CN1698604A - Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof - Google Patents
Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof Download PDFInfo
- Publication number
- CN1698604A CN1698604A CN 200510039175 CN200510039175A CN1698604A CN 1698604 A CN1698604 A CN 1698604A CN 200510039175 CN200510039175 CN 200510039175 CN 200510039175 A CN200510039175 A CN 200510039175A CN 1698604 A CN1698604 A CN 1698604A
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- beta
- cyclodextrin
- clavulanate potassium
- inclusion compound
- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a beta-cyclodextrin / amoxicillin inclusion compound medicinal composition which comprises amoxicillin and beta cyclodextrin by the weight ratio of 1:2.5-1:5. In a preferred embodiment, the composition also comprises clavulanate potassium, wherein the mass ratio of amoxicillin and clavulanate potassium is 14:1-2:1, the supplementary materials are selected from crystalline cellulose, maize starch, citric acid, talcum powder, sodium carboxymethylstarch, stearic acid, calcium stearate, magnesium stearate, amylopectin, lactose, mannitol, crosslinked povidone, talcum powder, polyethylene glycol 4000, and low substituted methylcellulose propylene glycol ether. The invention also discloses the preparing process.
Description
Technical field
The present invention relates to the pharmaceutical composition of the pharmaceutical composition of a kind of beta-cyclodextrin inclusion compound amoxicillin, the composite clavulanate potassium formation of this pharmaceutical composition, and these two kinds of preparation of drug combination methods.
Background technology
Beta-lactam antibiotic amoxicillin/clavulanate potassium compound formulation obtains FDA approval listing at first by the research and development of world-renowned GlaxoSmithKline PLC drugmaker on August 6th, 1984.Up to the present, the continuous status that kept its world's best-selling drugs in 13 years of this product, the first place that occupies world's anti-infective.This product China pharmacopeia is existing to be recorded.
Amoxicillin and clavulanic acid associating, therefore can suppress the destruction of the beta-lactamase of microorganisms such as staphylococcus, hemophilus influenza, micrococcus catarrhalis, escherichia coli, klebsiella bacillus, proteus mirabilis, proteus vulgaris, pouring ball mattress, legionella, bacteroides fragilis, to the product enzyme of above-mentioned pathogen or not produce the enzyme strain effective to the amoxicillin.This product still has antibacterial action to the streptococcus pneumoniae that do not produce beta-lactamase, micrococcus scarlatinae, viridans streptococci, clostruidium, dyspepsiacoccus, peptostreptococcus etc.Can be used for the site infection such as lower respiratory tract, middle ear, nasal sinuses, skin histology, urinary tract due to the above-mentioned sensitive organism.Also can be effective to the Enterobacter urinary tract infection.
At present, on the domestic market there be the amoxicillin/clavulanate potassium compound preparation: dosage forms such as tablet, capsule, chewable tablet, electuary, syrup, powder pin, suspensoid, its amoxicillin/clavulanate potassium proportioning has: product such as 2: 1,4: 1,5: 1,7: 1,10: 1 and 14: 1.The amoxicillin/clavulanate potassium compound recipe has remarkable advantages than single with the amoxicillin, but uses the amoxicillin far above its compound preparation at China's list.The reason that causes this contrast mainly is that product qualities such as the dissolution rate of preparation is slow, clavulanic acid potassium content instability are still waiting to improve.The amoxicillin is semi-synthetic beta-lactam antibiotic, contains three moles of water of crystallization, molecular weight 419, moisture 12.0%～15.0%.Molecule unsettled lactam nucleus in amoxicillin is subject to nucleophilic, electrophilic reagent attack, and easily degrades, because poorly water-soluble, its oral formulations dissolving out capability is not good.Clavulanate potassium good water solubility, but very easily oxidation, it is very fast that poor stability, preparation are easy to change in the shelf-life, content descends.At present formulation products mainly takes to add antioxidant, and tight tabletting, Cotton seeds and secluding air method such as pack solves stability problem.
Lot of research shows, many medical products are used beta-schardinger dextrin-s, and (the supermolecule preparation technique that β-CD) carries out molecule inclusion can significantly improve the pharmaceutical preparation quality, reduces the toxic and side effects of former medicine, improves curative effect, make things convenient for the patient to use.At present external existing 15 medicine preparation listings of using β-CD and β-CDD as adjuvant, supermolecule drug-delivery preparation The Application of Technology mainly is following several aspect: the stability of raising pharmaceutical preparation; Increase the dissolubility of medicine; Promote drug absorption, improve bioavailability of medicament; Alleviate the stimulation of medicine, reduce adverse effect body; Cover the bad smell of medicine, be beneficial to the patient and take; Carrier as slow release and targeting preparation; The powdered of oily medicine is convenient to formulation preparation.At present, amoxicillin and do not have as yet with the compound preparation of clavulanate potassium and to adopt beta-schardinger dextrin-to carry out the report of the supermolecule technology preparation of molecule inclusion.
Beta-schardinger dextrin-can form supermolecule (clathrate) with organic molecule such as medicine in aqueous solution.When forming clathrate, the higher β-CD hydrophobic cavity of cloud density produces to the medicine guest molecule that electron cloud is little to be held together, and makes the ultra-violet absorption spectrum spectral peak shift or the enhancing of object.The relative variation of uv absorption promptly reflects the enclose situation of medicine object and β-CD.
Summary of the invention
The objective of the invention is: adopt beta-schardinger dextrin-and amoxicillin to make the solid, powdery clathrate, make amoxicillin stability, machining property and dissolution characteristic significantly be strengthened raising.Further goal of the invention is that high pressure intensity is prepared new formulation with beta-cyclodextrin/amoxicillin inclusion compound and clavulanate potassium compatibility, strengthens clavulanate potassium stability, improves the pharmaceutical property of compound formulation, improves the compound formulation product quality.The application also will provide the clathrate and the preparation of compositions method of these two kinds of medicines respectively.
Need to prove: beta-cyclodextrin/amoxicillin inclusion compound adds after the clavulanate potassium, can be used as another kind of pharmaceutical composition and describes; The prioritization scheme that also can be used as beta-cyclodextrin/amoxicillin inclusion compound is described, and the scope that technical scheme comprised of two kinds of describing modes is identical.When asking for protection, the application adopt a kind of mode in back to describe.
Amoxicillin solution with the about 2.3ug/ml of mixed phosphate salt buffer (pH=6.86) compound concentration, for keeping the amoxicillin constant concentration, concentrated solution with this solution preparation β-CD, progressively increase β-CD concentration and carry out UV scanning, the result shows, the uv absorption of amoxicillin presents quick and regular enhancing, shows that amoxicillin and β-CD have good clathration with β-CD concentration increase.With accompanying drawing 1, β-CD concentration determines amoxicillin/beta-schardinger dextrin-to the quantitative relationship (Hildebrand-Benesi formula) of uv absorption and forms the formation constant of supermolecule (the enclose constant K a) is 357M-1 (Y=-0.0028X+0.141; R2=0.986).
The phase solubility test shows, when β-when CD concentration was 0, the amoxicillin intrinsic solubility equaled 4.58 * 10-6mol/L.Along with the increase of β-CD concentration, the amoxicillin dissolubility obviously increases, and β-CD of 0.7% makes the amoxicillin dissolubility increase by 3.89 times.The system changes in solubility has AL type curvilinear characteristic, shows to form 1: 1 clathrate, and the solubility curve equation is Y=0.0022x+5 * 10-6 (R2=0.9928).Trying to achieve enclose constant K a by curvilinear equation is 441M-1.
Organic molecules such as medicine and beta-schardinger dextrin-forms supramolecular structure and drug molecular structure has direct relation, 1: 1 clathrate of the general formation of less drug molecule, more macromolecular medicine can form 1: 1 or 1: 2 and more a high proportion of clathrate, and the mensuration of enclose ratio has important value to determining the pharmaceutical preparation prescription.Measure amoxicillin/beta-cyclodextrin inclusion compound ratio with continuous alternation laboratory method, mol ratio is respectively 1: 3～3: 1 serial solution with β-the CD total mol concentration is identical in the preparation amoxicillin, with buffer is the light absorption value A0 of the amoxicillin of mensuration system absorbance A cd of blank 228nm place and corresponding concentration, calculate the ratio DA (DA=Acd/A0) of light absorption value, the mol ratio of DA maximum correspondence is the enclose ratio, get the following table result
Amoxicillin xicillin: β-CD Δ A (10-2)
1∶3????????????????1.7
1∶2????????????????0.7
2∶3????????????????1.9
1∶1????????????????8.6
3∶2????????????????1.2
2∶1????????????????0.1
3∶1????????????????1.3
Wherein the system light absorption value with 1: 1 mixed in molar ratio differs maximum, so amoxicillin and β-CD carry out enclose with 1: 1 ratio, this result is consistent with the phase solubility test.
Prepared amoxicillin/beta-CD inclusion (mol ratio 1: 1) with polishing, with β-1～5 times of water gaging of CD adding and amoxicillin, ground 5 hours under the room temperature, cooling, filtration, washing solid, vacuum drying is 12 hours then, crosses 100 mesh sieves, gets white powder.
Get amoxicillin, β-CD, clathrate, the analysis of four kinds of sample undergo differential scanning calorimetry heat of physical mixture: with Al2O3 is reference, accurately takes by weighing the 5.0mg sample, and range is ± 25 μ V, the intensification scope is 40 ℃～400 ℃, heating rate is 10 ℃/min, makes the DTA collection of illustrative plates, sees accompanying drawing 2.
As seen from the figure, there is the water of crystallization of taking off peak the amoxicillin at 103.8 ℃, and the endothermic peak of 2 crystal formation conversions is arranged respectively near 155 ℃～200 ℃, near 280 ℃ for decomposing exothermic peak; It is respectively the remove enclose water endothermic peak of β-CD and the endothermic peak of crystal formation conversion that β-CD locates at 80.6 ℃ and 210 ℃, and 310.6 ℃ are fusion-decomposition peak.Mixture has kept the endothermic peak of β-CD and amoxicillin, is the stack of each chemical compound collection of illustrative plates basically, illustrates that there is not tangible intermolecular interaction in mixture.And variation has all taken place in the position at each peak and shape on the collection of illustrative plates of clathrate, taking off behind water of crystallization and the enclose water crystal formation converting characteristic peak, amoxicillin (155 ℃～200 ℃) in 110 ℃～230 ℃ intervals disappears and becomes the constant stable state of specific heat, and 230 ℃ system crystal formation conversion peak occurs, near 280 ℃ amoxicillin exothermic decomposition characteristic peak disappears, the enclose new system of aqueous solution preparation has kept water of crystallization and enclose water, therefore but the characteristic peak of amoxicillin and β-CD changes, and illustrates that new system is clathrate but not mechanical impurity.
Measure amoxicillin content in the clathrate, explored stable preparation process, fixedly amoxicillin and β-CD rate of charge changes the adding water yield, changes milling time and suitable attemperation, and the medicine assay of three batches of clathrates of preparation sees the following form
| Clathrate | Theoretical content | Actual content |
| ??X±RSD | ??14.29 | ??14.15±0.42 |
| ??Batch1 | ??14.21 | |
| ??Batch2 | ??14.29 | ??14.09 |
| ??Batch3 | ??14.29 | ??14.14 |
The result shows, preparation technology's favorable reproducibility (RSD=0.42%) of clathrate, and process is reliable and stable.
Enclose is tested the influence of the dissolution of amoxicillin: the clathrate of getting amoxicillin and the amoxicillin that contains same dose is respectively measured dissolution.Assay method is with reference to 2000 editions two ones of Chinese Pharmacopoeias, and mixed phosphate pH of buffer=6.86 are dissolution medium, and temperature is 37 ℃, and changeing the basket rotating speed is 100r/min; In 5,10,15,20,25,30 and 40min sampling 8ml, filter, add equivalent isothermal dissolution medium simultaneously immediately, sample liquid is in 228nm place mensuration light absorption value, substitution standard curve calculating concentration, measure the amoxicillin dissolution.The results are shown in accompanying drawing 3, experimental result shows that clathrate can significantly improve the amoxicillin dissolution.Clathrate 15min stripping promptly reaches 73%, far above crude drug (8.9%).Crude drug dissolution when 40min only is 33.6%, then stripping more than 95.0% of clathrate.Experiment showed, that cyclodextrin supermolecule technology can be used for the improvement of amoxicillin dosage form, is the key technology that improves the Wymox dissolution.
The common medicinal supplementary material (disintegrating agent, adhesive, filler and lubricant etc.) that further adds design flow clavulanate potassium and gross mass 10%～30% with clathrate, the peroral dosage form of various present existing amoxicillin/clavulanate potassium proportionings that adopted the dry granulation prepared, carry out the clavulanate potassium stability test with two methods of pharmacopeia version in 2000, measurement result shows, the clavulanate potassium stable content significantly is better than the conventional tablet product in the clathrate preparation (tablet), the raising that obviously is improved of preparation outward appearance and mechanical performance.The amoxicillin dissolution controlled trial of new formulation and clathrate is seen accompanying drawing 4, and the result shows that the new formulation of high pressure intensity preparation has kept the characteristic of enclose object height stripping substantially, disintegrate stripping fast, and the drug dissolution in the 15min is better than clathrate; But because the influence of other adjuvants and additive, the later dissolution of its 40min is a little less than clathrate, and the preparation dissolution can reach 91.7% during 45min.Experimental results show that, amoxicillin/Benexate Hydrochloride have quick stripping characteristic, with other adjuvants and clavulanate potassium the good compatibility is arranged, possess good machining property, inclusion technique becomes the important technology basis of improving the amoxycillin with clavulanate potassium compound formulation.
The scheme of finishing the aforementioned invention task of the application is:
Beta-cyclodextrin/amoxicillin inclusion compound, its composition comprises: amoxicillin, beta-schardinger dextrin-, both mass ratioes are 1: 2.5～1: 5.
Further scheme: with above-mentioned clathrate
Again composite with clavulanate potassiumMake the amoxycillin with clavulanate potassium compound formulation, the mass ratio of amoxicillin/clavulanate potassium proportioning is 2: 1～14: 1, and other adjuvants that need to add can be selected for use: microcrystalline Cellulose, corn starch, citric acid, Pulvis Talci, carboxymethylstach sodium, stearic acid, calcium stearate, magnesium stearate, pregelatinized Starch, lactose, mannitol, polyvinylpolypyrrolidone, Pulvis Talci, PEG4000 (Macrogol 4000), low-substituted hydroxypropyl cellulose, micropowder silica gel, carboxymethylstach sodium, PEG6000 (polyethylene glycol 6000).
Specifically can prepare solid preparation according to one of scheme in the following subordinate list:
Scheme:
| Component and ratio (mg) | ??1 | ??2 | ??3 | ??4 | ??5 | ??6 |
| The amoxicillin | ??100 | ??100 | ??100 | ??100 | ??100 | ??100 |
| Clavulanate potassium | ??7.14 | ??10 | ??14.28 | ??20 | ??25 | ??50 |
| Beta-schardinger dextrin- | ??500 | ??400 | ??400 | ??300 | ??250 | ??250 |
| Other adjuvants | ??70 | ??100 | ??100 | ??180 | ??150 | ??170 |
The preparation method of beta-cyclodextrin/amoxicillin inclusion compound may further comprise the steps:
The water of beta-schardinger dextrin-with 1～5 times of quality is mixed, make into suspended substance under the room temperature;
Add mass ratio 1/5～2/5 (optimal proportion 1/3) amount amoxicillin, mix homogeneously, fully grinding;
The solids drying is got in cooling, filtration, pulverizes 100 mesh sieves and promptly gets the solid, powdery clathrate.
More particularly, the actual conditions of the included step of this preparation method is:
Beta-schardinger dextrin-and mass ratio 1～5 times of amount pure water (optimal proportion 2) is mixed under 20～25 ℃ of temperature, make into suspended substance;
Add mass ratio 1/5～2/5 (optimal proportion 1/3) amount amoxicillin, fully mixed grinding is 2～15 hours;
12 hours after-filtration of 5 ℃ of coolings are got solids and are drying to obtain solid clathrates.
The method of further above-mentioned clathrate being made compound formulation is to increase following steps:
Clathrate and clavulanate potassium mix homogeneously, sieve, dry granulation, crushing screening obtains the composite powdery semi-finished product of beta-cyclodextrin/amoxicillin inclusion compound and clavulanate potassium.
Semi-finished product mix with other adjuvants, granulate and afterwards suppress in flakes or record capsule.
More optimize and more particularly, the step that is increased is:
Clathrate and clavulanate potassium mix homogeneously, mistake 80 mesh sieves, dry granulation was pulverized 100 mesh sieves, obtained the half-finished pharmaceutical composition of powdery.
Semi-finished product mix with other adjuvants, dry granulation under 15 ℃～30 ℃ conditions, 60 ℃ of dryings 4～20 hours, and the back compacting in flakes or record capsule.
Advantage of the present invention:
Strengthen amoxicillin and clavulanate potassium medicine stability: after the amoxicillin preparation became clathrate, outward appearance was a white solid, placed below 60 ℃ and did not see that medicament contg descended and decomposition is rotten in 72 hours, the solid appearance no change.DSC composes evidence, and the decomposition of enclose amoxicillin just appears in 80 ℃～105 ℃ volatilization phenomenons that enclose water and water of crystallization occur of temperature more than 300 ℃.Preparation clavulanate potassium stability reaches the standards of pharmacopoeia requirement.
The clathrate stripping property is good, machinability is good, easily and clavulanate potassium composite, play the effect that strengthens clavulanate potassium, with other pharmaceutic adjuvants have the good compatibility easily preparation become various solid orally ingestibles such as tablet, capsule, dispersible tablet, slow releasing tablet, slow releasing capsule, granule etc.
Dosage form easy disintegrating, medicine dissolution rate that the enclose mode prepares are fast, the dissolution height.
Portable easy storage: the solid preparation of preparation, resistance to pressure, operation processability and outward appearance all have very big improvement, are easy to produce preparation, are easy to packing, no variable color, fracture phenomena.
The specific embodiment
Embodiment 1, and 100 ml pure waters are mixed with 100 gram beta-schardinger dextrin-s, adds 33 gram amoxicillin under 20 ℃ of room temperatures, fully grinds 8 hours, places 12 hours down in 5 ℃ then; Filter washing solids 2 times.In 40 ℃ of vacuum dryings 12 hours, promptly get white solid inclusion compound.Solid clathrates was pulverized 100 mesh sieves, mixed with 2.36 gram clavulanate potassium, crossed 80 mesh sieves 2 times, and dry granulation is ground into powdery and gets pharmaceutical composition, and amoxycillin with clavulanate potassium dosage was than 14: 1 in the compositions.
Embodiment 2: substantially the same manner as Example 1, but add 200 ml pure waters, fully ground 5 hours.
Embodiment 3: substantially the same manner as Example 1, but add 20 gram amoxicillin.White solid inclusion compound that obtains and the mixed powdered drug compositions that gets of 1.4 gram clavulanate potassium.
Embodiment 4: substantially the same manner as Example 1, but add 40 gram amoxicillin.The white solid inclusion compound that obtains restrains the mixed powdered drug compositions that gets of clavulanate potassium with 2.8 again.
Embodiment 5: substantially the same manner as Example 3, mix with clathrate but add 10 gram clavulanate potassium, and make the powdered drug compositions of amoxycillin with clavulanate potassium dosage than 2: 1.
Embodiment 6: substantially the same manner as Example 3, mix with clathrate but add 5 gram clavulanate potassium, and make the powdered drug compositions of amoxycillin with clavulanate potassium dosage than 4: 1.
Embodiment 7: substantially the same manner as Example 3, mix with clathrate but add 4 gram clavulanate potassium, and make the powdered drug compositions of amoxycillin with clavulanate potassium dosage than 5: 1.
Embodiment 8: substantially the same manner as Example 4, mix with clathrate but add 5.7 gram clavulanate potassium, and make the powdered drug compositions of amoxycillin with clavulanate potassium dosage than 7: 1.
Embodiment 9: substantially the same manner as Example 4, mix with clathrate but add 4 gram clavulanate potassium, and make the powdered drug compositions of amoxycillin with clavulanate potassium dosage than 10: 1.
Claims (5)
1, a kind of beta-cyclodextrin/amoxicillin inclusion compound pharmaceutical composition, its composition comprises: amoxicillin, beta-schardinger dextrin-, both mass ratioes are 1: 2.5～1: 5.
2, according to the described beta-cyclodextrin/amoxicillin inclusion compound pharmaceutical composition of claim 1, it is characterized in that: compositions also contains clavulanate potassium; The mass ratio of amoxicillin and clavulanate potassium is 14: 1～2: 1.
3, according to claim 1 or 2 described beta-cyclodextrin/amoxicillin inclusion compound pharmaceutical compositions, it is characterized in that: the adjuvant in the compositions is selected from: microcrystalline Cellulose, corn starch, citric acid, Pulvis Talci, carboxymethylstach sodium, stearic acid, calcium stearate, magnesium stearate, pregelatinized Starch, lactose, mannitol, polyvinylpolypyrrolidone, Pulvis Talci, Macrogol 4000, low-substituted hydroxypropyl cellulose, micropowder silica gel, carboxymethylstach sodium or polyethylene glycol 6000.
4, the described beta-cyclodextrin/amoxicillin inclusion compound preparation of drug combination of a kind of claim 1 method may further comprise the steps:
Beta-schardinger dextrin-is mixed with water, make into suspended substance;
Add mass ratio 1/5～2/5 amount amoxicillin, fully mixed grinding;
Cooling, filtration, solids washing after drying promptly gets solid clathrates.
5, according to the described beta-cyclodextrin/amoxicillin inclusion compound preparation of drug combination of claim 4 method, it is characterized in that, also be provided with following steps:
Solid clathrates was pulverized 100 mesh sieves, mixed with clavulanate potassium, crossed 80 mesh sieves 2 times, and dry granulation is ground into powdery and gets pharmaceutical composition, and wherein amoxycillin with clavulanate potassium dosage was than 14: 1～2: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100391754A CN100391456C (en) | 2005-04-30 | 2005-04-30 | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100391754A CN100391456C (en) | 2005-04-30 | 2005-04-30 | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1698604A true CN1698604A (en) | 2005-11-23 |
| CN100391456C CN100391456C (en) | 2008-06-04 |
Family
ID=35474955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100391754A Expired - Fee Related CN100391456C (en) | 2005-04-30 | 2005-04-30 | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100391456C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103961351A (en) * | 2014-05-06 | 2014-08-06 | 康田制药(中山)有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
| CN104548122A (en) * | 2013-10-23 | 2015-04-29 | 洛阳惠中兽药有限公司 | Beta-cyclodextrin/amoxicillin inclusion complex, as well as preparation method and application thereof |
| CN107157936A (en) * | 2017-07-19 | 2017-09-15 | 山东福美乐动物药业有限公司 | A kind of amoxicillin soluble powder and preparation method thereof |
| CN109248150A (en) * | 2017-07-13 | 2019-01-22 | 鲁南制药集团股份有限公司 | A kind of amoxicillin and clavulanate potassium preparation and preparation method thereof |
| CN115364057A (en) * | 2021-05-20 | 2022-11-22 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DZ2028A1 (en) * | 1995-05-03 | 2002-10-23 | Smithkline Beecham Plc | Medicines used to treat bacterial infections in pediatrics. |
| JP2001058994A (en) * | 1999-08-19 | 2001-03-06 | Eisai Co Ltd | Stabilized amoxicillin inclusion complex |
| CN1473562A (en) * | 2003-06-27 | 2004-02-11 | 辉 刘 | Mouth cavity quick dissolving quick disintegrating freeze-dried tablet and its preparing method |
-
2005
- 2005-04-30 CN CNB2005100391754A patent/CN100391456C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104548122A (en) * | 2013-10-23 | 2015-04-29 | 洛阳惠中兽药有限公司 | Beta-cyclodextrin/amoxicillin inclusion complex, as well as preparation method and application thereof |
| CN103961351A (en) * | 2014-05-06 | 2014-08-06 | 康田制药(中山)有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
| CN109248150A (en) * | 2017-07-13 | 2019-01-22 | 鲁南制药集团股份有限公司 | A kind of amoxicillin and clavulanate potassium preparation and preparation method thereof |
| CN109248150B (en) * | 2017-07-13 | 2020-07-21 | 鲁南制药集团股份有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
| CN107157936A (en) * | 2017-07-19 | 2017-09-15 | 山东福美乐动物药业有限公司 | A kind of amoxicillin soluble powder and preparation method thereof |
| CN107157936B (en) * | 2017-07-19 | 2020-09-01 | 山东福美乐动物药业有限公司 | Amoxicillin soluble powder and preparation method thereof |
| CN115364057A (en) * | 2021-05-20 | 2022-11-22 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
| CN115364057B (en) * | 2021-05-20 | 2024-01-30 | 内蒙古联邦动保药品有限公司 | Amoxicillin and clavulanate potassium compound preparation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100391456C (en) | 2008-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6505659B2 (en) | Rifaximin complex | |
| CN101780085B (en) | Cefprozil medicinal composition | |
| CN104800221A (en) | Medicinal cefetamet pivoxil hydrochloride composition for treating sensitive bacteria infectious diseases | |
| CN103524533B (en) | A kind of cefprozil compound, its dispersible tablet, dry suspensoid and preparation method | |
| CN100391456C (en) | Beta-cyclodextrin / amoxicillin inclusion compound and its composition with clavulanic kalium and preparation thereof | |
| WO2008057058A1 (en) | Oral pharmaceutical compositions | |
| EP1389462B1 (en) | Amorphous cefditoren pivoxil composition and process for producing the same | |
| CN102327270B (en) | Beta-lactam compound antibiotic composition | |
| CN104688713A (en) | Cefradine capsule and preparation method thereof | |
| AU2012389714B2 (en) | Cocrystal of piperacillin sodium and sulbactam sodium and preparation method thereof, as well as pharmaceutical compositions containing same and uses thereof | |
| CN117379378A (en) | Compound amoxicillin soluble powder for livestock and preparation process thereof | |
| CN101862307A (en) | Bisulfate Cefdinir sodium capsule and preparation method thereof | |
| CN105919960B (en) | A kind of roxithromycin dispersing tablet and preparation method thereof | |
| CN103497204B (en) | A kind of Cefdinir compound, its dispersible tablet and preparation method | |
| CN1236814C (en) | Faropenem pharmaceutical composition containing glutathione | |
| CN101062418A (en) | Cyclodextrin inclusion compound of entecavir, the preparing method and the medicine combination including the same | |
| CN101468017A (en) | Ceftibuten dispersible tablet | |
| CN101496791A (en) | Cefixime sustained-release tablets and preparation method thereof | |
| US20170368055A1 (en) | Methods for treating infections | |
| CN1261439C (en) | Cefixime sodium pharmaceutical composition and its preparation and application | |
| CN113768892A (en) | A tablet composition for treating cardiovascular diseases, and its preparation method | |
| CN1546029A (en) | Gatifloxacin dispersible tablet and its preparation process | |
| CN116172963A (en) | Amoxicillin and clavulanate potassium dry suspension composition and preparation method thereof | |
| CN101899059B (en) | Pyrrolidine-containing dicyclic cephalosporin derivatives | |
| CN113456596A (en) | Diacerein granules, preparation method thereof and solid preparation containing diacerein granules |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: NANJING JUHUAN MEDICAL SCIENCE AND TECHNOLOGY DEVE Free format text: FORMER OWNER: NANJING NORMAL UNIVERSITY Effective date: 20100825 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 210097 NO.122, NINGHAI ROAD, NANJING CITY, JIANGSU PROVINCE TO: 210046 ROOM 621, NORTH BUILDING, COLLEGE OF LIFE SCIENCES, NANJING NORMAL UNIVERSITY, NO.1, WENYUAN ROAD, YADONGXINCHENG, NANJING CITY, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20100825 Address after: 210046 Jiangsu city in Nanjing Province town of Yuen Road Ya Dong College of life science Nanjing Normal University No. 1 north room 621 Patentee after: Nanjing Juhuan Pharma Technology Development Co., Ltd. Address before: Nanjing City, Jiangsu province 210097 Ninghai Road No. 122 Patentee before: Nanjing Normal University |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080604 Termination date: 20180430 |