CN106511351A - Application of polaprezinc in preparing medicine for eradicating helicobacter pylori - Google Patents
Application of polaprezinc in preparing medicine for eradicating helicobacter pylori Download PDFInfo
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- CN106511351A CN106511351A CN201611227897.7A CN201611227897A CN106511351A CN 106511351 A CN106511351 A CN 106511351A CN 201611227897 A CN201611227897 A CN 201611227897A CN 106511351 A CN106511351 A CN 106511351A
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
Abstract
The invention provides application of polaprezinc in preparing medicine for eradicating helicobacter pylori. Clinical tests prove that polaprezinc has high helicobacter pylori resisting activity and can effectively inhibit the activity of helicobacter pylori, the bactericidal efficacy of polaprezinc and medicine concentration are in positive correlation, and polaprezinc can be used for preparing related medicines for treating gastritis, gastric ulcer, gastric cancer, dodecadactylitis, duodenal ulcer, duodenal cancer and other diseases closely related to helicobacter pylori.
Description
Technical field
The invention belongs to pharmaceutical technology field, more particularly to polaprezinc are in eliminating pylorus medicine is prepared
Using.
Background technology
Helicobacter pylori is the Gram's staining negative bacterium of a kind of one pole, many flagellums, end blunt circle, helically bent, is led to
Often parasitize in the slime layer of people's gastric pitss, gastric acid is neutralized by the ammonia of its urease decomposition generation, so as in Gastric colonization.
Helicobacter pylori secretes two kinds of toxin CagA and VacA, and wherein CagA can make the protein N FAT relevant with cell propagation live
Property, promote abnormal cell proliferation, and cause a series of inflammatory reactions, be acute and chronic gastritis and taste-blindness rate
Primary pathogenic event, it is also closely related with the generation of gastric cancer.At present, triple therapy is clinically generally adopted international standards to pylorus
Helicobacter infection is treated, will bismuth, metronidazole and tetracycline or ampicillin combination, helicobacter pylori eradication rate
For 50-90%, the therapy large side effects, while the generation of helicobacter pylori persister may be caused, so as to further increase
Treatment difficulty, in addition, helicobacter pylori can form the L of Cell Wall Deficient under the induction of antibiotic and internal unfavorable factor
Type, this is also easy one of principal element of recurrence after clinically Helicobacter pylori infection is cured.Therefore, find one kind more to increase
Effect, safety helicobacter pylori resistant novel drugs it is very necessary.
Polaprezinc is the chelate of zinc and N-BETA-Alanyl-L-histidine, and N-BETA-Alanyl-L-histidine is the preferable transporter of zinc, by increasing capacitance it is possible to increase zinc is in vivo
Absorption and metabolism, it has antiinflammatory and antioxidative function concurrently, causes stomach to ethanol, acetic acid, hydrochloric acid and NSAID (non-steroidal anti-inflammatory drug) etc.
Mucosa injury has significant protection and repair.Prior art discloses the reasons such as many polaprezincs treatment gastric acid are unbalance
The technology of caused digestive tract ulcer, such as CN201310227401.6 disclose a kind of Polaprezinc compound, by sticking to
The impaired place of mucosa, improves effect of mucosal defense effect.But the not open polaprezinc of prior art is suppressing and is eradicating
Purposes on helicobacter pylori.
The content of the invention
The invention provides application of the polaprezinc in eliminating pylorus medicine is prepared.
Further, the medicine is used to treat the disease that helicobacter pylori causes.
Further, the disease includes gastritis, gastric ulcer, gastric cancer, duodenitis, duodenal ulcer and 12 fingers
Intestinal cancer.
Present invention also offers a kind of preparation, including polaprezinc and pharmaceutical carrier.
Further, the preparation includes but is not limited to capsule, granule, tablet, oral liquid or pellet preparations.
Further, the preparation is preferably tablet, and the tablet is mainly 1 by ratio of weight and number：The poly- Puri of 14-20
Zinc and pharmaceutical carrier are prepared from.
Further, the pharmaceutical carrier includes each composition of following parts by weight：
Using pregelatinized starch, pulullan polysaccharide, hydroxyethylmethyl-cellulose, polymethacrylate resin, lactose, wine
The tablet that stone acid potassium sodium and polaprezinc are prepared together can extend its action time in digestive tract, improve therapeutic effect.
Further, each composition of the pharmaceutical carrier also including following parts by weight：
Sodium starch glycol 0.6-1
Chitose 0.3-0.8
Nicotiamide 0.1-0.2.
Sodium starch glycol, chitose and nicotiamide is added further to extend work of the tablet in digestive tract in tablets
With the time, extend the effective time of tablet in treatment, reduce one of composition, or change one of composition, tablet it is effective
Action time shortens.
Further, each composition of the pharmaceutical carrier also including following parts by weight：
Sucrose monolaurate 0.2-0.4
Methyl salicylate sodium 0.05-0.1.
Add sucrose monolaurate and methyl salicylate sodium to be remarkably improved the stability of tablet in tablets, reduce which
In a composition, or change one of composition, the stability of tablet declines.
The present invention also provides a kind of preparation method of tablet, comprises the steps：
S1. pulullan polysaccharide and hydroxyethylmethyl-cellulose are dissolved in the distilled water of 8 times of quality and mixed solution is obtained；
S2. mix with mixed solution after polaprezinc, pregelatinized starch being mixed homogeneously with polymethacrylate resin
In even, then drug particles are made after granulation, dry, granulate；
S4. drug particles are added with lactose, sodium potassium tartrate tetrahydrate and is mixed 10 minutes in mixer, then be placed in tablet machine
Tabletting can be prepared by tablet.
The invention provides application of the polaprezinc in eliminating pylorus medicine is prepared, clinical trial confirmation,
Polaprezinc has very strong anti Helicobacter pylori activity, can effectively suppress the activity of helicobacter pylori, and its sterilization
Efficiency, can be used to prepare for treating the closely related gastritis of helicobacter pylori, gastric ulcer, stomach into positive correlation with drug level
The related drugs of the diseases such as cancer, duodenitis, duodenal ulcer and duodenal carcinoma.
Specific embodiment
Embodiment 1
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Embodiment 2
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
The preparation method of the tablet comprises the steps：
S1. pulullan polysaccharide and hydroxyethylmethyl-cellulose are dissolved in the distilled water of 8 times of quality and mixed solution is obtained；
S2. mix with mixed solution after polaprezinc, pregelatinized starch being mixed homogeneously with polymethacrylate resin
In even, then drug particles are made after granulation, dry, granulate；
S4. drug particles are added with lactose, sodium potassium tartrate tetrahydrate and is mixed 10 minutes in mixer, then be placed in tablet machine
Tabletting can be prepared by tablet.
Embodiment 3
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Embodiment 4
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Embodiment 5
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Embodiment 6
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Embodiment 7
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 1
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 2
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 3
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 4
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 5
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Reference examples 6
A kind of tablet, the weight for preparing each composition needed for 100 tablets are as follows：
Experimental technique used in following tests if no special instructions, is conventional method；Reagent used, biological material
Material etc., if no special instructions, commercially obtains.
Polaprezinc treatment or the effect test of eliminating pylorus
1. strains tested
Helicobacter pylori reference culture selects NCTC11637, NCTC11637 is uniformly inoculated in containing 8% de- fiber
In Colombia's blood agar culture-medium of Sanguis caprae seu ovis, using pumping ventilation, in 37 DEG C, micro- oxygen (5%O2, 10%CO2And 85%N2)
Under conditions of cultivate 2-3d, then collect antibacterial, Jing smear Gram’s staining, oxidase, catalase and urease are accredited as the positive
Afterwards, the Colombia's blood agar culture-medium containing 8% de- fiber Sanguis caprae seu ovis is coated again, in 37 DEG C, micro- oxygen (5%O2, 10%CO2
And 85%N2) under conditions of cultivate 2-3d, obtained strains are used as reference culture；
Helicobacter pylori clinical strains are taken from the positive chronic gastritiss of helicobacter pylori or Peptic Ulcers
Gastric mucosa tissue, abundant homogenate is spread evenly across helicobacter pylori selective medium, trains under 37 DEG C of micro- aerobic environments
Foster 3-5d, then collects antibacterial, and Jing smear Gram’s staining, after oxidase, catalase and urease are accredited as the positive, is coated with again
In the Colombia's blood agar culture-medium containing 8% de- fiber Sanguis caprae seu ovis, in 37 DEG C, micro- oxygen (5%O2, 10%CO2And 85%N2)
Under the conditions of cultivate 2-3d, obtained strains are used as clinical strains.
2. the measure of minimum inhibitory concentration
Configuration polaprezinc concentration is respectively 10.0,8.0,6.0,5.0,4.0,3.5,3.0,2.5,2.0,1.5,1.0,
The pastille agar plate of 0.5 and 0.25 μ g/mL；Respectively will be helicobacter pylori reference culture and 5 groups of helicobacter pylori clinical
Bacterial strain (Hp01, Hp02, Hp03, Hp04, Hp05) is diluted to 3 × 10 using brain heart spinal fluid8Cfu/ml, takes 1 μ of bacterium solution after dilution
L is inoculated in the pastille agar plate of said medicine concentration respectively, and while is inoculated in without medicine culture medium as control；After inoculation
In 37 DEG C, micro- oxygen (5%O2, 10%CO2And 85%N2) under conditions of cultivate 72h after observe result, occur without the fine jade of bacterium colony completely
The polaprezinc concentration of fat plate is minimum inhibitory concentration (MIC) of the polaprezinc to the bacterial strain, the results are shown in Table 1.
MIC value (μ g/mL) of 1 polaprezinc of table to helicobacter pylori reference culture and clinical strains
From the above results：Polaprezinc is equal to the reference culture NCTC11637 and clinical strains of helicobacter pylori
With significant fungistatic effect, 0.5 μ is to the MIC value of the reference culture NCTC11637 and clinical strains of helicobacter pylori
G/mL, its effective dose are less than clinical medicine dose.
3. Evaluation of Germicidal Efficacy
Arrange blank control group test and 3 groups of medicine bactericidal assay (0.5MIC drug level groups, 1MIC drug level groups,
2MIC drug level groups), blank control group is directly to adopt volume ratio for 9:1 brucella broth is made with the mixed liquor of hyclone
For test solution, 0.5MIC drug level groups, 1MIC drug level groups, 2MIC drug level groups are to add polaprezinc respectively
Volume ratio is 9:The test solution of different pharmaceutical concentration is configured in 1 brucella broth and the mixed liquor of hyclone；Collect new
The reference culture NCTC11637 of the helicobacter pylori of fresh culture is 9 in volume ratio:1 brucella broth is mixed with hyclone
Concentration is made in liquid for 1 × 106The bacteria suspension of cfu/ml, adds 100 μ L of bacteria suspension in the test solution of 4 groups of tests, mix
After be placed in constant temperature shake bed in 37 DEG C, micro- oxygen (5%O2, 10%CO2And 85%N2) under conditions of shaking culture；Prepare some cloth
Family name's broth dilution test tube, takes the 100 μ L of mother solution of bacterium solution of 4 groups of tests Jing after several times dilution, takes 100 μ L respectively at 0,4,8,24h
Diluent is inoculated in Columbia Blood Agar culture dish, is placed in constant incubator, in 37 DEG C, micro- oxygen (5%O2, 10%CO2With
85%N2) in the environment of cultivate 72h after do colony counting and draw the clump count of Each point in time according to extension rate conversion, meter
Calculate the sterilizing rate of the polaprezinc in Each point in time of variable concentrations, sterilizing rate=(blank control group clump count-medicine group bacterium
Fall number)/blank control group clump count × 100%, the results are shown in Table 2.
Sterilizing rate (%) of the polaprezinc of 2 variable concentrations of table in Each point in time
| Time (h) | 0.5MIC | 1MIC | 2MIC |
| 4 | 94.22 | 99.92 | 100 |
| 8 | 98.35 | 100 | 100 |
| 24 | 100 | 100 | 100 |
From the above results, polaprezinc has a significant bactericidal action to helicobacter pylori, and germicidal efficiency with
Drug level is directly proportional, and drug level is bigger, works faster, and bactericidal effect is better, when drug level is 0.5MIC values, 24h
Sterilizing rate can reach 100%；When drug level is 1MIC values, the sterilizing rate of 8h has reached 100%；Work as drug level
For 2MIC values when, the sterilizing rate of 4h has just reached 100%.
Comparison examination of the medicine of polaprezinc and other treatment helicobacter pylori in eliminating pylorus effect
Test
Collect the reference culture NCTC11637 of the helicobacter pylori of fresh cultured, in volume ratio be 9:1 brucella broth
It is 1 × 10 with concentration is made in hyclone mixed liquor6The bacteria suspension of cfu/ml, arranges test 1-4 and contrast test, tests 1-
Polaprezinc, tetracycline, ampicillin, first nitre file are added in bacteria suspension, to having a competition by 4 respectively according to the concentration of 0.5 μ g/mL
Medicine is added without in the bacteria suspension tested, and the bacterium solution that each group is tested is placed in into constant temperature and bed is shaken in 37 DEG C, micro- oxygen (5%O2、
10%CO2And 85%N2) under conditions of shaking culture；Prepare some brucella broth dilution test tubes, 4 groups are taken respectively at 0,4,8,24h
The 100 μ L of mother solution of the bacterium solution of test Jing after several times dilution take 100 μ L diluents and are inoculated in Columbia Blood Agar culture dish,
Constant incubator is placed in, in 37 DEG C, micro- oxygen (5%O2, 10%CO2And 85%N2) in the environment of cultivate 72h after do colony counting simultaneously
The clump count of Each point in time is drawn according to extension rate conversion, sterilizing rate of the different pharmaceutical in Each point in time is calculated, is killed
Bacterium rate=(contrast test group clump count-test group clump count)/contrast test group clump count × 100%, the results are shown in Table 3.
Sterilizing rate (%) of 3 different pharmaceutical of table in Each point in time
| Time (h) | Polaprezinc | Tetracycline | Ampicillin | First nitre is filed |
| 4 | 99.3 | 86.1 | 91.7 | 63.2 |
| 8 | 100 | 95.2 | 97.5 | 80.8 |
| 24 | 100 | 99.4 | 100 | 89.3 |
From the above results, polaprezinc has very strong anti Helicobacter pylori activity, in identical drug level
Under the conditions of, polaprezinc suppresses the ability of helicobacter pylori activity to be better than tetracycline, ampicillin and first nitre file.
Tablet delivery evaluation in vivo
Take the embodiment of the present invention 3, the tablet of embodiment 5, reference examples 1-4 respectively, put in medicament dissolution instrument, in 1h, 2h,
4h, 6h, 12h, 16h, 24h are separately sampled, detect tablet dissolution percentage rate with high performance liquid chromatography, and calculate the accumulation of tablet
Release percentage rate, the results are shown in Table 4.
Cumulative release percentage rate (%) result of the test of 4 tablet of table
| Time (h) | Embodiment 3 | Embodiment 6 | Reference examples 1 | Reference examples 2 | Reference examples 3 | Reference examples 4 |
| 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 1 | 41 | 20 | 47 | 52 | 36 | 40 |
| 2 | 68 | 33 | 69 | 75 | 60 | 65 |
| 4 | 87 | 48 | 93 | 98 | 82 | 85 |
| 6 | 92 | 58 | 100 | 100 | 90 | 92 |
| 12 | 100 | 72 | -- | -- | 100 | 100 |
| 16 | -- | 90 | -- | -- | -- | -- |
| 24 | -- | 100 | -- | -- | -- | -- |
From above-mentioned result of the test, the tablet that the embodiment of the present invention 3 is provided can continue slowly to discharge in 12h, and
Just release is finished the tablet that reference examples 1 and reference examples 2 are provided completely in the 6h, illustrate tablet that the present invention is provided can extend its
Action time in digestive tract, improve therapeutic effect.
The tablet that the embodiment of the present invention 5 is provided can continue slow release in 24h, and embodiment 3, reference examples 3 and right
4 tablets for providing just discharge completely in 12h and finish as usual, illustrate to add sodium starch glycol, chitose and cigarette in tablets
Amide can further extend action time of the tablet in digestive tract, extend the effective time of tablet in treatment, reduce one of them
Composition, or change one of composition, shorten the action time of tablet.
Tablet stability is evaluated
1. accelerated test
The tablet of Example 3, embodiment 7, reference examples 5-6, at 40 DEG C ± 2 DEG C of temperature, relative humidity is 75%
Under conditions of ± 5% place 6 months, 1 month during testing, 2 months, 3 months, 6 the end of month it is separately sampled once, detection lug
The character of agent, color and luster, abnormal smells from the patient, main constituent content (labelled amount %) and moisture, as a result find, the items of the tablet of embodiment 7 refer to
Mark has no significant change；And there is the phenomenon that moisture increases and darkens in the tablet of embodiment 3 and reference examples 5-6.
2. long term test
The tablet of Example 3, embodiment 7, reference examples 5-6, at 25 DEG C ± 2 DEG C of temperature, relative humidity is 60%
Place 12 months under conditions of ± 10%, 0 month during testing, 3 months, 6 months, 9 months, 12 the end of month separately sampled one
It is secondary, detect the character of tablet, color and luster, main constituent content (labelled amount %) and moisture, as a result find, the tablet of embodiment 7 it is each
Item index has no significant change；And there is different degrees of moisture and increases and color in the tablet of embodiment 3 and reference examples 5-6
Deepen phenomenon.
Knowable to the result of above-mentioned accelerated test and long term test, sucrose monolaurate and salicylic acid are added in tablets
Methyl ester sodium is remarkably improved the stability of tablet, reduces one of composition, or changes one of composition, the stability of tablet
Decline.
Finally it should be noted that above example is only to illustrate technical scheme and unrestricted, although reference
Preferred embodiment has been described in detail to the present invention, it will be understood by those within the art that, can be to the present invention's
Technical scheme is modified or equivalent, and without deviating from the spirit and scope of technical solution of the present invention, which all should be covered
In the middle of scope of the presently claimed invention.
Claims (10)
1. application of the polaprezinc in eliminating pylorus medicine is prepared.
2. application according to claim 1, it is characterised in that the medicine is used to treat the disease that helicobacter pylori causes
Disease.
3. application according to claim 2, it is characterised in that the disease includes gastritis, gastric ulcer, gastric cancer, 12 fingers
Enteritis, duodenal ulcer and duodenal carcinoma.
4. a kind of preparation, it is characterised in that：The preparation includes polaprezinc and pharmaceutical carrier.
5. preparation according to claim 4, it is characterised in that：The preparation is tablet, and the tablet is mainly by weight portion
Number is than being 1：The polaprezinc and pharmaceutical carrier of 14-20 is prepared from.
6. preparation according to claim 5, it is characterised in that：The pharmaceutical carrier include following parts by weight it is each into
Point：
7. preparation according to claim 6, it is characterised in that：The pharmaceutical carrier also including following parts by weight it is each into
Point：
Sodium starch glycol 0.6-1
Chitose 0.3-0.8
Nicotiamide 0.1-0.2.
8. preparation according to claim 6, it is characterised in that：The pharmaceutical carrier also including following parts by weight it is each into
Point：
Sucrose monolaurate 0.2-0.4
Methyl salicylate sodium 0.05-0.1.
9. the preparation method of preparation described in a kind of claim 6, methods described comprise the steps：
S1. pulullan polysaccharide and hydroxyethylmethyl-cellulose are dissolved in the distilled water of 8 times of quality and mixed solution is obtained；
S2. in mixing homogeneously with mixed solution after polaprezinc, pregelatinized starch being mixed homogeneously with polymethacrylate resin,
Drug particles are made after granulation, dry, granulate again；
S4. drug particles are added with lactose, sodium potassium tartrate tetrahydrate and is mixed 10 minutes in mixer, then be placed in tabletting in tablet machine
Can be prepared by tablet.
10. application of the preparation described in any one of claim 4-8 in eliminating pylorus medicine is prepared.
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| CN201611227897.7A CN106511351B (en) | 2016-12-27 | 2016-12-27 | Application of polaprezinc in preparation of anti-helicobacter pylori medicines |
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| CN201611227897.7A CN106511351B (en) | 2016-12-27 | 2016-12-27 | Application of polaprezinc in preparation of anti-helicobacter pylori medicines |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110917201A (en) * | 2019-12-02 | 2020-03-27 | 吉林省博大伟业制药有限公司 | Application of polaprezinc in preparation of medicine for treating atrophic gastritis with gastric mucosal epithelial dysplasia |
| CN110974833A (en) * | 2019-12-02 | 2020-04-10 | 吉林省博大伟业制药有限公司 | Medical application of medicine for treating atrophic gastritis by applying polaprezinc alone |
| CN111388482A (en) * | 2020-04-20 | 2020-07-10 | 吉林省博大伟业制药有限公司 | Application of polaprezinc in preparation of medicine for enhancing sensitivity of helicobacter pylori to antibiotics |
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|---|---|---|---|---|
| CN110917201A (en) * | 2019-12-02 | 2020-03-27 | 吉林省博大伟业制药有限公司 | Application of polaprezinc in preparation of medicine for treating atrophic gastritis with gastric mucosal epithelial dysplasia |
| CN110974833A (en) * | 2019-12-02 | 2020-04-10 | 吉林省博大伟业制药有限公司 | Medical application of medicine for treating atrophic gastritis by applying polaprezinc alone |
| CN111388482A (en) * | 2020-04-20 | 2020-07-10 | 吉林省博大伟业制药有限公司 | Application of polaprezinc in preparation of medicine for enhancing sensitivity of helicobacter pylori to antibiotics |
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