Lyophilized preparation of prostaglandin E1 methyl ester for injection and production and use thereof
The disclosure provides a lyophilized preparation of prostaglandin E1 methyl ester for injection and production and use thereof. The lyophilized preparation comprises the following components by weight: 0.1-10 parts of prostaglandin E1 methyl ester, 500-4000 parts of an oil for injection, 500-2000 parts of an emulsifier, 0-10 parts of a co-emulsifier, 5000-50000 parts of a lyoprotectant, and 200-1500 parts of glycerin. The prostaglandin E1 methyl ester lyophilized agent of the disclosure has less blood vessel irritation, good drug stability, and superior drug activity and therapeutic effect than similar prostaglandin E1 products.
1 . A method for producing a lyophilized preparation of prostaglandin E1 methyl ester for injection, wherein the method includes producing the lyophilized preparation with the following components as raw materials in weight percentage: 0.0001-0.01% of prostaglandin E1 methyl ester, 0.5-4% of an oil for injection, 0.5-1.5% of an emulsifier, 0-0.01% of a co-emulsifier, 5-50% of a lyoprotectant, 0.2-1.5% of glycerin, pH adjuster, and a balance of water for injection; the amount of the pH adjusting agent is such that the pH of the mixed solution is adjusted to 4.5-6.5 when the mixed solution is made up to the full volume with water for injection; the emulsifier is lecithin; the oil for injection is selected from one or more of soybean oil, olive oil, tea oil, corn oil, or castor oil; the co-emulsifier is selected from one or more of oleic acid, palmitic acid, stearic acid, linolenic acid, linoleic acid, and sodium oleate; the lyoprotectant is selected from one or more of lactose, sucrose, trehalose, mannitol, glucose, and maltose;
The method includes the following steps:
a. dispersing prostaglandin E1 methyl ester and ⅓ of the emulsifier uniformly in an oily solvent as an oil phase;
b. dissolving glycerin and the lyoprotectant and the remaining emulsifier in water for injection as a water phase, and adjusting the pH of the water phase to 4.5-6.5 with a pH regulator;
c. dissolving the co-emulsifier in the oil or water phase;
d. adding the oil phase to the water phase under stirring, or adding the water phase to the oil phase under stirring, and obtaining an initial emulsion by shearing, then diluting to full volume with water for injection;
e. homogenizing the initial emulsion to obtain a uniform emulsion; and
f. sterilizing the obtained emulsion by filtration, packing, lyophilizing, and sealing to obtain the lyophilized preparation,
wherein the lyophilizing includes pre-freezing at −50° C. to −35° C. for 100-200 minutes, and then vacuuming at 70-90 mTorr for 420-540 minutes at −25° C. to −15° C., then vacuuming at 50-70 mTorr for 240-360 minutes at 5° C. to 15° C., and then vacuuming at 35-45 mTorr for 300-420 minutes at 35° C. to 45° C.,
wherein the average particle size after lyophilizing is less than 100 nm and greater than or equal to about 77 nm; and
wherein the lyophilized preparation comprises the following components as raw materials by weight: 0.1-10 parts of prostaglandin E1 methyl ester, 500-4000 parts of soybean oil, 500-1500 parts of lecithin, 0-10 parts of sodium oleate, 5000-20000 parts of lactose, 20-1500 parts of glycerin, an appropriate amount of sodium citrate or hydrochloric acid, and a balance of water for injection based on 100×10 3 parts of the total weight of raw materials.
2 . The method according to claim 1 , wherein step d comprises shearing at a constant temperature of 20° C.-50° C.
3 . A lyophilized preparation of prostaglandin E1 methyl ester for injection, wherein the lyophilized preparation is prepared by the method of claim 1 .