CN101185653B - Breviscapine oral administration composition and preparation method thereof - Google Patents
Breviscapine oral administration composition and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the field of medicine preparation, which relates to oral breviscapine composition and preparation method thereof. The invention consists of breviscapine, fatty acid triglyceride, fatty acid monoglyceride or fatty acid diacylglycerol or any proportion of compound of the two and surface active agent according to certain proportion, wherein breviscapine can be suspended into the composition at any proportion. Proved by experiments, the digestion esterolysis products of the oral composition can promote the intestinal mucosa permeation ability and dissolvability of breviscapine; in vivo experiments demonstrate that the bioavailability of breviscapine intestinal absorption can be improved. The invention of the oral breviscapine composition can be prepared into solid dosage forms such as soft capsule, hard capsule, pellet or tablet, or the enteric-coated of these preparations. The invention also has the advantages of easy preparation, low toxicity and stable storage.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to breviscapine oral administration composition and preparation method thereof.
Background technology
Breviscapine (Brevescapine) is from feverfew Erigeron breviscapus (Vant.) Hand.-Mazz. (original name Herba Erigerontis; Have another name called Herba Erigerontis; Erigeron Breviscapus) separates the flavonoid material that obtains in, mainly contain scutellarin (Scutellarin, chemistry by name 4 '; 5,6-trihydroxyflavone-7-glucuronide).Pharmacodynamic study shows that breviscapine has expansion of cerebral vascular, reduces cerebral vascular resistance, cerebral blood flow increasing amount, microcirculation improvement, the effect that improves blood-brain barrier permeability.Breviscapine is widely used in disease such as paralyse after the uncertain apoplexy of treatment cerebral thrombosis, cerebral infarction and type clinically.
The listing preparation variety of breviscapine has Breviscapini injection, Herba Erigerontis injection, Herba Erigerontis tablet, erigeron breviscapus granule.Though the breviscapine drug administration by injection absorbs fast, bioavailability is high, and the patient uses poor compliance, and steps such as preparation, packing, transportation and storage are comparatively complicated; Breviscapine belongs to flavone compound; Water solublity and fat-soluble all very poor, its oral formulations organism-absorbing availability is extremely low, it is reported that the Herba Erigerontis tablet oral administration biaavailability is merely 0.40 ± 0.19% (Ge Qinghua etc.; Breviscapine is in intravital pharmacokinetics of dog and absolute bioavailability research; Chinese Journal of Pharmaceuticals, 2003,34 (12): 618-620).FDA (U.S. food Drug Administration) thinks that the biopharmaceutics character that the decision drug oral absorbs mainly is the height of drug solubility size and mucosa permeability, and as standard medicine is divided into I, II, III and IV class.Breviscapine belongs to the IV medicine, and promptly dissolubility hangs down and the low medicine of mucosa permeability, and such drug oral bioavailability is often lower.For this reason, the key factor of raising breviscapine oral administration bioavailability should be to improve its dissolubility and intestinal mucosal permeability.
The disclosed breviscapine oral administration preparation of prior art lacks the means that tool solves the above-mentioned defective of breviscapine targetedly simultaneously mostly, and the public technology that has only is the simple variation of peroral dosage form, like oral cavity disintegration tablet (CN1695629A; CN1698638A; CN1429618A; CN1582955A), dispersible tablet (CN1530113A; CN1416817A), slow release or controlled release preparation (CN1233327C; CN1212114C; CN1205940C; CN1172679C; CN1480147A; CN1530114A; CN1565472A; CN1515264A), Sublingual tablet (CN1634105A), soft capsule (CN1069520C) etc.; The employing preparation new technique that has for example prepares drop pill (CN1565471A to improve the dissolubility or the dissolution of breviscapine; CN1480148A; CN1408392A; CN1768763A; CN1437950A; CN1531929A; CN1444947A); Adopt solid dispersion technology (CN1102392C); Nanotechnology (CN1364516A); Adopt cyclodextrin inclusion technique (CN1739537A); Adopt self emulsifying technology (CN1593449A), but surfactant in the disclosed self-emulsifiable preparation and cosurfactant may produce the gastrointestinal toxicity up to 80% (optimal choice); With regard to increasing the breviscapine mucosa permeability; Document and patent report seldom only disclose breviscapine-phosphotide compound (CN1359682A) at present, utilize the stronger lipotropy of phospholipid to increase the penetrating ability of film of breviscapine in the complex; But it prepares complicated; Stability is not good enough, and the phospholipid price is more expensive, in produce or cost control be unfavorable.
In sum, solve the problem of breviscapine oral administration organism-absorbing availability, should take measures targetedly with regard to its bad biopharmaceutics character.
Summary of the invention
The object of the invention is to provide a kind of can effectively increase breviscapine oral administration composition of breviscapine oral administration bioavailability and preparation method thereof,
The present invention reaches the purpose that improves its oral administration biaavailability through increasing breviscapine mucosa permeability and dissolubility.
Breviscapine oral administration composition provided by the invention is made up of the mixture and the surfactant of breviscapine, fatty acid triglyceride and fatty acid monoglyceride or fatty acid two sweet esters or both any ratios.
Fatty acid triglyceride of the present invention, carbochain are C6-C18, saturated or unsaturated all can, the long-chain triglyceride of wherein selecting for use can be Semen Maydis oil (Maisine), the Labrafil that soybean oil, Semen Maydis oil or acyl group shift
M1944, Labrafil
M2125, Plurol
Oleique CC497, Gelucire
33/01 (Gattefosse) etc., available medium chain triglyceride, carbochain is C
8-C
10, trade name can be Miglycol
812N (Sasol), Captex
355EP, Captex
350, Captex
300EP (Abitec) etc. also can select the mixture of above-mentioned oil with any ratio for use.Preferred carbochain is C
8-C
10The medium chain triglyceride.
Described fatty acid monoglyceride, fatty acid two sweet esters or both are with the mixture of any ratio, and carbochain is C6-C18, saturated or unsaturatedly all can.Preferred carbochain is C
8-C
10Monoglyceride, diacylglycerol or list/diacylglycerol, the trade name of the C8 monoglyceride of wherein using always has Imwitor
988 (Sasol Corp.), Capmul
MCM C8 (Abitec Corp.) etc., C
8-C
10The trade name of list/two sweet esters has Imwitor
742 (SasolCorp.), CapMum
MCM (Abitec Corp.), Capmul
MCM C10 (Abitec Corp.), Labrafac
CC (Gattefosse) etc.;
Described surfactant can select for use following one or more:
1. polyoxyethylene sorbitan fatty acid ester (for example trade name Tween) comprises following product: polyoxyethylene 20 sorbitan monolaurate (Tween 20), polyoxyethylene 20 sorbitan monopalmitate (Tween40), polyoxyethylene 20 sorbitan monostearate (Tween 60), polyoxyethylene 20 sorbitan monooleate (Tween 80), polyoxyethylene 20 sorbitan trioleate (Tween 85);
2. polyoxyethylene aliphatic alcohol ether class (for example trade name Brij, Brij), preferably this series products is Brij 35;
3. polyoxyethylene fatty acid ester class (for example trade name Myrj, Myrij), preferably this series products is Myrj 52;
4. ethylene oxide-oxypropylene block copolymer (for example trade name Pluronic, poloxamer), preferably this series products is Pluronic F68 (poloxamer 188);
5. Cremophor RH40 (routine trade name Cremophor RH40) or Polyethylene Glycol Oleum Ricini (Cremophor EL);
6. tocopherol acid succinate macrogol ester (TPGS), the commercial Eastman FineChemical Company that derives from);
Polyethylene Glycol-8-glycerol sad/decanoin (commodity Labrasol by name for example, Gattefosse);
9. phospholipid comprises lecithin and fabaceous lecithin.
Preferred surfactants is Cremophor EL, Tween 80, TPGS and Labrasol.
Breviscapine oral administration composition of the present invention; The ratio that it is characterized in that fatty acid monoglyceride or fatty acid two sweet esters or both mixture and fatty acid triglyceride and surfactant is 1: 0.2～6: 0.2～2; Preferred proportion is 1: 1～4: 0.4～1, and most preferred ratio is 1: 3: 0.5.
The present invention prepares breviscapine oral administration composition through following method:
At first, add breviscapine, stir, add fatty acid triglyceride restir at last and evenly promptly get breviscapine oral administration composition of the present invention behind fatty acid monoglyceride or fatty acid two sweet esters or both mixture and the surfactant mix homogeneously.The breviscapine minimal amounts of dissolved is in compositions, and major part is a hybrid state, and breviscapine can any ratio be suspended in the compositions;
With above-mentioned compositions fill hard capsule, soft capsule, the enteric hard capsule for preparing, perhaps carry out enteric coating after the capsule fill again and can get preparations such as enteric hard capsule or enteric soft capsules;
With the above-mentioned compositions for preparing; Adsorb with solid carriers such as silicon dioxide, calcium sulfate, dextrin or crospolyvinylpyrrolidone; Make the formation pressed powder, process granule or micropill again, further be prepared into the enteric form of tablet, capsule, granule etc. or said preparation again.
Orally administered composition of the present invention is tested through external digestion experiment, the experiment of upset intestinal capsule, solubility experiment with in bulk absorption; The result confirms; In gastrointestinal tract, can improve breviscapine through the penetrating ability of intestinal mucosa and dissolubility and the dissolution that increases breviscapine; Significantly improve breviscapine intestinal absorption bioavailability; The present invention is directed to the oral bad biopharmaceutics character that breviscapine exists, solved the defective that prior art exists, realized in gastrointestinal tract, can improving through the penetrating ability of intestinal mucosa and the effect that increases dissolubility and dissolution; Significantly improve breviscapine intestinal absorption bioavailability, have simultaneously that preparation is simple and convenient, toxicity is low and advantage such as excellent storage stability.
Description of drawings
Fig. 1 is a breviscapine oral administration composition external digestion curve chart.
Fig. 2 is blood drug level-time graph (n=4) figure that the breviscapine compositions absorbs through duodenum.
Fig. 3 is the tissue slice microscope figure of intestinal mucosa behind the Orally administered composition duodenal administration.
Wherein, A is the slice map of matched group one breviscapine normal saline suspension, and microscopic examination shows that fine hair is kept perfectly, does not have phenomenon such as come off;
It is similar with matched group that B shows that duodenum gives embodiment 4 back intestinal villies, not damage;
C shows that duodenum gives embodiment 5 back intestinal villies and slightly shortens and obscission, but keeps fine hair than complete morphology generally;
The positive matched group of D, promptly duodenum gives 0.1% TritonX, makes sections observation and finds that intestinal villi seriously merges and comes off.
The specific embodiment:
Labrafac
CC 3.13g
Maisine 0.63g
Cremophor?EL 6.25g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing Labrafac
CC and Cremophor EL, mix homogeneously adds breviscapine under constantly stirring; Add Maisine at last again, stirring promptly gets.
Imwitor
988 1.39g
Labrafil
M1944?8.33g
Brij35 0.28g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing Imwitor
988 and Brij 35; Mix homogeneously; Under constantly stirring, add breviscapine, add Labrafil
M1944 at last again, stirring promptly gets.
CapMum
MCM 4.00g
Captex
350 4.00g
Phosphatidase 12 .00g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing CapMum
MCM and phospholipid; Mix homogeneously; Under constantly stirring, add breviscapine, add Captex
350 at last again, stirring promptly gets.
Imwitor
742 1.67g
Miglycol812N 6.67g
Tween80 1.67g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing Imwitor
742 and Tween80, mix homogeneously adds breviscapine under constantly stirring; Add Miglycol812N at last again, stirring promptly gets.
Capmul
MCM?C10?2.22g
Miglycol812N 6.67g
TPGS 1.11g
Breviscapine 0.04g
During preparation; By above-mentioned recipe quantity; Take by weighing Capmul
MCM C10 and TPGS, mix homogeneously adds breviscapine under constantly stirring; Add Miglycol812N at last again, stirring promptly gets.
CapMum
MCM 1.25g
Imwitor
742 1.25g
Soybean oil 5.00g
Cremophor?EL 2.50g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing Capmul
MCM, Imwitor
742 and CremophorEL; Mix homogeneously; Under constantly stirring, add breviscapine; Add soybean oil at last again, stirring promptly gets.
Imwitor
988 3.33g
Captex
355 3.33g
Cremophor?EL 1.67g
Labrasol 1.67g
Breviscapine 0.4g
During preparation; By above-mentioned recipe quantity; Take by weighing Imwitor
988, Cremophor EL and Labrasol; Mix homogeneously; Under constantly stirring, add breviscapine; Add Captex
355 at last again, stirring promptly gets.
Be prepared into soft capsule with embodiment 2 prepared breviscapine oral administration compositions as substrate, wherein every soft capsule contains breviscapine 20mg.
Embodiment 9
Dissolve hard capsule with the direct coloclysis of embodiment 5 prepared breviscapine oral administration compositions, wherein every capsules contains breviscapine 20mg.
Embodiment 10
Take by weighing embodiment 4 prepared breviscapine oral administration composition 10g, under grinding state, add altogether 5g of micropowder silica gel one by one, make the pressed powder of breviscapine oral administration composition, measuring this powder angle of repose is 39.5 °, and bulk density is 0.54g/cm
3
Embodiment 11
With No. 0 capsule of embodiment 10 obtained breviscapine oral administration composition pressed powder fills, capsule with enteric-coating material Eudragit L100-55 coating, obtains the breviscapine enteric coated capsule in the high-efficiency coating pot, and every capsules contains breviscapine 20mg or 40mg.
Embodiment 12
Microcrystalline Cellulose 120g
Distilled water 36g
Ethanol 18g
During preparation breviscapine oral administration composition micropill, take by weighing microcrystalline Cellulose, successively add distilled water and ethanol, kneading evenly adds the prepared breviscapine compositions of embodiment 1 again, processes soft material.Behind the airtight 1.5h of prepared soft material, prepare micropill with extruding rolling circle equipment then, account for more than 85% between the particle diameter 16-24 order.With micropill in fluid bed with enteric-coating material Eudragit L100-55 coating 1h, continue dry 0.5h after, take out and to be placed on that heat treatment 12h promptly makes the breviscapine micropill under the 45-50 ℃ of condition.With No. 0 capsule of micropill fill, every capsules contains breviscapine 20mg or 40mg.
Embodiment 13
Maltodextrin 15%
Crospolyvinylpyrrolidone 15%
Microcrystalline Cellulose 40%
During preparation breviscapine oral administration composition tablet, take by weighing the prepared breviscapine compositions of embodiment 6, priority adds maltodextrin and crospolyvinylpyrrolidone under stirring; Completion of cure, recording angle of repose is 38.5 °, adds microcrystalline Cellulose again; Mix homogeneously; Directly pressed powder promptly gets Herba Erigerontis tablet, and every contains breviscapine 20mg.
Embodiment 14 external digestions experiment
In order to explore oil digestion behavior and digestion esterlysis product thereof in vivo in the breviscapine oral administration composition to the influence of breviscapine mucosa permeability, it is following to set up the external digestion model according to the relevant physiological parameter of digestion system in the body:
At first prepare buffer, it consists of 50mM three hydroxyl first ammonia methane-maleic acids (Trizma maleate), 150mM NaCl and 5mM Ca
2+, regulate pH to 6.8; This buffer preparation cholate micellar solution (forming) of reuse by 5mM Taurodeoxycholate sodium and 1.25mM phosphatidylcholine; When digestion experiment begins; Add pancreatic lipase solution (concentration is 1000U/ml) 1ml after matched group (Miglycol 812N) mixing and stirring with Orally administered composition one embodiment 4 of the cholate micellar solution of 9ml and 0.5g and embodiment 5 (both do not contain breviscapine) or 0.5g; Timing immediately and with 0.2M NaOH titration to keep whole system pH6.8; With the percentage rate mapping of different time oil digestion esterlysis, see Fig. 2.
The result shows, compares with matched group, and embodiment 4 and embodiment 5 can be by quick digestion, and 5min esterlysis rate promptly reaches about 65%, and matched group is 40%.The esterlysis product of Orally administered composition such as sodium soap, fatty acid monoglyceride and cholate phospholipid form complicated mixed micelle, thereby effectively promote breviscapine penetrating through intestinal mucosa.
Embodiment 15 upset intestinal capsule experiments
Rat overnight fasting (can freely drink water), the urethane intraperitoneal injection of anesthesia (1g/kg) with 20%.After cutting off the abdominal cavity along ventrimeson, take out jejunal segment 6-7cm, place ice-cold tyrode's solution, aerating oxygen cuts off mesentery.Glass tubing with external diameter 2.5mm softly overturns intestinal segment, make intestinal mucosa towards outside, serosa side is inside, ligation intestinal anus side, sample tap is fixed in intestinal capsule upper end.Inject blank tyrode's solution as receiving liquid from sample tap to enteral.In the liquid of embodiment 14 after the digestion esterlysis, add K
+, glucose etc. makes with the composition of tyrode roughly the same; The concentration of breviscapine is formulated as 500ng/ml; In addition with the breviscapine solution of pH6.8 phosphate buffer preparation same concentrations as matched group, above solution as the supply liquid of upset intestinal capsule experiment to investigate the mucosa permeability of breviscapine.Respectively at 15,30,45,60, the 90min 0.6ml that takes a sample in the intestinal capsule, the centrifugal 10min of 10000rpm gets clear liquor 0.4ml and measures breviscapine concentration with HPLC, replenishes the isothermal tyrode's solution with volume simultaneously.
The penetrating percentage rate of accumulation and the increase multiple of breviscapine are seen table 1 behind upset intestinal capsule experiment the carrying out 1.5h, and the result shows that after the digestion esterlysis, its esterlysis product has significant promotion breviscapine mucosa permeation to Orally administered composition of the present invention at intestinal.
Table 1. breviscapine is accumulated penetrating percentage rate and is increased multiple through jejunum in rats
| Preparation | Accumulation sees through percentage rate (%) | Increase multiple |
| Matched |
6.15±1.02 15.23±2.54 18.41±3.06 | 1 2.5 3.0 |
Embodiment 16 solubility experiments
Take by weighing excessive breviscapine, the solution that places the digestion of pH6.8PBS solution and embodiment 14 to finish behind 37 ℃ of constant temperature jolting 10h, is got supernatant behind the high speed centrifugation 10min, measures with HPLC, measures the result and sees table 2.The result shows that the digestion product of breviscapine oral administration composition can significantly increase the dissolubility of breviscapine.
The dissolubility of table 2. breviscapine in different medium
| Medium | Dissolubility (mg/ml) | Increase multiple |
| |
7.23±0.45 16.52±2.56 21.85±3.55 | 1 2.28 3.02 |
Embodiment 17 breviscapine oral administration compositions are tested in bulk absorption
Get 16 of the SD rats of body weight 250g～280g, fasting overnight (can freely drink water), the pneumoretroperitoneum of weighing injection chloral hydrate (6.5%) solution 1ml/100g is fixed in its back of the body position on the operation platen after the anesthesia, makes the carotid artery intubate and uses for getting blood.Rat is divided into 4 groups at random, one group of lumbar injection breviscapine solution wherein, and dosage is 10mg/kg; Cut off abdominal part along ventrimeson for other three groups, breviscapine is respectively organized the preparation duodenal administration, is respectively matched group-breviscapine suspension (normal saline preparation), embodiment 5 and embodiment 10, and dosage is 80mg/kg.Above-mentioned respectively organize before administration and administration after different time get blood 0.3ml, add in the plastic centrifuge tube that contains heparin, the centrifugal 10min of 6000rpm gets blood plasma and is stored in rapidly in-20 ℃ of refrigerators,
The chromatographic condition that breviscapine blood drug level HPLC measures is: Tianjin, island LC-10AD highly effective liquid phase chromatographic system; The SPD-10A UV-detector; Chromatographic column is Phenomenex Luna C
18(250mm * 4.60mm, 5 μ m); Mobile phase is acetonitrile: 0.2% phosphate buffer (22: 78); Flow velocity is 1ml/min; The detection wavelength is 335nm; AUFS is 0.002,40 ℃ of column temperatures, sample size 30 μ l.
The accurate plasma sample that returns to room temperature of drawing adds isopyknic methanol, vortex oscillation 20s, and behind the centrifugal 10min of 6000rpm, separation of supernatant, direct injected is with the external standard standard measure.The standard curve equation is: concentration C (μ g/ml)=1.18*10
-5A+0.082 (r=0.9993), the range of linearity 0.1～10 μ g/ml.The withinday precision of the high, medium and low determination of plasma concentration of breviscapine is respectively 5.94%, 3.82% and 2.92%, and day to day precision is respectively 6.90%, 5.32% and 6.69%.The method specificity meets the requirements, and the impurity in the blood plasma does not disturb the mensuration of breviscapine.
Embodiment 18
According to the experimental technique of embodiment 17, blood drug level-time graph that the breviscapine duodenum absorbs is seen Fig. 2, and average pharmacokinetic parameters is seen table 3, wherein C
MaxAnd T
MaxThe treating excess syndrome measured value, trapezoidal method is calculated AUC.Calculate the bioavailability of Breviscapine duodenal administration as contrast with the breviscapine lumbar injection.The result shows that matched group-breviscapine suspension absorbs very poor, and bioavailability is merely 2.40%.Compare with matched group, the breviscapine of embodiment 5 and embodiment 10 absorbs significantly and increases, and compares with the AUC of lumbar injection, and bioavailability is respectively 38.07% and 35.18%, improves 15.9 times and 15.0 times respectively than the F of matched group.
Orally administered composition of the present invention can significantly improve breviscapine intestinal absorption bioavailability; Its reason possibly can promote cell membrane fluidity to increase, reduce rete malpighii viscosity etc. with its digestion esterlysis product and to help the intestinal of breviscapine penetrating; Also can increase the dissolubility of breviscapine simultaneously and help its passive intestinal mucosa that diffuses through, above-mentioned composite factor impels the absorption of breviscapine to increase.
The pharmacokinetic parameters (n=4) that table 3. breviscapine compositions absorbs at the body duodenum
| Dosage form | Tmax(h) | ?Cmax(ug/ml) | AUC (ug.h/ml) | ?F(％) | Increase doubly |
| |
0.25 0.5 6 | ?6.37±1.23 ?4.62±1.02 ?0.48±0.15 | 19.67±2.31 21.34±2.12 1.23±0.25 5.58 | ?38.07±3.36?35.18±3.81?2.40±1.70?100％ | 15.8614.991 |
Embodiment 19
According to the experimental technique of embodiment 17, after each administration group of duodenum is got blood and finished, till death with the etherization rat; Clip duodenum section; Be placed in the paraformaldehyde solution with pH6.8 PBS flushing, make paraffin section, with hematoxylin and eosin dyeing; Under optical microscope, observe intestinal villi and change, the result sees Fig. 3.Fig. 3 A is the slice map of matched group-breviscapine normal saline suspension, and microscopic examination shows that fine hair is kept perfectly, does not have phenomenon such as come off; It is similar with matched group that Fig. 3 B shows that duodenum gives embodiment 4 back intestinal villies, not damage; Fig. 3 C shows that duodenum gives embodiment 5 back intestinal villies and slightly shortens and obscission, but keeps fine hair than complete morphology generally; Fig. 3 D is the positive controls of otherwise designed, and promptly duodenum gives 0.1% TritonX, makes sections observation and finds that intestinal villi seriously merges and comes off.Experiment shows that breviscapine oral administration composition of the present invention does not almost have toxicity to mucous membrane of small intestine, can keep the integrity of intestinal villi.
Claims (10)
1. breviscapine oral administration composition is characterized in that being made up of the mixture of breviscapine, fatty acid monoglyceride or fatty acid two sweet esters or both any ratios and fatty acid triglyceride and surfactant; The ratio of described fatty acid monoglyceride or fatty acid two sweet esters or both mixture and fatty acid triglyceride and surfactant is 1: 0.2～6: 0.2～2.
2. breviscapine oral administration composition according to claim 1 is characterized in that the ratio of described fatty acid monoglyceride or fatty acid two sweet esters or both mixture and fatty acid triglyceride and surfactant is 1: 1～4: 0.4～1.
3. breviscapine oral administration composition according to claim 1 is characterized in that the ratio of described fatty acid monoglyceride or fatty acid two sweet esters or both mixture and fatty acid triglyceride and surfactant is 1: 3: 0.5.
4. breviscapine oral administration composition according to claim 1 is characterized in that described fatty acid monoglyceride, fatty acid two sweet esters or both mixture with any ratio, and its carbochain is C
6-C
18
5. according to claim 1 or 4 described breviscapine oral administration compositions, it is characterized in that described fatty acid monoglyceride, fatty acid two sweet esters or both mixture with any ratio, be that carbochain is C
8-C
10Medium chain monoglyceride, diacylglycerol or list/diacylglycerol mixture.
6. breviscapine oral administration composition according to claim 1 is characterized in that described fatty acid triglyceride, and its carbochain is C
6-C
18
7. according to claim 1 or 6 described breviscapine oral administration compositions, it is characterized in that described fatty acid triglyceride, is that carbochain is C
8-C
10The medium chain triglyceride.
8. breviscapine oral administration composition according to claim 1, it is characterized in that described surfactant is selected from polyoxyethylene sorbitan fatty acid ester, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene fatty acid ester class, ethylene oxide-oxypropylene block copolymer, Polyethylene Glycol is natural or castor oil hydrogenated, tocopherol acid succinate macrogol ester, Polyethylene Glycol-8-glycerol sad/decanoin, phospholipid or above-mentioned surfactant mixtures.
9. breviscapine oral administration composition according to claim 8 is characterized in that described surfactant is that Polyethylene Glycol is natural or castor oil hydrogenated, polyoxyethylene sorbitan fatty acid ester, tocopherol acid succinate macrogol ester or Polyethylene Glycol-8-glycerol is sad/decanoin.
10. the method for preparing of the described breviscapine oral administration composition of claim 1; It is characterized in that comprising the steps: in proportion with behind fatty acid monoglyceride or fatty acid two sweet esters or both mixture and the surfactant mix homogeneously; Add breviscapine; After stirring, adding fatty acid triglyceride restir is even, gets breviscapine oral administration composition.
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| CN103083683B (en) * | 2013-02-05 | 2015-02-11 | 广东华南药业集团有限公司 | Breviscapine phosphatide compound, and preparation method and application thereof |
| CN104906160B (en) * | 2015-05-25 | 2018-07-24 | 昆明理工大学 | A kind of enteric coated preparations of erigeron breviscapus extract |
| CN113995729B (en) * | 2021-10-22 | 2022-11-18 | 北京悦康科创医药科技股份有限公司 | Hydroxy safflor yellow A oral semisolid capsule and preparation method and application thereof |
| CN114557976B (en) * | 2022-04-02 | 2023-05-30 | 复旦大学 | Scutellarin sustained release tablet and preparation method thereof |
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