CN112168778A - Clevidipine butyrate emulsion for injection and production method thereof - Google Patents
Clevidipine butyrate emulsion for injection and production method thereof Download PDFInfo
- Publication number
- CN112168778A CN112168778A CN202011079173.9A CN202011079173A CN112168778A CN 112168778 A CN112168778 A CN 112168778A CN 202011079173 A CN202011079173 A CN 202011079173A CN 112168778 A CN112168778 A CN 112168778A
- Authority
- CN
- China
- Prior art keywords
- emulsion
- injection
- clevidipine butyrate
- emulsifier
- water
- 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.)
- Pending
Links
Images
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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an emulsion for injection of clevidipine butyrate, which comprises clevidipine butyrate, an oil-phase solvent, an emulsifier, an isotonic agent, an auxiliary emulsifier, a pH value regulator and water for injection, and also comprises a bacteriostatic agent which is edetate disodium; a production method of clevidipine butyrate injection emulsion comprises the steps of vacuumizing production equipment and filling nitrogen gas; preparing an aqueous phase and an oil phase; preparing primary emulsion, mixing water phase and oil phase, adding water for injection to required weight, and making into primary emulsion; carrying out homogenization for many times; and (5) filling, checking by lamp, packaging and warehousing. When the colostrum is prepared, the co-emulsifier is added in the preparation of the oil phase, and the qualification of the emulsion particles larger than 5um is ensured by adjusting the homogenization pressure; after homogenization, the pH value of the emulsion is adjusted to 6.0-8.0, so that the stability of the chloranthus japonicus is ensured.
Description
Technical Field
The invention relates to the field of pharmacy, in particular to clevidipine butyrate emulsion for injection and a production method thereof.
Background
Clevidipine Butyrate (Clevidipine Butyrate), a short-acting dihydropyridine calcium channel blocker, was developed and marketed by The physicians Company (TMC) in The united states, entitled AstraZeneca at 3 months 2003. In 8 months 2008, the emulsion for clevidipine butyrate injection (trade name: clevidirex) is approved by FDA and the market specification: 25mg in 50ml and 50mg in 100 ml. The clevidipine butyrate bulk drug and the preparation thereof are not imported into any pharmacopoeia, and the original research product is not applied for import registration.
In the domestic market, along with the improvement of the living standard and the economic standard of the people in China, the medicine is consistent with the level of the original medicine researched abroad, and the medicine with good curative effect and small side effect can gradually replace the original product, so that the clevidipine butyrate is expected to have great market potential.
In the production process of the chlorambucil, the size of emulsion particles in the production process needs to be paid attention, and the size of the emulsion particles in the fat emulsion injection directly influences the effect and the drug effect of the intravenous injection, so that the method is a very important detection index, particularly the size of the emulsion particles larger than 5 um. The diameter of human pulmonary microvasculature is about 5um, if the diameter of the emulsion particles exceeds 5um, the emulsion particles are easy to stay at the parts, pulmonary embolism of a patient is caused, meanwhile, the clevidipine butyrate injection emulsion can generate related substances under the condition that the pH value is not in an appropriate range in the production process, the effectiveness of the product can be influenced, serious harm can be caused to a human body, in addition, the result of the emulsion particles larger than 5um is high, and the unsafety of medication is caused. The clevidipine butyrate emulsion for injection and the production method thereof provided by the invention are used for solving the problems.
Disclosure of Invention
In order to solve the technical problems, the invention provides an emulsion for clevidipine butyrate injection and a production method thereof. The technical problem to be solved by the invention is realized by adopting the following technical scheme:
the emulsion for injection of the clevidipine butyrate comprises the clevidipine butyrate, an oil-phase solvent, an emulsifier, an isotonic agent, an auxiliary emulsifier, a pH value regulator and water for injection, and further comprises a stabilizer, wherein the stabilizer is disodium edetate.
The emulsion for injection contains the following components in each 50ml: 0.02g to 0.03g of clevidipine butyrate, 9g to 11g of oil phase solvent, 0.5g to 0.7g of emulsifier, 1.1g to 1.2g of isotonic agent, 14g to 17g of auxiliary emulsifier, 2g to 3g of bacteriostatic agent, 1.5g to 2.5g of pH value regulator and the balance of water for injection.
The oil phase solvent is soybean oil, the emulsifier is egg yolk lecithin, the isotonic agent is glycerol, the coemulsifier is oleic acid, and the pH value regulator is sodium hydroxide.
The concentration of the sodium hydroxide is 1 mol/L.
A production method of clevidipine butyrate emulsion for injection comprises the following steps: vacuumizing the production equipment, and simultaneously filling nitrogen;
the second step is that: preparing a water phase, mixing an isotonic agent with two thirds of injection water in a configured amount, adding a stabilizer, and uniformly stirring to obtain the water phase;
the third step: preparing an oil phase, fully mixing an oil phase solvent, a pH value regulator and a co-emulsifier, heating, adding an emulsifier for dissolving, and finally adding clevidipine butyrate for dissolving to prepare the oil phase;
the fourth step: preparing primary emulsion, mixing water phase and oil phase, adding water for injection to required weight, and shearing to obtain primary emulsion;
the fifth step: homogenizing for multiple times, and adjusting pH of the homogenized emulsion to 6.0-8.0;
and a sixth step: and (5) filling, checking by lamp, packaging and warehousing.
And in the fifth step, homogenizing for eight times by matching eight homogenizers, wherein the pressure of the homogenizers is 10MPa to 70 MPa.
After the first seven times of homogenization, the emulsion is cooled to 20-75 ℃ by a heat exchanger, the emulsion after the last time of homogenization is cooled to 20-50 ℃ by the heat exchanger, and the temperature of the last time of homogenization is lower than that after the first seven times of homogenization.
The invention has the beneficial effects that: when the colostrum is prepared, the co-emulsifier is added in the preparation of the oil phase, and the qualification of the emulsion particles larger than 5um is ensured by adjusting the homogenization pressure; after homogenization, the pH value of the emulsion is adjusted to 6.0-8.0, so that the stability of the chloranthus japonicus is ensured.
Drawings
The invention is further illustrated with reference to the following figures and examples.
FIG. 1 is experimental data for comparative example 1 of the present invention;
FIG. 2 is experimental data for comparative example 2 of the present invention;
FIG. 3 is experimental data for comparative example 3 of the present invention;
fig. 4 shows the results of a long-term experiment of an emulsion for injection prepared using the protocol of the present invention.
Detailed Description
In order to make those skilled in the art better understand the technical solution of the present invention, the present invention will be described more clearly and more completely with reference to the drawings in the following embodiments, and it is understood that the described embodiments are only a part of the present invention, rather than all of the present invention, and based on the embodiments, other embodiments obtained by those skilled in the art without inventive exercise are within the protection scope of the present invention.
The emulsion for injection of the clevidipine butyrate comprises the clevidipine butyrate, an oil-phase solvent, an emulsifier, an isotonic agent, an auxiliary emulsifier, a pH value regulator and water for injection, and further comprises a bacteriostatic agent which is disodium edetate.
The emulsion for injection contains the following components in each 50ml: 0.02g to 0.03g of clevidipine butyrate, 9g to 11g of oil phase solvent, 0.5g to 0.7g of emulsifier, 1.1g to 1.2g of isotonic agent, 14g to 17g of auxiliary emulsifier, 2g to 3g of bacteriostatic agent, 1.5g to 2.5g of pH value regulator and the balance of water for injection.
The oil phase solvent is soybean oil, the emulsifier is egg yolk lecithin, the isotonic agent is glycerol, the coemulsifier is oleic acid, and the pH value regulator is sodium hydroxide.
The concentration of the sodium hydroxide is 1 mol/L.
A production method of clevidipine butyrate emulsion for injection comprises the following steps: the production equipment comprises an oil tank, a primary emulsion tank, two preparation tanks and a liquid storage tank; vacuumizing, sequentially opening vacuum valves of the oil tank, the primary emulsion tank, the preparation tanks 1#, 2# and the liquid storage tank, closing the vacuum valves, filling nitrogen, and maintaining the pressure in the tank at a certain value.
The second step is that: preparing a water phase, opening a water valve for injection, injecting two thirds of injection water with the preparation amount into a glycerol preparation tank, then adding weighed and rechecked glycerol (for injection) into the glycerol preparation tank, starting circulation, starting cooling water to reduce the temperature, controlling the water temperature to be 20-80 ℃, and performing filtration circulation for 5-20 minutes. Adding edetate disodium and stirring for 10-20 min.
The third step: preparing an oil phase, (1) opening a feeding valve when the pressure in the oil tank is a certain value, and adding a rechecked soybean oil (for injection) raw material, 1mol/L NaOH solution and oleic acid;
(2) heating the oil phase to 20-80 deg.C, adding egg yolk lecithin and clevidipine butyrate, maintaining the temperature at 20-80 deg.C, and mixing for 10-20 min;
the fourth step: preparing primary emulsion, (1) mixing the water phase and the oil phase, sending the mixture into a primary emulsion tank, and then washing an oil tank with a little injection water and sending the oil tank into the primary emulsion tank;
(2) adding water for injection into the primary emulsion tank to required weight, uniformly preparing primary emulsion, controlling the temperature of the primary emulsion at 20-80 deg.C, adjusting pH and monitoring glycerol content;
the fifth step: homogenizing, opening a valve from a 1# preparation tank to a 1# homogenizer, starting the 1# homogenizer, adjusting the pressure of the homogenizer to 10MPa to 70MPa, and sending the emulsion to a 1# transfer tank;
opening a valve from the 1# transfer tank to the 2# homogenizer, starting the 2# homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 2# transfer tank;
opening a valve from the 2# transfer tank to the 3# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 3# transfer tank;
opening a valve from the 3# transfer tank to the 4# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 4# transfer tank;
opening a valve from the 4# transfer tank to the 5# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 5# transfer tank;
opening a valve from the 5# transfer tank to the 6# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 6# transfer tank;
opening a valve from the 6# transfer tank to the 7# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, and sending the emulsion to the 7# transfer tank;
opening a valve of a 7# transfer tank to an 8# homogenizer, starting the homogenizer, adjusting the pressure of the homogenizer to be 10MPa to 70MPa, conveying the emulsion to a 2# preparation tank, and filling nitrogen into the 1# preparation tank in the feeding process;
after the first seven times of homogenization, the emulsion is cooled to 20-75 ℃, the emulsion after the last homogenization is cooled to 20-50 ℃, and the temperature of the last homogenization is lower than that after the first seven times of homogenization.
The homogenized emulsion is directly sent into a liquid storage tank, and nitrogen is filled into the liquid storage tank after the emulsion is completely sent.
And a sixth step: bottle washing, filling, plugging, capping and capping: the infusion bottle is delivered to a filling room after fine washing, the liquid medicine is filled after being filtered by a 0.22um filter, and then the bottle is plugged and covered by a rolling cover.
And (3) sterilization: and (3) feeding the filled and rolled product into a water bath sterilization cabinet, sterilizing at 121 ℃, and quickly cooling to room temperature after sterilization to obtain the product.
Lamp inspection and packaging: and cooling the sterilized product, sending the cooled product into a lamp inspection room for lamp inspection, and packaging and warehousing the product qualified in the lamp inspection.
As shown in fig. 1, which is comparative example 1 of the present invention, the emulsion particle detection results of clevidipine butyrate emulsion prepared by adding oleic acid into the aqueous phase and adding oleic acid into the oil phase, respectively, for injection use; the data in the figure can show that only 0.0083% of the emulsion particles with the diameter larger than 5um, which are added into the oil phase, are basically consistent with the original preparation, while the emulsion particles with the diameter larger than 5um, which are added into the water phase, reach the standard limit of 0.039%, so that the oleic acid is firstly added into the oil phase when in colostrum.
As shown in fig. 2, which is a comparative example 2 of the present invention, it is the related substances, emulsion particles larger than 5um and the content of clevidipine butyrate emulsion for injection under different pH conditions; the data in the figure show that when the pH is 5.0, the impurity 1 and the impurity V in the related substances are obviously less than pH9.5, but the result of the emulsion particle with the pH more than 5 mu m is also close to the standard limit, so the pH of the product is controlled between 6.0 and 8.0 when the product is prepared.
As shown in fig. 3, which is comparative example 2 of the present invention, the result of the large emulsion particle detection of clevidipine butyrate injection emulsion under different homogenization pressure conditions; the data in the figure can show that the milk granules with the homogenization pressure of more than 5um under the conditions of 5-10MPa and 70-80MPa are respectively 0.026 percent and 0.039 percent which are obviously different from 10-70MPa, so the pressure of the product is determined to be 10-70MPa when the product is prepared.
As shown in figure 4, according to the scheme of the invention, a batch of clevidipine butyrate emulsion products for injection is produced, the specification is 50ml:25mg, and the batch number is as follows: 2118012501, long-term stability of each of the drug batches was investigated; the data in the figure show that each detection index of the emulsion for injection of clevidipine butyrate prepared according to the invention meets the specification after long-term stability investigation for 24 months, and the emulsion for injection of clevidipine butyrate produced according to the process of the invention is safe and feasible.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (7)
1. An emulsion for injection of clevidipine butyrate comprises clevidipine butyrate, an oil-phase solvent, an emulsifier, an isotonic agent, an auxiliary emulsifier, a pH value regulator and water for injection, and is characterized in that: the emulsion for injection also comprises a stabilizer, wherein the stabilizer is edetate disodium.
2. An emulsion of clevidipine butyrate for injection according to claim 1, wherein: the emulsion for injection contains the following components in each 50ml: 0.02g to 0.03g of clevidipine butyrate, 9g to 11g of oil phase solvent, 0.5g to 0.7g of emulsifier, 1.1g to 1.2g of isotonic agent, 14g to 17g of auxiliary emulsifier, 2g to 3g of bacteriostatic agent, 1.5g to 2.5g of pH value regulator and the balance of water for injection.
3. An emulsion of clevidipine butyrate for injection according to claim 1, wherein: the oil phase solvent is soybean oil, the emulsifier is egg yolk lecithin, the isotonic agent is glycerol, the coemulsifier is oleic acid, and the pH value regulator is sodium hydroxide.
4. An emulsion of clevidipine butyrate for injection according to claim 3, wherein: the concentration of the sodium hydroxide is 1 mol/L.
5. The method for producing clevidipine butyrate emulsion for injection according to any one of claims 1 to 4, wherein:
the first step is as follows: vacuumizing the production equipment, and simultaneously filling nitrogen;
the second step is that: preparing a water phase, mixing an isotonic agent with two thirds of injection water in a configured amount, adding a stabilizer, and uniformly stirring to obtain the water phase;
the third step: preparing an oil phase, fully mixing an oil phase solvent, a pH value regulator and a co-emulsifier, heating, adding an emulsifier for dissolving, and finally adding chloracetyl butyrate for dissolving to prepare the oil phase;
the fourth step: preparing primary emulsion, mixing the water phase and the oil phase, adding water for injection to required weight, and finally uniformly preparing the primary emulsion;
the fifth step: homogenizing for multiple times, and adjusting pH of the homogenized emulsion to 6.0-8.0;
and a sixth step: and (5) filling, checking by lamp, packaging and warehousing.
6. The method for producing clevidipine butyrate emulsion for injection according to claim 5, wherein the method comprises the following steps: homogenizing for eight times by matching eight homogenizers, wherein the pressure of the homogenizers is 10MPa to 70 MPa.
7. The method for producing clevidipine butyrate emulsion for injection according to claim 6, wherein the method comprises the following steps: after the first seven times of homogenization, the emulsion is cooled to 20-75 ℃ by a heat exchanger, the emulsion after the last time of homogenization is cooled to 20-50 ℃ by the heat exchanger, and the temperature of the last time of homogenization is lower than that after the first seven times of homogenization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011079173.9A CN112168778A (en) | 2020-10-10 | 2020-10-10 | Clevidipine butyrate emulsion for injection and production method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011079173.9A CN112168778A (en) | 2020-10-10 | 2020-10-10 | Clevidipine butyrate emulsion for injection and production method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112168778A true CN112168778A (en) | 2021-01-05 |
Family
ID=73948670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011079173.9A Pending CN112168778A (en) | 2020-10-10 | 2020-10-10 | Clevidipine butyrate emulsion for injection and production method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112168778A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113197853A (en) * | 2021-05-06 | 2021-08-03 | 上海上药第一生化药业有限公司 | Clevidipine butyrate emulsion for injection, and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878182A (en) * | 2014-12-30 | 2016-08-24 | 南京海纳医药科技有限公司 | Preparation method of clevidipine butyrate injection fat emulsion |
| CN109602704A (en) * | 2019-01-23 | 2019-04-12 | 广东嘉博制药有限公司 | Clevidipine butyrate fat emulsion injection and its preparation process |
-
2020
- 2020-10-10 CN CN202011079173.9A patent/CN112168778A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878182A (en) * | 2014-12-30 | 2016-08-24 | 南京海纳医药科技有限公司 | Preparation method of clevidipine butyrate injection fat emulsion |
| CN109602704A (en) * | 2019-01-23 | 2019-04-12 | 广东嘉博制药有限公司 | Clevidipine butyrate fat emulsion injection and its preparation process |
Non-Patent Citations (2)
| Title |
|---|
| 何海冰等: "丁酸氯维地平亚微乳注射液的制备与理化性质考察", 《沈阳药科大学学报》 * |
| 荣景宏等: "丁酸氯维地平脂微球注射液的制备及质量评价", 《沈阳药科大学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113197853A (en) * | 2021-05-06 | 2021-08-03 | 上海上药第一生化药业有限公司 | Clevidipine butyrate emulsion for injection, and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103550143B (en) | A kind of preparation method of levetiracetam injection | |
| CN109692154B (en) | Preparation method of propofol medium/long-chain fat emulsion injection | |
| CN104434786B (en) | Stable bromhexine hydrochloride sodium chloride injection composition | |
| CN113332239B (en) | Adrenaline hydrochloride injection and preparation method thereof | |
| CN112168778A (en) | Clevidipine butyrate emulsion for injection and production method thereof | |
| CN102188374A (en) | Medium/long fat emulsion injection and preparation method thereof | |
| CN103301062A (en) | Medium and long-chain lipid emulsion injection preparation method | |
| CN106265499A (en) | A kind of compound potassium dihydrogn phosphate pharmaceutical composition | |
| CN1399959A (en) | Etomidate fatty emulsion injection preparation method | |
| CN111643450A (en) | Bromfenac sodium eye drops and preparation method thereof | |
| CN112245386A (en) | Dexamethasone sodium phosphate injection and preparation method thereof | |
| US10543186B1 (en) | Cysteine composition and injection | |
| CN105832663A (en) | Injection for preventing phlebothrombosis after orthopedic or surgical operations and preparation method of injection | |
| CN101417105B (en) | Zedoary turmeric oil glucose injection and preparation method thereof | |
| CN115154421A (en) | Preparation process of flurbiprofen axetil fat emulsion injection | |
| CN103191431A (en) | Coenzyme Q10 sodium chloride injection uneasy to crystallize and preparation method thereof | |
| CN108066283B (en) | Preparation method of levobetaxolol hydrochloride eye drops | |
| CN113633610A (en) | Methotrexate injection and preparation method thereof | |
| CN100358513C (en) | Disoprofol injection preparation process | |
| CN107961215A (en) | A kind of levocetirizine injection | |
| CN101664385B (en) | Ibutilide fumarate injection and preparation method thereof | |
| CN105193722B (en) | Dimercaprol fat emulsion injection | |
| CN106265857A (en) | The preparation method of the fat milk of packed with three-cavity bag, aminoacid and glucose injection | |
| CN110876718A (en) | Tranexamic acid injection and preparation method thereof | |
| CN105769756A (en) | Sitafloxacin fumarate injection 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 |