CN1596889A - Vitamin E emulsion and its freeze-dried emulsion compound and preparation method - Google Patents
Vitamin E emulsion and its freeze-dried emulsion compound and preparation method Download PDFInfo
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- CN1596889A CN1596889A CN 200410021539 CN200410021539A CN1596889A CN 1596889 A CN1596889 A CN 1596889A CN 200410021539 CN200410021539 CN 200410021539 CN 200410021539 A CN200410021539 A CN 200410021539A CN 1596889 A CN1596889 A CN 1596889A
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Abstract
A VE emulsion and its freeze-dried containing freeze-drying supporting agent are prepared from VE, an oil phase, and emulsifier through proportional mixing and emulsifying (or further freeze frying).
Description
Technical field:
The present invention relates to medical technical field, exactly it is the prescription and the preparation method of a kind of vitamin E Emulsion and freeze-dried emulsion thereof.
Background technology:
Vitamin E is the tocopherol (also available its acetate) with multiple physiologically active.Anti-hemolysis, anticoagulant are arranged, prevent thrombosis, and antioxidation, aging resistance are arranged, prevent arteriosclerosis and effects such as neuropathy, antiinflammatory and prophylaxis of tumours generation.Vitamin E can protect hepatocyte to avoid the infringement of chemical toxicant.During vitamin E deficiency, liver lobule central authorities steatosis, hepatic necrosis can take place in severe patient.Vitimin supplement E has effects such as anti-hepatic fibrosis, anti-fatty liver and hepatic necrosis.Also can treat the steatorrhea that chronic hepatopathy, liver cirrhosis cause.The vitamin E injection records in " Chinese Pharmacopoeia 2000 version two ones ", solvent for use is the injection soybean oil, made injection is an oleo-injection, there is the author to adopt vitamin E injection therapeutic alliance hepatitis gravis (application megavitamin E such as Wang Yafan treatment hepatitis gravis clinical principium is inquired into world Chinese and digested 1999 the 12nd phases the 7th of magazine volume), obtain result preferably, but point out in the literary composition, because the vitamin E injection is the oily injection agent, local absorption is bad after the intramuscular injection, clinical expansion use there is certain harmful effect, more worthlessly be, this injection can not intravenous injection, thereby has limited the clinical practice of vitamin E greatly.Oil concentration in the existing emulsion-type injection is 10%, 20% or 30%, finds that by a large amount of tests oil concentration is high more, and the performance of drug effect is slow more, as be the vitamin K that solvent prepares with 10%, 20% or 30%
1Injection, under Isodose, the docking clotting time of mice obviously is longer than the clotting time of low concentration fat injection, is unfavorable for the clinical treatment application.
Summary of the invention:
The objective of the invention is to produce a kind of vitamin E Emulsion and freeze-dried emulsion thereof, and a kind of feasible preparation method is provided.The vitamin E that contains effective dosage is as medicine, and contains pharmaceutic adjuvant, and pharmaceutic adjuvant comprises: contain freeze drying protectant in oil phase, emulsifying agent, stabilizing agent, osmotic pressure regulator, pH regulator agent, antiseptic (or not containing antiseptic), the freeze-dried emulsion.In the injectable emulsion, medicine: oil (w/w)=1: 0～1: 100 (w/w); The injection freeze-dried emulsion, medicine: oil (w/w)=1: 0～1: 10 (w/w).
Wherein oil phase can be that vitamin E or vitamin E and a certain proportion of line of oils close, and the concentration of oil for injection (oil concentration is below 5%) is significantly smaller than present typical concentrations (oil concentration is 10%, 20%, 30%).After vitamin E is prepared into Emulsion, enlarge the route of administration of medicine, improved medicine stability, safety, accelerated the performance of curative effect of medication, be beneficial to emergence therapeutic.Its prescription and technology are as follows.
Injectable emulsion: contain in every 1-10ml medicinal liquid:
Vitamin E 5～100mg
Oil for injection 0-500mg
Emulsifying agent 10-200mg
Stabilizing agent 1mg-100mg
Glycerol is an amount of
The pH regulator agent is an amount of
The best applications dosage of oil for injection is 50-300mg; Can be the vegetable oil of any kind of, as: one or more mixture in Oleum Glycines, Oleum Camelliae, olive oil, the Flos Carthami wet goods.Granularity is 50nm-1000nm.Emulsifying agent: one or more mixture in phospholipid (soybean lecithin, Ovum Gallus domesticus Flavus lecithin), poloxamer, HS15 (Polyethylene Glycol 12-hydroxy stearic acid ester, polyethylene glycol 660 hydroxystearate as a nonionic solubilizer forinjection solutions), the vitamin E polyethylene glycol succinic acid ester (tocopherol polyethyleneglycol succinate TPGS) etc., consumption is 1-200mg.
Stabilizing agent: one or more mixture in nitrogen, anhydrous sodium sulphuric acid (hydrogen) sodium, sodium thiosulfate, sodium pyrosulfite, vitamin C (Vc), dibenzylatiooluene, the hydroquinone etc., consumption is 1-100mg.
Antiseptic: benzyl alcohol, consumption are 0-10mg.
The pH regulator agent: one or more mixture in hydrochloric acid, sodium hydroxide, sodium acetate, acetic acid, phosphate, the citric acid etc., adjusting pH is 3-9.
The injection freeze-dried emulsion:
Contain in every 1-10ml medicinal liquid:
Vitamin E 5～100mg
Oil for injection 0-50mg
Emulsifying agent 10-200mg
Stabilizing agent 1mg-100mg
The pH regulator agent is an amount of
Antiseptic is an amount of
Freeze drying protectant is an amount of
The best applications dosage of oil for injection is 0-30mg; Can be the vegetable oil of any kind of, as: one or more mixture in Oleum Glycines, Oleum Camelliae, olive oil, the Flos Carthami wet goods.Granularity is 10nm-1000nm.
Emulsifying agent, stabilizing agent, pH regulator agent etc. require identical with Emulsion.
Antiseptic: parabens, consumption are 0-1mg.
Freeze drying protectant: one or more mixture in glucose, lactose, mannitol, sorbitol, xylitol, sucrose, trehalose, dextran, the polyvinylpyrrolidone (PVP) etc., the content of freeze drying protectant is 4%-40% (W/V).
Prepared freeze-dried emulsion is measured on demand and is added water, is recovered to Emulsion, intramuscular injection or intravenously administrable after the hydration vibration.Experimental result shows that the lyophilizing vitamin E Emulsion of the present invention's preparation has improved the stability of vitamin E greatly.
Preparation process is as follows:
1) prepare oil phase (medicine phase) in preparing tank: in preparing tank, oil for injection is heated to 20-90 ℃ when medicine (simple non-refuelling), adds emulsifying agent, strong agitation is to dissolving in the time of 20～50 ℃; Be cooled to 20～40 ℃ again, in stirring, add medicine.
2) in preparing tank, prepare water: water and glycerol are stirred 5min down at 20～90 ℃, make it complete miscibility.
3) in the time of 20～50 ℃, water is added in the oil phase, strong agitation 10～30min forms colostrum.
4) colostrum is crossed G
3The funnel sucking filtration is regulated pH value to 3～9.
5) cross the homogenizing instrument, the first step is regulated homogenize pressure to 520～600kg/cm
2, second step re-adjustment to 100～140kg/cm
2(or the microjet instrument, the first step is regulated homogenize pressure to 4000-8000psi, and the second step re-adjustment is to 10000-16000psi), form Emulsion.Cross microporous filter membrane, packing (add freeze drying protectant, carry out lyophilization, promptly get freeze-dried emulsion), sterilization promptly gets injectable emulsion.
The assay of vitamin E is analyzed with HPLC:
The chromatographic condition of HPLC is: the chromatographic column octadecylsilane chemically bonded silica
Mobile phase methanol-water (98: 2)
Detect wavelength 285nm
Particle size analyzer: use PSS.NICOMP in this experiment
TM380 as the instrument of measuring particle diameter.
Advantage of the present invention is: processing technology is easy, good stability, curative effect height, has significantly improved the stability and the curative effect of vitamin E, for extensive patients provides safer, stable, effective preparation.
The specific embodiment:
Be illustrated with embodiment below, but be not limited to listed embodiment:
Embodiment 1:
Prescription is formed: alpha-tocopherol 0.5g, soybean lecithin 1.2g, glycerol 2.2g, anhydrous sodium sodium bisulfate 0.01g become 100ml altogether.
1) in dosing apparatus, drops into alpha-tocopherol 0.5g;
2), and add 0.01g anhydrous sodium sodium bisulfate with the soybean lecithin of 1.2g, the glycerol of 2.2g (anhydrous) and proper amount of water for injection mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 20, stirring, cross G
3The funnel sucking filtration, (first step is regulated homogenize pressure to 520kg/cm to gained liquid by even matter instrument
2, the second step re-adjustment is to 100/cm
2) (or the microjet instrument, the first step is regulated homogenize pressure to 4000psi, and the second step re-adjustment is to 10000psi), form Emulsion.With solution homogenize repeatedly, obtain uniform solution; Regulating pH with sodium hydroxide and hydrochloric acid is 3.0, makes medicinal liquid 100ml altogether.Cross the 0.45um microporous filter membrane, after the degerming of 0.22um microporous filter membrane, 100 grades are aseptic subpackaged down, every 1ml, and inflated with nitrogen seals, and promptly gets vitamin E injectable emulsion (adding benzyl alcohol 9mg in case of necessity).Granularity is: 50～500nm.Particle mean size 235nm.
Embodiment 2:
Prescription is formed: alpha-tocopherol acetate 1g, injection olive oil 1.0g, Ovum Gallus domesticus Flavus lecithin 1.2g, 0.5gHS15, glycerol 2.2g, anhydrous sodium sodium bisulfate 0.01g become 100ml altogether.
Method is with " embodiment 1 "
1) drops into tocopherol acetate 1.0g, injection olive oil 1.0g, mix homogeneously in the dosing apparatus;
2), and add the 0.01g anhydrous sodium sulfite with the Ovum Gallus domesticus Flavus lecithin of 1.2g, glycerol (anhydrous) and the proper amount of water for injection mix homogeneously of 0.5g HS15,2.2g;
3) with 2) under stirring condition, add 1) in, when 40, stir the back by even matter instrument, with solution homogenize repeatedly (microjet instrument, the first step are regulated homogenize pressure to 8000psi, and the second step re-adjustment is to 16000psi), obtain uniform solution; Regulating pH with sodium hydroxide and acetic acid is 6.0.Homogenizer is handled, and makes medicinal liquid 100ml altogether.Cross the 0.45um microporous filter membrane, after the degerming of 0.22um microporous filter membrane, 100 grades are aseptic subpackaged down, every 1ml, and inflated with nitrogen seals, and promptly gets vitamin E injectable emulsion (adding benzyl alcohol 9mg in case of necessity).
Granularity is: 50～500nm.Particle mean size 156nm.
Embodiment 3:
Prescription is formed: vitamin e1 0g, injection soybean oil 50g, 10gHS15, glycerol 22g, anhydrous sodium sulfite 0.5g, vitamin C 0.1g become 100ml altogether.
Method is with " embodiment 1 "
1) in the dosing apparatus, the 10g vitamin E is dissolved in the 50g injection soybean oil mix homogeneously;
2) with the glycerol (anhydrous) and proper amount of water for injection mix homogeneously of HS15 (Polyethylene Glycol 12-hydroxy stearic acid ester, polyethylene glycol 660hydroxystearate), the 22g of 10g; Add 0.5g anhydrous sodium sulfite, 0.1g vitamin C;
3) with 2) under stirring condition, add 1) in, when 90, stir the back by even matter instrument, with solution homogenize repeatedly (microjet instrument, the first step are regulated homogenize pressure to 7000psi, and the second step re-adjustment is to 14000psi), obtain uniform solution; Regulating pH with sodium hydroxide and phosphoric acid is 6.0.Homogenizer is handled, and makes medicinal liquid 1000ml altogether.Packing, logical nitrogen, every 10ml (10mg); Or 2ml (2mg), flowing steam sterilization 30 minutes promptly gets the vitamin E injectable emulsion.Granularity is: 50～800nm.Particle mean size 367nm.
Embodiment 4:
Prescription is formed: vitamin e1 .0g, BHT0.1g, injection soybean oil 10g, Ovum Gallus domesticus Flavus lecithin 10g, vitamin E polyethylene glycol succinic acid ester 1.0g, glycerol 2.2g become 500ml altogether.
Method is with " example one "
1) in the dosing apparatus, 1.0g vitamin E, 0.1g BHT are dissolved in the 10g injection soybean oil mix homogeneously;
2) with the glycerol (anhydrous) and proper amount of water for injection mix homogeneously of the Ovum Gallus domesticus Flavus lecithin of 10.0g, 1.0g vitamin E polyethylene glycol succinic acid ester (tocopherol polyethyleneglycol succinate TPGS), 2.2g;
3) with 2) under stirring condition, add 1) in, when 50, stir the back by even matter instrument, with solution homogenize repeatedly (microjet instrument, the first step are regulated homogenize pressure to 7000psi, and the second step re-adjustment is to 16000psi), obtain uniform solution; With sodium hydroxide and Fructus Citri Limoniae acid for adjusting pH is 7.0.Homogenizer is handled, and makes medicinal liquid 500ml altogether.Packing, logical nitrogen, every 5ml (10mg/5ml); Or 1ml (2mg/1ml), flowing steam sterilization 30 minutes promptly gets the vitamin E injectable emulsion.Granularity is: 50～400nm, particle mean size is 138nm.
Embodiment 5:
Prescription is formed: vitamin e1 .0g, BHA0.2g, injection safflower oil 10g, soybean lecithin 2g, 1.0g poloxamer F68, glycerol 2.2g, anhydrous sodium sodium bisulfate 0.01g become 100ml altogether.
Method is with " example one "
1) in the dosing apparatus, 1.0g vitamin E, 0.2gBHA are dissolved in the 10g injection safflower oil mix homogeneously;
2) glycerol (anhydrous) of the soybean lecithin of 2.0g, 1.0g poloxamer F68,2.2g and proper amount of water for injection mix homogeneously;
3) with 2) under stirring condition, add 1) in, when 50, stir the back by even matter instrument, with solution homogenize repeatedly (microjet instrument, the first step are regulated homogenize pressure to 6000psi, and the second step re-adjustment is to 14000psi), obtain uniform solution; Regulating pH with sodium hydroxide and hydrochloric acid is 9.0.Homogenizer is handled, and makes medicinal liquid 100ml altogether.Packing, logical nitrogen, every 2ml (20mg/ props up), flowing steam sterilization 30 minutes promptly gets the vitamin E injectable emulsion.Granularity is: 80～900nm, particle mean size is 253nm.
Embodiment 6:
Prescription is formed: the soybean lecithin of 0.5g vitamin E, 0.1gBHA, 2g, 1g mannitol, 5g glucose, total amount 100ml.
1) in the dosing apparatus, with 0.5g vitamin E, 0.1gBHA mix homogeneously;
2) soybean lecithin of 2g is scattered in proper amount of water for injection, mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 20, stirring, cross G
3The funnel sucking filtration, gained liquid forms Emulsion by even matter instrument (microjet instrument, the first step are regulated homogenize pressure to 4000psi, and the second step re-adjustment is to 12000psi).With solution homogenize repeatedly, obtain uniform solution; Regulating pH with sodium hydroxide and hydrochloric acid is 3.0～4.0, adds 1g mannitol, 5g glucose, makes medicinal liquid 100ml altogether.Cross the 0.22um microporous filter membrane, packing, every 1ml (5mg) removes moisture through lyophilization, and inflated with nitrogen seals, and gets the vitamin E freeze-dried emulsion.Granularity 20nm～400nm.Particle mean size is 213nm.
4) will make freeze-dried emulsion and measure on demand and add water, be recovered to Emulsion after the hydration vibration.Granularity 10nm～300nm.Particle mean size is 202nm.
Embodiment 7:
Prescription is formed: 1.0g vitamin E, 2g Ovum Gallus domesticus Flavus lecithin, 1g TPGS, 0.1g anhydrous sodium sodium bisulfate, 10g mannitol, 2g glucose, total amount 200ml.
1) in the dosing apparatus, adds the 1.0g vitamin E;
2) Ovum Gallus domesticus Flavus lecithin of 2g, 1g TPGS are scattered in proper amount of water for injection, mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 40, stirring, cross G
3The funnel sucking filtration, gained liquid forms Emulsion by even matter instrument (microjet instrument, the first step are regulated homogenize pressure to 6000psi, and the second step re-adjustment is to 16000psi).With solution homogenize repeatedly, obtain uniform solution; With sodium hydroxide and Fructus Citri Limoniae acid for adjusting pH is 5.0～7.0, adds 10g mannitol, 2g glucose, makes medicinal liquid 200ml altogether.Cross the 0.22um microporous filter membrane, packing, every 2ml (10mg) removes moisture through lyophilization, and inflated with nitrogen seals, and gets the vitamin E freeze-dried emulsion.Particle mean size is 178nm.
4) will make freeze-dried emulsion and measure on demand and add water, be recovered to Emulsion after the hydration vibration.Granularity 10nm～510nm.Particle mean size is 153nm.
Embodiment 8:
Prescription is formed: 5.0g vitamin E, 10g HS15,1g injection soybean oil, 0.5g vitamin C, 10g mannitol, total amount 100ml.
1) in the control equipment, adds 5.0g vitamin E, 1g injection soybean oil, the dissolving mixing;
2) 10g HS15 is scattered in the water for injection of 50 ml, adds the 0.5g vitamin C, mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 40, stirring, cross G
3The funnel sucking filtration, gained liquid forms Emulsion by even matter instrument (microjet instrument, the first step are regulated homogenize pressure to 5000psi, and the second step re-adjustment is to 15000psi).With solution homogenize repeatedly, obtain uniform solution; Regulating pH with sodium hydroxide and phosphoric acid is 6.0～8.0, adds 10g mannitol, and the dissolving back adds water for injection to 100ml.Cross the 0.22um microporous filter membrane, packing, every 1ml (50mg) or 2ml (100mg) remove moisture through lyophilization, and inflated with nitrogen seals, and gets the vitamin E freeze-dried emulsion.
4) will make freeze-dried emulsion and measure on demand and add water, be recovered to Emulsion after the hydration vibration.Granularity 10nm～460nm.Particle mean size is 203nm.
Embodiment 9:
Prescription is formed: 5.0g vitamin E, 5g injection soybean oil, 12g Ovum Gallus domesticus Flavus lecithin, 10g vitamin E polyethylene glycol succinic acid ester (tocopherol polyethyleneglycol succinate TPGS), nitrogen, sorbitol 30g, trehalose 50g, ethyl hydroxybenzoate 0.1g, total amount 1000ml.
1) in the configuration device, adds 5.0g vitamin E, 5g injection soybean oil, the dissolving mixing;
2) 12g Ovum Gallus domesticus Flavus lecithin, 10g vitamin E polyethylene glycol succinic acid ester (tocopherol polyethyleneglycol succinate TPGS) are scattered in the water for injection of 500ml, mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 60, stirring, cross G
3The funnel sucking filtration, gained liquid forms Emulsion by even matter instrument (microjet instrument, the first step are regulated homogenize pressure to 5000psi, and the second step re-adjustment is to 15000psi).With solution homogenize repeatedly, obtain uniform solution; With sodium hydroxide and hydrochloric acid acid for adjusting pH is 7.0～9.0, adds sorbitol 30g, trehalose 50g, ethyl hydroxybenzoate 0.1g, and the dissolving back adds water for injection to 1000ml.Cross the 0.22um microporous filter membrane, packing, every 1ml (5mg) removes moisture through lyophilization, and inflated with nitrogen gets the vitamin E freeze-dried emulsion.
4) will make freeze-dried emulsion and measure on demand and add water, be recovered to Emulsion after the hydration vibration.Granularity 50nm～1000nm, particle mean size is 336nm.
Embodiment 10:
Prescription is formed: 5g vitamin E, 4g soybean lecithin, 0.1g anhydrous sodium sulfite, 6g mannitol, 6g glucose, total amount 200ml.
1) in the dosing apparatus, adds the 5.0g vitamin E;
2) soybean lecithin of 4g is scattered in proper amount of water for injection, mix homogeneously;
3) with 2) under stirring condition, add 1) in, get colostrum after when 40, stirring, cross G
3The funnel sucking filtration, gained liquid forms Emulsion by even matter instrument (microjet instrument, the first step are regulated homogenize pressure to 6000psi, and the second step re-adjustment is to 16000psi).With solution homogenize repeatedly, obtain uniform solution; With sodium hydroxide and Fructus Citri Limoniae acid for adjusting pH is 7.0～9.0, adds 6g mannitol, 6g glucose, makes medicinal liquid 200ml altogether.Cross the 0.22um microporous filter membrane, packing, every 2ml (50mg) removes moisture through lyophilization, and inflated with nitrogen seals, and gets the vitamin E freeze-dried emulsion.Particle mean size is 156nm.
4) will make freeze-dried emulsion and measure on demand and add water, be recovered to Emulsion after the hydration vibration.Granularity 10nm-361nm.Particle mean size is 157nm.
Embodiment 11: vitamin E is to the protective effect of acute liver damage
The SD rat is male, and body weight 165-225g. is by 800mg/kg body weight lumbar injection D-Gal. and 24h can produce typical liver damage animal model after the injection.Above-mentioned animal is divided into 2 groups at random, i.e. matched group and treatment group.Matched group is behind the injection D-Gal 24,48,72, and 96h puts to death animal in batches, measures hepatic tissue and serum MDA level; The treatment group then before the injection D-Gal 1d begin the intraperitoneal injection vitamin E, 150mg/kg body weight, 1 time/12h, totally 2 times. it is identical with matched group to put to death the animal method.The results are shown in Table 1,2.
MDA in table 1. hepatic tissue (nmol/g liver) changes
(implement the Emulsion group (implements time matched group oleo-injection Emulsion group
(h) group example one) example six)
24 1162.0±119.0 947.5±120.1 638.2±61.6 661.6±90.2
48 1086.1±138.2 908.5±126.3 561.1±68.9 553.6±63.3
72 1006.3±223.6 871.6±127.8 406.3±58.8 391.2±60.2
96 663.2±160.1 401.6±108.5 326.8±33.6 302.3±36.9
MDA in table 2. serum (nmol/ml serum) changes
The commercially available oiliness of time matched group is annotated the Emulsion group, and (implementing the Emulsion group (implements
(h) penetrate liquid group example one) example six)
24 8.0±1.0 5.3±1.2 4.1±1.0 4.8±1.2
48 7.1±1.2 4.6±1.3 3.5±1.0 3.6±0.8
72 6.2±2.6 4.1±1.2 2.8±0.7 3.2±0.9
96 5.2±1.1 3.6±1.0 2.3±0.8 2.9±0.6
Hence one can see that, vitamin E is made Emulsion after, protective effect obviously is better than existing commercially available oleo-injection group.
Embodiment 12: the test of different dosage form rat peak reaching time of blood concentration
Injection different dosage form vitamin E in the rat abdominal cavity, dosage is 150mg/kg, measures blood drug level with HPLC, relatively different dosage form domesticated dog peak reaching time of blood concentration and peak concentration.The results are shown in Table 3.
Table 3, peak reaching time of blood concentration and peak concentration
Commercially available oiliness embodiment one embodiment of group six embodiment eight
Injection
Peak time (hour) 2.5 0.5 1.0 1.0
Peak concentration (ug/ml) 8.6 17.3 19.2 16.1
Hence one can see that, vitamin E is made Emulsion after, peak time shortens greatly, peak concentration improves greatly, drug effect is fast, is beneficial to clinical treatment.
Claims (7)
1, vitamin E Emulsion and freeze-dried emulsion thereof, it is characterized in that: the vitamin E that contains effective dosage is as medicine, and contain pharmaceutic adjuvants such as oil phase, emulsifying agent, stabilizing agent, osmotic pressure regulator, pH regulator agent, antiseptic, also can not contain antiseptic, wherein contain freeze drying protectant in the freeze-dried emulsion, in the injectable emulsion, medicine: oil (w/w)=1: 0～1: 100 (w/w); In the injection freeze-dried emulsion, medicine: oil (w/w)=1: 0～1: 10 (w/w).
2, injectable emulsion according to claim 1 is characterized in that, its prescription is:
Contain in per 1～10ml medicinal liquid:
Vitamin E 5～100mg
Oil for injection 0～500mg
Emulsifying agent 10～200mg
Stabilizing agent 1mg～100mg
Glycerol is an amount of
The pH regulator agent is an amount of
3, injection vitamin E freeze-dried emulsion according to claim 1 is characterized in that its prescription is:
Contain in per 1～10ml medicinal liquid:
Vitamin E 5～100mg
Oil for injection 0～50mg
Emulsifying agent 10～200mg
Stabilizing agent 1mg～100mg
The pH regulator agent is an amount of
Antiseptic is an amount of
Freeze drying protectant is an amount of
4, injection vitamin E Emulsion according to claim 2 is characterized in that:
Oil for injection can be one or more mixture in the vegetable oil of Oleum Glycines, Oleum Camelliae, olive oil, Flos Carthami wet goods any kind of, and particle mean size is 10nm～1000nm;
Emulsifying agent is one or more mixture in phospholipid, poloxamer, HS15 (Polyethylene Glycol 12-hydroxy stearic acid ester, polyethyleneglycol 660 hydroxystearate), the vitamin E polyethylene glycol succinic acid ester (TPGS) etc., and consumption is 10～200mg;
Stabilizing agent is one or more mixture in nitrogen, anhydrous sodium sulphuric acid (hydrogen) sodium, Vc, dibenzylatiooluene, the hydroquinone etc., and consumption is 1mg～100mg;
Antiseptic is a benzyl alcohol, and consumption is 0～10mg;
The pH regulator agent is one or more mixture in hydrochloric acid, sodium hydroxide, sodium acetate, acetic acid, phosphate, the citric acid etc., and regulating pH is 3～9;
5, injection vitamin E freeze-dried emulsion according to claim 3 is characterized in that:
Oil for injection can be one or more mixture in the vegetable oil of Oleum Glycines, Oleum Camelliae, olive oil, Flos Carthami wet goods any kind of, and granularity is 10nm～1000nm;
Emulsifying agent, stabilizing agent, pH regulator agent etc. require identical with Emulsion;
Antiseptic is a parabens, and consumption is 0～1mg;
Freeze drying protectant is one or more mixture in glucose, lactose, mannitol, sorbitol, xylitol, sucrose, trehalose, dextran, the polyvinylpyrrolidone (PVP) etc., and the content of freeze drying protectant is 4%～40% (W/V);
Prepared freeze-dried emulsion is measured on demand and is added water, is recovered to Emulsion, intramuscular injection or intravenously administrable after the hydration vibration.
6, injection vitamin E freeze-dried emulsion according to claim 5, it is characterized in that: freeze drying protectant can be glucose and mannitol, and both proportionings are: 1: 0.01～0.01: 1.
7, a kind of preparation method of injectable emulsion as claimed in claim 2, it is characterized in that: preparation process is as follows;
1) in preparing tank, prepare oil phase (medicine phase):
In preparing tank, oil for injection is heated to 20～90 ℃, non-refuelling during simple medicine adds emulsifying agent, is stirred to dissolving in the time of 20～50 ℃; Be cooled to 20～40 ℃ again, in stirring, add medicine;
2) in preparing tank, prepare water:
Water and glycerol are stirred 5min down at 20～90 ℃, make it complete miscibility;
3) in the time of 20～50 ℃, water is added in the oil phase, stir 10～30min, form colostrum;
4) colostrum is crossed G3 funnel sucking filtration, regulated pH value to 3～9;
5) cross the homogenizing instrument, the first step is regulated homogenize pressure to 520～600kg/cm2, and second step re-adjustment to 100～140kg/cm2 forms Emulsion; Cross microporous filter membrane, packing, sterilization promptly get injectable emulsion; Or cross the microjet instrument, and the first step is regulated homogenize pressure to 4000～8000psi, and second step re-adjustment to 10000～16000psi crosses microporous filter membrane, and packing, sterilization promptly get injectable emulsion; Add freeze drying protectant, carry out lyophilization, promptly get freeze-dried emulsion.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101227952B (en) * | 2005-07-27 | 2010-12-01 | 昭和电工株式会社 | Emulsified skin external preparation and method for stabilizing the skin external preparation |
| CN102125520A (en) * | 2011-02-24 | 2011-07-20 | 美迪思生物科技(北京)有限公司 | Emulsion containing hydrophilic biological macromolecule, preparation method and application thereof |
| CN109260149A (en) * | 2018-04-19 | 2019-01-25 | 周晋 | It is a kind of to contain γ-tocotrienols nanoemulsions and its preparation method and application |
-
2004
- 2004-07-23 CN CN 200410021539 patent/CN1596889A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101227952B (en) * | 2005-07-27 | 2010-12-01 | 昭和电工株式会社 | Emulsified skin external preparation and method for stabilizing the skin external preparation |
| CN102125520A (en) * | 2011-02-24 | 2011-07-20 | 美迪思生物科技(北京)有限公司 | Emulsion containing hydrophilic biological macromolecule, preparation method and application thereof |
| CN109260149A (en) * | 2018-04-19 | 2019-01-25 | 周晋 | It is a kind of to contain γ-tocotrienols nanoemulsions and its preparation method and application |
| CN109260149B (en) * | 2018-04-19 | 2021-04-06 | 周晋 | Nano emulsion containing gamma-tocotrienol and preparation method and application thereof |
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