CN101601737A - A kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion thereof - Google Patents
A kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion thereof Download PDFInfo
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- CN101601737A CN101601737A CNA2009101161921A CN200910116192A CN101601737A CN 101601737 A CN101601737 A CN 101601737A CN A2009101161921 A CNA2009101161921 A CN A2009101161921A CN 200910116192 A CN200910116192 A CN 200910116192A CN 101601737 A CN101601737 A CN 101601737A
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Abstract
The invention discloses a kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion formulation, form by Radix Paeoniae Alba total glucosides and effective ingredient, surfactant, cosurfactant, oil phase and water.This microemulsion appearance transparent, particle diameter is at 10-100nm; This microemulsion good stability; Can significantly improve the absorption of peoniflorin, thereby improve bioavailability of medicament, reduce toxic and side effects, improve curative effect.
Description
One, technical field
The present invention relates to a kind of Chinese medicine preparation, the preparation of effective site of particularly extracting in Chinese herbal medicine and effective ingredient processing thereof exactly is a kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion thereof.
Two, background technology
Microemulsion (abbreviation microemulsion) is transparent or semitransparent shape, low viscosity, Thermodynamically stable and isotropic profit mixed system, plays Stabilization jointly by surfactant and cosurfactant.Its drop is generally between 10～100nm, and appearance transparent, viscosity are near water; Thermodynamically stable, put not stratified, breakdown of emulsion not for a long time.It has stablely as novel drug-supplying system, and slow release can improve drug bioavailability and effect such as performance targeting etc.
Radix Paeoniae Alba total glucosides (TGP) is the effective site of extracting from motherland's Chinese medicine Radix Paeoniae Alba root, regulates medicine as first anti inflammatory immunity and is produced listing by official approval, for important function has been brought into play in the treatment of inflammatory-immune diseases.。Though TGP treatment RA is effectively, safety, TGP also comes with some shortcomings, and comprises that onset is slow, the curative effect individual variation is big, main mechanism and action target spot and pharmacokinetics characteristics are unclear.Because TGP contains a plurality of effective ingredient such as peoniflorin, Hydroxy peoniflorin, peonin, lactone glucoside of Radix Paeoniae, benzoylpaeoniflorin, so it is clear that its main mechanism and action target spot are difficult to illustrate, pharmacokinetics characteristics such as absorption in its body, distribution, metabolism and drainage also are not easy to illustrate.During clinical use Radix Paeoniae Alba total glucosides, find that the biological utilisation of peoniflorin is low; After strengthening oral dose, gastrointestinal reactions such as abdominal distention, diarrhoea, inappetence appear in some patients in early days in the course of treatment, or stomachache, feel sick, performance such as dizziness.
Three, summary of the invention
The present invention is for avoiding above-mentioned existing in prior technology weak point, aim to provide a kind of appearance transparent, particle diameter Radix Paeoniae Alba total glucosides and effective ingredient microemulsion at 10～100nm, to improve the bioavailability of peoniflorin, increase targeting, reduce dosage and toxic and side effects, improve curative effect and safety.Technical problem to be solved is to select suitable various auxiliary agent processing microemulsions.
The alleged Radix Paeoniae Alba total glucosides microemulsion of the present invention be meant the effective site of in Radix Paeoniae Alba root, extracting promptly contain Chinese herbaceous peony before a plurality of effective ingredient such as glycosides, Hydroxy peoniflorin, peonin, lactone glucoside of Radix Paeoniae and benzoylpaeoniflorin be referred to as the microemulsion of Radix Paeoniae Alba total glucosides processing.Described Radix Paeoniae Alba total glucosides is meant paeoniflorin content 〉=60% Radix Paeoniae Alba total glucosides of (percentage by weight down together).It is characterized in that each component has following percentage by weight:
Radix Paeoniae Alba total glucosides 0.5%-5%
Surfactant 10.0%-30.0%
Cosurfactant 1.0%-15.0%
Oil 3.0%-75.0%
Distilled water or water for injection 10.0.%-75.0%.
Described surfactant is selected from one or more mixed surfactants in Tweens, poloxamer 188, ethylene glycol-vitamin e succinate, polyoxyethylene castor oil, the lecithin.Preferred Tween 80 is or/and lecithin.
Described cosurfactant is selected from one or more mixing cosurfactants in sorbester p17, lecithin, dehydrated alcohol, glycerol, PEG400, normal propyl alcohol, the propylene glycol.Preferred PEG400 is or/and dehydrated alcohol.
Described grease separation one or more miscellas in medium chain triglyceride, soybean oil, olive oil, oleic acid, ethyl oleate, isopropyl myristate.The preferred oil acetoacetic ester is or/and isopropyl myristate.
The alleged Radix Paeoniae Alba total glucosides effective ingredient microemulsion of the present invention is meant and uses column chromatography peoniflorin microemulsion and the benzoylpaeoniflorin microemulsion that the effective ingredient peoniflorin that obtains and benzoylpaeoniflorin are processed respectively in Radix Paeoniae Alba total glycosides.Described peoniflorin purity 〉=90%, benzoylpaeoniflorin purity 〉=90% (high performance liquid chromatography).
Each component of peoniflorin microemulsion has following percentage by weight:
Peoniflorin 0.5%-5%
Surfactant 10.0%-30.0%
Cosurfactant 1.0%-15.0%
Oil 3.0%-75.0%
Distilled water or water for injection 10.0.%-75.0%.
Each component of benzoylpaeoniflorin microemulsion has following percentage by weight:
Benzoylpaeoniflorin 0.5%～5%
Surfactant 10.0%～30.0%
Cosurfactant 1.0%～15.0%
Oil 3.0%～75.0%
Distilled water or water for injection 10.0%～75.0%
Surfactant, cosurfactant and oil used in processing peoniflorin microemulsion and benzoylpaeoniflorin are identical with the Chinese herbaceous peony total glycosides microemulsion of processing.
This microemulsion prepares according to the following steps:
A, the Radix Paeoniae Alba total glucosides that takes by weighing proportional quantity or peoniflorin or benzoylpaeoniflorin, surfactant, cosurfactant, You Heshui, standby;
B, with surfactant, cosurfactant, stirring, drip oil and water simultaneously and mix the solution that stirs until system formation clear;
C, adding Radix Paeoniae Alba total glucosides or peoniflorin or benzoylpaeoniflorin, stirring and dissolving, promptly getting particle diameter is Radix Paeoniae Alba total glucosides microemulsion or peoniflorin microemulsion or the benzoylpaeoniflorin microemulsion of 10～100nm.
Perhaps, in the b step, do not add water or add low amounts of water and be stirred to the solution that system forms clear, in the c step with Radix Paeoniae Alba total glucosides or peoniflorin or benzoylpaeoniflorin adds in the entry or stirring and dissolving in the excess water, then it is added stirring and dissolving in the solution that the b step obtains, promptly getting particle diameter is Radix Paeoniae Alba total glucosides microemulsion or peoniflorin microemulsion or the benzoylpaeoniflorin microemulsion of 10～100nm.
One, stability test:
1, high speed centrifugation is to the influence of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion stability
Microemulsion is put into high speed centrifuge, with the centrifugal 20min of 10000r/min speed, observe, do not see phenomenons such as layering, precipitation, muddiness, microemulsion solution all keeps clear.
2, illumination accelerated tests
With Radix Paeoniae Alba total glucosides microemulsion, peoniflorin microemulsion, benzoylpaeoniflorin microemulsion formulation, place light cupboard (intensity of illumination is 4500Lx) respectively, kept sample under the room temperature 10 days, respectively at placement sampling in the time of the 5th day, the 10th day, measure the microemulsion nature parameters, the result does not all find phenomenons such as layering, precipitation, muddiness, and microemulsion solution all keeps clear.The electrical conductivity of microemulsion, viscosity, drug loading do not have significant change.
3 high temperature accelerated tests
The sample of Radix Paeoniae Alba total glucosides microemulsion, peoniflorin microemulsion, benzoylpaeoniflorin microemulsion will be housed respectively, place 40,60 ℃ calorstat sealing lucifuge to investigate 10 days, the microemulsion nature parameters is measured in sampling during respectively at the 5th day, the 10th day.
The test that keeps sample of 4 low temperature and room temperature
Place 4 ℃ in refrigerator and 25 ℃ of airtight lucifuges of room temperature to place respectively Radix Paeoniae Alba total glucosides microemulsion, peoniflorin microemulsion, benzoylpaeoniflorin microemulsion formulation, respectively 0,1,2, during March sample carried out a series of microemulsion property testings such as mode of appearance observation, electrical conductivity, viscosity and drug loading.From the data that keep sample, when 4 ℃ of temperature, the microemulsion character does not have significant change substantially after placing three months, show microemulsion temperature under cryogenic conditions.When temperature was 25 ℃, electrical conductivity, the drug loading of microemulsion did not have significant change, and viscosity is big slightly, but replied clarification again after being vibrated.
Two, the peoniflorin microemulsion is tested in the body intestinal absorption
Take from rat, according to 4ml.kg by fasting 12～18h under the conditions of water drinking
-1Dosage lumbar injection pentobarbital sodium anesthetized rat (10g.L
-1), back of the body position is fixed on the operating board, keep 37 ℃ of body temperature, along the about 3cm of ventrimeson hara kiri, in accordance with the following methods to each intestinal segment ligation: the duodenum section is from the beginning of pylorus 1cm place, and jejunal segment is from the beginning of pylorus 15cm place, and ileal segment is the beginning of the up 20cm of caecum place, colonic segment is for being close to caecum to rectum, and each Duan Jun gets about 10cm.Full intestinal is to the ileum bottom from duodenal cap.The flexible pipe pipe of the about 0.5cm of diameter is respectively inserted in each section top and the bottom, prick with toe-in.After with an amount of 37 ℃ of normal saline small intestine contents being rinsed well then, change 37 ℃ of KShi liquid circulation 10min into, then use the 100mL test liquid with 5ml.min
-1Flow velocity circulation, be 2.5mL.min with flow rate regulation behind the 10min
-1, respectively at 0.25,0.5,1,1.5,2,3, the 4h 3mL that from the test liquid beaker, takes a sample, replenish immediately with concentration phenol red solution 3mL, institute's sample thief is with 0.45 μ m filtering with microporous membrane, discard filtrate just, get subsequent filtrate and measure peoniflorin and phenol red content, substitution standard curve calculating concentration.Press document
[11]The different change calculations of phenol red concentration constantly of method utilization go out the different volumes of test liquids constantly, and then calculate rat at body intestinal absorption dose, absorption rate constant Ka (h
-1) and absorb the half-life (h).The results are shown in Table 1,2.
Table 1 peoniflorin solution, the peoniflorin microemulsion is at the absorption dose of full intestinal segment, absorption rate constant Ka (h
-1) and the absorption half-life (h) (n=5, x ± s)
Compare with the peoniflorin aqueous solution,
*P＜0.05,
*P＜0.01
Table 2 peoniflorin solution, peoniflorin microemulsion is at the absorption dose of each section of small intestinal, absorption rate constant and absorb half-life (n=5, x ± s)
Compare with the peoniflorin aqueous solution,
*P＜0.05,
*P＜0.01
By data in the table as can be seen, at 2.0～20mg.L
-1The drug absorption and the mass concentration of peoniflorin microemulsion solution are linear in the concentration range, and the Ka value is constant substantially, and the prompting medicine spreads with passive mode; The drug absorption and the Ka number average of the peoniflorin microemulsion solution under three concentration are higher than the peoniflorin aqueous solution, and 10,20mg.L
-1Difference has significance during two concentration.
Microemulsion formulation is all having absorption at whole intestinal segment, the absorption dose and the Ka of colon, ileum all are higher than duodenum and jejunum, the absorption half-life at colon, ileum all is lower than duodenum and jejunum, and difference has significance, points out its main absorption site at colon and ileum.And the peoniflorin microemulsion solution is higher than the corresponding intestinal segment of peoniflorin aqueous solution at the absorption dose and the ka of ileum and colon, is lower than the corresponding intestinal segment of peoniflorin aqueous solution in jejunum, ileum, colon absorption half-life, and difference has significance.
Three, the research of Radix Paeoniae Alba total glucosides and active ingredient microemulsion acute toxicity
Give mice and irritate stomach respectively and give Radix Paeoniae Alba total glucosides microemulsion, peoniflorin microemulsion, benzoylpaeoniflorin microemulsion, mice Non Apparent Abnormality toxic reaction, its oral medication MTD value is respectively 12g/kg, 18g/kg, 18g/kg; Radix Paeoniae Alba total glucosides microemulsion, peoniflorin microemulsion, benzoylpaeoniflorin microemulsion give the mouse peritoneal injecting drug use respectively, and animal does not have reactions such as obviously turning round body, observe none example death of a week, and its lumbar injection medication MTD value is 4g/kg, 6g/kg, 6g/kg.
Four, intersection dish glue is induced the experiment of rat paw edema degree
3 dosage groups of peoniflorin (25,50,100mgkg
-1), 3 dosage groups of peoniflorin oral microemulsion (25,50,100mgkg
- 1), 3 dosage groups of Radix Paeoniae Alba total glucosides (25,50,100mgkg
-1), 3 dosage groups of Radix Paeoniae Alba total glucosides microemulsion (25,50,100mgkg
- 1), 3 dosage groups of benzoylpaeoniflorin (25,50,100mgkg
-1), 3 dosage groups of benzoylpaeoniflorin microemulsion (25,50,100mgkg
-1) gastric infusion, every day 1 time, continuous 5 days.Inject 10gL in the right back sufficient sole of the foot of each Mus behind the 5th day administration 1h
-1Carrageenin (preparing with normal saline) 0.1ml causes inflammation, with sufficient pawl volumetric measurement instrument measure respectively right back sufficient pawl cause scorching before with cause scorching back 1,3,5,7h causes scorching parapodum volume.The result shows peoniflorin and Radix Paeoniae Alba total glucosides and microemulsion formulation is heavy dose of and middle dosage all can suppress the inductive rat paw edema degree of carrageenin, and difference has significance; Isodose peoniflorin and Radix Paeoniae Alba total glucosides relatively find that peoniflorin is faster than the onset time that Radix Paeoniae Alba total glucosides suppresses sufficient pawl swelling, and inhibitory action is stronger, and difference has significance; Isodose peoniflorin oral microemulsion and peoniflorin relatively find that the peoniflorin oral microemulsion is faster than the onset time that peoniflorin suppresses sufficient pawl swelling, and inhibitory action is stronger, and difference has significance.Isodose Radix Paeoniae Alba total glucosides oral microemulsion and Radix Paeoniae Alba total glucosides relatively find that the peoniflorin oral microemulsion is faster than the onset time that peoniflorin suppresses sufficient pawl swelling, and inhibitory action is stronger, and difference has significance.Benzoylpaeoniflorin and microemulsion thereof all can suppress the inductive rat paw edema degree of carrageenin at middle dosage, and its microemulsion formulation suppresses that the onset time of sufficient pawl swelling is faster, and inhibitory action is stronger, and difference has significance.
Five, single is irritated the pharmacokinetics test that stomach gives former medicine of peoniflorin and peoniflorin oral microemulsion
Rat oral gavage gives the former medicine 25 of peoniflorin, 50mgkg
-1After, the HPLC method does not detect the blood drug level of peoniflorin, gives peoniflorin former medicine 100mgkg
-1Curve and pharmacokinetic parameters see the following form during back medicine.
The pharmacokinetic parameters of high dose group peoniflorin behind the table 3 rat single filling stomach peoniflorin (x ± s, n=5)
After rat single filling stomach gives basic, normal, high 3 dosage Radix Paeoniae Alba total glucosidess and effective ingredient microemulsion, respectively by 0.5h, 1h, 1.5h, 2h,, 3h, 4h, 6h, 8h, 12h, 24h, 48h time point get blood successively, blood sample after treatment, carry out chromatography, record and respectively organize each time point chromatographic peak area, be converted to blood drug level (Fig. 8, table 13), and draw and respectively organize average blood drug level-time graph.
The pharmacokinetic parameters of peoniflorin after each dosage group of table 4 rat single filling stomach peoniflorin microemulsion (x ± s, n=5)
Said medicine dynamics research result shows that the peoniflorin oral microemulsion is higher than the former medicine of peoniflorin at the absorbtivity and the absorbance of intestinal; The absorption half-life of peoniflorin oral microemulsion all is lower than the former medicine of peoniflorin, and the bioavailability of prompting peoniflorin oral microemulsion is higher than the former medicine of peoniflorin.
Six, the single vein gives the pharmacokinetics test of former medicine of peoniflorin and peoniflorin oral microemulsion
Rat is divided into 6 groups at random: peoniflorin aqueous solution small dose group (4.375mgkg
-1); Middle dosage group (8.75mgkg
-1); High dose group (17.5mgkg
-1); Radix Paeoniae Alba total glucosides and effective ingredient microemulsion small dose group (4.375mgkg
-1); Middle dosage group (8.75mgkg
-1); High dose group (17.5mgkg
-1).Each is organized in the tail intravenously administrable once, respectively at before the administration and after the administration with 5,10,15,20,30,45,60,90,120, the 180min time gets blood 1ml from the rat eye socket.Anticoagulant heparin, after room temperature is placed 60min, 4 ℃ of centrifugal (4000rmin
-1, 15min), it is standby to get blood plasma.Adopt the paeoniflorin content of each sample of high effective liquid chromatography for measuring behind the processing biological sample.
The pharmacokinetic parameter of peoniflorin behind the table 5 normal rat intravenous injection peoniflorin aqueous solution (x ± s, n=5)
The pharmacokinetic parameter of peoniflorin behind the table 6 normal rat intravenous injection peoniflorin microemulsion (x ± s, n=5)
Result of the test shows that the peoniflorin microemulsion can improve medicine at the intravital blood drug level of rat, reduces clearance rate, increases mean residence time.
More than test shows: the Radix Paeoniae Alba total glucosides and the effective ingredient microemulsion stable in properties of the present invention's preparation,, can improve bioavailability of medicament, reduce toxic and side effects.
Route of administration of the present invention mainly adopts oral or the intravenous injection mode.The present invention is to autoimmune disease (rheumatoid arthritis, osteoarthritis town, systemic lupus erythematosus (sle), dry syndrome, ankylosing spondylitis, psoriasis, chronic eczema), the liver protecting and ALT lowering, hepatic fibrosis, hepatocellular carcinoma, treatments such as pulmonary fibrosis have positive role.
Compared with the prior art, beneficial effect of the present invention is embodied in:
1, the consumption of the present invention by increasing surfactant to recipe quantity 10% or more or the use cosurfactant, gentle agitation can be made the microemulsion of particle diameter at 10～100nm, increased the dispersibility of peoniflorin greatly, it is low to have improved drug bioavailability, and has slow-releasing.
2, the Radix Paeoniae Alba total glucosides and the effective ingredient microemulsion that make of the present invention is oil/water microemulsion or water/oil microemulsion, and dilution experiment shows that it can further add dilutions such as water for injection, normal saline, glucose solution, forms the microemulsion of clear.
3, preparation method of the present invention is simple, stirs to realize emulsifying, is convenient to suitability for industrialized production.
Four, description of drawings
Fig. 1 peoniflorin microemulsion transmission electron microscope picture (* 20000).
Average blood drug level-the time graph of high dose group peoniflorin behind Fig. 2 rat single filling stomach peoniflorin (x ± s, n=5).
Average blood drug level-the time graph of peoniflorin after Fig. 3 rat single filling stomach Radix Paeoniae Alba total glucosides and each dosage group of effective ingredient microemulsion (x ± s, n=5).
Average blood drug level-the time graph of each dosage group PF behind Fig. 4 normal rat intravenous injection peoniflorin aqueous solution.
Average blood drug level-the time graph of each dosage group PF behind Fig. 5 normal rat intravenous injection Radix Paeoniae Alba total glucosides and the effective ingredient microemulsion.
Five, the specific embodiment
Embodiment 1:
A, get peoniflorin 1.2g, tween 80 36g, PEG400 36g, oleic acid 9g and distilled water 190g, standby;
B, with tween 80, PEG400, oleic acid mixing, stir, drip distilled water simultaneously and form clear and bright liquid until system;
C, adding peoniflorin, stirring and dissolving forms clear and bright liquid until system at normal temperatures and pressures, and promptly getting particle diameter is the peoniflorin microemulsion of 10～100nm;
D, the peoniflorin microemulsion is carried out fill, sterilization makes peoniflorin microemulsion oral liquid.
Embodiment 2:
A, get Radix Paeoniae Alba total glucosides 1.5g, tween 80 36g, PEG400 36g, oleic acid 9g and distilled water 190g, standby;
B, with tween 80, PEG400, oleic acid mixing, stir, drip distilled water simultaneously and form clear and bright liquid until system;
C, adding Radix Paeoniae Alba total glucosides, stirring and dissolving forms clear and bright liquid until system at normal temperatures and pressures, and promptly getting particle diameter is the Radix Paeoniae Alba total glucosides microemulsion of 10～100nm;
D, the Radix Paeoniae Alba total glucosides microemulsion is carried out fill, make Radix Paeoniae Alba total glucosides microemulsion oral liquid.
Embodiment 3:
A, get peoniflorin 0.6g, Polyethylene Glycol-vitamin e succinate 15.0g, propylene glycol 8.0g, injection soybean oil 10.0g and water for injection 62g, standby;
B, will be in the mixed liquor of Polyethylene Glycol-vitamin e succinate and propylene glycol, add the injection soybean oil, mixing, standby;
C, stirring at normal temperatures and pressures slowly drip the described amount water for injection that has dissolved peoniflorin simultaneously, form clear and bright liquid until system, promptly get particle diameter at 10～100nm, the peoniflorin microemulsion of appearance transparent.
D, the peoniflorin microemulsion is carried out fill, sterilization, make the peoniflorin micro-emulsion injecta.
Embodiment 4:
A, get peoniflorin 0.6g, tween 80 36g, PEG400 36g, oleic acid 4.5g, ethyl oleate 4.5g and distilled water 190g, standby;
B, with tween 80, PEG400, oleic acid, ethyl oleate mixing, stir, drip distilled water simultaneously and form clear and bright liquid until system;
C, adding peoniflorin, stirring and dissolving forms clear and bright liquid until system at normal temperatures and pressures, and promptly getting particle diameter is the peoniflorin microemulsion of 10～100nm;
D, the peoniflorin microemulsion is carried out fill, repressed then legal system gets the peoniflorin microemulsion soft capsules.
Embodiment 5:
A, get peoniflorin 1.2g, lecithin 23g, ethanol 36g, isopropyl myristate 140g and distilled water 32g, standby;
B, lecithin, ethanol are mixed, lecithin is fully dissolved, add the isopropyl myristate mixing again, stir at normal temperatures and pressures, slowly drip distilled water simultaneously and form clear and bright liquid until system;
C, adding peoniflorin, stirring and dissolving promptly gets particle diameter at 10～100nm, the peoniflorin microemulsion of appearance transparent;
D, the peoniflorin microemulsion is carried out fill, sterilization, make peoniflorin microemulsion oral liquid.
Embodiment 6:
A, get benzoylpaeoniflorin 2.4g, lecithin 23g, ethanol 36g, isopropyl myristate 140g and distilled water 32g, standby;
B, lecithin, ethanol are mixed, lecithin is fully dissolved, add the isopropyl myristate mixing again, stir at normal temperatures and pressures, slowly drip distilled water simultaneously and form clear and bright liquid until system;
C, adding benzoylpaeoniflorin, stirring and dissolving promptly gets particle diameter at 10～100nm, the benzoylpaeoniflorin microemulsion of appearance transparent;
D, the benzoylpaeoniflorin microemulsion is carried out fill, sterilization, make benzoylpaeoniflorin microemulsion oral liquid.
Embodiment 7:
A, get peoniflorin 0.6g, lecithin 23g, ethanol 36g, isopropyl myristate 140g and water for injection 32g, standby;
B, lecithin, ethanol are mixed, lecithin is fully dissolved, add the isopropyl myristate mixing again, stir at normal temperatures and pressures, slowly drip water for injection simultaneously and form clear and bright liquid until system;
C, adding peoniflorin, stirring and dissolving promptly gets particle diameter at 10～100nm, the peoniflorin microemulsion of appearance transparent;
D, the peoniflorin microemulsion is carried out fill, sterilization, then through record the peoniflorin microemulsion injection.
Embodiment 8:
A, get peoniflorin 1.2g, lecithin 24.5g, normal propyl alcohol 36.8g, isopropyl myristate 143g and distilled water 27g, standby;
B, lecithin, normal propyl alcohol are mixed, lecithin is fully dissolved, add the isopropyl myristate mixing again, stir at normal temperatures and pressures, slowly drip distilled water simultaneously and form clear and bright liquid until system;
C, adding peoniflorin, stirring and dissolving promptly gets particle diameter at 10～100nm, the peoniflorin microemulsion of appearance transparent;
D, the peoniflorin microemulsion is carried out fill, sterilization, then through record peoniflorin microemulsion drop pill.
Embodiment 9:
A, get Radix Paeoniae Alba total glucosides 1.5g, lecithin 24.5g, normal propyl alcohol 36.8g, isopropyl myristate 143g and distilled water 27g, standby;
B, lecithin, normal propyl alcohol are mixed, lecithin is fully dissolved, add the isopropyl myristate mixing again, stir at normal temperatures and pressures, slowly drip distilled water simultaneously and form clear and bright liquid until system;
C, adding Radix Paeoniae Alba total glucosides, stirring and dissolving promptly gets particle diameter at 10～100nm, the Radix Paeoniae Alba total glucosides microemulsion of appearance transparent;
D, the Radix Paeoniae Alba total glucosides microemulsion is carried out fill, sterilization, then through record Radix Paeoniae Alba total glucosides microemulsion drop pill.
Claims (9)
1, a kind of Radix Paeoniae Alba total glucosides microemulsion formulation, it is characterized in that: each component has following percentage by weight:
Radix Paeoniae Alba total glucosides 0.5%-5%
Surfactant 10.0%-30.0%
Cosurfactant 1.0%-15.0%
Oil 3.0%-75.0%
Distilled water or water for injection 10.0.%-75.0%.
2, Radix Paeoniae Alba total glucosides microemulsion formulation according to claim 1 is characterized in that:
Described surfactant is selected from one or more surfactants in Tweens, poloxamer 188, ethylene glycol-vitamin e succinate, polyoxyethylene castor oil, the lecithin;
Described cosurfactant is selected from one or more cosurfactants in sorbester p17, lecithin, dehydrated alcohol, glycerol, PEG400, normal propyl alcohol, the propylene glycol;
Described grease separation one or more oil in medium chain triglyceride, soybean oil, olive oil, oleic acid, ethyl oleate, isopropyl myristate.
3, Radix Paeoniae Alba total glucosides microemulsion according to claim 1 and 2 is characterized in that:
Described surfactant is that Tween 80 is or/and lecithin;
Described cosurfactant is that PEG400 is or/and dehydrated alcohol;
Described oil is that isopropyl myristate is or/and ethyl oleate.
4, a kind of peoniflorin microemulsion formulation, it is characterized in that: each component has following percentage by weight:
Peoniflorin 0.5%-5%
Surfactant 10.0%-30.0%
Cosurfactant 1.0%-15.0%
Oil 3.0%-75.0%
Distilled water or water for injection 10.0.%-75.0%.
5, peoniflorin microemulsion according to claim 4 is characterized in that:
Described surfactant is selected from one or more surfactants in Tweens, poloxamer 188, ethylene glycol-vitamin e succinate, polyoxyethylene castor oil, the lecithin;
Described cosurfactant is selected from one or more cosurfactants in sorbester p17, lecithin, dehydrated alcohol, glycerol, PEG400, normal propyl alcohol, the propylene glycol;
Described grease separation one or more oil in medium chain triglyceride, soybean oil, olive oil, oleic acid, ethyl oleate, isopropyl myristate.
6, according to claim 4 or 5 described peoniflorin microemulsion formulations, it is characterized in that:
Described surfactant is that Tween 80 is or/and lecithin;
Described cosurfactant is that Polyethylene Glycol is or/and dehydrated alcohol;
Described oil is that isopropyl myristate is or/and ethyl oleate.
7, a kind of benzoylpaeoniflorin microemulsion, it is characterized in that: each component has following percentage by weight:
Benzoylpaeoniflorin 0.5%～5%
Surfactant 10.0%～30.0%
Cosurfactant 1.0%～15.0%
Oil 3.0%～75.0%
Distilled water or water for injection 10.0%～75.0%
8, benzoylpaeoniflorin microemulsion formulation according to claim 7 is characterized in that:
Described surfactant is selected from one or more surfactants in Tweens, poloxamer 188, ethylene glycol-vitamin e succinate, polyoxyethylene castor oil, the lecithin;
Described cosurfactant is selected from one or more cosurfactants in sorbester p17, lecithin, dehydrated alcohol, glycerol, PEG400, normal propyl alcohol, the propylene glycol;
Described grease separation one or more oil in medium chain triglyceride, soybean oil, olive oil, oleic acid, ethyl oleate, isopropyl myristate.
9, according to claims 7 or 8 described benzoylpaeoniflorin microemulsion formulations, it is characterized in that:
Described surfactant is that Tween 80 is or/and lecithin;
Described cosurfactant is that PEG400 is or/and dehydrated alcohol;
Described oil is that isopropyl myristate is or/and ethyl oleate.
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| CN102603827A (en) * | 2012-02-10 | 2012-07-25 | 魏伟 | Paeoniflorin aromatic ester derivative, preparation method and applications thereof |
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| CN111184725A (en) * | 2020-02-27 | 2020-05-22 | 慈溪市人民医院医疗健康集团(慈溪市人民医院) | Medicinal preparation for preventing and treating cerebral infarction and preparation method thereof |
| CN114306434A (en) * | 2021-12-20 | 2022-04-12 | 澳门科技大学 | Composition containing total glucosides of paeony, self-microemulsion preparation, and preparation method and application thereof |
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