CN109364035B - Clonidine hydrochloride sustained release tablet and preparation method thereof - Google Patents
Clonidine hydrochloride sustained release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN109364035B CN109364035B CN201811454995.3A CN201811454995A CN109364035B CN 109364035 B CN109364035 B CN 109364035B CN 201811454995 A CN201811454995 A CN 201811454995A CN 109364035 B CN109364035 B CN 109364035B
- Authority
- CN
- China
- Prior art keywords
- clonidine hydrochloride
- parts
- release tablet
- sustained release
- scutellarin
- 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.)
- Active
Links
Classifications
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
The invention relates to a clonidine hydrochloride sustained release tablet and a preparation method thereof, belonging to the field of pharmaceutical preparations. The invention relates to a clonidine hydrochloride sustained release tablet, which comprises the following components: 0.1-0.5 part of active ingredient, 8-18 parts of composite polymer skeleton system, 10-18 parts of disintegrating agent, 12-18 parts of adhesive, 15-30 parts of diluent and 0.1-2 parts of lubricant, wherein the active ingredient consists of clonidine hydrochloride and scutellarin, and the composite polymer skeleton system consists of methylcellulose and polyvinyl alcohol. According to the invention, the clonidine hydrochloride and scutellarin are combined for preparing the sustained release tablets for reducing blood pressure for the first time, and the effect test researches show that the combined application of the clonidine hydrochloride and the scutellarin can obviously improve the blood pressure reducing effect and obtain the synergistic effect by optimizing and screening the formula.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a clonidine hydrochloride sustained release tablet and a preparation method thereof.
Background
Clonidine hydrochloride is an imidazoline derivative synthesized in the early 60 th of the 20 th century, is an alpha 2-adrenergic receptor agonist, directly excites central postsynaptic membrane alpha 2 receptors of hypothalamus and brain extension, enables inhibitory neurons to be excited, reduces central sympathetic nerve impulse effervescence, and inhibits peripheral sympathetic nerve activity.
At present, clonidine hydrochloride is sold in the market to prepare tablets, dripping pills, injection, transdermal patches and the like. Clonidine hydrochloride sustained release tablets were developed by AddrenexPharmaceuticals, usa, and were approved by FDA for the treatment of hypertension on 9/29 of 2009, with specifications: 0.1mg, 0.2 mg. In 30/9/2009, ShionogiPharma submits a new drug supplement application for adding clonidine hydrochloride sustained-release tablet indications to FDA, and in 28/9/2010, ADHD approved by the United states FDA for treating 6-17-year-old children and adolescents is obtained, and the clonidine hydrochloride sustained-release tablet with the specification of 0.1mg is sold in the United states in 2011 in 1/2011.
Scutellarin is the main chemical component of erigeron breviscapus, and modern pharmacological studies show that scutellarin has the effects of resisting inflammation, oxidation, apoptosis and the like, has the effect of dilating cerebral vessels, can reduce the resistance of cerebral vessels, increase the blood flow of brain, improve microcirculation, has the effect of resisting platelet aggregation, and is clinically used for treating ischemic cerebrovascular diseases.
In the prior art, the combined application of clonidine hydrochloride and scutellarin is not researched.
Disclosure of Invention
The invention aims to provide clonidine hydrochloride sustained-release tablets with excellent antihypertensive effect and a preparation method thereof.
The technical scheme for solving the technical problem is that the clonidine hydrochloride sustained release tablet comprises the following components:
0.1 to 0.5 portion of active ingredient
8-18 parts of composite polymer skeleton system
10-18 parts of disintegrating agent
12 to 18 portions of adhesive
15-30 parts of diluent
0.1 to 2 portions of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
Preferably, it consists of:
0.2 to 0.4 portion of active ingredient
10-15 parts of composite polymer skeleton system
12-16 parts of disintegrating agent
14-16 parts of adhesive
18-26 parts of diluent
0.2 to 1 portion of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
More preferably, it consists of:
active ingredient 0.3 part
Composite polymer skeleton system 12 parts
14 portions of disintegrating agent
15 portions of adhesive
Diluent 22 portions
0.5 part of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
The weight ratio of the clonidine hydrochloride to the scutellarin is 1:1-3: 1.
The weight ratio of the methyl cellulose to the polyvinyl alcohol is 1:4-4:1, and preferably, the weight ratio of the methyl cellulose to the polyvinyl alcohol is 4: 1.
The diluent comprises one or more of calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrin and mannitol.
The binder comprises one or more of lactose, compressible starch and povidone.
The disintegrant comprises one or more of dried starch, silicon dioxide, alginic acid, and crospovidone.
The invention also provides a preparation method of the clonidine hydrochloride sustained release tablet, which comprises the following steps: weighing the raw materials according to the formula proportion, uniformly mixing active ingredients of clonidine hydrochloride and scutellarin with a composite polymer skeleton system, adding a diluent, an adhesive, a disintegrating agent and a lubricant, granulating and tabletting to obtain the pharmaceutical composition.
The invention has the beneficial effects that:
according to the invention, the clonidine hydrochloride and scutellarin are combined for preparing the sustained release tablets for reducing blood pressure for the first time, and the effect test researches show that the combined application of the clonidine hydrochloride and the scutellarin can obviously improve the blood pressure reducing effect and obtain the synergistic effect by optimizing and screening the formula.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
EXAMPLES preparation of clonidine hydrochloride sustained Release tablets
The clonidine hydrochloride sustained release tablets of examples 1 to 3 and comparative examples 1 to 2 were prepared by granulating and tableting according to the formulation of the parts by weight in table 1.
TABLE 1 clonidine hydrochloride sustained release tablet formulation
| Example 1 | Example 2 | Example 3 | Comparative example 1 | Comparative example 2 | |
| Clonidine hydrochloride | 0.1 | 0.12 | 0.15 | 0.2 | 0 |
| Scutellarin | 0.1 | 0.08 | 0.05 | 0 | 0.2 |
| Methyl cellulose | 12 | 12 | 12 | 12 | 12 |
| Polyvinyl alcohol | 3 | 3 | 3 | 3 | 3 |
| Dried starch | 6 | 6 | 6 | 6 | 6 |
| Cross-linked polyvidone | 6 | 6 | 6 | 6 | 6 |
| Lactose | 15 | 15 | 15 | 15 | 15 |
| Calcium sulfate | 10 | 10 | 10 | 10 | 10 |
| Microcrystalline fiberVitamin (vitamin) | 10 | 10 | 10 | 10 | 10 |
| Magnesium stearate | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
Test of the Effect of a single administration of clonidine hydrochloride sustained-release tablet on the blood pressure decrease of Spontaneously Hypertensive Rats (SHR)
90 male Spontaneous Hypertensive Rats (SHR) of 10 weeks old weighing 190-. Before the experiment, the blood pressure of each group of Spontaneous Hypertensive Rats (SHR) is measured three times when they are awake, and whether they are normal or not is observed, and abnormal rats are replaced. Blood pressure was measured as a basal value before administration, and then administered by gavage separately, and blood pressure was measured at 1h, 2h, 4h, 6h, 8h, 12h, 24h and 36h after administration, and the results are shown in table 2.
TABLE 2 Effect of a single administration of clonidine hydrochloride extended release tablets on the extent of blood pressure decrease in Spontaneously Hypertensive Rats (SHR)
| Blank control group | EXAMPLE 1 group | EXAMPLE 2 group | EXAMPLE 3 group | Comparative example 1 group | Comparative example 2 group | |
| 0 | 181.23±4.23 | 182.34±4.34 | 184.34±5.21 | 184.32±3.43 | 188.43±1.32 | 182.98±5.34 |
| 1h | 181.45±3.45 | 148.45±2.24 | 151.76±2.54 | 148.34±2.45 | 162.67±1.24 | 170.23±2.32 |
| 2h | 182.34±1.43 | 150.23±1.45 | 153.87±1.24 | 149.34±2.34 | 169.54±2.34 | 169.45±3.45 |
| 4h | 184.23±2.32 | 149.23±2.76 | 152.46±1.83 | 150.26±2.41 | 161.24±2.45 | 171.34±3.54 |
| 6h | 182.32±1.32 | 151.24±1.66 | 151.98±1.35 | 148.26±3.04 | 169.45±2.54 | 172.23±2.34 |
| 8h | 181.98±2.43 | 152.58±2.98 | 153.34±1.45 | 149.54±2.78 | 169.34±2.45 | 168.45±3.42 |
| 12h | 183.43±1.89 | 152.26±3.01 | 150.45±1.23 | 151.23±2.31 | 168.34±3.68 | 168.89±4.35 |
| 24h | 183.54±1.54 | 153.34±1.56 | 154.98±2.45 | 153.25±2.54 | 168.34±4.24 | 171.65±1.56 |
| 36h | 183.34±2.43 | 170.54±3.45 | 171.23±2.56 | 170.34±2.43 | 180.65±1.56 | 180.45±3.35 |
From the above results, it was found that the effect of single administration on the blood pressure decrease of Spontaneous Hypertensive Rats (SHR) was different in each group, wherein the blood pressure of the blank control group was not changed within 36 hours by administration of distilled water, the blood pressure of the comparative example 1 was decreased by about 20, the blood pressure of the comparative example 2 was decreased by about 12, and the blood pressure of the examples 1 to 3 was decreased by about 35, which was significant.
Test of the Effect of multiple administrations of clonidine dihydrochloride sustained-release tablets on the blood pressure decrease of Spontaneously Hypertensive Rats (SHR)
90 male Spontaneous Hypertensive Rats (SHR) of 10 weeks old weighing 190-. Spontaneous hypertensive rats were measured as baseline blood pressure while awake and then administered by gavage once a day for two consecutive weeks. The blood pressure of Spontaneously Hypertensive Rats (SHR) in the awake state was measured before administration, 2 hours after administration, and 24 hours after administration (every other day). The recovery period after drug withdrawal continued to measure changes in SHR blood pressure until the indicators returned to pre-dose levels. The results are shown in Table 3.
TABLE 3 Effect of multiple administration of clonidine hydrochloride sustained-release tablets on the blood pressure decrease in Spontaneously Hypertensive Rats (SHR)
| Blank control group | EXAMPLE 1 group | EXAMPLE 2 group | EXAMPLE 3 group | Comparative example 1 group | Comparative example 2 group | |
| 0 | 182.17±5.01 | 181.15±2.45 | 182.43±1.32 | 182.55±2.15 | 182.54±2.15 | 181.93±4.13 |
| 1d | 183.14±4.41 | 150.12±4.02 | 153.13±1.51 | 151.13±3.22 | 165.13±2.21 | 171.21±2.33 |
| 2d | 181.79±2.12 | 149.21±2.14 | 152.14±2.11 | 150.11±1.31 | 163.51±1.21 | 172.41±1.44 |
| 4d | 182.77±3.12 | 148.12±1.14 | 151.15±2.05 | 149.54±2.43 | 160.31±2.11 | 172.09±2.06 |
| 6d | 181.34±2.11 | 150.21±2.11 | 152.91±1.31 | 150.14±2.11 | 169.44±1.51 | 171.26±2.65 |
| 8d | 182.14±1.33 | 149.12±2.14 | 151.04±2.11 | 148.98±1.35 | 169.66±1.21 | 169.45±1.14 |
| 10d | 181.48±2.03 | 151.43±2.11 | 151.11±1.54 | 150.21±1.65 | 172.12±4.02 | 170.35±2.16 |
| 12d | 182.13±2.14 | 155.13±1.41 | 152.15±1.32 | 150.21±1.57 | 169.31±2.14 | 172.61±2.43 |
| 15d | 181.79±2.11 | 173.23±2.55 | 172.21±2.52 | 172.11±2.45 | 181.43±3.03 | 182.15±2.08 |
From the above results, it was found that the effect of multiple administrations on the blood pressure decrease of Spontaneous Hypertensive Rats (SHR) was similar to the effect of single administration on the blood pressure decrease of Spontaneous Hypertensive Rats (SHR) in each group, and the blood pressure decrease of the groups of examples 1 to 3 was large, resulting in a synergistic effect.
The foregoing detailed description of the invention has been presented for purposes of illustration and description, and is intended to be by way of illustration only and is not intended to limit the scope of the invention, its application, or uses, including the best mode, of manufacture, of the invention. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention. The scope of the invention is defined by the claims and may include other embodiments that occur to those skilled in the art. Such other embodiments are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.
Claims (10)
1. A clonidine hydrochloride sustained release tablet is characterized by comprising the following components:
0.1 to 0.5 portion of active ingredient
8-18 parts of composite polymer skeleton system
10-18 parts of disintegrating agent
12 to 18 portions of adhesive
15-30 parts of diluent
0.1 to 2 portions of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
2. The clonidine hydrochloride sustained release tablet according to claim 1, characterized in that it consists of:
0.2 to 0.4 portion of active ingredient
10-15 parts of composite polymer skeleton system
12-16 parts of disintegrating agent
14-16 parts of adhesive
18-26 parts of diluent
0.2 to 1 portion of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
3. The clonidine hydrochloride sustained release tablet according to claim 2, characterized in that it consists of:
active ingredient 0.3 part
Composite polymer skeleton system 12 parts
14 portions of disintegrating agent
15 portions of adhesive
Diluent 22 portions
0.5 part of lubricant
The active ingredients consist of clonidine hydrochloride and scutellarin,
the composite polymer skeleton system consists of methyl cellulose and polyvinyl alcohol.
4. The clonidine hydrochloride sustained release tablet according to any one of claims 1 to 3, wherein the weight part ratio of the clonidine hydrochloride to the scutellarin is 1:1-3: 1.
5. The clonidine hydrochloride sustained-release tablet according to any one of claims 1 to 3, wherein the weight ratio of the methylcellulose to the polyvinyl alcohol is 1:4 to 4: 1.
6. The clonidine hydrochloride sustained release tablet of claim 5, wherein the weight ratio of the methylcellulose to the polyvinyl alcohol is 4: 1.
7. A clonidine hydrochloride sustained release tablet according to any one of claims 1 to 3, wherein the diluent comprises one or more of calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrin and mannitol.
8. A clonidine hydrochloride sustained release tablet according to any one of claims 1 to 3, wherein the binder comprises one or more of lactose, compressible starch and povidone.
9. The clonidine hydrochloride sustained-release tablet of any one of claims 1 to 3, wherein the disintegrant comprises one or more of dried starch, alginic acid and crospovidone.
10. A method for preparing a clonidine hydrochloride sustained release tablet according to any one of claims 1 to 9, characterized by comprising the steps of: weighing the raw materials according to the formula proportion, uniformly mixing active ingredients of clonidine hydrochloride and scutellarin with a composite polymer skeleton system, adding a diluent, an adhesive, a disintegrating agent and a lubricant, granulating and tabletting to obtain the pharmaceutical composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811454995.3A CN109364035B (en) | 2018-11-30 | 2018-11-30 | Clonidine hydrochloride sustained release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811454995.3A CN109364035B (en) | 2018-11-30 | 2018-11-30 | Clonidine hydrochloride sustained release tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109364035A CN109364035A (en) | 2019-02-22 |
| CN109364035B true CN109364035B (en) | 2021-02-09 |
Family
ID=65375505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811454995.3A Active CN109364035B (en) | 2018-11-30 | 2018-11-30 | Clonidine hydrochloride sustained release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109364035B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101125126A (en) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | Method for preparing medical freeze-dried powder (injection) preparation |
| WO2013131270A1 (en) * | 2012-03-08 | 2013-09-12 | Liu Li | Scutellarin hydrate and preparation method and use thereof |
| CN103705531A (en) * | 2013-12-20 | 2014-04-09 | 昆明医科大学 | Application of scutellarin in preventing and treating specific vascular endothelial injury |
| CN105288648A (en) * | 2015-10-14 | 2016-02-03 | 东南大学 | Phospholipid compound of hydrophilic drugs as well as pharmaceutical composition and application of phospholipid compound |
| CN105395518A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride sustained-release capsule |
| CN105395506A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride sustained-release tablet |
| WO2016192680A1 (en) * | 2015-06-03 | 2016-12-08 | Triastek, Inc. | Dosage forms and use thereof |
-
2018
- 2018-11-30 CN CN201811454995.3A patent/CN109364035B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101125126A (en) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | Method for preparing medical freeze-dried powder (injection) preparation |
| WO2013131270A1 (en) * | 2012-03-08 | 2013-09-12 | Liu Li | Scutellarin hydrate and preparation method and use thereof |
| CN103705531A (en) * | 2013-12-20 | 2014-04-09 | 昆明医科大学 | Application of scutellarin in preventing and treating specific vascular endothelial injury |
| WO2016192680A1 (en) * | 2015-06-03 | 2016-12-08 | Triastek, Inc. | Dosage forms and use thereof |
| CN105288648A (en) * | 2015-10-14 | 2016-02-03 | 东南大学 | Phospholipid compound of hydrophilic drugs as well as pharmaceutical composition and application of phospholipid compound |
| CN105395518A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride sustained-release capsule |
| CN105395506A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Clonidine hydrochloride sustained-release tablet |
Non-Patent Citations (3)
| Title |
|---|
| ARB类药物联合灯盏花素治疗糖尿病肾病的有效性及安全性;邱英等;《山东医药》;20151231;第55卷(第19期);第35-37页 * |
| Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review;Jialiang Gao et al.;《Frontiers in Pharmacology》;20170523;第8卷;第1-13页 * |
| 注射用灯盏花素联合厄贝沙坦片治疗早期糖尿病肾病疗效观察;张莲莲等;《中国民康医学》;20140531;第26卷(第10期);第75-76页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109364035A (en) | 2019-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI395583B (en) | Solid pharmaceutical composition comprising amlodipine and losartan | |
| DE05852057T1 (en) | COMPOSITION OF A COATING OR MATRIX WITH DELAYED RELEASE AND A NMDA RECEPTOR ANTAGONIST AND METHOD FOR THE ADMINISTRATION OF SUCH A NMDA RECEPTOR ANTAGONIST TO A SUBJECT | |
| CN101797230B (en) | Liposome solid preparation of losartan potassium hydrochlorothiazide pharmaceutical composition | |
| CN105935358B (en) | One seed sand library is than bent Valsartan sustained release agent and preparation method thereof | |
| AU2014374259A1 (en) | Novel compositions | |
| EP3932407B1 (en) | Enteric coated tablet composition comprising tetramethylpyrazine nitrone | |
| CN109364035B (en) | Clonidine hydrochloride sustained release tablet and preparation method thereof | |
| WO2008025780A1 (en) | Titration schedule for bifeprunox for treating schizophrenia and kits for use therein | |
| CN103249415B (en) | Compound formulation comprising Lercanidipine hydrochloride and Valsartan and preparation method thereof | |
| EP1655029B1 (en) | Medicinal compositions | |
| CN106943368A (en) | Mirtazapine tablet and preparation method thereof | |
| EP2236160A2 (en) | Modified release dimebolin formulations | |
| CN101317842A (en) | Treating uses of imidazole-5-carboxylic acid derivant | |
| CN104644589B (en) | A kind of isosorbide mononitrate sustained release tabletses and its preparation technology | |
| US20100249103A1 (en) | combination treatment | |
| CN106580899B (en) | Method for preparing imidafenacin tablets | |
| CN104740636B (en) | A kind of composite antihypertensive preparation and its application | |
| CN102670535A (en) | Clopidogrel hydrochloride tablet | |
| CN108853044A (en) | A kind of Nifedipine sustained release tablets and preparation method thereof | |
| CN101849914A (en) | Slow-release solid preparation taking carvedilol as main component and preparation method thereof | |
| EP2976067B1 (en) | Pharmaceutical composition comprising a fluoroquinolone antibacterial agent and method for the preparation thereof | |
| CN102367257A (en) | Single-crystal crystal forms of clopidogrel hydrochloride and preparation method and application thereof | |
| CN112870213B (en) | Pharmaceutical composition for treating hypertension, solid oral preparation and application thereof | |
| CN110292637B (en) | A pharmaceutical composition for preventing and treating hypertension | |
| CN106562965A (en) | Compound medicinal preparation for treating renal hypertension |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |