CN1887272A - Slow released dry azithromycin suspension and its prepn - Google Patents
Slow released dry azithromycin suspension and its prepn Download PDFInfo
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- CN1887272A CN1887272A CN 200610091077 CN200610091077A CN1887272A CN 1887272 A CN1887272 A CN 1887272A CN 200610091077 CN200610091077 CN 200610091077 CN 200610091077 A CN200610091077 A CN 200610091077A CN 1887272 A CN1887272 A CN 1887272A
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- azithromycin
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Abstract
The present invention provides one kind of slow released dry azithromycin suspension and its preparation process. The medicine of the present invention has slow released azithromycin microsphere prepared through spray drying process, and capsule wall material for coating azithromycin medicine made of viscous medicinal polymer material or insoluble medicine polymer material, such as acrylic polymer, gelatin, Arabic gum, carboxymethyl cellulose salt, etc. and preferably of acrylic polymer. The slow released dry azithromycin suspension has improved administration compliance and convenience, and high bioavailability.
Description
Technical field
The present invention relates to slow released dry azithromycin suspension and preparation method thereof, belong to medical technical field.
Background technology
Its chemical name of azithromycin is: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-nuclear-own pyrans glycosyl) oxygen]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-seven methyl isophthalic acid 1-[[3,4,6-three deoxidations-3 (dimethylamino)-β-D-wood-own pyrans glycosyl] oxygen]-1-oxa--6-azacyclo-pentadecane-15-ketone.
Its structural formula is:
Molecular formula: C
38H
72N
2O
12
Molecular weight: 749.00
The development of azithromycin starts from the discovery of the erythromycin of phase early 1950s, that continues is 16 yuan of rings such as kitasamycin Macrolidees, afterwards be to belong to the Roxithromycin that is referred to as new Macrolide and the clarithromycin of stability raising 14 yuan of rings,, absorbance increase, relieving side effects with erythromycin, and develop azithromycin gastric acid.The dosage form of azithromycin exploitation at present is more complete, as capsule, tablet, granule, syrup, microcapsule, suspensoid preparation, dry suspension and injection etc.Because the azithromycin good effect, toxic and side effects is low, adds the pharmacokinetic characteristics that it is good, and therefore, in recent years widely by domestic clinical the use, and consumption still is ascendant trend year by year.
Azithromycin has stronger antibacterial action to G-coccus, G-bacillus and anaerobe.Antibacterial action to mucositis brinell ball bacterium, Neisseria gonorrhoeae, salmonella, shigella dysenteriae, pneumobacillus, Campylobacter, hemophilus influenza, legionella pneumophilia, aerogenesis folder film clostridium and anaerobic cocci is also strong than erythromycin.To pasteurella multocida, yersinia, mycoplasma pneumoniae, chlamydia psittaci, treponema pallidum, borrelia vincentii and organize entamoeba etc. that obvious effect is also arranged.Azithromycin also has the obvious sterilization effect to some antibacterial.Experiment shows, Azithromycin 4 is hour internal energy kills 99.9% hemophilus influenza fast, can kill that alveolar is huge has a liking for intracellular legionella pneumophilia, and erythromycin only has bacteriostasis.Observe from animal infection modal, azithromycin all presents bactericidal activity in the body to streptococcus pneumoniae, pneumobacillus, hemophilus influenza and escherichia coli etc. when high concentration.
Compare with other Macrolidees, azithromycin has the influenza bacillus of height, the activity of moraxelle catarrhalis, easily enter in the phagocyte such as tissue and neutrophilic granulocyte, macrophage, 1 logotype on the 1st got final product on the 3rd, advanced age, dosed administration routinely still when person and renal dysfunction seldom had characteristics such as interaction with other medicine as other Macrolidees.Azithromycin plays a significant role in the upper and lower respiratory tract infectious disease of treatment.Azithromycin in American-European pneumonia diagnosis and treatment guide as choice drug, in the community acquired pneumonia diagnosis and treatment guide of Japan then as the choice drug of atypical pneumonia.
Azithromycin can be absorbed by macrophage and assemble in cell, but azithromycin can not destroy the function of macrophage, and macrophage is transported to infection site with azithromycin, thereby the drug level in causing organizing is more than 100 times of serum Chinese medicine concentration.Ordinary preparation was taken the 0.5g azithromycin in first day, took the 0.25g azithromycin later every day, and the 5th day blood drug level is lower than behind the disposable 2.0g of the taking azithromycin the 5th day blood drug level.A kind of high dose release oral azithromycin preparation can be widely used in the single dose azithromycin treatment, and therefore obviously improves the compliance and the convenience of administration, is a kind of preparation with clinical meaning.
During azithromycin oral, regular meeting causes stomachache, feel sick and side effect such as diarrhoea.For example the patent No. is 95192938.0 patent, provides a kind of slow release formulation of azithromycin just to have this class problem.
Summary of the invention
The purpose of this invention is to provide a kind of obvious compliance that improves administration and convenience, the dried mixed suspension preparation of high dose release oral azithromycin that bioavailability is high, and the simple and convenient preparation method that this dried mixed suspension preparation is provided.
Realize that the technical scheme that a kind of dry suspension is provided in the object of the invention is: dry suspension of the present invention is prepared from by sustained-release micro-spheres that contains azithromycin and the adjuvant of pharmaceutically using always; The described sustained-release micro-spheres that contains azithromycin is made up of the azithromycin and the capsule material of parcel azithromycin; Described capsule material is medicinal macromolecule viscous material or macromolecule poorly soluble pharmaceutical adjuvant.
Above-mentioned capsule material is one or more mixing of following material: gelatin, arabic gum, carboxymethyl cellulose salt, hydroxypropyl emthylcellulose, ethyl cellulose or acrylate copolymer; And also add the moderate lubrication agent in the described capsule material.The capsule material is preferably the crylic acid resin material in the acrylate copolymer, further preferred You Liqi (Eudragit) class material; Lubricant is preferably Pulvis Talci.
In the above-mentioned sustained-release micro-spheres that contains azithromycin, the weight ratio of capsule material and azithromycin is 1: 2 to 5: 1; Be preferably 1: 1 to 4: 1.
The sustained-release micro-spheres of above-mentioned azithromycin forms with spray drying method for preparation.
A kind of optimal technical scheme of sustained-release micro-spheres that preparation 1000g contains azithromycin is as follows: the consumption of azithromycin and capsule material is: azithromycin 500g, acrylic resin II 300g, Pulvis Talci 200g; The method for preparing sustained-release micro-spheres has following steps: 1. azithromycin was pulverized 120 mesh sieves, and it is standby to get recipe quantity; 2. be solvent with 0.5% ammonia spirit, compound concentration is 0.6% acrylic resin II solution; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 170 ℃ of inlet temperatures, and 90 ℃ of outlet temperatures make the Azithromycin slow-release microsphere.
Another optimal technical scheme of sustained-release micro-spheres that preparation 1000g contains azithromycin is as follows: the consumption of azithromycin and capsule material is: azithromycin 200g, gelatin 600g, sodium carboxymethyl cellulose 100g, Pulvis Talci 100g; The method for preparing sustained-release micro-spheres has following steps: 1. azithromycin was pulverized 120 mesh sieves, and it is standby to get recipe quantity; 2. preparation contains gelatin 3%, contains the aqueous solution of sodium carboxymethyl cellulose 0.5%; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 170 ℃ of inlet temperatures, and 90 ℃ of outlet temperatures make the Azithromycin slow-release microsphere.
The technical scheme that realizes the preparation method that a kind of dry suspension is provided in the object of the invention is: this preparation method comprises the steps: 1. azithromycin to be pulverized 120 mesh sieves, and it is standby to get recipe quantity; 2. with capsule material swelling, be dissolved or dispersed in the solvent fully; 3. the azithromycin that 1. the adding step obtains in the liquid that 2. step obtains stirs and makes suspension; 4. adding Pulvis Talci in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, inlet temperature 160-180 ℃, outlet temperature 85-95 ℃, makes the Azithromycin slow-release microsphere; 6. this microsphere is measured content, after the calculating, add corresponding adjuvant in proportion, granulate, promptly as dilution correctives and suspensoid etc.
The present invention has positive effect: the dosage form of (1) azithromycin preparation provided by the invention is a slow-release dry suspension, specification is 1.0～2.5g, is unit dose package, instructions of taking: add an amount of cold water, it is oral to shake up the back, takes once 1 hour ante cibum or 2 hours after meal to get final product.Compare with common Azithromycin for Suspension, orally using dosage increases, and medicining times reduces, and can significantly increase patient's compliance, and the disposable medicine that gives whole therapeutic doses, can reduce the generation of Resistant strain.(2) Azithromycin slow-release dry suspension provided by the invention is a slow release formulation, reach the purpose of slow release, slow release has the following advantages: the one, can reduce the rate of release after azithromycin enters gastrointestinal tract, and can reduce the bad reflection that high concentration medicine causes the gastrointestinal stimulation.The 2nd, reduce the rate of release of medicine azithromycin, thereby reduce the infiltration rate of medicine, can reduce that azithromycin blood drug level increases suddenly and the untoward reaction that causes is dizzy as dizziness, tinnitus etc.The 3rd, the rate of release of reduction medicine azithromycin can increase mouthfeel, thereby increases patient's compliance.(3) purpose of Azithromycin slow-release dry suspension slow release provided by the invention stimulates for reducing gastrointestinal, its medicine meets zero level substantially and discharges by the oral rate of release that enters behind the gastrointestinal tract, substantially fully discharge after 6 hours, that is: discharged 5～25% in 1 hour, discharging 35～55%, 6 hours in 3 hours is released in more than 80%.(4) the present invention is with respect to prior art, and production cost is low, the bioavailability height, and side effect is little, has obviously improved the compliance and the convenience of administration, is a kind of preparation with clinical meaning.(5) characteristics of Azithromycin slow-release dry suspension provided by the invention are that technological parameter is simple, are fit to industrial amplification production.Its Chinese medicine is discharged in the medium by diffusion, and releasing mechanism is similar to erodible framework material, and prescription is directly determined release.
The specific embodiment
(embodiment 1)
Pastille is partly write out a prescription:
| Azithromycin (120 order) | ?500g |
| Acrylic resin II number | ?300g |
| Pulvis Talci | ?200g |
| Make | ?1000g |
Preparation technology has following steps:
1. get in the prescription azithromycin and pulverized 120 mesh sieves, standby.2. be solvent with 0.5% ammonia spirit, compound concentration is 0.6% acrylic resin II solution; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 160～180 ℃ of inlet temperatures, about 90 ℃ of outlet temperature, the Azithromycin slow-release microsphere of system; 6. this microsphere is measured content, after the calculating, add corresponding adjuvant in proportion, granulate, promptly as diluting agent of tender flavor and suspensoid.
(embodiment 2)
Pastille is partly write out a prescription:
| Azithromycin (120 order) | ?200g |
| Gelatin | ?600g |
| Sodium carboxymethyl cellulose | ?100g |
| Pulvis Talci | ?100g |
| Make | ?1000g |
Preparation technology has following steps:
1. get in the prescription azithromycin and pulverized 120 mesh sieves, standby.2. preparation contains gelatin 3%, contains the aqueous solution of sodium carboxymethyl cellulose 0.5%; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 160～180 ℃ of inlet temperatures, about 90 ℃ of outlet temperature, the Azithromycin slow-release microsphere of system; 6. this microsphere is measured content, after the calculating, add corresponding adjuvant in proportion, granulate, promptly as diluting agent of tender flavor and suspensoid.
Claims (10)
1, a kind of slow released dry azithromycin suspension is characterized in that: be prepared from by sustained-release micro-spheres that contains azithromycin and the adjuvant of pharmaceutically using always; The described sustained-release micro-spheres that contains azithromycin is made up of the azithromycin and the capsule material of parcel azithromycin; Described capsule material is medicinal macromolecule viscous material or macromolecule poorly soluble pharmaceutical adjuvant.
2, a kind of slow released dry azithromycin suspension according to claim 1 is characterized in that: the mixing of one or more that wherein said capsule material is following material: gelatin, arabic gum, carboxymethyl cellulose salt, hydroxypropyl emthylcellulose, ethyl cellulose or acrylate copolymer; And also add lubricant in the described capsule material.
3, a kind of slow released dry azithromycin suspension according to claim 2 is characterized in that: wherein said acrylate copolymer is the crylic acid resin material; Lubricant is a Pulvis Talci.
4. according to claim 1,2 or 3 described a kind of slow released dry azithromycin suspensions, it is characterized in that: contain in the sustained-release micro-spheres of azithromycin, the weight ratio of capsule material and azithromycin is 1: 2 to 5: 1.
5, a kind of slow released dry azithromycin suspension according to claim 4 is characterized in that: contain in the sustained-release micro-spheres of azithromycin, the weight ratio of capsule material and azithromycin is 1: 1 to 4: 1.
6, a kind of slow released dry azithromycin suspension according to claim 5, it is characterized in that: the sustained-release micro-spheres of azithromycin is to form with spray drying method for preparation.
7, a kind of slow released dry azithromycin suspension according to claim 6 is characterized in that: the sustained-release micro-spheres of preparation 1000g azithromycin, and the consumption of azithromycin and capsule material is: azithromycin 500g, acrylic resin II 300g, Pulvis Talci 200g; The method for preparing sustained-release micro-spheres has following steps: 1. azithromycin was pulverized 120 mesh sieves, and it is standby to get recipe quantity; 2. be solvent with 0.5% ammonia spirit, compound concentration is 0.6% acrylic resin II solution; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 170 ℃ of inlet temperatures, and 90 ℃ of outlet temperatures make the Azithromycin slow-release microsphere.
8, a kind of slow released dry azithromycin suspension according to claim 6, it is characterized in that: the sustained-release micro-spheres of preparation 1000g azithromycin, the consumption of azithromycin and capsule material is: azithromycin 200g, gelatin 600g, sodium carboxymethyl cellulose 100g, Pulvis Talci 100g; The method for preparing sustained-release micro-spheres has following steps: 1. azithromycin was pulverized 120 mesh sieves, and it is standby to get recipe quantity; 2. preparation contains gelatin 3%, contains the aqueous solution of sodium carboxymethyl cellulose 0.5%; 3. the azithromycin of the recipe quantity that 1. the adding step obtains in the solution that 2. step obtains stirs and makes suspension; 4. the Pulvis Talci that adds recipe quantity in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, 170 ℃ of inlet temperatures, and 90 ℃ of outlet temperatures make the Azithromycin slow-release microsphere.
9, a kind of preparation method of slow released dry azithromycin suspension is characterized in that: comprise the steps: 1. azithromycin to be pulverized 120 mesh sieves, it is standby to get recipe quantity; 2. with capsule material swelling, be dissolved or dispersed in the solvent fully; 3. the azithromycin that 1. the adding step obtains in the liquid that 2. step obtains stirs and makes suspension; 4. adding Pulvis Talci in the suspension that 3. step obtains stirs; 5. the material that 4. step is obtained carries out spray drying, inlet temperature 160-180 ℃, outlet temperature 85-95 ℃, makes the Azithromycin slow-release microsphere; 6. this microsphere is measured content, after the calculating, add corresponding adjuvant in proportion, granulate, promptly.
10, preparation method according to claim 9 is characterized in that: step 5. in, inlet temperature is 170 ℃, outlet temperature is 90 ℃; Step 6. in, the composition that adds adjuvant is dilution correctives and suspensoid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610091077 CN1887272A (en) | 2006-07-13 | 2006-07-13 | Slow released dry azithromycin suspension and its prepn |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610091077 CN1887272A (en) | 2006-07-13 | 2006-07-13 | Slow released dry azithromycin suspension and its prepn |
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| CN1887272A true CN1887272A (en) | 2007-01-03 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744773A (en) * | 2010-02-10 | 2010-06-23 | 张明正 | Preparation method of bitter-free azithromycin granular composite |
| CN101829045A (en) * | 2010-03-05 | 2010-09-15 | 南京海陵中药制药工艺技术研究有限公司 | Azithromycin slow-release dry suspension and preparation method thereof |
| CN103054813A (en) * | 2012-12-31 | 2013-04-24 | 广东先强药业有限公司 | Azithromycin oral sustained-release dry suspension and preparation method thereof |
| CN103417483A (en) * | 2012-05-25 | 2013-12-04 | 杭州赛利药物研究所有限公司 | Memantine hydrochloride slow-release dry suspension and preparation method thereof |
| CN111904935A (en) * | 2020-09-02 | 2020-11-10 | 苏州东瑞制药有限公司 | Azithromycin dry suspension |
-
2006
- 2006-07-13 CN CN 200610091077 patent/CN1887272A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744773A (en) * | 2010-02-10 | 2010-06-23 | 张明正 | Preparation method of bitter-free azithromycin granular composite |
| CN101829045A (en) * | 2010-03-05 | 2010-09-15 | 南京海陵中药制药工艺技术研究有限公司 | Azithromycin slow-release dry suspension and preparation method thereof |
| CN103417483A (en) * | 2012-05-25 | 2013-12-04 | 杭州赛利药物研究所有限公司 | Memantine hydrochloride slow-release dry suspension and preparation method thereof |
| CN103417483B (en) * | 2012-05-25 | 2017-09-12 | 杭州赛利药物研究所有限公司 | memantine hydrochloride slow-release dry suspension and preparation method thereof |
| CN103054813A (en) * | 2012-12-31 | 2013-04-24 | 广东先强药业有限公司 | Azithromycin oral sustained-release dry suspension and preparation method thereof |
| CN111904935A (en) * | 2020-09-02 | 2020-11-10 | 苏州东瑞制药有限公司 | Azithromycin dry suspension |
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