CN111494311A - Dopamine hydrochloride injection and preparation method thereof - Google Patents
Dopamine hydrochloride injection and preparation method thereof Download PDFInfo
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- CN111494311A CN111494311A CN202010383788.4A CN202010383788A CN111494311A CN 111494311 A CN111494311 A CN 111494311A CN 202010383788 A CN202010383788 A CN 202010383788A CN 111494311 A CN111494311 A CN 111494311A
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- dopamine hydrochloride
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- calcium glycerophosphate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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Abstract
The invention relates to dopamine hydrochloride injection and a preparation method thereof. The injection contains 10-40 g dopamine hydrochloride per 1000ml injection, sodium caprylate and calcium glycerophosphate. The dopamine hydrochloride injection prepared according to the prescription process has extremely high quality stability, increases the medication safety, is obviously superior to the prior art and reference preparations, and meets the requirement of consistency evaluation of injections.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a dopamine hydrochloride injection and a preparation method thereof.
Background
Dopamine hydrochloride, chemical name is 4- (2-aminoethyl) -1, 2-benzenediol hydrochloride, dopamine is a precursor of noradrenaline biosynthesis, is one of central transmitters, has the effects of exciting β -receptors, α -receptors and dopamine receptors, exciting heart β -receptors can increase myocardial contractility and increase cardiac output, exciting dopamine receptors and α -receptors expand kidneys, intestinal membranes, coronary vessels and cerebral vessels and increase blood flow, has a mild contraction effect on peripheral blood vessels, increases arterial blood pressure, has the prominent effect of increasing renal blood flow and increasing glomerular filtration rate, thereby promoting urine volume to increase and increasing natriuresis, is clinically used for various types of shock, is particularly suitable for shock with weakened cardiac contractility and renal insufficiency, is a common injection of dopamine hydrochloride, is a dopamine hydrochloride injection, is a common injection for myocardial infarction, trauma, endotoxemia, cardiac surgery, renal failure, congestive heart failure, is suitable for patients caused by myocardial infarction, or peripheral blood sulfite, is a common injection, is a hydrochloric acid injection, is a normal injection, is a hydrochloric acid injection, is a common injection for clinical treatment of myocardial infarction, is a dopamine injection, is a common injection for clinical medicine injection, is a common injection for treating asthma caused by cardiovascular failure, and the problem of cardiovascular disease caused by the central nervous dysfunction caused by the urinary tract, the urinary tract allergy caused by the urinary tract, the urinary tract allergy, the urinary tract stress of the urinary tract, the urinary tract.
Disclosure of Invention
The invention aims to provide dopamine hydrochloride injection and a preparation method thereof, the injection does not contain sodium bisulfite, and simultaneously has stable quality indexes compared with the prior art and a reference preparation, and impurities have no new impurities and lower content of related substances compared with the reference preparation, thereby meeting the requirement of consistency evaluation.
The scheme adopted by the invention for solving the technical problems is as follows:
the dopamine hydrochloride injection comprises 10-40 g of dopamine hydrochloride, sodium caprylate and calcium glycerophosphate per 1000ml of injection.
Preferably, the amount of sodium caprylate is 2.2g and the amount of calcium glycerophosphate is 4.5g per 1000ml of injection.
Preferably, the specification of the dopamine hydrochloride injection is 2ml or 5ml, and the dopamine hydrochloride injection contains 20mg and 200mg of dopamine hydrochloride respectively.
The invention also provides a preparation method of the dopamine hydrochloride injection, which comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose into 600ml of water for injection at the temperature of 36-42 ℃;
(2) keeping the temperature at 36-42 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
The calcium glycerophosphate and the sodium caprylate are used as the auxiliary materials of the dopamine hydrochloride injection, the combined use of the 2 auxiliary materials is favorable for improving the stability of the dopamine hydrochloride injection, can replace sodium bisulfite, and has unexpected effects, and especially, the effect of the specific ratio of 2.2g of the sodium caprylate and 4.5g of the calcium glycerophosphate added in each 1000ml is optimal.
Detailed Description
The following examples are provided to further illustrate the present invention for better understanding, but the present invention is not limited to the following examples.
Example 1
Injections were prepared according to the following prescription of table 1:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose in 600ml of water for injection at 36 ℃;
(2) keeping the temperature at 36 ℃, adding dopamine hydrochloride of the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification of 2ml to 20mg, and then sterilizing the solution at 121 ℃ for 15 minutes to obtain the dopamine hydrochloride injection.
TABLE 1 calcium glycerophosphate and sodium caprylate injection in different prescription dose
The above 8 prescription samples were subjected to influence factor tests, and were placed at 60 ℃ under strong light (4500lx ± 500lx) for 10 days, respectively, and sampled and examined on the 10 th day, and the results were compared with 0 day to examine the stability of the samples, and the results are shown in tables 2 to 3:
TABLE 260 ℃ stability test results
TABLE 3 Strong light (4500L X) stability test results
The test results in tables 2-3 show that the combination of sodium caprylate and calcium glycerophosphate is beneficial to increase the stability of dopamine hydrochloride injection, and especially, the specific ratio of 2.2g of sodium caprylate and 4.5g of calcium glycerophosphate in each 1000ml has the best effect, and even if the dosage is slightly changed, the technical effect is obviously different.
Example 2
Prescription:
dopamine hydrochloride: 10g
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
The water for injection is added to 1000ml to prepare 500 pieces.
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose in 600ml of water for injection at 36 ℃;
(2) keeping the temperature at 36 ℃, adding dopamine hydrochloride of the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
Example 3
Prescription:
dopamine hydrochloride: 10g
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
The water for injection is added to 1000ml to prepare 500 pieces.
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose in 600ml of water for injection at 42 ℃;
(2) keeping the temperature at 42 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
Example 4
Prescription:
dopamine hydrochloride: 10g
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
The water for injection is added to 1000ml to prepare 500 pieces.
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription amount in 600ml of water for injection at the temperature of 39 ℃;
(2) keeping the temperature at 39 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
Example 5
Prescription:
dopamine hydrochloride: 40g of
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
The water for injection is added to 1000ml to prepare 200 pieces.
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose in 600ml of water for injection at 36 ℃;
(2) keeping the temperature at 36 ℃, adding dopamine hydrochloride of the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
Example 6
Prescription:
dopamine hydrochloride: 40g of
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
Adding 1000ml of water for injection to obtain 200 pieces
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose in 600ml of water for injection at 42 ℃;
(2) keeping the temperature at 42 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
Example 7
Prescription:
dopamine hydrochloride: 40g of
Sodium caprylate: 2.2g
Calcium glycerophosphate: 4.5g
The water for injection is added to 1000ml to prepare 200 pieces.
The preparation method comprises the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription amount in 600ml of water for injection at the temperature of 39 ℃;
(2) keeping the temperature at 39 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
The present invention provides the following test and comparative results:
1. sample 1 (dopamine hydrochloride injection prepared in example 2 of the invention, 2ml:20 mg);
2. sample 2 (dopamine hydrochloride injection prepared in example 5 of the present invention, 5 ml: 200 mg);
3. sample 3 (commercially available dopamine hydrochloride injection, 2ml:20 mg);
4. sample 4 (commercially available Hospira Inc dopamine hydrochloride injection, 5 ml: 200mg from original Mill).
Samples 1 to 4 were subjected to accelerated stability studies (40 ℃. + -. 2 ℃ C., RH 75%. + -. 5%) for 6 months, with the results shown in Table 4:
TABLE 4 stability results of accelerated testing
The influencing factor tests of the samples 1 to 4 are carried out, the samples are respectively placed for 10 days at 60 ℃ and strong light (4500lx +/-500 lx), the samples are respectively sampled and detected on the 10 th day, the results are compared with 0 day, the stability of the samples is examined, and the results are shown in the table 5:
table 5 stability results of influential tests
The results in tables 4 to 5 show that the dopamine hydrochloride injection prepared by the formula and the process of the invention keeps extremely high stability, has obvious advantages compared with the marketed products and the original developers, and the dopamine hydrochloride injection prepared by other embodiments of the invention is also subjected to the same tests to obtain similar results.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (4)
1. Dopamine hydrochloride injection, its characteristic is: each 1000ml of injection contains 10g to 40g of dopamine hydrochloride, sodium caprylate and calcium glycerophosphate.
2. The dopamine hydrochloride injection of claim 1, wherein: the dosage of sodium caprylate and calcium glycerophosphate in each 1000ml injection is 2.2g and 4.5g respectively.
3. The dopamine hydrochloride injection of claim 1, wherein: the specification of the dopamine hydrochloride injection is 2ml or 5ml, and the dopamine hydrochloride injection respectively contains 20mg and 200mg of dopamine hydrochloride.
4. The preparation method of dopamine hydrochloride injection as claimed in any one of claims 1 to 3, characterized by comprising the following steps:
(1) sequentially dissolving calcium glycerophosphate and sodium caprylate with the prescription dose into 600ml of water for injection at the temperature of 36-42 ℃;
(2) keeping the temperature at 36-42 ℃, adding dopamine hydrochloride with the prescription amount, stirring and dissolving, and adding water for injection to 1000 ml;
(3) measuring the pH value and the content of the solution, filtering the solution by using a 0.22 mu m filter membrane, filling the solution into an ampoule according to the specification, and then sterilizing the solution for 15 minutes at 121 ℃ to obtain the dopamine hydrochloride injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010383788.4A CN111494311B (en) | 2020-05-08 | 2020-05-08 | Dopamine hydrochloride injection and preparation method thereof |
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| CN202010383788.4A CN111494311B (en) | 2020-05-08 | 2020-05-08 | Dopamine hydrochloride injection and preparation method thereof |
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| CN111494311B CN111494311B (en) | 2021-02-02 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112842992A (en) * | 2021-03-24 | 2021-05-28 | 合肥市未来药物开发有限公司 | Dopamine hydrochloride injection serving as reference preparation and preparation method thereof |
| CN114518423A (en) * | 2022-02-25 | 2022-05-20 | 南京嘉晨医药科技有限公司 | Method for detecting impurities in dopamine hydrochloride injection |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953782A (en) * | 2009-07-21 | 2011-01-26 | 上海禾丰制药有限公司 | Production method for dopamine hydrochloride injection |
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2020
- 2020-05-08 CN CN202010383788.4A patent/CN111494311B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953782A (en) * | 2009-07-21 | 2011-01-26 | 上海禾丰制药有限公司 | Production method for dopamine hydrochloride injection |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112842992A (en) * | 2021-03-24 | 2021-05-28 | 合肥市未来药物开发有限公司 | Dopamine hydrochloride injection serving as reference preparation and preparation method thereof |
| CN114518423A (en) * | 2022-02-25 | 2022-05-20 | 南京嘉晨医药科技有限公司 | Method for detecting impurities in dopamine hydrochloride injection |
| CN114518423B (en) * | 2022-02-25 | 2023-07-25 | 南京嘉晨医药科技有限公司 | Method for detecting impurities in dopamine hydrochloride injection |
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