CN105147609A - Diethylstilbestrol fat emulsion injection - Google Patents
Diethylstilbestrol fat emulsion injection Download PDFInfo
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- CN105147609A CN105147609A CN201510710954.6A CN201510710954A CN105147609A CN 105147609 A CN105147609 A CN 105147609A CN 201510710954 A CN201510710954 A CN 201510710954A CN 105147609 A CN105147609 A CN 105147609A
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Abstract
The invention relates to a diethylstilbestrol fat emulsion injection. The diethylstilbestrol fat emulsion injection is prepared from 0.1-100 mg of diethylstilbestrol, 20-50 g of seal oil for injection, 10-40 g of lecithin, 4-10 g of glycerin, 1-10 mg of EDTA and 850-990 g of water for injection. The homogeneous diethylstilbestrol fat emulsion injection is prepared by adopting medicine-carrying fat emulsion, emulsion droplet particles are even in the long-time standing process, and the stability and safety are higher.
Description
Technical field
The invention belongs to medical art, specifically, the present invention relates generally to a kind of diethylstilbestrol fat emulsion injection and preparation method thereof.
Background technology
Diethylstilbestrol is a kind of nonsteroidal estrogens (estrogen) of synthesis, be a kind of in 1938 by the nonsteroidal estrogen of synthetic synthesized first, it is designed to the castrate levels (castratelevels) realizing Testosterone.Androgen impels the growth of carcinoma of prostate, and removing androgen by surgical operation castration is the first Androgen deprivation therapy in prostate cancer therapy.By suppressing testis to produce androgen, DES is developed for realizing androgen deprivation.
Diethylstilbestrol is used to the treatment of Androgen-dependent type and androgen independent prostate cancer.The manufacturing expense of diethylstilbestrol is cheap, and the estrogens of its biological property and naturally occurring costliness seemingly.
Oral diethylstilbestrol, has the first pass effect of intestinal and liver, causes the high hormone concentration promoting blood coagulating protein as fibrinogenic synthesis in liver, there is thromboembolism toxicity.This makes employing 3mg every day as the most frequently used DES oral dose being used for the treatment of carcinoma of prostate.But thromboembolism toxicity remains a problem.
Diethylstilbestrol tool is fat-soluble and water insoluble.Indissoluble or the medicine that is slightly soluble in water are made rapid delivery preparation, and avoid the harmful side effect that first pass effect causes, conventional method comprises makes intravenous formulations simultaneously.
Indissoluble or the medicine that is slightly soluble in water are made intravenous formulations, and conventional solution has: 1. make soluble-salt; 2. add cosolvent; 3. use mixed solvent; 4. use solubilizing agent.
Be formally approved for since clinical in Sweden from blank fat milk Intralipid in 1961, auxotype fat milk used for intravenous injection is used widely, and it is used as the important component part of parenteral nutrition, for critical patient provides nutrition.And in recent years, along with the needs of disease treatment and going deep into further of research, the research of fat milk is no longer confined in the application of parenteral nutrition, medicine is dissolved in the drug-loaded emulsion making 100-1000nm in fatty oil through lecithin emulsifying redispersion in aqueous phase, the selectivity of route of administration can be increased, be widely used in the aspects such as intravenous injection, pulmonary, eye and nasal-cavity administration.In pastille fat emulsion injection, most of drug distribution, at oil phase or oil-water interfaces, is avoided directly contacting with water, for facile hydrolysis or the medicine to water sensitive, serves the effect increasing stability.Fat milk avoids introduces organic solvent generation intravenous injection zest.
But not all insoluble drug all can be made into fat emulsion injection, and when also may there is dilution medicine separate out, injection site pain or cause phlebitis, additives produce the problem such as toxicity to human body.Therefore, the fat emulsion injection of exploitation diethylstilbestrol is valuable, needs to overcome a large amount of technical problems simultaneously.
Technical scheme
Diethylstilbestrol fat emulsion injection, prepared by following component and obtain:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram
Technical scheme of the present invention is preferably as follows:
Diethylstilbestrol fat emulsion injection, prepared by following component and obtain:
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
The preferred Ovum Gallus domesticus Flavus lecithin of lecithin.
Injection seal oil soybean oil, Semen Maydis oil are replaced.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection soybean oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
Diethylstilbestrol 0.1-100 milligram, injection Semen Maydis oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
The present invention relates to diethylstilbestrol fat emulsion injection, preparation technology is as follows:
The preparation of feed proportioning system: whole feed proportioning system boiling water 115 DEG C ~ 121 DEG C high temperature sterilize process, gets rid of the air in whole feed proportioning system, and with nitrogen displacement, 3 ~ 5 times so repeatedly;
The preparation of water for subsequent use: put into appropriate water for injection in colostrum tank, inflated with nitrogen drives oxygen, insulation 50-60 DEG C, for subsequent use;
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C ~ 121 DEG C high temperature sterilize 15min, be cooled to 50-60 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50-60 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, takes diethylstilbestrol, injection seal oil in oil phase tank, opens nitrogen from bottom bubbling, stir, be heated to 50 DEG C ~ 60 DEG C, under the protection of nitrogen current, slowly add lecithin, high-speed stirred is uniformly dispersed to lecithin;
Colostric fluid is prepared: by oil phase and aqueous phase according to a certain percentage (1:5-1:20) mixed by emulsification pump, benefit adds to the full amount of water for injection, control temperature 50 DEG C ~ 60 DEG C, regulates colostrum pH to 8.0 ~ 8.5 with sodium hydroxide;
Fill nitrogen fill: homogeneous latex emulsion is filtered fill under nitrogen current protection, in cleaning in infusion bottle with conventional method, rolling plug, sealing, makes remaining oxygen in bottle be less than 3%; Described filtration is through 5 μm of microporous filter membrane mistakes.
Rotate sterilizing: after rolling lid, bottled emulsion is put in high steam rotation sterilizing cabinet, and 115 DEG C ~ 121 DEG C hot pressing rotate sterilizing 30 ~ 45 minutes.
The present invention relates to diethylstilbestrol fat emulsion injection, preparation technology is as follows:
High pressure homogenize: make colostric fluid under nitrogen current protection, between two tanks, by homogenizer, regulate certain pressure and temperature, carry out homogenizing, pressure adopts one-step valve pressure 150bar, secondary valve pressure 500bar, by colostrum homogenizing (2-6 time) repeatedly, is 8.0 ~ 8.5 to medicinal liquid pH, temperature 50 C ~ 60 DEG C, newborn grain is qualified;
Lower pressure homogenisation: unload first class pressure, adjustment secondary pressure is 80bar, is cooled to 28 ~ 32 DEG C through heat exchanger.
The present invention relates to diethylstilbestrol fat emulsion injection, preparation technology is as follows:
The preparation of oil phase: oil phase tank drying with steam; take diethylstilbestrol, injection seal oil, oleic acid or, enuatrol or, vitamin E is in oil phase tank; open nitrogen from bottom bubbling; stir; be heated to 30 DEG C ~ 50 DEG C; under the protection of nitrogen current, slowly add lecithin, high-speed stirred is uniformly dispersed to lecithin.
Technique preferred process:
Diethylstilbestrol crude drug is put into respectively the calorstat of 30 DEG C-70 DEG C, respectively at sampling in the 0th, 5,10 day, it is appropriate that precision measures diethylstilbestrol crude drug, adds methanol dilution to every 1mL about containing the solution of diethylstilbestrol 0.1mg.HPLC measures the changes of contents of diethylstilbestrol.
Diethylstilbestrol is under 30 DEG C of-70 DEG C of temperature conditions, and after 55 DEG C, decompose generation impurity obviously increases.
The oily kind of use of diethylstilbestrol fat emulsion injection and the optimization (N=3, X ± s) of consumption.
Diethylstilbestrol 0.4mg, injection seal oil 10-100g,
Diethylstilbestrol 0.4mg, injection medium chain triglyceride 10-100g.
Diethylstilbestrol 0.4mg, injection seal oil 5-50g, injection medium chain triglyceride 5-50g,
Diethylstilbestrol 0.4mg, injection seal oil 5-50g, injection medium chain triglyceride 5-50g,
Prepare drug-loaded emulsion agent, precondition is that principal agent should have a certain amount of dissolubility in oil for injection.Otherwise stable drug-loaded emulsion agent cannot be prepared.Diethylstilbestrol fat emulsion injection of the present invention, plan is a kind of drug-loaded emulsion agent of long term storage, at least should stablize in 2 years.Therefore must ensure that selected oil for injection has enough dissolubility to diethylstilbestrol, and stability, also need the drug loading improving oil for injection.
The process modification of the oil phase of diethylstilbestrol fat emulsion injection
In this research, directly diethylstilbestrol and phospholipid are joined in oil phase, 55 DEG C heating 1.0h after still have insoluble matter, illustrate that medicine is not dissolved in oil phase completely, and high temperature dissolve for a long time the chemical stability of diethylstilbestrol also very unfavorable.First be dissolved in appropriate dehydrated alcohol by diethylstilbestrol and Ovum Gallus domesticus Flavus lecithin, 50-60 DEG C of heating 0.5h, then flings to ethanol and adds oil phase under nitrogen current.Experimental result shows, and medicine and Ovum Gallus domesticus Flavus lecithin all dissolve rapidly and completely, can avoid the degraded that phospholipid and medicine long-time heating cause, and can obtain the medicine carrying oil phase clarified, and stores 72 hours and keep clarification under the refrigerated condition of 4-6 DEG C.
The dehydrated alcohol of diethylstilbestrol fat emulsion injection and the optimization (N=3, X ± s) of heating-up temperature.
Diethylstilbestrol 0.4mg, Ovum Gallus domesticus Flavus lecithin 8g, injection seal oil 8g, 35 DEG C of heating 0.5h
Diethylstilbestrol 0.4mg, Ovum Gallus domesticus Flavus lecithin 8g, dehydrated alcohol 0.5g, injection seal oil 8g, 40 DEG C of heating 0.5h
Diethylstilbestrol 0.4mg, Ovum Gallus domesticus Flavus lecithin 8g, dehydrated alcohol 1g, injection seal oil 8g, 35 DEG C of heating 0.5h
Diethylstilbestrol 0.4mg, Ovum Gallus domesticus Flavus lecithin 8g, dehydrated alcohol 2g, injection seal oil 8g, 30 DEG C of heating 0.5h
The optimization (N=3, X ± s) of the lecithin consumption of diethylstilbestrol fat emulsion injection.
Diethylstilbestrol 2mg, injection seal oil 40g, dehydrated alcohol 2g, oleic acid 2g, glycerol 5g, Ovum Gallus domesticus Flavus lecithin 1-40g, water for injection adds to 500mL.
When the content of Ovum Gallus domesticus Flavus lecithin is increased to a certain degree, fat milk particle diameter no longer reduces, and forms saturation, and Ovum Gallus domesticus Flavus lecithin is preferably 20g/1000ml.
The optimization (N=3, X ± s) of the oleic acid consumption of diethylstilbestrol fat emulsion injection.
Diethylstilbestrol 2mg, injection seal oil 40g, dehydrated alcohol 2g, oleic acid 0.5-8g, glycerol 5g, Ovum Gallus domesticus Flavus lecithin 10g, water for injection adds to 500mL.
When the content of oleic acid is increased to a certain degree, fat milk particle diameter no longer reduces, and forms saturation, and oleic acid is preferably 4g/1000ml.
The formulation optimization of diethylstilbestrol fat emulsion injection.
By experiment of single factor, evaluate with the index such as outward appearance, particle diameter, study and inquired into stabilizing agent and antioxidant to the impact of diethylstilbestrol fat emulsion injection.
Diethylstilbestrol 2mg, injection seal oil 40g, dehydrated alcohol 2g, oleic acid 2g, glycerol 5g, Ovum Gallus domesticus Flavus lecithin 8g, EDTA (0-4mg), VE (0-4g), water for injection adds to 500mL.40 DEG C of placements quality evaluation of 10 days.
Homogenization pressure preferred
Medicinal liquid raw material forms: diethylstilbestrol 2mg, injection seal oil 40g, dehydrated alcohol 2g, oleic acid 2g, glycerol 5g, Ovum Gallus domesticus Flavus lecithin 8g, EDTA2mg, VE2g, water for injection adds to 500mL.
High pressure homogenize: make colostric fluid under nitrogen current protection, between two tanks, by homogenizer, regulate certain pressure and temperature, carry out homogenizing, pressure adopts one-step valve pressure (100,150,200) bar, secondary valve pressure (500,550,600) bar, by colostrum homogenizing (3 times) repeatedly, is 8.0 ~ 8.5 to medicinal liquid pH, temperature 50 C ~ 60 DEG C, newborn grain is qualified;
Get colostric fluid 500mL9 gram and carry out pressure preferably, evaluation index comprises: the percent accounting for more than 100nm particle with more than 200-300nm particle.
Homogenize temperature, number of times preferred
Medicinal liquid forms: diethylstilbestrol 2mg, injection seal oil 40g, dehydrated alcohol 2g, oleic acid 2g, glycerol 5g, Ovum Gallus domesticus Flavus lecithin 8g, EDTA2mg, VE2g, water for injection adds to 500mL.
High pressure homogenize: make colostric fluid under nitrogen current protection, between two tanks, by homogenizer, regulate certain pressure and temperature, carry out homogenizing, pressure adopts one-step valve pressure 150bar, secondary valve pressure 500bar, by colostrum homogenizing (2,3,4 times) repeatedly, is 8.0 ~ 8.5 to medicinal liquid pH, temperature (45,50,55,60,65) DEG C, newborn grain is qualified;
Get colostric fluid 500mL9 gram and carry out pressure preferably, evaluation index comprises: the percent accounting for more than 100nm particle with more than 200-300nm particle.
Specific embodiments
Embodiment 1
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, appropriate dehydrated alcohol, injection seal oil 80 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of feed proportioning system: whole feed proportioning system boiling water 115 DEG C of high temperature sterilize process, gets rid of the air in whole feed proportioning system, and with nitrogen displacement, 3 times so repeatedly;
The preparation of water for subsequent use: put into appropriate water for injection in colostrum tank, inflated with nitrogen drives oxygen, is incubated 40 DEG C, for subsequent use;
The preparation of aqueous phase: get water for injection 10%, glycerol, puts in aqueous phase tank, and 115 DEG C of high temperature sterilize 15min, are cooled to 50 DEG C, are mixed homogeneously with water for subsequent use by filter, continues inflated with nitrogen and drives oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 50 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
Colostric fluid is prepared: by oil phase and aqueous phase according to a certain percentage (1:15) mixed by emulsification pump, benefit adds to the full amount of water for injection, control temperature 35 DEG C, regulates colostrum pH to 8.2 with sodium hydroxide;
High pressure homogenize: make colostric fluid under nitrogen current protection, between two tanks, by homogenizer, regulate certain pressure and temperature, carry out homogenizing, pressure adopts one-step valve pressure 150bar, secondary valve pressure 500bar, by colostrum homogenizing (3 times) repeatedly, is 8.0 to medicinal liquid pH, temperature 50 C, newborn grain is qualified;
Lower pressure homogenisation: unload first class pressure, adjustment secondary pressure is 80bar, is cooled to 28 DEG C through heat exchanger.
Fill nitrogen fill: homogeneous latex emulsion is filtered fill under nitrogen current protection, in cleaning in infusion bottle with conventional method, rolling plug, sealing, makes remaining oxygen in bottle be less than 3%; Described filtration is through 5 μm of microporous filter membrane mistakes.
Rotate sterilizing: after rolling lid, bottled emulsion is put in high steam rotation sterilizing cabinet, and 115 DEG C of pressures rotate sterilizing 30 minutes.
Embodiment 2
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 80 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, enuatrol 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, enuatrol in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 35 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 3
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 80 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, oleic acid in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 4
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 80 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, enuatrol 5 grams, vitamin E 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, enuatrol, vitamin E in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 35 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 5
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 80 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, vitamin E 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, vitamin E in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 6
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 80 grams, medium chain triglyceride 10 grams, Ovum Gallus domesticus Flavus lecithin 10 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, medium chain triglyceride in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 7
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 20 grams, medium chain triglyceride 25 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, enuatrol 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, medium chain triglyceride, enuatrol in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 8
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 20 grams, medium chain triglyceride 25 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, medium chain triglyceride, oleic acid in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 9
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection seal oil 20 grams, medium chain triglyceride 25 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, vitamin E 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection seal oil, appropriate dehydrated alcohol, medium chain triglyceride, oleic acid, vitamin E in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 10
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection soybean oil 20 grams, medium chain triglyceride 25 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, vitamin E 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection soybean oil, medium chain triglyceride, oleic acid, vitamin E in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 11
The raw material composition of diethylstilbestrol fat emulsion injection: diethylstilbestrol 5 milligrams, injection Semen Maydis oil 20 grams, medium chain triglyceride 25 grams, Ovum Gallus domesticus Flavus lecithin 20 grams, oleic acid 5 grams, vitamin E 5 grams, glycerol 10 grams, EDTA5 milligram, injects with 100 grams, water.
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C of high temperature sterilize 15min, be cooled to 50 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, take diethylstilbestrol, injection Semen Maydis oil, medium chain triglyceride, oleic acid, vitamin E in oil phase tank, open nitrogen from bottom bubbling, stir, be heated to 45 DEG C, fling to ethanol, under the protection of nitrogen current, slowly add Ovum Gallus domesticus Flavus lecithin, high-speed stirred is uniformly dispersed to Ovum Gallus domesticus Flavus lecithin;
All the other preparation processes are with embodiment 1.
Embodiment 12
Fat emulsion injection of the present invention has good stability and clinical safety, / long chain fat emulsion injection (C8 ~ 24) is prepared in the present invention according to embodiment 1-11, sterilising conditions selects 117 DEG C of hot pressing to rotate sterilizing 35min, obtains product 1-10 of the present invention.Place it in room temperature environment, respectively at when just placing, place the inspection of 3,6,12,24 months sample thiefs, observe its character and measure pH value, newborn grain, aseptic, medium chain triglyceride content, fat content, lysophosphatide and diethylstilbestrol value, result of the test is as follows:
Fat emulsion injection of the present invention is after room temperature deposits 24 months, and product characteristics do not change.
Breast grain is less, more even.Be not greater than the newborn grain of 500nm, the newborn grain of 200 ~ 300nm accounts for more than 98.7%.Microorganism is all qualified.Injection seal oil, injection soybean oil, injection Semen Maydis oil, medium chain triglyceride content are with depositing preliminary phase than substantially not changing.Lysophosphatide content, diethylstilbestrol, and deposit preliminary phase than substantially not changing.
Product 1-11 Hypersensitive tests result of the present invention is negative.Product 1-11 hemolytic test result of the present invention is negative.Intravenous drip product of the present invention 1-11 is without obvious vascular stimulation effect.
Diethylstilbestrol fat emulsion injection selectivity delivery of active medicine of the present invention, avoids gastrointestinal irritation and activating agent inactivation in the gastrointestinal tract.When without gastrointestinal tract inactivation, less activating agent can produce therapeutic effect.In addition, diethylstilbestrol fat emulsion injection rapid delivery of pharmaceuticals activating agent of the present invention, it to be conveyed into rapidly in blood stream of patients, improves bioavailability, rapid action.
Claims (10)
1. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
2. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
3. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 50-200 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
4. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
5. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, EDTA1-10 milligram, water for injection 800-990 gram.
6. a diethylstilbestrol fat emulsion injection, is characterized in that: be made up of following component:
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, enuatrol 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, water for injection 800-990 gram; Or;
Diethylstilbestrol 0.1-100 milligram, appropriate dehydrated alcohol, injection seal oil 25-100 gram, medium chain triglyceride 25-100 gram, lecithin 10-20 gram, oleic acid 1-10 gram, glycerol 10-30 gram, vitamin e1-10 grams, EDTA1-10 milligram, water for injection 800-990 gram.
7. according to the diethylstilbestrol fat emulsion injection of claim 1-6, it is characterized in that: lecithin is Ovum Gallus domesticus Flavus lecithin, injection seal oil with soybean oil or, Semen Maydis oil replace.
8., according to the diethylstilbestrol fat emulsion injection of claim 1-6, it is characterized in that:
Preparation technology is as follows:
The preparation of feed proportioning system: whole feed proportioning system boiling water 115 DEG C ~ 121 DEG C high temperature sterilize process, gets rid of the air in whole feed proportioning system, and with nitrogen displacement, 3 ~ 5 times so repeatedly;
The preparation of water for subsequent use: put into appropriate water for injection in colostrum tank, inflated with nitrogen drives oxygen, is incubated 50 ~ 60 DEG C, for subsequent use;
The preparation of aqueous phase: get water for injection 10%, glycerol, EDTA, puts in aqueous phase tank, 115 DEG C ~ 121 DEG C high temperature sterilize 15min, be cooled to 50 ~ 60 DEG C, mixed homogeneously with water for subsequent use by filter, continue inflated with nitrogen and drive oxygen, add sodium hydroxide solution mix homogeneously, be incubated to 50 ~ 60 DEG C, for subsequent use;
The preparation of oil phase: drying with steam oil phase tank, takes diethylstilbestrol, injection seal oil in oil phase tank, opens nitrogen from bottom bubbling, stir, be heated to 50 DEG C ~ 60 DEG C, under the protection of nitrogen current, slowly add lecithin, high-speed stirred is uniformly dispersed to lecithin;
Colostric fluid is prepared: oil phase and aqueous phase are mixed by emulsification pump according to a certain percentage, benefit adds to the full amount of water for injection, control temperature 50 DEG C ~ 60 DEG C, regulates colostrum pH to 8.0 ~ 8.5 with sodium hydroxide;
Fill nitrogen fill: homogeneous latex emulsion is filtered fill under nitrogen current protection, in cleaning in infusion bottle with conventional method, rolling plug, sealing, makes remaining oxygen in bottle be less than 3%; Described filtration is through 5 μm of microporous filter membrane mistakes;
Rotate sterilizing: after rolling lid, bottled emulsion is put in high steam rotation sterilizing cabinet, and 115 DEG C ~ 121 DEG C hot pressing rotate sterilizing 30 ~ 45 minutes.
9., according to the diethylstilbestrol fat emulsion injection of claim 1-6, it is characterized in that:
Preparation technology is as follows:
High pressure homogenize: make colostric fluid under nitrogen current protection, between two tanks, by homogenizer, regulate certain pressure and temperature, carry out homogenizing, pressure adopts one-step valve pressure 150bar, secondary valve pressure 500bar, by colostrum homogenizing (2-6 time) repeatedly, is 8.0 ~ 8.5 to medicinal liquid pH, temperature 50 ~ 60 DEG C, newborn grain is qualified;
Lower pressure homogenisation: unload first class pressure, adjustment secondary pressure is 80bar, is cooled to 28 ~ 32 DEG C through heat exchanger.
10. diethylstilbestrol fat emulsion injection according to claim 8, is characterized in that:
The preparation of oil phase: oil phase tank drying with steam; take diethylstilbestrol, injection seal oil, oleic acid or, enuatrol or, vitamin E is in oil phase tank; open nitrogen from bottom bubbling; stir; be heated to 30 DEG C ~ 50 DEG C; under the protection of nitrogen current, slowly add lecithin, high-speed stirred is uniformly dispersed to lecithin.
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