CN106511277A - Polaprezinc granule and preparation method thereof - Google Patents
Polaprezinc granule and preparation method thereof Download PDFInfo
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- CN106511277A CN106511277A CN201611026946.0A CN201611026946A CN106511277A CN 106511277 A CN106511277 A CN 106511277A CN 201611026946 A CN201611026946 A CN 201611026946A CN 106511277 A CN106511277 A CN 106511277A
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- 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
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Abstract
The invention discloses a polaprezinc granule and a preparation method thereof. The granule is prepared from the components: polaprezinc, mannitol, sodium carboxymethyl starch, croscarmellose sodium, povidone K30, 30 percent of polymethylacrylic acid resin latex solution, and appropriate amount of ethyl alcohol with the concentration being 95 percent. According to the polaprezinc granule and the preparation method thereof provided by the invention, the polaprezinc granule is prepared through selecting appropriate auxiliary material species and dosage thereof, and adopting the appropriate preparation method, so that the problems of hygroscopicity and disintegration speed are effectively solved, the stability is improved, and a favorable effect of clinical application is also achieved.
Description
Technical field
The invention belongs to pharmaceutical technology field, more particularly to a kind of polaprezinc granule and preparation method thereof.
Background technology
Gastric ulcer and duodenal ulcer simultaneously claim peptic ulcer, and sickness rate is up to 10%.
Drug therapy is the primary treatments of peptic ulcer, what medicine was conventional at present have proton pump inhibitor,
The drug combination of H2 acceptor inhibitors, gastric mucosa protective agent and anti-helicobacter pylori.
Polaprezinc granule is the N-BETA-Alanyl-L-histidine complex of zinc.N-BETA-Alanyl-L-histidine is one and is made up of β-Phenylalanine and L-Histidine
Dipeptides, it is a kind of antioxidant.
Experiment shows polaprezinc as antioxidative membrane stabilizing action is so as to improve gastric mucosal defense power, reaches cell guarantor
The effect of shield, while it can also promote injury tissue to heal, strengthens defense factor effect, reaches the work of preventing and treating peptic ulcer
With while the effect with the propagation and suppression urease activity for suppressing helicobacter pylori.
The medicine in 1993 submits application for registration in Japan, and 1994 in Japanese Initial Public Offering, trade name Promac.
Polaprezinc granule Promac to Japan's listing（Hereinafter referred to as Promac）Quality investigation is carried out, it is found which is steady
It is qualitative poor, place 6 months under the conditions of the accelerated test of 40 DEG C ± 2 DEG C of temperature, relative humidity for 75% ± 5% and in temperature be
25 DEG C ± 2 DEG C, relative humidity to place 12 months under the conditions of 60% ± 10% long term test when, loss on drying increases, relevant thing
Matter goes up.Temperature be 37 DEG C ± 0.5 DEG C, rotating speed be 50 turns per minute, dissolution medium be water under conditions of, its dissolution situation compared with
Difference.Accordingly, it would be desirable to a kind of stable storing, all right polaprezinc granule of aqueous medium dissolution.
Therefore, it is special to propose this invention.
The content of the invention
The technical problem to be solved is to overcome the deficiencies in the prior art, there is provided one kind meets Chinese Pharmacopoeia requirement
The polaprezinc granule that storage stability is good, disintegrate result of extraction is good.
The technical problem to be solved is achieved through the following technical solutions：A kind of polaprezinc granule
Agent, its raw material composition include：
| Polaprezinc | 150 weight portions |
| Mannitol | 370-390 weight portions |
| Carboxymethyl starch sodium | 290-310 weight portions |
| Croscarmellose Sodium | 100-120 weight portions |
| Povidone K 30 | 38-42 weight portions |
| 30% latex liquid of polymethacrylic resin | 66.7 weight portions |
| 95% ethanol | In right amount |
Preferably, the raw material composition of above-mentioned polaprezinc granule includes：
| Polaprezinc | 150 weight portions |
| Mannitol | 380 weight portions |
| Carboxymethyl starch sodium | 300 weight portions |
| Croscarmellose Sodium | 110 weight portions |
| Povidone K 30 | 40 weight portions |
| 30% latex liquid of polymethacrylic resin | 66.7 weight portions |
| 95% ethanol | In right amount |
The technical problem to be solved is to provide a kind of method for preparing above-mentioned polaprezinc granule.
Preferably, the preparation method of above-mentioned polaprezinc granule provided by the present invention is comprised the following steps:
1）The process of supplementary material
The supplementary material of recipe quantity is weighed, and is pulverized and sieved standby；
2）Premix
Polaprezinc, Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium are weighed by recipe quantity, take polaprezinc and
Mannitol carry out equivalent progressively increase mixing 2 times, obtain mixture；Take mixtureEquivalent carried out with carboxymethyl starch sodium progressively increase to mix
2 times, obtain mixture；Take mixtureEquivalent carried out with Croscarmellose Sodium progressively increase to mix 3 times；
3）Pelletize, be dried
Povidone K 30 is weighed by recipe quantity, 95% ethanol of about 350 weight portions is dissolved in；Resulting solution is uniformly sprayed onto step
1）Gained mixed powder, sprinkling, while mixing；Again 30% latex liquid of polymethacrylic resin of recipe quantity is uniformly sprayed
Intermediate soft material is spread across, is sprayed, while mixing；Then spray 95% ethanol, 5 ~ 10 weight portion；Gained soft material is used
0.4mm aperture sieves bowl is extruded, and reuses spheronizator round as a ball；Gained granule is added in heated-air circulation oven, in 55 ~ 65 DEG C of dryings
2% is less than to loss on drying；
4）Screening, granulate
By dried granule respectively with 30 mesh and 40 mesh sieves, below 30 mesh sieves and granules more than 40 mesh sieves are collected, will
Granules more than 30 mesh sieves collects below 30 mesh sieves and granules more than 40 mesh sieves with 32 mesh sieve granulate；
5）Total mixed, subpackage
Polaprezinc midbody particle obtained in step 4 is mixed, subpackage, obtains final product after the assay was approved.
Preferably, in above-mentioned steps 1,200 mesh sieves, Mannitol, carboxymethyl starch sodium, crosslinking carboxylic after polaprezinc is crushed, are crossed
Sodium carboxymethylcellulose pyce crosses 80 mesh sieves after crushing.
Preferably, in above-mentioned steps 1, by polaprezinc micronization, Mannitol, carboxymethyl starch sodium, cross-linked carboxymethyl fiber
80 mesh sieves are crossed after plain sodium powder is broken.
Advantages of the present invention：
Description of the drawings
Measure stripping curve when Fig. 1 is the dissolution medium pH=1.0 in test example 3；
Measure stripping curve when Fig. 2 is the dissolution medium pH=5.5 in test example 3；
Measure stripping curve when Fig. 3 is the dissolution medium pH=6.8 in test example 3；
Fig. 4 is measure stripping curve of the dissolution medium in test example 3 when being water.
Specific embodiment
Below against accompanying drawing, by the description to embodiment, further details of is made to the specific embodiment of the present invention
Explanation, it is therefore an objective to help those skilled in the art to have more complete, accurate and deep reason to design of the invention, technical scheme
Solution, and contribute to its enforcement.
Embodiment one
Prescription in the present embodiment
Polaprezinc 150g
Mannitol 390g
Carboxymethyl starch sodium 290g
Croscarmellose Sodium 100g
Povidone K 30 42g
30% latex liquid of polymethacrylic resin 66.7g
95% appropriate amount of ethanol
Make 2000 bags
Preparation technology in the present embodiment
1）The process of supplementary material
The supplementary material of recipe quantity is weighed, and is pulverized and sieved standby；
2）Premix
Polaprezinc, Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium are weighed by recipe quantity, take polaprezinc and
Mannitol carry out equivalent progressively increase mixing 2 times, obtain mixture；Take mixtureEquivalent carried out with carboxymethyl starch sodium progressively increase to mix
2 times, obtain mixture；Take mixtureEquivalent carried out with Croscarmellose Sodium progressively increase to mix 3 times；
3）Pelletize, be dried
Povidone K 30 is weighed by recipe quantity, 95% ethanol of about 350 weight portions is dissolved in；Resulting solution is uniformly sprayed onto step
1）Gained mixed powder, sprinkling, while mixing；Again 30% latex liquid of polymethacrylic resin of recipe quantity is uniformly sprayed
Intermediate soft material is spread across, is sprayed, while mixing；Then spray 95% ethanol, 5 ~ 10 weight portion；Gained soft material is used
0.4mm aperture sieves bowl is extruded, and reuses spheronizator round as a ball；Gained granule is added in heated-air circulation oven, in 55 ~ 65 DEG C of dryings
2% is less than to loss on drying；
4）Screening, granulate
By dried granule respectively with 30 mesh and 40 mesh sieves, below 30 mesh sieves and granules more than 40 mesh sieves are collected, will
Granules more than 30 mesh sieves collects below 30 mesh sieves and granules more than 40 mesh sieves with 32 mesh sieve granulate；
5）Total mixed, subpackage
Polaprezinc midbody particle obtained in step 4 is mixed, subpackage, obtains final product after the assay was approved.
In the present embodiment, the step 1）After polaprezinc is crushed cross 200 mesh sieves, Mannitol, carboxymethyl starch sodium,
Croscarmellose Sodium crosses 80 mesh sieves after crushing.
In the present embodiment, step 1）By polaprezinc micronization, Mannitol, carboxymethyl starch sodium, cross-linked carboxymethyl are fine
80 mesh sieves are crossed after the plain sodium powder of dimension is broken.
Embodiment two
Prescription in the present embodiment
Polaprezinc 150g
Mannitol 370g
Carboxymethyl starch sodium 310g
Croscarmellose Sodium 120g
Povidone K 30 38g
30% latex liquid of polymethacrylic resin 66.7g
95% appropriate amount of ethanol
Make 2000 bags
The preparation technology of the present embodiment
1）The process of supplementary material
The supplementary material of recipe quantity is weighed, and is pulverized and sieved standby；
2）Premix
Polaprezinc, Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium are weighed by recipe quantity, take polaprezinc and
Mannitol carry out equivalent progressively increase mixing 2 times, obtain mixture；Take mixtureEquivalent carried out with carboxymethyl starch sodium progressively increase to mix
2 times, obtain mixture；Take mixtureEquivalent carried out with Croscarmellose Sodium progressively increase to mix 3 times；
3）Pelletize, be dried
Povidone K 30 is weighed by recipe quantity, 95% ethanol of about 350 weight portions is dissolved in；Resulting solution is uniformly sprayed onto step
1）Gained mixed powder, sprinkling, while mixing；Again 30% latex liquid of polymethacrylic resin of recipe quantity is uniformly sprayed
Intermediate soft material is spread across, is sprayed, while mixing；Then spray 95% ethanol, 5 ~ 10 weight portion；Gained soft material is used
0.4mm aperture sieves bowl is extruded, and reuses spheronizator round as a ball；Gained granule is added in heated-air circulation oven, in 55 ~ 65 DEG C of dryings
2% is less than to loss on drying；
4）Screening, granulate
By dried granule respectively with 30 mesh and 40 mesh sieves, below 30 mesh sieves and granules more than 40 mesh sieves are collected, will
Granules more than 30 mesh sieves collects below 30 mesh sieves and granules more than 40 mesh sieves with 32 mesh sieve granulate；
5）Total mixed, subpackage
Polaprezinc midbody particle obtained in step 4 is mixed, subpackage, obtains final product after the assay was approved.
In the present embodiment, the step 1）After polaprezinc is crushed cross 200 mesh sieves, Mannitol, carboxymethyl starch sodium,
Croscarmellose Sodium crosses 80 mesh sieves after crushing.
In the present embodiment, step 1）By polaprezinc micronization, Mannitol, carboxymethyl starch sodium, cross-linked carboxymethyl are fine
80 mesh sieves are crossed after the plain sodium powder of dimension is broken.
Embodiment three
Prescription in the present embodiment
Polaprezinc 150g
Mannitol 380g
Carboxymethyl starch sodium 300g
Croscarmellose Sodium 110g
Povidone K 30 40g
30% latex liquid of polymethacrylic resin 66.7g
95% appropriate amount of ethanol
Make 2000 bags
Preparation technology in the present embodiment
1）The process of supplementary material
The supplementary material of recipe quantity is weighed, and is pulverized and sieved standby；
2）Premix
Polaprezinc, Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium are weighed by recipe quantity, take polaprezinc and
Mannitol carry out equivalent progressively increase mixing 2 times, obtain mixture；Take mixtureEquivalent carried out with carboxymethyl starch sodium progressively increase to mix
2 times, obtain mixture；Take mixtureEquivalent carried out with Croscarmellose Sodium progressively increase to mix 3 times；
3）Pelletize, be dried
Povidone K 30 is weighed by recipe quantity, 95% ethanol of about 350 weight portions is dissolved in；Resulting solution is uniformly sprayed onto step
1）Gained mixed powder, sprinkling, while mixing；Again 30% latex liquid of polymethacrylic resin of recipe quantity is uniformly sprayed
Intermediate soft material is spread across, is sprayed, while mixing；Then spray 95% ethanol, 5 ~ 10 weight portion；Gained soft material is used
0.4mm aperture sieves bowl is extruded, and reuses spheronizator round as a ball；Gained granule is added in heated-air circulation oven, in 55 ~ 65 DEG C of dryings
2% is less than to loss on drying；
4）Screening, granulate
By dried granule respectively with 30 mesh and 40 mesh sieves, below 30 mesh sieves and granules more than 40 mesh sieves are collected, will
Granules more than 30 mesh sieves collects below 30 mesh sieves and granules more than 40 mesh sieves with 32 mesh sieve granulate；
5）Total mixed, subpackage
Polaprezinc midbody particle obtained in step 4 is mixed, subpackage, obtains final product after the assay was approved.
In the present embodiment, the step 1）After polaprezinc is crushed cross 200 mesh sieves, Mannitol, carboxymethyl starch sodium,
Croscarmellose Sodium crosses 80 mesh sieves after crushing.
In the present embodiment, step 1）By polaprezinc micronization, Mannitol, carboxymethyl starch sodium, cross-linked carboxymethyl are fine
80 mesh sieves are crossed after the plain sodium powder of dimension is broken.
Below by way of the test example and comparatively beneficial effect of the polaprezinc granule in bright the present embodiment:
Test example 1The accelerated stability test of the polaprezinc granule of the present invention
Take the polaprezinc granule of the present invention（Embodiment 3）With Promac granules, by commercially available back, in 40 DEG C ± 2 of temperature
DEG C, relative humidity for 75% ± 5% accelerated test under the conditions of place 6 months.Take respectively at the 0th, 1,2,3,6 the end of month of test
Sample, is detected by stability high spot reviews project.The results are shown in Table 1
1 present invention of table investigates results contrast with the accelerated stability of the polaprezinc granule of prior art
Above experimental result shows that the polaprezinc granule of the present invention is 75% ± 5% in 40 DEG C ± 2 DEG C of temperature, relative humidity
Accelerated test under the conditions of place 6 months, indices compared with 0 month without significant change, the polaprezinc granule of the present invention
Have good stability.Compared with the polaprezinc granule of prior art, its stability is better than prior art.
Test example 2The long-term stable experiment of the polaprezinc granule of the present invention
Take the polaprezinc granule of the present invention（Embodiment 3）With Promac granules, by commercially available back, it is 25 DEG C ± 2 in temperature
DEG C, relative humidity for 60% ± 10% long term test under the conditions of place 12 months.Respectively at test the 0th, 3,6,9,12 months
End sampling, is detected by stability high spot reviews project.The results are shown in Table 2.
2 present invention of table investigates results contrast with the accelerated stability of the polaprezinc granule of prior art
Above experimental result shows, the polaprezinc granule of the present invention temperature be 25 DEG C ± 2 DEG C, relative humidity be 60% ±
Place 12 months under the conditions of 10% long term test, indices are compared with 0 month without significant change, the polaprezinc of the present invention
Granule has good stability.Compared with the polaprezinc granule of prior art, its stability is better than prior art.
Test example 3The stripping curve of the polaprezinc granule of the present invention is determined
Take the polaprezinc granule of the present invention（Embodiment 3）With Promac granules, it is 37 DEG C ± 0.5 DEG C in temperature, rotating speed is
50 turns per minute, dissolution medium pH value is to determine stripping curve respectively under 1.0,5.5,6.8 and water condition.As a result see accompanying drawing 1-4.
Above result of the test shows that the polaprezinc granule of the present invention is in the dissolution medium that pH value is 1.0,5.5,6.8
In it is similar to the polaprezinc granule dissolution of prior art；In aqueous medium, its dissolution rate is better than prior art.
Test example 4The clinical trial of the polaprezinc granule of the present invention
First, human pharmacokineticses research
For the polaprezinc granule of the research present invention（Embodiment 3）Absorption, distribution, metabolism and excretion in the healthy human body
Dynamic change characteristic, we have carried out pharmacokinetic to which.
Research method
Experimenter does not drink drinks, coffee-type beverage or fruit juice in first 1 day of test and experimental period；Overnight fasting 10 before test
Hour.Morning next day about 7:00 starts by design time point blood sampling；Overnight fasting 10 hours before medication, takes medicine the 1st day morning
About 7:00 starts medication, uses 250ml warm water delivery services；Medication can be drunk water after 2 hours again, unified feed low fat after 4 hours
Diet.Strenuous exercise should be avoided after experimenter's medication, also must not be liied in bed for a long time.Breakfast, lunch and dinner during test unify pantry.Medication
Dosage：Take the oral 0.5g of empty stomach from the 1st day morning；Take medicine the 2nd～6 day, each after early, supper daily to take medicine once, each 0.5g；
Take medicine the 7th day, the oral 0.5g of empty stomach from morning.Blood-sample withdrawal time point：-24、-23、-22、-21、-18、-12h；Take medicine the 1st day 0,
0.5th, 1,1.5,2,3,4,5,7,9,12,15,24h (0h is the same day point to be administered)；Take medicine the 2nd～6 day 0h；Take medicine the 7th day 0,
0.5、1、1.5、2、3、4、5、7、9、12、15、24h.The blood drug level of zinc, observation experimenter's medication are determined with atomic emission spectrum
Process during rear blood drug level Jing.
Test medicine
| Dosage group | Specification | Lot number | Usage | Consumption |
| Single | 0.5g/ bags | Embodiment 3 | Single oral | 1 bag/time |
| Repeatedly | 0.5g/ bags | Embodiment 3 | 2 times/day, continuous 5 days | 1 bag/time × 2 times/day |
| After stable state | 0.5g/ bags | Embodiment 3 | Single oral | 1 bag/time |
Evaluation criterion
Pharmacokinetic parameter Cmax, Tmax, background AUC, △ AUC0-24, Css, Cmin, DF etc..
1st, single-dose：Draw each experimenter's according to the blood concentration-time data of each experimenter measured in test
Drug-time curve and average drug-time curve, carry out the estimation and analysis of pharmacokinetic parameter, to reflect medicine in human body interior suction
The characteristics of receiving, be distributed and eliminate.
2nd, multiple dosing：According to five Grain volumes and steady plasma-drug concentration-time data that determine in test, draw multiple
Drug-time curve after administration, tries to achieve corresponding pharmacokinetic parameter, specifies the Pharmacokinetic Characteristics of multiple dosing.While with
The pharmacokinetic parameter of single dose administration is compared, the difference observed between them.
Safety indexes：Observation clinical adverse
And conclusion as a result
10 health volunteers（Men and women half and half）, oral polaprezinc granule, with aes determination blood plasma gather it is general
Auspicious zinc concentration, after the polaprezinc granule of 10 health volunteer's single oral dose Jilin Broadwell Pharmaceutical Co., Ltd.,
Estimate that polaprezinc pharmacokinetic parameters are：Background AUC is 6.55 ± 1.12 h μ g/ml, △ AUC0-24For 3.81 ± 1.14h
μ g/ml, CmaxFor 1.3000 ± 0.4991 μ g/ml, TmaxFor 3 ± 2.4h；10 health volunteer's multi-dose oral Jilin Province medicines
After the polaprezinc granule of thing institute, estimation polaprezinc pharmacokinetic parameters are：Background AUC is 6.55 ± 1.12 h μ g/
Ml, △ AUC0-24For 9.73 ± 2.39 h μ g/ml, CmaxFor 1.4455 ± 0.3558 μ g/ml, CminFor 0.5957 ± 0.2507
μ g/ml, TmaxFor 1.6 ± 0.7h, CssFor 0.6768 ± 0.0985 μ g/ml, DF is 160% ± 83.9%.To single dose and multiple dose
Doubled haploid population is carried out respectively, there are no significance between the pharmacokinetic parameters for as a result showing masculinity and femininity health volunteer
Difference.During test, experimenter has no clinical adverse.
2nd, Clinical efficacy research
To evaluate effectiveness and the safety of the polaprezinc granule of the present invention, it is right for We conducted with bismuth potassium citrate granule
According to medicine, using multicenter, the clinical research of random, Double-blind double-dummy, parallel control.
The random enrolled subject of this research 224, wherein, test group 112；Matched group 112.Test group：Breakfast
Front half an hour, oral bismuth potassium citrate simulated 2 bags of granule, 1 bag of the oral polaprezinc granule of breakfast half an hour after；Sleep front half an hour mouth
Take bismuth potassium citrate simulation 2 bags of granule, 1 bag of polaprezinc granule, warm water is taken after mixing it with water.The course for the treatment of 8 weeks.Matched group：Half an hour mouth before breakfast
2 bags of bismuth potassium citrate is taken, the oral polaprezinc of breakfast half an hour after simulates 1 bag of granule；2 bags of oral bismuth potassium citrate of front half an hour is slept,
Polaprezinc simulates 1 bag of granule, and warm water is taken after mixing it with water.The course for the treatment of：8 weeks.
Gastric ulcer efficacy analysis
FAS analysis results：After two groups of patient's medications, the comparing difference of gastric ulcer curative effect grade is not statistically significant（P=
0.8391）；Healing rate test group 72.97%, matched group 71.43%, between two groups, comparing difference is not statistically significant（P=
0.7774）；Total effective rate test group 83.78%, matched group 79.46%, between two groups, comparing difference is not statistically significant（P=
0.3749）.PPS analysis results：After two groups of patient's medications, the comparing difference of gastric ulcer curative effect grade is not statistically significant（P=
0.8671）；Healing rate test group 80.20%, matched group 77.67%, between two groups, comparing difference is not statistically significant（P=
0.6288）；Total effective rate test group 92.08%, matched group 86.41%, between two groups, comparing difference is not statistically significant（P=
0.1881）.
This results show：The polaprezinc Granules in Treating gastric ulcer of the present invention, its effectiveness and bismuth potassium citrate
Grain is close, it is adaptable to treat gastric ulcer.
The research of clinical safety
Adverse events incidence rate test group 7.21%, matched group 11.61%, adverse reaction rate test group 3.60%, matched group
6.25%, transaminase disorder, feeling of oppression and pain in the chest, constipation, dizziness headache are shown as, above untoward reaction is slightly, is not required to process,
Recover after drug withdrawal.Occur without serious adverse events.Between two groups, comparing difference is not statistically significant.
This results show：The polaprezinc granule of the present invention is safely and effectively to treating gastric ulcer.
The present invention is exemplarily described above in association with accompanying drawing, it is clear that the present invention is implemented
The restriction of formula, as long as employ the improvement of the various unsubstantialities that method of the present invention design and technical scheme are carried out；Or not
It is improved, the above-mentioned design of the present invention and technical scheme are directly applied to into other occasions, in protection scope of the present invention
Within.
Claims (5)
1. a kind of polaprezinc granule, it is characterised in that the raw material composition of the polaprezinc granule includes：
150 weight portion of polaprezinc
Mannitol 370-390 weight portion
Carboxymethyl starch sodium 290-310 weight portions
Croscarmellose Sodium 100-120 weight portion
Povidone K 30 38-42 weight portion
30% latex liquid of polymethacrylic resin, 66.7 weight portion
95% appropriate amount of ethanol.
2. polaprezinc granule according to claim 1, it is characterised in that the raw material group of the polaprezinc granule
Into including：
150 weight portion of polaprezinc
380 weight portion of Mannitol
300 weight portion of carboxymethyl starch sodium
110 weight portion of Croscarmellose Sodium
40 weight portion of Povidone K 30
30% latex liquid of polymethacrylic resin, 66.7 weight portion
95% appropriate amount of ethanol.
3. the method for preparing the polaprezinc granule described in claim 1, it is characterised in that methods described includes following step
Suddenly：
1）The process of supplementary material
The supplementary material of recipe quantity is weighed, and is pulverized and sieved standby；
2）Premix
Polaprezinc, Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium are weighed by recipe quantity, take polaprezinc and
Mannitol carry out equivalent progressively increase mixing 2 times, obtain mixture；Take mixtureEquivalent carried out with carboxymethyl starch sodium progressively increase to mix
2 times, obtain mixture；Take mixtureEquivalent carried out with Croscarmellose Sodium progressively increase to mix 3 times；
3）Pelletize, be dried
Povidone K 30 is weighed by recipe quantity, 95% ethanol of about 350 weight portions is dissolved in；Resulting solution is uniformly sprayed onto step
1）Gained mixed powder, sprinkling, while mixing；Again 30% latex liquid of polymethacrylic resin of recipe quantity is uniformly sprayed
Intermediate soft material is spread across, is sprayed, while mixing；Then spray 95% ethanol, 5 ~ 10 weight portion；Gained soft material is used
0.4mm aperture sieves bowl is extruded, and reuses spheronizator round as a ball；Gained granule is added in heated-air circulation oven, in 55 ~ 65 DEG C of dryings
2% is less than to loss on drying；
4）Screening, granulate
By dried granule respectively with 30 mesh and 40 mesh sieves, below 30 mesh sieves and granules more than 40 mesh sieves are collected, will
Granules more than 30 mesh sieves collects below 30 mesh sieves and granules more than 40 mesh sieves with 32 mesh sieve granulate；
5）Total mixed, subpackage
Polaprezinc midbody particle obtained in step 4 is mixed, subpackage, obtains final product after the assay was approved.
4. preparation method according to claim 3, it is characterised in that step 1 crosses 200 mesh sieves after polaprezinc is crushed,
Mannitol, carboxymethyl starch sodium, Croscarmellose Sodium cross 80 mesh sieves after crushing.
5. preparation method according to claim 3, it is characterised in that step 1 is by polaprezinc micronization, Mannitol, carboxylic
Methyl starch sodium, Croscarmellose Sodium cross 80 mesh sieves after crushing.
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| Application Number | Priority Date | Filing Date | Title |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111196837A (en) * | 2018-11-20 | 2020-05-26 | 皕达生物科技(上海)有限公司 | Preparation method of polaprezinc and polaprezinc preparation |
| CN113769059A (en) * | 2021-09-10 | 2021-12-10 | 北京鑫开元医药科技有限公司 | Popregnen zinc granules and preparation method thereof |
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| CN103120646A (en) * | 2011-11-21 | 2013-05-29 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
| CN105025888A (en) * | 2013-02-22 | 2015-11-04 | 志瑞亚新药工业株式会社 | Enteric coated tablet |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111196837A (en) * | 2018-11-20 | 2020-05-26 | 皕达生物科技(上海)有限公司 | Preparation method of polaprezinc and polaprezinc preparation |
| CN111196837B (en) * | 2018-11-20 | 2023-07-28 | 皕达生物科技(上海)有限公司 | Preparation method of polyprenone and polyprenone preparation |
| CN113769059A (en) * | 2021-09-10 | 2021-12-10 | 北京鑫开元医药科技有限公司 | Popregnen zinc granules and preparation method thereof |
| CN113769059B (en) * | 2021-09-10 | 2024-02-13 | 北京鑫开元医药科技有限公司 | Poly (zinc prasugrel) granule and preparation method thereof |
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