CN105663092A - Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof - Google Patents
Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof Download PDFInfo
- Publication number
- CN105663092A CN105663092A CN201610119562.7A CN201610119562A CN105663092A CN 105663092 A CN105663092 A CN 105663092A CN 201610119562 A CN201610119562 A CN 201610119562A CN 105663092 A CN105663092 A CN 105663092A
- Authority
- CN
- China
- Prior art keywords
- solid dispersion
- tacrolimus
- capsule containing
- slow releasing
- lactose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
Abstract
The invention belongs to the field of pharmaceutical preparations and particularly discloses a sustained-release capsule containing tacrolimus solid dispersion and a preparation method thereof. The sustained-release capsule contains 1 part by weight of tacrolimus, 0.6-6.0 parts by weight of polyvidone K30 and ethyl cellulose, lactose, excipient and lubricating agent. The sustained-release capsule containing tacrolimus solid dispersion is simple in preparation process, easy to reproduce and suitable for industrial popularization.
Description
Technical field
The invention belongs to field of medicine preparations, be specifically related to a kind of slow releasing capsule containing tacrolimus solid dispersion and preparation method thereof.
Background technology
Tacrolimus is to build, from Japan, the neutral macrolide antibiotics separated in a kind of streptomycete main fermentation product ripple Soils In The Region in 1979, is a kind of novel potent immunosuppressant inhibitor. Its main pharmacological is in that effectively suppress T lymphocyte activator, is combined with endogenous cell receptor, forms an immunophilin complex, thus playing pharmacological action. A large amount of zooperies and clinical application research find, it is high 10～100 times that the immunosuppressive action ratio of tacrolimus encircles rhzomorph A, and toxicity is with encircling rhzomorph A, and to compare incidence rate low, and degree is also light. It is widely used in treating organs clinically and transplants the reaction of (liver, kidney, bone marrow transplantation etc.) immunologic rejection and autoimmune disease; It addition, tacrolimus topical application also has anti-inflammatory activity, can be used for treating diseases associated with inflammation.
Tacrolimus is dissolved in the non-polar solvens such as methanol, ethanol, chloroform, and almost insoluble in water, dissolubility is 1-2 μ g/ml. It addition, tacrolimus therapeutic index is low, its using dosage is excessive, can cause hepatic and renal function injure and nervous system disorders, also can strong inhibition self immune system, make the dangerous increase that patient infects. Therefore, in order to reduce the toxic and side effects of medicine, reduce medication accumulated dose (namely the available dosage less than routine dose also can reach the curative effect of routine dose) and reduce medicining times, improving the compliance of patient, slow releasing preparation can be made into.
1994, the tacrolimus capsules of Astellas company was with trade nameList in the U.S., for accepting the prevention of the rejection of liver, kidney or heart transplant operation patient. In order to improve therapeutic effect, reduce the incidence rate of Adverse Event and reduce medicining times, improving patient compliance, the prolongation delivery formulations of Astellas company continual exploitation tacrolimus. The tacrolimus slow release capsule of Astellas company lists in the U.S. in 2013 with trade name " ASTAGRAFXLTM ", for accepting the prevention of the rejection of kidney transplantation operation patient.
Patent application CN99806415.7 (applies for artificial Fujisawa Pharmaceutical Co., Ltd) and discloses a kind of delayed release dosage system containing solid dispersion compositions.Being dissolved in the organic solution containing hydroxypropyl methylcellulose and ethyl cellulose by fujimycin 506 or its compositions, in this solution, hydroxypropyl methylcellulose is suspended state. Then, granulate as excipient using lactose, within 24 hours, make solid dispersion by degassed for organic solvent again through vacuum drying. Then be crushed to certain particle diameter, then with excipient and mix lubricant be packaged in capsule. Owing to, in this organic solution, hydroxypropyl methylcellulose is suspended state, easily it is trapped in dosing tank skin and bottom causes active component content to reduce. Generally, can pass through to add organic solvent rinse Agitation Tank to reduce its residual. But excessively add organic solvent, often cause lactose gelatinizing in pelletization, it is difficult to forming granule and drying time extends, dried product exhibited is easily bonded to the problems such as block. Therefore, in order to solve the problems referred to above, its preparation process needs to use particular device vacuum drying oven, and relatively extends drying time. This not only considerably increases production cost, is also unfavorable for industrialization promotion.
Summary of the invention
It is an object of the invention to the deficiency overcoming prior art to exist, it is provided that a kind of patient's of minimizing medicining times, improve patient's Compliance and be more easy to slow releasing capsule and preparation method thereof containing tacrolimus solid dispersion of industrialization promotion.
The slow releasing capsule containing tacrolimus solid dispersion of the present invention, it comprises:
Tacrolimus 1 weight portion, PVP K30 and ethyl cellulose totally 0.6～6.0 weight portion, lactose, excipient and lubricant.
Preferably, described tacrolimus is 1:0.1～3.0 with the weight ratio of PVP K30, it is preferable that 1:0.3～0.5.
Preferably, described tacrolimus is 1:0.3～5.0 with the weight ratio of ethyl cellulose, it is preferable that 1:1.0～3.0.
Preferably, the viscosity of described ethyl cellulose is 10cps, 20cps or 45cps, it is preferable that 10cps.
Preferably, described lactose is 45～55 weight portions. Preferably, described excipient is 45～55 weight portions, for one or more in lactose, starch, sucrose, mannitol or maltose, more preferably lactose. Preferably, described lubricant is 0.8～1.0 weight portion, for one or more in magnesium stearate, micropowder silica gel or Pulvis Talci, more preferably magnesium stearate.
Preferably, solid dispersion in the slow releasing capsule containing tacrolimus solid dispersion of the present invention is first to be dispersed or dissolved in organic solvent with solid dispersible carrier PVP K30 and ethyl cellulose by tacrolimus, then granulates with lactose and make through common drying mode.
Most preferably, the slow releasing capsule containing tacrolimus solid dispersion of the present invention, it comprises:
Tacrolimus 1 weight portion, PVP K30 0.3～0.5 weight portion, viscosity are ethyl cellulose 1.0～3.0 weight portion of 10cps, lactose 45～55 weight portion, excipient lactose 45～55 weight portion and magnesium stearate lubricant 0.8～1.0 weight portion.
The preparation method of the slow releasing capsule containing tacrolimus solid dispersion of the present invention, it comprises the following steps:
A tacrolimus is dispersed or dissolved in organic solvent obtains solution with solid dispersible carrier PVP K30 and ethyl cellulose by ();
B () adopts wet granulation mode, make above-mentioned solution mix homogeneously with lactose, and form granule;
C () obtains solid dispersion after above-mentioned particle drying, pulverized and sieved, and then mixes with excipient and lubricant and refills capsule.
Preferably, described dry employing a conventional oven carries out.
The present invention containing the slow releasing capsule of tacrolimus solid dispersion, be first prepare the solid dispersion containing tacrolimus, then with excipient and mix lubricant be packaged in capsule.
The solid dispersion containing tacrolimus of the present invention, is first be dispersed or dissolved in organic solvent with the solid dispersible carrier being made up of PVP K30 and ethyl cellulose by tacrolimus, then granulates with lactose and make through common drying mode.
Wherein, described tacrolimus is 1:0.6～6.0 with the weight ratio of PVP K30 and ethyl cellulose.
Wherein, described tacrolimus is 1:0.1～3.0 with the weight ratio of PVP K30, it is preferable that 1:0.3～0.5.
Wherein, described tacrolimus is 1:0.3～5.0 with the weight ratio of ethyl cellulose, it is preferable that 1:1.0～3.0.
Wherein, the viscosity of described ethyl cellulose is 10cps, 20cps or 45cps, it is preferable that 10cps.
Wherein, described organic solvent is ethanol, methanol, chloroform or its mixture; Preferred alcohol, its concentration is 90～100% (aqueous solutions).
Wherein, described lactose is 45～55 weight portions.
Wherein, described excipient is 45～55 weight portions, for one or more in lactose, starch, sucrose, mannitol or maltose, it is preferable that lactose.
Wherein, described lubricant is 0.8～1.0 weight portion, for one or more in magnesium stearate, micropowder silica gel or Pulvis Talci, it is preferable that magnesium stearate.
The slow releasing capsule containing tacrolimus solid dispersion of the present invention has the advantage that relative to prior art and beneficial effect:
The present invention containing the slow releasing capsule of tacrolimus solid dispersion be the present inventor by big quantity research to solid dispersion rises slow release and peptizaiton adjuvant component and each component between proportioning screen, it is surprised to find that, use and can be effectively reduced the risk that active component tacrolimus remains by consoluet PVP K30 in organic solvent, avoid being excessively used of organic solvent so that the present invention adopts common drying to realize simultaneously.
On the other hand, the present invention preferably obtains the optimum proportioning of each adjuvant in the stable best of breed being made up of ethyl cellulose and PVP K30 and lactose of Release Properties and this combination, extracorporeal releasing experiment shows, the slow releasing capsule containing tacrolimus solid dispersion of the present invention can effectively control the Stable Release of tacrolimus medicine, such that it is able to make medicine can remain stable in a long time in vivo further and effective blood drug level.
The slow releasing capsule containing tacrolimus solid dispersion of the present invention only need to be administered orally once every day, decreases patient's medicining times, and patient's Compliance is improved.
The preparation method of the slow releasing capsule containing tacrolimus solid dispersion of the present invention adopts wet granulation, and common drying can realize, and preparation technology is simple, it is easy to reappearing, low for equipment requirements, conventional equipment can meet, and is suitable for industrialization promotion.
Accompanying drawing explanation
Fig. 1 is the embodiment of the present invention 3 (1mg) and the commercially available prod vitro release curve chart in the phosphate solution of pH4.5.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further illustrated, but does not limit the present invention in any way.
Embodiment 1
Tacrolimus is dissolved in ethanol, adds ethyl cellulose and stirring makes it dissolve, in above-mentioned solution, be slowly added to PVP K30, be stirred continuously until it and fully dissolve.The lactose pulverizing and crossing 200 mesh sieves is added in wet granulation pot, premix 5 minutes, it is then slowly added into above-mentioned solution and is granulated by wet granulation machine equipment. After granulation terminates, being placed in pallet, 40 DEG C of a conventional ovens are dried, and then cross 70 mesh sieve granulate and obtain SD1. In mixer, add lactose, SD1 and magnesium stearate, mixing successively, obtain preparation 1. Preparation 1 is filled in capsule.
Embodiment 2
Adopt and method identical described in embodiment 1 prepares preparation 2. Preparation 2 is filled in capsule.
Embodiment 3
Adopt and method identical described in embodiment 1 prepares preparation 3. Preparation 3 is filled in capsule.
Embodiment 4
Adopt and method identical described in embodiment 1 prepares preparation 4. Preparation 4 is filled in capsule.
Embodiment 5
Adopt and method identical described in embodiment 1 prepares preparation 5. Preparation 5 is filled in capsule.
Embodiment 6
Adopt and method identical described in embodiment 1 prepares preparation 6. Preparation 6 is filled in capsule.
Embodiment 7
Adopt and method identical described in embodiment 1 prepares preparation 7. Preparation 7 is filled in capsule.
Embodiment 8
Adopt and method identical described in embodiment 1 prepares preparation 8. Preparation 8 is filled in capsule.
Embodiment 9
Vitro release is tested
The second method is measured according to Chinese Pharmacopoeia second annex XL of version in 2010, slurry processes, dissolution medium is containing 0.10% sodium lauryl sulphate and 0.005% hydroxypropyl cellulose, pH4.5 is regulated with phosphate solution, 900ml, 50 turns/min of rotating speed, respectively sampling detection in 0.5 hour, 1 hour, 1.5 hours, 3 hours, 7 hours and 24 hours. Test sample is the slow releasing capsule containing 1mg tacrolimus solid dispersion of embodiment 3 preparation, and comparison medicine is ASTAGRAFXLTM1mg slow releasing capsule (lot number 1M4335G), Astellas Pharma Inc produces (Astellas). Vitro release result is shown in Fig. 1.
As shown in Figure 1, the In-vitro release curves of the slow releasing capsule containing 1mg tacrolimus solid dispersion (embodiment 3) that prepared by the present invention and ASTAGRAFXLTM1mg is basically identical. The In-vitro release curves early stage of the slow releasing capsule containing 1mg tacrolimus solid dispersion (embodiment 3) of the present invention is immediate release section, medicine is conducive to reach treatment concentration in vivo as early as possible, mid-term is constant release part, contribute to maintaining blood drug level steady, avoid the impact on curative effect of crest and trough, reduce the generation of untoward reaction, later stage vitro release is held essentially constant, show medicine continuous and effective in a long time, thus patient only need to be administered orally once every day, patient's Compliance is improved.
Claims (10)
1. the slow releasing capsule containing tacrolimus solid dispersion, it is characterised in that comprise:
Tacrolimus 1 weight portion, PVP K30 and ethyl cellulose totally 0.6～6.0 weight portion, lactose, excipient and lubricant.
2. the slow releasing capsule containing tacrolimus solid dispersion according to claim 1, it is characterised in that the weight ratio of described tacrolimus and PVP K30 is 1:0.1～3.0, it is preferable that 1:0.3～0.5.
3. the slow releasing capsule containing tacrolimus solid dispersion according to claim 1, it is characterised in that the weight ratio of described tacrolimus and ethyl cellulose is 1:0.3～5.0, it is preferable that 1:1.0～3.0.
4. the slow releasing capsule containing tacrolimus solid dispersion according to claim 1, it is characterised in that the viscosity of described ethyl cellulose is 10cps, 20cps or 45cps, it is preferable that 10cps.
5. the slow releasing capsule containing tacrolimus solid dispersion according to claim 1, it is characterised in that described lactose is 45～55 weight portions; Described excipient is 45～55 weight portions, for one or more in lactose, starch, sucrose, mannitol or maltose, it is preferable that lactose; Described lubricant is 0.8～1.0 weight portion, for one or more in magnesium stearate, micropowder silica gel or Pulvis Talci, it is preferable that magnesium stearate.
6. the slow releasing capsule containing tacrolimus solid dispersion according to claim 1, it is characterized in that, described solid dispersion is first to be dispersed or dissolved in organic solvent with solid dispersible carrier PVP K30 and ethyl cellulose by tacrolimus, then granulates with lactose and make through common drying mode.
7. the slow releasing capsule containing tacrolimus solid dispersion, it is characterised in that comprise:
Tacrolimus 1 weight portion, PVP K30 0.3～0.5 weight portion, viscosity are ethyl cellulose 1.0～3.0 weight portion of 10cps, lactose 45～55 weight portion, excipient lactose 45～55 weight portion and magnesium stearate lubricant 0.8～1.0 weight portion.
8. the preparation method of the slow releasing capsule containing tacrolimus solid dispersion according to any one of claim 1～7, it is characterised in that comprise the following steps:
A tacrolimus is dispersed or dissolved in organic solvent obtains solution with solid dispersible carrier PVP K30 and ethyl cellulose by ();
B () adopts wet granulation mode, make above-mentioned solution mix homogeneously with lactose, and form granule;
C () obtains solid dispersion after above-mentioned particle drying, pulverized and sieved, and then mixes with excipient and lubricant and refills capsule.
9. the preparation method of the slow releasing capsule containing tacrolimus solid dispersion according to claim 8, it is characterised in that described dry employing a conventional oven carries out.
10. the preparation method of the slow releasing capsule containing tacrolimus solid dispersion according to claim 8, it is characterised in that described organic solvent is ethanol, methanol, chloroform or its mixture; Preferred alcohol, its concentration is 90～100%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610119562.7A CN105663092A (en) | 2016-03-03 | 2016-03-03 | Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610119562.7A CN105663092A (en) | 2016-03-03 | 2016-03-03 | Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105663092A true CN105663092A (en) | 2016-06-15 |
Family
ID=56306506
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610119562.7A Pending CN105663092A (en) | 2016-03-03 | 2016-03-03 | Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105663092A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107595784A (en) * | 2017-08-29 | 2018-01-19 | 杭州中美华东制药有限公司 | Tacrolimus slow releasing medicinal compositions |
| CN112263567A (en) * | 2020-10-19 | 2021-01-26 | 南京易亨制药有限公司 | Ibuprofen sustained-release capsule and preparation method thereof |
| CN113577032A (en) * | 2021-08-27 | 2021-11-02 | 国药集团川抗制药有限公司 | Preparation method of tacrolimus solid dispersion, quick-release pharmaceutical composition and application |
| CN115463097A (en) * | 2021-06-11 | 2022-12-13 | 杭州中美华东制药有限公司 | Preparation process of tacrolimus slow-release intermediate particles |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1245424A (en) * | 1996-12-06 | 2000-02-23 | 藤泽药品工业株式会社 | Medicinal composition |
| CN104940334A (en) * | 2015-06-24 | 2015-09-30 | 绍兴文理学院元培学院 | Hawthorn leaf extract solid dispersion sustained release capsule and preparation method thereof |
-
2016
- 2016-03-03 CN CN201610119562.7A patent/CN105663092A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1245424A (en) * | 1996-12-06 | 2000-02-23 | 藤泽药品工业株式会社 | Medicinal composition |
| CN104940334A (en) * | 2015-06-24 | 2015-09-30 | 绍兴文理学院元培学院 | Hawthorn leaf extract solid dispersion sustained release capsule and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| DAISUKE TSUNASHIMA等: "Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method", 《JOURNAL OF PHARMACY AND PHARMACOLOGY》 * |
| 闫丽霞: "《中药制剂技术》", 31 August 2004, 化学工业出版社 * |
| 韩敏等: "不同载体他克莫司固体分散体的制备及溶出特性", 《中国医药工业杂志》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107595784A (en) * | 2017-08-29 | 2018-01-19 | 杭州中美华东制药有限公司 | Tacrolimus slow releasing medicinal compositions |
| CN107595784B (en) * | 2017-08-29 | 2018-09-28 | 杭州中美华东制药有限公司 | Tacrolimus slow releasing medicinal compositions |
| CN112263567A (en) * | 2020-10-19 | 2021-01-26 | 南京易亨制药有限公司 | Ibuprofen sustained-release capsule and preparation method thereof |
| CN112263567B (en) * | 2020-10-19 | 2022-05-03 | 南京易亨制药有限公司 | Ibuprofen sustained-release capsule and preparation method thereof |
| CN115463097A (en) * | 2021-06-11 | 2022-12-13 | 杭州中美华东制药有限公司 | Preparation process of tacrolimus slow-release intermediate particles |
| CN115463097B (en) * | 2021-06-11 | 2024-04-19 | 杭州中美华东制药有限公司 | Preparation process of tacrolimus slow-release intermediate particles |
| CN113577032A (en) * | 2021-08-27 | 2021-11-02 | 国药集团川抗制药有限公司 | Preparation method of tacrolimus solid dispersion, quick-release pharmaceutical composition and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105663092A (en) | Sustained-release capsule containing tacrolimus solid dispersion and preparation method thereof | |
| NO333301B1 (en) | Pharmaceutical composition containing fenofibrate and process for its preparation | |
| AU2002350082B9 (en) | Process for preparing quick dissolving, high loading ribavirin compositions | |
| CN103655486B (en) | Sirolimus microemulsion particles and its preparation method and application | |
| CN101167697B (en) | Donepezils compound long-acting slow-releasing and controlled-releasing composition and preparation method thereof | |
| CN101816637B (en) | Leflunomide tablet preparation and preparation method thereof | |
| CN106074465A (en) | Cannabinol compounds application in preparation treatment gouty arthritis medicine | |
| CN104844600A (en) | Tadalafil compound and composition thereof | |
| CN102525876B (en) | Aspirin solid dispersion, as well as preparation method, pharmaceutical composition and use thereof | |
| CN103893258A (en) | Oral solid preparation containing desmodium styracifolium general flavone and application thereof | |
| CN115624525A (en) | Tacrolimus sustained-release pharmaceutical composition and preparation method thereof | |
| CN105534932A (en) | Preparation for improving release efficiency | |
| CN1245212C (en) | Cyclosporin A dispersion solid and its preparation method | |
| CN1927185B (en) | Maleic acid trimebutine slow release tablet comprising quick release part and preparing method thereof | |
| CN102068419A (en) | Curcumin composition | |
| CN103301083A (en) | Nifedipine slow release tablet and preparation method thereof | |
| CN114681406A (en) | Carilazine long-acting slow-release microsphere and preparation method thereof | |
| CN102885810B (en) | A kind of candesartan cilexetil double-release capsule and preparation method thereof | |
| CN101129362A (en) | Sirolimus dispersible tablets and method of producing the same | |
| CN111565714A (en) | Pharmaceutical preparation comprising everolimus and capable of achieving stabilization | |
| KR20130097088A (en) | Sustained-release formulation | |
| CN102579344B (en) | Losartan potassium liposome solid preparation | |
| CN101829071B (en) | Aliskiren liposome tablet | |
| WO2024066765A1 (en) | Antiviral pharmaceutical composition, preparation process therefor, and use thereof | |
| CN102125693A (en) | Tiagabine hydrochloride pharmaceutical composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160615 |