Freeze-dried alprostadil composition for injection and preparation method thereof

A technology of alprostadil and its composition, which is applied in the field of alprostadil freeze-dried composition for injection and its preparation, can solve the problems of destroying red blood cell membrane, increasing concentration, vascular irritation, etc., and achieves high safety, low concentration, Effect of small change in particle size

Inactive Publication Date: 2014-08-06
SHANGHAI INST OF PHARMA IND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

We have found through a large number of studies that co-emulsifiers can significantly increase the solubility of alprostadil in the aqueous phase, thereby increasing the concentration of free alprostadil in the external water phase of the microemulsion, and free alprostadil can cause vascular irritation, and free alprostadil Dil has low storage stability and is more prone to degradation
At the same time, oleate or bile salt is an ionic surfactant, which has the potential risk of damaging the red blood cell membrane in the body

Method used

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  • Freeze-dried alprostadil composition for injection and preparation method thereof
  • Freeze-dried alprostadil composition for injection and preparation method thereof
  • Freeze-dried alprostadil composition for injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034]Weigh 0.9g of Solutol HS 15, 0.3g of lecithin E80, and 1.5g of medium-chain triglycerides, mix well, heat and stir to disperse the phospholipids evenly, add 0.5mg of alprostadil, stir to dissolve, and use it as the oil phase; Mannitol 5g, dissolved in 80ml of water for injection, as the water phase; slowly add the water phase into the oil phase under stirring, add about 2mL of 0.1mol / L hydrochloric acid, adjust the pH to 5, add water for injection to 100mL, and pass through 0.22μm Membrane filtration, sub-package according to 1mL / cartridge, freeze-drying, capping, packaging, to obtain.

Embodiment 2

[0036] Weigh 3g of Solutol HS 15, 1.5g of medium-chain triglycerides, mix well, add 0.5mg of alprostadil, stir to dissolve, and use it as the oil phase; weigh 4g of lactose, 0.01g of calcium sodium edetate, dissolve in 80ml In water for injection, as the water phase; slowly add the water phase to the oil phase under stirring, add 0.1mol / L hydrochloric acid and sodium hydroxide solution to adjust the pH to 6, supplement water for injection to 100mL, filter through a 0.22μm filter membrane, and 1mL / cartridge, freeze-dried, capped, packaged, ready to use.

Embodiment 3

[0038] Weigh 0.4g of Solutol HS 15, 0.1g of lecithin E80, and 0.5g of medium-chain triglycerides, mix well, heat and stir to disperse the phospholipids evenly, add 0.2mg of alprostadil, stir to dissolve, and use it as the oil phase; Dissolve 1 g of sorbitol, 4 g of glucose, and 0.001 g of edetate disodium in 80 ml of water for injection as the water phase; slowly add the water phase into the oil phase while stirring, add water for injection to 100 mL, and filter through a 0.22 μm filter membrane. Subpackage according to 1mL / cartridge, freeze-dry, press cap, pack, and get ready.

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Abstract

The invention relates to the technical field of a freeze-dried alprostadil composition for injection and a preparation method thereof. The freeze-dried alprostadil composition for injection comprises, by weight, 0.001 to 0.05 part of alprostadil, 1 to 50 parts of an emulsifier which is polyethylene glycol hydroxystearate or a mixture of polyethylene glycol hydroxystearate and phosphatide, 1 to 50 parts of medium chain triglyceride and 10 to 200 parts of other pharmaceutical adjuvant. According to stability test, the freeze-dried alprostadil composition can be stored in a shade place for 2 years, and the content of PGA1 is lower than 10%; the particle size of the composition changes a little before and after freeze-drying; after redissolving, the freeze-dried alprostadil composition appears to be transparent or has little opalescence, visible foreign matters can be inspected, and the redissolved composition has an average particle size of 10 to 100 nm, contains no emulsion droplet with a size of greater than 1 mu m and does not cause embolism of capillary vessels; the freeze-dried alprostadil composition does not contain short-chain alcohol co-emulsifiers, and the concentration of free alprostadil is low; and the freeze-dried alprostadil composition does not contain cyclodextrin adjuvant and has high security.

Description

technical field [0001] The invention relates to the technical field of an alprostadil freeze-dried composition for injection and a preparation method thereof. Background technique [0002] Alprostadil also known as prostaglandin E1 (PGE1), PGE 1 The chemical name is: (1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-Hydroxy-1-octenyl]-5-oxocyclopentaneheptanoic acid. Alprostadil can increase the level of cyclic adenosine monophosphate (cAMP) in platelets by activating adenylate cyclase, and at the same time inhibit the release of thromboxane A2 (TXA2), so as to inhibit platelet aggregation and prevent thrombosis; By increasing the deformability of red blood cells, stiff red blood cells can easily pass through capillaries, reduce blood viscosity, and improve microcirculation; it can also reduce the cholesterol content of arterial walls and prevent arteriosclerosis. Alprostadil injection is indicated for the treatment of limb ulcers caused by chronic arterial occlusive disease (thromboangi...

Claims

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Application Information

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IPC IPC(8): A61K31/5575A61K9/19A61P7/02A61P9/10
Inventor 金方蔡伟惠
Owner SHANGHAI INST OF PHARMA IND
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