A kind of nimodipine injection composition and preparation method thereof

Abstract

A nimodipine injection composition and a preparation method thereof. The nimodipine injection composition comprises the following components in terms of mass concentration: 0.02-0.23% of nimodipine, 2-30% of oil for injection, 0.8-3% of emulsifier, and 0-0.1% of complexing agent , stabilizer 0‑0.3%, osmotic pressure regulator 1‑3%. The composition does not contain ethanol as a solubilizing agent, co-emulsifiers such as Tween-80, and co-solvents such as benzyl alcohol.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a composition injection of the invention, a preparation method thereof and non-clinical safety. Background technique

[0002] Nimodipine (Nim), also known as Nimotop, is a second-generation pyridine calcium antagonist. Nimodipine injection was developed and listed by Bayer, Germany in April 1985. At present, There are more than 100 manufacturers in my country. Because of its high lipophilicity, it easily penetrates the blood-brain barrier, selectively expands cerebral blood vessels, and significantly reverses the spasm of the basilar artery and anterior spinal artery. It is clinically used to treat hypertension, stroke, migraine, and spider webs. Submembranous hemorrhage and other cerebral hemorrhage diseases are the first choice drugs for cerebrovascular treatment, especially for senile dementia with high clinical application value.

[0003] In the prior art, clinically commonly...

Examples

Embodiment 1

[0057] Nimodipine 1g, soybean oil 40g, medium-chain triglycerides 60g, lecithin 12g, edetate disodium 0.05g, oleic acid 0.3g, glycerin 22.5g, pH regulator amount, water for injection up to 1000ml. The method is as follows:

[0058] (1) Take the prescribed amount of water for injection, adjust the pH with 2% sodium hydroxide solution, add disodium edetate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C:

[0059] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, add 40% of the prescription amount of lecithin and oleic acid for shearing and mixing, heat it in a water bath to 50-70°C, add the prescription amount of nimodipine and stir to make it dissolve.

[0060] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0061] (4) Slowly add the oil phase to th...

Embodiment 2

[0067] Nimodipine 1.5g, soybean oil 40g, medium-chain triglycerides 60g, lecithin 12g, edetate disodium 0.05g, oleic acid 0.3g, glycerin 22.5g, pH regulator amount, water for injection up to 1000ml. The method is as follows:

[0068] (1) Take the prescribed amount of water for injection, adjust the pH with 2% sodium hydroxide solution, add disodium edetate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C:

[0069] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, add 40% of the prescription amount of lecithin and oleic acid for shearing and mixing, heat it in a water bath to 50-70°C, add the prescription amount of nimodipine and stir to make it dissolve.

[0070] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0071] (4) Slowly add the oil phase to ...

Embodiment 3

[0077] 0.2g of nimodipine, 50g of soybean oil, 8g of lecithin, 0g of calcium sodium edetate, 0.2g of sodium oleate, 25g of glycerin, an appropriate amount of pH regulator, and up to 1000ml of water for injection. The method is as follows:

[0078] (1) Take the prescribed amount of water for injection, adjust the pH, add sodium oleate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C.

[0079] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, heat it in a water bath to 50-70°C, add 40% of the prescription amount of lecithin, shear and mix evenly, add the prescription amount of nimodipine and stir to dissolve it.

[0080] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0081] (4) Slowly add the oil phase to the water phase, and cut to make colostrum.

...

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a composition injection of the invention, a preparation method thereof and non-clinical safety. Background technique

[0002] Nimodipine (Nim), also known as Nimotop, is a second-generation pyridine calcium antagonist. Nimodipine injection was developed and listed by Bayer, Germany in April 1985. At present, There are more than 100 manufacturers in my country. Because of its high lipophilicity, it easily penetrates the blood-brain barrier, selectively expands cerebral blood vessels, and significantly reverses the spasm of the basilar artery and anterior spinal artery. It is clinically used to treat hypertension, stroke, migraine, and spider webs. Submembranous hemorrhage and other cerebral hemorrhage diseases are the first choice drugs for cerebrovascular treatment, especially for senile dementia with high clinical application value.

[0003] In the prior art, clinically commonly...

Examples

Embodiment 1

[0057] Nimodipine 1g, soybean oil 40g, medium-chain triglycerides 60g, lecithin 12g, edetate disodium 0.05g, oleic acid 0.3g, glycerin 22.5g, pH regulator amount, water for injection up to 1000ml. The method is as follows:

[0058] (1) Take the prescribed amount of water for injection, adjust the pH with 2% sodium hydroxide solution, add disodium edetate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C:

[0059] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, add 40% of the prescription amount of lecithin and oleic acid for shearing and mixing, heat it in a water bath to 50-70°C, add the prescription amount of nimodipine and stir to make it dissolve.

[0060] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0061] (4) Slowly add the oil phase to th...

Embodiment 2

[0067] Nimodipine 1.5g, soybean oil 40g, medium-chain triglycerides 60g, lecithin 12g, edetate disodium 0.05g, oleic acid 0.3g, glycerin 22.5g, pH regulator amount, water for injection up to 1000ml. The method is as follows:

[0068] (1) Take the prescribed amount of water for injection, adjust the pH with 2% sodium hydroxide solution, add disodium edetate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C:

[0069] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, add 40% of the prescription amount of lecithin and oleic acid for shearing and mixing, heat it in a water bath to 50-70°C, add the prescription amount of nimodipine and stir to make it dissolve.

[0070] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0071] (4) Slowly add the oil phase to ...

Embodiment 3

[0077] 0.2g of nimodipine, 50g of soybean oil, 8g of lecithin, 0g of calcium sodium edetate, 0.2g of sodium oleate, 25g of glycerin, an appropriate amount of pH regulator, and up to 1000ml of water for injection. The method is as follows:

[0078] (1) Take the prescribed amount of water for injection, adjust the pH, add sodium oleate and stir to dissolve, then add glycerin, stir and mix evenly. The water temperature is controlled at 50-70°C.

[0079] (2) Take the prescription amount of soybean oil and mix it with medium-chain triglycerides, heat it in a water bath to 50-70°C, add 40% of the prescription amount of lecithin, shear and mix evenly, add the prescription amount of nimodipine and stir to dissolve it.

[0080] (3) Weigh 60% of the prescribed amount of lecithin, add it into the water phase, and under the protection of nitrogen, shear the emulsifier until it is uniformly dispersed.

[0081] (4) Slowly add the oil phase to the water phase, and cut to make colostrum.

...

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