Alprostadil injection and preparation method thereof

Abstract

The invention relates to an alprostadil injection and a preparation method thereof. The alprostadil injection has a prescription as follows: a, a main drug is alprostadil with concentration of 5mu g-15mu g / ml; b, an oil phase is soybean oil with concentration of respectively 10.0-12.0 percent; c, soyabean lecithin and poloxamer 188 are selected as emulsifying agents and have concentrations of respectively 1.0-1.8 percent and 0.02-0.2 percent; d, citric acid is adopted as a pH regulating agent with concentration of 5nM to 50Mm and pH of 5.0-6.0; e, glycerol is adopted as an osmotic pressure regulating agent with concentration of respectively 2.0-2.5 percent; and f, the balance is injection water.

Description

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a safe and stable alprostadil injection and a preparation method thereof. Background technique

[0002] Alprostadil aka prostaglandin E 1 (Alprostadil), whose chemical name is: (1R,2R,3R,)-3-Hydroxy 2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane Heptanoic acid, chemical structural formula:

[0003]

[0004] Alprostadil is an endogenous physiologically active substance with various physiological and pharmacological activities.

[0005] Specific indications are as follows:

[0006] 1. Treat limb ulcers caused by chronic arterial occlusive disease (thromboangiitis obliterans, arteriosclerosis obliterans, etc.) and rest pain in limbs caused by microvascular circulation disturbance. Improve cardiovascular and cerebrovascular microcirculation disorders.

[0007] 2. Antithrombotic therapy after organ transplantation to inhibit thrombosis in blood vessels after tran...

Examples

Embodiment 1

[0056] Add 5mg alprostadil, 12g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 0.8g of poloxamer 188 was added and stirred at a low speed for 5 minutes to form a water phase, and the pH value of the water phase was adjusted to 5.5 with 25mM citric acid; After running, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-fluidic nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12, for the overkill method) to obtain.

Embodiment 2

[0058] Add 5mg alprostadil, 18g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 2g of Poloxamer 188 was added and stirred at low speed for 5 minutes to form a water phase, and the pH value of the water phase was adjusted to 5.5 with 25mM citric acid; Finally, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-jet nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12, for the overkill method) to obtain.

Embodiment 3

[0060] Add 10mg alprostadil, 18g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 2g of poloxamer 188 was added and stirred at a low speed for 5 minutes to form an aqueous phase, and the pH value of the aqueous phase was adjusted to be within 5.5 with 10mM citric acid; the aqueous phase was placed under the working head of a high-shear dispersing emulsifier, After running at high speed, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-fluidic nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12...

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a safe and stable alprostadil injection and a preparation method thereof. Background technique

[0002] Alprostadil aka prostaglandin E 1 (Alprostadil), whose chemical name is: (1R,2R,3R,)-3-Hydroxy 2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane Heptanoic acid, chemical structural formula:

[0003]

[0004] Alprostadil is an endogenous physiologically active substance with various physiological and pharmacological activities.

[0005] Specific indications are as follows:

[0006] 1. Treat limb ulcers caused by chronic arterial occlusive disease (thromboangiitis obliterans, arteriosclerosis obliterans, etc.) and rest pain in limbs caused by microvascular circulation disturbance. Improve cardiovascular and cerebrovascular microcirculation disorders.

[0007] 2. Antithrombotic therapy after organ transplantation to inhibit thrombosis in blood vessels after tran...

Examples

Embodiment 1

[0056] Add 5mg alprostadil, 12g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 0.8g of poloxamer 188 was added and stirred at a low speed for 5 minutes to form a water phase, and the pH value of the water phase was adjusted to 5.5 with 25mM citric acid; After running, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-fluidic nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12, for the overkill method) to obtain.

Embodiment 2

[0058] Add 5mg alprostadil, 18g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 2g of Poloxamer 188 was added and stirred at low speed for 5 minutes to form a water phase, and the pH value of the water phase was adjusted to 5.5 with 25mM citric acid; Finally, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-jet nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12, for the overkill method) to obtain.

Embodiment 3

[0060] Add 10mg alprostadil, 18g soybean lecithin (for injection) and 100g soybean oil into the container, and disperse with high shear for 15 minutes to dissolve to form an oil phase; get another container and add 850g water for injection, and 22g glycerin (for injection) ), 2g of poloxamer 188 was added and stirred at a low speed for 5 minutes to form an aqueous phase, and the pH value of the aqueous phase was adjusted to be within 5.5 with 10mM citric acid; the aqueous phase was placed under the working head of a high-shear dispersing emulsifier, After running at high speed, slowly add the oil phase, emulsify for 20 minutes to form colostrum, and set the volume to 1000ml. Put the colostrum into the feed port of the high-pressure micro-fluidic nano-disperser, and homogenize it for 3 times under the pressure of 18000-20000Psi. Filling, corking, capping. to a rotary water bath sterilizer, and sterilized at 126°C for 4 minutes (verified sterilization F 0 Value greater than 12...

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