CN110339340A - A kind of preparation method of oxytocin injection - Google Patents
A kind of preparation method of oxytocin injection Download PDFInfo
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- CN110339340A CN110339340A CN201910797094.2A CN201910797094A CN110339340A CN 110339340 A CN110339340 A CN 110339340A CN 201910797094 A CN201910797094 A CN 201910797094A CN 110339340 A CN110339340 A CN 110339340A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/095—Oxytocins; Vasopressins; Related peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
The present invention provides the preparation methods in a kind of oxytocin injection, the preparation method of oxytocin injection of the present invention, pass through the temperature in control preparation process, it is passed through the mode of nitrogen and precisely adjusts pH value, keep the anesin in injection more stable, it is not easy to be oxidized degradation, volatilization, obtains the oxytocin injection good with prescription labelled amount correspondence, have practical application promotional value.
Description
Technical field
The present invention relates to a kind of preparation methods of oxytocin injection.
Background technique
Oxytocin injection is achromatism and clarity or almost clear and bright liquid, be for induced labor, hasten parturition, postpartum and post-abortion because
Uterine atony or contracting it is multiple it is bad caused by uterine hemorrhage, and understand the drug of placenta reserve function (oxytocin challenge test (OCT)),
Its main component is oxytocin, anesin, glacial acetic acid, water for injection.
Often there is adverse reaction in clinical application discovery oxytocin injection, therefore the quality for controlling injection has very
Important clinical meaning.Anesin is commonly used for antiseptic and inhibiting bacteria function agent and plasticizer etc., existing research shows that it is infused in oxytocin
The effect penetrated in liquid is not only antiseptic and inhibiting bacteria function agent, also acts preferable peptizaiton, but anesin itself also has one
Fixed toxic effect, therefore anesin concentration must be controlled appropriately, if anesin content is low in injection,
Influence whether the homogeneity of effective component oxytocin and the fungistatic effect of solution, but when anesin content height in injection
When, side effect probability of happening can be increased significantly.And anesin content is criticized between enterprise, in enterprise in presently commercially available preparation
Between differ greatly, and it is poor with prescription labelled amount correspondence, great hidden danger is caused to the medication of patient.
Summary of the invention
In order to solve the above technical problems, it includes as follows the present invention provides a kind of preparation method of oxytocin injection
Step:
A, take the water with liquid total volume 70-90%, 30 DEG C of temperature of control hereinafter, inflated with nitrogen 25-30min, adjust pH value to
3.5~4.0；
B, anesin is added into step a solution, inflated with nitrogen to container inner pressure stops when reaching 0.10MPa or more, stirs
It mixes to solution and clarifies；
C, oxytocin is added into step b solution, mixes thoroughly, adjust pH value to 3.5~4.0, inflated with nitrogen supplies excess water, stops
Only lead to nitrogen, mix thoroughly, filtering to get.
Further, the water with liquid total volume 90% is taken described in step a.
Further, the control temperature is at 20~28 DEG C, and preferably 25 DEG C.
Further, inflated with nitrogen time 30min described in step a.
Further, stop when inflated with nitrogen described in step b reaches 0.12MPa or more to container inner pressure.
Further, adjust pH value to 3.5~3.7 described in step c.
Further, the reagent for adjusting pH value is 2mol/L glacial acetic acid solution.
Further, filtering described in step c is successively twice with 0.22 μm of hydrophily degerming filter element filtering.
Further, the mass ratio of the water, anesin and oxytocin is 55000:275:1.
Further, the nitrogen gas purity is 99.99%.
Further, the water is water for injection.
The present invention also provides a kind of oxytocin injections that aforementioned preparation process is prepared.
The preparation method of oxytocin injection of the present invention is passed through the mode of nitrogen by the temperature in control preparation process
And pH value is precisely adjusted, keep the anesin in injection more stable, is not easy to be oxidized degradation, volatilization, obtain and prescription mark
The good oxytocin injection of the amount of showing correspondence, has practical application promotional value.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Specific embodiment
The preparation of the oxytocin injection of the present invention of embodiment 1
Formula: water 110kg, anesin 550g, oxytocin 2g
Preparation method:
1) water for injection for matching liquid total volume 90% is added in dilute preparing tank, controls temperature at 25 DEG C, liquid internal is passed through
Nitrogen 30min, then pH value is adjusted to 3.5~4.0 with 2mol/L glacial acetic acid solution.
2) anesin is taken to be added in step 1) dilute preparing tank, closed tank body is passed through nitrogen to pressure inside the tank and reaches
Stop being passed through nitrogen when 0.12MPa or more, continues stirring to solution and clarify.
3) oxytocin is taken to be added in step 2) dilute preparing tank, stirring is to being uniformly mixed, sample detection, and with 2mol/L ice vinegar
Acid solution is adjusted to pH value to 3.5~3.7, continues inflated with nitrogen, benefit adds to the full amount of water for injection, and stopping is passed through nitrogen, and stirring makes
Solution is uniformly mixed, and medical fluid is filtered through 0.22 μm of hydrophily degerming filter core (PVDF) of level-one into fluid reservoir, then through 0.22 μ of level-one
M hydrophily degerming filter core (PVDF) filtering is potted into compensator.
The preparation of the oxytocin injection of the present invention of embodiment 2
Formula: water 110kg, anesin 550g, oxytocin 2g
Preparation method:
1) water for injection for matching liquid total volume 70% is added in dilute preparing tank, controls temperature at 27 DEG C, liquid internal is passed through
Nitrogen 25min, then pH value is adjusted to 3.5~4.0 with 2mol/L glacial acetic acid solution.
2) anesin is taken to be added in step 1) dilute preparing tank, closed tank body is passed through nitrogen to pressure inside the tank and reaches
Stop being passed through nitrogen when 0.12MPa or more, continues stirring to solution and clarify.
3) oxytocin is taken to be added in step 2) dilute preparing tank, stirring is to being uniformly mixed, sample detection, and with 2mol/L ice vinegar
Acid solution is adjusted to pH value to 3.5~3.7, continues inflated with nitrogen, benefit adds to the full amount of water for injection, and stopping is passed through nitrogen, and stirring makes
Solution is uniformly mixed, and medical fluid is filtered through 0.22 μm of hydrophily degerming filter core (PVDF) of level-one into fluid reservoir, then through 0.22 μ of level-one
M hydrophily degerming filter core (PVDF) filtering is potted into compensator.
The preparation of the oxytocin injection of the present invention of embodiment 3
Formula: water 110kg, anesin 550g, oxytocin 2g
Preparation method:
1) water for injection for matching liquid total volume 85% is added in dilute preparing tank, controls temperature at 26 DEG C, liquid internal is passed through
Nitrogen 30min, then pH value is adjusted to 3.5~4.0 with 2mol/L glacial acetic acid solution.
2) anesin is taken to be added in step 1) dilute preparing tank, closed tank body is passed through nitrogen to pressure inside the tank and reaches
Stop being passed through nitrogen when 0.12MPa or more, continues stirring to solution and clarify.
3) oxytocin is taken to be added in step 2) dilute preparing tank, stirring is to being uniformly mixed, sample detection, and with 2mol/L ice vinegar
Acid solution is adjusted to pH value to 3.5~3.7, continues inflated with nitrogen, benefit adds to the full amount of water for injection, and stopping is passed through nitrogen, and stirring makes
Solution is uniformly mixed, and medical fluid is filtered through 0.22 μm of hydrophily degerming filter core (PVDF) of level-one into fluid reservoir, then through 0.22 μ of level-one
M hydrophily degerming filter core (PVDF) filtering is potted into compensator.
Beneficial effects of the present invention are further illustrated below by way of test example.
1 present invention of test example is compared with oxytocin injection made from former oxytocin injection preparation method
1, oxytocin injection of the present invention
1.1 the preparation method is the same as that of Example 1
2.1 testing result
Oxytocin injection made from preparation method of the present invention, takes three batches of detections, and specific detection method is that injection is taken to make
For test solution, another precision weighs anesin reference substance, and methanol is added to be configured to the solution conduct in every 1ml containing about 5mg
Reference substance solution.Precision takes test solution and control solution appropriate, measures in injecting chromatograph, the results are shown in Table 1.
The oxytocin injection detection data produced by the invention of table 1
Note: the calculation of anesin content results is the numerical value and 5mg that detect in terms of 5mg anesin
Compare (i.e. content be labelled amount percentage).
2, former oxytocin injection
2.1 preparation methods:
Formula: water 109.7L, anesin 583.06g, oxytocin 2.1g
Technique:
1) water for injection for matching liquid total volume 50% is added in dense preparing tank, is cooled to no more than 40 DEG C, trichlorine uncle is added
Butanol, stirring is to being completely dissolved.
2) stirring is opened in dilute preparing tank, and the oxytocin solution stirring and dissolving of formula ratio is added.
3) solution in dense preparing tank is delivered in dilute preparing tank, it is stirring while adding, continue to stir after the completion of conveying, adds injection
Continue to stir evenly to full dose with water.
4) sample detection pH value adjusts pH value in 3.5-3.7 with appropriate 2mol/L glacial acetic acid solution.
5) step 4) medical fluid is filtered through 0.22 μm of sterilizing filter into fluid reservoir.Medical fluid in fluid reservoir is again through 0.22
μm sterilizing filter, which is filtered to compensator, to be potted.
2.2, testing result
The oxytocin injection that former preparation method obtains, takes three batches of detections, as a result specific detection method is shown in test example 1
Table 2.
The oxytocin injection detection data of 2 original process of table production
Note: the calculation of anesin content results is the numerical value and 5mg that detect in terms of 5mg anesin
Compare (i.e. content be labelled amount percentage).
It is visible to compare Tables 1 and 2: in the oxytocin injection that preparation method of the present invention obtains, the content of anesin
It is more stable, do not occur reduction phenomenon, avoid the volatilization of anesin in process of production, the product made and formula are marked
The amount of showing correspondence is good, further avoid it is unstable due to anesin, caused by injection is antibacterial and plasticization effect
The case where difference and oxytocin distributing inhomogeneity, it ensure that the drug safety of patient.
To sum up, the preparation method of oxytocin injection of the present invention is passed through nitrogen by the temperature in control preparation process
Mode and pH value is precisely adjusted, keep the anesin in injection more stable, is not easy to be oxidized degradation, volatilization, obtain and locate
The good oxytocin injection of square labelled amount correspondence, makes oxytocin injection quality be protected, has practical application promotion price
Value.
Claims (10)
1. a kind of preparation method of oxytocin injection, it is characterised in that: it includes the following steps:
A, take the water with liquid total volume 70-90%, 30 DEG C of temperature of control hereinafter, inflated with nitrogen 25-30min, adjust pH value to 3.5~
4.0；
B, anesin is added into step a solution, inflated with nitrogen to container inner pressure stops when reaching 0.10MPa or more, and stirring is extremely
Solution clarification；
C, oxytocin is added into step b solution, mixes thoroughly, adjust pH value to 3.5~4.0, inflated with nitrogen supplies excess water, stops filling
Nitrogen is mixed thoroughly, filtering to get.
2. preparation method according to claim 1, which is characterized in that take the water with liquid total volume 90% described in step a；Institute
State control temperature at 20~28 DEG C, preferably 25 DEG C.
3. preparation method according to claim 1, which is characterized in that inflated with nitrogen 30min described in step a.
4. preparation method according to claim 1, which is characterized in that inflated with nitrogen described in step b to container inner pressure reaches
Stop when 0.12MPa or more.
5. preparation method according to claim 1, which is characterized in that tune pH value described in step c to 3.5~3.7.
6. preparation method according to claim 1 or 4, it is characterised in that: the reagent for adjusting pH value is 2mol/L ice vinegar
Acid solution.
7. preparation method according to claim 1, which is characterized in that step c filtering is successively hydrophilic with 0.22 μm twice
Property degerming filter element filtering.
8. preparation method according to claim 1, which is characterized in that the quality of the water, anesin and oxytocin
Than for 55000:275:1；The nitrogen gas purity is 99.99%.
9. preparation method according to claim 1 or 8, which is characterized in that the water is water for injection.
10. the oxytocin injection that claim 1-8 any one preparation method is prepared.
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| CN201910797094.2A CN110339340A (en) | 2019-08-27 | 2019-08-27 | A kind of preparation method of oxytocin injection |
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| CN201910797094.2A CN110339340A (en) | 2019-08-27 | 2019-08-27 | A kind of preparation method of oxytocin injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110960488A (en) * | 2019-12-30 | 2020-04-07 | 成都市海通药业有限公司 | Preparation method for improving stability of oxytocin injection |
| CN111249231A (en) * | 2020-03-18 | 2020-06-09 | 成都市海通药业有限公司 | Oxytocin injection taking ethanol as chlorobutanol solvent and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110960488A (en) * | 2019-12-30 | 2020-04-07 | 成都市海通药业有限公司 | Preparation method for improving stability of oxytocin injection |
| CN111249231A (en) * | 2020-03-18 | 2020-06-09 | 成都市海通药业有限公司 | Oxytocin injection taking ethanol as chlorobutanol solvent and preparation method thereof |
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