CN114557969B - Creatine phosphate sodium powder injection for injection and preparation method thereof - Google Patents
Creatine phosphate sodium powder injection for injection and preparation method thereof Download PDFInfo
- Publication number
- CN114557969B CN114557969B CN202210150989.9A CN202210150989A CN114557969B CN 114557969 B CN114557969 B CN 114557969B CN 202210150989 A CN202210150989 A CN 202210150989A CN 114557969 B CN114557969 B CN 114557969B
- Authority
- CN
- China
- Prior art keywords
- injection
- creatine phosphate
- parts
- phosphate sodium
- mixture
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/664—Amides of phosphorus acids
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/24—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
-
- 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
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- 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
-
- 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
- Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
- Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
- Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of creatine phosphate sodium powder injection for injection, which takes creatine phosphate sodium, sodium deoxycholate, alpha-tocopheryl succinate, polylactic acid, egg yolk lecithin and water for injection as raw materials to prepare the creatine phosphate sodium powder injection for injection, the effective period of the prepared creatine phosphate sodium powder injection for injection is 36 months, pharmacological tests prove that the creatine phosphate sodium powder injection for injection has better treatment effect, and the concentration of drugs in myocardial tissues after injection for 20min reaches 13.5nmol/mL.
Description
Technical Field
The invention relates to the field of creatine phosphate sodium, and particularly relates to creatine phosphate sodium powder injection for injection and a preparation method thereof.
Background
Chemical name: n- [ imino (phosphino) methyl ] -N-methylglycine disodium salt tetrahydrate. The product is suitable for cardiac operation, and can be added into cardioplegia solution for protecting myocardial metabolism abnormality under myocardial ischemia state. Creatine phosphate plays an important role in the energy metabolism of muscle contraction. It is a chemical energy reserve for cardiac and skeletal muscle and is used for the resynthesis of ATP, the hydrolysis of which provides energy for the actomyosin contraction process. Insufficient energy supply due to slowed oxidative metabolism is an important factor in the development and progression of myocardial cell injury. Insufficient creatine phosphate levels have important clinical implications in the impairment of myocardial contractility and functional recovery. In fact, in myocardial injury, there is a close relationship between the amount of intracellular high-energy phosphate compounds and the ability of cells to survive and recover contractile function. Therefore, maintaining the level of high-energy phosphate compounds becomes the basic principle of various methods for limiting myocardial damage and is also the basis of heart metabolism protection.
Chinese patent CN201210014132.0 creatine phosphate sodium composition powder injection is prepared by taking creatine phosphate sodium and lidocaine hydrochloride as raw materials, and the powder injection prepared by the invention can relieve the pain effect of injection in the using process; CN200710039651.1 is a process for preparing creatine phosphate sodium powder injection, wherein creatine phosphate sodium is dissolved in water, filtered, filled, freeze-dried and corked to obtain creatine phosphate sodium powder injection, and no expiration date is recorded in the creatine phosphate sodium powder injection prepared by the process. Since creatine phosphate is extremely hygroscopic, it is desirable to prepare a composition that has a long shelf life and good reconstitution properties and that increases blood levels in tissues shortly after injection.
Disclosure of Invention
Therefore, the invention provides a preparation method of creatine phosphate sodium powder injection for injection, which improves the stability of creatine phosphate sodium powder injection for injection, prolongs the effective period and improves the blood concentration in tissues in a short time after injection.
The technical scheme of the invention is realized as follows: a creatine phosphate sodium powder injection for injection comprises, by weight, 20-25 parts of creatine phosphate sodium, 40-50 parts of sodium deoxycholate, 1-3 parts of alpha-tocopheryl succinate, 28-32 parts of polylactic acid, 35-37 parts of egg yolk lecithin and 60-70 parts of water for injection.
Further, the preparation method of the creatine phosphate sodium powder injection for injection comprises the following steps:
(1) Mixing sodium deoxycholate, alpha-tocopheryl acid succinate, polylactic acid, egg yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, and filtering to prepare a mixture 1, wherein the mass ratio of the material liquid is 1;
(2) Mixing creatine phosphate sodium with water for injection to prepare creatine phosphate sodium solution;
(3) Adding the mixture 1 into a creatine phosphate sodium solution, and adjusting the pH value to 6.5-7.5 to obtain a mixture 2;
(4) Mixing the mixture 2 with a high-pressure homogenizer, subpackaging the mixed mixture 2, sterilizing, lyophilizing and drying to obtain the final product.
Further, in the step (1), the stirring is performed by firstly stirring for 30-40min at 30-40 ℃, the stirring speed is 350-400r/min, then the temperature is raised to 65-70 ℃, and the stirring is performed for 2-3h, and the stirring speed is 100-120r/min.
According to the invention, different stirring speeds and temperatures are selected for stirring in sections, the raw materials are fully dissolved in absolute ethyl alcohol, the number of microspheres formed in the solution is increased at the initial stage of volatilization of the absolute ethyl alcohol, and the temperature is increased for stirring for a long time, so that the ethanol in the mixed solution can be removed, the viscosity of the mixed solution is increased, and the encapsulation efficiency of the finished product is further improved.
Further, in the step (1), the filtration is carried out by sequentially passing through 0.8 μm and 0.22 μm microporous filter membranes.
The invention selects the 0.8 μm and 0.22 μm microporous filter membranes for filtration, which not only can filter insoluble impurities in the raw materials, but also can regulate and control the particle size and uniformity of particles in the mixture.
Further, in the step (3), the adding rate of the mixture 1 is 5-15ml/10s.
In the invention, the dropping rate of the mixture 1 is controlled, so that the mixture 1 is favorably mixed with creatine phosphate sodium, and the drug loading rate of polylactic acid and the encapsulation rate of microemulsion are improved.
Further, in the step (3), the stirring speed is 80-100r/min.
Further, in the step (3), sodium hydroxide solution with the molar concentration of 0.1-1mol/L is used for adjusting the pH value.
Further, in the step (4), the pressure of the high-pressure homogenizer is 80-90MPa, the homogenizing time is 4-6 times, and the homogenizing time is 5-10min.
Further, in step (4), the freeze-drying is as follows:
s1: pre-freezing: the pre-freezing temperature is-28 to-24 ℃, and the pre-freezing time is 3 to 5 hours;
s2: sublimation: the sublimation temperature is-8 to-4 ℃, and the sublimation time is 10 to 12 hours;
s3: and (3) drying: the drying temperature is 30-35 deg.C, and the drying time is 2-2.5h.
Further, the injection comprises, by weight, 23 parts of creatine phosphate sodium, 45 parts of sodium deoxycholate, 2 parts of alpha-tocopheryl succinate, 30 parts of polylactic acid, 36 parts of egg yolk lecithin and 65 parts of water for injection.
Compared with the prior art, the invention has the beneficial effects that:
the creatine phosphate sodium powder injection for injection is prepared by taking creatine phosphate sodium, sodium deoxycholate, alpha-tocopheryl succinate, polylactic acid, egg yolk lecithin and water for injection as raw materials, the stability of the powder injection is improved, and particularly, the stability of a finished product is easily reduced because the creatine phosphate sodium raw material has hygroscopicity. The raw materials of the invention have synergistic effect, polylactic acid is used as a carrier, sodium deoxycholate has the function of stabilizing the structure of a finished product, the pH value is adjusted to 6.5-7.5, the adsorption of creatine phosphate sodium, polylactic acid and egg yolk lecithin is facilitated, and the encapsulation efficiency is improved. The creatine phosphate sodium powder injection for injection prepared by the invention has good permeation effect on cells such as cardiac muscle, skeletal muscle and the like, and the drug concentration in cardiac muscle tissue 20min after injection is 13.5nmol/mL.
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention are commercially available unless otherwise specified.
EXAMPLE 1 preparation method of creatine phosphate sodium powder for injection
(1) Weighing the following raw materials in parts by weight: 23 parts of creatine phosphate sodium, 45 parts of sodium deoxycholate, 2 parts of alpha-tocopheryl succinate, 30 parts of polylactic acid, 36 parts of egg yolk lecithin and 65 parts of water for injection for later use.
(2) Mixing sodium deoxycholate, alpha-tocopheryl acid succinate, polylactic acid, yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, wherein the stirring is performed by firstly stirring for 35min at 35 ℃, the stirring speed is 380r/min, then increasing the temperature to 68 ℃, stirring for 2.5h, the stirring speed is 110r/min, the material-liquid mass ratio is 1;
(3) Mixing creatine phosphate sodium with water for injection to prepare creatine phosphate sodium solution;
(4) Adding the mixture 1 into a creatine phosphate sodium solution, wherein the adding speed of the mixture 1 is 10ml/10s, the stirring speed is 90r/min, and the pH value is adjusted to 7.0 by using a sodium hydroxide solution with the molar concentration of 0.5mol/L to prepare a mixture 2;
(5) Mixing the mixture 2 by using a high-pressure homogenizer with the pressure of 85MPa, the homogenizing times of 5 times and the homogenizing time of 8min, subpackaging, sterilizing and freeze-drying the mixed mixture 2 to obtain a finished product, wherein the freeze-drying step is S1: pre-freezing: the pre-freezing temperature is-26 ℃, and the pre-freezing time is 4 hours; s2: sublimation: the sublimation temperature is-6 ℃, and the sublimation time is 11h; s3: and (3) drying: the drying temperature is 33 ℃, and the drying time is 2.3h.
EXAMPLE 2 preparation method of creatine phosphate sodium powder for injection
(1) Weighing the following raw materials in parts by weight: 20 parts of creatine phosphate sodium, 40 parts of sodium deoxycholate, 1 part of alpha-tocopheryl acid succinate, 28 parts of polylactic acid, 35 parts of egg yolk lecithin and 60 parts of water for injection for later use.
(2) Mixing sodium deoxycholate, alpha-tocopheryl succinate, polylactic acid, egg yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, wherein the stirring is performed by stirring for 30min at 30 ℃ at the stirring speed of 350r/min, then raising the temperature to 65 ℃ and stirring for 2h at the stirring speed of 100r/min, the feed liquid mass ratio is 1;
(3) Mixing creatine phosphate sodium with water for injection to prepare creatine phosphate sodium solution;
(4) Adding the mixture 1 into a creatine phosphate sodium solution, wherein the adding speed of the mixture 1 is 5ml/10s, the stirring speed is 80r/min, and the pH value is adjusted to 6.5 by using a sodium hydroxide solution with the molar concentration of 0.1mol/L to prepare a mixture 2;
(5) Mixing the mixture 2 by using a high-pressure homogenizer with the pressure of 80MPa, the homogenizing times of 4 times and the homogenizing time of 5min, subpackaging, sterilizing and freeze-drying the mixed mixture 2 to obtain a finished product, wherein the freeze-drying step is S1: pre-freezing: the pre-freezing temperature is-28 ℃, and the pre-freezing time is 3 hours; s2: sublimation: the sublimation temperature is-8 ℃, and the sublimation time is 10h; s3: and (3) drying: the drying temperature is 30 ℃, and the drying time is 2h.
Example 3 preparation method of creatine phosphate sodium powder for injection
(1) Weighing the following raw materials in parts by weight: 25 parts of creatine phosphate sodium, 50 parts of sodium deoxycholate, 3 parts of alpha-tocopheryl succinate, 32 parts of polylactic acid, 37 parts of egg yolk lecithin and 70 parts of water for injection for later use.
(2) Mixing sodium deoxycholate, alpha-tocopheryl acid succinate, polylactic acid, yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, wherein the stirring is performed by using a stirrer at 40 ℃ for 40min at a stirring speed of 400r/min, raising the temperature to 70 ℃ and stirring for 3h at a stirring speed of 120r/min and a feed liquid mass ratio of 1;
(3) Mixing creatine phosphate sodium with water for injection to prepare creatine phosphate sodium solution;
(4) Adding the mixture 1 into a creatine phosphate sodium solution, wherein the adding speed of the mixture 1 is 15ml/10s, the stirring speed is 100r/min, and the pH value is adjusted to 7.5 by using a sodium hydroxide solution with the molar concentration of 1mol/L to prepare a mixture 2;
(5) Mixing the mixture 2 by using a high-pressure homogenizer with the pressure of 90MPa, the homogenizing times of 6 times and the homogenizing time of 10min, subpackaging, sterilizing and freeze-drying the mixed mixture 2 to obtain a finished product, wherein the freeze-drying step is S1: pre-freezing: the pre-freezing temperature is-24 ℃, and the pre-freezing time is 5 hours; s2: sublimation: the sublimation temperature is-4 ℃, and the sublimation time is 12h; s3: and (3) drying: the drying temperature is 35 ℃, and the drying time is 2.5h.
Comparative example 1
Adjusting the raw material components in the step (1) on the basis of the embodiment 1, specifically: weighing the following raw materials in parts by weight: 23 parts of creatine phosphate sodium, 45 parts of algal polysaccharide, 2 parts of vitamin E, 30 parts of polylactic acid, 36 parts of soybean lecithin and 65 parts of water for injection for later use.
Comparative example 2
On the basis of the example 1, the usage amount of the raw materials in the step (1) is adjusted, and specifically: weighing the following raw materials in parts by weight: 23 parts of creatine phosphate sodium, 30 parts of sodium deoxycholate, 2 parts of alpha-tocopheryl acid succinate, 50 parts of polylactic acid, 45 parts of egg yolk lecithin and 65 parts of water for injection for later use.
Comparative example 3
Adjusting the stirring parameters in the step (2) on the basis of the embodiment 1, which specifically comprises the following steps: mixing sodium deoxycholate, alpha-tocopheryl acid succinate, polylactic acid, egg yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, wherein the stirring is performed at 35 ℃ for 4 hours at 380r/min, the material liquid mass ratio is 1.
Comparative example 4
Adjusting the pH value in the step (4) on the basis of the embodiment 1, which comprises the following specific steps: mixture 1 was added to the creatine phosphate sodium solution, said mixture 1 was added at a rate of 10ml/10s and stirred at a rate of 90r/min, and the pH was adjusted to 9.0 using a sodium hydroxide solution having a molar concentration of 0.5mol/L to give mixture 2.
Test example 1
And (3) detecting the content, related substances, properties and clarity of the sample for 0 day, accelerated test and long-term test according to a sodium creatine phosphate detection standard in the second part of the 'Chinese pharmacopoeia' 2020 edition.
TABLE 1 quality test results of creatine phosphate sodium powder for injection in 0 day
| Name (R) | Content (%) | Total hetero (%) | Traits | Clarity of the product |
| Example 1 | 99.9 | 0.106 | White loose block | Clear and colorless |
| Example 2 | 100.2 | 0.115 | White loose block | Clear and colorless |
| Example 3 | 99.9 | 0.110 | White loose block | Clear and colorless |
| Comparative example 1 | 99.7 | 0.233 | White loose block | Clear and colorless |
| Comparative example 2 | 99.6 | 0.256 | White loose block | Clear and colorless |
| Comparative example 3 | 99.8 | 0.199 | White loose block | Clear and colorless |
| Comparative example 4 | 100.3 | 0.304 | White loose block | Clear and colorless |
TABLE 2 accelerated test 6-month sodium creatine phosphate powder for injection quality test results (40 ℃. + -. 2 ℃, RH 75%. + -. 5%)
TABLE 3 Long-term test results of 36 months injection sodium creatine phosphate powder for injection quality detection (25 deg.C + -2 deg.C, RH60% + -10%, light shielding)
Experimental results show that the creatine phosphate sodium powder injection for injection prepared by the invention has stable property and the effective period is as long as 36 months. Through the comparison of the results of accelerated tests, long-term tests and 0-day sample detection, the raw material components are changed in comparative example 1, so that the impurities are increased too fast and the content is reduced; compared with the prior art, the preparation process is changed, the stirring process is favorable for fully dissolving the raw materials in the absolute ethyl alcohol, the number of microspheres formed in the solution is increased at the initial stage of the volatilization of the absolute ethyl alcohol, the temperature is increased for long-time stirring, the ethanol in the mixed solution can be removed, the viscosity of the mixed solution is increased, the encapsulation efficiency of the finished product is further improved, and the preparation quality is improved; comparative example 4 changes the pH resulting in a decrease in the raw material binding effect, further affecting the formulation stability.
Test example 2 pharmacological test of creatine phosphate sodium powder for injection
(1) 35 rats were divided into 7 groups on average, and the sodium creatine phosphate powder injections prepared in examples 1-3 and comparative examples 1-4 were used for the test at a dose of 10mg/kg -1 The administration mode is intravenous injection, and the injection site is ratAt the tail, the rats were sacrificed 20min after injection, myocardial tissue was extracted, and the drug concentration was measured using high performance liquid chromatography.
| Name (R) | Drug concentration (nmol/mL) |
| Example 1 | 14.5 |
| Example 2 | 13.9 |
| Example 3 | 14.1 |
| Comparative example 1 | 7.4 |
| Comparative example 2 | 9.2 |
| Comparative example 3 | 10.3 |
| Comparative example 4 | 9.9 |
Experimental results show that the creatine phosphate sodium powder injection for injection prepared by the invention has a good effect, and the drug concentration in the myocardial tissue 20min after injection is 13.5nmol/mL.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A creatine phosphate sodium powder injection for injection is characterized by comprising, by weight, 20-25 parts of creatine phosphate sodium, 40-50 parts of sodium deoxycholate, 1-3 parts of alpha-tocopheryl succinate, 28-32 parts of polylactic acid, 35-37 parts of egg yolk lecithin and 60-70 parts of water for injection;
the preparation method comprises the following steps:
(1) Mixing sodium deoxycholate, alpha-tocopheryl succinate, polylactic acid, egg yolk lecithin and absolute ethyl alcohol, stirring by using a magnetic stirring pot, and filtering to obtain a mixture 1, wherein the mass ratio of the material liquid to the material liquid is 1; the stirring is carried out at 30-40 ℃ for 30-40min at a stirring speed of 350-400r/min, and then the temperature is raised to 65-70 ℃ for stirring for 2-3h at a stirring speed of 100-120r/min;
(2) Mixing creatine phosphate sodium with water for injection to prepare creatine phosphate sodium solution;
(3) Adding the mixture 1 into a creatine phosphate sodium solution, and adjusting the pH value to 6.5-7.5 to obtain a mixture 2;
(4) Mixing the mixture 2 with a high-pressure homogenizer, subpackaging the mixed mixture 2, sterilizing, lyophilizing and drying to obtain the final product.
2. The method for preparing creatine phosphate sodium powder for injection as claimed in claim 1, wherein in step (1), the filtration is sequentially by 0.8 μm and 0.22 μm microporous filter membranes.
3. The method for preparing creatine phosphate sodium powder injection for injection as claimed in claim 1, wherein in step (3), the adding rate of the mixture 1 is 5-15ml/10s.
4. The method for preparing creatine phosphate sodium powder injection for injection as claimed in claim 1, wherein in step (3), sodium hydroxide solution with molar concentration of 0.1-1mol/L is used for pH value adjustment.
5. The method for preparing creatine phosphate sodium powder for injection as claimed in claim 1, wherein in step (4), the pressure of the high pressure homogenizer is 80-90MPa, the homogenizing times are 4-6 times, and the homogenizing time is 5-10min.
6. The method for preparing creatine phosphate sodium powder for injection according to claim 1, wherein in the step (4), the freeze-drying is:
s1: pre-freezing: the pre-freezing temperature is-28 to-24 ℃, and the pre-freezing time is 3 to 5 hours;
s2: sublimation: the sublimation temperature is-8 to-4 ℃, and the sublimation time is 10 to 12 hours;
s3: and (3) drying: the drying temperature is 30-35 ℃, and the drying time is 2-2.5h.
7. The creatine phosphate powder injection according to claim 1, wherein the creatine phosphate powder injection comprises, by weight, 23 parts of creatine phosphate sodium, 45 parts of sodium deoxycholate, 2 parts of alpha-tocopheryl succinate, 30 parts of polylactic acid, 36 parts of egg yolk lecithin and 65 parts of water for injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210150989.9A CN114557969B (en) | 2022-02-18 | 2022-02-18 | Creatine phosphate sodium powder injection for injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210150989.9A CN114557969B (en) | 2022-02-18 | 2022-02-18 | Creatine phosphate sodium powder injection for injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114557969A CN114557969A (en) | 2022-05-31 |
| CN114557969B true CN114557969B (en) | 2023-04-18 |
Family
ID=81713420
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210150989.9A Active CN114557969B (en) | 2022-02-18 | 2022-02-18 | Creatine phosphate sodium powder injection for injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114557969B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101288649A (en) * | 2007-04-19 | 2008-10-22 | 上海慈瑞医药科技有限公司 | Preparation technique of sodium phosphocreatine powder and injection preparation |
| CN101474159A (en) * | 2008-12-16 | 2009-07-08 | 海南美大制药有限公司 | Creatine phosphate sodium microballoon lyophilized preparation and method for producing the same |
| CN101530391A (en) * | 2009-04-07 | 2009-09-16 | 王明 | Creatine phosphate sodium lipidosome freeze-dried preparation and preparation method thereof |
| CN101732263A (en) * | 2008-11-14 | 2010-06-16 | 杨军 | Creatine phosphate sodium freeze-dried preparation and method for preparing same |
| CN102525962A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Power injection for injecting creatine phosphate sodium composition |
| CN102772375A (en) * | 2012-08-23 | 2012-11-14 | 孙威 | Creatine phosphate sodium for injection and preparation method for creatine phosphate sodium for injection |
| WO2019180199A1 (en) * | 2018-03-22 | 2019-09-26 | Alfasigma S.P.A. | Stable aqueous composition of phosphocreatine |
-
2022
- 2022-02-18 CN CN202210150989.9A patent/CN114557969B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101288649A (en) * | 2007-04-19 | 2008-10-22 | 上海慈瑞医药科技有限公司 | Preparation technique of sodium phosphocreatine powder and injection preparation |
| CN101732263A (en) * | 2008-11-14 | 2010-06-16 | 杨军 | Creatine phosphate sodium freeze-dried preparation and method for preparing same |
| CN101474159A (en) * | 2008-12-16 | 2009-07-08 | 海南美大制药有限公司 | Creatine phosphate sodium microballoon lyophilized preparation and method for producing the same |
| CN101530391A (en) * | 2009-04-07 | 2009-09-16 | 王明 | Creatine phosphate sodium lipidosome freeze-dried preparation and preparation method thereof |
| CN102525962A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Power injection for injecting creatine phosphate sodium composition |
| CN102772375A (en) * | 2012-08-23 | 2012-11-14 | 孙威 | Creatine phosphate sodium for injection and preparation method for creatine phosphate sodium for injection |
| WO2019180199A1 (en) * | 2018-03-22 | 2019-09-26 | Alfasigma S.P.A. | Stable aqueous composition of phosphocreatine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114557969A (en) | 2022-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108186575B (en) | Embedding system based on eutectic solvent as solvent | |
| CN102367254B (en) | More stable doxofylline compound and pharmaceutical composite thereof | |
| CN101264064B (en) | Vinpocetine freeze-dried powder for injection and preparation thereof | |
| CN114557969B (en) | Creatine phosphate sodium powder injection for injection and preparation method thereof | |
| CN104027329A (en) | Isosorbide dinitrate sodium chloride injection | |
| CA2900120C (en) | Hpph lyophilized powder injection for injection and preparation method thereof | |
| DE112016001715T5 (en) | Stable liquid pharmaceutical compositions of Bortezomib | |
| MX2007012166A (en) | Stannsoporfin compositions and administration. | |
| CN102247373A (en) | Composition of methionine vitamin B1 compound | |
| CN103877032B (en) | Vecuronium bromide pharmaceutical composition for injection and preparation method thereof | |
| CN102895178B (en) | Strong solution-type moxifloxacin hydrochloride injection and preparation method thereof | |
| CN1493283A (en) | Edalavon powder for ampoul injection having good stability and its preparation method | |
| EP1798235A1 (en) | Acid addition salt of irinotecan | |
| CN102757471B (en) | Novel active cytidine disodium triphosphate compound and pharmaceutical composition thereof | |
| CN109044969B (en) | Preparation method of paclitaxel injection | |
| CN103494778B (en) | Esomeprazole sodium freeze-dried preparation and preparation method thereof | |
| CN104367550A (en) | Belotecan long circulation nano liposome and preparation method thereof | |
| CN110151707B (en) | Ropivacaine mesylate pharmaceutical composition and preparation method thereof | |
| CN110314143A (en) | Injection dextrorotation Oxiracetam lyophilized preparation and preparation method thereof | |
| CN114983948B (en) | Pharmaceutical composition containing creatine phosphate sodium and preparation method thereof | |
| CN1267096C (en) | Ginkgo leaf extract injection and its preparation method | |
| CN102949351B (en) | Preparation method of temozolomide lyophilized preparation | |
| CN113908129B (en) | Rifampicin freeze-dried powder for injection and production method thereof | |
| CN115073368B (en) | Milrinone-5-sulfosalicylic acid crystal form | |
| CN112451520B (en) | Valsartan amlodipine 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 |