CN110755373B - Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof - Google Patents
Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN110755373B CN110755373B CN201911129979.1A CN201911129979A CN110755373B CN 110755373 B CN110755373 B CN 110755373B CN 201911129979 A CN201911129979 A CN 201911129979A CN 110755373 B CN110755373 B CN 110755373B
- Authority
- CN
- China
- Prior art keywords
- parts
- injection
- fasudil hydrochloride
- pharmaceutical composition
- phenylalanine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
-
- 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
-
- 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
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to a fasudil hydrochloride injection pharmaceutical composition and a preparation method thereof. The fasudil hydrochloride injection pharmaceutical composition comprises the following raw materials in parts by weight: 35-50 parts of fasudil hydrochloride; 1-10 parts of nicotinamide; 1-10 parts of phenylalanine; 5-20 parts of N-acetylcysteine; 10-20 parts of sodium chloride; 1000-3000 parts of water for injection; the pH of the injection is adjusted to 5.7-6.3 by using a pharmaceutically acceptable pH regulator. The hydrochloric acid faxsul injection pharmaceutical composition is colorless and clear, does not contain visible impurities, is stable to light under the condition that the pH value is 5.7-6.3, has low impurity content and controllable quality, and improves the medication safety.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a fasudil hydrochloride injection pharmaceutical composition and a preparation method thereof.
Background
The chemical name of fasudil hydrochloride is hexahydro-1- (5-sulfonyl isoquinoline) -1(H) -1, 4-diazepine salt, which is a Rho kinase inhibitor and a novel intracellular calcium ion antagonist and is mainly applicable to cerebrovascular diseases.
According to the record of the original patent literature, the preparation process of fasudil hydrochloride comprises the following steps: the method comprises the steps of adopting 5-isoquinoline sulfonic acid as a starting material, firstly forming 5-isoquinoline sulfonyl chloride hydrochloride with thionyl chloride, then reacting with homopiperazine to obtain fasudil, and further salifying and refining to obtain the fasudil hydrochloride. Based on the analysis of the structure of fasudil hydrochloride, as the main starting raw materials of fasudil hydrochloride comprise homopiperazine and 5-isoquinoline sulfonic acid, the degradation mode of fasudil hydrochloride is mainly due to the dissociation of homopiperazine and 5-isoquinoline sulfonic acid to generate impurities. For the generation conditions of impurities, the prior art clearly indicates that the fasudil hydrochloride injection needs to be stored away from light, namely, the fasudil hydrochloride injection is degraded by light. In addition, piperazine or homopiperazine structure is relatively easily oxidized to generate oxidation products, that is, oxygen also plays a role in degrading fasudil hydrochloride.
At present, the formulation of fasudil hydrochloride only is injection, the stability of fasudil hydrochloride can be affected after the fasudil hydrochloride is prepared into aqueous solution, meanwhile, a plurality of links are inevitably required in the process of producing the preparation, and the degradation reaction of fasudil hydrochloride is easily caused by the pH environment, the sterilization condition, the illumination and the like. In the degradation reaction of fasudil hydrochloride, people are more studying how to avoid photodegradation by lowering the pH value and maintaining the pH value. For example, Chinese patent CN104840418A discloses a fasudil hydrochloride injection composition and a preparation method thereof, and specifically discloses a composition consisting of fasudil hydrochloride, reduced glutathione, poloxamer 188, sodium chloride and water for injection, wherein the pH of the injection is adjusted to 4.5-5.5 by using a pharmaceutically acceptable pH regulator. Further, as disclosed in chinese patent CN103222953A, a fasudil hydrochloride injection composition and a preparation method thereof specifically disclose that the composition consists of the following components: fasudil hydrochloride, calcium disodium edentate and water for injection, wherein the weight ratio of the fasudil hydrochloride to the calcium disodium edentate in each unit of preparation is 30mg:0.2 mg. Therefore, it is necessary to monitor the quality of fasudil hydrochloride comprehensively and reduce the medication risk.
Disclosure of Invention
The fasudil hydrochloride injection pharmaceutical composition is colorless and clear, does not contain visible impurities, is stable to light under the condition that the pH value is 5.7-6.3, has low impurity content and controllable quality, and improves the medication safety.
In order to achieve the purpose, the invention adopts the following technical scheme:
a fasudil hydrochloride injection pharmaceutical composition comprises the following raw materials in parts by weight:
35-50 parts of fasudil hydrochloride;
1-10 parts of nicotinamide;
1-10 parts of phenylalanine;
5-20 parts of N-acetylcysteine;
10-20 parts of sodium chloride;
1000-3000 parts of water for injection;
the pH of the injection is adjusted to 5.7-6.3 by using a pharmaceutically acceptable pH regulator.
According to the invention, the nicotinamide and the phenylalanine are compounded, and can perform a complex reaction with fasudil hydrochloride, so that under the condition that the pH value is 5.7-6.3, the photostability of the fasudil hydrochloride injection pharmaceutical composition is favorably improved, and the photostability of the fasudil hydrochloride injection pharmaceutical composition is further improved after N-acetylcysteine is added into the pharmaceutical composition.
Further, the weight ratio of nicotinamide to phenylalanine is 1: (1.5-2), preferably the weight ratio of nicotinamide to phenylalanine is 1:1.6, in long-term tests, the fasudil hydrochloride injection pharmaceutical composition added with the proportion is found to have better long-term stability.
Further, the feed comprises the following raw materials in parts by weight:
35 parts of fasudil hydrochloride;
5 parts of nicotinamide;
8 parts of phenylalanine;
10 parts of N-acetylcysteine;
15 parts of sodium chloride;
2000 parts of water for injection;
the injection is adjusted to pH 6.0 by using a pharmaceutically acceptable pH regulator.
Further, the pH regulator is hydrochloric acid or sodium hydroxide.
The invention provides a method for preparing the hydrochloric acid legal suler injection pharmaceutical composition, which comprises the following steps:
s1) degassing the injection water according to the prescription amount for 20-30 min, removing pyrogens, and introducing carbon dioxide until the mixture is saturated;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total amount, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10-20 min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60-90 min, introducing nitrogen for 30min, and fine-filtering by a 0.22 mu m microporous filter membrane to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
Furthermore, the adding amount of the activated carbon is 2-5 parts.
Compared with the prior art, the invention has the following beneficial effects:
(1) the hydrochloric acid faxsul injection pharmaceutical composition is colorless and clear, does not contain visible impurities, is stable to light under the condition that the pH is 5.7-6.3, has low impurity content and controllable quality, improves the medication safety, has the pH closer to the pH of a human body (7.35-7.45), and reduces the harm to the human body.
(2) The hydrochloric acid faxsulare injection medicine composition has good long-term stability and is convenient to store.
(3) The hydrochloric acid legal suler injection pharmaceutical composition avoids illumination in the preparation process, avoids introducing excessive air, and reduces the degradation probability of the hydrochloric acid legal suler injection pharmaceutical composition.
Detailed Description
The present invention will be described in further detail with reference to the following examples. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples.
Example 1A fasudil hydrochloride injection pharmaceutical composition
The composite material comprises the following raw materials in parts by weight:
35 parts of fasudil hydrochloride;
4 parts of nicotinamide;
8 parts of phenylalanine;
10 parts of N-acetylcysteine;
10 parts of sodium chloride;
2000 parts of water for injection;
the pH of the injection is adjusted to 6.0 by hydrochloric acid.
The method for preparing the hydrochloric acid legal suler injection pharmaceutical composition comprises the following steps:
s1) degassing the prescription amount of water for injection for 30min, removing pyrogen, and introducing carbon dioxide to saturation;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total dose, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60min, introducing nitrogen for 30min, and fine-filtering by a microporous filter membrane of 0.22 mu m to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
Example 2 fasudil hydrochloride injection pharmaceutical composition
The composite material comprises the following raw materials in parts by weight:
35 parts of fasudil hydrochloride;
5 parts of nicotinamide;
8 parts of phenylalanine;
10 parts of N-acetylcysteine;
15 parts of sodium chloride;
2000 parts of water for injection;
the pH of the injection is adjusted to 6.0 by hydrochloric acid.
The method for preparing the hydrochloric acid legal suler injection pharmaceutical composition comprises the following steps:
s1) degassing the prescription amount of water for injection for 30min, removing pyrogen, and introducing carbon dioxide to saturation;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total dose, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60min, introducing nitrogen for 30min, and fine-filtering by a microporous filter membrane of 0.22 mu m to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
Example 3A fasudil hydrochloride injection pharmaceutical composition
The composite material comprises the following raw materials in parts by weight:
40 parts of fasudil hydrochloride;
5 parts of nicotinamide;
10 parts of phenylalanine;
12 parts of N-acetylcysteine;
12 parts of sodium chloride;
2000 parts of water for injection;
the pH of the injection is adjusted to 6.0 by hydrochloric acid.
The method for preparing the hydrochloric acid legal suler injection pharmaceutical composition comprises the following steps:
s1) degassing the prescription amount of water for injection for 30min, removing pyrogen, and introducing carbon dioxide to saturation;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total dose, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60min, introducing nitrogen for 30min, and fine-filtering by a microporous filter membrane of 0.22 mu m to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
Example 4A fasudil hydrochloride injection pharmaceutical composition
The composite material comprises the following raw materials in parts by weight:
40 parts of fasudil hydrochloride;
6 parts of nicotinamide;
10 parts of phenylalanine;
10 parts of N-acetylcysteine;
10 parts of sodium chloride;
2000 parts of water for injection;
the pH of the injection is adjusted to 6.0 by hydrochloric acid.
The method for preparing the hydrochloric acid legal suler injection pharmaceutical composition comprises the following steps:
s1) degassing the prescription amount of water for injection for 30min, removing pyrogen, and introducing carbon dioxide to saturation;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total dose, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60min, introducing nitrogen for 30min, and fine-filtering by a microporous filter membrane of 0.22 mu m to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
Comparative example 1, fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: nicotinamide, phenylalanine and N-acetylcysteine were not added, and the remaining parameters were the same as in example 2.
Comparative example 2, fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: phenylalanine was not added and the remaining parameters were the same as in example 2.
Comparative example 3, fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: no niacinamide was added and the remaining parameters were the same as in example 2.
Comparative example 4 fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: n-acetylcysteine was not added, and the remaining parameters were the same as in example 2.
Comparative example 5 fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: nicotinamide and phenylalanine were not added, and the remaining parameters were the same as in example 2.
Comparative example 6 fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: the weight ratio of nicotinamide to phenylalanine is 2: 1, the remaining parameters are the same as in example 2.
Comparative example 7 fasudil hydrochloride injection pharmaceutical composition
Similar to example 2, except that: the N-acetylcysteine was replaced with cysteine, and the remaining parameters were the same as in example 2.
Test I, influence factor test
The fasudil hydrochloride injection pharmaceutical composition is subjected to an influence factor test according to the appendix XIXC of the second part of the Chinese pharmacopoeia version 2010, is respectively placed under a high-temperature condition (60 ℃) and a strong-light condition (4500 +/-500 lx) for 10 days, is sampled on the 10 th day to carry out appearance, pH value, visible foreign matters, related substances and content measurement, and is compared with the results before the test, wherein the results are shown in tables 1 and 2.
TABLE 1pH and appearance observations
As can be seen from Table 1, the fasudil hydrochloride injection pharmaceutical compositions of examples 1-4 are colorless and clear in appearance and free of visible foreign substances at a pH of 6. In the comparative examples 1-5, after 10 days at high temperature and 10 days at illumination, the appearance and visible foreign matters of the fasudil hydrochloride injection pharmaceutical composition are changed to different degrees.
TABLE 2 results of content measurement
Wherein the impurity A is
As can be seen from Table 2, the pharmaceutical composition of fasudil hydrochloride injection in examples 1-4 has less increase of impurity content after 10 days at high temperature and 10 days at light, which indicates that the pharmaceutical composition can maintain better stability at high temperature and under strong light, wherein example 2 is the best example of the present invention.
Comparative example 1 is a reference comparative example; in comparative example 2 (without adding phenylalanine), the impurity type and impurity content were high at 0 day, which indicates that the fasudil hydrochloride injection pharmaceutical composition without adding phenylalanine was degraded during the preparation process, and was degraded to different extents at 10 days under high temperature and 10 days under high light, where the largest impurity was homopiperazine. Comparative example 3 (without nicotinamide addition) shows the same trend as comparative example 2, showing better stability after 10 days under high light conditions when nicotinamide and phenylalanine are present in a weight ratio of 1:1.6 compared to example 2. In comparative example 4 (without N-acetylcysteine), the largest impurity is impurity A after 10 days under the strong light condition, which shows that the oxygen contained in the impurity A promotes the degradation of fasudil hydrochloride, and the stability of the fasudil hydrochloride is affected.
Test II, Long term test
Carrying out long-term test on the fasudil hydrochloride injection according to the appendix XIX C of the second part of the 2010 version of Chinese pharmacopoeia, wherein the long-term test conditions are as follows: the temperature is 25 +/-2 ℃, the relative humidity is 60 +/-10%, the product is placed according to a commercial package, and samples are taken at the end of 3 months, 6 months, 9 months and 12 months respectively for content detection and related substance detection.
TABLE 3 Long-term test results
As seen from Table 3, the long-term stability of example 2 (weight ratio of nicotinamide to phenylalanine 1:1.6) and comparative example 6 (weight ratio of nicotinamide to phenylalanine 2: 1) are different, example 2 has better long-term stability, and example 7 does not achieve the same stability as example 2 by replacing N-acetylcysteine with cysteine.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (5)
1. The fasudil hydrochloride injection pharmaceutical composition is characterized by comprising the following raw materials in parts by weight:
35-50 parts of fasudil hydrochloride;
1-10 parts of nicotinamide;
1-10 parts of phenylalanine;
5-20 parts of N-acetylcysteine;
10-20 parts of sodium chloride;
1000-3000 parts of water for injection;
adjusting the pH of the injection to 5.7-6.3 by using a pharmaceutically acceptable pH regulator;
the method for preparing the hydrochloric acid legal suler injection pharmaceutical composition comprises the following steps:
s1) degassing the injection water according to the prescription amount for 20-30 min, removing pyrogens, and introducing carbon dioxide until the mixture is saturated;
s2) taking prescription dose nicotinamide, phenylalanine, N-acetylcysteine and sodium chloride, mixing uniformly, adding 80% of injection water in the step S1 of the total amount, stirring to dissolve the injection water, adjusting the pH value, adding fasudil hydrochloride, adding activated carbon to adsorb for 10-20 min, filtering to remove the carbon, adding the rest prescription dose of injection water to the full dose, degassing for 60-90 min, introducing nitrogen for 30min, and fine-filtering by a 0.22 mu m microporous filter membrane to obtain a liquid medicine;
s3) detecting and filling the liquid medicine obtained in the step S2, pumping out air in a closed space, filling high-purity nitrogen into a medium borosilicate glass ampoule bottle filled with the injection, sterilizing and packaging to obtain a finished product.
2. The fasudil hydrochloride injection pharmaceutical composition according to claim 1, wherein the weight ratio of nicotinamide to phenylalanine is 1: (1.5-2).
3. The fasudil hydrochloride injection pharmaceutical composition according to claim 2, which is characterized by comprising the following raw materials in parts by weight:
35 parts of fasudil hydrochloride;
5 parts of nicotinamide;
8 parts of phenylalanine;
10 parts of N-acetylcysteine;
15 parts of sodium chloride;
2000 parts of water for injection;
the injection is adjusted to pH 6.0 by using a pharmaceutically acceptable pH regulator.
4. The fasudil hydrochloride injection pharmaceutical composition according to any one of claims 1 to 3, wherein the pH regulator is hydrochloric acid or sodium hydroxide.
5. The fasudil hydrochloride injection pharmaceutical composition according to claim 1, wherein the amount of the added activated carbon is 2-5 parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911129979.1A CN110755373B (en) | 2019-11-18 | 2019-11-18 | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911129979.1A CN110755373B (en) | 2019-11-18 | 2019-11-18 | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110755373A CN110755373A (en) | 2020-02-07 |
| CN110755373B true CN110755373B (en) | 2020-09-08 |
Family
ID=69338304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911129979.1A Active CN110755373B (en) | 2019-11-18 | 2019-11-18 | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110755373B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6407278B2 (en) * | 1998-11-16 | 2002-06-18 | Medimmune Oncology, Inc. | Stable amorphous amifostine compositions and methods for the preparation and use of the same |
| CN101756963A (en) * | 2008-11-25 | 2010-06-30 | 海南四环医药有限公司 | Medicine composition of edaravone and nicotinamide and preparation method thereof |
| CN102008433A (en) * | 2010-12-01 | 2011-04-13 | 广东三信药业有限公司 | Fasudil salt injection for improving stability and preparation method thereof |
| CN102266343A (en) * | 2011-09-05 | 2011-12-07 | 天津市汉康医药生物技术有限公司 | Fasudil hydrochloride pharmaceutical composition for injection |
-
2019
- 2019-11-18 CN CN201911129979.1A patent/CN110755373B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110755373A (en) | 2020-02-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2192249C2 (en) | Paracetamol-base liquid stable composition and method of its preparing | |
| CN102008727B (en) | Injection-purpose medicine composition for improving stability of ligustrazine medicine injection formulation | |
| AU2009270823B2 (en) | Pharmaceutical formulations containing dopamine receptor ligands | |
| CN112516077B (en) | Phloroglucinol injection and preparation method thereof | |
| CN101439031B (en) | Pharmaceutical composition containing 18 kinds of amino acid | |
| IL207400A (en) | Composition comprising degarelix for use in the treatment of prostate cancer | |
| CN102512363A (en) | Oxiracetam injection and preparation method thereof | |
| CN109998990B (en) | Small-size epinephrine hydrochloride injection and preparation method thereof | |
| CN101933922B (en) | Amino acid composition containing new antioxidant | |
| CN104840418B (en) | A kind of fasudil hydrochloride injection composition and preparation method thereof | |
| CN110755373B (en) | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof | |
| CN105919931A (en) | Stable fasudil hydrochloride injection and preparation method thereof | |
| CN108743527B (en) | Tirofiban hydrochloride injection and preparation method thereof | |
| CN111374942B (en) | Steroid muscle relaxant injection and preparation method thereof | |
| CN106860446B (en) | Compound amino acid injection 19AA-I composition for children and method for reducing oxygen content of compound amino acid injection | |
| CN114288385B (en) | Preparation method of octreotide acetate preparation | |
| CN102166185A (en) | Isotonic naloxone injection and preparation method thereof | |
| CN110327371B (en) | Sodium bicarbonate ringer's injection and preparation method thereof | |
| CN104997728A (en) | Nalmefene hydrochloride injection medicinal composition and preparation method thereof | |
| CN107028968B (en) | A pharmaceutical composition containing morphine glucuronide or its pharmaceutically acceptable salt | |
| CN110314132B (en) | Ornithine aspartate injection and preparation method thereof | |
| CN114159384B (en) | Low-irritation ketorolac tromethamine injection with stable chemical properties | |
| CN114886847B (en) | Promethazine hydrochloride injection and preparation method thereof | |
| CN116650414B (en) | Tofacitinib citrate oral solution and preparation method thereof | |
| CN116999433A (en) | Brivaracetam pharmaceutical composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |