CN100360134C - Injection liquid containing alprostadic and its production process - Google Patents
Injection liquid containing alprostadic and its production process Download PDFInfo
- Publication number
- CN100360134C CN100360134C CNB2003101022531A CN200310102253A CN100360134C CN 100360134 C CN100360134 C CN 100360134C CN B2003101022531 A CNB2003101022531 A CN B2003101022531A CN 200310102253 A CN200310102253 A CN 200310102253A CN 100360134 C CN100360134 C CN 100360134C
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- Prior art keywords
- alprostadil
- injection
- dehydrated alcohol
- peg400
- solution
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The present invention discloses an injection containing alprostadil which is prepared from the raw materials of alprostadil, anhydrous alcohol, polyethyleneglycol 400, dimethyl acetamide, 2-hydroxypropyl-beta-cyclodextrin, cysteine and sterile water for injection. Simultaneously, the present invention also discloses a production process of the injection containing alprostadil. The injection containing alprostadil can be used for treating various cardio-cerebrovascular diseases, diabetes and complications thereof, hepatitis A, hepatitis B, hepatitis C, various tumors and the like, and has broad application prospects.
Description
Technical field
The present invention relates to a kind of injection and production technology thereof, particularly relate to a kind of injection and production technology thereof that contains Alprostadil.
Technical background
At present, contain Alprostadil (prostaglandin E in the world
1) the low dose of injection prescription and the manufacturing process of effective ingredient be simple, causes the Alprostadil poor stability.Along with time lengthening, Alprostadil content successively decreases gradually, and impurity increases, and side effect increases, and curative effect reduces.
Summary of the invention
The objective of the invention is to overcome the defective of prior art, at prescription, improve on the production technology, provide that a kind of stability is strong, the injection that contains Alprostadil and the production technology thereof of determined curative effect.
The present invention is achieved through the following technical solutions.
The injection that the present invention contains Alprostadil adopts following weight portion prescription:
Alprostadil 0.02-0.40
Dehydrated alcohol 2000-15000
PEG400 2000-15000
Dimethyl acetylamide 1000-5000
2-HP-1-3
Cysteine 10-15
Sterile water for injection 50-100
Wherein, dehydrated alcohol can be by the replacing than mixture arbitrarily of glycerol or glycerol and dehydrated alcohol, and the weight portion prescription is constant; PEG400 can be by the replacing than mixture arbitrarily of 1,2 propylene glycol or 1,2 propylene glycol and PEG400, and the weight portion prescription is constant.
Alprostadil in the present invention prescription is the effective ingredient of injection, according to the sick difference of planting of treatment, the suitable dose scope be the 20-400 microgram/, preferred 30-200 microgram/.
Dehydrated alcohol or glycerol and PEG400 or 1,2 propylene glycol are the major parts of solvent as the double solvents of injection.PEG400 can also prolong the curative effect of Alprostadil, overcomes short defective of half-life.
Dimethyl acetylamide is uniformly dispersed injection as the stabilizing agent and the binding agent of injection, destroys effects such as pyrogen;
The 2-HP-is used for increasing the solubility property of Alprostadil at water.The dissolubility of Alprostadil in water is minimum, and the 2-HP-can increase the dissolubility of Alprostadil in injection greatly.In addition, the 2-HP-can also increase the stability of Alprostadil to light, heat, oxygen, disperses injection, reduces the side effect of Alprostadil.
Cysteine is an antioxidant, and the protection Alprostadil is not oxidized because of effects such as light, heat, oxygen.
Sterile water for injection joins dehydrated alcohol-PEG400 double solvents after being used for dissolving cysteine.
Therefore, alprostadil injection agent of the present invention is actually the dehydrated alcohol-PEG400-double solvents of sterile water for injection three composition and the compositions of Alprostadil.
The production technology of alprostadil injection agent of the present invention is as follows:
1, takes by weighing the injection effective ingredient Alprostadil,, make homogeneous solution with the dehydrated alcohol or the glycerol dissolving Alprostadil of about 80 times of its weight;
2, dissolve the 2-HP-and the cysteine of formula ratio with the injection water of formula ratio, stir and make homogeneous solution, the hydrochloric acid of reuse 10% is transferred the scope of pH value at 6.0-6.5;
3, with PEG400 or 1,2 propylene glycol and the dimethyl acetylamide of remaining dehydrated alcohol or glycerol dissolving formula ratio, stir and make homogeneous solution;
4, the 1st drips of solution that makes of step is added in the solution that the 2nd step made, the limit drips to become rapidly and stirs, and continues after being added dropwise to complete to stir 1 hour again, makes the mixture solution of Alprostadil and 2-HP-;
5, the 4th solution that makes of step is slowly joined while stirring in the double solvents that the 3rd step made, stir, the medicinal liquid that makes filters through 0.22 micron membranes, degerming, whether qualified, the underproof filter membrane of will changing filters again if all using bubble point method (method according to " Good Manufacturing Practice and Quality Control of Drug " record is carried out) mensuration filter membrane before and after filtering;
6, measure medicinal liquid content and adjust content (increase solvent or increase the meltage of Alprostadil).The mensuration clarity is qualified, underproofly changes 0.22 filter membrane again to be filtered to clarity qualified.
7, carry out the embedding packing under the aseptic condition, lamp inspection, it is qualified that product quality detects, packing, warehouse-in makes alprostadil injection agent of the present invention.
More than produce all and should produce and quality management in strict accordance with the requirement of country's " Good Manufacturing Practice and Quality Control of Drug ".
Alprostadil injection agent good stability of the present invention, Alprostadil content does not successively decrease gradually along with time lengthening, and impurity is few, and side effect is little, the curative effect height.Treatable sick the kind has: cardiovascular and cerebrovascular disease, diabetes and complication thereof, first, second, hepatitis C and various tumor.Production technology is simple, and not high to equipment requirements, production cost is low, and is good in economic efficiency.
The specific embodiment
Specify the present invention below by specific embodiment.
Embodiment 1
Prescription: Alprostadil 0.12g
Dehydrated alcohol 2000g
PEG400 2000g
Dimethyl acetylamide 1000g
2-HP-3.0g
Cysteine 10g
Sterile water for injection 100g
Production technology:
1, takes by weighing injection effective ingredient Alprostadil 0.12g, use 10 anhydrous alcohol solutions, stir, make homogeneous solution.
2, with 100g injection water dissolving 3g 2-HP-and 10g cysteine, stir and make homogeneous solution, the hydrochloric acid of reuse 10% is transferred pH value to 6.3;
3, with remaining 1990g anhydrous alcohol solution 2000g PEG400 and 1000g dimethyl acetylamide, stir and make homogeneous solution;
4, the 1st drips of solution that makes of step is added in the solution that the 2nd step made, the limit drips to become rapidly and stirs, and continues after being added dropwise to complete to stir 1 hour again, makes the mixture solution of Alprostadil and 2-HP-;
5, the 4th solution that makes of step is slowly joined while stirring in the double solvents that the 3rd step made, stir, the medicinal liquid that makes is through 0.22 micron membranes filtration sterilization;
6, measure medicinal liquid content and adjust content to qualified, it is qualified to measure clarity;
7, carry out embedding under the aseptic condition and be distributed into 100, making specification is the alprostadil injection agent of 120 micrograms/5ml, lamp inspection, and it is qualified that product quality detects, packing, warehouse-in.
Embodiment 2
Prescription: Alprostadil 0.03g
Glycerol 2000g
1,2 propylene glycol 2000g
Dimethyl acetylamide 1000g
2-HP-3g
Cysteine 10g
Sterile water for injection 100g
According to the production technology of embodiment 1, making specification is the alprostadil injection agent of 30 micrograms/5ml.
Embodiment 3
Prescription: Alprostadil 0.2g
Dehydrated alcohol and
Glycerol is arbitrarily than mixture 2000g
PEG400 and
1,2 propylene glycol is arbitrarily than mixture 2000g
Dimethyl acetylamide 1000g
2-HP-3g
Cysteine 10g
Sterile water for injection 100g
According to the production technology of embodiment 1, making specification is the alprostadil injection agent of 200 micrograms/5ml.
Claims (9)
1, a kind of injection that contains Alprostadil is characterized in that being made by following component: Alprostadil, dehydrated alcohol, PEG400, dimethyl acetylamide, 2-HP-, cysteine and sterile water for injection.
2, the injection that contains Alprostadil according to claim 1 is characterized in that being made by following weight portion prescription:
Alprostadil 0.02-0.40
Dehydrated alcohol 2000-15000
PEG400 2000-15000
Dimethyl acetylamide 1000-5000
2-HP-1-3
Cysteine 10-15
Sterile water for injection 50-100.
3, the injection that contains Alprostadil according to claim 2 is characterized in that the consumption of Alprostadil is 0.03-0.20 in the formulation by weight.
4, the injection that contains Alprostadil according to claim 2 is characterized in that dehydrated alcohol in the formulation by weight by the replacing than mixture arbitrarily of glycerol or glycerol and dehydrated alcohol, and weight portion is constant.
5, according to claim 2 or the 4 described injections that contain Alprostadil, it is characterized in that PEG400 in the formulation by weight by the replacing than mixture arbitrarily of 1,2 propylene glycol or 1,2 propylene glycol and PEG400, weight portion is constant.
6, any described production method that contains the injection of Alprostadil of claim 1-5 is characterized in that comprising the steps:
(1) takes by weighing Alprostadil,, make homogeneous solution with the dehydrated alcohol or the glycerol dissolving Alprostadil of about 80 times of its weight;
(2) the 2-hydroxypropyl-B-cyclodextrin and the cysteine of the injection water dissolving formula ratio of usefulness formula ratio stirs and makes homogeneous solution, transfers the scope of pH value to 6.0-6.5;
(3) with PEG400 or 1,2 propylene glycol and the dimethyl acetylamide of remaining dehydrated alcohol or glycerol dissolving formula ratio, stir and make homogeneous solution;
(4) (1) drips of solution that makes of step is added in the solution that (2) step made, stirs rapidly, continue stirring 1 hour after being added dropwise to complete again, make mixture solution while dripping;
(5) (4) solution that makes of step is slowly joined while stirring in the double solvents that (3) step made, stir, the medicinal liquid that makes is through membrane filtration, degerming;
(6) measure medicinal liquid content and adjust content, it is qualified to measure clarity;
(7) carry out the embedding packing under the aseptic condition, lamp inspection, it is qualified that product quality detects, packing, warehouse-in.
7, the production method that contains the injection of Alprostadil according to claim 6 is characterized in that described membrane filtration is to adopt 0.22 micron membranes to filter.
8, the production method that contains the injection of Alprostadil according to claim 6 is characterized in that described accent pH value is to adopt hydrochloric acid to adjust to 6.0-6.5.
9, the application of the described alprostadil injection agent of claim 1 in the medicine of preparation treatment cardiovascular and cerebrovascular disease, diabetes and complication, first, second, hepatitis C and various tumors.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101022531A CN100360134C (en) | 2003-10-29 | 2003-10-29 | Injection liquid containing alprostadic and its production process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101022531A CN100360134C (en) | 2003-10-29 | 2003-10-29 | Injection liquid containing alprostadic and its production process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1611221A CN1611221A (en) | 2005-05-04 |
| CN100360134C true CN100360134C (en) | 2008-01-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003101022531A Expired - Fee Related CN100360134C (en) | 2003-10-29 | 2003-10-29 | Injection liquid containing alprostadic and its production process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100360134C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102335179A (en) * | 2011-06-03 | 2012-02-01 | 蔡海德 | Alprostadil composite medicine, preparation method thereof, quality controlling method thereof, and purpose thereof |
| CN110269860A (en) * | 2018-03-16 | 2019-09-24 | 蔡海德 | A kind of drug for treating cancer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1182592A (en) * | 1996-10-31 | 1998-05-27 | 新丰制药株式会社 | Stable prostaglandin E1-containing injectable composition |
| CN1391899A (en) * | 2002-08-12 | 2003-01-22 | 蔡海德 | Aseptic freeze-dried prostaglandin injection and its preparing method and use |
-
2003
- 2003-10-29 CN CNB2003101022531A patent/CN100360134C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1182592A (en) * | 1996-10-31 | 1998-05-27 | 新丰制药株式会社 | Stable prostaglandin E1-containing injectable composition |
| CN1391899A (en) * | 2002-08-12 | 2003-01-22 | 蔡海德 | Aseptic freeze-dried prostaglandin injection and its preparing method and use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1611221A (en) | 2005-05-04 |
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Granted publication date: 20080109 Termination date: 20101029 |