CN106511351B - Application of polaprezinc in preparation of anti-helicobacter pylori medicines - Google Patents
Application of polaprezinc in preparation of anti-helicobacter pylori medicines Download PDFInfo
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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
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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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Abstract
Clinical tests prove that the polyprenyl zinc has strong activity of resisting the helicobacter pylori, can effectively inhibit the activity of the helicobacter pylori, has positive correlation between the sterilization efficiency and the concentration of the medicament, and can be used for resisting related medicaments for treating diseases such as gastritis, gastric ulcer, gastric cancer, duodenitis, duodenal ulcer, duodenal cancer and the like closely related to the helicobacter pylori.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of polaprezinc in preparation of a helicobacter pylori resistant medicine.
Background
Helicobacter pylori is a gram-negative bacterium with monopole, multiple flagella, blunt-end and spiral bend, usually parasitizes in the mucus layer of the human stomach, and neutralizes gastric acid by ammonia generated by the decomposition of urease, thereby planting in the stomach. Helicobacter pylori secretes two toxins, namely CagA and VacA, wherein the CagA can activate NFAT (protein NFAT) related to cell proliferation, promote abnormal cell proliferation and cause a series of inflammatory reactions, and the toxins are the main pathogenic causes of acute and chronic gastritis and gastric and duodenal ulcers and are closely related to the occurrence of gastric cancer. At present, the international standard triple therapy is generally adopted clinically to treat the helicobacter pylori infection, namely bismuth, metronidazole and tetracycline or ampicillin are combined, the eradication rate of the helicobacter pylori is 50-90%, the therapy has great side effect and can cause the generation of helicobacter pylori drug-resistant strains, thereby further increasing the treatment difficulty, in addition, the helicobacter pylori can form an L type with cell wall defect under the induction of antibiotics and in-vivo adverse factors, and the L type is also one of the main factors which are easy to relapse after the helicobacter pylori infection is cured clinically. Therefore, it is necessary to find a new drug against helicobacter pylori, which is more efficient and safer.
The polyprenyl zinc is a chelate of zinc and L-carnosine, the L-carnosine is an ideal transporter of zinc, can increase the absorption and metabolism of zinc in vivo, has the functions of anti-inflammation and antioxidation, and has remarkable protection and repair effects on gastric mucosa injury caused by alcohol, acetic acid, hydrochloric acid, non-steroidal anti-inflammatory drugs and the like. The prior art discloses a plurality of techniques for treating digestive tract ulcer caused by gastric acid imbalance and the like by using polyprenyl zinc, for example, CN201310227401.6 discloses a polyprenyl zinc compound which is adhered to a damaged part of a mucous membrane to improve the efficacy of the defense effect of the mucous membrane. However, the prior art does not disclose the use of polyprenyl zinc for inhibiting and combating helicobacter pylori.
Disclosure of Invention
The invention provides an application of polaprezinc in preparing a helicobacter pylori resistant medicament.
Further, the medicine is used for treating diseases caused by helicobacter pylori.
Further, the diseases include gastritis, gastric ulcer, gastric cancer, duodenitis, duodenal ulcer and duodenal cancer.
The invention also provides a preparation which comprises the polaprezinc and a medicinal carrier.
Further, the preparation includes, but is not limited to, capsule, granule, tablet, oral liquid or pellet preparation.
Further, the preparation is preferably a tablet, and the tablet is prepared by mixing the following components in parts by weight of 1: 14-20 of polaprezinc and a medicinal carrier.
Further, the medicinal carrier comprises the following components in parts by weight:
the tablet prepared by adopting the pregelatinized starch, the pullulan, the hydroxyethyl methylcellulose, the polymethacrylic resin, the lactitol, the sodium potassium tartrate and the polaprezinc can prolong the action time of the tablet in the digestive tract and improve the treatment effect.
Further, the medicinal carrier also comprises the following components in parts by weight:
starch sodium glycolate 0.6-1
0.3-0.8% of chitose
0.1-0.2 of nicotinamide.
The addition of sodium starch glycolate, chitose and nicotinamide to the tablet can further prolong the action time of the tablet in digestive tract, prolong the effective duration of the tablet treatment, reduce one of the components, or change one of the components, so that the effective action time of the tablet is shortened.
Further, the medicinal carrier also comprises the following components in parts by weight:
sucrose monolaurate 0.2-0.4
0.05-0.1 part of sodium methyl salicylate.
The addition of sucrose monolaurate and sodium methyl salicylate to the tablet can significantly improve the stability of the tablet, reduce one of the components, or change one of the components, thus reducing the stability of the tablet.
The invention also provides a preparation method of the tablet, which comprises the following steps:
s1, dissolving pullulan polysaccharide and hydroxyethyl methyl cellulose in distilled water with the mass of 8 times that of the pullulan polysaccharide and the hydroxyethyl methyl cellulose to prepare a mixed solution;
s2, uniformly mixing the polyprenyl zinc, the pregelatinized starch and the polymethacrylic resin, uniformly mixing with the mixed solution, and granulating, drying and finishing to prepare medicine granules;
s4, adding the medicine particles, the lactitol and the sodium potassium tartrate into a mixer, mixing for 10 minutes, and then putting the mixture into a tablet machine to perform tabletting so as to obtain the tablet.
Clinical tests prove that the polyprenyl zinc has strong activity of resisting the helicobacter pylori, can effectively inhibit the activity of the helicobacter pylori, has positive correlation between the sterilization efficiency and the concentration of the medicine, and can be used for preparing the related medicines for treating diseases such as gastritis, gastric ulcer, gastric cancer, duodenitis, duodenal ulcer, duodenal cancer and the like closely related to the helicobacter pylori.
Detailed Description
Example 1
A tablet, the weight of each component required for preparing 100 tablets is as follows:
example 2
A tablet, the weight of each component required for preparing 100 tablets is as follows:
the preparation method of the tablet comprises the following steps:
s1, dissolving pullulan polysaccharide and hydroxyethyl methyl cellulose in distilled water with the mass of 8 times that of the pullulan polysaccharide and the hydroxyethyl methyl cellulose to prepare a mixed solution;
s2, uniformly mixing the polyprenyl zinc, the pregelatinized starch and the polymethacrylic resin, uniformly mixing with the mixed solution, and granulating, drying and finishing to prepare medicine granules;
s4, adding the medicine particles, the lactitol and the sodium potassium tartrate into a mixer, mixing for 10 minutes, and then putting the mixture into a tablet machine to perform tabletting so as to obtain the tablet.
Example 3
A tablet, the weight of each component required for preparing 100 tablets is as follows:
example 4
A tablet, the weight of each component required for preparing 100 tablets is as follows:
example 5
A tablet, the weight of each component required for preparing 100 tablets is as follows:
example 6
A tablet, the weight of each component required for preparing 100 tablets is as follows:
example 7
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 1
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 2
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 3
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 4
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 5
A tablet, the weight of each component required for preparing 100 tablets is as follows:
comparative example 6
A tablet, the weight of each component required for preparing 100 tablets is as follows:
the experimental methods used in the following experiments are all conventional methods unless otherwise specified; the reagents, biological materials, etc. used are commercially available unless otherwise specified.
Test of Effect of Polyprim on therapy or prevention of helicobacter pylori
1. Test strains
Selecting standard strain of helicobacter pylori NCTC11637, inoculating NCTC11637 uniformly into Columbia blood agar medium containing 8% defibrinated sheep blood, and performing gas extraction and ventilation at 37 deg.C with micro-oxygen (5% O)2、10％CO2And 85% N2) Culturing for 2-3 days, collecting bacteria, determining to be positive by smear gram stain, oxidase, catalase and urease, coating on Columbia blood agar medium containing 8% defibrinated sheep blood, and culturing at 37 deg.C with micro-aerobic (5% O)2、10％CO2And 85% N2) Culturing for 2-3d under the condition of (1), and taking the obtained strain as a standard strain;
the helicobacter pylori clinical strain is prepared from gastric mucosa tissue of helicobacter pylori-positive chronic gastritis or peptic ulcer patient by homogenizing, uniformly coating on helicobacter pylori selective culture medium, culturing at 37 deg.C under microaerophilic environment for 3-5 days, collecting bacteria, performing gram staining by smear, oxidizing enzyme, sterilizing, and sterilizing,After positive identification of catalase and urease, the cells were again plated on Columbia blood agar medium containing 8% defibrinated sheep blood, and micro-aerobic (5% O) culture was performed at 37 deg.C2、10％CO2And 85% N2) Culturing for 2-3d under the condition of (1), and taking the obtained strain as a clinical strain.
2. Determination of minimum inhibitory concentration
Preparing a drug-containing agar plate with the concentration of the polyprenyl zinc of 10.0, 8.0, 6.0, 5.0, 4.0, 3.5, 3.0, 2.5, 2.0, 1.5, 1.0, 0.5 and 0.25 mug/mL respectively; respectively diluting helicobacter pylori standard strain and 5 groups of helicobacter pylori clinical strains (Hp01, Hp02, Hp03, Hp04 and Hp05) to 3 × 10 with cerebrospinal fluid8cfu/ml, respectively inoculating 1 μ L of diluted bacterial liquid into the drug-containing agar plates with the above drug concentration, and simultaneously inoculating into a drug-free culture medium as a control; micro-aerobic (5% O) at 37 ℃ after inoculation2、10％CO2And 85% N2) The result of observation after 72h of culture under the conditions of (1) is that the concentration of the polyprenyl zinc in the agar plate without bacterial colony is the Minimum Inhibitory Concentration (MIC) of the polyprenyl zinc to the strain, and the result is shown in Table 1.
TABLE 1MIC values (μ g/mL) of polaprezinc against standard and clinical strains of H.pylori
From the above results, it can be seen that: the polaprezinc has obvious bacteriostatic effect on the standard strain NCTC11637 and clinical strains of the helicobacter pylori, the MIC values of the standard strain NCTC11637 and the clinical strains of the helicobacter pylori are both 0.5 mu g/mL, and the effective dose of the polaprezinc is lower than the clinical medication dose.
3. Evaluation of Sterilization Effect
Setting a blank control group test and 3 groups of drug sterilization tests (0.5MIC drug concentration group, 1MIC drug concentration group and 2MIC drug concentration group), wherein the blank control group directly adopts the mixed solution of the Brookfield broth and the fetal bovine serum with the volume ratio of 9:1 as a test solution, and the 0.5MIC drug concentration group, the 1MIC drug concentration group and the 2MIC drug concentration group are respectively added with the polyprenum with the volume ratioPreparing test solutions with different drug concentrations in a mixed solution of 9:1 Brucella broth and fetal calf serum; collecting freshly cultured helicobacter pylori standard strain NCTC11637, and mixing with a 9:1 volume ratio of Brookfield broth and fetal bovine serum to obtain a mixture with a concentration of 1 × 106cfu/ml bacterial suspension, adding 100 μ L bacterial suspension into 4 groups of test solutions, mixing, placing in constant temperature shaking table at 37 deg.C and micro-oxygen (5% O)2、10％CO2And 85% N2) Culturing with shaking under the condition of (1); preparing several Brucella broth dilution test tubes, diluting 100 μ L of mother liquor of 4 groups of tested bacteria liquid at 0, 4, 8, and 24h, inoculating 100 μ L of diluted solution into Columbia blood agar culture dish, placing in constant temperature incubator at 37 deg.C and micro-oxygen (5% O)2、10％CO2And 85% N2) The bacterial colonies are counted after being cultured for 72 hours in the environment, the bacterial colony number of each time point is obtained according to the reduction of the dilution factor, the sterilization rate of the different concentrations of the polyprenyl at each time point is calculated, and the sterilization rate is (the bacterial colony number of the blank control group-the bacterial colony number of the medicine group)/the bacterial colony number of the blank control group multiplied by 100 percent, and the result is shown in table 2.
TABLE 2 Sterilization rates (%)
| Time (h) | 0.5MIC | 1MIC | 2MIC |
| 4 | 94.22 | 99.92 | 100 |
| 8 | 98.35 | 100 | 100 |
| 24 | 100 | 100 | 100 |
The results show that the polaprezinc has an obvious bactericidal effect on helicobacter pylori, the bactericidal efficiency is in direct proportion to the drug concentration, the higher the drug concentration is, the faster the effect is, the better the bactericidal effect is, and when the drug concentration is 0.5MIC value, the bactericidal rate in 24h can reach 100%; when the concentration of the medicine is 1MIC value, the sterilization rate of 8h reaches 100%; when the concentration of the medicine is 2MIC, the sterilization rate of 4h reaches 100 percent.
Comparative test of anti-helicobacter pylori effect of polaprezinc and other drugs for treating helicobacter pylori
Collecting freshly cultured helicobacter pylori standard strain NCTC11637, and preparing into 1 × 10 concentration mixture of Brookfield broth and fetal calf serum at volume ratio of 9:16cfu/mL bacterial suspension, setting tests 1-4 and comparison tests, wherein the tests 1-4 are respectively to add the polyprenyl zinc, the tetracycline, the ampicillin and the metronidazole according to the concentration of 0.5 mu g/mL into the bacterial suspension, the therapeutic drug is not added into the bacterial suspension of the comparison tests, and the bacterial liquid of each group of tests is placed in a constant temperature shaking table at 37 ℃ and micro-oxygen (5% O)2、10％CO2And 85% N2) Culturing with shaking under the condition of (1); preparing several Brucella broth dilution test tubes, diluting 100 μ L of mother liquor of 4 groups of tested bacteria liquid at 0, 4, 8, and 24h, inoculating 100 μ L of diluted solution into Columbia blood agar culture dish, placing in constant temperature incubator at 37 deg.C and micro-oxygen (5% O)2、10％CO2And 85% N2) Cultured for 72 hours in the environment of (1), and then counted according to the conversion of dilution timesThe number of colonies at each time point was counted, and the bactericidal rate of each drug at each time point was calculated as (number of colonies in comparative test group-number of colonies in test group)/number of colonies in comparative test group × 100%, and the results are shown in table 3.
TABLE 3 Sterilization rates (%)
| Time (h) | Poprenezinc | Tetracycline derivatives | Ampicillin | Nail nitre file |
| 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, it can be seen that polyprenyl has a strong anti-helicobacter pylori activity, and under the same drug concentration conditions, the ability of polyprenyl to inhibit the activity of helicobacter pylori is stronger than that of tetracycline, ampicillin and metronidazole.
Evaluation of in vitro Release degree of tablets
The tablets of example 3, example 5 and comparative examples 1 to 4 of the present invention were each sampled in a drug dissolution apparatus for 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours and 24 hours, and the dissolution percentage of the tablets was measured by high performance liquid chromatography, and the cumulative release percentage of the tablets was calculated, and the results are shown in Table 4.
Table 4 cumulative percent release (%) test results for tablets
| Time (h) | Example 3 | Example 6 | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 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 the above test results, it can be seen that the tablet provided by the present invention in example 3 can be released slowly within 12 hours, while the tablets provided by comparative examples 1 and 2 can be released completely within 6 hours, which indicates that the tablet provided by the present invention can prolong the acting time in the digestive tract and improve the therapeutic effect.
The tablet provided by the embodiment 5 of the invention can be released continuously and slowly within 24 hours, and the tablets provided by the embodiment 3, the comparison example 3 and the comparison example 4 are completely released within 12 hours, which shows that the action time of the tablet in the digestive tract can be further prolonged by adding the starch sodium glycolate, the chitose and the nicotinamide into the tablet, the effective duration of the tablet treatment can be prolonged, one of the ingredients can be reduced, or one of the ingredients can be changed, and the action time of the tablet can be shortened.
Evaluation of tablet stability
1. Accelerated test
Taking the tablets of the example 3, the example 7 and the comparative examples 5-6, placing the tablets for 6 months under the conditions that the temperature is 40 ℃ plus or minus 2 ℃ and the relative humidity is 75% + orminus 5%, sampling once respectively at the end of 1 month, 2 months, 3 months and 6 months during the test period, and detecting the properties, the color, the smell, the main component content (marked amount%) and the moisture of the tablets, wherein the results show that all indexes of the tablets of the example 7 have no obvious change; the tablets of example 3 and comparative examples 5 to 6, on the other hand, exhibited increased moisture content and increased color.
2. Long term test
Taking the tablets of the example 3, the example 7 and the comparative examples 5 to 6, placing the tablets at a temperature of 25 +/-2 ℃ and a relative humidity of 60 +/-10% for 12 months, sampling once at the end of 0 month, 3 months, 6 months, 9 months and 12 months during the test period, and detecting the properties, the color, the main component content (marked amount%) and the moisture of the tablets, wherein the results show that all indexes of the tablets of the example 7 have no obvious change; the tablets of example 3 and comparative examples 5 to 6, on the other hand, exhibited increased moisture content and color deepening.
From the results of the above accelerated test and the long-term test, it is known that the stability of the tablet is remarkably improved by adding sucrose monolaurate and sodium methyl salicylate to the tablet, and the stability of the tablet is reduced by reducing one of the components or changing one of the components.
Finally, it should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered by the claims of the present invention.
Claims (4)
1. A tablet characterized by: the tablet is mainly prepared from the following components in parts by weight of 1: 14-20 parts of polaprezinc and a medicinal carrier, wherein the medicinal carrier comprises the following components in parts by weight:
the tablet is prepared by the following steps:
s1, dissolving pullulan polysaccharide and hydroxyethyl methyl cellulose in distilled water with the mass of 8 times that of the pullulan polysaccharide and the hydroxyethyl methyl cellulose to prepare a mixed solution;
s2, uniformly mixing the polyprenyl zinc, the pregelatinized starch and the polymethacrylic resin, uniformly mixing with the mixed solution, and granulating, drying and finishing to prepare medicine granules;
s3, adding the medicine particles, the lactitol and the sodium potassium tartrate into a mixer, mixing for 10 minutes, and then putting the mixture into a tablet machine to perform tabletting so as to obtain the tablet.
2. The tablet of claim 1, wherein: the medicinal carrier also comprises the following components in parts by weight:
starch sodium glycolate 0.6-1
0.3-0.8% of chitose
0.1-0.2 of nicotinamide.
3. The tablet of claim 1, wherein: the medicinal carrier also comprises the following components in parts by weight:
sucrose monolaurate 0.2-0.4
0.05-0.1 part of sodium methyl salicylate.
4. Use of a tablet according to any one of claims 1 to 3 for the manufacture of a medicament against helicobacter pylori.
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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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| CN101854920A (en) * | 2007-10-19 | 2010-10-06 | 大塚制药株式会社 | Pharmaceutical solid preparation |
| JP2011001324A (en) * | 2009-06-22 | 2011-01-06 | Sawai Pharmaceutical Co Ltd | Polaprezinc-containing orally disintegrating tablet |
| CN102755332A (en) * | 2011-04-29 | 2012-10-31 | 上海医药工业研究院 | Asiatic acid salt tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPM456894A0 (en) * | 1994-03-18 | 1994-04-14 | Glyzinc Pharmaceuticals Limited | Treatment for gastric disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101854920A (en) * | 2007-10-19 | 2010-10-06 | 大塚制药株式会社 | Pharmaceutical solid preparation |
| JP2011001324A (en) * | 2009-06-22 | 2011-01-06 | Sawai Pharmaceutical Co Ltd | Polaprezinc-containing orally disintegrating tablet |
| CN102755332A (en) * | 2011-04-29 | 2012-10-31 | 上海医药工业研究院 | Asiatic acid salt tablet and preparation method thereof |
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| Title |
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| Effect of Z-103, a new antiulcer agent, on Helicobacter pylori. Antimicrobial, antiurease, and antiadhesive activities;Michio Sunairi et al.;《Jpn Pharmacol Ther》;19941231;第22卷(第9期);3771-3775 * |
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