CN101125125A - Methylergometrine Maleate powder injection and preparation method thereof - Google Patents
Methylergometrine Maleate powder injection and preparation method thereof Download PDFInfo
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- CN101125125A CN101125125A CNA200710121608XA CN200710121608A CN101125125A CN 101125125 A CN101125125 A CN 101125125A CN A200710121608X A CNA200710121608X A CN A200710121608XA CN 200710121608 A CN200710121608 A CN 200710121608A CN 101125125 A CN101125125 A CN 101125125A
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- maleate
- injection
- acceptable carrier
- powder injection
- methylergometrine
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Abstract
The present invention relates to a methylergometrine maleate powder injection, which pertains to the field of pharmaceutical preparations; the present invention contains the methylergometrine maleate which is taken as the active ingredient and the pharmaceutically acceptable carriers, wherein, the weight ratio of the methylergometrine maleate and the pharmaceutically acceptable carriers is 1: 15 to 1: 300, the pharmaceutically acceptable carriers are one or more of the lactose, glucose, mannitol, low molecular weight dextran, sodium chloride and aminoacetic acid. The present invention also provides a preparation method of methylergometrine maleate powder injection. The powder injection of the present invention has good stability, easy storage and transportation, furthermore, the irritation is significantly decreased and the compliance of the patients is increased.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, particularly, the present invention relates to a kind of A maleate ergometrine injection and its preparation method.
Background technology
Methylergonovine maleate (Methylergonovine Maleate) is a uterotonic, and molecular formula is: C
20H
25N
3O
2C
4H
4O
4, structural formula is:
Be mainly used in clinically puerperal or post-abortion inertia of uterus or recover the not good metrorrhagia that causes.Domestic the production as yet of this medicine gone on the market at present, and the dosage form of external listing is tablet and aqueous injection.Aqueous injection is the aqueous solution that 1ml contains methylergonovine maleate 0.2mg.Methylergonovine maleate is all unstable to light, heat, needs heat sterilization when its aqueous injection of preparation, and therefore easily cause medicine to decompose and destroy, and the aqueous injection poor stability, need the lucifuge cryopreservation.These have all influenced the safe and effective clinically use of this medicine.
The present invention is through research, and finding to adopt cryodesiccated method that methylergonovine maleate is made the sterile injection powder preparation can address the aforementioned drawbacks, and the invention provides a kind of freezing-dried powder injection of methylergonovine maleate for this reason.
Summary of the invention
The invention provides a kind of freezing-dried powder injection of methylergonovine maleate, this injection is become to be grouped into the medicine acceptable carrier by the active component methylergonovine maleate, and wherein said medicine acceptable carrier is one or more in lactose, glucose, mannitol, low molecular dextran, sodium chloride, the glycine.
The prescription of injection of the present invention consists of the active component methylergonovine maleate, medicine acceptable carrier and low amounts of water, wherein the weight ratio of methylergonovine maleate and medicine acceptable carrier is 1: 15～1: 300, preferred 1: 40～1: 200, and more preferably 1: 50～1: 150.Employed medicine acceptable carrier is preferably lactose, glucose, mannitol, sodium chloride.Wherein more preferably lactose, glucose.
The present invention also provides the method for preparing this freezing-dried powder injection, adopts following method preparation:
1. take by weighing drug acceptable carrier and dissolve standardize solution to certain volume with water for injection;
2. use activated carbon adsorption, coarse filtration;
3. take by weighing methylergonovine maleate, dissolve in the solution of adding step 2, use the water for injection standardize solution to certain volume;
4. with 0.45 μ M membrane filtration;
5. with 0.22 μ M membrane filtration;
6. divide to install in the cillin bottle, carry out lyophilization, obtain lyophilized injectable powder.
The injection methylergonovine maleate is aseptic freeze-dried injectable powder, the purpose that the present invention is prepared into freeze-dried powder injection with methylergonovine maleate will eliminate methylergonovine maleate exactly and water interacts for a long time, to reduce Effect of Environmental, stability is significantly better than aqueous injection.Simultaneously, freeze-dried powder adopts cillin bottle, and liquid drugs injection adopts ampoule, and the intensity of cillin bottle is significantly better than ampoule, and steady quality is easy to keeping and transportation.
In addition, the pH of aqueous injection is 2.88, and need not to add the pH regulator agent in the lyophilized injectable powder of the present invention, redissolves back pH near neutral, and when intramuscular injection, subcutaneous injection or intravenous injection, zest obviously reduces, and has increased patient's compliance.
The specific embodiment
Following examples and influence factor's test data are used to further specify technical scheme of the present invention, are not to be restriction to the technology of the present invention feature.
The detailed process and the step of preparation lyophilized injectable powder of the present invention are as follows:
(1) dosing
Prepare: various dosing articles for use on deck;
The dissolving adjuvant: take by weighing the medicinal carrier of accepting of recipe quantity, add an amount of sterilized water for injection, the room temperature dissolving adds an amount of needle-use activated carbon, stirring at room 30 minutes, coarse filtration;
Dissolving principal agent: take by weighing the methylergonovine maleate of recipe quantity, add the suitable quantity of water dissolving, add in the above-mentioned coarse filtration liquid, add water to the prescription full dose;
Filtration sterilization: with 0.45 μ M membrane filtration, reuse 0.22 μ M membrane filtration;
(2) fill
Test run: install machine, energized is checked each working order, by low speed to high-speed cruising intact after, can use;
Prepare: the bottling top plug, cillin bottle is sent into bottle arranging disk, plug is packed into manage in the plug device;
Transfer loading amount: the result determines loading amount by the semi-finished product assay;
Fill: the reason dish turns clockwise, bottle is sent into reason bottle track, enter the calibration fluted disc, the calibration fluted disc is with 10～50 intermittently speed rotations of per minute, bottle is pushed filling position, filling mechanism carries out fill with the motion up and down at synchronous intermittence, and the cillin bottle after the fill goes to by the plug position, carries out by plug.
With the medicine bottle sabot of fill false add plug, send into freeze dryer.
(3) lyophilization
1, baffle temperature is controlled at-35 ℃ to-40 ℃, and products temperature reaches below-35 ℃, and from the visible glaciation of form, the pre-freeze time is 2～4 hours;
2, distillation: baffle temperature is risen to about-20 ℃, simultaneously the system vacuum degree is remained on 6～8Pa, the distillation time is about 7～11 hours;
3, drying: baffle temperature is risen to about 20 ℃, kept 4～6 hours;
4, gland.
According to said method, can prepare following preparation of the present invention:
Preparation 1:
Methylergonovine maleate: 0.2mg
Lactose: 10～60mg
Preparation 2:
Methylergonovine maleate: 0.2mg
Lactose: 6～20mg
Glucose: 20 ~ 6mg
Preparation 3:
Methylergonovine maleate: 0.2mg
Mannitol: 5～60mg
Preparation 4:
Methylergonovine maleate: 0.2mg
Dextran: 10～60mg
Preparation 5:
Methylergonovine maleate: 0.2mg
Glycine: 5～60mg
Preparation 6:
Methylergonovine maleate: 0.2 mg
Lactose: 20mg
Preparation 7:
Methylergonovine maleate: 0.2mg
Lactose: 30mg
Preparation 8:
Methylergonovine maleate: 0.2mg
Lactose: 20mg
Glucose: 6mg
Preparation 9:
Methylergonovine maleate: 0.2mg
Mannitol: 5mg
Preparation 10:
Methylergonovine maleate: 0.2mg
Mannitol: 10mg
Preparation 11:
Methylergonovine maleate: 0.2mg
Sodium chloride: 30mg
Preparation 12:
Methylergonovine maleate: 0.2mg
Dextran: 20mg
Methylergometrine Maleate powder injection influence factor result of the test and conclusion:
Exposure experiments to light: it is an amount of to get sample of the present invention, with 4500 ± 500Lx rayed 10 days, 5,10 days sampling and measuring, sees Table 1 respectively; Hot test: it is an amount of to get sample of the present invention, puts in 60 ℃ of baking boxs 10 days, 5,10 days sampling and measuring, sees Table 1 respectively.
Table 1 injection methylergonovine maleate influence factor result of the test
| The placement condition | Standing time (my god) | Outward appearance | pH | Clarity | Solution colour | Related substance (%) | Content (%) |
| 0 | The white block | 5.51 | ≤ No. 0.5 | ＜yellow No. 1 | 0.59 | 104.4 | |
| Illumination (4500Lx) | 5 | The white block | 5.41 | ≤ No. 0.5 | ＜yellow No. 1 | 0.80 | 102.5 |
| 10 | The white block | 5.37 | ≤ No. 0.5 | ＜yellow No. 1 | 0.92 | 101.3 | |
| High temperature (60 ℃) | 5 | The white block slightly shrinks | 5.62 | ＜No. 1 | ＜yellow No. 1 | 1.20 | 103.2 |
| 10 | The white block slightly shrinks | 5.59 | ＜No. 1 | ＜yellow No. 1 | 2.30 | 102.1 |
This product is behind strong illumination, and sample appearance, content, clarity of solution, solution colour, pH there is no variation, and related substance slightly increases; After 10 days, slightly shrink by sample appearance through hot test for this product, and related substance slightly increases, and content, clarity of solution, solution colour, pH there is no significant change; Show that through influence factor's test this product is very stable to light, to better heat stability.
Claims (4)
1. Methylergometrine Maleate powder injection, it is characterized in that, contain methylergonovine maleate and medicine acceptable carrier as active component, the weight ratio of described methylergonovine maleate and medicine acceptable carrier is 1: 15～1: 300, and described medicine acceptable carrier is one or more in lactose, glucose, mannitol, low molecular dextran, sodium chloride, the glycine.
2. Methylergometrine Maleate powder injection as claimed in claim 1 is characterized in that, wherein the weight ratio of methylergonovine maleate and medicine acceptable carrier is 1: 40～1: 200.
3. Methylergometrine Maleate powder injection as claimed in claim 1 is characterized in that, wherein the weight ratio of methylergonovine maleate and medicine acceptable carrier is 1: 50～1: 150.
4. a method for preparing the described Methylergometrine Maleate powder injection of claim 1 is characterized in that, this method may further comprise the steps:
A., take by weighing drug acceptable carrier and with water for injection dissolving standardize solution to certain volume;
B, use activated carbon adsorption, coarse filtration;
C, take by weighing methylergonovine maleate, add in the solution of step b and dissolve, with the water for injection standardize solution to certain volume;
D, with 0.45 μ M membrane filtration;
E, with 0.22 μ M membrane filtration;
F, branch install in the cillin bottle, carry out lyophilization, obtain lyophilized injectable powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710121608XA CN101125125A (en) | 2007-09-11 | 2007-09-11 | Methylergometrine Maleate powder injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710121608XA CN101125125A (en) | 2007-09-11 | 2007-09-11 | Methylergometrine Maleate powder injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
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| CN101125125A true CN101125125A (en) | 2008-02-20 |
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|---|---|---|---|
| CNA200710121608XA Pending CN101125125A (en) | 2007-09-11 | 2007-09-11 | Methylergometrine Maleate powder injection and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055361A (en) * | 2015-08-19 | 2015-11-18 | 河北智同医药控股集团有限公司 | Methyl ergometrine maleate tablets and preparation method thereof |
| CN105085514A (en) * | 2015-08-19 | 2015-11-25 | 河北智同医药控股集团有限公司 | Methyl ergometrine maleate compound and preparation method thereof |
| CN105125481A (en) * | 2015-08-19 | 2015-12-09 | 河北智同医药控股集团有限公司 | Methylergometrine maleate injection and preparation method thereof |
| CN108977476A (en) * | 2017-12-15 | 2018-12-11 | 北大方正集团有限公司 | A kind of fermentation liquid and preparation method thereof rich in ergometrine |
-
2007
- 2007-09-11 CN CNA200710121608XA patent/CN101125125A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055361A (en) * | 2015-08-19 | 2015-11-18 | 河北智同医药控股集团有限公司 | Methyl ergometrine maleate tablets and preparation method thereof |
| CN105085514A (en) * | 2015-08-19 | 2015-11-25 | 河北智同医药控股集团有限公司 | Methyl ergometrine maleate compound and preparation method thereof |
| CN105125481A (en) * | 2015-08-19 | 2015-12-09 | 河北智同医药控股集团有限公司 | Methylergometrine maleate injection and preparation method thereof |
| CN105055361B (en) * | 2015-08-19 | 2018-02-23 | 河北智同医药控股集团有限公司 | A kind of methylergonovine maleate tablet and preparation method thereof |
| CN105125481B (en) * | 2015-08-19 | 2019-01-29 | 河北智同医药控股集团有限公司 | A kind of methylergonovine maleate injection and preparation method thereof |
| CN108977476A (en) * | 2017-12-15 | 2018-12-11 | 北大方正集团有限公司 | A kind of fermentation liquid and preparation method thereof rich in ergometrine |
| CN108977476B (en) * | 2017-12-15 | 2021-12-03 | 北大方正集团有限公司 | Fermentation liquor rich in ergometrine and preparation method thereof |
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Legal Events
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Taiyangshi (Tangshan) Pharm Ind Co.,Ltd. Assignor: Han Zhiqiang Contract fulfillment period: 2007.09.12 to 2027.09.11 Denomination of invention: Methylergometrine maleate powder injection and preparation method thereof Granted publication date: unauthorized License type: Exclusive license Record date: 20071012 |
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| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENCE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.9.12 TO 2027.9.11 Name of requester: TAIYANGSHI (TANGSHAN) PHARMACEUTICAL CO. LTD. Effective date: 20071012 |
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| PB01 | Publication | ||
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| RJ01 | Rejection of invention patent application after publication |
Open date: 20080220 |