CN105769773A - Loxoprofen sodium sustained-release pellet - Google Patents
Loxoprofen sodium sustained-release pellet Download PDFInfo
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- CN105769773A CN105769773A CN201610201063.2A CN201610201063A CN105769773A CN 105769773 A CN105769773 A CN 105769773A CN 201610201063 A CN201610201063 A CN 201610201063A CN 105769773 A CN105769773 A CN 105769773A
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- loxoprofen sodium
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
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Abstract
The invention provides a loxoprofen sodium sustained-release pellet. The pellet comprises a drug-loaded pellet core, an isolating layer coating the drug-loaded pellet core and a sustained-release layer coating the isolating layer, wherein the weight ratio of the drug-loaded pellet core to the isolating layer to the sustained-release layer is 80:(1-15):(2-20). The loxoprofen sodium sustained-release pellet shows an excellent release characteristic in vitro, the frequency of administration can be reduced, the medication compliance of patients can be improved, the blood concentration can be stabilized, and toxic and side effects of drugs on the stomach and intestines can be reduced. The invention further discloses a method for preparing the loxoprofen sodium sustained-release pellet. The method is simple in process, and is easy to industrially produce.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of loxoprofen sodium slow-release micro-pill and preparation method thereof.
Background technology
Loxoprofen sodium (LoxoprofenSodium), is first phenoxy propionic acid precursor type NSAID (non-steroidal anti-inflammatory drug) (NSAIDs), is researched and developed the earliest by Sankyo Co., Ltd of Japan, lists in Japan in July, 1986, the happy pine of trade name.Trans-OH type active medicine it is metabolized in vivo after this medicine is oral, suppress the biosynthesis of prostaglandin, namely by being combined with Cycloxygenase, cover the active center of enzyme, thus blocking this enzyme catalysis arachidonic acid to be converted into the metabolism of PG, play analgesia, antiinflammatory and refrigeration function.Loxoprofen sodium is as novel NSAIDs, and with other drug the difference is that this medicine is a prodrug, itself does not have activity, and changing into rapidly through liver just has activity after trans-OH metabolite.Its analgesic effect is 20 times of indomethacin, and the experiment of mice pawl carrageenin edema shows that its anti-inflammatory effects is the twice of indomethacin.This medicine onset rapidly and has potent, lasting analgesia, antiinflammatory, refrigeration function.It is currently used primarily in the pain after treatment rheumatoid arthritis, osteoarthritis, lumbago, scapulohumeral periarthritis, neck shoulder wrist syndrome and operation, exodontia, the disease such as acute upper respiratory tract inflammation.
Loxoprofen sodium includes loxoprofen sodium without hydrate, monohydrate or dihydrate, wherein Pharmacopeia of Japan and China's ministry standard all record loxoprofen sodium dihydrate, it is water soluble drug, this medicine peroral dosage form that current domestic and international market has listed is mainly loxoprofen sodium tablet, consumption is 180mg every day, dividing and take for three times, ease of use is poor.Compared with its conventional tablet, loxoprofen sodium slow-release micro-pill has steady blood drug level, reduces administration number of times, improves the compliance that patient takes medicine, and reduces the excessive generation prostaglandin of blood peak concentration of drug and crosses the advantages such as gastrointestinal tract toxic and side effects that high inhibition effect induces.Additionally, compared with slow releasing tablet (unit medicine-releasing system), loxoprofen sodium slow-release micro-pill, as multiple-unit drug delivery system, 1) owing to after being administered orally, it is at gastrointestinal tract rapid dispersion, thus reducing the gastric mucosa injury caused because local concentration is too high.2) micropill is owing to its particle size range is less than 1.5mm, it is possible to be easy to by Human Physiology anatomical structure stomachus pyloricus, thus avoiding administration difference between food effect and individuality.3) multiple-unit drug delivery system avoids " the having " of the existence of unit medicine-releasing system or the generation of "None" phenomenon, the i.e. drug release behavior that can't affect whole system out of control of Individual cells, thus has higher safety and toleration.
Aqueous polymer dispersion is due to its environmental protection, and toxicity is little, and cost is low, and slow releasing function is obvious, has been constantly subjected to the favor of art of pharmaceutical industry since the eighties last century.The presently commercially available aqueous dispersion for release film coating mainly includes crylic acid resin water borne dispersion liquid (such as EudragitRL30D, EudragitRS30D, EudragitNE30) and Ethylcellulose aqueous dispersion (such as Surelease and Aquecoat).The wherein EudragitRL30D main component ethyl acrylate containing 30%w/w: methyl methacrylate: methacrylic acid trimethyl ammonium chloride base ethyl ester, its mol ratio is 1: 2: 0.2, the main component of the EudragitRS30D ethyl acrylate containing 30%w/w: methyl methacrylate: methacrylic acid trimethyl ammonium chloride base ethyl ester, its mol ratio is 1: 2: 0.1.The main component of the EudragitNE butyl acrylate containing 28.5%w/w: methyl methacrylate, its mol ratio is 2: 1, is about the stabilizer (nonionic surfactant NPE 100) of 1.5% in addition with content.Sulisi (Surelease) dispersion is mainly composed of the ethyl cellulose of solid content 25%, also includes dibutyl sebacate, oleic acid, ammonia and lightweight silica gel etc..And Aquecoat dispersion total solid content is 30%, wherein contains the ethyl cellulose of 25%w/w, and be equivalent to the sodium lauryl sulphate of ethyl cellulose weight 2.7% and the hexadecanol of 5%.
When slow-release micro-pill prepared by water soluble drug aqueous liquid dispersion coating, because micropill surface area is bigger, the more serious phenomenon of burst release of ratio usually occurs, the present invention adopts and first wraps up sealing coat in capsule core with acid insulating liquid, again by the technique of aqueous dispersion bundled slow-releasing layer, prepare water-soluble basic drug loxoprofen sodium slow-release micro-pill, reduce phenomenon of burst release, obtain meeting the slow-release micro-pill of slow releasing preparation requirement, it is adaptable to the slow releasing preparation being administered 2 times (slow release 12h) or be administered once for 1 day (slow release 24h) in 1 day.
Summary of the invention
The invention provides a kind of slow-release micro-pill containing loxoprofen sodium and preparation method thereof, this micropill in-vitro release rate slowly and is stablized controlled, favorable reproducibility, and its preparation technology is simple, it is easy to industrialized production.
It is an object of the present invention to provide a kind of loxoprofen sodium slow-release micro-pill.This slow-release micro-pill comprises loxoprofen sodium medicine carrying capsule core, is coated with the sealing coat in medicine carrying capsule core and is coated on the slow release layer on this sealing coat.Wherein, described medicine carrying capsule core is 80: 1～15: 2～20 with the weight ratio of described sealing coat and described slow release layer.
Loxoprofen sodium slow-release micro-pill of the present invention, it is characterised in that the particle diameter of described medicine carrying capsule core is 0.6～1.5mm.By weight percentage, the prescription of described medicine carrying capsule core is:
Medicine carrying capsule core prescription in loxoprofen sodium slow-release micro-pill of the present invention, it is characterised in that described binding agent is selected from sucrose, dextrin and the one in pregelatinized Starch or two kinds and thing mixed above；Described wetting agent one or both mixture in water and ethanol.
Loxoprofen sodium slow-release micro-pill of the present invention, it is characterised in that described sealing coat coating solution is environmentally friendly polymer aqueous solutions, by weight percentage, described sealing coat coating fluid prescription is:
Sealing coat coating fluid prescription in loxoprofen sodium slow-release micro-pill of the present invention, it is characterized in that, described plain edition thin film coating material is selected from hypromellose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, one or both and the above mixture in polyethylene glycol vinyl alcohol block copolymer；Described pH adjusting agent is selected from citric acid, tartaric acid, succinic acid, fatty acid, malic acid, oxalic acid, 1,3-propanedicarboxylic acid, maleic acid, glutamic acid, mandelic acid and a kind of or two kinds and above mixture in fumaric acid；Described plasticizer includes triethyl citrate, glycerol, propylene glycol, Polyethylene Glycol, phthalate, dibutyl sebacate, one or both and the thing mixed above in diethyl oxalate；Described emulsifying agent is selected from spans, Tweens, lecithin, one or both and the thing mixed above in sodium lauryl sulphate.
Sealing coat coating fluid prescription in loxoprofen sodium slow-release micro-pill of the present invention, it is characterized in that, the preparation method of sealing coat coating solution includes plain edition thin film coating material distilled water wiring solution-forming, add pH adjusting agent, plasticizer, emulsifying agent and Pulvis Talci, it is sufficiently stirred for, mixing, adds water to enough, is configured to the isolation coat liquid that solid content is 5～20%.
Loxoprofen sodium slow-release micro-pill of the present invention, it is characterised in that described slow release layer coating solution is environmentally friendly polymer aqueous dispersion, the one in ethylcellulose aqueous dispersion liquid and crylic acid resin water borne dispersion liquid.
The preparation method of loxoprofen sodium slow-release micro-pill of the present invention, it is characterised in that comprise the following steps:
(1) preparation of loxoprofen sodium capsule core: weigh loxoprofen sodium, microcrystalline Cellulose and binding agent mix homogeneously in proportion, then with appropriate wetting agent soft material；Make soft material extruder extrusion by above-mentioned, extrude bar；Gained bar is round as a ball in spheronizator, obtains circular pills, through baking oven or fluid bed drying, crosses 18～30 mesh sieves and collects loxoprofen sodium capsule core.
(2) bag sealing coat: take above-mentioned loxoprofen sodium capsule core, uses aqueous spacer coating, product temperature 30～60 DEG C, feed liquor speed 2-40rmp in fluid bed or centrifugal granulator, after fluid bed or oven drying, must wrap up the pill of sealing coat,
(3) bag slow release layer: take the pill of parcel sealing coat, in fluid bed or centrifugal granulator, with slow release aqueous liquid dispersion coating; product temperature 30～80 DEG C; feed liquor speed 5～50rmp, after fluid bed or oven drying, obtains loxoprofen sodium slow-release micro-pill.
The rate of releasing drug of described loxoprofen sodium slow-release micro-pill depends primarily on pH adjusting agent concentration in sealing coat, sealing coat coating amount and slow release layer coating amount.The present invention studies discovery by experiment, when the amount of pH adjusting agent accounts for the 10～30% of sealing coat solid content, the covering amount of sealing coat is the 5～10% of medicine carrying capsule core weight, when the covering amount of slow release layer is the 15～20% of medicine carrying capsule core weight, prepared loxoprofen sodium slow-release micro-pill in the release scope that release medium is water is: 5%～30% (2 hours), 40～70% (5 hours) and 70-90% (10 hours).
In sum, loxoprofen sodium slow-release micro-pill provided by the invention, not only suppresses the phenomenon of burst release that loxoprofen sodium easily produces owing to being highly soluble in water, and can realize good slow-release characteristic.Its preparation technology is simple, it is easy to industrialized production.
The research of loxoprofen sodium slow-release micro-pill is significant, which not only reduces gastrointestinal zest, and decrease administration number of times, improve the compliance that patient takes medicine, slow rate of releasing drug simultaneously, make it can not only reach required blood drug level, and held stationary, thus avoiding ordinary tablet side effect produced by blood medicine crest phenomenon.
Accompanying drawing explanation
The release profiles of the loxoprofen sodium sustained-release micro-pill capsules that Fig. 1 embodiment 1～5 provides
The release profiles of the loxoprofen sodium sustained-release micro-pill capsules that Fig. 2 embodiment 6 provides.
Detailed description of the invention
Further explain and describe present invention by the following examples.Described embodiment, only for helping to understand present invention, is understood not to the restriction to present subject matter and protection domain.
Embodiment 1 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core
2) sealing coat coating solution
3) slow release layer coating solution
Sulisi aqueous liquid dispersion 180g
Distilled water 120g
Preparation technology:
1) medicine carrying capsule core processed: by first by loxoprofen sodium, starch, microcrystalline Cellulose crosses 80 mesh sieves respectively, by prescription proportioning mix homogeneously, add 50% ethanol, prepare soft material, bar extruded to obtain by extruded machine sieve plate, and bar is put into spheronizator, round as a ball, obtain circular granular, after 50 DEG C dry 12 hours, sieve 0.6～1.25mm micropill, obtain pellet core, result gained pellet core smooth appearance, rounding, hardness is big, is suitable to coating.
2) preparation sealing coat coating solution: solution made by the 130g distilled water weighing HPMC-E5, is subsequently adding recipe quantity PEG3350, sorbester p17, sorbester p37, citric acid, stirring and dissolving, add recipe quantity Pulvis Talci, stir, finally supplement distilled water to 300g, stir evenly, stand-by.
3) preparation slow release layer coating solution: take recipe quantity Sulisi and distilled water, stir, stand-by.
4) adopting bottom spraying type fluidized-bed process to carry out sealing coat coating the medicine carrying capsule core of above-mentioned preparation, its temperature of charge is 35～40 DEG C, and liquid inlet volume is 15rmp, and hydrojet pressure is 15～20bar, and the blow rate required is 80m3/ h, sealing coat weightening finish 6～9%.
5) adopting bottom spraying type fluidized-bed process to carry out slow release layer coating the pill of above-mentioned parcel sealing coat, its temperature of charge is 40～45 DEG C, and liquid inlet volume is 20rmp, and hydrojet pressure is 15～20bar, and the blow rate required is 80m3/ h, slow release layer weightening finish 16～18%.After fluid bed or 60 DEG C of baking oven dry 2～12h again, take out and load No. 0 capsule.
Embodiment 2 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core is with embodiment 1
2) sealing coat coating solution
3) slow release layer coating solution
Sulisi aqueous liquid dispersion 240
Distilled water 160g
Preparation technology: with embodiment 1.
Embodiment 3 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core is with embodiment 1
2) sealing coat coating solution
3) slow release layer coating solution
Sulisi aqueous liquid dispersion 270g
Distilled water 180g
Preparation technology: with embodiment 1.
Embodiment 4 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core
2) sealing coat coating solution
3) slow release layer coating solution
Sulisi aqueous liquid dispersion 270g
Distilled water 180g
Preparation technology: with embodiment 1.
Embodiment 5 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core: with embodiment 1.
2) sealing coat coating solution
3) slow release layer coating solution
Preparation technology: except slow release layer coating weight gain is except 16～19%, all the other techniques are with embodiment 1.
Embodiment 6 loxoprofen sodium sustained-release micro-pill capsules (2000)
Prescription:
1) medicine carrying capsule core
2) sealing coat
3) slow release layer
Sulisi aqueous liquid dispersion 270g
Distilled water water 180g
Preparation technology: with embodiment 1.
Embodiment 7 drug release determination is tested
According to drug release determination method (two annex XD the first methods of " Chinese Pharmacopoeia " version in 2010), adopt dissolution method (two annex XC of " Chinese Pharmacopoeia " version in 2010) paddle method device, measure the vitro release of the sustained-release micro-pill capsules agent prepared in embodiment 1～6.With purified water 900mL for medium, rotating speed is 100 turns per minute, 1,2,4,5,6,8,10,12h take solution 5mL respectively, through 0.45 μm of filtering with microporous membrane, and the instant medium supplementing same volume in process container.Take subsequent filtrate, dilute twice, according to spectrophotography (two annex IVA of " Chinese Pharmacopoeia " version in 2010), measure trap respectively at 223nm wavelength place；Take loxoprofen sodium reference substance appropriate, be configured to aqueous solution that concentration is 30 μ g/mL as reference substance solution, measure trap at 223nm wavelength place.Calculating Accumulation dissolution, result is shown in Fig. 1,2.
From Fig. 1, 2 results can be seen that, the drug release of all loxoprofen sodium sustained-release pellet preparations can continue more than 10 hours, this slow-release micro-pill in the release scope that release medium is water is: 5%～30% (2 hours), 40～70% (5 hours) and 70-90% (10 hours), suitable in the slow releasing preparation being administered 2 times (slow release 12h) or be administered once for 1 day (slow release 24h) for 1 day, the peak valley phenomenon of drug level can be avoided, reduce medicine to gastrointestinal zest and damage, reduce the administration number of times of medicine, improve the drug compliance of patient, and this preparation method technique is simple, favorable reproducibility, equipment requirements is low, it is prone to industrialized production.
Claims (8)
1. a loxoprofen sodium slow-release micro-pill, described loxoprofen sodium slow-release micro-pill includes loxoprofen sodium medicine carrying capsule core, it is wrapped in the sealing coat in medicine carrying capsule core, and it is wrapped in the slow release layer on sealing coat, wherein, the weight ratio of described medicine carrying capsule core, described sealing coat and described slow release layer is 80: 1～15: 2～20；This slow-release micro-pill can use directly as preparation oral, it is possible to is packed in capsulae vacuus and orally uses.
2. loxoprofen sodium slow-release micro-pill according to claim 1, it is characterised in that the particle diameter of described medicine carrying capsule core is 0.6～1.5mm, by weight percentage, the prescription of described medicine carrying capsule core is:
3. the medicine carrying capsule core prescription in loxoprofen sodium slow-release micro-pill according to claim 2, it is characterised in that described binding agent is selected from sucrose, dextrin and the one in pregelatinized Starch or two kinds and thing mixed above；Described wetting agent one or both mixture in water and ethanol.
4. loxoprofen sodium slow-release micro-pill according to claim 1, it is characterised in that described sealing coat coating solution is environmentally friendly polymer aqueous solutions, by weight percentage, described sealing coat coating fluid prescription is:
5. the sealing coat coating fluid prescription in loxoprofen sodium slow-release micro-pill according to claim 4, it is characterized in that, described plain edition thin film coating material is selected from hypromellose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, one or both and the above mixture in polyethylene glycol vinyl alcohol block copolymer；Described pH adjusting agent is selected from citric acid, tartaric acid, succinic acid, fatty acid, malic acid, oxalic acid, 1,3-propanedicarboxylic acid, maleic acid, glutamic acid, mandelic acid and a kind of or two kinds and above mixture in fumaric acid；Described plasticizer includes triethyl citrate, glycerol, propylene glycol, Polyethylene Glycol, phthalate, dibutyl sebacate, one or both and the thing mixed above in diethyl oxalate；Described emulsifying agent is selected from spans, Tweens, lecithin, one or both and the thing mixed above in sodium lauryl sulphate.
6. the sealing coat coating fluid prescription in loxoprofen sodium slow-release micro-pill according to claim 4, it is characterized in that, the preparation method of sealing coat coating solution includes plain edition thin film coating material distilled water wiring solution-forming, add pH adjusting agent, plasticizer, emulsifying agent and Pulvis Talci, it is sufficiently stirred for, mixing, adds distilled water to enough, is configured to the isolation coat liquid that solid content is 5～20%.
7. loxoprofen sodium slow-release micro-pill according to claim 1, it is characterized in that, described slow release layer coating solution is environmentally friendly polymer aqueous dispersion, one or both mixture in ethylcellulose aqueous dispersion liquid and crylic acid resin water borne dispersion liquid.
8. loxoprofen sodium slow-release micro-pill according to claim 1, its preparation method comprises the following steps:
(1) preparation of loxoprofen sodium capsule core: weigh loxoprofen sodium, microcrystalline Cellulose and binding agent mix homogeneously in proportion, then with appropriate wetting agent soft material；Make soft material extruder extrusion by above-mentioned, extrude bar；Gained bar is round as a ball in spheronizator, obtains circular pills, through baking oven or fluid bed drying, crosses 18～30 mesh sieves and collects loxoprofen sodium capsule core；
(2) bag sealing coat: take above-mentioned loxoprofen sodium capsule core, uses aqueous spacer coating, product temperature 30～60 DEG C, feed liquor speed 2-40rmp in fluid bed or centrifugal granulator, after fluid bed or oven drying, must wrap up the pill of sealing coat；
(3) bag slow release layer: take the pill of parcel sealing coat, in fluid bed or centrifugal granulator, with slow release aqueous liquid dispersion coating; product temperature 30～80 DEG C; feed liquor speed 5～50rmp, after fluid bed or oven drying, obtains loxoprofen sodium slow-release micro-pill.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113750077A (en) * | 2021-10-16 | 2021-12-07 | 河南省人民医院 | Amlodipine besylate sustained-release pellet and preparation method thereof |
| CN114983973A (en) * | 2022-05-31 | 2022-09-02 | 石家庄四药有限公司 | Urapidil sustained-release capsule and preparation method thereof |
| CN116650444A (en) * | 2023-07-31 | 2023-08-29 | 国药集团川抗制药有限公司 | Tacrolimus slow-release drug and preparation method thereof |
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| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
| CN101489536A (en) * | 2006-07-19 | 2009-07-22 | 旭化成化学株式会社 | Process for producing spherical elementary granule containing readily water-soluble drug |
| CN102525989A (en) * | 2011-01-04 | 2012-07-04 | 北京天衡药物研究院 | Loxoprofen sodium matrix sustained-release tablet |
| JP2014111565A (en) * | 2012-11-09 | 2014-06-19 | Taisho Pharmaceutical Co Ltd | Pharmaceutical composition |
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| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
| CN101489536A (en) * | 2006-07-19 | 2009-07-22 | 旭化成化学株式会社 | Process for producing spherical elementary granule containing readily water-soluble drug |
| CN102525989A (en) * | 2011-01-04 | 2012-07-04 | 北京天衡药物研究院 | Loxoprofen sodium matrix sustained-release tablet |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113750077A (en) * | 2021-10-16 | 2021-12-07 | 河南省人民医院 | Amlodipine besylate sustained-release pellet and preparation method thereof |
| CN113750077B (en) * | 2021-10-16 | 2022-12-20 | 河南省人民医院 | Amlodipine besylate sustained-release pellet and preparation method thereof |
| CN114983973A (en) * | 2022-05-31 | 2022-09-02 | 石家庄四药有限公司 | Urapidil sustained-release capsule and preparation method thereof |
| CN116650444A (en) * | 2023-07-31 | 2023-08-29 | 国药集团川抗制药有限公司 | Tacrolimus slow-release drug and preparation method thereof |
| CN116650444B (en) * | 2023-07-31 | 2023-10-31 | 国药集团川抗制药有限公司 | Tacrolimus slow-release drug and preparation method thereof |
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| CN105769773B (en) | 2021-05-14 |
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