CN101584660A - Intravenous injection perilla alcohol submicron emulsion and preparation method thereof - Google Patents
Intravenous injection perilla alcohol submicron emulsion and preparation method thereof Download PDFInfo
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- CN101584660A CN101584660A CNA2008100498276A CN200810049827A CN101584660A CN 101584660 A CN101584660 A CN 101584660A CN A2008100498276 A CNA2008100498276 A CN A2008100498276A CN 200810049827 A CN200810049827 A CN 200810049827A CN 101584660 A CN101584660 A CN 101584660A
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Abstract
The invention relates to an intravenous injection perilla alcohol submicron emulsion and a preparation method thereof, belonging to the technical field of medicine. The intravenous injection perilla alcohol submicron emulsion is a submicron emulsion prepared by oil for injection, an emulsifying agent, an auxiliary emulsifying agent, a stabilizing agent, an antioxidizer, an osmotic adjusting agent and perilla alcohol, wherein the weight volume concentration of the perilla alcohol ranges from 1mg/ml to 30mg/ml; and the submicron emulsion has uniform grain diameters, and has an average grain diameter of 217.5nm. The invention has the advantages of simple preparation technology, large medicine carrying amount, high stability, controllable quality, suitability for industrialized production, and the like. The prepared intravenous injection perilla alcohol submicron emulsion can better enhance the solubility of the submicron emulsion prepared by medicine and prolong the acting time of the medicine inside bodies, also plays roles of sustained and controlled release and targeting and can enhance the treatment effect of the medicine and reduce the toxic side effect.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of cancer therapy drug intravenous injection perilla alcohol submicron emulsion, the invention still further relates to the preparation method of said preparation.
Background technology
Perilla alcohol is commonly called as dihydro hay alcohol, and chemical name (4-isopropenyl-1-cyclohexene) methanol is from the leaf of labiate Folium Perillae or the volatile oil of being with leaf twig steam distillation to obtain, is light brown or dark-brown supernatant liquid, and gas is special, and is warm in nature, acrid in the mouth.Perilla alcohol also is present in the various plants such as mandarin orange, Fructus Pruni pseudocerasi, Herba Menthae, bergamot, Rhizoma Zingiberis Recens grass with the form of free state or ester, is the monoterpene that plant mevalonate metabolic pathway produces.The pharmacologically active of perilla alcohol mainly contains immunostimulant, effects such as antitumor.Perilla alcohol presses down by inhibition method Geordie transferring enzyme, and the myeloid cell of selective induction bcr/abl vicious transformation is cell cycle arrest and apoptosis and bring into play antitumor action.Perilla alcohol can make breast carcinoma disappear fully, and is also relatively good to the therapeutic effect of pulmonary carcinoma, cancer of pancreas, leukemia.
Domestic research to perilla alcohol mainly concentrates on senior spice and various Folium Perillae tea, the application of Folium Perillae wet goods aspect, and its research as medicine is not also drawn attention.U.S. FDA approved perilla alcohol carries out clinical research as antitumor drug, Bailey etc. have carried out II phase clinical research (Bailey HH to the antitumor action of perilla alcohol, Levy D, Harris LS, etal.A phase II trial of daily perillyl alcohol in patients with advanced ovariancancer:Eastern Cooperative Oncology Group Study E2E96.Gynecol Oncol.2002,85 (3): 464-468).Perilla alcohol now only has two kinds of dosage forms of emulsifiable paste of oral capsule and treatment skin carcinoma.II phase clinical research shows that oral perilla alcohol capsule can produce more serious gastrointestinal side effect.
The used for intravenous injection submicron emulsion is to develop one of dosage form faster in the present field of medicaments; as the intravenously administrable carrier, fatty submicron emulsion can protect encapsulated medicine, drug loading big, can improve medicine stability, prolong drug action time, reduce toxic and side effects, make medicine have slow controlled release and targeting.In addition, injection submicron emulsion preparation technology is simple, quality controllable, be fit to suitability for industrialized production, so the intravenous injection submicron emulsion has good application prospects.The intravenous injection submicron emulsion is as the carrier of antitumor drug, its targeting can obviously improve antitumous effect, Emulsion also can prevent the transfer of tumor, therefore this class medicine is made Emulsion abroad, as paclitaxel breast, Docetaxel breast, fluorouracil breast and tegafur breast morely.As pharmaceutical carrier, in administration, the intravenous injection submicron emulsion can also and provide energy to patient's extra-nutrition, and this cancer patient to malnutrition has great importance.
Summary of the invention
The objective of the invention is to overcome the more serious gastrointestinal side effect of oral perilla alcohol capsule generation in the prior art, provide a kind of have slow controlled release and targeting, therapeutic effect height, the intravenous injection perilla alcohol submicron emulsion preparation that toxic and side effects is little.The present invention also aims to provide the preparation method of said preparation.
The objective of the invention is to be achieved through the following technical solutions:
Intravenous injection perilla alcohol submicron emulsion of the present invention contains perilla alcohol 1～30mg in every milliliter of submicron emulsion, injection vegetable oil 0.05～0.2g, emulsifying agent 8～24mg, co-emulsifier 0～20mg, stabilizing agent 0.1～3mg, antioxidant 0.8mg, isoosmotic adjusting agent 22.5mg.
Mean diameter＜the 300nm of submicron emulsion decentralized photo of the present invention.
Used injection vegetable oil is selected from a kind of in soybean oil, Oleum Ricini, Oleum Camelliae, Oleum Sesami, safflower oil, Oleum Gossypii semen, the olive oil or the mixture of any two kinds or any two or more materials in the middle of them among the present invention.
Used emulsifying agent is selected from a kind of in Ovum Gallus domesticus Flavus lecithin, soybean phospholipid, hydrogenated soya phosphatide, the synthetic phospholipid or the mixture of any two kinds or any two or more materials in the middle of them.
Used co-emulsifier is selected from a kind of in poloxamer, polyglycol distearate, cholesterol, the chitosan or the mixture of any two kinds or any two or more materials in the middle of them.
Used stabilizing agent is oleic acid or enuatrol or their mixture.Used antioxidant is a vitamin E.Used isoosmotic adjusting agent is a glycerol.
The preparation method of intravenous injection perilla alcohol submicron emulsion of the present invention may further comprise the steps:
(1) preparation oil phase: under 55～85 ℃ of conditions, stabilizing agent, emulsifying agent, perilla alcohol, vitamin E are joined in the oil for injection, stir, form oil phase;
(2) preparation water: under 55～85 ℃ of conditions, co-emulsifier, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 55～85 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 4～9, standardize solution, homogenizing 2～15min under even matter speed 6000～12000rpm makes colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, under the pressure of 3000～18000 PSI, even matter 6～20 times; Make perilla alcohol submicron emulsion;
(5) perilla alcohol submicron emulsion that makes is sub-packed in the ampoule, inflated with nitrogen, sealing by fusing, 121 ℃ of sterilization 15min or 115 ℃ of sterilization 30min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Advantage of the present invention is: because the present invention is prepared into submicron emulsion with emulsifying agent, oil for injection and perilla alcohol, with the matrix material of co-emulsifier, stabilizing agent, isoosmotic adjusting agent modification submicron emulsion, increase the dissolubility of perilla alcohol.Thereby prolong drug action time in vivo, and have slow controlled release and targeting, improve the therapeutic effect of medicine, reduce toxic and side effects; The preparation technology that the present invention adopts is simple, drug loading is high, quality controllable, be fit to suitability for industrialized production.
The specific embodiment
Below in conjunction with embodiment the present invention is elaborated, but protection scope of the present invention is not limited to this.
Embodiment 1
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 100mg
Soybean lecithin for injection 800mg
Injection soybean oil 5g
Poloxamer 188 200mg
Oleic acid 10mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 55 ℃ of conditions, oleic acid, soybean lecithin for injection, perilla alcohol, vitamin E are joined in the injection soybean oil, stir, form oil phase;
(2) preparation water: under 55 ℃ of conditions, poloxamer 188, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 55 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 4, standardize solution.Through the even matter 15min of the even matter 6000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 3000 PSI, even matter 20 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 121 ℃ of sterilization 15min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Embodiment 2
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 500mg
Soybean lecithin for injection 1200mg
Injection soybean oil 10g
Poloxamer 188 500mg
Enuatrol 50mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 80 ℃ of conditions, enuatrol, soybean lecithin for injection, perilla alcohol, vitamin E are joined in the injection soybean oil, stir, form oil phase;
(2) preparation water: under 80 ℃ of conditions, poloxamer 188, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 80 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 6, standardize solution.Through the even matter 10min of the even matter 8000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 6000 PSI, even matter 15 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 121 ℃ of sterilization 15min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Embodiment 3
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 1000mg
Ovum Gallus domesticus Flavus lecithin 1600mg
Injection soybean oil 5g
Olive oil 5g
Polyglycol distearate 800mg
Enuatrol 100mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 65 ℃ of conditions, enuatrol, injection Ovum Gallus domesticus Flavus lecithin, perilla alcohol, vitamin E are joined in injection soybean oil and the olive oil, stir, form oil phase;
(2) preparation water: under 65 ℃ of conditions, polyglycol distearate, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 65 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 8, standardize solution.Through the even matter 5min of the even matter 10000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 10000PSI, even matter 10 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 115 ℃ of sterilization 30min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Embodiment 4
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 2000mg
Ovum Gallus domesticus Flavus lecithin 2000mg
Injection soybean oil 15g
Poloxamer 188 1400mg
Enuatrol 200mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 70 ℃ of conditions, enuatrol, injection Ovum Gallus domesticus Flavus lecithin, perilla alcohol, vitamin E are joined in the injection soybean oil, stir, form oil phase;
(2) preparation water: under 70 ℃ of conditions, poloxamer 188, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 70 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 7, standardize solution.Through the even matter 5min of the even matter 10000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 16000 PSI, even matter 8 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 115 ℃ of sterilization 30min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Embodiment 5
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 2500mg
Ovum Gallus domesticus Flavus lecithin 2000mg
Hydrogenated soya phosphatide 200mg
Injection soybean oil 20g
Poloxamer 188 1800mg
Oleic acid 250mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 75 ℃ of conditions, oleic acid, injection Ovum Gallus domesticus Flavus lecithin and hydrogenated soya phosphatide, perilla alcohol, vitamin E are joined in the injection soybean oil, stir, form oil phase;
(2) preparation water: under 75 ℃ of conditions, poloxamer 188, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 75 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 9, standardize solution.Through the even matter 2min of the even matter 12000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 16000 PSI, even matter 8 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 115 ℃ of sterilization 30min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
Embodiment 6
1. the primary raw material for preparing intravenous injection perilla alcohol submicron emulsion:
Perilla alcohol 3000mg
Ovum Gallus domesticus Flavus lecithin 1200mg
Soybean phospholipid 1200mg
Injection soybean oil 20g
Poloxamer 188 2000mg
Oleic acid 300mg
Glycerol 2.25g
Vitamin E 80mg
Water for injection adds to 100mL
2. the method for preparing intravenous injection perilla alcohol submicron emulsion:
(1) preparation oil phase: under 85 ℃ of conditions, oleic acid, injection Ovum Gallus domesticus Flavus lecithin and soybean phospholipid, perilla alcohol, vitamin E are joined in the injection soybean oil, stir, form oil phase;
(2) preparation water: under 85 ℃ of conditions, poloxamer 188, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 85 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 5, standardize solution.Through the even matter 2min of the even matter 12000rpm of high speed homogenizer, make colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, and under the pressure of 18000 PSI, even matter 6 times makes perilla alcohol submicron emulsion.
(5) perilla alcohol submicron emulsion that makes is sub-packed in the 2mL ampoule, inflated with nitrogen, sealing by fusing, 121 ℃ of sterilization 15min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
The intravenous injection perilla alcohol submicron emulsion of the foregoing description preparation adopts Nano-ZS90 type laser nano particle size analyzer to measure emulsion droplet particle diameter and zeta current potential.The emulsion droplet of intravenous injection perilla alcohol submicron emulsion is evenly distributed as a result, and mean diameter is 217.5nm, and average zeta current potential is-32.5mV.
Embodiment 7～22
1. the raw material and the proportioning raw materials of preparation intravenous injection perilla alcohol submicron emulsion are as shown in table 1.
2. the method for preparing intravenous injection perilla alcohol submicron emulsion adopts the preparation method in the foregoing description 1～6.
The proportioning raw materials that reaches for preparing intravenous injection perilla alcohol submicron emulsion among each embodiment of table 1
Continuous table 1
Used antioxidant can also adopt the antioxidant of other commercially available type in the foregoing description, and isoosmotic adjusting agent can adopt the isoosmotic adjusting agent of other commercially available type.
The intravenous injection perilla alcohol submicron emulsion of the foregoing description preparation adopts Nano-ZS90 type laser nano particle size analyzer to measure emulsion droplet particle diameter and zeta current potential.The emulsion droplet of intravenous injection perilla alcohol submicron emulsion is evenly distributed as a result, and mean diameter is 217.5nm, and average zeta current potential is-32.5mV.
Assay: get intravenous injection perilla alcohol submicron emulsion 2mL, place the 200mL volumetric flask, add 15mL methanol, the vortex mixing makes the dissolving of POH Emulsion,, shakes up to scale with distilled water diluting, filters.Precision is measured subsequent filtrate 20 μ L, injects chromatograph of liquid record chromatogram, and as external standard, by external standard method, with calculated by peak area, the average percentage composition that gets perilla alcohol in the sample is 97.19% with reference substance solution.
Stability test
Regulation with reference to 2005 editions medicine stability test guidelines of Chinese Pharmacopoeia Chinese medicine accelerated test is carried out as follows: submicron emulsion is at 30 ℃, relative humidity 60% was placed 6 months under the condition, prepared three batches of perilla alcohol submicron emulsions respectively, place 30 ℃ of climatic chambers respectively, in the 0th, 1,2,3, took out in 6 months, and investigated the changes of contents of outward appearance, particle diameter, pH value and the submicron emulsion Chinese medicine of Emulsion, the results are shown in Table 2.
Table-2 intravenous injection perilla alcohol submicron emulsion stability test results (x ± s, n=3)
By the stability experiment result as can be known: the intravenous injection perilla alcohol submicron emulsion good stability, every index all meets the requirements.
The research of intravenous injection perilla alcohol submicron emulsion rat interior medicine dynamics
Get 12 of SD rats, be divided into 2 groups at random, one group of perilla alcohol solution, one group gives intravenous injection perilla alcohol submicron emulsion.Slowly inject through rat tail vein with 65mg/kg dosage, respectively at after the administration 5,10,15,30,45min, 1,2,4,6,8, the 10h eye socket is got 0.5ml blood, put in the 1.5m1 point end centrifuge tube of heparinization in advance the centrifugal 10min of 8000rpm, separated plasma, the accurate upper plasma 100 μ L that draw, after plasma sample was handled, HPLC analyzed.The blood drug level of each time point adopts Kinetica 4.4.1 pharmacokinetics software to carry out the model match behind laboratory animal intravenous injection perilla alcohol solution and the intravenous injection perilla alcohol submicron emulsion.With gained blood drug level through the time data carry out curve fitting with Kinetica 4.4.1 program, according to the check of AIC criterion and F value comprehensive judge medicine in the moving scholarship and moral conduct of rat body giving drugs into nose for meeting two chamber models, its pharmacokinetic parameters sees Table 3.
Pharmacokinetic parameters (n=6) in table-3 rat bodies
The result shows that perilla alcohol submicron emulsion prolonged in the rat intravital elimination half-life, and elimination speed slows down, and AUC increases.Therefore, submicronized emulsion is as the perilla alcohol carrier, prolonged medicine intravital action time.
Extracorporeal anti-tumor function
The breast carcinoma cell strain MDA-MB-435s of exponential phase, 0.25% pancreas egg are diluted to 1 * 10 from enzymic digestion with the DMEM culture fluid that contains 10% calf serum
5The single cell suspension of/mL concentration.With cell suspension inoculation 96 orifice plates, every hole 100 μ L, totally 6 groups, 5 culture plates are inoculated, 5%CO altogether in 4 every group multiple holes
2In the incubator, 37 ℃ of overnight incubation.After 24 hours, 6 drug treating groups are cultivated, and cell culture fluid is replaced by the culture fluid that contains different pharmaceutical concentration, and zeroing group and matched group add the culture fluid of respective volume., every hole 200 μ L, behind continuation cultivation 24,36,48,72, the 96h, every hole adds MTT solution (5gL
-1) 20 μ L (except the zeroing group), continue to hatch 4h.Carefully remove culture fluid, blue first a ceremonial jade-ladle, used in libation dissolution of crystals is in 100 μ L dimethyl sulfoxide, and after the jolting evenly, the absorbance (table 4 and 5) in each hole of record, wavelength 570nm place is asked administration group inhibition rate of tumor cell and IC
50Value.
Table-4 perilla alcohol solution to the toxicity of MDA-MB-435S cell (x ± s, n=4)
Compare P＜0.01 with matched group
Table-5 perilla alcohol submicron emulsions to the toxicity of MDA-MB-435S cell (x ± s, n=4)
Compare P＜0.01 with matched group
The IC of perilla alcohol solution and perilla alcohol submicron emulsion
50Concentration is respectively 1236.3 μ mol/L and 528.43 μ mol/L.The result shows that perilla alcohol submicron emulsion is better than perilla alcohol solution to the cytotoxicity of MDA-MB-435S.
Claims (9)
1. an intravenous injection perilla alcohol submicron emulsion is characterized in that: contain perilla alcohol 1～30mg in every milliliter of submicron emulsion, injection vegetable oil 0.05～0.2g, emulsifying agent 8～24mg, co-emulsifier 0～20mg, stabilizing agent 0.1～3mg, antioxidant 0.8mg, isoosmotic adjusting agent 22.5mg.
2. intravenous injection perilla alcohol submicron emulsion according to claim 1 is characterized in that: the mean diameter＜300nm of submicron emulsion decentralized photo.
3. intravenous injection perilla alcohol submicron emulsion according to claim 1 and 2 is characterized in that: described injection vegetable oil is selected from a kind of in soybean oil, Oleum Ricini, Oleum Camelliae, Oleum Sesami, safflower oil, Oleum Gossypii semen, the olive oil or the mixture of any two kinds or any two or more materials in the middle of them.
4. intravenous injection perilla alcohol submicron emulsion according to claim 3 is characterized in that: described emulsifying agent is selected from a kind of in Ovum Gallus domesticus Flavus lecithin, soybean phospholipid, hydrogenated soya phosphatide, the synthetic phospholipid or the mixture of any two kinds or any two or more materials in the middle of them.
5. according to claim 1 or 2 or 4 described intravenous injection perilla alcohol submicron emulsions, it is characterized in that: described co-emulsifier is selected from a kind of in poloxamer, polyglycol distearate, cholesterol, the chitosan or the mixture of any two kinds or any two or more materials in the middle of them.。
6. intravenous injection perilla alcohol submicron emulsion according to claim 5 is characterized in that: described stabilizing agent is oleic acid or enuatrol or their mixture.
7. according to claim 1 or 2 or 6 described intravenous injection perilla alcohol submicron emulsions, it is characterized in that: described antioxidant is a vitamin E.
8. intravenous injection perilla alcohol submicron emulsion according to claim 7 is characterized in that: described isoosmotic adjusting agent is a glycerol.
9. the preparation method of the described intravenous injection perilla alcohol submicron emulsion of claim 1, it is characterized in that: preparation method may further comprise the steps:
(1) preparation oil phase: under 55～85 ℃ of conditions, stabilizing agent, emulsifying agent, perilla alcohol, vitamin E are joined in the oil for injection, stir, form oil phase;
(2) preparation water: under 55～85 ℃ of conditions, co-emulsifier, glycerol etc. are added in the water for injection, stir, form water;
(3) preparation colostrum: remain in temperature under the prerequisite of 55～85 ℃ of constant temperature and constantly stirring, oil phase slowly is injected into water, stir fast, regulate pH value 4～9, standardize solution, homogenizing 2～15min under even matter speed 6000～12000rpm makes colostrum;
(4) preparation of breast eventually: the colostrum that makes is crossed the microjet instrument, under the pressure of 3000～18000PSI, even matter 6～20 times; Make perilla alcohol submicron emulsion;
(5) perilla alcohol submicron emulsion that makes is sub-packed in the ampoule, inflated with nitrogen, sealing by fusing, 121 ℃ of sterilization 15min or 115 ℃ of sterilization 30min, quality inspection obtains intravenous injection perilla alcohol submicron emulsion.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103517892A (en) * | 2010-12-17 | 2014-01-15 | 尼昂克技术公司 | Method and device for using isoperillyl alcohol |
| CN105213311A (en) * | 2015-11-05 | 2016-01-06 | 南阳农业职业学院 | The preparation method of diclazuril submicron emulsion |
| CN112870182A (en) * | 2021-03-18 | 2021-06-01 | 中南大学 | Application of perillyl alcohol and derivatives thereof in preparation of drugs for relieving side effects of chemotherapy |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5110832A (en) * | 1990-10-09 | 1992-05-05 | Doyle E. Chastain | Using perillyl alcohol to kill bacteria and yeasts |
-
2008
- 2008-05-21 CN CN2008100498276A patent/CN101584660B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103517892A (en) * | 2010-12-17 | 2014-01-15 | 尼昂克技术公司 | Method and device for using isoperillyl alcohol |
| CN103517892B (en) * | 2010-12-17 | 2016-01-27 | 尼昂克技术公司 | Use the method and apparatus of different perillalcohol |
| CN105213311A (en) * | 2015-11-05 | 2016-01-06 | 南阳农业职业学院 | The preparation method of diclazuril submicron emulsion |
| CN112870182A (en) * | 2021-03-18 | 2021-06-01 | 中南大学 | Application of perillyl alcohol and derivatives thereof in preparation of drugs for relieving side effects of chemotherapy |
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| CN101584660B (en) | 2011-06-08 |
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