CN101549159A - Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof - Google Patents
Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof Download PDFInfo
- Publication number
- CN101549159A CN101549159A CNA2009100945166A CN200910094516A CN101549159A CN 101549159 A CN101549159 A CN 101549159A CN A2009100945166 A CNA2009100945166 A CN A2009100945166A CN 200910094516 A CN200910094516 A CN 200910094516A CN 101549159 A CN101549159 A CN 101549159A
- Authority
- CN
- China
- Prior art keywords
- chloramphenicol
- chloromycetin
- eyedrops
- eye drop
- content
- 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.)
- Granted
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention is application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof. Adding hydroxypropyl-belta-cyclodextrin into formula of the eyedrops of chloramphenicol, the addition is 10-80 g/L. The invention finds HP-belta-CD (hydroxypropyl-belta-cyclodextrin) for improving stability of the eyedrops of chloramphenicol by a series of experiments, capable of improving dissolvability of the chloramphenicol for six times, and because of inclusion of the cavity structure to chloramphenicol, blocking chloramphenicol hydrolysis reaction catalyzed by various ions in solution effectively, degradation of the chloramphenicol in aqueous solution is greatly relieved, by experiments, accelerating for six months and normal temperature storing for 24 months, every index of the chloramphenicol eyedrops still conforms to request of the <china pharmacopeia > standard, content of chloramphenicol glycol is less than 8%, content of methyl aldehyde is 0, so stability of the chloramphenicol eyedrops is greatly improved.
Description
Technical field
The present invention relates to field of pharmaceutical technology, specifically application and the method for HP-in eyedrops of chloramphenicol.
Background technology
Chloromycetin (Chloramphenicol) is D-Su Shi-(-)-N-[α-(hydroxymethyl)-beta-hydroxy-p-nitrophenyl ethyl]-2, the 2-dichloro acetamide.Be white needles or little yellowish green needle-like, the crystallization of lengthy motion picture shape or crystalline powder be with, bitter in the mouth, easily molten in methanol, ethanol, acetone, propylene glycol; Slightly soluble in water.
Chloromycetin was found in nineteen forty-seven, was a kind of broad ectrum antibiotic that streptomyces venezuelae produces, and also was the antibiotic of first full chemosynthesis in the world.Because antimicrobial spectrum is wide, effective and cheap, once with various dosage forms, as tablet, capsule, oral administration mixed suspension, solution, unguentum, oil preparation, injection powder injection and eye agent etc., apply to clinical widely, but, cause aplastic anemia, so clinical practice is limited because it suppresses medulla hematopoietic system, but still applicable for some severe infections chloromycetin that other antibiotic medicines are invalid, infect as typhoid fever, meningitis, rickettsiosis and other Salmonellas.
Although the less clinically application of most of dosage forms of chloromycetin, but chloromycetin still is widely used in acute ear of treatment and ocular infection all the time, often use, under this application form, can effectively avoid the toxicity of chloromycetin with the form of chloramphenicol eye oinment, Chloramphenicol Eye Drop, chloramphenicol ear drop.
Chloramphenicol Eye Drop is a kind of common ophthalmic remedy, is applicable to acute or chronic conjunctivitis, comprises margo palpebrae inflammation, corneal ulcer, trachoma, hordeolum, dacryocystisis etc.Include in BP (British Pharmacopoeia), BNF (BNF), USP (American Pharmacopeia), JP (Pharmacopeia of Japan), " two ones of Chinese pharmacopoeia versions in 2005, once on the market, circulated extensively use as OTC Class A medicine, at present still occupy the very big market share, be sure to occupy sales volume first in ophthalmic remedy market.
Chloromycetin is unstable in solution, chloromycetin is decomposed into chloromycetin glycol, paranitrobenzaldehyde etc. easily, chloromycetin glycol and paranitrobenzaldehyde have than strong and stimulating eyes, influencing the patient uses, so " in two ones of the Chinese pharmacopoeia versions in 2005 content of chloromycetin glycol and paranitrobenzaldehyde in the Chloramphenicol Eye Drop has all been made clearly regulation, the content that is the chloromycetin glycol must not be higher than 8%, and the content of paranitrobenzaldehyde must not be higher than 0.5%.
The common shelf-life of medicine is decided to be 2 years according to the rules, because chloromycetin instability in the Chloramphenicol Eye Drop, in the market circulation process, its shelf-life can only reach 8 months usually, the underproof before the deadline phenomenon of normal appearance; Because the amount ratio of Chloramphenicol Eye Drop is bigger, for guaranteeing people's drug safety, a kind ofly can stablize the Chloramphenicol Eye Drop quality at ambient temperature so press for now to find, guarantee to meet before the deadline " the method for Chinese pharmacopoeia version two ministerial standards in 2005.
In the eyedrops of chloramphenicol stability study, old state extensively waits the people to adopt beta-schardinger dextrin-to the stability of eyedrops of chloramphenicol and the improvement of formulation and technology (stability of Chloramphenicol Eye Drop and the improvement of formulation and technology thereof, the West China pharmaceutical journal, 2006,21 (5): 443-445) report in the research adds beta-schardinger dextrin-and can strengthen eyedrops of chloramphenicol stability; Guo Weier adopts stability study (beta-schardinger dextrin-enhancing Chloramphenicol Eye Drop stability study, northwest pharmaceutical journal, 1998,13 (3): 11) in show beta-schardinger dextrin-can prolong the stability of eyedrops of chloramphenicol of beta-schardinger dextrin-to eyedrops of chloramphenicol.But beta-schardinger dextrin-can cause eyedrops of chloramphenicol precipitation to occur in storage because its dissolubility in water is little, does not meet eyedrops of chloramphenicol pharmacopeia (2005 editions) prescription.
Summary of the invention
The purpose of this invention is to provide a kind of method that simply and effectively improves eyedrops of chloramphenicol stability, i.e. the application of HP-in eyedrops of chloramphenicol.Can effectively improve the stability of eyedrops of chloramphenicol.
There are amide groups, chlorine, nitro isoreactivity group in the chloromycetin structure, the amido link hydrolysis often take place generate the volatility dichloroacetic acid and have the chloromycetin glycol of optical activity, the hydrolysis of chlorine, the reduction reaction that oxidation reaction generates aldehydes or ketones and nitro etc.These reactions also may be recurred simultaneously.As can be seen, the decomposition reaction in the Chloramphenicol Eye Drop is mainly the hydrolysis of general acid-base catalysis and then the redox reaction that causes from the mechanism of degradation of chloromycetin.
The non-polar group size is suitable for entering in HP-β-CD cylinder cavity in the chloromycetin molecule, so inclusion reaction carries out easily, more minus Gibbs free occurs.After the Nitrobenzol group enters HP-β-CD cavity in the chloromycetin, with on the C that phenyl ring links to each other-OH easily with HP-β-CD cavity outside-OH forms hydrogen bond, thereby makes the stability reinforcement of clathrate.
The present invention adopts HP-to improve eyedrops of chloramphenicol stability, HP-(Hydroxypropyl-β-cyclodextrin, HP-β-CD) be widely used in water solublity, stability, dissolution rate and the bioavailability that increases insoluble medicine as a kind of pharmaceutic adjuvant, the guest molecule that it can be complementary with some polarity, size, shape and character with the molecular structure of its special " outer hydrophilic, interior hydrophobic " or the hydrophobic group of some guest molecule form inclusion complex.(Hydroxypropyl-β-cyclodextrin, HP-β-CD) are because good water solubility, and nontoxic to kidney to thermally-stabilised, almost non-stimulated to muscle and mucosa, haemolysis is low, are considered to one of the most promising drug carrier material for HP-.
Find in the process of the test of Chloramphenicol Eye Drop use β-CD of the present invention, because β-CD to the enclose of chloromycetin, has promoted the dissolution velocity of chloromycetin, but its enclose product is also unstable in aqueous solution, the heating cooling back generation of being everlasting precipitates, and has influenced the quality of eye drop.The water solublity that the present invention has found β-CD is derivant HP-β-CD (HP-) preferably, it can improve about 6 times with the dissolubility of chloromycetin, and owing to the enclose of its cavity structure to chloromycetin, effectively blocked the chloromycetin hydrolysis of various ionic catalysises in the aqueous solution, made the degraded of chloromycetin in aqueous solution obtain huge alleviation.Can effectively improve eyedrops of chloramphenicol stability.
Below be some tests that the present invention did, in the test accelerated test, long term test adopt " 2005 editions relevant regulations enforcements of Chinese pharmacopoeia:
Experiment one:
Rx0. chloromycetin 2.625g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | Quicken February | |
Content | 104.58 | 102.32 | 99.41 |
Chloromycetin glycol % | 0.63 | 4.53 | 6.66 |
The result: chloromycetin glycol content when quickening 2 months is higher, is difficult to protect quality conformance with standard requirement before the deadline.
Rx1. chloromycetin 2.625g/L
β-CD 2.5g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | Quicken February | |
Content | 102.75 | 99.39 | 96.18 |
Chloromycetin glycol % | 0.37 | 3.36 | 4.66 |
The result: than basic components, chloromycetin glycol content reduces, and certain Stabilization can be arranged, but its solution has the precipitation situation.
Rx2. chloromycetin 2.625g/L
β-CD 2.5g/L
PVP-K30 2.5g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | Quicken February | |
Content | 102.22 | 99.92 | 96.68 |
Chloromycetin glycol % | 0.45 | 3.28 | 6.41 |
The result: than basic components, chloromycetin glycol content reduces, and certain Stabilization can be arranged, but its solution has the precipitation situation, 1 makes moderate progress but write out a prescription.
Rx3. chloromycetin 2.625g/L
β-CD 2.5g/L
Hyaluronic acid 2.5g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | Quicken February | |
Content | 102.30 | 98.36 | 94.78 |
Chloromycetin glycol % | 0.42 | 3.90 | 5.12 |
The result: than basic components, chloromycetin glycol content reduces, and certain Stabilization can be arranged, but its solution has the precipitation situation, 1 makes moderate progress but write out a prescription.
Rx4. chloromycetin 2.625g/L
β-CD 2.5g/L
Hydroxypropyl emthylcellulose 2.5g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | Quicken February | |
Content | 101.29 | 97.31 | 94.55 |
Chloromycetin glycol % | 0.40 | 4.09 | 4.45 |
The result: than basic components, chloromycetin glycol content reduces, and certain Stabilization can be arranged, and its solution has the precipitation situation, 1 makes moderate progress but write out a prescription.
From testing a series of tests of one as can be seen, in eye drop, add β-CD, can effectively reduce the content of chloromycetin glycol; But because the water solublity of β-CD is bad, saturated concentration is 1.9% under the room temperature, in the room temperature storage process, easily produce precipitation, influence the quality of eye drop, still add PVP-K30, hyaluronic acid, hydroxypropyl emthylcellulose on this basis once more to change the steady dissolution of β-CD in water, all obtained effect preferably.But on the whole, its improvement situation is limited, can't reach to produce quality conformance with standard in the keeping life in batches.
Experiment two:
Rx1. chloromycetin 2.625g/L
α-CD 10g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 101.41 | 97.95 |
Chloromycetin glycol % | 0.67 | 4.01 |
Result: be not significantly increased with β type contrast chloromycetin stability, occur the precipitation situation in the solution.
Rx2. chloromycetin 2.625g/L
γ-CD 10g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 100.09 | 96.52 |
Chloromycetin glycol % | 0.45 | 3.53 |
Result: be not significantly increased with β type contrast chloromycetin stability, occur the precipitation situation in the solution.
Rx3. chloromycetin 2.625g/L
HP-β-CD 10g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 100.31 | 97.05 |
Chloromycetin glycol % | 0.45 | 3.17 |
Result: be significantly increased with β type contrast chloromycetin stability, do not have precipitation in the solution and occur.
A series of evidences of two by experiment, the CD of α type, γ type and β type are more or less the same to the raising effect of chloromycetin stability, and have the bad problem of water solublity equally.HP-β-CD to the raising effect of chloromycetin stability above three kinds all good, simultaneously its water solublity is better, can sharply amplify and produce.
Experiment three:
Rx0. chloromycetin 2.625g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 104.83 | 93.39 |
Chloromycetin glycol % | 0.46 | 6.10 |
Rx1. chloromycetin 2.625g/L
HP-β-CD 5g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 100.12 | 95.01 |
Chloromycetin glycol % | 0.48 | 3.99 |
The result: chloromycetin glycol content is blank to be reduced, and proves that this concentration has certain improvement effect to chloromycetin stability.
Rx2. chloromycetin 2.625g/L
HP-β-CD 10g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 100.70 | 97.7 |
Chloromycetin glycol % | 0.43 | 3.17 |
The result: chloromycetin glycol content is blank to be reduced, and proves that this concentration has certain improvement effect to chloromycetin stability.
Rx3. chloromycetin 2.625g/L
HP-β-CD 15g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 104.64 | 99.7 |
Chloromycetin glycol % | 0.32 | 2.96 |
The result: chloromycetin glycol content is blank to be reduced, and proves that this concentration has certain improvement effect to chloromycetin stability.
Rx4. chloromycetin 2.625g/L
HP-β-CD 50g/L
Pharmaceutic adjuvant adds to 1L
Quickened 0 month | Quicken January | |
Content | 100.67 | 97.84 |
Chloromycetin glycol % | 0.32 | 1.96 |
The result: chloromycetin glycol content is blank to be reduced, and proves that this concentration has certain improvement effect to chloromycetin stability.
A series of evidences of three by experiment: the HP-β-CD of above-mentioned concentration all can improve eyedrops of chloramphenicol stability, and along with the raising of HP-β-CD concentration, the content of chloromycetin glycol constantly descends, and HP-β-CD can significantly improve the stability of chloromycetin.
Experiment four:
Comprehensive above experiment one to three result who obtains draws: adding HP-β-CD is best to the stabilizing effect that improves chloromycetin in eyedrops of chloramphenicol, but because HP-β-CD costs an arm and a leg, cost for the control eye drop, make it to have actual productive value, summed up experiment three again, the consumption of choosing a HP-β-CD amplifies pilot scale, is by " situation of accelerated test, long term test observation is carried out in 2005 editions requirements of Chinese pharmacopoeia below to the eyedrops of chloramphenicol under this consumption.
Rx:
Chloromycetin 2.625g/L
HP-β-CD 15g/L
Pharmaceutic adjuvant adds to 1L
The accelerated test situation:
Quickened 0 month | Quicken January | Quicken February | Quicken March | Quicken June | |
Content | 100.73 | 98.70 | 95.69 | 92.44 | 85.51 |
Chloromycetin glycol % | 0.29 | 2.43 | 4.54 | 5.19 | 7.81 |
Paranitrobenzaldehyde % | 0 | 0 | 0 | 0 | 0 |
The long term test situation:
0 month | March | June | JIUYUE | December | 18 months | 24 months | |
Content | 100.73 | 100.09 | 98.43 | 96.26 | 95.44 | 93.07 | 86.20 |
Chloromycetin glycol % | 0.29 | 1.95 | 3.01 | 4.29 | 5.17 | 7.05 | 7.82 |
Paranitrobenzaldehyde % | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The result: paranitrobenzaldehyde content is qualified in the accelerated test 6 months, long term test 24 months, and chloromycetin glycol content is qualified, proves that HP-β-CD can significantly effectively improve the stability of Chloramphenicol Eye Drop.
Technical scheme of the present invention is:
Add HP-β-CD (HP-) in the standard prescription of Chloramphenicol Eye Drop, its addition is 10~80g/L.
The pH value of the Chloramphenicol Eye Drop that uses is 6~7.
The application process of HP-in eyedrops of chloramphenicol, carry out according to the following steps:
1) chloromycetin in the prescription of Chloramphenicol Eye Drop, HP-are put into 150mL water, stirring 30min places after making it fully dissolving and mix homogeneously, and is standby;
2) with the buffer salt in the prescription of Chloramphenicol Eye Drop or etc. ooze salt (sodium chloride) and put into 300mL water, stir make it dissolving fully after, standby;
3) antibacterial in the prescription of Chloramphenicol Eye Drop is put into 500mL water, after stirring makes it dissolving fully, place, standby;
4) with above-mentioned 1), 2), 3) solution of step packs in the container together, adds water to 1L, after stirring 10min and making it mix homogeneously, is filled into bottle, promptly.
The present invention has found the HP-β-CD (HP-) that improves Chloramphenicol Eye Drop stability through a series of experiment, it can improve about 6 times with the dissolubility of chloromycetin, and owing to the enclose of its cavity structure to chloromycetin, effectively blocked the chloromycetin hydrolysis of various ionic catalysises in the aqueous solution, make the degraded of chloromycetin in aqueous solution obtain huge alleviation, by experiment, quickening 6 months, after room temperature is deposited 24 months, every index of Chloramphenicol Eye Drop still can meet " Chinese pharmacopoeia standard-required, chloromycetin glycol content is less than 8%, paranitrobenzaldehyde content is 0, thereby has improved the stability of Chloramphenicol Eye Drop greatly.
Description of drawings
Fig. 1 is a HP-enclose chloromycetin sketch map.
The specific embodiment
Embodiment 1:
Medicine components:
Chloromycetin 2.625g/L
Borax 0.625g/L
Boric acid 17g/L
Phenylmercuric acetate 0.02g/L
HP-β-CD 15g/L
Water adds to 1L
Standard: contain that the chloromycetin glycol must not surpass 8%, paranitrobenzaldehyde must not surpass 0.5%.
Method for making:
1. chloromycetin, the HP-β-CD with formula ratio puts into 150mL water, and stirring 30min places after making it fully dissolving and mix homogeneously, and is standby;
2. Borax, the boric acid of formula ratio are put into 300mL water, after stirring makes it dissolving fully, standby;
3. the phenylmercuric acetate of formula ratio (or benzalkonium bromide, thimerosal) is put into 500mL water, stir fully make it dissolving after, place, standby;
4. above-mentioned 1,2,3 solution is packed into together in the container, add water to 1L, after stirring 10min makes it mix homogeneously, be filled into bottle, promptly.
Embodiment 2:
In the medicine components, the consumption of HP-β-CD is 10g/L, and other composition is identical with embodiment 1 with method for making.
Embodiment 3:
In the medicine components, the consumption of HP-β-CD is 25g/L, and other composition is identical with embodiment 1 with method for making.
Embodiment 4:
In the medicine components, the consumption of HP-β-CD is 50g/L, and other composition is identical with embodiment 1 with method for making.
Embodiment 5:
In the medicine components, the consumption of HP-β-CD is 80g/L, and other composition is identical with embodiment 1 with method for making.
Claims (3)
1, the application of HP-in eyedrops of chloramphenicol is characterized in that adding HP-in the standard recipe of Chloramphenicol Eye Drop, and its addition is 10~80g/L.
2, the application of HP-according to claim 1 in eyedrops of chloramphenicol, the pH value that it is characterized in that the Chloramphenicol Eye Drop that uses is 6~7.
3, the application process of the described HP-of claim 1 in eyedrops of chloramphenicol is characterized in that carrying out according to the following steps:
1) chloromycetin in the prescription of Chloramphenicol Eye Drop, HP-are put into 150mL water, stirring 30min places after making it fully dissolving and mix homogeneously, and is standby;
2) with the buffer salt in the prescription of Chloramphenicol Eye Drop or etc. ooze salt and put into 300mL water, stir make it dissolving fully after, standby;
3) antibacterial in the prescription of Chloramphenicol Eye Drop is put into 500mL water, after stirring makes it dissolving fully, place, standby;
4) with above-mentioned 1), 2), 3) solution of step packs in the container together, adds water to 1L, after stirring 10min and making it mix homogeneously, is filled into bottle, promptly.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100945166A CN101549159B (en) | 2009-05-25 | 2009-05-25 | Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100945166A CN101549159B (en) | 2009-05-25 | 2009-05-25 | Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101549159A true CN101549159A (en) | 2009-10-07 |
CN101549159B CN101549159B (en) | 2012-02-29 |
Family
ID=41153797
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2009100945166A Active CN101549159B (en) | 2009-05-25 | 2009-05-25 | Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101549159B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113288866A (en) * | 2021-07-12 | 2021-08-24 | 山东诺明康药物研究院有限公司 | Antibacterial eye drops and preparation method thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT101446B (en) * | 1994-01-24 | 1996-11-29 | Oftalder Produtos Farmaceutico | METHOD FOR INCREASING THE SOLUBILITY AND STABILITY OF CHLORANFENICOL, BY FORMING COMPLEX INCLUSIONS WITH CYCLODEXTRINS, SOLUTIONS CONTAINING THE INVENTION COMPLEX AND PROCESS FOR THE PREPARATION OF THESE SOLUTIONS. |
CN101468205A (en) * | 2007-12-27 | 2009-07-01 | 凌沛学 | Aqueous medicinal composition |
-
2009
- 2009-05-25 CN CN2009100945166A patent/CN101549159B/en active Active
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113288866A (en) * | 2021-07-12 | 2021-08-24 | 山东诺明康药物研究院有限公司 | Antibacterial eye drops and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
CN101549159B (en) | 2012-02-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR920003332B1 (en) | Process for preparing etoposide preparations | |
US6387400B1 (en) | Process for preparing pharmaceutical compositions for use with soft gelatin formulations | |
US20070297990A1 (en) | Self-preserving composition | |
JP6603785B2 (en) | Aqueous solution containing water-soluble polymer | |
CN1649603A (en) | Aqueous compositions containing metronidazole | |
KR20150017002A (en) | Stabilized ophthalmic compositions comprising oxidatively unstable components | |
EP3086776B1 (en) | Topical brimonidine tartrate ophthalmic solution | |
CN101077352A (en) | Eye preparation containing lactose-azithromycin | |
JP6462201B2 (en) | Aqueous ophthalmic composition | |
CN102784382B (en) | Argatroban drug composition and preparation method and application of argatroban drug composition | |
CN101549159B (en) | Application of the hydroxypropyl-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof | |
EP1453489B1 (en) | Acetaminophen compositions | |
CN103417473B (en) | Adapalene gel and method for preparing same | |
CN104644551A (en) | Hydroxyfasudil-containing pharmaceutical composition for injection | |
US9789080B2 (en) | Ophthalmic formulations of mycophenolic acid | |
CN101549160A (en) | Application of the sulfur-butyl ether-belta-cyclodextrin in eyedrops of chloramphenicol and method thereof | |
US20080161405A1 (en) | Biguanide Composition and Method of Treatment and Prevention of Infections | |
JP7238773B2 (en) | OPHTHALMIC COMPOSITION FOR SOFT CONTACT LENS AND METHOD FOR PREVENTING VITAMIN A SEPARATION | |
CN101653613A (en) | Application and method of hydroxypropyl -sulfonylurea-beta-cyclodextrin in chloramphenicol eye drops | |
JP2012144509A (en) | Ophthalmic solution compounded with many ingredients | |
US11337921B2 (en) | Multi-use torasemide composition | |
EP2419081B1 (en) | Aqueous ophthalmic compositions containing anionic therapeutic agents | |
JP2010532349A (en) | Stabilized ophthalmic solution | |
CN104586768A (en) | Linezolid-containing anti-infection pharmaceutical composition and preparation method thereof | |
CA2486571C (en) | Pharmaceutical composition |
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 | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20171019 Address after: High tech Zone Jinpu Ma Cheng Road 650503 Yunnan city of Kunming province No. 2899 Patentee after: Yunnan Plant Pharmaceutical Industry Co., Ltd. Address before: 650000 Kunming meteorological Road, Yunnan, Wang PA No. 22 Patentee before: Kunming Zhenhua Pharmacy Co., Ltd. |