CN1726945A - Solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb - Google Patents
Solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb Download PDFInfo
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- CN1726945A CN1726945A CN 200410070463 CN200410070463A CN1726945A CN 1726945 A CN1726945 A CN 1726945A CN 200410070463 CN200410070463 CN 200410070463 CN 200410070463 A CN200410070463 A CN 200410070463A CN 1726945 A CN1726945 A CN 1726945A
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Abstract
A dispersed solid of the ngai flavone is prepared from the ngai flavone and hydrophilic carrier through mixing in the Wt ratio of 1: (0.5-2.0). Its preparing process features that the ngai flavone in dispersed in said hydrophilic carrier. Its advantage is high solubility.
Description
Technical field
The present invention relates to the novel formulation of Herba Blumeae Balsamiferae total flavones extract, relate in particular to the solid dispersion that contains Herba Blumeae Balsamiferae total flavones extract.
The invention still further relates to the pharmaceutical composition that contains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
The invention still further relates to the purposes of Herba Blumeae Balsamiferae total flavones extract solid aspect the preparation cardiovascular drugs.
Background technology
Herba Blumeae Balsamiferae (Blumea balsamfera (L.) DC) is a feverfew, has another name called Balsamiferou Blumea Herb, Da Ai, and its classical purposes is to extract Borneolum Syntheticum (Borneol) from this plant, has another name called Borneolum Syntheticum or camphol).Flavone compound refers to belong on the structure flavonoid, flavonols, flavanone, flavanone alcohols, anthocyan, flavanol compound, two benzene pyrrones, the chemical compound of osajin, chalcones, dihydrochalcone-type, aurones class, homoisoflavone class etc., and they and monosaccharide or the oligosaccharide glucosides or the other forms of derivant that form.Herba Blumeae Balsamiferae total flavones extract and preparation method thereof is disclosed in the Chinese patent application 02134927.4 (CN1403451A), wherein Herba Blumeae Balsamiferae total flavones extract extracts acquisition from the plant Herba Blumeae Balsamiferae, as main component (or main functional component), wherein the gross weight sum of flavone compound accounts for 25～100% of extract gross weight with flavone compound.
The preparation that is used as medicine with Herba Blumeae Balsamiferae extract in the prior art, its reactive compound is mainly Oleum Blumeae Balsamiferae, and composition is a terpene substances, as " the upright refreshing drop pill of pharynx ", Jinjian larynx spray, the mould peace Oral preparation of match etc.The disclosed Chinese patent relevant with Herba Blumeae Balsamiferae extract relates generally to Oleum Blumeae Balsamiferae, as 97107723.1 (treatment oral cavity and laryngopharyngeal diseasess), 98112092.X (treatment laryngopharyngeal diseases), 951100521.9 (treatment hyperosteogeny diseases), 94102037.1 (specially controlling various skin scalds and many places dermatopathy).The bibliographical information relevant with Herba Blumeae Balsamiferae relates generally to plant culture, plant component etc., and pharmaceutical research relates generally to the liver protective effect.Relate in the prior art with the total flavones is that the made preparation of Herba Blumeae Balsamiferae extract of effective ingredient only is with Herba Blumeae Balsamiferae total flavones extract and the compositions that makes after some carrier or excipient simply mix, the dissolution of these preparations is very poor, has directly influenced the application and the drug effect of medicine.
Solid dispersion technology be with solid dispersion in solid, be the new technique of formulation art.Normally a kind of insoluble drug is with molecule, colloidal state, crystallite or amorphous state, be dispersed in the another kind of water-soluble material or slightly solubility, enteric solubility material in be solid dispersion (solid dispersion), to reach the purpose that improves dissolution rate or slow release.
For being the solid dispersion technology of purpose to improve dissolution, the dissolution rate of solid dispersion depends on used carrier properties of materials and formulation method to a great extent.Which kind of solid dispersion technology different pharmaceutical adopts, depend primarily on structural property, dissolubility and the solubility property etc. of pharmaceutical properties and carrier material, therefore most important for the preparation solid dispersion at specific ingredient selection carrier material and formulation method.
Summary of the invention
One object of the present invention is to provide a kind of solid dispersion that contains Herba Blumeae Balsamiferae total flavones extract.The Herba Blumeae Balsamiferae total flavones extract high degree of dispersion that makes slightly solubility is in the strongly hydrophilic carrier, the high degree of dispersion state that not only can keep insoluble drug, and make medicine have good wettability, can improve drug solubility, quickening medicine dissolution rate, raising bioavailability thereby make.
Another object of the present invention is to provide the pharmaceutical composition that contains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
A further object of the present invention is to provide the application of Blumea balsamifera total flavones solid dispersion in preparing treatment or prevention coronary heart disease, hyperlipemia, atherosclerotic medicine.
According to an aspect of the present invention, the solid dispersion that contains Blumea balsamifera total flavones comprises Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier, and wherein the weight ratio of Herba Blumeae Balsamiferae total flavones extract and carrier material is 1: 0.5～1: 20; The formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier can be prepared solid dispersion, 45 minutes stripping quantities of single dose are not less than and indicate 70% of content in the solid dispersion preparation that is obtained with the Herba Blumeae Balsamiferae total flavones extract of aforementioned proportion and hydrophilic carrier.
In the present invention, select suitable hydrophilic carrier according to the physicochemical property of Herba Blumeae Balsamiferae total flavones extract, preferred hydrophilic carrier is selected from least a or several mixture in polyvinylpyrrolidone (PVP) class, Polyethylene Glycol (PEG) class, cyclodextrin, surfactant-based, ureas, organic acid and the saccharide.Wherein more preferably PVP K15, PVP K30, PVP K90, PVPK29/32 or PVP XL in the polyvinylpyrrolidone class material, more preferably PEG 4000 or PEG 6000 in the polyethylene glycols material, cyclodextrin can be selected β-CD for use, surfactant-based more preferably poloxamer 188, polyethyleneglycol glyceride (Gelucire44/14) or VitE TPGS NF, ureas can be selected carbamide for use, organic acid can be selected citric acid, succinic acid, cholic acid or deoxycholic acid for use, and saccharide is dextran, lactose, galactose, mannitol or sucrose more preferably.The weight ratio of Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier is 1: 0.5～1: 20, more preferably 1: 3～1: 9, most preferably is 1: 9.
The formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier for example can be comprised, solvent method, polishing and spray drying method can be selected suitable method and process conditions according to the physicochemical property of Herba Blumeae Balsamiferae total flavones extract and employed hydrophilic carrier.Wherein solvent method is that Herba Blumeae Balsamiferae total flavones extract is dissolved in the organic solvent, the optional solvent that is used in solubilized medicine under room temperature and the heating condition of organic solvent, for example ethanol, dichloromethane, chloroform, acetonitrile; Hydrophilic carrier is dissolved in this organic solvent, mix homogeneously; Rotary evaporation makes the organic solvent volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.Polishing is with Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier mix homogeneously, places beveller, grinds 1～3 hour with the rotating speed of 300～600rpm/min, promptly gets solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.The spray drying rule is with the dissolving of Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier or is suspended in the alcoholic solution, with ultrasonic 15 minutes of this mixed solution, carries out spray drying again, promptly gets solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.When one or both of hydrophilic carrier material selection polyethylene glycols and surfactant apoplexy due to endogenous wind, also can use solvent-fusion method: Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of organic solvent, this organic solvent is the solvent of solubilized medicine under room temperature and heating condition, ethanol for example, dichloromethane, chloroform or acetonitrile, hydrophilic carrier is heated to 50～60 ℃, make fusion, add drug solution, stir evenly, evaporation removes and desolvates, fused mass is placed the rustless steel pallet of ice bath, make straticulation, blow with cold wind, make its rapid cooling curing, place exsiccator dry 2 days, and pulverized, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Its preparation single dose of the solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb 45 minutes stripping quantity (calling dissolution in the following text) that contains of the present invention is not less than and indicates 70% of content, preferably 45 minutes stripping quantities are not less than and indicate 80% of content, and more preferably 45 minutes stripping quantities are not less than and indicate 90% of content.
In a preferred embodiment of the invention, a kind of solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb is provided, it is active ingredient with the Herba Blumeae Balsamiferae total flavones extract, with PVP K29/32 is hydrophilic carrier, the employing solvent method in hydrophilic carrier, has prepared the active ingredient high degree of dispersion dissolution and has reached 98.5% solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb; In another preferred embodiment of the present invention, with the Herba Blumeae Balsamiferae total flavones extract is active ingredient, with galactose and PVP K90 is hydrophilic carrier, adopts polishing to prepare dissolution and reaches 96.2% solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb; In another preferred embodiment of the present invention, be active ingredient with the Herba Blumeae Balsamiferae total flavones extract, be hydrophilic carrier with PEG 6000, adopting solvent-fusion method to prepare dissolution is 95.6% solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb; In another preferred embodiment of the present invention, be active ingredient with the Herba Blumeae Balsamiferae total flavones extract, with the lactose hydrophilic carrier, adopting spray drying method for preparation to obtain dissolution is 95.3% solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
According to a further aspect in the invention, the pharmaceutical composition that contains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb comprises solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of the present invention and pharmaceutically acceptable excipient, and these excipient include but not limited to: starch, lactose, mannitol, sorbitol, microcrystalline Cellulose, pregelatinized Starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, magnesium stearate, Pulvis Talci, micropowder silica gel etc.Pharmaceutical composition of the present invention generally is prepared to solid dosage forms, for example tablet, capsule, granule, powder etc.
The Herba Blumeae Balsamiferae total flavones extract that the present invention is low with dissolubility combines with hydrophilic carrier, through the formulation method of active ingredient high degree of dispersion in carrier of total flavones having been prepared solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.The present invention has following good effect:
1. increase the medicine dispersion: the present invention is active component with the Herba Blumeae Balsamiferae total flavones extract, with its load in the strongly hydrophilic carrier, by multiple preparation technology it is disperseed at the carrier camber, exist with amorphous or molecularity, increased the surface area of medicine dissolution greatly, thereby can improve the dissolubility of medicine, accelerate the dissolution rate of medicine, improve bioavailability.
2. increase the wettability of medicine: have the wettability that surface-active carrier can increase active component, and the on-surface-active carrier can tightly be centered around around the active component particle, make active component be difficult for condensing and assembling, increase contacts with water, improves the wettability of active component.
3. formation upper state: active component is amorphous or metastable polymorphic in the solid dispersion system, metastable state molecular diffusion energy height, and stripping is fast; Amorphous also is upper state.In process in leaching, along with the increase that disperses the thing stripping, active component has formed supersaturated solution in solution, and the continuity of hypersaturated state can further cause separating out the polymorphous phenomenon of the metastable state with high-dissolvability.
Absorb in the external stripping of medicine and the body and have dependency, therefore the present invention is with the test method of dissolution method as absorbing state in the analogue body, the Blumea balsamifera total flavones solid dispersion that is obtained is carried out the dissolution in vitro test, use the facilitation of technology of the present invention active component stripping and bioavailability to judge.
Below by detailed description, illustrate but do not limit the present invention better embodiment of the present invention:
The specific embodiment of invention
Judge the method for invention effect
Adopt the dissolution in vitro assay method: the basket method algoscopy that Chinese Pharmacopoeia is 2000 editions.Dissolution medium is a water, and 900ml accurately takes by weighing sample an amount of (being equivalent to Blumea balsamifera total flavones 60mg), adds in the dissolution medium, and temperature is 37 ± 0.5 ℃, and rotating speed is 100r/m.Pick up counting during with sample contact solution, to 1h location sampling 10ml, with 0.8 μ m filtering with microporous membrane, filtrate is measured trap in 287nm, used instrument is Tianjin, island UV-2501 UV, visible light spectrophotometer, and the used carrier material is noiseless to the mensuration of Blumea balsamifera total flavones.
Material source:
Herba Blumeae Balsamiferae total flavones extract: can be according to disclosed method preparation among the Chinese patent application CN1403451A, concrete a kind of preparation method is as follows:
Get Herba Blumeae Balsamiferae crude drug (dry stem and leaf) 150g, pulverize, under 77～85 ℃ of temperature, with the 70% ethanol water reflux, extract, 2 times (1500ml * 2) of 1500ml, each 1.5 hours.Merge extractive liquid,, precipitation is filtered, gone to standing over night under the room temperature, and filtrate decompression concentrates (50 ℃, 0.07～0.1Mpa) to cumulative volume 1000ml, concentrated solution adds 5g calcium chloride, stirs 2min, left standstill centrifugal (4000rpm/min * 10min), remove residue under 4 ℃ about 3～6 hours.Supernatant is crossed the D101 macroporous adsorptive resins (whether the about 500ml of column volume, the about 500ml/hr of flow velocity adsorb saturated with hydrochloric acid-magnesium powder reaction monitoring effluent with the conclusive evidence resin column) of new processing.Subsequently, successively with 1500ml water, 1000ml 20% ethanol water, 1500ml 70% ethanol water elution, the about 500ml/hr of elution speed.Collect 70% ethanol water elution liquid, and concentrating under reduced pressure (50 ℃, 0.07～0.1Mpa) near dried, (room temperature in the vacuum drying oven, 0.08～0.1Mpa, silica-gel desiccant) dry 12～72 hours, get the about 2.2g of yellow powder shape Herba Blumeae Balsamiferae total flavones extract (water content≤5%).
Other materials: commercially available purchase
Employed instrument is conventional instrument.
The preparation of Blumea balsamifera total flavones solid dispersion and dissolution in vitro are measured
[embodiment 1]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 0.5 weight portion PVP-K30, be dissolved in an amount of dehydrated alcohol, with this mixed solution ultrasonic mixing 15min in the supersonic oscillations instrument, the elimination insoluble impurities is with this mixed liquor spray drying.The spray drying condition is: inlet temperature is 45 ℃, and charging rate is 25ml/min, and the nebulizer rotating speed is 45Hz, and cyclone separator pressure reduction is the 50mm water column.The gained dried powder is the Blumea balsamifera total flavones solid dispersion.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 83.1%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with spray drying method.
[embodiment 2]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of dichloromethane, adds 1 weight portion sodium citrate and be dissolved in this organic solvent, mix homogeneously; Rotary evaporation makes the organic solvent volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 85.4%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent method.
[embodiment 3]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 1.5 weight portion PVP-XL mix homogeneously, place planetary beveller, ground 1.5 hours with the rotating speed of 300r/m, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 84.8%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with polishing.
[embodiment 4]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of dehydrated alcohol, 2.5 weight portion surfactant Gelucire 44/14 are heated to 55 ℃, make fusion, add drug solution, stir evenly, evaporation removes and desolvates, and fused mass is placed the rustless steel pallet of ice bath, make straticulation, blow with cold wind, make its rapid cooling curing, placed exsiccator dry 2 days, pulverize, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion 3.5 grams, mix with 5 gram microcrystalline Cellulose, 3 gram starch, 1 gram cross-linking sodium carboxymethyl cellulose, with 1% polyvidone ethanol liquid (75% concentration) is binding agent system soft material, crossing 40 mesh sieves granulates, 60 ℃ of dryings, cross 30 mesh sieve granulate, promptly get the Blumea balsamifera total flavones granule.
Get made granule an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 86.9%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent-fusion method.
[embodiment 5]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 4 weight portion PVP-K15, be dissolved in an amount of dehydrated alcohol, with this mixed solution ultrasonic mixing 15min in the supersonic oscillations instrument, the elimination insoluble impurities is with this mixed liquor spray drying.The spray drying condition is: inlet temperature is 45 ℃, and charging rate is 20ml/min, and the nebulizer rotating speed is 45Hz, and cyclone separator pressure reduction is the 50mm water column.The gained dried powder is the Blumea balsamifera total flavones solid dispersion.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 89.5%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with spray drying method.
[embodiment 6]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 5 weight portions β-CD mix homogeneously, place planetary beveller, ground 2 hours with the rotating speed of 300r/m, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get the Blumea balsamifera total flavones solid dispersion
(be equivalent to Blumea balsamifera total flavones 60mg) in right amount, measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 93.4%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with polishing.
[embodiment 7]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of dehydrated alcohol, 8 weight portion PEG-6000 are heated to 60 ℃, make fusion, add drug solution, stir evenly, evaporation removes and desolvates, and fused mass is placed the rustless steel pallet of ice bath, make straticulation, blow with cold wind, make its rapid cooling curing, placed exsiccator dry 2 days, pulverize, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 95.6%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent-fusion method.
[embodiment 8]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of ethanol, adds 9 weight portion PVPK29/32, mix homogeneously makes abundant dissolving; Rotary evaporation makes the ethanol volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion 10 grams, mix with 5 gram lactose, 3 gram pregelatinized Starch, 1 gram carboxymethyl starch sodium, cross 80 mesh sieves 2 times, mix homogeneously is a binding agent system soft material with 1% low-substituted hydroxypropyl cellulose alcoholic solution (concentration 50%), crossing 40 mesh sieves granulates, 60 ℃ of dryings are crossed 30 mesh sieve granulate, add 0.15 gram Pulvis Talci mix homogeneously, tabletting can prepare 100 of Blumea balsamifera total flavones sheets.
Get 1 of the Herba Blumeae Balsamiferae sheet (being equivalent to Blumea balsamifera total flavones 60mg) of gained, measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 98.5%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent method.
[embodiment 9]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 4 weight portion galactose, 8 weight portion PVP K90 mix homogeneously, place planetary beveller, ground 1 hour with the rotating speed of 400r/m, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Getting Blumea balsamifera total flavones solid dispersion 13 grams, with 6 gram mannitol, 1 gram polyvinylpolypyrrolidone mix homogeneously, is binding agent system soft material with 1% polyvidone ethanol liquid (concentration 50%), crosses 40 mesh sieves and granulates, and 60 ℃ of dryings are crossed 30 mesh sieve granulate, 100 of fill capsules.
Get 1 of the Herba Blumeae Balsamiferae capsule (being equivalent to Blumea balsamifera total flavones 60mg) of gained, measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 96.2%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with polishing.
[embodiment 10]:
With 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 18 weight portion lactose, be dissolved in an amount of dehydrated alcohol, with this mixed solution ultrasonic mixing 15min in the supersonic oscillations instrument, the elimination insoluble impurities is with this mixed liquor spray drying.The spray drying condition is: inlet temperature is 46 ℃, and charging rate is 16ml/min, and the nebulizer rotating speed is 45Hz, and cyclone separator pressure reduction is the 50mm water column.The gained dried powder is the Blumea balsamifera total flavones solid dispersion.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 95.3%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with spray drying method.
[embodiment 11]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of chloroform, adds 19 weight portion dextrans, mix homogeneously makes abundant dissolving; Rotary evaporation makes the chloroform volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 97.0%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent method.
[embodiment 12]:
1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of dehydrated alcohol,, makes fusion the mixture heated to 60 of the VitE TPGS NF of 15 weight portion PEG-4000 and 5 weight portions ℃, add drug solution, stir evenly, evaporation removes and desolvates, and fused mass is placed the rustless steel pallet of ice bath, make straticulation, blow with cold wind, make its rapid cooling curing, placed exsiccator dry 2 days, pulverize, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
Get Blumea balsamifera total flavones solid dispersion an amount of (being equivalent to Blumea balsamifera total flavones 60mg), measure dissolution in vitro, the accumulative total stripping percentage rate that gets 1h is 97.9%, as seen makes the dissolution that solid dispersion can significantly improve Blumea balsamifera total flavones with solvent-fusion method.
[comparative examples]
The dissolution determination of Herba Blumeae Balsamiferae total flavones extract
Adopt the dissolution in vitro assay method: the basket method algoscopy that Chinese Pharmacopoeia is 2000 editions.Dissolution medium is a water, and 900ml accurately takes by weighing Herba Blumeae Balsamiferae total flavones extract an amount of (being equivalent to Blumea balsamifera total flavones 60mg), adds in the dissolution medium, and temperature is 37 ± 0.5 ℃, and rotating speed is 100r/m.Pick up counting during with sample contact solution, to 1h location sampling 10ml, with 0.8 μ m filtering with microporous membrane, filtrate is measured trap in 287nm, and used instrument is Tianjin, island UV-2501 UV, visible light spectrophotometer.
The 1h of Herba Blumeae Balsamiferae total flavones extract (n=6) accumulative total stripping percentage rate is 23.1% after measured.
The result of above each embodiment is summarized as follows table, makes that technical scheme of the present invention and beneficial effect are clearer:
More than the description of the various embodiments of the present invention is not limited the present invention, those skilled in the art can make various changes and distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to claims of the present invention institute restricted portion.
The preparation and the dissolution of table solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb
| The embodiment numbering | The Herba Blumeae Balsamiferae total flavones extract weight portion | The hydrophilic carrier weight portion | With the method for Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in carrier | 45 minutes dissolutions of solid dispersion |
| 123456789 10 11 12 contrasts | 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part 1 part | 5 parts of 15 parts of TPGS NF of 9 parts of galactolipin PVP of 8 parts of PVP K29/32 of 5 parts of PEG6000 of 4 parts of β-CD of 2.5 parts of PVP K15 of 1.5 parts of Gelucire44/14 of 1 part of PVP XL of 0.5 part of sodium citrate of PVP K30 K90,18 parts of dextrans of 4 parts of 8 parts of lactose, 19 parts of PEG4000 Vit E // | The polishing solvent-(ethanol is solvent to spray-drying solvent method (carrene is solvent) to dissolve method; 55 ℃) spray-drying polishing solvent-(ethanol is solvent to dissolve method; 60 ℃) solvent method (ethanol is solvent) polishing spray-drying solvent method (chloroform is solvent) solvent-dissolve method (ethanol is solvent, 60 ℃)/ | 83.1％ 85.4％ 84.8％ 86.9％ 89.5％ 93.4％ 95.6％ 98.5％ 96.2％ 95.3％ 97.0％ 97.9％ 23.1％ |
Claims (14)
1, a kind of solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb is characterized in that, it contains
Herba Blumeae Balsamiferae total flavones extract 1 weight portion; And
Hydrophilic carrier 0.5～20 weight portion;
Wherein with described Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier the formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier can be prepared described solid dispersion;
45 minutes stripping quantities of single dose are not less than and indicate 70% of content in the described solid dispersion preparation.
2, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 1 is characterized in that described hydrophilic carrier is selected from least a or several mixture in polyvinylpyrrolidone class, polyethylene glycols, cyclodextrin, surfactant-based, ureas, organic acid and the saccharide.
3, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 2 is characterized in that, described polyvinylpyrrolidone class material is selected from PVP K15, PVP K30, PVP K90, PVP K29/32 and PVP XL; The polyethylene glycols material is selected from PEG 4000 or PEG 6000; Cyclodextrin is β-CD; Surfactant-based poloxamer 188, polyethyleneglycol glyceride and the VitE TPGS NF of being selected from; Ureas is a carbamide; Organic acid is citric acid, succinic acid, cholic acid or deoxycholic acid; Saccharide is selected from dextran, lactose, galactose, mannitol and sucrose; The weight ratio of wherein said Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier is 1: 3～1: 9.
4, claim 1,2 or 3 described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb, it is characterized in that described is solvent method with the formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier, comprises the steps:
Described Herba Blumeae Balsamiferae total flavones extract is dissolved in the organic solvent, and wherein said organic solvent is selected from ethanol, dichloromethane, chloroform or acetonitrile;
Described hydrophilic carrier is dissolved in this organic solvent, mix homogeneously;
Rotary evaporation makes described organic solvent volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
5, claim 1,2 or 3 described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb, it is characterized in that described is polishing with the formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier, comprises the steps:
With Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier mix homogeneously, place beveller;
Rotating speed with 300～600rpm/min ground 1～3 hour, promptly got solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
6, claim 1,2 or 3 described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb, it is characterized in that described is spray drying method with the formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier, comprises the steps:
With the dissolving of Herba Blumeae Balsamiferae total flavones extract and hydrophilic carrier or be suspended in the alcoholic solution;
With this mixed solution supersound process 15 minutes, carry out spray drying again, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
7, claim 1,2 or 3 described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb, it is characterized in that described is solvent-fusion method with the formulation method of Herba Blumeae Balsamiferae total flavones extract high degree of dispersion in hydrophilic carrier, comprises the steps:
Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of organic solvent, and described organic solvent is selected from ethanol, dichloromethane, chloroform or acetonitrile;
Hydrophilic carrier is heated to 50～60 ℃, makes fusion, add the described Herba Blumeae Balsamiferae total flavones extract solution that is dissolved in the organic solvent, stir evenly;
Evaporation removes desolvates, and fused mass is placed the rustless steel pallet of ice bath, makes straticulation, blows with cold wind, makes its rapid cooling curing, places exsiccator dry, pulverizes, and promptly gets solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
8, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 7, it is characterized in that described hydrophilic carrier is selected from least a of PEG-4000, PEG-6000, poloxamer 188, polyethyleneglycol glyceride and VitE TPGS NF, or for being selected from least a and at least a mixture that is selected among poloxamer 188, polyethyleneglycol glyceride and the VitE TPGS NF among PEG-4000, the PEG-6000.
9, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 4 is characterized in that it contains
Herba Blumeae Balsamiferae total flavones extract 1 weight portion; And
PVP K29/32 9 weight portions;
Wherein formulation method is: 1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of ethanol, adds 9 weight portion PVP K29/32, mix homogeneously makes abundant dissolving; Rotary evaporation makes the ethanol volatilization, cooling, and drying is solidified, and is pulverized, and promptly obtains solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
10, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 5 is characterized in that it contains
Herba Blumeae Balsamiferae total flavones extract 1 weight portion;
Galactose 4 weight portions; And
PVP K90 8 weight portions;
Wherein formulation method is: with 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 4 weight portion galactose, 8 weight portion PVP K90 mix homogeneously, place planetary beveller, rotating speed with 400r/m ground 1 hour, promptly got solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
11, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 7 is characterized in that it contains
Herba Blumeae Balsamiferae total flavones extract 1 weight portion; And
PEG 6,000 8 weight portions;
Wherein formulation method is: 1 weight portion Herba Blumeae Balsamiferae total flavones extract is dissolved in an amount of dehydrated alcohol, 8 weight portion PEG 6000 are heated to 60 ℃, make fusion, add drug solution, stir evenly, evaporation removes and desolvates, and fused mass is placed the rustless steel pallet of ice bath, make straticulation, blow with cold wind, make its rapid cooling curing, placed exsiccator dry 2 days, pulverize, promptly get solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb.
12, the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 6 is characterized in that it contains
Herba Blumeae Balsamiferae total flavones extract 1 weight portion; And
Lactose 18 weight portions;
Wherein formulation method is: with 1 weight portion Herba Blumeae Balsamiferae total flavones extract and 18 weight portion lactose, be dissolved in an amount of dehydrated alcohol, with this mixed solution ultrasonic mixing 15min in the supersonic oscillations instrument, the elimination insoluble impurities is with this mixed liquor spray drying; The spray drying condition is: inlet temperature is 46 ℃, and charging rate is 16ml/min, and the nebulizer rotating speed is 45Hz, and cyclone separator pressure reduction is the 50mm water column, and the gained dried powder is the Blumea balsamifera total flavones solid dispersion.
13, a kind of pharmaceutical composition contains described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 1 and pharmaceutically acceptable excipient.
14, the application of the described solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb of claim 1 in preparing treatment or prevention coronary heart disease, hyperlipemia, atherosclerotic medicine.
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| CNB2004100704631A CN100420453C (en) | 2004-08-03 | 2004-08-03 | Solid dispersion of extractive of general flavone of Balsamiferou Blumea Herb |
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| CN100420453C CN100420453C (en) | 2008-09-24 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502553B (en) * | 2008-12-19 | 2013-04-10 | 深圳海创医药科技发展有限公司 | Rhizoma atractylodis total terpene alcohol solid dispersoid, medicament composition and preparation method thereof |
| CN109134193A (en) * | 2017-06-27 | 2019-01-04 | 贵州艾源生态药业开发有限公司 | A kind of method that Blumea balsamifera extracts borneol |
| CN110193013A (en) * | 2019-07-02 | 2019-09-03 | 力品药业（厦门）有限公司 | A kind of deacetylase fungal epoxy ethyl ester solid dispersions and preparation method thereof |
| CN111419887A (en) * | 2020-03-07 | 2020-07-17 | 福建医科大学附属协和医院 | Selaginella chinensis total biflavone solid dispersion and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1071575C (en) * | 1994-02-23 | 2001-09-26 | 陈俊彪 | Burn and scald slurry and health cosmetics made of Blumea balsamifera oil |
| CN1403451A (en) * | 2002-10-08 | 2003-03-19 | 深圳海王药业有限公司 | Balsamiferous biumea general flavone extractive and its extraction process and medicinal application |
-
2004
- 2004-08-03 CN CNB2004100704631A patent/CN100420453C/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502553B (en) * | 2008-12-19 | 2013-04-10 | 深圳海创医药科技发展有限公司 | Rhizoma atractylodis total terpene alcohol solid dispersoid, medicament composition and preparation method thereof |
| CN109134193A (en) * | 2017-06-27 | 2019-01-04 | 贵州艾源生态药业开发有限公司 | A kind of method that Blumea balsamifera extracts borneol |
| CN110193013A (en) * | 2019-07-02 | 2019-09-03 | 力品药业（厦门）有限公司 | A kind of deacetylase fungal epoxy ethyl ester solid dispersions and preparation method thereof |
| CN111419887A (en) * | 2020-03-07 | 2020-07-17 | 福建医科大学附属协和医院 | Selaginella chinensis total biflavone solid dispersion and preparation method thereof |
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| Publication number | Publication date |
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| CN100420453C (en) | 2008-09-24 |
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