CN1562063A - Medicinal preparation containing erythromycine ethylsuccinate - Google Patents
Medicinal preparation containing erythromycine ethylsuccinate Download PDFInfo
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- CN1562063A CN1562063A CN 200410025961 CN200410025961A CN1562063A CN 1562063 A CN1562063 A CN 1562063A CN 200410025961 CN200410025961 CN 200410025961 CN 200410025961 A CN200410025961 A CN 200410025961A CN 1562063 A CN1562063 A CN 1562063A
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- erythromycin ethylsuccinate
- formula
- ethylsuccinate
- cyclodextrin
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Abstract
A medicine in the form of water-soluble powder is prepared from erythromycin ethylsuccinate and hydroxy-beta-cyclodextrin through proportional mixing and freeze drying. It is applied by intravenous injection or intramuscular injection.
Description
Technical field
The invention belongs to the improvement that contains the erythromycin ethylsuccinate pharmaceutical dosage form, relate to medical technical field.
Background technology
Erythromycin ethylsuccinate (Erythromycin Ethylsuccinate) chemical name erythromycin 2 ' ethyl succinates; Molecular formula: C
43H
75NO
16, molecular weight: 862.07, belong to macrolide antibiotics, be broad spectrum activity antibiosis anti-inflammatory drug of new generation, included by American Pharmacopeia, European Pharmacopoeia and Chinese Pharmacopoeia (2000 editions).Its maximum characteristics are has a broad antifungal spectrum, and the medication face width is applicable to various inflammation, are particularly useful for penicillins and cephalo-type allergy and drug resistance patient.The erythromycin ethylsuccinate determined curative effect, effect is rapid, particularly for the upper respiratory tract infection effect highly significant that is caused by atypia pathogen such as legionella, mycoplasma, chlamydia.This medicine has intestinal canal administration dosage forms such as tablet, capsule, granule.And the maximum side effect of this medicine intestinal canal administration is the stimulation to the intestines and stomach, and the patient takes the back inappetence more, feel sick even vomiting, and relatively slow because of absorbing, affect the treatment.Because erythromycin ethylsuccinate is water-soluble hardly, therefore, be difficult to develop have the storage life long enough, the dosage form that can be used for drug administration by injection that speed is water-soluble.These problems are particularly serious for macrolides compound, and this means generally can't be by conventional methods (can miscible auxiliary agent as oil, surfactant or water) with this compound dissolution.
HYDROXYPROPYL BETA-CYCLODEXTRIN is the hydroxyalkylation chemical compound of betacyclodextrin, the characteristics of this chemical compound are to change by the physical characteristic of envelope material as solid solution agent and envelope agent, as dissolubility, stability etc., can reach comparatively ideal effect with purpose through different process meanses to different envelope objects.
Do not see the pertinent literature that the success of erythromycin ethylsuccinate parenterai administration formulation development is arranged and the report of product up to now as yet.
Summary of the invention
The purpose of this invention is to provide a kind of can speed water-soluble pharmaceutical preparation of erythromycin ethylsuccinate and preparation method thereof that contains, make it be applicable to parenterai administration (as intravenously administrable or muscle administration), and have that preparation is simple, stable performance, safe, advantage that side effect is low, widely applicable.
The composition of the pharmaceutical preparation that contains erythromycin ethylsuccinate proposed by the invention has: cyclodextrin derivative shown in erythromycin ethylsuccinate and the formula I, and formula I is:
Wherein Ra1, Ra1, Ra2, Ra3, Ra4, Ra5, Ra6, Ra7, Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rc1, Rc2, Rc3, Rc4, Rc5, Rc6, Rc7 represent independently H or-[CH2-CH (CH3)-O] n-H, n 〉=1.
Each formula I molecule of the present invention-[CH
2-CH (CH
3)-O]
nThe average of-H is preferably 2.8-10.5 (for example 5.5), can strengthen the effect of molecule envelope, thereby improve the dissolubility of erythromycin ethylsuccinate, this effect is unpredictable, because increase the replacement degree cyclodextrin cavity steric hindrance is on every side strengthened, thereby reduced compounding efficiency.
In the preparation of the present invention, the content of erythromycin ethylsuccinate is 10-300mg/g (preferred 50mg/g-100mg/g); The cyclodextrin derivative of formula I will be with 1: 1-1: 50 erythromycin ethylsuccinate: the cyclodextrin derivative weight ratio exists, and preferred 1: 5-1: 17, best 1: 10-1: 11.
Preparation of the present invention is to exist with the water-soluble powder form.Said preparation is applicable to parenterai administration, for example intravenously administrable or muscle administration.
The preparation method that contains the pharmaceutical preparation of erythromycin ethylsuccinate of the present invention is that elder generation joins stirring and dissolving in the medicinal alcohol aqueous solution with cyclodextrin derivative shown in the formula I, adds erythromycin ethylsuccinate again and is stirred to dissolving, through the sterilization postlyophilization, can encapsulate; Ethanol content is 0%-100% (V/V) in the described ethanol water.Be preferably 80%-100%, the best is 100%.In the described preparation method, after adding the erythromycin ethylsuccinate stirring and dissolving, need to adopt the physical method that produces collision between compound molecule is handled, for example ultrasound wave or microwave treatment.The molecule of two kinds of chemical compounds is fully collided, reach better envelope purpose.
Cyclodextrin derivative shown in the formula I of the present invention is referred to as HYDROXYPROPYL BETA-CYCLODEXTRIN usually, because hydroxypropyl is or/and the polymeric quantity of hydroxypropyl and replace the uncertainty of position is difficult to structure title statement accurately, Gu Te row formula I expresses.
The preparating mechanism of novel form of the present invention is to utilize the good aqueous solubility of cyclodextrin derivative shown in the formula I and remarkable envelope effect to make erythromycin ethylsuccinate water-soluble.And utilize lyophilization (lyophilizing) can further improve the erythromycin ethylsuccinate-stability of cyclodextrin derivative complex in water.The cyclodextrin derivative that is applicable to preparation of the present invention can guarantee that final lyophilized products contains high-level moisture (up to 2.5%), but its stability is had no adverse effect.In addition, utilize the decomposition of above-mentioned cyclodextrin derivative may command and minimizing erythromycin ethylsuccinate.
Cyclodextrin derivative shown in the formula I that the present invention selects for use is equivalent to glucose through the toxicity test demonstration, and no teratogenesis, mutagenesis do not have long-term and acute toxicity; Erythromycin ethylsuccinate itself is as for many years medicinal, and therefore preparation of the present invention is safe.
Preparation of the present invention can make erythromycin ethylsuccinate content reach 10-300mg/g, and the shelf-life was not less than 1 year.Can find out obviously that also the present invention has that preparation is simple, stable performance, safe, side effect is low, curative effect is rapid, widely applicable advantage; Solved contain at present the erythromycin ethylsuccinate medicine can only be singlely by the drawback of intestinal canal administration.
The specific embodiment
In following example, the average hydroxypropyl substitution value of each cyclodextrin molecular of HYDROXYPROPYL BETA-CYCLODEXTRIN is 5.5.Prepared medicament is the intravenous administration of erythromycin ethylsuccinate or the water-soluble powder of intramuscular administration.
Embodiment 1
Component specification mg
The sharp monarch of erythromycin ethylsuccinate group 10
HYDROXYPROPYL BETA-CYCLODEXTRIN Shaanxi Institute of Microbiology 500
Glucose Chinese Pharmacopoeia 2000 editions 490
Total amount 1000
Under stirring condition, HYDROXYPROPYL BETA-CYCLODEXTRIN is joined in the 5ml water, continue to be stirred to dissolving fully; Add erythromycin ethylsuccinate and be stirred to dissolving fully; Microwave treatment is 2 minutes in the ice bath; Gained solution filters through the 0.2mm nylon leaching film of sterilization; Add medicinal glucose powder, be stirred to dissolving; After lyophilization, can encapsulate use.
Embodiment 2
Component specification mg
The sharp monarch of erythromycin ethylsuccinate group 50
HYDROXYPROPYL BETA-CYCLODEXTRIN Shaanxi Institute of Microbiology 500
Total amount 550
Under stirring condition, HYDROXYPROPYL BETA-CYCLODEXTRIN is joined among the anhydrous alcohol for medical use 5ml, continue to be stirred to dissolving fully; Add erythromycin ethylsuccinate and be stirred to dissolving fully; Gained solution is sterilized through membrane filtration; After lyophilization, can encapsulate use again.
Embodiment 3
Component specification mg
The sharp monarch of erythromycin ethylsuccinate group 100
HYDROXYPROPYL BETA-CYCLODEXTRIN Shaanxi Institute of Microbiology 500
Total amount 600
Under stirring condition, HYDROXYPROPYL BETA-CYCLODEXTRIN is joined among the anhydrous alcohol for medical use 5ml, continue to be stirred to dissolving fully; Add erythromycin ethylsuccinate and be stirred to dissolving fully; Ultrasonic Treatment is 10 minutes in the ice bath; Gained solution filters through the 0.2mm nylon leaching film of sterilization; After lyophilization, can encapsulate use.
Embodiment 4
Component specification mg
The sharp monarch of erythromycin ethylsuccinate group 200
HYDROXYPROPYL BETA-CYCLODEXTRIN Shaanxi Institute of Microbiology 1800
Total amount 2000
Prepare 50% alcoholic solution with 2000 editions waters for injection of recording of Chinese Pharmacopoeia.Under stirring condition, HYDROXYPROPYL BETA-CYCLODEXTRIN joined among 50% the alcoholic solution 5ml, continue to be stirred to dissolving fully; Add erythromycin ethylsuccinate and be stirred to dissolving fully; Gained solution filters through the nylon leaching film of sterilization; After lyophilization, can encapsulate use again.
Embodiment 5
Component specification mg
The sharp monarch of erythromycin ethylsuccinate group 300
HYDROXYPROPYL BETA-CYCLODEXTRIN Shaanxi Institute of Microbiology 1700
Total amount 2000
Prepare 80% alcoholic solution with 2000 editions waters for injection of recording of Chinese Pharmacopoeia.Under stirring condition, HYDROXYPROPYL BETA-CYCLODEXTRIN joined among 80% the alcoholic solution 5ml, be stirred to dissolving fully; Add erythromycin ethylsuccinate and be stirred to dissolving fully; Microwave treatment is 5 minutes in the ice bath; Ultrasonic Treatment is 10 minutes in the ice bath; Gained solution is through the membrane filtration of sterilization; After lyophilization, can encapsulate use again.
Claims (10)
1, a kind of pharmaceutical preparation that contains erythromycin ethylsuccinate is characterized in that, the composition of said preparation has: cyclodextrin derivative shown in erythromycin ethylsuccinate and the formula I; Formula I is:
Wherein: Ra1, Ra1, Ra2, Ra3, Ra4, Ra5, Ra6, Ra7, Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rc1, Rc2, Rc3, Rc4, Rc5, Rc6, Rc7 represent independently H or-[CH2-CH (CH3)-O] n-H, n 〉=1.
2, preparation according to claim 1 is characterized in that, in described each formula I molecule-[CH
2-CH (CH
3)-O]
n-H average is 2.8-10.5.
3, preparation according to claim 1 is characterized in that, the weight ratio of erythromycin ethylsuccinate and formula I cyclodextrin derivative is 1: 1-1: 50.
4, preparation according to claim 3 is characterized in that, the weight ratio of erythromycin ethylsuccinate and formula I cyclodextrin derivative is 1: 5-1: 17.
According to described any preparation of claim 1-4, it is characterized in that 5, said preparation is the water-soluble powder.
6, preparation according to claim 5 is characterized in that, said preparation is suitable for parenterai administration.
7, require the preparation method of described pharmaceutical preparation according to aforesaid right, it is characterized in that, earlier cyclodextrin derivative shown in the formula I is joined stirring and dissolving in the medicinal alcohol aqueous solution, add erythromycin ethylsuccinate again and be stirred to dissolving, through the sterilization postlyophilization, can encapsulate; Ethanol content is 0%-100% (V/V) in the described ethanol water.
8, preparation method according to claim 7 is characterized in that, ethanol content is 80-100% (V/V) in the described ethanol water.
9, preparation method according to claim 8 is characterized in that, ethanol content is 100% in the described ethanol water.
10, according to described any preparation method of claim 7-9, it is characterized in that, after adding the erythromycin ethylsuccinate stirring and dissolving, need to adopt the physical method that produces collision between compound molecule is handled.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410025961 CN1259053C (en) | 2004-03-17 | 2004-03-17 | Medicinal preparation containing erythromycine ethylsuccinate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410025961 CN1259053C (en) | 2004-03-17 | 2004-03-17 | Medicinal preparation containing erythromycine ethylsuccinate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1562063A true CN1562063A (en) | 2005-01-12 |
| CN1259053C CN1259053C (en) | 2006-06-14 |
Family
ID=34480501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410025961 Expired - Fee Related CN1259053C (en) | 2004-03-17 | 2004-03-17 | Medicinal preparation containing erythromycine ethylsuccinate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1259053C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006042858A3 (en) * | 2004-10-21 | 2006-07-20 | Pf Medicament | Complex comprising an antibiotic, a cyclodextrin and an interaction agent |
| CN104523572A (en) * | 2014-12-25 | 2015-04-22 | 海南卫康制药(潜山)有限公司 | Erythromycin ethylsuccinate composition freeze-dried tablets and preparation method thereof |
-
2004
- 2004-03-17 CN CN 200410025961 patent/CN1259053C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006042858A3 (en) * | 2004-10-21 | 2006-07-20 | Pf Medicament | Complex comprising an antibiotic, a cyclodextrin and an interaction agent |
| CN104523572A (en) * | 2014-12-25 | 2015-04-22 | 海南卫康制药(潜山)有限公司 | Erythromycin ethylsuccinate composition freeze-dried tablets and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1259053C (en) | 2006-06-14 |
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Granted publication date: 20060614 |