: the Cefetamet Pivoxil Hydrochloride crystal that the embodiment of the present invention 1 prepares；
Reference substance: commercially available Cefetamet Pivoxil Hydrochloride raw material, is provided by Zhuhai United Laboratories Ltd.
The content of high molecular polymer in table 1, accelerated test each sample
(2) long term test
Each sample at room temperature, respectively at the 3rd, 6,9, sampling in 12 months, according to " HPLC method measures Cefetamet Pivoxil Hydrochloride
In have related substance and polymer " [king builds, and wangdan is red, Hong Liya. it is relevant that HPLC method measures in Cefetamet Pivoxil Hydrochloride
Material and polymer (J), pharmaceutical analysis magazine, 2015, (2)] measure the content of polymer in each sample, and with 0 day result
Relatively.Result of the test is shown in Table 2:
The assay result of polymer in table 2, long term test each sample
Find out from above-mentioned result of the test, compared with commercially available prod, the polymerization of the cefetamet pivoxil hydrochloride compound crystal of the present invention
Thing content is relatively low, good stability, and the content of polymer is along with the prolongation of period of storage, and it increases seldom.
Test example 2: antibacterial activity is tested
1, materials and methods
1.1 antibacterial
Certain clinical laboratory of institute is collected in the blood of clinical patient, expectorant, secretions, Urine specimens and isolates 90 strain clinical bacterias, warp
VITEK-AMS microbiological analysis instrument is identified, has 21 strain streptococcus pneumoniae, 23 influenzae strain bacillus, 23 strain enterococcus, 24 strain Fructus Vitis viniferae balls
Bacterium.Quality-control strains is provided by Ministry of Public Health Clinical Laboratory center.
1.2 culture medium
Isolation medium is 5% blood plate, and drug test MH agar is purchased from Oxoid company.
1.3 antibacterials
Trial target: the Cefetamet Pivoxil Hydrochloride crystal that the embodiment of the present invention 3 prepares；
Reference substance: commercially available Cefetamet Pivoxil Hydrochloride raw material, is provided by Zhuhai United Laboratories Ltd.
1.4 criterion
Standard bacteria and tested bacterium drug sensitivity tests are judged by NCCLS standard in 2000.
1.5 statistical method
Calculate various antibacterials to the Sensitivity rate of different bacterium, medium sensitivity rate, resistant rate, and use χ2Check more each
The Sensitivity rate of Cefetamet Pivoxil Hydrochloride.
2, the results are shown in Table 3, table 4, table 5, table 6
Table 3, antibacterials are to the 19 pneumococcal antibacterial activity in vitro of strain
Table 4, the antibacterials antibacterial activity in vitro to 23 influenzae strain bacillus
Table 5, antibacterials are to the 23 enterococcal antibacterial activity in vitro of strain
Table 6, antibacterials are to the 24 staphylococcic antibacterial activity in vitro of strain
From above-mentioned result of the test it can be seen that the cefetamet pivoxil hydrochloride compound prepared by the present invention is to streptococcus pneumoniae, influenza
Bacillus has more significantly antibacterial activity；Commercially available Cefetamet Pivoxil Hydrochloride to enterococcus, staphylococcus without antibacterial activity, and this
The Cefetamet Pivoxil Hydrochloride that invention provides has stronger antibacterial activity to enterococcus, staphylococcus.
Claims (3)
1. the method for the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease, it is characterised in that
Comprise the steps:
1) supplementary material processes: with vibration screen-dividing machine by amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose, carboxymethylstarch
Sodium, Cefetamet Pivoxil Hydrochloride sieve；
2) all supplementary materials are weighed: in parts by weight, the Cefetamet Pivoxil Hydrochloride of 1.0-1.5 weight portion, 0.5-1.5 weight portion
Amylum pregelatinisatum, the microcrystalline Cellulose 102 of 1.0-1.5 weight portion, the carboxymethylstach sodium of 0.3-0.4 weight portion, 0.1-0.3 weight
The hydroxypropylcellulose of part, the Glyceryl Behenate of 0.05-0.15 weight portion, the magnesium stearate of 0.04-0.06 weight portion；
3) mixing: join in mixer by load weighted supplementary material, arranges motor rotation frequency, opens mixer and mixes 25 points
Clock；
4) selecting high speed tablet press tabletting, regulation pressure makes slice, thin piece energy molding and hardness be not more than 1% at 4-9kgf, friability；
5) packaging；
Described Cefetamet Pivoxil Hydrochloride is crystal, uses X-ray powder diagram such as Fig. 1 institute that Cu-K alpha ray measurement obtains
Showing, its preparation method is as follows: take Cefetamet Pivoxil Hydrochloride crude drug, and addition volume is 8 times of Cefetamet Pivoxil Hydrochloride weight
The mixed solution that ether forms with ethanol, wherein ether is 4:2.5 with the volume ratio of ethanol, is heated to 30-35 DEG C；Hydrochloric acid cephalo
His U.S. ester crude drug molten clear after, add activated carbon decolorizing, filter；Temperature 35-40 DEG C is heated and kept to filtrate, and drip volume and be
Dimethylformamide that Cefetamet Pivoxil Hydrochloride weight is 6 times and the volume ratio of acetone mixed solvent, dimethylformamide and acetone
For 2:1；Dripping and finish, stirring cooling, described stirring cooling is for being dropped by 1.5-3.5 DEG C/min speed under being 50-75rmp stirring at rotating speed
Temperature is to 20-25 DEG C, then is cooled to 5-10 DEG C by 0.5-1 DEG C/min speed under rotating speed 30-45rmp stirs, and stands 5 hours, mistake
Filter, washing, it is dried to obtain white crystalline powder.
The medicine Cefetamet Pivoxil Hydrochloride compositions of preparation treatment sensitive organism infectious disease the most according to claim 1
Method, it is characterised in that: in described step 1), amylum pregelatinisatum, microcrystalline Cellulose 102, hydroxypropylcellulose cross 60 mesh sieves, carboxylic first
Starch Sodium crosses 120 mesh sieves, and Cefetamet Pivoxil Hydrochloride crosses 80 mesh sieves.
The medicine Cefetamet Pivoxil Hydrochloride compositions of preparation treatment sensitive organism infectious disease the most according to claim 1
Method, it is characterised in that: arranging motor rotation frequency in described step 3) is 200r/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610858325.2A CN106265574A (en) | 2015-05-15 | 2015-05-15 | A kind of method of the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610858325.2A CN106265574A (en) | 2015-05-15 | 2015-05-15 | A kind of method of the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease |
| CN201510246057.4A CN104800221B (en) | 2015-05-15 | 2015-05-15 | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510246057.4A Division CN104800221B (en) | 2015-05-15 | 2015-05-15 | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106265574A true CN106265574A (en) | 2017-01-04 |
Family
ID=53685714
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610858325.2A Pending CN106265574A (en) | 2015-05-15 | 2015-05-15 | A kind of method of the medicine Cefetamet Pivoxil Hydrochloride compositions preparing treatment sensitive organism infectious disease |
| CN201510246057.4A Active CN104800221B (en) | 2015-05-15 | 2015-05-15 | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases |
| CN201610858218.XA Pending CN106420761A (en) | 2015-05-15 | 2015-05-15 | Pharmaceutical cefetamet pivoxil hydrochloride composition for treating sensitive bacterium infected disease |
| CN201610858574.1A Pending CN106236724A (en) | 2015-05-15 | 2015-05-15 | The method of the medicine Cefetamet Pivoxil Hydrochloride tablet composition of preparation treatment sensitive organism infectious disease |
| CN201610858632.0A Pending CN106420641A (en) | 2015-05-15 | 2015-05-15 | Method for preparing cefetamet pivoxil hydrochloride tablet composition |
| CN201610858214.1A Pending CN106344528A (en) | 2015-05-15 | 2015-05-15 | Medicine cefetamet pivoxil hydrochloride tablet composition for treating sensitive bacterium infectious diseases |
| CN201610858217.5A Pending CN106176759A (en) | 2015-05-15 | 2015-05-15 | A kind of cefetamet pivoxil hydrochloride tablets agent compositions |
| CN201610858371.2A Pending CN106389440A (en) | 2015-05-15 | 2015-05-15 | Method used for preparing pharmaceutical cefetamet pivoxil hydrochloride composition used for treating sensitive bacterium infected diseases |
Family Applications After (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510246057.4A Active CN104800221B (en) | 2015-05-15 | 2015-05-15 | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases |
| CN201610858218.XA Pending CN106420761A (en) | 2015-05-15 | 2015-05-15 | Pharmaceutical cefetamet pivoxil hydrochloride composition for treating sensitive bacterium infected disease |
| CN201610858574.1A Pending CN106236724A (en) | 2015-05-15 | 2015-05-15 | The method of the medicine Cefetamet Pivoxil Hydrochloride tablet composition of preparation treatment sensitive organism infectious disease |
| CN201610858632.0A Pending CN106420641A (en) | 2015-05-15 | 2015-05-15 | Method for preparing cefetamet pivoxil hydrochloride tablet composition |
| CN201610858214.1A Pending CN106344528A (en) | 2015-05-15 | 2015-05-15 | Medicine cefetamet pivoxil hydrochloride tablet composition for treating sensitive bacterium infectious diseases |
| CN201610858217.5A Pending CN106176759A (en) | 2015-05-15 | 2015-05-15 | A kind of cefetamet pivoxil hydrochloride tablets agent compositions |
| CN201610858371.2A Pending CN106389440A (en) | 2015-05-15 | 2015-05-15 | Method used for preparing pharmaceutical cefetamet pivoxil hydrochloride composition used for treating sensitive bacterium infected diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (8) | CN106265574A (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012244A (en) * | 2015-08-03 | 2015-11-04 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicine ezetimibe composition granules for treating hyperlipidemia |
| CN105012245A (en) * | 2015-08-10 | 2015-11-04 | 青岛蓝盛洋医药生物科技有限责任公司 | Phlegm-dispersing drug ambroxol hydrochloride composition granules and preparing method thereof |
| CN105168147A (en) * | 2015-09-11 | 2015-12-23 | 青岛蓝盛洋医药生物科技有限责任公司 | Pharmaceutical cefetamet pivoxil hydrochloride composite granule for treating bacterial infection |
| CN105030697A (en) * | 2015-09-15 | 2015-11-11 | 青岛华之草医药科技有限公司 | Anti-infective drug cefetamet pivoxil hydrochloride composite capsule |
| CN105106120A (en) * | 2015-09-17 | 2015-12-02 | 青岛华之草医药科技有限公司 | Antibacterial agents cefetamet pivoxil hydrochloride composition |
| CN105055334A (en) * | 2015-09-18 | 2015-11-18 | 青岛华之草医药科技有限公司 | Postoperative antiemetic tropisetron hydrochloride composition granule |
| CN105078902A (en) * | 2015-09-24 | 2015-11-25 | 青岛华之草医药科技有限公司 | Cefetamet pivoxil hydrochloride composite granules for treating bacterial infection |
| CN105193729A (en) * | 2015-10-08 | 2015-12-30 | 杨献美 | Pharmaceutical tropisetron hydrochloride composition dry suspension for treating nausea and vomiting both caused by chemotherapy |
| CN105147698A (en) * | 2015-10-09 | 2015-12-16 | 杨献美 | Drug, namely cefetamet pivoxil hydrochloride composition tablets, for treating infectious diseases |
| CN108159052A (en) * | 2018-03-08 | 2018-06-15 | 董贵雨 | A kind of pharmaceutical composition containing Cefetamet Pivoxil Hydrochloride |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219124A (en) * | 2008-02-04 | 2008-07-16 | 山东罗欣药业股份有限公司 | Hydrochloric acid cefetamet pivoxil dispersible tablet and method for preparing the same |
| CN103467494A (en) * | 2013-09-24 | 2013-12-25 | 山东罗欣药业股份有限公司 | Novel crystal form of cefdinir and preparation method thereof |
| CN103497205A (en) * | 2013-09-24 | 2014-01-08 | 山东罗欣药业股份有限公司 | New crystal form of cephalothin sodium and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1319533C (en) * | 2003-09-28 | 2007-06-06 | 东北制药总厂 | Cefetamet pivoxil hydrochloride dispersion dispersion tablets and preparation method |
| CN101550146A (en) * | 2009-05-07 | 2009-10-07 | 郑仙锋 | Cefetamet pivoxil hydrochloride compound and preparation method thereof |
| WO2013109202A2 (en) * | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical compounds comprising cefetamet |
| CN104382849B (en) * | 2014-11-28 | 2016-09-21 | 石家庄市华新药业有限责任公司 | A kind of cefaclor dry suspension and preparation method thereof |
-
2015
- 2015-05-15 CN CN201610858325.2A patent/CN106265574A/en active Pending
- 2015-05-15 CN CN201510246057.4A patent/CN104800221B/en active Active
- 2015-05-15 CN CN201610858218.XA patent/CN106420761A/en active Pending
- 2015-05-15 CN CN201610858574.1A patent/CN106236724A/en active Pending
- 2015-05-15 CN CN201610858632.0A patent/CN106420641A/en active Pending
- 2015-05-15 CN CN201610858214.1A patent/CN106344528A/en active Pending
- 2015-05-15 CN CN201610858217.5A patent/CN106176759A/en active Pending
- 2015-05-15 CN CN201610858371.2A patent/CN106389440A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219124A (en) * | 2008-02-04 | 2008-07-16 | 山东罗欣药业股份有限公司 | Hydrochloric acid cefetamet pivoxil dispersible tablet and method for preparing the same |
| CN103467494A (en) * | 2013-09-24 | 2013-12-25 | 山东罗欣药业股份有限公司 | Novel crystal form of cefdinir and preparation method thereof |
| CN103497205A (en) * | 2013-09-24 | 2014-01-08 | 山东罗欣药业股份有限公司 | New crystal form of cephalothin sodium and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 侯玉荣，等: "β-内酰胺类抗生素中高分子杂质的研究和检测方法进展", 《药学与临床研究》 * |
| 李正化: "《药物化学》", 31 January 2000, 人民卫生出版社 * |
| 胡泽富，等: "粉末直接压片法制备盐酸头孢他美酯片", 《中国药业》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106420761A (en) | 2017-02-22 |
| CN106420641A (en) | 2017-02-22 |
| CN106389440A (en) | 2017-02-15 |
| CN106344528A (en) | 2017-01-25 |
| CN106236724A (en) | 2016-12-21 |
| CN104800221B (en) | 2017-01-11 |
| CN104800221A (en) | 2015-07-29 |
| CN106176759A (en) | 2016-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104800221B (en) | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases | |
| JP5866737B2 (en) | Reborokitamicin, its drug composition, preparation method and application | |
| CN104788470A (en) | Cefetamet pivoxil hydrochloride compound for treating sensitive bacteria infectious diseases | |
| CN104910186B (en) | A kind of cefathiamidine compound | |
| CN109516989A (en) | One kind inhibits and the compound for the CDK that degrades | |
| CN104546686B (en) | A kind of mosapride citrate is co-mulled and made into thing and preparation method thereof and containing its pharmaceutical composition | |
| CN101555215A (en) | Preparation technology of doxycycline hydrochloride for injection | |
| CN105193736A (en) | Medicinal cefetamet pivoxil hydrochloride dry suspension for treating sensitive bacterial infection diseases | |
| CN104530082B (en) | Cefathiamidine compound | |
| JP2022506635A (en) | Oligosaccharide composition and its usage | |
| CN105796523A (en) | Levofloxacin mesylate tablets and preparation process thereof | |
| CN105030697A (en) | Anti-infective drug cefetamet pivoxil hydrochloride composite capsule | |
| CN105147698A (en) | Drug, namely cefetamet pivoxil hydrochloride composition tablets, for treating infectious diseases | |
| CN105106120A (en) | Antibacterial agents cefetamet pivoxil hydrochloride composition | |
| CN105147637A (en) | Anti-infective drug cefetamet pivoxil hydrochloride composition capsule | |
| CN105168147A (en) | Pharmaceutical cefetamet pivoxil hydrochloride composite granule for treating bacterial infection | |
| CN105106136A (en) | Cefetamet pivoxil hydrochloride dry suspension for treating diseases infected by sensitive bacteria | |
| CN105106220A (en) | Pharmic cefetamet pivoxil hydrochloride composition for treating sensitive bacterium infection diseases | |
| CN105106119A (en) | Medicine cefetamet pivoxil hydrochloride composition for treating infectious diseases | |
| CN105193820A (en) | Anti-infection drug cefetamet pivoxil hydrochloride composition | |
| CN108047253A (en) | A kind of Ceftriaxone Sodium crystal-form compound | |
| CN103384523B (en) | Use of nifuratel to treat infections caused by clostridium species | |
| CN105078902A (en) | Cefetamet pivoxil hydrochloride composite granules for treating bacterial infection | |
| CN103450086A (en) | Ozagrel compound, preparation method and pharmaceutical composition of ozagrel compound | |
| CN103304604A (en) | Clindamycin phosphate compound and preparation method and pharmaceutical composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wu Xiangyang Inventor after: Zhao Kongbo Inventor before: Zhao Kongbo |
|
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170104 |
|
| RJ01 | Rejection of invention patent application after publication |