CN102526049A - Compound diclofenac sodium slow-release preparation and preparation method thereof - Google Patents
Compound diclofenac sodium slow-release preparation and preparation method thereof Download PDFInfo
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- CN102526049A CN102526049A CN2012100246479A CN201210024647A CN102526049A CN 102526049 A CN102526049 A CN 102526049A CN 2012100246479 A CN2012100246479 A CN 2012100246479A CN 201210024647 A CN201210024647 A CN 201210024647A CN 102526049 A CN102526049 A CN 102526049A
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Abstract
The invention discloses a compound diclofenac sodium slow-release preparation and a preparation method of the compound diclofenac sodium slow-release preparation. The compound preparation consists of the following ingredients in percentage by mass: 20 to 30 percent of diclofenac sodium, 4 to 8 percent of omeprazole or sodium salt of the omeprazole and the balance of auxiliary materials allowed on the pharmacy. The preparation method of the compound preparation comprises the steps that: the diclofenac sodium and the omeprazole are respectively prepared into enteric granules or pellets, the prepared omeprazole enteric granules or pellets are mixed with the diclofenac sodium enteric granules or pellets, and the tabletting or the capsule filling is carried out. In compound diclofenac sodium enteric slow-release tablets or enteric slow-release capsules prepared by the preparation method, the medicine release of the main omeprazole medicine is carried out at the normal release speed, but the diclofenac sodium is slowly released from the preparation. Therefore, the omeprazole or the sodium salt of the omeprazole is firstly released for realizing the effect of protecting the gastrointestinal mucosa, the diclofenac sodium is prevented from irritating the gastrointestinal mucosa of a patient in the medicine release process, and the gastrointestinal tract adverse reaction occurrence rate of the diclofenac sodium is reduced.
Description
Technical field
The present invention relates to pharmaceutical product and preparation method thereof, specifically a kind of compound diclofenac natrium slow releasing preparation and preparation method thereof.
Background technology
Diclofenac sodium is that (Nonsteroidal Anti-inflammatory Drugs, NSAIDs), its analgesic activity is 2～2.5 times of indomethacin to third generation NSAID, is 26～50 times of aspirin.Be used to treat rheumatism, rheumatoid arthritis, scapulohumeral periarthritis clinically, injure the inflammation that operation causes outward.Though diclofenac sodium belongs to the higher NSAIDs medicine of clinical safety, still there is gastrointestinal side effect in it, uncomfortable like upper abdomen, feel sick, vomiting etc., gastrointestinal hemorrhage can appear when serious.Take diclofenac sodium for a long time, even can increase gastrointestinal ulceration risk of bleeding property.
Summary of the invention
The object of the invention will provide a kind of compound diclofenac natrium slow releasing preparation exactly, and a kind of method of making preparation is provided simultaneously, with the untoward reaction of effective minimizing diclofenac sodium.
The objective of the invention is to realize like this:
Compound diclofenac natrium slow releasing preparation provided by the present invention is made up of following component by mass percent:
The adjuvant that allows on the wherein said pharmaceutics comprises filler, binding agent, disintegrating agent, fluidizer, pH regulator agent, lubricant, enteric materials, isolated material, and wherein filler is selected from a kind of or wherein any two kinds mixture in starch, pre-paying starch, dextrin, cellulose, mannitol and the lactose; Binding agent is selected from a kind of or wherein any two kinds mixture in ethanol, starch slurry, dextrin slurry, sodium carboxymethylcellulose pyce and the polyvinylpyrrolidone; Disintegrating agent is selected from a kind of or wherein any two kinds mixture in starch, pre-paying starch, carboxymethyl starch sodium, microcrystalline Cellulose, hydroxypropyl cellulose and the methylcellulose; Lubricant is selected from magnesium stearate; Fluidizer is selected from Pulvis Talci or micropowder silica gel; Cosolvent is selected from a kind of in polyoxyethylene sorbitan monoleate and the poloxamer 188; The pH regulator agent is selected from sodium bicarbonate, sodium dihydrogen phosphate or calcium hydroxide; Enteric materials is selected from a kind of in acrylic resin, cellulose acetate phthalate ester, hypromellose phthalate ester, phthalic acid, hydroxypropyl emthylcellulose, diethyl phthalate, the Opadry or two kinds mixture wherein, and isolated material is selected from a kind of in ethyl cellulose, hydroxypropyl methyl fiber, cellulose acetate, diethyl phthalate, methyl methacrylate-EUDRAGIT S100 polyethylene, the polypropylene.
Surplus is the preferred mannitol of adjuvant, Pulvis Talci, 10% polyvinylpyrrolidone K30 solution, sodium dihydrogen phosphate, lactose or pre-paying starch, hydroxypropyl emthylcellulose, microcrystalline Cellulose, acrylic resin, the diethyl phthalate that allows on the pharmaceutics.
Compound diclofenac natrium slow releasing preparation provided by the present invention can be made into oral common formulations such as enteric coated tablet, enteric coated capsule, slow releasing tablet, slow releasing capsule.Can be used for various arthritic arthralgia symptoms such as rheumatoid arthritis, osteoarthritis, SpA, gouty arthritis, rheumatic arthritis.
The method for preparing of compound diclofenac natrium slow releasing preparation provided by the present invention, it may further comprise the steps:
A, take by weighing following component by mass percent:
Diclofenac sodium 25～35%; Omeprazole or its sodium salt 4～8%, mannitol 6～8.0%, Pulvis Talci 6～8.%, polyvinylpyrrolidone K301～2%, sodium dihydrogen phosphate 0.8～1.2%, lactose or pre-paying starch 8～12%, hydroxypropyl emthylcellulose 5～12%, microcrystalline Cellulose 15～25%, enteric materials 1.8～2.6%, isolated material 1.8～2.6%;
B, a is gone on foot the described polyvinylpyrrolidone K30 of operation, and to be mixed with quality be that 10% aqueous solution is subsequent use than concentration;
C, with diclofenac sodium and lactose or pre-paying starch, hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, be made into granule or micropill, dry back is subsequent use;
D, omeprazole or its sodium salt mix with mannitol, Pulvis Talci, sodium dihydrogen phosphate, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, are made into granule or micropill, and dry back is subsequent use;
E, use 95% ethanol or dehydrated alcohol respectively enteric materials, isolated material to be mixed with quality than casing solution and the sealing coat solution of concentration as 4-8%;
F, with sealing coat solution with diclofenac sodium granule or micropill coating after, reuse casing solution coating, it is subsequent use to make diclofenac sodium enteric coated particles or micropill;
G, with behind sealing coat solution omeprazole or its sodium salt granule or the micropill coating, reuse casing solution coating, it is subsequent use to make omeprazole enteric-coated granule or micropill;
H, the omeprazole enteric-coated granule that will prepare or micropill mix tabletting or encapsulated with diclofenac sodium enteric coated particles or micropill.
The preferred following component by mass percent of crude drug that the described a step takes by weighing:
Diclofenac sodium 28.5%; Omeprazole or its sodium salt 7.6%, mannitol 8.0%, Pulvis Talci 8.0%, polyvinylpyrrolidone K301.5%, sodium dihydrogen phosphate 1.2%, lactose 10.4%, hydroxypropyl emthylcellulose 5.0%, microcrystalline Cellulose 25%, enteric materials 2.4%, isolated material 2.4%.
Described enteric materials preferred acrylic resins II number, diethyl phthalate are the mixture of 100: 4～8 proportionings according to weight part ratio.
The preferred hydroxypropyl emthylcellulose of described isolated material.
The described h step can be that omeprazole enteric-coated granule of the omeprazole for preparing or micropill tabletting are formed ground floor, on the ground floor basis, presses diclofenac sodium enteric coated particles or micropill to obtain compound double-layer tablet again.
Compound diclofenac natrium enteric-coated sustained-release tablet or enteric-soluble controlled-release capsule that the inventive method is prepared, omeprazole principal agent wherein are to carry out release with routine release degree, and diclofenac sodium then slowly discharges from preparation.Omeprazole or its salt can at first discharge the gastrointestinal tract mucous effect of performance protection thus, thereby prevent that diclofenac sodium from drug release process moderate stimulation patient's gastrointestinal tract mucosa, having reduced the gastrointestinal side effect incidence rate of diclofenac sodium.
Medicine of the present invention can increase the compliance of patient's medication, reduces administration frequency.Administering mode can adopt oral, and 1 time on the one, or follow the doctor's advice, obey after the meal.
Description of drawings
Fig. 1 is omeprazole and the omeprazole enteric-coated commercially available release profiles comparison diagram in the compound diclofenac natrium slow releasing preparation provided by the present invention.Wherein :-◆-be the contained omeprazole curve chart of medicine of the present invention ,-■-be commercially available omeprazole curve chart.
Fig. 2 is the release profiles comparison diagram of its omeprazole of compound diclofenac natrium slow releasing preparation provided by the present invention and diclofenac sodium.Wherein :-◆-be the omeprazole curve ,-■-be the diclofenac sodium curve.
Beneficial effect of the present invention has obtained confirmation through following experiment.
Test method
Select 6～8 ages in week 180 of cleaning level SD rats, male and female half and half, body weight 200g ± 20g is divided into 3 groups at random: experimental group of the present invention 1, experimental group 2 and matched group, 60 every group.The sufficient sole of the foot intradermal injection complete Freund's adjuvant 0.1ml in a rat left side prepares adjuvant type arthritis model.Each group difference gastric infusion 10mg/kg.d is (by diclofenac sodium; Be equivalent to clinical dosage 100mg/d); Experimental group 1 is taken embodiment 1 drug prepared; Experimental group 2 is taken embodiment 2 drug prepared, and matched group is taken commercially available diclofenac sodium extended release capsule (Simcere Pharmaceutical Co., Ltd., product batch number 090518).Once a day, successive administration is put to death rat and is carried out index observation after 6 months.Observe the degree of impairment (ulcer, erosion, hemorrhage etc.) of gastrointestinal mucosa after untoward reaction (comprising gastrointestinal side effect and other untoward reaction such as diarrhoea, vomiting) and the drug withdrawal during the rat medication.Statistics takes place in the untoward reaction of each group sees table 1.
Table 1
The result shows that compare with commercially available diclofenac sodium extended release capsule, the present invention can significantly reduce the gastrointestinal side effect incidence rate and the gastrointestinal hemorrhage rate of diclofenac sodium period in a medicine.
Animal test results shows that pharmaceutical preparation of the present invention gives rat, and its gastrointestinal side effect incidence rate, gastrointestinal hemorrhage rate all are lower than matched group, and wherein the gastrointestinal side effect rate 5.0% of preferred formulation group is starkly lower than matched group 13.3%.
The specific embodiment
Below in conjunction with specific embodiment the present invention is done further explanation.
Embodiment 1:
A, take by weighing following component:
Diclofenac sodium 28.5g; Omeprazole 7.6g, mannitol 8.0g, Pulvis Talci 8.0g, polyvinylpyrrolidone K301.5g, sodium dihydrogen phosphate 1.2g, lactose 10.4g, hydroxypropyl emthylcellulose 5.0g, microcrystalline Cellulose 25g, enteric materials 2.4g, isolated material 2.4g.Wherein enteric materials is acrylic resin II number and diethyl phthalate, is 100: 4 blended mixture of proportioning according to weight part ratio.Isolated material is a hydroxypropyl emthylcellulose.
B, a is gone on foot the described polyvinylpyrrolidone K30 of operation, and to be mixed with quality be that 10% aqueous solution is subsequent use than concentration;
C, with diclofenac sodium and lactose, hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, be made into micropill, dry back is subsequent use;
D, omeprazole mix with mannitol, Pulvis Talci, sodium dihydrogen phosphate, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, are made into micropill, and dry back is subsequent use;
E, the 2.4g enteric materials is dissolved in 60g 95% ethanol; The 2.4g isolated material is dissolved in 60g 95% ethanol, obtains quality respectively and be 4% casing solution and sealing coat solution than concentration;
F, with isolate solution with the sodium dichlorophenolate micro-pill pharmaceutical coating after, reuse casing solution coating, it is subsequent use to make the diclofenac sodium enteric-coated pellet;
After g, usefulness are isolated solution Omeprazole Pellets coating, reuse casing solution coating, it is subsequent use to make omeprazole enteric-coated micro-pill;
H, the omeprazole enteric-coated micro-pill for preparing is mixed with the diclofenac sodium enteric-coated pellet, filled capsules, being prepared into specification is the compound diclofenac natrium enteric-soluble controlled-release capsule agent of every of omeprazole 20mg/ diclofenac sodium 75mg/.
Embodiment 2:
A, take by weighing following component:
Diclofenac sodium 28.5g; Omeprazole 7.6g, mannitol 6.0g, Pulvis Talci 8.0g, polyvinylpyrrolidone K302g, sodium dihydrogen phosphate 1.2g, starch 12g, hydroxypropyl emthylcellulose 12g, microcrystalline Cellulose 19.1g, enteric materials 1.8g, isolated material 1.8g.Wherein enteric materials is acrylic resin II number and diethyl phthalate, is 100: 8 blended mixture of proportioning according to weight part ratio.Isolated material is a hydroxypropyl emthylcellulose.
B, a is gone on foot the described polyvinylpyrrolidone K30 of operation, and to be mixed with quality be that 10% aqueous solution is subsequent use than concentration;
C, with diclofenac sodium and starch, hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, be made into granule, dry back is subsequent use;
D, omeprazole mix with mannitol, Pulvis Talci, sodium dihydrogen phosphate, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, are made into granule, and dry back is subsequent use;
E, to use 95% ethanol that enteric materials, isolated material are mixed with quality respectively be 10% casing solution and sealing coat solution than concentration;
F, with isolate solution with the diclofenac sodium granule coating after, reuse casing solution coating, it is subsequent use to make the diclofenac sodium enteric coated particles;
After g, usefulness are isolated solution omeprazole granules coating, reuse casing solution coating, it is subsequent use to make omeprazole enteric-coated granule;
H, the omeprazole enteric-coated granule tabletting that will prepare form ground floor, on the ground floor basis, press the diclofenac sodium enteric coated particles to obtain the compound diclofenac natrium sustained-release double-layer tablet again.Its specification is every of omeprazole 20mg/ diclofenac sodium 75mg/
Embodiment 3
A, take by weighing following component:
Diclofenac sodium 35g; Omeprazole sodium salt 4.2g, mannitol 7g, Pulvis Talci 8.0g, polyvinylpyrrolidone K302g, sodium bicarbonate 1.2g, pre-paying starch 10g, magnesium stearate 2g, carboxymethyl starch sodium 12, microcrystalline Cellulose 15g, enteric materials 1.8g, isolated material 1.8g.Wherein enteric materials be acrylic resin II number with diethyl phthalate, polysorbate, be 100: 8: 2 blended mixture of proportioning according to weight part ratio.Isolated material is a hydroxypropyl emthylcellulose.
B, a is gone on foot the described polyvinylpyrrolidone K30 of operation, and to be mixed with quality be that 10% aqueous solution is subsequent use than concentration;
C, with diclofenac sodium and pre-paying starch methyl starch sodium, microcrystalline Cellulose mix homogeneously, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, be made into granule, dry back adding magnesium stearate is subsequent use;
D, omeprazole sodium salt mix with mannitol, Pulvis Talci, sodium bicarbonate, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, are made into granule, and dry back is subsequent use;
E, to use 95% ethanol that enteric materials, isolated material are mixed with quality respectively be 5% casing solution and sealing coat solution than concentration;
F, with isolate solution with the diclofenac sodium granule coating after, reuse casing solution coating, it is subsequent use to make the diclofenac sodium enteric coated particles;
G, with isolate solution with the omeprazole granules coating after, reuse casing solution coating, it is subsequent use to make omeprazole enteric-coated granule;
H, the omeprazole enteric-coated granule that will prepare mix with the diclofenac sodium enteric coated particles, and tabletting is processed the compound diclofenac natrium slow releasing tablet.
Embodiment 4 release degree tests (1)
Get the prepared compound diclofenac natrium slow releasing tablet of embodiment 1 and omeprazole enteric-coated commercially available (Jiangsu Lianhuan Pharmaceutical Co., Ltd.; Lot number 090603); With phosphate buffer (pH6.8) is medium, and according to the test of Chinese Pharmacopoeia method degree of release, result of the test is seen Fig. 1.
The result shows that the omeprazole in the medicine of the present invention is basic identical with omeprazole enteric-coated commercially available release profiles, explain its contained diclofenac sodium of the prepared compound diclofenac natrium slow releasing tablet of the present invention to the release of omeprazole less than interference.
Embodiment 5 release degree tests (2)
Getting the prepared compound diclofenac natrium slow releasing tablet of embodiment 2, is medium with phosphate buffer (pH6.8), and according to the test of Chinese Pharmacopoeia method degree of release, result of the test is seen Fig. 2.
As shown in Figure 2, but the rapid release of the omeprazole in the medicine of the present invention (its release degree can reach more than 80% at short notice), and the release degree of each time point all is higher than diclofenac sodium.
Claims (8)
1. compound diclofenac natrium slow releasing preparation is characterized in that this compound preparation is made up of following component by mass percent:
Diclofenac sodium 20 ~ 30%, omeprazole or its sodium salt 4 ~ 8%, surplus is the adjuvant that allows on the pharmaceutics.
2. compound diclofenac natrium slow releasing preparation according to claim 1; It is characterized in that the adjuvant that allows on the described pharmaceutics comprises filler, binding agent, disintegrating agent, fluidizer, pH regulator agent, lubricant, enteric materials, isolated material, wherein filler is selected from a kind of or wherein any two kinds mixture in starch, pre-paying starch, dextrin, cellulose, mannitol and the lactose; Binding agent is selected from a kind of or wherein any two kinds mixture in ethanol, starch slurry, dextrin slurry, sodium carboxymethylcellulose pyce and the polyvinylpyrrolidone; Disintegrating agent is selected from a kind of or wherein any two kinds mixture in starch, pre-paying starch, carboxymethyl starch sodium, microcrystalline Cellulose, hydroxypropyl cellulose and the methylcellulose; Lubricant is selected from magnesium stearate; Fluidizer is selected from Pulvis Talci or micropowder silica gel; Cosolvent is selected from a kind of in polyoxyethylene sorbitan monoleate and the poloxamer 188; The pH regulator agent is selected from sodium bicarbonate, sodium dihydrogen phosphate or calcium hydroxide; Enteric materials is selected from a kind of in acrylic resin, cellulose acetate phthalate ester, hypromellose phthalate ester, phthalic acid, hydroxypropyl emthylcellulose, diethyl phthalate, the Opadry or two kinds mixture wherein, and isolated material is selected from a kind of in ethyl cellulose, hydroxypropyl methyl fiber, cellulose acetate, diethyl phthalate, methyl methacrylate-EUDRAGIT S100 polyethylene, the polypropylene.
3. compound diclofenac natrium slow releasing preparation according to claim 1 is characterized in that described surplus is that the adjuvant that allows on the pharmaceutics is mannitol, Pulvis Talci, 10% polyvinylpyrrolidone K30 solution, sodium dihydrogen phosphate, lactose or starch, hydroxypropyl emthylcellulose, microcrystalline Cellulose, acrylic resin, diethyl phthalate.
4. the method for preparing of a compound diclofenac natrium slow releasing preparation is characterized in that it may further comprise the steps:
A, take by weighing following component by mass percent:
Diclofenac sodium 25 ~ 35%; Omeprazole or its sodium salt 4 ~ 8%, mannitol 6 ~ 8.0%, Pulvis Talci 6 ~ 8.%, polyvinylpyrrolidone K30 1 ~ 2%, sodium dihydrogen phosphate 0.8 ~ 1.2%, lactose or pre-paying starch 8 ~ 12%, hydroxypropyl emthylcellulose 5 ~ 12%, microcrystalline Cellulose 15 ~ 25%, enteric materials 1.8 ~ 2.6%, isolated material 1.8 ~ 2.6%;
B, a is gone on foot the described polyvinylpyrrolidone K30 of operation, and to be mixed with quality be that 10% aqueous solution is subsequent use than concentration;
C, with diclofenac sodium and lactose or pre-paying starch, hydroxypropyl emthylcellulose, microcrystalline Cellulose mix homogeneously, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, be made into granule or micropill, dry back is subsequent use;
D, omeprazole or its sodium salt mix with mannitol, Pulvis Talci, sodium dihydrogen phosphate, add the polyvinylpyrrolidone K30 aqueous solution of 1/2 prepared amount of b step operation, are made into granule or micropill, and dry back is subsequent use;
E, use 95% ethanol or dehydrated alcohol respectively enteric materials, isolated material to be mixed with quality than casing solution and the sealing coat solution of concentration as 4-8%;
F, with sealing coat solution with diclofenac sodium granule or micropill coating after, reuse casing solution coating, it is subsequent use to make diclofenac sodium enteric coated particles or micropill;
G, with behind sealing coat solution omeprazole or its sodium salt granule or the micropill coating, reuse casing solution coating, it is subsequent use to make omeprazole enteric-coated granule or micropill;
H, the omeprazole enteric-coated granule that will prepare or micropill mix tabletting or encapsulated with diclofenac sodium enteric coated particles or micropill.
5. the method for preparing of compound diclofenac natrium slow releasing preparation according to claim 4 is characterized in that the described a step is: take by weighing following component by mass percent:
Diclofenac sodium 28.5%; Omeprazole or its sodium salt 7.6%, mannitol 8.0%, Pulvis Talci 8.%, polyvinylpyrrolidone K30 1.5%, sodium dihydrogen phosphate 1.2%, lactose 10.4%, hydroxypropyl emthylcellulose 5.0%, microcrystalline Cellulose 25%, enteric materials 2.4%, isolated material 2.4%.
6. according to the method for preparing of claim 4 or 5 described compound diclofenac natrium slow releasing preparation, it is characterized in that described enteric materials is that acrylic resin II number, diethyl phthalate are the mixture of 100:4 ~ 8 proportionings according to weight part ratio.
7. according to the method for preparing of claim 4 or 5 described compound diclofenac natrium slow releasing preparation, it is characterized in that described interlayer material is a hydroxypropyl emthylcellulose.
8. according to the method for preparing of claim 4 or 5 described compound diclofenac natrium slow releasing preparation; It is characterized in that the described g step is that omeprazole enteric-coated granule of the omeprazole for preparing or micropill tabletting are formed ground floor, on the ground floor basis, press diclofenac sodium enteric coated particles or micropill to obtain compound double-layer tablet again.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107530294A (en) * | 2015-03-31 | 2018-01-02 | 莱博瑞特瑞欧斯巴戈公司 | Enteric coated pellets containing proton pump inhibitor |
| CN113855707A (en) * | 2021-11-10 | 2021-12-31 | 黄琛 | Medicine composition for treating femoral head necrosis and application thereof |
| CN114159410A (en) * | 2021-12-08 | 2022-03-11 | 药大制药有限公司 | Diclofenac sodium sustained-release capsule and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022108A1 (en) * | 2000-09-11 | 2002-03-21 | Andrx Corporation | Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022108A1 (en) * | 2000-09-11 | 2002-03-21 | Andrx Corporation | Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107530294A (en) * | 2015-03-31 | 2018-01-02 | 莱博瑞特瑞欧斯巴戈公司 | Enteric coated pellets containing proton pump inhibitor |
| CN107530294B (en) * | 2015-03-31 | 2021-11-30 | 莱博瑞特瑞欧斯巴戈公司 | Enteric coated pellets containing proton pump inhibitor |
| CN113855707A (en) * | 2021-11-10 | 2021-12-31 | 黄琛 | Medicine composition for treating femoral head necrosis and application thereof |
| CN114159410A (en) * | 2021-12-08 | 2022-03-11 | 药大制药有限公司 | Diclofenac sodium sustained-release capsule and preparation method thereof |
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Application publication date: 20120704 |