CN100464750C - Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate - Google Patents
Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate Download PDFInfo
- Publication number
- CN100464750C CN100464750C CNB2006100338526A CN200610033852A CN100464750C CN 100464750 C CN100464750 C CN 100464750C CN B2006100338526 A CNB2006100338526 A CN B2006100338526A CN 200610033852 A CN200610033852 A CN 200610033852A CN 100464750 C CN100464750 C CN 100464750C
- Authority
- CN
- China
- Prior art keywords
- supercritical fluid
- amoxicillin sodium
- medicine
- solvent
- solution
- 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
Images
Abstract
The present invention relates to a method for preparing medicine mixture containing amoxicillin sodium and potassium clavulunate. Said method includes the following processes: (a), dissolving two medicine active components in solvent according to a certain ratio so as to form a solution; (b), mixing said solution with supercritical fluid; and (c), separating out medicine micropowder from supercritical fluid. Said medicine granules have good fluidity.
Description
Technical field
The present invention relates to medical preparation field, particularly a kind of preparation contains the method for the medicinal mixture of Amoxicillin Sodium and clavulanate potassium.
Background technology
Contain the mixed product that two or more antibiotic pharmaceutical composition mostly is dried powder greatly, in order to guarantee the uniformity of preparation of Chinese medicine content, need the processing such as pulverize, sieve of each composition is made each composition mix homogeneously in the compositions.Because the difference of granular size, density, form and apparent condition and surface energy is brought difficulty to mixed process between heterogeneity, and the material that has mixed also can separate in course of conveying once more.With two or more medicament mixed evenly and the conventional production method of making granule or mixed powder mechanical lapping, lyophilization, spray drying etc. are arranged.But all there is suitable defective in these traditional methods.
Polishing be with each composition through grinding and mixing, obtain final product.Yet this method has several obvious defects.The most outstanding defective is: is used for grinding and directly contacts, make medicine be subjected to the pollution of pyrogen and other impurity with ingredient with blended plant equipment, and very unfavorable for the sterile production of non-enterally administer.Secondly, grinding can destroy the surface and the crystallographic property of material, and produces static, makes between the granule inter-adhesively, mobile poor, is unfavorable for further processing and packing.In addition, this method also needs special installation to capture the dust that produces; Other shortcomings also comprise: need the long period just can reach desired mixing homogeneity; And the grinding of high shear can cause the degraded of ingredient.
Freeze-drying is not suitable for water-insoluble medicine, and granular size and distribute is waywardly brought some problems to following process; Final products contain certain moisture.
Another mixed method commonly used is a spray drying.Its process is with medicine dissolution or is suspended in (mixture of single solvent or several solvents) in the suitable solvent, then this solution or suspension is sprayed into drying in the thermal current, obtains fine drug powder or granule.The shortcoming of this method is to need to use a large amount of solvents; Thermally labile medicine meeting decomposes; Product yield is lower; Need to reclaim the equipment of solvent; And need carry out after drying usually to remove residual solvent.
After two kinds of medicament mixed become uniform powder body, need further process or packing usually.The flowability of powder body is the critical nature that must consider in the solid preparation preparation process, and mobile difference not only influences normal production process, and influences the quality of preparation, makes indexs such as weight differential and uniformity of dosage units defective.
Amoxicillin Sodium and clavulanate potassium are intravenous injection, are used for the treatment of infectious disease.Be present clinical topmost anti-infectives, have selectivity height, characteristics that toxicity is low.
The amoxicillin is a penbritin class antibiotic, and clavulanate potassium itself has only faint antibacterial activity, but has the enzyme inhibition of powerful broad-spectrum beta-lactam, and both share, and can protect the amoxicillin to exempt from the beta-lactam enzyme hydrolysis.The in-vitro antibacterial that amoxicillin and clavulanic acid share is discovered, clavulanic acid improve the amoxicillin minority intestinals such as Klebsiella, proteus vulgaris are produced inha enzyme etc. antibacterial action 4-32 doubly, the antibacterial activity of hemophilus influenza is improved 32 times.For moraxelle catarrhalis, clavulanic acid can improve amoxicillin antibacterial activity 4-32 doubly.The antimicrobial spectrum of this product is identical with the amoxicillin, and enlarges to some extent.To producing enzyme staphylococcus aureus, staphylococcus epidermidis, coagulase-negative Fructus Vitis viniferae ball and the equal tool good action of enterococcus, some enterobacteriaceae lactobacteriaceae, hemophilus influenza, moraxelle catarrhalis, bacteroides fragilis etc. that produce beta lactamase also there is better antibacterial activity.
The indication of this medicine is:
1, upper respiratory tract infection: sinusitis, tonsillitis, pharyngitis.
2, lower respiratory infection: acute bronchitis, acute episode of chronic bronchitis, pneumonia, pulmonary abscess and concurrent infection of bronchiectasis.
3, urinary system infection: cystitis, urethritis, pyelonephritis, prostatitis, pelvic inflammatory disease, Diplococcus gonorrhoeae urinary tract infection.
4, skin and soft tissue infection: furuncle, abscess, peak nest are knitted inflammation, wound infection, the interior sepsis of abdomen etc.
5, other infection: otitis media, osteomyelitis, septicemia, peritonitis and post-operative infection.
(as multidirectional mixer) carried out in the routine production of Amoxicillin Sodium/clavulanate potassium at present in mixing apparatus.Because clavulanate potassium causes blast because of bump or friction easily, and at high temperature decomposes easily, should mix filling under the condition of nitrogen.Gained mixes the problem that there is mobile difference in powder, gives the aseptic subpackaged certain difficulty of bringing.Therefore, be necessary to study a kind of mixed method, make final products have favorable uniformity and flowability, and reduce dissolvent residual, correspondingly reduce toxic and side effects, improve curative effect.
Summary of the invention
The object of the present invention is to provide a kind of preparation to contain the medicament mixed method of Amoxicillin Sodium and clavulanate potassium, make product mix have good processing properties, and Determination of Residual Organic Solvents significantly reduces.
The objective of the invention is to realize by the following technical solutions:
A kind of preparation contains the method for the medicinal mixture of Amoxicillin Sodium and clavulanate potassium, comprises following process: (a) two kinds of active constituents of medicine are dissolved in proportion and form solution in the solvent; (b) solution that will comprise two kinds of active constituents of medicine mixes with supercritical fluid; (c) from supercritical fluid, isolate drug powder.
In process (b), earlier supercritical fluid is compressed to predetermined pressure range, imports in the hermetic container after the preheating.
Spray in the described supercritical fluid by nozzle at solution described in the process (b).
Described solution flow rate 0.4-1.8ml/min, preferred 0.8-1.2ml/min.
20-50 ℃ of described supercritical fluid temperature, preferred 25-40 ℃, more preferably 30-35 ℃.
Described supercritical fluid pressure 7.4-22MPa, preferred 8.0-10MPa
Described supercritical fluid is selected from a kind of in supercritical carbon dioxide, ammonia, ethylene, propane, propylene, pentane, CHF3, ethanol, the water.
Described supercritical fluid is a supercritical carbon dioxide.
Described solvent is a kind of in water and the methanol or mixture that both form with arbitrary proportion.
The ratio of described Amoxicillin Sodium and clavulanate potassium is 1:1-100:1.
The angle of repose of described drug powder is less than 30 °.
The application of supercritical fluid technology is one of quite popular in recent years research theme.Supercritical fluid (supercritical fluid, SCF) be meant the fluid that is in more than critical temperature (TC) and the critical pressure (PC), near critical point, all fluidic rerum naturas such as fluidic density, viscosity, dissolubility, thermal capacity, dielectric constant can occur phenomenon jumpy takes place.
Supercritical fluid is owing to liquid and gas boundary disappearance, even be the non-coherency gas that pressurize does not also liquefy.The rerum natura of supercritical fluid has gas, the biphase dual characteristics of liquid concurrently, has both had high diffusion coefficient and the low viscosity suitable with gas, has the density close with liquid again and to the material good dissolving ability.Its density changes very responsive to temperature and pressure, and proportional in the certain pressure scope with solvability, so can change solubility of substances by the control temperature and pressure.Has very strong physical force.Most of supercritical fluid be gaseous state under normal pressure, therefore after use, only need reduce pressure promptly can become gas phase, and with other solid, liquid separating substances mutually, so easy recycling; This also is one of advantage of supercritical fluid.
The application of supercritical fluid in medical industry mainly contains supercritical fluid chromatography (supercritical fluid chromatography, SFC), supercritical fluid extraction (supercriticalfluid extraction, SFE), using supercritical fluid quick expansion technology (rapid expansion ofsupercritical fluid solution, RESS), the super-critical anti-solvent technology (supercriticalanti-solvent, SAS) etc.In medicament mixed and crystallization is coprecipitated mainly can adopt RESS and SAS aspect analysing.
The principle of RESS is: solute is dissolved in the supercritical fluid, form behind the supercritical solution by a special nozzle atomization ejection, rapid expanding form to the big degree of supersaturation of solute then precipitating become granule.Generally speaking, the dissolubility of nonvolatile matter in SCF be than big several to tens orders of magnitude in the perfect condition gas under uniform temp pressure, therefore as the SCF that be dissolved with difficult volatile material by ad hoc approach at the utmost point in the short time (1 * 10
-6-1 * 10
-5When s) rapid expanding is to normal pressure even vacuum,, the variation of pressure forms very big degree of supersaturation, the very fast precipitating of solute owing to causing the variation that the fluid solvability takes place.Be accompanied by ultrasonic concussion during the SCF rapid expanding, form consistent nucleation condition, make further miniaturization of its granule and particle size distribution narrower.
For many in supercritical fluid the less material of dissolubility then can adopt the SAS process.In the method, solute at first is dissolved in the The suitable solvent, because of solute is insoluble in SCF, solvent then dissolves each other fully with it, introduce SCF in this solution after, owing to SCF absorbs the dissolving of solvent, liquor capacity expands and changes active force between solvent and solute, reduce the solvability of solvent, make solute form supersaturation and precipitate and separate out.By selecting suitable supercritical fluid operating condition, solvent for use can be anti-molten by supercritical fluid fully, do not have any residual in drug microparticles.In addition, by the mixing rate of control supercritical fluid and solution, with regard to the precipitation rate of may command solute, thereby the size and shape of microgranule is separated out in control.It is one of characteristics of SAS that degree of supersaturation is easy to control, owing to can under near ambient temperature, operate, so the SAS process can be used for the processing and the preparation of thermal sensitivity, oxidisability, fearness bump material.
The common feature of SAS process and RESS process is: if select a kind of suitable supercritical fluid, operating process is carried out under near the condition of room temperature.But RESS crosses the solute that range request separates out must be able to be dissolved in the supercritical fluid, and this tends to meet difficulty in the selection of supercritical fluid.For most medicine, its complex structure, dissolubility is quite limited in the most frequently used CO2 that makes supercritical fluid, is difficult for effectively utilizing the rapid expanding method to carry out the granulating of medicine.In this case, the SAS process can remedy the deficiency of RESS process, because it only needs to select a kind of solvent that can be dissolved in CO2 to get final product.
In the present invention, preferred SAS process prepares the medicament composition granule that contains Amoxicillin Sodium and clavulanate potassium.
The present invention makes final products have favorable uniformity and flowability, and reduces dissolvent residual owing to adopted the supercritical fluid technology preparation to contain the medicinal mixture of Amoxicillin Sodium and clavulanate potassium, correspondingly reduces toxic and side effects, improves curative effect; Particularly using the CO 2 supercritical technology to prepare pharmaceutical composition of the present invention further has the following advantages whole process of preparation:
(1) operating condition gentleness can not cause medicine decomposition and rotten;
(2) whole process is carried out in the container of sealing, helps keeping the aseptic condition of medicine;
(3), can obtain the product of uniform particles, no solvent residue by reasonable control to process conditions; And the product good fluidity has good post-treatment performance;
(4) the recyclable utilization of solvent for use and carbon dioxide, economic environmental protection.
Description of drawings
Fig. 1 is the conventional gas chromatogram that mixes powder;
Fig. 2 and 3 is respectively the gas chromatogram of sample 1 and sample 2;
Fig. 4 is the conventional high-efficient liquid phase chromatogram that mixes the powder sample;
Fig. 5 and Fig. 6 are respectively the high-efficient liquid phase chromatograms of sample 1 and sample 2.
The specific embodiment
Further specify the present invention below by specific embodiment, but therefore do not limit the present invention among the described scope of embodiments.
Embodiment one
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in the methanol, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 100mg/ml and 20mg/ml.Be compressed to predetermined pressure 8.0MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 0.8ml/min, separate out actuator temperature and remain on 30 ℃.After the decompression, collect the gained microgranule, get sample 1 in separating out the device bottom.
Embodiment two
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in the distilled water, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 50mg/ml and 5mg/ml.Be compressed to predetermined pressure range 10MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 1.0ml/min, separate out actuator temperature and remain on 35 ℃.After the decompression, collect the gained microgranule, get sample 2 in separating out the device bottom.
The supercritical fluid equipment that is adopted among the present invention is commercially available commercially produced product, as the anti-solvent-granulation of the supercritical system of U.S. Thar Technologies company.
Get the production method mixing routinely of same Amoxicillin Sodium and clavulanate potassium raw material, compare discovery, be greatly improved aspect mobile through the sample of treatment with supercritical fluid, before dissolvent residual also significantly is lower than processing with sample 1 and sample 2.
(1), measure fluidity testing--angle of repose
Be that the free inclined-plane of powder body accumulation horizon is under immobilized poised state, with the formed maximum angular of horizontal plane angle of repose.It drops on the particular platform powder body naturally by ad hoc fashion and forms.Angle of repose, angle of repose was more little to the flowability affects maximum of powder body, and the flowability of powder body is good more.Also claim angle of repose such as angle of repose, angle of repose etc.In the pharmaceutical production, can satisfy production requirement less than 40 ° angle of repose, and angle of repose is good less than 30 ° of expression powder fluidities, helps producing.
We adopt powder body overall characteristic tester to measure the angle of repose of three kinds of powder.After testing, be significantly less than the angle of repose that conventional production method gained mixes powder with the blended sample of supercritical fluid technology, flowability is greatly improved, and helps following process angle of repose.Table 1 is data angle of repose of each powder sample.
Data angle of repose of three samples of table 1
| Sample | Angle of repose |
| Amoxicillin Sodium/clavulanate potassium (the conventional powder that mixes) | 56° |
| Amoxicillin Sodium/clavulanate potassium of the present invention (sample 1) | 24° |
| Amoxicillin Sodium/clavulanate potassium of the present invention (sample 2) | 28° |
(2), the organic solvent residue amount detects
Methyl acetate, ethanol, three kinds of organic solvents of acetone have been used in the Amoxicillin Sodium building-up process; Used n-butyl alcohol in the clavulanate potassium production, raw materials used middle possible residual have acetone, two kinds of organic solvents of ethyl acetate; Owing to use solvent methanol in this technology,, following organic solvent residue amount is checked: methanol, methyl acetate, ethanol, acetone, n-butyl alcohol, ethyl acetate simultaneously in order to prove conclusively technogenic influence.
Still detect organic solvent in routine mixing finished product, as shown in Figure 1, it is residual to detect acetone, methyl acetate and ethyl acetate.Though residual quantity below the limit of pharmacopeia regulation, still has certain influence to the quality of medicine.Shown in Fig. 2 and 3, do not detect dissolvent residual, methanol does not detect yet; Show through the sample of treatment with supercritical fluid and not only can not bring dissolvent residual into, and can remove the solvent that exists in the raw material, make that Determination of Residual Organic Solvents significantly reduces in the finished product, help improving the quality of products.
(3), whether assessment treatment with supercritical fluid process makes medicine decompose or produces other influences
For whether assessment treatment with supercritical fluid process makes the medicine decomposition or produce other influences, take a sample respectively and carried out the related substance detection by official method.
As Fig. 4, Fig. 5 and shown in Figure 6, the related substance that mixes the sample of powder with the sample and the routine of treatment with supercritical fluid does not have significant difference, illustrates that this technology can not exert an influence to product quality.
Embodiment three
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in distilled water and the methanol mixture, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 100mg/ml and 1mg/ml.Be compressed to predetermined pressure range 15MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 1.5ml/min, separate out actuator temperature and remain on 40 ℃.After the decompression, collect the gained microgranule, get sample in separating out the device bottom.
Embodiment four
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in the distilled water, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 50mg/ml and 50mg/ml.Be compressed to predetermined pressure range 22MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 1.8ml/min, separate out actuator temperature and remain on 50 ℃.After the decompression, collect the gained microgranule, get sample in separating out the device bottom.
Embodiment five
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in distilled water and the methanol mixture, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 80mg/ml and 1mg/ml.Be compressed to predetermined pressure range 7.4MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 0.4ml/min, separate out actuator temperature and remain on 20 ℃.After the decompression, collect the gained microgranule, get sample in separating out the device bottom.
Embodiment six
Take by weighing Amoxicillin Sodium/clavulanate potassium in proportion and be dissolved in the distilled water, make the concentration of Amoxicillin Sodium and clavulanate potassium be respectively 50mg/ml and 50mg/ml.Be compressed to predetermined pressure range 12MPa after the CO2 gas filtration, separate out in the device by the pump input after the preheating.Drug solution is sprayed in the supercritical fluid with flow velocity 1.2ml/min, separate out actuator temperature and remain on 25 ℃.After the decompression, collect the gained microgranule, get sample in separating out the device bottom.
In the foregoing description, supercritical fluid CO2 can also be comprised replacements such as ammonia, ethylene, propane, propylene, pentane, CHF3, ethanol, water by other supercritical fluids commonly used.Table 2 is near common supercritical fluid some physical propertys critical point.
The critical data of table 2 supercritical fluid commonly used
| Solvent | Tc，℃ | Pc，MPa | ρc，Kg/m3 |
| Carbon dioxide (CO 2) | 30.9 | 7.375 | 468 |
| Water (H 2O) | 373.9 | 22.06 | 322 |
| Methanol (CH 3OH) | 239.4 | 8.092 | 272 |
| Ethane (C 2H 6) | 32.2 | 4.884 | 203 |
| Ethylene (C 2H 4) | 9.1 | 5.041 | 214 |
| Ethanol (CH 3CH 2OH) | 240.7 | 6.137 | 276 |
| Propane (C 3H 8) | 96.6 | 4.250 | 217 |
| Toluene (C 7H 8) | 318.55 | 4.013 | 291 |
Tc: critical temperature Pc: critical pressure ρ c: critical density
In the present invention, preferably carbon dioxide is as supercritical fluid, and it has following characteristics:
(1) the CO2 critical-temperature is 31 ℃, and critical pressure is that 7.4MPa critical condition is moderate, and is few to the destruction of active ingredient.
(2) CO2 chemical property torpescence, colorless and odorless is nontoxic, does not fire, and security is good. Free from environmental pollution, and can avoid the oxidation of product.
(3) low price, purity is high, obtains easily.
Claims (8)
1, a kind of preparation contains the method for the medicinal mixture of Amoxicillin Sodium and clavulanate potassium, comprises following process: (a) two kinds of active constituents of medicine are dissolved in proportion and form solution in the solvent; (b) solution that will comprise two kinds of active constituents of medicine mixes with supercritical fluid; (c) from supercritical fluid, isolate drug powder; Spray in the described supercritical fluid by nozzle at solution described in the process (b), it is characterized in that, described solution flow rate 0.8-1.2ml/min; 20-50 ℃ of described supercritical fluid temperature; Described supercritical fluid pressure 7.4-22Mpa; Described solvent is a kind of in water and the methanol or mixture that both form with arbitrary proportion.
2, method according to claim 1 is characterized in that, 25-40 ℃ of described supercritical fluid temperature.
3, method according to claim 2 is characterized in that, 30-35 ℃ of described supercritical fluid temperature.
4, method according to claim 1 is characterized in that, described supercritical fluid pressure 8.0-10Mpa.
5, method according to claim 1 is characterized in that, described supercritical fluid is selected from supercritical carbon dioxide, ammonia, ethylene, propane, propylene, pentane, CHF
3, a kind of in the ethanol, water.
6, method according to claim 5 is characterized in that, described supercritical fluid is a supercritical carbon dioxide.
7, method according to claim 1 is characterized in that, the ratio of described Amoxicillin Sodium and clavulanate potassium is 1:1-100:1.
8, method according to claim 1 is characterized in that, the angle of repose of described drug powder is less than 30 °.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100338526A CN100464750C (en) | 2006-02-23 | 2006-02-23 | Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100338526A CN100464750C (en) | 2006-02-23 | 2006-02-23 | Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1850074A CN1850074A (en) | 2006-10-25 |
| CN100464750C true CN100464750C (en) | 2009-03-04 |
Family
ID=37131586
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100338526A Active CN100464750C (en) | 2006-02-23 | 2006-02-23 | Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100464750C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101647779B (en) * | 2008-08-11 | 2013-01-23 | 湘北威尔曼制药股份有限公司 | Novel almoxicillin sodium and clavulanate potassium compound powder preparation for injection and technology for preparing same |
| CN105476988A (en) * | 2015-11-19 | 2016-04-13 | 杭州长典医药科技有限公司 | Amoxicillin sodium-clavulanate potassium special superfine-powder preparation and preparing method thereof |
| CN115672451B (en) * | 2022-10-17 | 2023-11-07 | 江苏波杜农牧股份有限公司 | Self-adaptive updraft fluid pulverizer and working method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998035672A1 (en) * | 1997-02-14 | 1998-08-20 | Smithkline Beecham Laboratoires Pharmaceutiques | Pharmaceutical formulations comprising amoxocyllin and clavulanate |
| CN1686262A (en) * | 2005-04-21 | 2005-10-26 | 上海大学 | Method of preparing dragon's blood ultrafine powder using super crifical fluid reverse solvent method |
| CN1726010A (en) * | 2002-12-19 | 2006-01-25 | 巴克斯特国际公司 | Process for preparing combination pharmaceutical formulations using supercritical fluids |
-
2006
- 2006-02-23 CN CNB2006100338526A patent/CN100464750C/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998035672A1 (en) * | 1997-02-14 | 1998-08-20 | Smithkline Beecham Laboratoires Pharmaceutiques | Pharmaceutical formulations comprising amoxocyllin and clavulanate |
| CN1726010A (en) * | 2002-12-19 | 2006-01-25 | 巴克斯特国际公司 | Process for preparing combination pharmaceutical formulations using supercritical fluids |
| CN1686262A (en) * | 2005-04-21 | 2005-10-26 | 上海大学 | Method of preparing dragon's blood ultrafine powder using super crifical fluid reverse solvent method |
Non-Patent Citations (4)
| Title |
|---|
| 超临界反溶剂过程在生物制药中的应用. 韩冰等.药学进展，第27卷第1期. 2003 |
| 超临界反溶剂过程在生物制药中的应用. 韩冰等.药学进展，第27卷第1期. 2003 * |
| 超临界流体技术试制阿莫西林缓释微粒. 陈岚等.中国医药工业杂志，第36卷第2期. 2005 |
| 超临界流体技术试制阿莫西林缓释微粒. 陈岚等.中国医药工业杂志，第36卷第2期. 2005 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1850074A (en) | 2006-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102106806B (en) | Method for preparing solid preparation and solid preparation | |
| CN101537184A (en) | Composition containing water-insoluble high-activity drug and preparation method thereof | |
| Miura et al. | Enhancement of dissolution rate and oral absorption of a poorly water-soluble drug, K-832, by adsorption onto porous silica using supercritical carbon dioxide | |
| CN100464750C (en) | Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate | |
| KR20010032251A (en) | Pharmaceutical compositions having the shape of powders of cross-linked polymers loaded with drugs and related preparation process by supercritical fluids | |
| CN104666262B (en) | A kind of razaxaban piece | |
| CN103417512B (en) | A kind of Biomox and preparation method thereof | |
| CN105982870A (en) | Apixaban tablet | |
| CN103110595B (en) | Cefdinir dispersible tablet and preparation method thereof | |
| CN109718215A (en) | A kind of Ezetimibe piece | |
| CN110638768B (en) | Preparation method of medicine for treating male erectile dysfunction | |
| CN105085549A (en) | Cefaclor compound, medicine composition of cefaclor compound and bromhexine hydrochloride, and preparation of cefaclor compound | |
| Valle et al. | Supercritical fluid technique for particle engineering: drug delivery applications | |
| EP1401404B1 (en) | Method of encapsulating an active substance | |
| CN102106824B (en) | Eszopiclone solid preparation and preparation method thereof | |
| CN102552161A (en) | Preparation method of medicament solid preparation and obtained medicament solid preparation | |
| CN106389428A (en) | Composition capable of improving Azilsartan bioavailability and stability and preparation method of composition | |
| CN106860407A (en) | A kind of razaxaban piece | |
| CN103181905A (en) | Process for preparing pramipexole dihydrochloride tablets | |
| CN114557966B (en) | Method for producing everolimus solid dispersion through vacuum crawler-type oven | |
| CN104771380A (en) | Tacrolimus capsule capable of being rapidly dissolved out | |
| CN101890007A (en) | Amoxicillin sodium potassium clavulanate composition microballoon injection | |
| CN103919780B (en) | Calming soporific preparation, its compound preparation, preparation method and pharmaceutical composition | |
| CN103417535B (en) | A kind of amoxicillin and clavulanate potassium tablets and preparation method thereof | |
| CN103755694B (en) | A kind for the treatment of process of azilsartan crude drug |
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 | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Federal Pharmaceutical (Chengdu) Limited by Share Ltd Assignor: Zhuhai Lianbang Pharmaceutical Co., Ltd. Contract fulfillment period: 2007.3.9 to 2017.3.8 contract change Contract record no.: 2009510000083 Denomination of invention: Method for preparing medicinal mixture containing amoxicillin sodium and potassium clavulanate Granted publication date: 20090304 License type: Exclusive license Record date: 2009.9.27 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.3.9 TO 2017.3.8; CHANGE OF CONTRACT Name of requester: UNION PHARMACY( CHENGDU ) CO., LTD. Effective date: 20090927 |