CN101103962A - Vinpocetine oral self-microemulsion drug delivery system and preparation method thereof - Google Patents
Vinpocetine oral self-microemulsion drug delivery system and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a vinpocetine oral self-micro-emulsifying drug delivery system and the preparation method. The vinpocetine oral self-micro-emulsifying drug delivery system is composed of vinpocetine, fat phase, emulsifier and coemulsifier. The mass ratio percentage preferential scope of the ingredients is that the vinpocetine occupies 1-10 per cent, the fat phase occupies 20-60 per cent, the emulsifier occupies 25-70 per cent and the coemulsifier occupies 0-25 per cent. The vinpocetine oral self-micro-emulsifying drug delivery system can be spontaneously emulsified into micro-emulsion with 10-100 mm granule diameter after taken orally, promoting drug to be quickly absorbed. The drug delivery system has the advantages of improving the solubility of the vinpocetine in water, improving the availability of the vinpocetine and eliminating the influence of food to the absorption and bioavailability of the vinpocetine.
Description
Technical field
The present invention relates to medical technical field, is a kind of new oral medicine-releasing system of vinpocetine, exactly is Vinpocetine oral self-micro-emulsification medicine-releasing system and preparation method thereof.
Background technology
Vinpocetine (Vinpocetine) is the derivant of the indoles alkaloid vincamine that extracts in the apocynaceae plant periwinkle, it is a kind of cerebral circulation metabolism improving agent, can improve the blood circulation of brain, promote the energy metabolism of brain, high blood viscosity to prevention and treatment cerebral arteriosclerosis, apoplexy sequela and coronary heart disease of hypertension has better curative effect, and can be used for improving brain function, hypermnesis, improve emotion, improve the audition and the visual abnormality of aging, delay brain aging, prolonged application safety and toleration height.
Vinpocetine is succeeded in developing in the seventies first by Hungary Gedeon Richter company, oral medication dosage 5～10mg/ time, and 3 times on the one, in the extensive metabolism of liver, distributed more widely general in the tissue, the original shape medicine can enter brain by blood brain barrier.The healthy people oral absolute bioavailability of state on an empty stomach only is 6.7%, and can reach 60～100% after meal.
Cause the low reason of vinpocetine bioavailability to have: 1. vinpocetine is water-soluble hardly, has had a strong impact on medicine stripping and absorption; 2. the first pass effect of liver; 3. food effect influences the absorption of medicine greatly, the Vinpocetine oral absolute bioavailability can by 6.7% of empty stomach state rise to after meal 60%～100%, illustrate that food can stimulate biliary secretion after the meal, bile salt in the bile and lecithin can obviously increase, dissolubility and dissolution rate by micellar solubilization and the increase medicine wettability insoluble drug of anti-the increase, promoted the absorption of medicine, thereby the lymph that increases small intestinal simultaneously absorbs the first pass metabolism that reduces liver at small intestine epithelium.
About the dosage form research of vinpocetine,, tablet, sustained-release matrix tablets, micropill, injection, paster agent and exterior-applied emulsion are arranged according to domestic and foreign literature and patent report.This medicine is to get the Green Light in China the nineties, and raw material, tablet and injection listing are only arranged.At present, only carried out Chinese patent application with the relevant dosage form of vinpocetine liposome (application number CN200410054738.2) relevant for vinpocetine freeze-dried powder and preparation technology (application number CN200410046419.7) thereof.
Vinpocetine notable therapeutic effect and low toxic and side effects have been subjected to clinical affirming, but bioavailability is low, take often, and dosage form is single, for solving the vinpocetine formulation products in the shortcoming aspect the clinical practice, demand carrying out the secondary development of the degree of depth and range urgently.
Self-micro-emulsification medicine-releasing system (Self-microemulsifying Drug Delivery System, SMEDDS) be the solution of the Thermodynamically stable that forms by oil phase, emulsifying agent and co-emulsifier, homogeneous, transparent or semitransparent, each homogeny, under the situation of ambient temperature (being often referred to about 37 ℃) and gentle agitation, spontaneous emulsification forms the Emulsion of common particle diameter＜100nm.
SMEDDS is as a kind of new drug carrier, and its formulation characteristic and advantage are: 1. contain oil phase, emulsifying agent and co-emulsifier in the system simultaneously, can contain some poorly water soluble drugs as much as possible, increase their dissolubility; 2. can form tiny emulsion particles oil droplet, be distributed in equably in the gastrointestinal tract rapidly, rely on these tiny huge specific surface areas, the stripping that can improve medicine greatly; 3. the microemulsion interfacial area of Xing Chenging is big, and surface tension is low, is easy to the hydrated sheath by gastrointestinal wall, increases penetrance, promotes to absorb and improve bioavailability; 4. the microemulsion of Xing Chenging can absorb through lymph, thereby has overcome first pass effect and the obstacle when the gastrointestinal tract epithelial cell; 5. can reduce or remit the hydrolysis of water unstable medicine; 6. the gastrointestinal pessimal stimulation that can avoid medicine to cause with direct contact of gastrointestinal wall; 7. traditional relatively Emulsion has higher stability, absorbs rapidlyer, and bioavailability is higher; Simultaneously SMEDDS have also that volume is little, dosage accurately, taking convenience, preparation be simple, be suitable for the advantage that large-scale industrialization is produced.8. SMEDDS's is various informative, on the basis of SMEDDS, can further make soft capsule, hard capsule, tablet, granule, oral liquid, slow releasing preparation etc., compare with respect to traditional tablet, capsule, can be fast, equably with drug delivery to absorption site, make absorption rapider, bioavailability is higher.Therefore, SMEDDS provides a very promising novel form for oral absorption and the bioavailability that improves slightly water-soluble/fat-soluble medicine.
The present invention adopts the self-emulsifying microemulsion technology, the dissolubility and the stripping of vinpocetine have been significantly improved, improve its absorption and bioavailability, eliminate the influence of food to vinpocetine absorption and bioavailability, improve the curative effect of medicine, in the hope of being fit to patient's demand more, for the development and use of vinpocetine provide more wide prospect.
Summary of the invention:
The purpose of this invention is to provide a kind of Vinpocetine oral self-micro-emulsification medicine-releasing system and preparation method thereof.After oral in vivo spontaneous emulsification form the microemulsion of particle diameter at 10～100nm, improve dissolubility and absorption in the water of vinpocetine; Improve the vinpocetine bioavailability; Eliminate the influence of food to vinpocetine absorption and bioavailability; Improve the clinical drug curative effect.
Changchun two spit of fland oral self-micro-emulsification medicine-releasing systems are made up of vinpocetine, oil phase, emulsifying agent and co-emulsifier, and the shared quality of each component than general range is: vinpocetine 0.1～20%, oil phase 10～80%, emulsifying agent 5%～80% and co-emulsifier 0～45%.Preferable range is: two spits of fland 1～10%, Changchun, oil phase 20～60%, emulsifying agent 25～70% and co-emulsifier 0～25%.After oral in vivo spontaneous emulsification form the microemulsion of mean diameter at 10～100nm.
The Vinpocetine oral self-micro-emulsification medicine-releasing system that makes can contain poorly water soluble drugs-vinpocetine (the about 5.0 μ g/ml of dissolubility) as much as possible, makes its dissolubility increase more than 2000 times; After running into gastro-intestinal Fluid, can form tiny emulsion particles, the stripping that improves medicine greatly with huge specific surface area; Be easy to hydrated sheath simultaneously, increase penetrance, promote to absorb and improve bioavailability by gastrointestinal wall; By producing similar feed back cholate solubilization, promoted the absorption of medicine, thereby the lymph that increases small intestinal simultaneously absorbs the first pass metabolism that reduces liver and reduces the influence of food to drug absorption at small intestine epithelium.
The oil phase of Vinpocetine oral self-micro-emulsification medicine-releasing system: applied in the present invention oil phase has medium chain (C
8～C
10) fatty glyceride (GTCC or MCT), oleic acid, soybean oil, olein (Peceol, HLB=3), glyceryl linoleate (Maisine, HLB=3), Oleum Cocois C
8/ C
10Triglyceride (Captex355) can be used for Vinpocetine oral self-micro-emulsification medicine-releasing system.
Can select wherein a kind ofly as oil phase among the present invention, also can select two kinds or above mixture as oil phase, shared quality is an oil phase 20～60% than preferable range.
Preferred MCT Oil and oleic mixture are oil phase among the present invention, and mass ratio (W/W) is 1～16: 1.
The emulsifying agent of Vinpocetine oral self-micro-emulsification medicine-releasing system: it is to have strong emulsifying capacity that emulsifying agent requires, self emulsifying and keep the Emulsion state in gastrointestinal tract, itself also can dissolve a large amount of relatively hydrophobic drugs, can prevent that medicine from depositing in gastrointestinal tract and the dissolved state of prolong drug molecule.The general nonionic emulsifier that adopts high HLB (between 11～15), the self emulsifying process is fast, has best stripping; Simultaneously, a large amount of emulsifying agents may the stimulating gastrointestinal road, so should take into full account the safety of emulsifying agent, nonionic emulsifier is lower than ionic emulsifying agent toxicity, only causes that the infiltrative reversibility of gastrointestinal tract wall changes.
The applied emulsifying agent of the present invention have polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, Polyethylene Glycol-8 glycerol sad/the certain herbaceous plants with big flowers acid esters (Labrasol, HLB=14), Oleum Cocois C
8/ C
10Polyethyleneglycol glyceride (LabrafacCM10, HLB=10).
Can select wherein a kind ofly as emulsifying agent among the present invention, also can select two kinds or above mixture as emulsifying agent, shared quality is 25～70% than preferable range.
Preferred polyoxyethylene castor oil is an emulsifying agent among the present invention.
It is to reduce interfacial tension that the co-emulsifier of Vinpocetine oral self-micro-emulsification medicine-releasing system co-emulsifier: SMEDDS requires, and increases the flowability of interfacial film, can reduce the consumption of emulsifying agent, regulates the HLB value, simultaneously can the assist in dissolving medicine.
At the applied co-emulsifier of the present invention Transcutol P (ethylene glycol monomethyl ether), ethanol, isopropyl alcohol are arranged.
Can select wherein a kind ofly as co-emulsifier among the present invention, the mixture that also can select two kinds is as co-emulsifier, and shared quality is 0～25% than preferable range.
Preferred Transcutol P (ethylene glycol monomethyl ether) is a co-emulsifier among the present invention.
The preparation method of Vinpocetine oral self-micro-emulsification medicine-releasing system: the present invention has developed Vinpocetine oral self-micro-emulsification soft capsule and self-emulsifying microemulsion oral liquid on the basis of Vinpocetine oral self-micro-emulsification medicine-releasing system.
Preparation method is as follows: Vinpocetine oral self-micro-emulsification medicine-releasing system of the present invention is particularly useful for soft capsule dosage form, promptly add oil phase, emulsifying agent, co-emulsifier (also can add antioxidant) in proportion, fully behind the mixing, get the clear and bright oily liquid of homogeneous, the medicine that under stirring at room, adds recipe quantity again, about mixing 1h it is fully dissolved, make soft capsule and get final product.Method is simple, but suitability for industrialized production is convenient to store transportation.
Vinpocetine oral self-micro-emulsification medicine-releasing system of the present invention is equally applicable to oral liquid formulation, promptly on aforementioned Vinpocetine oral self-micro-emulsification medicine-releasing system basis, adds suitable cosolvent and correctives, behind the dilute with water, obtains oral liquid.
The specific embodiment:
Embodiment 1
Prescription is formed:
Vinpocetine 5g
GTCC 80g
Oleic acid 20g
Cremophor EL 80g
Transcutol P 20g
Make 1000 soft capsules altogether
Preparation technology:
Take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, make soft capsule, promptly get the vinpocetine self-emulsification soft capsules.Can obtain electronegative Vinpocetine oral self-micro-emulsification concentrated solution (i.e. (-) VIN-SMEDDS by the preparation of above prescription, be abbreviated as VIN-SMEDDS), after adding 1% oleyl amine, can obtain the Vinpocetine oral self-micro-emulsification concentrated solution (i.e. (+) VIN-SMEDDS) of positively charged, will further promote the medicine intestinal absorption.
The pharmaceutics feature of the vinpocetine self-micro-emulsification medicine-releasing system (concentrated solution) of preparation:
Physicochemical property:
Adopt current potential and determination of laser light scattering instrument to measure the particle diameter and the zeta potential of negative, positive electric charge Vinpocetine oral self-micro-emulsification concentrated solution (VIN-SMEDDS); Adopt the viscosity of viscometer determining VIN-SMEDDS.
The physicochemical property mensuration of table 1 vinpocetine self-emulsifying microemulsion concentrated solution (37 ℃, n=5)
| Index | (-)VIN-SMEDDS | (+)VIN-SMEDDS |
| Particle diameter (nm) zeta potential (mV) viscosity (mPas) self emulsifying time settlement is than (C 3h/C 0h×100％) | 40.16±5.58-32.30±2.44208.81±12.22＜1min99.38％±0.66％ | 42.78±3.79 +4.35±1.85 206.44±10.52 ＜1min 99.05％±0.75％ |
Electron microscopic observation:
Getting 1 of VIN-SMEDDS (about 50mg) drips in the 10ml distilled water, shake up 1min gently, point sample, negative staining, transmission electron microscope observing, the result shows, VIN-SMEDDS forms the spherical emulsion droplet of uniform oil-in-water after the water dilution, drug main will be distributed in the hydrophobic core that partly is made of oil phase and emulsifying agent lipophile.The transmission electron microscope scintigram is seen Figure of description 1.
Dissolution determination:
By " the 3rd law regulation is carried out rotating speed of agitator 50rmin among Chinese pharmacopoeia (2005 editions) the appendix XC
-1, bath temperature (37 ± 0.5) ℃, release medium is simulated intestinal fluid (pH=6.8) 250ml.Input is equivalent to the VIN-SMEDDS of vinpocetine 5mg, respectively at 10,30,60,90,120, and the 180min 2ml that takes a sample, 0.22 μ m filtering with microporous membrane, the release medium of replenishing synthermal 2ml is simultaneously got subsequent filtrate 20 μ l and is carried out HPLC and measure.Substitution standard curve calculating concentration as a result, and be converted into the cumulative release percentage rate.The result shows that vinpocetine self-emulsification soft capsules 2h accumulation stripping percentage composition in simulated intestinal fluid (pH=6.8) is 90.01%, is 8.1 times of vinpocetine material powder (11.07%), is 4.1 times of vinpocetine marketed tablet (21.85%).Vinpocetine-positive negativity of SMEDDS electric charge is to medicine stripping also not influence substantially.
The different preparation dissolution in vitro of vinpocetine comparison diagram is seen Figure of description 2.
The intestinal absorption characteristics of Vinpocetine oral self-micro-emulsification concentrated solution:
Adopt rat in body intestinal circulation absorption experiment method, carry out vinpocetine self-emulsifying microemulsion concentrated solution, marketed tablet and crude drug powder (10mgL
-1) the jejunum in rats Duan Zaiti intestinal absorption experiment of circulation fluid, condition is: the balance circulation rate is 1.0mlmin
-1, it is 10 μ gml that the pastille preparation is diluted to drug level with phenol red K-R circulation fluid
-1, in refluxing 0.5,0.75,1.0,1.5,2.0,3.0, get perfusate during 4.0h and measure, calculate absorption rate constant, see Table 2, the result shows that the vinpocetine self-microemulsifying drug delivery system can promote dissolving and the absorption of medicine in small intestinal, drug absorption speed constant Ka (h
-1) compare with crude drug powder, marketed tablet, significant difference is arranged.And marketed tablet is compared with the crude drug powder, there was no significant difference.
The drug absorption of the different preparation jejunum in rats of table 2 vinpocetine Duan Zaiti intestinal circulation 4h is (n=5) relatively
| Different preparations | Drug absorption speed constant Ka (h -1) | PA (%) |
| Vinpocetine self-emulsifying microemulsion concentrated solution vinpocetine marketed tablet (Duo Likang) vinpocetine crude drug powder | 0.151±0.018 ＊0.106±0.0110.091±0.015 | 65.71±8.16 ＊ 45.26±5.45 39.32±3.56 |
Compare with the crude drug powder,
*P＜0.05
Vinpocetine oral self-micro-emulsification concentrated solution pharmacokinetic characteristics:
Get the SD male rat, according to dosage VIN10mgkg
-1Body weight is irritated stomach and is given VIN-SMEDDS, after administration 30,60,90,120,180,240,300,360min gets blood from eye socket respectively, and the centrifugal 10min of 5000rpm gets upper plasma and measures drug level, with vinpocetine marketed tablet (Duo Likang), vinpocetine material powder is contrast, blood drug level-time graph is seen Fig. 3, compares with the vinpocetine crude drug, and the relative bioavailability of vinpocetine self microemulsifying preparation (VIN-SMEDDS) has had significant increase, reach 187.50%, and the vinpocetine marketed tablet is suitable with its crude drug.The moving parametrics parameter of main medicine sees Table 3, and the result shows the parameters C of Vinpocetine oral self-micro-emulsification medicine-releasing system and its marketed tablet or material powder
Max, T
Max, AUC, CL/F all has utmost point significant difference (P＜0.01) between Vz/F, and there was no significant difference (P＞0.05) between vinpocetine marketed tablet and its material powder pharmacokinetic parameters.
Average blood drug level-the time plot of each preparation of rat oral gavage administration (10mg/kg) is seen Figure of description 3.
Each preparation of table 3 VIN low dosage (10mg/Kg) ig the intravital main pharmacokinetic parameters of rat (n=3,
)
| Parameter | The self-emulsifying microemulsion concentrated solution | Marketed tablet | Material powder |
| MRT 0-t(min)t1/2z(min)T max(min)C max(μg/L)CLz/F(L/h/kg)Vz/F(L/kg)AUC 0-t(μg/L*min)AUC 0-∞(μg/L*min) | 175.60±48.9887.276±22.92180.00±23.04 **1005.60±269.76 **0.037±0.009 **4.68±2.02 **234074.8 **±35877.37268660.94 **±30123.56 | 146.58 ±29.98 116.77 ±8.01 60.00 ±7.85 725.40 ±212.03 0.066 ±0.0052 11.17 ±3.59 129116.88 ±7707.44 150918.88 ±8563.74 | 147.07 ±33.53 103.02 ±45.63 60.00 ±12.02 706.80 ±252.86 0.071 ±0.02 10.62 ±4.45 124838.28 ±25859.14 139915.79 ±26863.45 |
Compare with marketed tablet,
*P＜0.05,
*P＜0.01
Characteristic distributions in the Vinpocetine oral self-micro-emulsification concentrated solution gastric infusion rat body:
Above with each preparation of vinpocetine (suitable medicine 10mgkg
-1) in the pharmacokinetics experiment of gastric infusion, treat that eye socket is got blood after, sacrificed by decapitation is taken out the cerebral tissue of each time point in each preparation experiment immediately, makes tissue homogenate with normal saline, the centrifugal 10min of 8000rpm gets supernatant and measures drug level and compare.In addition, get 30min behind the gastric infusion, each tissue of the rat of 120min is made tissue homogenate as spleen, lung etc. with method, the distribution situation of mensuration medicine.The results are shown in Figure 4, the result shows that VIN is distributed more widely in the rat body, under the 10mg/Kg dosage, behind the gastric infusion 30, the concentration of 120min medicine in overwhelming majority tissue is higher than blood plasma, it is fat-soluble relevant with it to distribute, and can record the original shape medicine in brain, illustrates that medicine can arrive brain by blood brain barrier and play a role, improve the blood circulation of brain, promote the energy metabolism of brain; VIN-SMEDDS compares with marketed tablet or crude drug, respectively organizes the increase that all has in various degree, wherein increases comparatively obviously in lung, liver, intestinal portion, and marketed tablet and crude drug be there was no significant difference relatively; Behind the VIN-SMEDDS gastric infusion, compare with marketed tablet, arriving different time points medicament contg in the cerebral tissue by blood brain barrier all has in various degree increase, is 3.4 times of tablet at 360min cerebral tissue Chinese medicine content VIN-SMEDDS, 3.1 times of crude drug; And marketed tablet and crude drug compare there was no significant difference.The relative conventional tablet of self microemulsifying preparation is described, can be better in brain performance drug action.
Each time point cerebral tissue Chinese medicine concentration is seen Figure of description 4 behind the different preparation rat oral gavages of vinpocetine.
Description of drawings
Fig. 1 vinpocetine self-micro-emulsification medicine-releasing system (VIN-SMEDDS) transmission electron microscope scintigram
The different preparation dissolution in vitro comparison diagrams (n=5) of Fig. 2 vinpocetine
The different preparation rat oral gavage blood drug level-time plots (n=4) of Fig. 3 vinpocetine
Each time point cerebral tissue Chinese medicine scattergram (n=4) behind the different preparation rat oral gavages of Fig. 4 vinpocetine
Embodiment 2
Prescription forms:
Vinpocetine 4g
GTCC 70g
Oleic acid 5g
Cremophor EL 90g
Transcutol P 50g
Make altogether 1000 soft capsules
Preparation technology:
Take by weighing each auxiliary material of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add again the medicine of recipe quantity, about mixing 1h it is fully dissolved, make soft capsule, namely get the vinpocetine self-emulsification soft capsules.
Embodiment 3
Prescription forms:
Vinpocetine 5g
GTCC 60g
Oleic acid 10g
Cremophor EL 95g
Transcutol P 30g
Isopropyl alcohol 20g
Make altogether 1000 soft capsules
Preparation technology:
Take by weighing each auxiliary material of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add again the medicine of recipe quantity, about mixing 1h it is fully dissolved, make soft capsule, namely get the vinpocetine self-emulsification soft capsules.
Embodiment 4
Prescription forms:
Vinpocetine 8g
GTCC 80g
Oleic acid 25g
Cremophor RH40 80g
Transcutol P 30g
VitE 0.3g
Make altogether 1000 soft capsules
Preparation technology:
Take by weighing each auxiliary material of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add again the medicine of recipe quantity, about mixing 1h it is fully dissolved, make soft capsule, namely get the vinpocetine self-emulsification soft capsules.
Embodiment 5
Prescription is formed:
Vinpocetine 5g
Medium chain triglyceride 70g
Olein 20g
Cremophor EL 80g
Labrasol 20g
Transcutol P 10g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, pour into soft capsule, promptly get the vinpocetine self-emulsification soft capsules.
Embodiment 6
Prescription is formed:
Vinpocetine 5g
Medium chain triglyceride 90g
Oleic acid 10g
Cremophor EL 80g
Labrasol 30g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, pour into soft capsule, promptly get the vinpocetine self-emulsification soft capsules.
Embodiment 7
Prescription is formed:
Vinpocetine 4g
GTCC 80g
Glyceryl linoleate 10g
Cremophor RH40 70g
Transcutol P 40g
VitE 0.3g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, pour into soft capsule, promptly get the vinpocetine self-emulsification soft capsules.
Embodiment 8
Prescription is formed:
Vinpocetine 5g
GTCC 80g
Olein 20g
Cremophor RH40 50g
Labrafac CM10 40g
Dehydrated alcohol 10g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, pour into soft capsule, promptly get the vinpocetine self-emulsification soft capsules.
Embodiment 9
Prescription is formed:
Vinpocetine 5g
GTCC 70g
Glyceryl linoleate 30g
Labrafac CM10 90g
Cremophor EL 20g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, under stirring at room, add the medicine of recipe quantity again, about mixing 1h it is fully dissolved, pour into soft capsule, promptly get the vinpocetine self-emulsification soft capsules.
Prescription is formed (g):
Vinpocetine 10g
Captex355 80g
Olein 20g
Cremophor EL 80g
Labrasol 20g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, add the vinpocetine of recipe quantity under the stirring at room, fully make its dissolving about mixing 1h, make soft capsule, promptly get self-emulsifying soft capsule.
Embodiment 11
Prescription is formed:
Vinpocetine 5g
Soybean oil 58g
Glyceryl linoleate 58g
Cremophor EL 70g
Dehydrated alcohol 15ml
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, add the medicine of recipe quantity again, add vinpocetine under the stirring at room, fully make its dissolving about mixing 1h, make soft capsule, promptly get self-emulsifying soft capsule.
Embodiment 12
Prescription is formed:
Vinpocetine 3g
Soybean oil 50g
Glyceryl linoleate 30g
Cremophor EL 100g
Transcutol P 40g
Make 1000 soft capsules altogether
Preparation technology: take by weighing each adjuvant of recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, add the medicine of recipe quantity again, add vinpocetine under the stirring at room, fully make its dissolving about mixing 1h, make soft capsule, promptly get self-emulsifying soft capsule.
Embodiment 12
Prescription is formed:
Vinpocetine 10g
GTCC 100g
Olein 10g
Cremophor EL 70g
Transcutol P 15g
Ethyl hydroxybenzoate 0.3g
Aspartame 2g
Make 1000 bottles altogether
Preparation technology: each adjuvant that takes by weighing recipe quantity, after stirring, get the clear and bright oily liquid of homogeneous, add the medicine of recipe quantity again, add vinpocetine under the stirring at room, fully make its dissolving about mixing 1h, add ethyl hydroxybenzoate antibacterial and aspartame at last, behind the mixing, direct packaging is gone into tool scale oral liquid bottle, promptly get vinpocetine self-emulsifiable oral liquid oil, add suitable quantity of water after jog have the oil-in-water oral microemulsion of one's own, but also the time spent adds entry again to make into Emulsion oral.
Claims (7)
1. Vinpocetine oral self-micro-emulsification medicine-releasing system, it is characterized in that: comprise vinpocetine, oil phase, emulsifying agent and co-emulsifier, the shared quality of each component than preferable range is: vinpocetine 1～10%, oil phase 20～60%, emulsifying agent 25～70% and co-emulsifier 0～25%.
2. Vinpocetine oral self-micro-emulsification medicine-releasing system according to claim 1, it is characterized in that: emulsifying agent is a nonionic emulsifier, be selected from following a kind of, or two or more mixture: selection have polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, Polyethylene Glycol-8 glycerol sad/certain herbaceous plants with big flowers acid esters (Labrasol, HLB=14), Oleum Cocois C8/C10 polyethyleneglycol glyceride (LabrafacCM10, HLB=10), shared mass ratio is: 25～70%.
3. Vinpocetine oral self-micro-emulsification medicine-releasing system according to claim 1, it is characterized in that: co-emulsifier is selected from following a kind of, or two kinds, or three kinds mixture: Transcutol P (ethylene glycol monomethyl ether), ethanol, isopropyl alcohol, shared mass ratio is: 0～25%.
4. Vinpocetine oral self-micro-emulsification medicine-releasing system according to claim 1 is characterized in that: oil phase is selected from following a kind of, or two or more mixture: medium chain (C
8～C
10) fatty glyceride (GTCC or MCT), oleic acid, soybean oil, olein (Peceol, HLB=3), glyceryl linoleate (Maisine, HLB=3), Oleum Cocois C
8/ C
10Triglyceride (Captex355), shared mass ratio is: 20～60%.
5. Vinpocetine oral self-micro-emulsification medicine-releasing system according to claim 1 is characterized in that content can carry out self-emulsifying microemulsion in water-bearing media, forms the microemulsion of particle diameter at 10～100nm.
6. Vinpocetine oral self-micro-emulsification medicine-releasing system according to claim 1, its preparation is characterised in that: the oil phase, emulsifying agent, the co-emulsifier that accurately take by weighing recipe quantity, behind the mix homogeneously, get the clear and bright oily liquid of homogeneous, the vinpocetine that adds recipe quantity again, fully stir under the room temperature and make its dissolving about 1h fully, promptly get vinpocetine self-emulsifying microemulsion concentrated solution.
7. according to claim 1 and the described Vinpocetine oral self-micro-emulsification medicine-releasing system of claim 6, it is characterized in that: it is a kind of dosage form of oral administration, on the basis of Vinpocetine oral self-micro-emulsification concentrated solution, can be made into soft capsule and oral liquid.
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| CNA2006100196169A CN101103962A (en) | 2006-07-13 | 2006-07-13 | Vinpocetine oral self-microemulsion drug delivery system and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2010127541A1 (en) * | 2009-05-06 | 2010-11-11 | 江苏恒瑞医药股份有限公司 | A nano-emulsion injection of vinca alkaloids and the preparation method thereof |
| CN101264064B (en) * | 2008-04-17 | 2011-04-20 | 孙向阳 | Vinpocetine freeze-dried powder for injection and preparation thereof |
| CN102836140A (en) * | 2011-06-22 | 2012-12-26 | 鲁南制药集团股份有限公司 | Arctigenin micro-emulsion enteric soft capsule preparation |
| CN104705316A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Abamectin microemulsion concentrate and preparation method and application thereof |
| CN104706588A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Vinpocetine fat emulsion concentrated solution, preparation method and application thereof |
| CN104706585A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Vinorelbine bitartrate fat emulsion concentrated solution, preparation method and application thereof |
| CN107137568A (en) * | 2017-06-26 | 2017-09-08 | 陕西中医药大学 | The preparation method of Chinese paris rhizome total saponin self-emulsifying microemulsion granule |
| CN113499311A (en) * | 2021-08-16 | 2021-10-15 | 沈阳药科大学 | Vinpocetine nano-emulsion for nose and preparation method and application thereof |
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- 2006-07-13 CN CNA2006100196169A patent/CN101103962A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264064B (en) * | 2008-04-17 | 2011-04-20 | 孙向阳 | Vinpocetine freeze-dried powder for injection and preparation thereof |
| WO2010127541A1 (en) * | 2009-05-06 | 2010-11-11 | 江苏恒瑞医药股份有限公司 | A nano-emulsion injection of vinca alkaloids and the preparation method thereof |
| CN102836140A (en) * | 2011-06-22 | 2012-12-26 | 鲁南制药集团股份有限公司 | Arctigenin micro-emulsion enteric soft capsule preparation |
| CN102836140B (en) * | 2011-06-22 | 2015-03-18 | 鲁南制药集团股份有限公司 | Arctigenin micro-emulsion enteric soft capsule preparation |
| CN104705316A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Abamectin microemulsion concentrate and preparation method and application thereof |
| CN104706588A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Vinpocetine fat emulsion concentrated solution, preparation method and application thereof |
| CN104706585A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Vinorelbine bitartrate fat emulsion concentrated solution, preparation method and application thereof |
| CN107137568A (en) * | 2017-06-26 | 2017-09-08 | 陕西中医药大学 | The preparation method of Chinese paris rhizome total saponin self-emulsifying microemulsion granule |
| CN113499311A (en) * | 2021-08-16 | 2021-10-15 | 沈阳药科大学 | Vinpocetine nano-emulsion for nose and preparation method and application thereof |
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