CN101829064B - Dexibuprofen particle and preparation method thereof - Google Patents
Dexibuprofen particle and preparation method thereof Download PDFInfo
- Publication number
- CN101829064B CN101829064B CN2010101580082A CN201010158008A CN101829064B CN 101829064 B CN101829064 B CN 101829064B CN 2010101580082 A CN2010101580082 A CN 2010101580082A CN 201010158008 A CN201010158008 A CN 201010158008A CN 101829064 B CN101829064 B CN 101829064B
- Authority
- CN
- China
- Prior art keywords
- ibuprofen
- sucrose
- granules
- aspartame
- sodium carbonate
- 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
Abstract
The invention discloses a dexibuprofen particle which is mainly prepared from the following raw materials in parts by weight: 1-10 parts of dexibuprofen, 1-6 parts of sodium carbonate, 1-35 parts of sucrose, 0.1-0.8 part of aspartame and 3-12 parts of ethanol. The invention also discloses a preparation method of the dexibuprofen particle, which comprises the following steps of: sieving each raw material, and then, fully mixing the raw materials uniformly; granulating; and drying at high temperature, and then, refining to obtain the dexibuprofen particle. The dexibuprofen particle of the invention can endure high-temperature drying, has qualified indexes of microbial limit, solubility and the like and has stable and controllable quality; in addition, the preparation method is simple to operate has short production cycle and low cost, and is suitable for industrialized production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of (s)-ibuprofen granules and preparation method thereof.
Background technology
Ibuprofen belongs to propionic non-steroid antiphlogistic; Tool analgesia, antiinflammatory, refrigeration function; Its mechanism of action is to reduce the synthetic of prostaglandin through the inhibition to epoxidase; Alleviate congested, the swelling of the tissue that causes because of prostaglandin thus, reduce the sensitivity of the peripheral nerve pain sensation, it plays refrigeration function through the hypothalamus center of body temperature regulation.
Though ibuprofen is a NSAID commonly used at present, because oral dose is big, reasons such as mouthfeel difference and GI irritation have influenced its extensive use.Many clinical adverse have appearred in ibuprofen in recent years, like anaphylaxis, anaphylactic shock, lower limbs edema, nauseating, vomiting, dyspepsia etc.The clinical application DL ibuprofen of also having taked replaces ibuprofen; As antiinflammatory, analgesic; Existing 30 years of its clinical practice, the DL ibuprofen is made up of left-handed ibuprofen and (S)-ibuprofen, and 50%～60% left-handed ibuprofen becomes (S)-ibuprofen competence exertion therapeutical effect through " metabolic counter-rotating " in body; Thereby the raising therapeutical effect, the dosage of minimizing medicine.; Left-handed ibuprofen in the DL ibuprofen has also produced other covert isomer when being converted into (S)-ibuprofen; Cause occurring some side reactions: gastrointestinal toxicity, water-sodium retention, stomach perfusion reduce and anaphylaxis, and incidence rate is 15%～30%.Discovering in recent years, the activity of (S)-ibuprofen are 160 times of its levo form, are 16 times of raceme ibuprofen.Therefore; (S)-ibuprofen has higher activity and curative effect, and smaller dose can reach therapeutical effect, can effectively reduce toxic and side effects; Its 1996 begin to be widely used in the treatment rheumatoid arthritis in Austria; Approved by everybody, and seek the affiliate to the whole world, promote collaboration application to the whole world by Switzerland.
The oral easy absorption of (S)-ibuprofen absorbs when taking together with food and slow down, but absorbtivity does not reduce; Do not influence absorption with the antacid that contains aluminum and magnesium with clothes, plasma protein binding rate is 99%, 1.2～2.1 hours blood drug level peakings in back of taking medicine; Consumption 200mg; Blood drug level is 22～27 μ g/ml, is 23～45 μ g/ml during consumption 400mg, is 43～57 μ g/ml during consumption 600mg.T behind the single administration
1/2Be generally 1.8～2 hours, the 5 hours posterior joint liquid concentration of taking medicine equates that with blood drug level intrinsic articulation liquid concentration was higher than PC in later 12 hours.This medicine oral absorption is good, plasma protein binding rate 99%, and about 2 hours of plasma half-life, mainly through liver metabolism, 60%～90% through renal excretion, and original shape accounts for 1%, and a part is discharged with feces.
The oral solid formulation that ibuprofen has gone on the market has ordinary preparations such as tablet, capsule, slow releasing tablet, slow releasing capsule, slow-release suppository, suspensoid and gel; These existing Motrins are the same with other NSAID (NSAIDs); Absorption difference, bioavailability is low, onset is relatively slow, and the patient of child, old people and the solid preparation of can not swallowing is made troubles.Although (S)-ibuprofen has overcome shortcomings such as existing Motrin side effect is big, taking dose is big, its dissolubility is little, be difficult for processing diffluent dosage form, brought a lot of inconvenience for patient's medication.And granule has taking convenience, bioavailability is high, onset is rapid, compares also to have with the common liq preparation and carries advantage more easily.Thereby, be necessary to develop (s)-ibuprofen granules.
Application number is to disclose a kind of (s)-ibuprofen granules and preparation method thereof in 200610070783.6 the Chinese invention patent application; During forming, its (s)-ibuprofen granules contains following materials of weight proportions: (S)-ibuprofen 1; Alkaline auxiliary solvent 0-100, filler 0.1-100, binding agent 0.1-12; Correctives 0.01-0.5, lubricant 0.1-2.Its preparation method is each component mixing, granulation, packing.Because it is low that (S)-ibuprofen gets fusing point, is 48 ℃～52 ℃, this method adopts cold drying to prepare (s)-ibuprofen granules; The temperature of its cold drying is 35 ℃～40 ℃, and this temperature is fit to growth of microorganism, causes the product microbial limit defective; And the cold drying required time is long; Not only the moisture of product is not easy control, and quality can not guarantee, and cost is high.If can develop a kind of new (s)-ibuprofen granules prescription and preparation method thereof, low-cost high-quality to realize, will have good market prospect.
Summary of the invention
The invention provides that a kind of cost is low, the measured (s)-ibuprofen granules of matter.
The present invention also provides a kind of operation simple, quality controllable and be suitable for the method for preparing of the (s)-ibuprofen granules of suitability for industrialized production; Fundamentally avoid the underproof phenomenon of (s)-ibuprofen granules microbial limit of existing method for preparing preparation, improved the qualification rate of product greatly.
A kind of (s)-ibuprofen granules, mainly process by following bulk drugs and pharmaceutic adjuvant:
1～10 part of (S)-ibuprofen
1～6 part of sodium carbonate
1～35 part of sucrose
0.1～0.8 part of aspartame
3～12 parts of ethanol.
As preferably:
Described (s)-ibuprofen granules, mainly process by following bulk drugs and pharmaceutic adjuvant:
1～5 part of (S)-ibuprofen
1～5 part of sodium carbonate
10～28 parts of sucrose
0.1～0.6 part of aspartame
3～10 parts of ethanol.
Described ethanol is as wetting agent, and the preferred volume percent concentration is 75% ethanol water (i.e. 75% ethanol).75% ethanol is volatile, can remove in preparation process and dry run, and simultaneously, 75% ethanol also is disinfectant, is unfavorable for growing of microorganism, guarantees that the microbial limit of (s)-ibuprofen granules reaches the requirement of criterion of acceptability.
In order to make the fragrant odour of granule, described pharmaceutic adjuvant can also comprise essence, can select this area medicinal essence commonly used for use.
Described sodium carbonate is as cosolvent, and itself and (S)-ibuprofen mol ratio guarantee to have better clarity after the granule dissolving, and ornamental were good, increased the oral toleration of granule simultaneously more than or equal to 1: 1.
In order to make the agent of particle diameter homogeneous granules, the grain diameter of described (S)-ibuprofen, sodium carbonate, sucrose or aspartame (being aspartame) is all smaller or equal to 80 orders.
The method for preparing of described (s)-ibuprofen granules may further comprise the steps:
Aspartame, (S)-ibuprofen and sodium carbonate mix homogeneously are obtained mixture; Divide sucrose 3 times and add said mixture; Each addition is 1/3 of a sucrose gross weight, all need mix mixing after adding sucrose at every turn, adds ethanol then and processes soft material; After granulating,, promptly obtain (s)-ibuprofen granules behind the granulate 50 ℃～100 ℃ dryings.
Described exsiccant temperature is preferably 60 ℃～80 ℃.
The described exsiccant time is 2 hours～4 hours.
In order to make the fragrant odour of granule, described soft material through granulate and dry after can spray into essence, granulate again behind the mix homogeneously makes (s)-ibuprofen granules.
Described essence can be selected this area medicinal essence commonly used for use, and the consumption of essence can be adjusted according to practical situation, not strict restriction.
General 20 mesh sieves that adopt of described pelletization; General 18 mesh sieves that adopt of described granulate process.
Because the fusing point of (S)-ibuprofen is lower; Be 48 ℃～52 ℃, very easily melt during high temperature drying that the present invention is controlled at least 1: 10 with sucrose and (S)-ibuprofen weight ratio; Utilize the big skeleton of sucrose molecule to support (S)-ibuprofen; Even (S)-ibuprofen has melted during high temperature drying (its skeleton avalanche), it also is to be present in the built on stilts crack of the DAGU of sucrose, guarantees finally to process granule.If the consumption of sucrose is less, (S)-ibuprofen can melt during high temperature drying, and the product that finally makes will be a block or thick, can't obtain granule.
In addition; Sucrose in the (s)-ibuprofen granules is water soluble compound; Sodium carbonate is that alkaline matter also is a water-soluble substances, with (s)-ibuprofen granules water-soluble after, sodium carbonate and sucrose very easily are dissolved in the water; The acid (S)-ibuprofen that is positioned at the built on stilts crack of sucrose molecule DAGU this moment forms the sodium salt of good water solubility because the dissolving of support frame sucrose can come out fast with alkaline carbonic acid sodium, thereby improves the dissolubility of medicine.
These article specification is the 200mg/ bag; Usage: warm water is taken after mixing it with water.Consumption: child's consumption sees the following form:
Adult's consumption: take every day 2～3 times, each 1～2 bag, or follow the doctor's advice.
Advantage of the present invention is:
The (S)-ibuprofen mixture that specified raw material of the present invention is formed can stand high temperature drying, and quality index such as the (s)-ibuprofen granules microorganism that makes is limited the quantity of, dissolubility are all qualified, stable and controllable for quality.
Method for preparing of the present invention is simple, adopts high temperature drying, and the granule moisture, the microorganism that make are controlled easily, and drying time is short, with short production cycle, need not any special installation, and cost is low, is suitable for suitability for industrialized production.
The specific embodiment
Embodiment 1
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use.
Take by weighing the raw material of following recipe quantity:
(S)-ibuprofen 200g
Sodium carbonate 200g
Sucrose 2480g
Aspartame 60g
75% ethanol 860g
Lychee flavor 10g.
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding, add 75% ethanol behind the mixing and process soft material, adopt 20 mesh sieves to granulate the back at 60 ℃ of forced air drying 2h; Spray into lychee flavor, total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate; Intermediate after the assay was approved; Be distributed into 14600 bags with Aluminum-plastic composite bag by the 200mg/ bag, packing gets product.
Embodiment 2
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use.
Take by weighing the raw material of following recipe quantity:
(S)-ibuprofen 100g
Sodium carbonate 300g
Sucrose 2360g
Aspartame 14g
75% ethanol 460g
Fragrant citrus essence 5g.
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding, add 75% ethanol behind the mixing and process soft material, adopt 20 mesh sieves to granulate the back at 70 ℃ of forced air drying 1.5h; Spray into fragrant citrus essence, total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate; Intermediate after the assay was approved; Be distributed into 13480 bags with Aluminum-plastic composite bag by the 200mg/ bag, packing gets product.
Embodiment 3
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use.
Take by weighing the raw material of following recipe quantity:
(S)-ibuprofen 400g
Sodium carbonate 500g
Sucrose 4360g
Aspartame 60g
75% ethanol 1300g
Green apple essence 20g.
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding, add 75% ethanol behind the mixing and process soft material, adopt 20 mesh sieves to granulate the back at 80 ℃ of forced air drying 1h; Spray into green apple essence, total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate; Intermediate after the assay was approved; Be distributed into 25280 bags with Aluminum-plastic composite bag by the 200mg/ bag, packing gets product.
The (s)-ibuprofen granules that embodiment 1～3 is made carries out quality inspection, concrete assay such as table 1:
The related check data of table 1 (s)-ibuprofen granules
| Lot number | Character | Content uniformity | Granularity | Loss on drying (%) | Dissolubility (%) | Microbial limit | Related substance (%) | Content (%) |
| Embodiment 1 | Faint yellow granule | Up to specification | Up to specification | 0.80 | Up to specification | Up to specification | 0.10 | 99.45 |
| Embodiment 2 | Faint yellow granule | Up to specification | Up to specification | 0.84 | Up to specification | Up to specification | 0.13 | 99.57 |
| Embodiment 3 | Faint yellow granule | Up to specification | Up to specification | 0.76 | Up to specification | Up to specification | 0.10 | 101.1 8 |
Testing data from table 1 can know that the (s)-ibuprofen granules that the inventive method makes is up to specification, and the feasibility and the reliability of prescription of the present invention and method also has been described.
Mobility of particle is investigated (mensuration of angle of repose)
Foundation: measure angle of repose to investigate particulate flowability with the fixed funnel method.
Method: funnel is fixed on the diagram paper of horizontal positioned, the (s)-ibuprofen granules that carefully the foregoing description 2 is made is poured in the funnel, measures three times, and the result sees table 2.The cone height that is formed with granules is H, and the radius of cone bottom is r, then tan α=H/r (α is angle of repose); Angle of repose is more little, and then mobility of particle is good more.
Table 2 (s)-ibuprofen granules is measured table as a result angle of repose
According to said method the (s)-ibuprofen granules that embodiment 1 and 3 makes is carried out fluidity testing, its angle of repose is also 1.4 ± 0.5.
Conclusion can be known by above result of the test, and (s)-ibuprofen granules of the present invention is less angle of repose, explains that mobility of particle of the present invention is better, is easy to packing.
Comparative Examples 1
Except baking temperature is 35 ℃, be outside the 10h drying time, and all the other are operated with embodiment 1, make (s)-ibuprofen granules.
Comparative Examples 2
Except baking temperature is 40 ℃, be outside the 8h drying time, and all the other are operated with embodiment 1, make (s)-ibuprofen granules.
The (s)-ibuprofen granules of embodiment 1～3 preparation and the (s)-ibuprofen granules of Comparative Examples 1～2 preparation are carried out quality inspection, the testing result such as the table 3 of projects.
All according to the record method in the version Pharmacopoeia of the People's Republic of China in 2005, the standard of microbial limit is the detection method of loss on drying, melting, limit test of microbe project: the every 1g of bacterial population must not surpass 1000cfu and every 1ml must not surpass 100cfu; Every 1g of mycete and yeast count or 1ml must not surpass 100cfu; Every 1g of escherichia coli or 1ml must not detect.
Table 3
| Sequence number | Drying time (h) | Loss on drying (%) | Microbial limit (every 1g or 1ml) | Related substance (%) |
| Embodiment 1 | 2.0 | 0.80 | The every 1g of bacterial population is＜10cfu; The every 1g of mycete and yeast count is＜10cfu; The every 1g of escherichia coli does not detect, so up to specification | 0.10 |
| Embodiment 2 | 1.5 | 0.84 | The every 1g of bacterial population is＜10cfu; The every 1g of mycete and yeast count is＜10cfu; The every 1g of escherichia coli does not detect, so up to specification | 0.13 |
| Embodiment 3 | 1.0 | 0.76 | The every 1g of bacterial population is＜10cfu; The every 1g of mycete and yeast count is＜10cfu; The every 1g of escherichia coli does not detect, so up to specification | 0.10 |
| Comparative Examples 1 | 10 | 1.02 | The every 1g of bacterial population is 180cfu; The every 1g of mycete and yeast count is 120cfu; The every 1g of escherichia coli does not detect, so against regulation | 0.26 |
| Comparative Examples 2 | 8 | 2.52 | The every 1g of bacterial population is 60cfu; The every 1g of mycete and yeast count is 20cfu; The every 1g of escherichia coli does not detect, and is up to specification | 0.27 |
Testing data from table 3 can be known; The inventive method makes (s)-ibuprofen granules drying time is short, moisture is controlled, microorganism is up to specification and content is extremely low, with short production cycle, quality controllable, be beneficial to the saving cost; And it is simple to operate; Meet the suitability for industrialized production requirement, be superior to existing method for preparing.
Claims (3)
1. (s)-ibuprofen granules, the method for preparing of described (s)-ibuprofen granules is:
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use;
Take by weighing the raw material of following recipe quantity:
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding; Adding concentration expressed in percentage by volume behind the mixing is that 75% ethanol water is processed soft material, adopts 20 mesh sieves to granulate the back at 60 ℃ of forced air drying 2h, sprays into lychee flavor; Total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate.
2. (s)-ibuprofen granules, the method for preparing of described (s)-ibuprofen granules is:
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use;
Take by weighing the raw material of following recipe quantity:
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding; Adding concentration expressed in percentage by volume behind the mixing is that 75% ethanol water is processed soft material, adopts 20 mesh sieves to granulate the back at 70 ℃ of forced air drying 1.5h, sprays into fragrant citrus essence; Total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate.
3. (s)-ibuprofen granules, the method for preparing of described (s)-ibuprofen granules is:
(S)-ibuprofen, sodium carbonate, aspartame are crossed 80 mesh sieves respectively, and sucrose is pulverized the back and crossed 80 sieves, and is subsequent use;
Take by weighing the raw material of following recipe quantity:
Aspartame, (S)-ibuprofen, the abundant mix homogeneously of sodium carbonate are obtained mixture, sucrose is equally divided into etc. heavy 3 parts, divide 3 times and add said mixture; All to mix 10 minutes after each the adding; Adding concentration expressed in percentage by volume behind the mixing is that 75% ethanol water is processed soft material, adopts 20 mesh sieves to granulate the back at 80 ℃ of forced air drying 1h, sprays into green apple essence; Total mixing promptly obtains (s)-ibuprofen granules behind the 18 mesh sieve granulate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101580082A CN101829064B (en) | 2010-04-27 | 2010-04-27 | Dexibuprofen particle and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101580082A CN101829064B (en) | 2010-04-27 | 2010-04-27 | Dexibuprofen particle and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101829064A CN101829064A (en) | 2010-09-15 |
| CN101829064B true CN101829064B (en) | 2012-04-25 |
Family
ID=42713386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101580082A Active CN101829064B (en) | 2010-04-27 | 2010-04-27 | Dexibuprofen particle and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101829064B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400896A (en) * | 2000-01-28 | 2003-03-05 | 巴斯福股份公司 | Ibuprofen containing active agent preparation |
| CN101077343A (en) * | 2006-12-12 | 2007-11-28 | 汪洪湖 | Dexibuprofen granule and preparation method thereof |
| CN101219128A (en) * | 2007-01-14 | 2008-07-16 | 海南高升医药科技开发有限公司 | Dexibuprofen pharmaceutical composition with improved dissolving out capability and method for preparing the same |
| WO2009084041A2 (en) * | 2008-01-01 | 2009-07-09 | Shasun Chemicals And Drugs Limited | Pharmaceutical compositions of dexibuprofen |
-
2010
- 2010-04-27 CN CN2010101580082A patent/CN101829064B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400896A (en) * | 2000-01-28 | 2003-03-05 | 巴斯福股份公司 | Ibuprofen containing active agent preparation |
| CN101077343A (en) * | 2006-12-12 | 2007-11-28 | 汪洪湖 | Dexibuprofen granule and preparation method thereof |
| CN101219128A (en) * | 2007-01-14 | 2008-07-16 | 海南高升医药科技开发有限公司 | Dexibuprofen pharmaceutical composition with improved dissolving out capability and method for preparing the same |
| WO2009084041A2 (en) * | 2008-01-01 | 2009-07-09 | Shasun Chemicals And Drugs Limited | Pharmaceutical compositions of dexibuprofen |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101829064A (en) | 2010-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101352449B (en) | Vitamin orally disintegrating tablet and preparation method thereof | |
| CN101766648B (en) | Polyethylene glycol electrolyte granular preparation and production method | |
| CN105142618A (en) | Mosapride sustained-release preparation for providing pharmacological clinical effects with once-a-day administration | |
| CN101272768A (en) | Diclofenac formulations and methods of use | |
| CN104906064A (en) | Pregabalin intragastric floating sustained release tablet and preparation method thereof | |
| CN102379869A (en) | Oral preparation containing saxagliptin and application thereof | |
| BR112019016118A2 (en) | dosage form of lamotrigine oral suspension | |
| CN101077343B (en) | Dexibuprofen granule and preparation method thereof | |
| CN103610658A (en) | Immunomodulator slow-release preparation and preparation method thereof | |
| CN102488670B (en) | Preparation method of dual slow-release potassium citrate sustained release preparation | |
| CN101829064B (en) | Dexibuprofen particle and preparation method thereof | |
| CN101023917A (en) | Technology for preparing medicine and relative oral preparations | |
| CN101632661A (en) | Compound amoxicillin slow release dry suspension composition and preparation method thereof | |
| CN101856331B (en) | Arginine (s)-ibuprofen granules and preparation method thereof | |
| CN100448431C (en) | Oral disintegrated Anfenmame tablet for treating children's cold and its prepn | |
| CN101480397B (en) | Cefixime orally disintegrating tablet and preparation method thereof | |
| CN102885774B (en) | Prasugrel composition and preparation method thereof | |
| CN103772378B (en) | Meloxicam compound and tablet thereof | |
| CN107456444B (en) | Mosapride sustained-release dry suspension and preparation method thereof | |
| CN102311452A (en) | Cefixime crystal, preparation method thereof and tablet composition containing same | |
| CN106176622A (en) | A kind of isorhynchophylline slow releasing preparation treating hypertension and preparation method thereof | |
| CN102335153B (en) | Piperazine ferulate sustained-release tablet and its preparation method | |
| CN101496818B (en) | Kidney-nourishing and bone-tonifying chewable tablet and preparation method thereof | |
| CN103432082A (en) | Glucosamine composition and preparation method thereof | |
| CN102600108A (en) | Flurbiprofen sustained release capsules 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 | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: HAINAN GOURD DOLL PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINAN XINZHONGZHENG PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 570216 West B District, No. 6 workshop, Haikou Free Trade Zone, Hainan Patentee after: Hainan Gourd Doll Pharmaceutical Co., Ltd. Address before: 570216 West B District, No. 6 workshop, Haikou Free Trade Zone, Hainan Patentee before: Hainan Xinzhongzheng Pharmaceutical Co., Ltd. |
|
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 570216 West B District, No. 6 workshop, Haikou Free Trade Zone, Hainan Patentee after: HAINAN HULUWA PHARMACEUTICAL GROUP CO., LTD. Address before: 570216 West B District, No. 6 workshop, Haikou Free Trade Zone, Hainan Patentee before: Hainan Gourd Doll Pharmaceutical Co., Ltd. |