CN102166234A - Oil-in-water type nanoemulsion oral liquid with bupleurum oil and preparation method thereof - Google Patents
Oil-in-water type nanoemulsion oral liquid with bupleurum oil and preparation method thereof Download PDFInfo
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- CN102166234A CN102166234A CN2011100859172A CN201110085917A CN102166234A CN 102166234 A CN102166234 A CN 102166234A CN 2011100859172 A CN2011100859172 A CN 2011100859172A CN 201110085917 A CN201110085917 A CN 201110085917A CN 102166234 A CN102166234 A CN 102166234A
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Abstract
The invention discloses an oil-in-water type nanoemulsion oral liquid with bupleurum oil. The oral liquid has the particle size of 1-100 nm and is prepared from the following raw materials in percentage by weight: 20.00-40.00% of surfactant, 6.00-14.00% of cosurfactant, 1.00-5.00% of oil, 0.01-10.00% of bupleurum oil and the balance of distilled water, wherein the sum of mass percentages of the raw materials is 100%. By using the nanoemulsion oral liquid with the bupleurum oil, the bioavailability of the bupleurum oil is increased, the medicine stability is enhanced, the medicine metabolism time of the bupleurum oil in vivo is prolonged, and various adverse reactions caused by adopting a bupleurum oil injection can be effectively avoided; and the nanoemulsion oral liquid with the bupleurum oil has the advantages of less usages of auxiliary materials, low production cost and broad market prospect in the medicine field.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of Oleum Bupleuri novel form, particularly oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of a kind of transparent and stable and preparation method thereof with antiinflammatory, calmness, refrigeration function.
Background technology
The Oleum Bupleuri refrigeration function and the antiinflammatory sedation that extract from bupleurum Chinese are evident in efficacy, are the diaphoretic medicines that a kind of quilt is extensively recommended.Injection of Radix Bupleuri is the most general a kind of Oleum Bupleuri goods, contains dry former medicine 1 gram in every milliliter.But injection of Radix Bupleuri stability is low, and route of administration is single, is only applicable to intramuscular injection; Bioavailability is low; Can cause untoward reaction.The routine dose injection just can cause anaphylaxis and toxic reaction.Anaphylaxis is based on anaphylactic shock and allergic rash.Toxic reaction causes that body temperature descends after with intramuscular injection, and it is main that decreased heart rate, blood pressure temporarily descend the degradation symptom, can cause acute lung edema in the time of seriously.For blood circulation the patient of disease is arranged, very easily cause untoward reaction because of body reduces the toleration of this medicine.These deficiencies have restricted its application clinically greatly.
Summary of the invention
At above-mentioned problems of the prior art and defective, the object of the present invention is to provide a kind of dissolubility height, good stability, slow-releasing is strong, safety is distinguished oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid.
The technical scheme that realizes the foregoing invention purpose is a kind of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid, and the particle diameter of this oral liquid is 1nm～100nm, is made by following weight percentages:
Surplus is a distilled water
The mass percent sum of above-mentioned raw materials is 100%.
The optimum ratio of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention is:
Surplus is a distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
The best proportioning of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention is:
Described surfactant is any one of tween 80, RH-40.
Described cosurfactant is an ethanol, 1, the mixture of any one or a few in 2-propylene glycol, the glycerol.
Described oil is any one or a few the mixture in ethyl acetate, isopropyl myristate, the liquid paraffin.
Described surfactant is by surfactant and cosurfactant is composite according to a certain percentage forms.
Oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention in the selection of surfactant, is selected the non-ionic surface active agent of avirulence and good biocompatibility for use.Nonionic surfactant is more stable in solution, is not subject to the influence of strong electrolyte, inorganic salts, also is not subject to the influence of soda acid, and good with the compatibility of other surfactants, and haemolysis is less.Consider the easy formation and the stability of nano-emulsion, the present invention selects the liquid nonionic surfactant of HLB between 10～15 for use.Available surfactant has: any one among tween 80, the RH-40.
The formation of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention needs the participation of cosurfactant, and its effect mainly is the HLB value of reconciliation statement surface-active agent, assists surfactant to reduce interfacial tension between profit; Reduce the mutual repulsive force and the charge repulsion of surfactant, impel interfacial film to have good compliance and flowability, required interface bending energy when reducing nano-emulsion and generating promotes the formation of the film that radius of curvature is very little, enlarge microemulsion and form the zone, make nano-emulsion be easy to form.Can select the cosurfactant of HLB＜10 for use: ethanol, 1, the mixture of any one or a few in 2-propylene glycol, the glycerol.
Oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention according to when the emulsifying oil phase required surfactant HLB value and surfactant be worth mutually when close, the principle that formed emulsion is stable, the oil phase of selecting for use has: the mixture of any one or a few in ethyl acetate, isopropyl myristate, the liquid paraffin.Be in a liquid state under these oily room temperature, do not have bad abnormal smells from the patient.
The surfactant phase of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention and the preparation of oil phase are undertaken by following method: undertaken composite by formula proportion surfactant and cosurfactant, calculate the HLB value of this system, stir, get the HLB value mutually according to surfactant again, select one or more oil, transfer its ratio, make the required HLB value of its emulsifying close with the HLB value mutually of surfactant.
A further object of the invention provides the above-mentioned method of stating oil-in-water type Oleum Bupleuri nano-emulsion preparation, it is characterized in that, comprises the following steps:
1) it is standby to take by weighing surfactant, cosurfactant, oil, Oleum Bupleuri and distilled water;
2) with surfactant and cosurfactant mix homogeneously;
3) Oleum Bupleuri is added in the oil, change oil phase and surfactant ratio mutually in 1: 9～9: 1 rules, fully stir at 20 ℃～25 ℃ slow adding distil waters, until the formation system is stable, faint yellow or colourless, clear, viscosity is little and the O/W type nanometer emulsion of good fluidity.
Oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid provided by the invention is a kind of clearing away heat and expelling pathogen in the exterior medicine.Be used for the treatment of the heating that flu, influenza and malaria etc. cause, the disease that upper respiratory tract infection such as flu, influenza are caused has significant curative effect simultaneously.Usage and dosage of the present invention is to press the 14g/kg oral administration, twice of every day.
Oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention is compared the bioavailability that has improved Oleum Bupleuri with common Oleum Bupleuri injection, strengthened stability of drug, delayed Oleum Bupleuri medicine in vivo for the time, can effectively avoid various anaphylaxiss and toxic reaction, reduce the stress stimulation of animal because of using the Oleum Bupleuri injection to cause.Supplementary product consumption is few, and production cost is low, has vast market prospect at field of medicaments.
Description of drawings
The particle diameter microscope figure of figure-1 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention.
The specific embodiment
Below the stability test, drug effect and the contrast test that provide by the inventor further specify the beneficial effect of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention.
The particle diameter of test example 1 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention detects
Sample thief 1ml with 20 times of distilled water dilutings, measures its particle diameter with laser particle size analyzer, and droplet diameter distribution is between 1nm～100nm, and as shown in Figure 1, outward appearance is faint yellow or the achromaticity and clarification transparent yellow liquid, has good stable.。
The stability test of test example 2 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquids of the present invention
Prepare 3 batches of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquids of the present invention, sealing by fusing places-4 ℃ of refrigerators, room temperature and 60 ℃ of constant temperature ovens interior (relative humidity is 75%) respectively in the 5mL ampoule bottle, and sample thief in the time of 20,40 days carries out outward appearance and investigates.
Table-1 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid reserved sample observing result of the test of the present invention
The test of pesticide effectiveness and the contrast test of test example 3 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquids of the present invention
Get 36 of the qualified healthy rabbits of body temperature, be divided into 4 groups, that is: blank group, model control group, Oleum Bupleuri nanometer emulsion oral liquid group and Oleum Bupleuri injection group by sex, body weight stratified random.Survey the anus temperature respectively 2 times, with average as normal body temperature.Blank group auricular vein injecting normal saline 1ml/kg; The other auricular vein injection of model control group and each drug component typhoid fever, paratyphoid fever vaccine 1ml/kg.After treating that fervescence surpasses 1 ℃, it is 030015137 Oleum Bupleuri injection 14g/kg that the administration group is irritated the accurate font size of stomach Radix Bupleuri nanometer emulsion oral liquid of the present invention 14g/kg and injection Hebei Yuanzheng Medicine Co., Ltd country respectively, and blank group and model control group are all irritated stomach 0.5% sodium carboxymethyl cellulose 10ml/kg.After the administration 60,90,120,180,240, during 300min, measure the anus temperature with WSC-411P type portable digital temperature measurer respectively.And the state of respectively organizing after laboratory animal is taken medicine is observed in attention.
The drug effect and the comparative test result of table-1 oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention
Compare P＜0.05, P＜0.01, P＜0.001 with the matched group model
Behind model control group and each medicine group auricular vein injection typhoid fever, the paratyphoid fever vaccine 1.5h, fervescence is between 1.05～1.13 ℃, and behind the blank group auricular vein injecting normal saline 1.5h, body temperature only raises 0.03 ℃, shows that typhoid fever, paratyphoid fever vaccine can prepare experimental rabbit fever models.In the 300min of experimental observation, the fervescence of model control group continue to exist, and with blank group comparing difference highly significant, it is reliable and stable to further specify the experimental rabbit fever models that typhoid fever, paratyphoid fever vaccine production go out.
Oleum Bupleuri injection and oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention all have significant curative effect to the heating that typhoid fever, paratyphoid fever vaccine cause by testing as can be known, but 9 rabbits of Oleum Bupleuri injection group have 3 decreased heart rate to occur, blood pressure temporarily descends the degradation untoward reaction, this shows that the drug effect of oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid of the present invention is safe in the Oleum Bupleuri injection.
Below in conjunction with the specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
1) with tween 80 30g and dehydrated alcohol 10g mix homogeneously;
2) Oleum Bupleuri 6g is added ethyl acetate 4g mix homogeneously;
3) change oil phase and surfactant ratio mutually in 1: 9～9: 1 rule, fully stir at 20 ℃～25 ℃ slow adding distil water 50g, until the formation system is stable, faint yellow or colourless, clear, viscosity is little and the O/W type nanometer emulsion of good fluidity.
Embodiment 2
Tween 80 35g, dehydrated alcohol 14g, ethyl acetate 2g, Oleum Bupleuri 4g, distilled water 45g.
Embodiment 3
Tween 80 20g, dehydrated alcohol 12g, ethyl acetate 3g, Oleum Bupleuri 9g, distilled water 56g.
Embodiment 4
Tween 80 40g, dehydrated alcohol 8g, ethyl acetate 1.99g, Oleum Bupleuri 0.01g, distilled water 50g.
Embodiment 5
Tween 80 20g, dehydrated alcohol 13g, ethyl acetate 1g, Oleum Bupleuri 1g, distilled water 65g.
Embodiment 6
RH-40 25g, dehydrated alcohol 6g, ethyl acetate 5g, Oleum Bupleuri 10g, distilled water 54g.
Embodiment 7
Tween 80 30g, ethanol 4g, 1,2 propylene glycol 2g, isopropyl myristate 3g,, Oleum Bupleuri 1g, distilled water 60g.
Embodiment 8
Tween 80 20g, ethanol 4g, 1,2 propylene glycol 2g, isopropyl myristate 4g, Oleum Bupleuri 5g, distilled water 65g.
Embodiment 9
Tween 80 25g, glycerol 7g, 1,2 propylene glycol 3g, liquid paraffin 4g, Oleum Bupleuri 6g, distilled water 55g.
Claims (4)
1. oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid is characterized in that the particle diameter of this oral liquid is 1nm～100nm, is made by following weight percentages:
Surplus is a distilled water
The mass percent sum of above-mentioned raw materials is 100%;
Described surfactant is any one among tween 80, the RH-40;
Described cosurfactant is an ethanol, 1, the mixture of any one or a few in 2-propylene glycol, the glycerol;
Described oil is any one or a few the mixture in ethyl acetate, isopropyl myristate, the liquid paraffin.
2. oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid according to claim 1 is characterized in that, is made up of following weight percentages:
Surplus is a distilled water
The mass percent sum of above-mentioned raw materials is 100%.
3. oil-in-water type Oleum Bupleuri nanometer emulsion oral liquid according to claim 1 is characterized in that, is made up of following weight percentages:
4. the preparation method of the described oil-in-water type Oleum Bupleuri of claim 1 nano-emulsion preparation is characterized in that, comprises the following steps:
1) it is standby to take by weighing surfactant, cosurfactant, oil, Oleum Bupleuri and distilled water;
2) with surfactant and cosurfactant mix homogeneously;
3) Oleum Bupleuri is added in the oil, change oil phase and surfactant ratio mutually in 1: 9～9: 1 rules, fully stir at 20 ℃～25 ℃ slow adding distil waters, until the formation system is stable, faint yellow or colourless, clear, viscosity is little and the O/W type nanometer emulsion of good fluidity.
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Cited By (4)
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| WO2014198173A1 (en) * | 2013-06-12 | 2014-12-18 | Zhang Xiaoyan | Compound fructus forsythiae-radix bupleuri oil nanoemulsion preparation |
| CN105901713A (en) * | 2016-04-26 | 2016-08-31 | 广西三椿生物科技有限公司 | Constipation preventing microemulsion and preparation method thereof |
| CN106727311A (en) * | 2016-12-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | A kind of oil-in-water type orixine nano-emulsion and preparation method thereof |
| CN110664750A (en) * | 2019-10-23 | 2020-01-10 | 贵州中医药大学 | Radix bupleuri nano preparation, preparation method, detection method and application |
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| CN1748777A (en) * | 2004-09-15 | 2006-03-22 | 上海医药工业研究院 | Chinese medicine volatoile oil self-mciro emulsifying nano composition and preparing method |
| CN101176741A (en) * | 2006-11-12 | 2008-05-14 | 黑龙江大学 | Hydroxypropyl-beta-cyclodextrin clathrate, preparing method and application of radix bupleuri volatile oil |
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2011
- 2011-04-06 CN CN2011100859172A patent/CN102166234A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1748777A (en) * | 2004-09-15 | 2006-03-22 | 上海医药工业研究院 | Chinese medicine volatoile oil self-mciro emulsifying nano composition and preparing method |
| CN101176741A (en) * | 2006-11-12 | 2008-05-14 | 黑龙江大学 | Hydroxypropyl-beta-cyclodextrin clathrate, preparing method and application of radix bupleuri volatile oil |
Non-Patent Citations (1)
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| 孙秀萍等: "柴胡解热的物质基础、机制及影响因素探讨", 《山东中医药大学学报》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014198173A1 (en) * | 2013-06-12 | 2014-12-18 | Zhang Xiaoyan | Compound fructus forsythiae-radix bupleuri oil nanoemulsion preparation |
| EA029387B1 (en) * | 2013-06-12 | 2018-03-30 | Сяоянь Чжан | Compound forsythia suspensa-radix bupleuri oil nanoemulsion preparation |
| CN105901713A (en) * | 2016-04-26 | 2016-08-31 | 广西三椿生物科技有限公司 | Constipation preventing microemulsion and preparation method thereof |
| CN106727311A (en) * | 2016-12-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | A kind of oil-in-water type orixine nano-emulsion and preparation method thereof |
| CN110664750A (en) * | 2019-10-23 | 2020-01-10 | 贵州中医药大学 | Radix bupleuri nano preparation, preparation method, detection method and application |
| CN110664750B (en) * | 2019-10-23 | 2022-03-15 | 贵州中医药大学 | Radix bupleuri nano preparation, preparation method, detection method and application |
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