CN106177511A - A kind of compound alprenolol nano-emulsion antihypertensive drug - Google Patents

A kind of compound alprenolol nano-emulsion antihypertensive drug Download PDF

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CN106177511A
CN106177511A CN201610503134.4A CN201610503134A CN106177511A CN 106177511 A CN106177511 A CN 106177511A CN 201610503134 A CN201610503134 A CN 201610503134A CN 106177511 A CN106177511 A CN 106177511A
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alprenolol
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emulsion
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antihypertensive drug
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张鸿利
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Abstract

The invention discloses a kind of compound alprenolol nano-emulsion antihypertensive drug, its raw material and mass percent thereof be: alprenolol 0.1%～13%, surfactant 5%～45%, cosurfactant 1%～25%, oil 5%～35%, cosolvent 0～30%, Ramulus Uncariae Cum Uncis water extract 0.5%～15%, Rhizoma Gastrodiae water extract 0.5%～15%, remaining composition is distilled water, and the mass percent sum of above-mentioned raw materials is 100%.This nano-emulsion emulsion droplet granule is little, be evenly distributed, viscosity is little, good fluidity.Nano-emulsion can improve medicine dissolution and the penetrating power of alprenolol, increases the stability of alprenolol, is raised by blood brain barrier level.After alprenolol is prepared as nano-emulsion dosage form, hence it is evident that add its antihypertensive effect, extend the half-life of its medicine, decrease administration number of times.There is boundless market prospect.

Description

A kind of compound alprenolol nano-emulsion antihypertensive drug
Technical field
The invention belongs to field of medicaments, relate to the novel form of a kind of antihypertensive drug alprenolol, particularly to one Compound alprenolol nano-emulsion antihypertensive drug.
Technical background
Alprenolol (Alprenolol) i.e. 1-(isopropylamino)-3-(2-allyl benzene epoxide)-2-propanol [1- (Isopropylamino)-3-(2-allylphenoxy)-2-propanol].Molecular formula C15H23NO2.Molecular weight 249.35. CAS 13655-52-2.This product has epinephrine beta receptor position to suppress the effect of catecholamine competitively.By weakening or Prevent beta receptor excited and make the contractility of heart and contraction speed decline, by the conduct velocity of conducting system, make heart To motion or stress habituation.This product is by maincenter, adrenergic neuron blockade, anti-renin activity and heart row's blood Amount attenuating etc. reduces blood pressure, it is adaptable to treatment hypertension.Due to this product energy antagonism catecholamine effect, it is also used for treatment thin addicted to chromium Born of the same parents' tumor and hyperthyroidism, make the activity of β 1 and beta 2 receptor be in inhibitory state.This product belongs to intrinsic sympathomimetic acitivity , the beta receptor blocking agent of non-selectivity, it can make blood pressure reduce, but less to the inhibitory action of cardiac muscle and Atrioventricular Conduction.Oral Absorb good.
Existing such as the antihypertensive drugs of alprenolol tablet currently on the market, although from gastrointestinal absorption, but to inhale after Kou Fu Receiving not exclusively, additionally the dissolution rate of tablet Chinese traditional medicine is slow, bioavailability extreme difference so that the drug effect of alprenolol cannot be rapid It is obtained by；On the other hand, Rhizoma Gastrodiae and the significant Chinese medicine of these effects of Ramulus Uncariae Cum Uncis do not have suitable dosage form to be applied yet.
Summary of the invention
For shortcomings and deficiencies present in prior art, it is an object of the invention to provide one and be evenly distributed, stable Property good, permeability is high, dissolubility is good, bioavailability is high compound alprenolol nano-emulsion antihypertensive drug.
The technical scheme realizing foregoing invention purpose is:
A kind of compound alprenolol nano-emulsion antihypertensive drug, its raw material and mass percent thereof be:
Remaining composition is distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
Described surfactant is polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or pool In Luo Shamu 188 any one or with the mixture of span80, these surfactants are to human body low toxicity, safe, non-stimulated.
The oil oil that is that the present invention selects is any in isopropyl myristate, ethyl acetate, oleic acid or ethyl oleate The mixture of one or more, safe and nontoxic.
Described cosurfactant is any one in dehydrated alcohol, 1,2-PD, PEG400 or glycerol Kind or several mixture.
Compound alprenolol nano-emulsion antihypertensive drug of the present invention, it is characterised in that: the particle diameter of this medicine between 10～ Between 100nm.
The present invention selects Ramulus Uncariae Cum Uncis to have good hypotensive effect.Ramulus Uncariae Cum Uncis decoct, no matter to anesthetized animal or not anesthetized animal, just Often animal or hypertension animal, no matter also intravenous injection or gastric infusion all have hypotensive effect.And without tachylaxis.Anesthesia Intravenous rabbit injection Ramulus Uncariae Cum Uncis decoct 2～3g/kg or anesthetized dog intravenous injection this decoct 0.05g/kg, all can make blood pressure drop than former level Low 30～40%, continue more than 3～4 hours.Anesthetized cat intravenous injection an ancient unit of weight rattan decoct 6.25g/kg, Rhomotoxine hydrochlorate 20mg/kg, Ramulus Uncariae cum Uncis alkali hydrochlorate 20mg/kg, blood pressure is all in three phase change: first blood pressure lowering, the most quickly gos up, declines the most again, Amplitude of Hypotensive is respectively 30～70%, 13.9～23.2% and 11.7～41.7%, maintains 3～4 hours.But Ramulus Uncariae Cum Uncis decoct is decocted for a long time Then hypotensive effect weakens, to be advisable within decocting 20 minutes.The underpressure of an ancient unit of weight rattan ethanol water extract 3g/kg and decoct 2g/kg phase Seemingly.Cat intravenous injection Ramulus Uncariae cum Uncis alkali 20mg/kg or Rhomotoxine 20mg/kg all has hypotensive effect；Rat oral gavage Rhomotoxine 50mg/ Kg. 20 days, sky or Ramulus Uncariae cum Uncis alkali 50mg/kg. days 15 days, all have notable hypotensive effect.With renal hypertensive rat, respectively gavage an ancient unit of weight Rattan decoct 8g/kg, Rhomotoxine 50mg/kg mitrinermine 50mg/kg, every day 1 time, continuous 15～20 days, blood pressure was in the 3rd～5 It begins to decline, and within the 7th～15 day, is down to minimum, and average blood pressure lowering is respectively 16.9mmHg, 12mmHg and 18mmHg；Ramulus Uncariae cum Uncis alkali 20mg/kg, lumbar injection, rat blood pressure drops on the same day, medication 8 days, average blood pressure lowering 24mmHg can be made.Anesthetized dog 12, vein After constant speed perfusion Rhomotoxine 20mg/kg, blood pressure drops occurs；Cardiac output first of short duration increase the most slightly reduces；Total peripheral blood Pipe resistance substantially reduced at the blood pressure lowering initial stage；Heart rate significantly slows down；Stroke volume substantially increases.Rhomotoxine is by reducing Peripheral resistance (in early days) and reduce cardiac output (later stage) cause blood pressure lowering.From the impact on anesthetized dog and cat myocardiac mechanics of an ancient unit of weight rattan alkali, use Dp/dt is as using multi-proxy investigations, while measuring dp/dt, measures left locular wall muscular tension with stressometer bow, as One myocardial contraction index, and it is little to combine load dependence, the VcE class of reflection shrinkage level acute change sensitivity refers to Mark, observes an ancient unit of weight rattan alkali muscular strength effect to its heart.After intravenous injection Ramulus Uncariae cum Uncis alkali 20mg/kg, significantly reduce LVP, dp/dtmax, The myocardial contractility indexs such as LVMT, Vpm, and Vmax；Ramulus Uncariae cum Uncis alkali can make intraventricular pressure decline, therefore TTI reduces, and represents cardiac energy And O2Consumption reduce, myocardium under-supply time be likely to be of Protection significance.Though Ramulus Uncariae cum Uncis alkali has obvious negative inotropic action And O can be reduced2, but indices tends to recovering for about 15 minutes after medicine, shows the effect of its suppression myocardial contractility It is reversible.This medicine hypotensive effect is in addition to vasodilation, Peripheral resistance reduce, and part is suppressed with myocardial contractility the most relevant System.Use isolated rabbit thoracic aorta strips, inquire into the mechanism of Ramulus Uncariae cum Uncis alkali expansion blood vessel, and compared with verapamil.Both can make K+With Shrink tension caused by norepinephrine declines, K+The effect shunk is noticeably greater than norepinephrine, and two medicines substantially weaken Ca in norepinephrine contractile response+Release part, and make K+, norepinephrine and Ca2+Amount-effect curve moves to right, Big reaction is forced down, and prompting an ancient unit of weight rattan alkali blocks outer Ca2+Interior stream and interior Ca2+Release, its feature is similar to verapamil.The methanol of an ancient unit of weight rattan Water extract, to rat intravenous injection 0.1mg/kg, also has strong and lasting hypotensive effect.
Rhizoma Gastrodiae (Gastrodia elata Bl), sweet in the mouth, slightly warm in nature.There are the functions such as suppressing the hyperactive liver, endogenous wind stopping, spasmolytic.Rhizoma Gastrodiae is to fiber crops Liquor-saturated dog and the impact of rabbit blood kinetic parameter.Anesthetized dog hemodynamic experiments: take experimental dog 16, male and female dual-purpose, body weight 11.9 ± SD1.9kg, random decile two groups, pentobarbital sodium 30mg/kg, intravenous injection is anaesthetized, with MPU-0.5A pressure transducing Device measures mean arterial blood pressure (mAP), leads physiograph record by RM-6000 type more.Duodenal administration, tests and mixes with 20%AG Suspension, comparison normal saline.Give the vertebral artery flows increase by 15 in 10～60 minutes after AG～30% (P ＜ 0.05,0.01), At 30～40 minutes during its effect peak.All other kinetic parameters are all without substantially changing.Show as AG selectivity increase vertebra to move Other cardiovascular effect any is had no while arteries and veins flow.Anesthetized rabbit internal carotid artery flow and cardiac output experiment: Japan plants big Ear rabbit 24, male and female dual-purpose, body weight 2.2 ± 0.4kg, it is randomly divided into three groups, duodenal administration, 20%AG suspendible is used in experiment Liquid, flat (250ug/ml) that positive control blocks with Buddhist nun, comparison normal saline.Give after Rhizoma Gastrodiae water extract in 10～60 minutes necks Arterial flow increases by 24～111%, and at 40～60 minutes during its effect peak, cardiac output there is no substantially change.Normal saline group Above-mentioned two indexs have no significant change.Flat group of Buddhist nun's card after medication 20-60 minute, internal carotid artery flow increase by 41～ 88%, at 30～50 minutes during its effect peak, cardiac output had slight increase at 10～40 minutes.From above-mentioned experiment prompting due to Rhizoma Gastrodiae water extract, absorbs rapidly, effective soon, oral several avirulences, therefore cerebrovascular disease is had Development volue.
In the present invention all little, so adding ethanol, acetic acid or phosphorus due to alprenolol dissolubility in water and oil Acid is cosolvent.
The present invention adds in medicine and bland helps surface such as ethanol, 1,2-PD, glycerol or Polyethylene Glycol 400, in addition to hydrotropy effect, cosurfactant primarily to adjust surfactant hydrophile-lipophile balance value (HLB), Oil water interfacial tension is reduced further, increases profit and the rigidity of limitans.Cosurfactant is incorporated in interfacial film, Promote the formation of radius of curvature very membranelle, expand the newborn district area of compound recipe alprenolol nano-emulsion.
The compound recipe alprenolol nano-emulsion of the present invention is administered orally, and greatly improves the dissolubility of medicine, reduces Medicine first pass effect in vivo, promotes the gastrointestinal absorption of medicine.Alprenolol is extremely difficult dissolving in water, makes the transhipment of medicine And absorption becomes difficulty, nano-emulsion substrate is that alprenolol provides good dissolving environment.Time oral can through Lymphatic, gram Take first pass effect and molecule by barrier during gastrointestinal tract.Additionally, compound recipe adds Ramulus Uncariae Cum Uncis water extract and the Rhizoma Gastrodiae water of pure natural Extract, improves the curative effect of this nano-emulsion, and it is more lasting to pressurize.
The compound recipe alprenolol nano-emulsion of the present invention compared with prior art, has the advantage that
1. the diameter of aspirin particle of the alprenolol resisting hypertension nano-emulsion of the present invention is between 10～100nm, and mean diameter is 39.8nm, is to be dissolved in cosolvent by alprenolol, then dissolves each other with oil phase, addition surfactant (or and help surface activity Agent), it is titrated to uniform, transparent nano-emulsion system with distilled water.The compound recipe alprenolol nano-emulsion formed reaches containing alprenolol More than 6.3%.
2. the alprenolol resisting hypertension nano-emulsion of the present invention is evenly distributed, and system is transparent, good stability, has relatively low table Surface tension, water-in-oil type nanoemulsion has good mobility.
3. the alprenolol resisting hypertension nano-emulsion of the present invention is swallowed by reticuloendothelial cell rapidly after being administered, and makes medicine fast Speed onset, and maintain constant blood drug level and pharmacodynamics effect, improve the bioavailability of medicine, reduce the consumption of medicine and make Use number of times.
4. compound recipe adds Ramulus Uncariae Cum Uncis water extract and the Rhizoma Gastrodiae water extract of pure natural, improves the curative effect of this nano-emulsion, and Pressurize more lasting.
5. the alprenolol resisting hypertension nano-emulsion preparation method of the present invention is simple, efficacy stability, and raw power consumption is low.
6. can be made into after the present invention makes nanometer oral liquid directly take, also can be through capsule encapsulating or lyophilised powder technology etc. Process.
Accompanying drawing explanation
Fig. 1 is compound recipe alprenolol nano-emulsion electromicroscopic photograph of the present invention.
Fig. 2 is compound recipe alprenolol nano-emulsion granularmetric analysis figure of the present invention.
Detailed description of the invention
Inventor provides concrete preparation method embodiment and uses the test of pesticide effectiveness to further illustrate the effect of medicine of the present invention Really.
Test example 1 compound alprenolol nano-emulsion antihypertensive drug of the present invention size is analyzed
The present invention detects (Fig. 1) through transmission electron microscope, and drop is that class is spherical, and good dispersion, without adhesion.Through Malvern Particle Size Analyzer detection (Fig. 2) its diameter Distribution is between 21.4～60.1nm, and mean diameter is 39.8nm.
Test example 2 compound alprenolol nano-emulsion antihypertensive drug of the present invention stability analysis
Compound recipe alprenolol of the present invention is observed by following centrifugal test, photo-stability testing, temperature stability test etc. The stability of nanoemulsion antihypertensive drug, observes whether the present invention has the wild effects such as layering, muddiness or crystal precipitation.
1. high speed centrifugation test
Take the compound alprenolol nano-emulsion antihypertensive drug of the present invention prepared in right amount in centrifuge tube, with 15 The rotating speed of 000r/min is centrifuged 10min, and after centrifugal test, compound alprenolol nano-emulsion antihypertensive drug of the present invention is still protected Hold the clear before being centrifuged, have no the wild effects such as layering, muddiness or crystal precipitation.
2. photo-stability testing
The compound alprenolol nano-emulsion antihypertensive drug prepared in right amount is loaded transparent good little glass colourless, transparent In glass bottle, seal, be positioned over 10d under normal lighting conditions, observe every 24h sampling.Result shows compound recipe alprenolol nanometer Breast antihypertensive drug every part sample all keeps clear, has no the wild effects such as layering, muddiness or crystal precipitation.
3. temperature stability test
The compound alprenolol nano-emulsion antihypertensive drug prepared in right amount is loaded transparent good colourless, clear glass In Ping, seal, be positioned in 4 DEG C, room temperature (25 DEG C) and 40 DEG C three each 30d of investigation that keeps sample under temperature conditions, see every 3d sampling Examine.Result shows, compound alprenolol nano-emulsion antihypertensive drug all keeps clear, not under these three kinds of temperature conditionss See the wild effects such as layering, muddiness or crystal precipitation.
4. long-term stable experiment
3 batches of nano-emulsions are sealed in Brown Glass Brown glass bottles and jars only, are placed under the conditions of (25 ± 2) DEG C, relative humidity (60 ± 5) % 12 Individual month, sample when 0,3,6,9 and 12 months, investigate character and the changes of contents of nano-emulsion, and list of references statistical Analysis method, calculates the effect duration of compound alprenolol nano-emulsion antihypertensive drug.Result of the test shows in long term test condition Under, the outward appearance of compound alprenolol nano-emulsion antihypertensive drug is always maintained at clear and bright, homogeneous, have no layering, complexion changed, flocculation and The phenomenons such as breakdown of emulsion；Alprenolol content in system extends in time and is gradually lowered, and its content-time changing curve provides Equation of linear regression, the effect duration calculating compound alprenolol nano-emulsion antihypertensive drug is 27.13 months.
Test example 3 rat tails manometry measures the drug effect of compound alprenolol nano-emulsion antihypertensive drug (with commercially available Alprenolol sheet contrasts)
SHR rat 30 is only randomly divided into 3 groups, and often group 10, is set to alprenolol sheet intervention group, compound recipe alprenolol Nano-emulsion group and positive controls, first two groups give alprenolol sheet suspension and compound recipe alprenolol nano-emulsion is each respectively 15mg/kg d, is dissolved in drinking-water, is all administered from drinking-water, 1 time/d, continuous 14 weeks.WKY rat 10 is Normal group, SHR rat 10 is positive controls, matched group not drug, normal water.
Measure each group of rat tail artery blood pressure.(before medication) pressure measurement 1 time when Mus age is 6 weeks, 7 weeks ages of Mus are (after medication 1 Week) pressure measurement 1 time, surveying 1 blood pressure every two weeks later, terminating until testing.The results are shown in Table 1.
The comparison (x ± s, n=10) of rat SBP respectively organized by table 1
Result shows, compound recipe alprenolol nano-emulsion compares with positive controls, and difference is extremely notable, shows that alprenolol is not But the blood pressure of positive rats can be significantly reduced, and antihypertensive effect effect compared with alprenolol tablet is more preferable.
Test example 4 toxicity test
Product of the present invention is carried out with the contrast of commercially available alprenolol tablet in strict accordance with new drug nonphosphorylated neurofilament H method Acute toxicity test, repeated dose toxicity test, genetic toxicity test (include the test of Salmonella reversion test, Micronuclei In The Mouse Bone Marrow, body Outer cultivation mammalian cell chromosome mutation test), reproductive toxicity test (General Reproductiv e Toxicity Assessment, sensitive period to teratogenic agent poison Property test, perinatal toxicity test), carcinogenic test, immunotoxicity test and Local irritation study, result of the test is as follows.
This product is to Mouse Acute Toxicity experiment conclusion: contrast with commercially available alprenolol tablet, compound recipe alprenolol nano-emulsion Do not occur measuring interior untoward reaction and death.
The genetoxic examinations such as the Salmonella reversion test of product of the present invention, mouse inbred strain and testis chromosomal aberration test The result tested is feminine gender.
Rat 30d feeds the result of product of the present invention and shows: contrast with commercially available alprenolol tablet, within experimental period, multiple In side's alprenolol nano-emulsion metering, each test group of animals growth promoter is good, body weight, food ration, routine blood test, blood biochemistry, internal organs The indexs such as coefficient all within normal range, histopathologic examination's also no abnormality seen.
This product long term toxicity test conclusion: contrasting with commercially available alprenolol tablet, within experimental period, compound recipe alprenolol is received In rice breast metering, this medicine has no rat untoward reaction for three months at continuous gastric infusion, and every Index for examination is all at normal model In enclosing, its main organs of pathologic finding and target organ are showed no the toxic pathological change that this guiding drug rises.
The median lethal dose(LD 50) of Ramulus Uncariae cum Uncis alkali and the injection of Rhomotoxine mouse peritoneal is respectively 162.3mg/kg and 144.2mg/kg, During poisoning, activity reduces, general weakness；Decoct 10g/kg every day divides 2 times and gavages 10 days to rabbit, and Rhomotoxine is given big with 50mg/kg Mus gavage 14 days, is showed no the change of signs of toxicity and internal organs pathomorphism；Rhomotoxine presses per kilogram 50mg Yu 100mg respectively Give children rats gavaged February, low dose group to growth, grow, Liver and kidney function and hemogram all have no significant effect, and the cause of high agent group The dead heart of animal, liver, kidney are all in obvious pathological change, therefore when heavy dose or long-term taking, it should be noted that the inspection of Liver and kidney function Look into.The median lethal dose(LD 50) that mouse peritoneal is injected by Ramulus Uncariae Cum Uncis decoct is 26.1 ± 4.3g/kg or 29.05 ± 0.8g/kg.Ramulus Uncariae Cum Uncis twig Decoct is then 35.2 ± 5.4g/kg.The median lethal dose(LD 50) of mouse stomach and lumbar injection is respectively by Rhomotoxine hydrochlorate 514.6 ± 29.1mg/kg and 144.2 ± 3.1mg/kg.An ancient unit of weight rattan alkali is to mouse peritoneal injection and hypodermic median lethal dose(LD 50) It is respectively 162.3mg/kg and 165mg/kg.Rabbit gavage Ramulus Uncariae Cum Uncis decoct 5g/kg, every day 2 times, continuous 10 days, without substantially poisoning Symptom.Infant rats gavage Rhomotoxine hydrochlorate 50mg/kg (therapeutic dose), every day 1 time, anatomic observation after 14 days, not See internal organs method sick reason morphologic change.But when dosage doubles, liver occurs that mild inflammatory changes, and can quickly recover after drug withdrawal.Disconnected Small rat gavage an ancient unit of weight rattan total alkali hydrochlorate 50-100mg/kg, every day 1 time, in continuous February, observes January after drug withdrawal again, low dose of (50mg/kg) growth of animal, growth, Liver and kidney function and hemogram are all had no significant effect, nutrition that the rarely seen kidney of pathologic finding is slight Sexual disorders.Heavy dose of (100mg/kg) then can make animal lethal.The animal heart of death, liver, kidney all have obvious pathological changes.
Test example 5 pharmacokinetics
Blood drug level peaking after this product 45min；It is 89% with plasma protein binding rate.In liver, almost all is metabolized Become still to have the 4-hydroxyl alprenolol of pharmacologically active.
Embodiment 1
Accurately weighing 12g cosolvent ethanol, the most dissolves in alprenolol, and obtaining its meltage is 6.3g, then with 7gIPM dissolves each other；Accurately weigh surfactant EL40 28g and cosurfactant ethanol 4g, and the oil of solubilized solution alprenolol Stir under the conditions of room temperature (25 DEG C), be slowly dropped into the distillation dissolving Ramulus Uncariae Cum Uncis water extract with Rhizoma Gastrodiae water extract the most wherein Water.Along with the increase of the distillation water yield, system stickiness increases, when the amount adding distilled water makes system be become oil-in-water from Water-In-Oil During type nano-emulsion, system viscosity is thinning from the state of thickness, and now produce is i.e. the compound recipe alprenolol of clear Nano-emulsion, the amount now adding distilled water is 32.5g, and Ramulus Uncariae Cum Uncis water extract is 4.8g, and Rhizoma Gastrodiae water extract is 5.4g.This ratio is The optimal proportion of alprenolol resisting hypertension nano-emulsion.
Following example step is with embodiment 1:
Embodiment 2
Cosolvent ethanol 10g, alprenolol 5.7g, IPM 6.5g, EL40 24g, 1,2-PD 8g, Ramulus Uncariae Cum Uncis water extract For 5.2g, Rhizoma Gastrodiae water extract is 6g, distilled water 34.6g.
Embodiment 3
Cosolvent ethanol 14g, alprenolol 8.1g, ethyl acetate 9.5g, PLURONICS F87 24g, glycerol 12g, hook Rattan water extract is 1.8g, and Rhizoma Gastrodiae water extract is 2.7g, distilled water 27.9g.
Embodiment 4
Cosolvent ethanol 10g, alprenolol 5.1g, ethyl oleate 6g, RH40 24g, ethanol 4g, Ramulus Uncariae Cum Uncis water extract is 5.8g, Rhizoma Gastrodiae water extract is 6.4g, distilled water 38.7g.
Embodiment 5
Cosolvent ethanol 11g, alprenolol 6.7g, ethyl oleate 7g, Tween 80 20g, glycerol 12g, Ramulus Uncariae Cum Uncis water extract For 4.4g, Rhizoma Gastrodiae water extract is 5.8g, distilled water 33.1g.

Claims (2)

1. a compound alprenolol nano-emulsion antihypertensive drug, it is characterised in that its raw material and mass percent thereof be:
Remaining composition is distilled water, and the mass percent sum of above-mentioned raw materials is 100%；
Described surfactant is that polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or pool Lip river are husky In nurse 188 any one or with the mixture of span80；
Described oil is any one or a few the mixing in isopropyl myristate, ethyl acetate, ethyl oleate or oleic acid Thing；
Described cosurfactant be in dehydrated alcohol, 1,2-PD, PEG400 or glycerol any one or Several mixture.
Compound alprenolol nano-emulsion antihypertensive drug the most according to claim 1, it is characterised in that: the particle diameter of this medicine Between 10～100nm.
CN201610503134.4A 2016-06-23 2016-06-23 A kind of compound alprenolol nano-emulsion antihypertensive drug Pending CN106177511A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106474061A (en) * 2016-12-08 2017-03-08 黑龙江童医生儿童生物制药有限公司 A kind of propranolol hydrochloride Orally taken emulsion and preparation method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106474061A (en) * 2016-12-08 2017-03-08 黑龙江童医生儿童生物制药有限公司 A kind of propranolol hydrochloride Orally taken emulsion and preparation method thereof
CN106474061B (en) * 2016-12-08 2019-01-22 黑龙江童医生儿童生物制药有限公司 A kind of Propranolol Hydrochloride Orally taken emulsion and preparation method thereof

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