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CN101703468A - Nano-emulsion of vitamin E oil and preparation method thereof - Google Patents

Nano-emulsion of vitamin E oil and preparation method thereof Download PDF

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CN101703468A
CN101703468A CN200910154931A CN200910154931A CN101703468A CN 101703468 A CN101703468 A CN 101703468A CN 200910154931 A CN200910154931 A CN 200910154931A CN 200910154931 A CN200910154931 A CN 200910154931A CN 101703468 A CN101703468 A CN 101703468A
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vitamin
nanoemulsion
emulsion
emulsifier
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金�一
张萍
王成润
胡建鸿
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Zhejiang University ZJU
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Abstract

本发明公开了一种维生素E油纳米乳制剂与制备方法,维生素E纳米乳制剂由维生素E、乳化剂、助乳化剂和溶媒剂组成;本发明的维生素E纳米乳剂,其平均粒径在20nm左右的乳粒有效的解决了制剂的物理稳定性和维生素E油的化学稳定性,降低了它们的毒副作用和不良反应,提高了药物的治疗效果。The invention discloses a vitamin E oil nanoemulsion preparation and a preparation method thereof. The vitamin E nanoemulsion preparation is composed of vitamin E, an emulsifier, a co-emulsifier and a solvent; the vitamin E nanoemulsion of the present invention has an average particle diameter of 20nm The left and right milk particles effectively solve the physical stability of the preparation and the chemical stability of the vitamin E oil, reduce their toxic side effects and adverse reactions, and improve the therapeutic effect of the drug.

Description

Vitamin E oil nano-emulsion preparation and preparation method
Technical field
The present invention relates to a kind of powerful antioxidant, relate in particular to a kind of vitamin E oil nano-emulsion preparation and preparation method.
Background technology
Vitamin E is only by the fat-soluble powerful antioxidant of the synthetic class of photosynthetic organism.Generally be from vegetable oil (oil such as Semen sojae atricolor, Semen Allii Tuberosi, Semen Gossypii, Testa oryzae, corn, sunflower seed, Semen Flos Carthami) refining process, to extract in the deodorization distillate.As far back as 60~seventies of 20th century, researcher just by the biosynthesis of radioisotope labeling research alpha-tocopherol, is illustrated alpha-tocopherol biosynthesis pathway of higher plant and the synthetic site in chloroplast thereof basically to the eighties.Photosynthetic organism is by the series of enzymatic reactions synthetic alpha-tocopherol.The main dosage form of the Vitamin E preparation that existing market is sold has tablet, soft capsule, powder, these four kinds of dosage forms of injection.
Vitamin E is mainly used in defying age, prevention habitual abortion, threatened abortion, menopausal syndrome etc.The auxiliary treatment that also can be used for amyotrophy, muscular dystrophy, hepatitis, liver cirrhosis, coronary heart disease.In recent years along with the progress of vitamin E, exploration to its mechanism of action deepens continuously, clinical application range enlarges day by day, and cardiovascular disease, digestive system disease, ophthalmology illness, tumor, genitourinary system, respiratory system disease, dermatosis and anti-ageing waiting for a long time are all had certain curative effect.
When medicine reached blood system, classical pharmaceutical dosage form (as tablet, ointment, injection) can not be adjusted medicine behavior (distributing and elimination) in vivo.This moment, thereby medicine determined its physicochemical property to influence its biological nature (tissue and plasma protein affinity, membrane receptor affinity and to the sensitivity of enzyme biotransformation etc.) according to its chemical constitution.Modern biopharmaceutics and pharmacokinetic have proved particle when drug delivery system less than 200nm the time, i.e. Nano medication drug-supplying system, and the change of matter will take place in the absorption of drug delivery system and the substrate that turns round.Nano medication can improve drug absorption, change fate of drug, makes medicine have characteristics such as slow release targeting, can improve the curative effect of medicine, reduces untoward reaction, and drug manufacture will realize low cost, high efficiency, automatization and extensive.
Now existing vitamin E tablet, soft gelatin capsule, injection, powder, but at fatsoluble vitamin, vitamin E is prepared into nano-emulsion not only can increase medicine stability, can also improve bioavailability of medicament and curative effect and increase lympha targeted property.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, a kind of vitamin E oil nano-emulsion preparation and preparation method are provided.
The objective of the invention is to be achieved through the following technical solutions: a kind of vitamin E nano Emulsion, contain the component of following content in this Emulsion: vitamin E 0.1~50g/L, emulsifying agent 2~100g/L, coemulsifier: 1~80g/L, surplus is the solvent agent.
Further, vitamin E is preferably 0.5~30g/L, and emulsifying agent is preferably 5~80g/L, and coemulsifier is preferably 2~50g/L, and surplus is the solvent agent.
Further, described emulsifying agent is one or more the mixing in tween 80, poloxamer and the polyoxyethylene hydrogenated Oleum Ricini; Described co-emulsifier is one or more the mixing in n-butyl alcohol, propylene glycol and the glycerol; Described solvent is one or both the mixing in water and the ethanol.
Further, described vitamin E nano Emulsion also contains additive, and this additive is selected from one or more in antioxidant, antibacterial and the antiseptic; Described antioxidant is selected from: tea polyphenols, phytic acid, sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate; Described antibacterial is selected from: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzoic acid, sodium benzoate, sorbic acid.
Further, described vitamin E nano Emulsion also contains the pH regulator agent, and this pH value regulator is selected from: sodium hydroxide, potassium chloride, sodium chloride, phosphate, carbonate, citrate, nicotiamide, Benzoylamide.
A kind of preparation method of said vitamin E nano-emulsion comprises the steps:
(1) preparation vitamin E primary emulsion: emulsifying agent and co-emulsifier are stirred, in whipping process, add vitamin E oil then, continue to stir formation milky colostrum, add an amount of solvent agent again, stir, make dissolving fully.
(2) add pH regulator agent and each additive as required, be supplemented to full dose, obtain microemulsion white to being bordering on the opalescent nano-emulsion of zona pellucida with solvent.
(3) filter: the membrane filtration of gained nano-emulsion through 0.22 μ m.
The invention has the beneficial effects as follows:
(1) 90% breast grain particle diameter is no more than 200nm in the nano-emulsion of the present invention, preferably is no more than 20nm, and its mean diameter mostly reaches 0.02 μ m (20nm), is bordering on transparent Emulsion.0.02 the emulsion droplet about μ m belongs to the Emulsion of dynamic stabilization, this vitamin E nano Emulsion can stand autoclaving (121 ℃, 20 minutes), and the content of sterilization back Emulsion does not have significant change.
(2) medicine realizes that by the Nano medication drug-supplying system initiatively target administration is one of main application of administration nano-drug administration system.The mean diameter of this vitamin E nano Emulsion is about 20nm, formed born of the same parents by cytophagy after nano level breast grain enters in the body and draw absorption, the easier arrival focus of the medicine that is cell is better brought into play curative effect, reduces the toxic and side effects of medicine to normal structure or cell simultaneously.
(3) vitamin E nano Emulsion of the present invention, its mean diameter breast grain about 20nm has effectively solved the physical stability of preparation and the chemical stability of vitamin E oil, has reduced their toxic and side effects and untoward reaction, has improved the therapeutic effect of medicine.
Description of drawings
Fig. 1 is the potential measurement of vitamin E nano Emulsion embodiment of the present invention figure as a result;
Fig. 2 is the particle size determination of vitamin E nano Emulsion embodiment of the present invention figure as a result.
The specific embodiment
Vitamin E nano Emulsion of the present invention, wherein 90% breast grain particle diameter is no more than 200nm in the Emulsion; Preferably, be no more than 150nm; More preferably, be no more than 100nm.
Preferably, the mean diameter of this breast grain is no more than 100nm, generally in 10~60nm scope, mostly is about 20~30nm.
Vitamin E nano Emulsion of the present invention, the component that contains following content: vitamin E 0.01~5%, emulsifying agent 0.2~10%, coemulsifier: 0.1~8%, this content is that the gram number in contained each component in every 100mL nano-emulsion is solvent agent polishing to 100% volume.
More preferably vitamin E 0.05~3% in the nano-emulsion of the present invention, emulsifying agent 0.5~8%, coemulsifier: 0.2~5%.
Emulsifying agent is meant and contains hydrophilic, lipophilic group on the molecular structure, can be with oil, the biphase Emulsion that is dispersed into of water under the effect of external force. the present invention is preferably tween 80, poloxamer, polyoxyethylene hydrogenated Oleum Ricini or its mixture.
Coemulsifier is meant that to assist emulsifying agent oil emulsion, water biphase, and it is more small to be simultaneously that particle diameter becomes again, the material that whole emulsifier system is more stable.The preferred n-butyl alcohol of the present invention, propylene glycol, glycerol or its mixture.
Solvent of the present invention is the various water that meet medicinal specification, as water for injection, pure water etc., or ethanol, or water and alcoholic acid mixture, it also can be used as the water and the diluent of Emulsion in prescription.
Certainly, as required, also can in vitamin E nano Emulsion, add various additives, as the pH value regulator: sodium hydroxide, potassium chloride, sodium chloride, phosphate, carbonate, citrate, nicotiamide, Benzoylamide; Be selected from as antioxidant: tea polyphenols, phytic acid, sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate; The antibacterial that need add as unsterilised oral or external preparation time the: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzoic acid, sodium benzoate, sorbic acid.
The preparation method of vitamin E nano Emulsion of the present invention comprises the steps:
A. vitamin E primary emulsion preparation process: an amount of emulsifying agent and co-emulsifier are stirred, under higher speed stirs, add appropriate vitamin E oil then, continue to stir and form the milky colostrum, add an amount of solvent again, stir, make dissolving fully.
B. add pH regulator agent and each additive as required, the pH that regulates colostrum is supplemented to full dose with solvent about 7.0, obtain microemulsion white to being bordering on the opalescent nanoscale Emulsion of zona pellucida.
C. filtration step: with the membrane filtration of step b gained nano-emulsion, to remove the impurity of greater particle size through 0.22 μ m.
Certainly, preparation method of the present invention also can adopt any existing equipment and technology that is used to prepare nano-emulsion.
Following examples are used to describe the present invention, but not as limitation of the present invention.
Various component raw material in the following example are conventional commercially available prod.
Embodiment 1
1) accurately take by weighing the 6.75g tween 80,2.25g glycerol on the thermostatic mixer stirs emulsifying agent and co-emulsifier;
2) under higher speed stirs, add the 1g vitamin E oil, continue to stir formation milky colostrum, add an amount of pure water again, stir, make dissolving fully;
3) regulate pH to 7.0 with the sodium hydroxide solution of 0.1mol/L;
4) be supplemented to 100mL with pure water, the volumetric flask standardize solution.Obtain microemulsion white to being bordering on the opalescent nanoscale Emulsion of zona pellucida;
5) nano-emulsion is through the membrane filtration of 0.22 μ m, and filtrate is irritated in suitable brown bottle, the gland encapsulation, promptly.
Embodiment 2
1) accurately take by weighing the 5.6g tween 80,1.4g glycerol on the thermostatic mixer stirs emulsifying agent and co-emulsifier;
2) under higher speed stirs, add the 1g vitamin E oil, continue to stir formation milky colostrum, add an amount of pure water again, stir, make dissolving fully;
3) regulate pH to 7.0 with the sodium hydroxide solution of 0.1mol/L;
4) be supplemented to 100mL with pure water, the volumetric flask standardize solution.Obtain microemulsion white to being bordering on the opalescent nanoscale Emulsion of zona pellucida;
5) nano-emulsion is through the membrane filtration of 0.22 μ m, and filtrate is irritated in suitable brown bottle, the gland encapsulation, promptly.
Embodiment 3
1) accurately take by weighing the 4g tween 80,2g glycerol on the thermostatic mixer stirs emulsifying agent and co-emulsifier;
2) under higher speed stirs, add the 1g vitamin E oil, continue to stir formation milky colostrum, add an amount of pure water again, stir, make dissolving fully;
3) regulate pH to 7.0 with the sodium hydroxide solution of 0.1mol/L;
4) be supplemented to 100mL with pure water, the volumetric flask standardize solution.Obtain microemulsion white to being bordering on the opalescent nanoscale Emulsion of zona pellucida;
5) nano-emulsion is through the membrane filtration of 0.22 μ m, and filtrate is irritated in suitable brown bottle, the gland encapsulation, promptly.
Embodiment 4
Prescription according to embodiment 2 prepares vitamin E nano Emulsion, measures current potential and particle diameter, the results are shown in Figure 1~2.Dilute 5,10,50,100,200 times and measure particle diameter gradually, table 1 shows that its change of size of nano-emulsion dilution back is not obvious as a result, and visible dilution is little to the size influence of nano-emulsion.Dynamic light scattering particle size instrument (Malvern Zetasizer-3000HS, Britain).
Table 1: the size after the nano-emulsion dilution
Figure G2009101549316D0000051
Embodiment 5
Prepare vitamin E nano Emulsion according to the prescription of embodiment 2 and carry out influence factor and study on the stability, the result shows that this product is at autoclaving (120 ℃), (60 ℃ of high temperature, 40 ℃), under room temperature (30 ℃, the 25 ℃) condition and illumination (each influence factor of 10 days test under the condition of 4500lx ± 500lx).The results are shown in Table 2~6.Agilent 1100 high performance liquid chromatographs (online degasser, VWD UV-detector, column oven).
Show 2:120 ℃ of heating to V in the nano-emulsion EThe influence of content (n=3)
Figure G2009101549316D0000052
Table 3:V ENano-emulsion high temperature (60 ℃) influence factor test
Table 4:V ENano-emulsion high temperature (40 ℃) influence factor test
Table 5:V E30 ℃ of tests of nano-emulsion and 25 ℃ of tests of room temperature (n=3)
Figure G2009101549316D0000063
Table 6:V ENano-emulsion high light influence factor test
Figure G2009101549316D0000064
Figure G2009101549316D0000071
The foregoing description is used for the present invention that explains, rather than limits the invention, and in the protection domain of spirit of the present invention and claim, any modification and change to the present invention makes all fall into protection scope of the present invention.

Claims (9)

1.一种维生素E纳米乳剂,其特征在于,该乳剂中含有下列含量的组分:维生素E 0.1~50g/L,乳化剂2~100g/L,辅助乳化剂:1~80g/L。余量为溶媒剂。1. a vitamin E nanoemulsion, is characterized in that, contains the component of following content in this emulsion: vitamin E 0.1~50g/L, emulsifier 2~100g/L, auxiliary emulsifier: 1~80g/L. The balance is solvent. 2.如权利要求1所述的纳米乳剂,其特征在于,维生素E优选为0.5~30g/L,乳化剂5~80g/L,辅助乳化剂:2~50g/L。余量为溶媒剂。2. The nanoemulsion as claimed in claim 1, characterized in that vitamin E is preferably 0.5-30 g/L, emulsifier 5-80 g/L, auxiliary emulsifier: 2-50 g/L. The balance is solvent. 3.如权利要求1所述的纳米乳剂,其特征在于,所述乳化剂为吐温-80、泊洛沙姆和聚氧乙烯氢化蓖麻油中的一种或几种的混合。3. nanoemulsion as claimed in claim 1, is characterized in that, described emulsifying agent is the mixing of one or more in Tween-80, poloxamer and polyoxyethylene hydrogenated castor oil. 4.如权利要求1所述的纳米乳剂,其特征在于,所述助乳化剂为正丁醇、丙二醇和甘油中的一种或几种的混合。4. nanoemulsion as claimed in claim 1, is characterized in that, described auxiliary emulsifier is the mixing of one or more in n-butanol, propylene glycol and glycerol. 5.如权利要求1所述的纳米乳剂,其特征在于,所述溶媒为水和乙醇中的一种或两种的混合。5. The nanoemulsion as claimed in claim 1, wherein the solvent is one or a mixture of water and ethanol. 6.如权利要求1所述的纳米乳剂,其特征在于,所述维生素E纳米乳剂还含有添加剂,该添加剂选自抗氧化剂、抑菌剂及防腐剂中的一种或几种。6. nanoemulsion as claimed in claim 1, is characterized in that, described vitamin E nanoemulsion also contains additive, and this additive is selected from one or more in antioxidant, antibacterial agent and preservative. 7.如权利要求6所述的纳米乳剂,其特征在于,所述抗氧化剂选自:茶多酚,植酸,亚硫酸钠、亚硫酸氢钠、焦亚硫酸钠、硫代硫酸钠。所述抑菌剂选自:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯,对羟基苯甲酸丁酯、苯甲酸、苯甲酸钠、山梨酸。7. nanoemulsion as claimed in claim 6, is characterized in that, described antioxidant is selected from: tea polyphenol, phytic acid, sodium sulfite, sodium bisulfite, sodium metabisulfite, sodium thiosulfate. The antibacterial agent is selected from: methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzoic acid, sodium benzoate, sorbic acid. 8.如权利要求1所述的纳米乳剂,其特征在于,所述维生素E纳米乳剂还含有pH调节剂,该pH值调节剂选自:氢氧化钠、氯化钾、氯化钠、磷酸盐、碳酸盐、柠檬酸盐、烟酰胺、苯甲酰胺。8. nanoemulsion as claimed in claim 1, is characterized in that, described vitamin E nanoemulsion also contains pH regulator, and this pH regulator is selected from: sodium hydroxide, potassium chloride, sodium chloride, phosphate , Carbonate, Citrate, Niacinamide, Benzamide. 9.一种权利要求1所述维生素E纳米乳剂的制备方法,其特征在于,包括如下步骤:9. a preparation method of vitamin E nanoemulsion according to claim 1, is characterized in that, comprises the steps: (1)制备维生素E初乳剂:将乳化剂和助乳化剂搅拌均匀,然后在搅拌过程中加入维生素E油,继续搅拌形成乳白色初乳,再加入适量溶媒剂,搅拌,使完全溶解。(1) Preparation of vitamin E colostrum: Stir the emulsifier and co-emulsifier evenly, then add vitamin E oil during the stirring process, continue to stir to form milky white colostrum, then add an appropriate amount of solvent, stir to dissolve completely. (2)按需加入pH调节剂和各添加剂,用溶媒补充至全量,得到微乳白色至近于透明带乳光的纳米乳剂。(2) Adding a pH regulator and various additives as required, and replenishing to the full amount with a solvent, to obtain a nanoemulsion that is slightly milky white to nearly transparent with opalescence. (3)过滤:将所得纳米乳剂经0.22μm的滤膜过滤。(3) Filtration: the obtained nanoemulsion was filtered through a 0.22 μm filter membrane.
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101982176A (en) * 2010-10-18 2011-03-02 齐鲁动物保健品有限公司 Compound sodium selenite-vitamin E oral nano-emulsion preparation for livestock and preparation method thereof
CN102551056A (en) * 2012-01-10 2012-07-11 江南大学 O/W (Water in Oil) type microemulsion model of fat-soluble nutrient with carbon chain length of (15 and preparation method thereof
CN104707499A (en) * 2015-02-13 2015-06-17 西北农林科技大学 Preparation method for nonionic bitter almond oil microemulsion
CN105168129A (en) * 2015-07-29 2015-12-23 山东迅达康生物科技有限公司 Vitamin E nanoemulsion and preparation method thereof
CN105726478A (en) * 2016-01-28 2016-07-06 武汉欧米嘉生物医药有限公司 Oral EPA(Eicoeapentaenoic acid) O/W type nanoemulsion and preparation method thereof
CN105813480A (en) * 2013-12-11 2016-07-27 帝斯曼知识产权资产管理有限公司 A nutritional reinforced composition and a process for preparation thereof
CN106389152A (en) * 2016-08-24 2017-02-15 登封市科创商务咨询有限公司 Vitamin E nourishing and skin-care lotion
CN107115349A (en) * 2017-05-05 2017-09-01 宁夏智弘生物科技有限公司 A kind of vitaminAD E microemulsion injections for animals and preparation method thereof
CN107802512A (en) * 2017-12-07 2018-03-16 武汉大学 A kind of vitamin E nano-emulsion, nanometer emulsifiable paste and preparation method thereof

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101982176A (en) * 2010-10-18 2011-03-02 齐鲁动物保健品有限公司 Compound sodium selenite-vitamin E oral nano-emulsion preparation for livestock and preparation method thereof
CN101982176B (en) * 2010-10-18 2012-07-04 齐鲁动物保健品有限公司 Compound sodium selenite-vitamin E oral nano-emulsion preparation for livestock and preparation method thereof
CN102551056A (en) * 2012-01-10 2012-07-11 江南大学 O/W (Water in Oil) type microemulsion model of fat-soluble nutrient with carbon chain length of (15 and preparation method thereof
CN105813480A (en) * 2013-12-11 2016-07-27 帝斯曼知识产权资产管理有限公司 A nutritional reinforced composition and a process for preparation thereof
CN104707499A (en) * 2015-02-13 2015-06-17 西北农林科技大学 Preparation method for nonionic bitter almond oil microemulsion
CN105168129A (en) * 2015-07-29 2015-12-23 山东迅达康生物科技有限公司 Vitamin E nanoemulsion and preparation method thereof
CN105168129B (en) * 2015-07-29 2018-02-23 山东迅达康生物科技有限公司 A kind of vitamin E nano-emulsion and preparation method thereof
CN105726478A (en) * 2016-01-28 2016-07-06 武汉欧米嘉生物医药有限公司 Oral EPA(Eicoeapentaenoic acid) O/W type nanoemulsion and preparation method thereof
CN106389152A (en) * 2016-08-24 2017-02-15 登封市科创商务咨询有限公司 Vitamin E nourishing and skin-care lotion
CN107115349A (en) * 2017-05-05 2017-09-01 宁夏智弘生物科技有限公司 A kind of vitaminAD E microemulsion injections for animals and preparation method thereof
CN107802512A (en) * 2017-12-07 2018-03-16 武汉大学 A kind of vitamin E nano-emulsion, nanometer emulsifiable paste and preparation method thereof

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