CN102988484B - Phosphatide complexes of Radix Scutellariae active skull cap components and preparation method thereof and preparation - Google Patents
Phosphatide complexes of Radix Scutellariae active skull cap components and preparation method thereof and preparation Download PDFInfo
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Abstract
The invention discloses phosphatide complexes and the formulation preparation method thereof of a kind of Radix Scutellariae active skull cap components.Radix Scutellariae active skull cap components means and extracts baicalin (Baicalein) effective site (baicalin content is more than 50%) of isolated or effective ingredient (baicalin content is more than 90%) and wogonin (wogomin) effective site (wogonin content is more than 50%) or effective ingredient (wogonin content is more than 90%) from baikal skullcap root.Radix Scutellariae active skull cap components water solublity and fat-soluble the most poor, increases along with solution ph rises high-dissolvability, but in alkalescence condition, chemical degradation easily occurs.The deficiency of Radix Scutellariae active skull cap components physicochemical property makes it cannot make injecting and administering preparations, and oral rear bioavailability is relatively low.The present invention passes through phosphatide complexes technology, the water dispersible and the lipotropy that make Radix Scutellariae active component are obviously improved, and can prepare high bioavailability oral formulations on this basis, or make injection freeze-dried powder, or make lipomul, meet injection or the requirement of mucosa delivery.
Description
The application is the divisional application of the Chinese patent application of filing date on June 12nd, 2006, Application No. 200610087480.5, invention entitled " phosphatide complexes of Radix Scutellariae active skull cap components and preparation method thereof and preparation ".
Technical field
The present invention relates to phosphatide complexes and the preparation thereof of a kind of Radix Scutellariae active skull cap components.Medicine carrying phosphatide complexes is prepared for material with phospholipid, both can obviously improve the hydrophilic of Radix Scutellariae active skull cap components, its lipotropy can have been improved again, carry out design and the preparation of all kinds of preparation on this basis, oral administration biaavailability can be improved, or meet the requirement of drug administration by injection and mucosa delivery.
Background technology
The root of labiate Radix Scutellariae Scutellaria baicalensis Georgi has heat clearing and damp drying, eliminating fire and detoxication, hemostasis and antiabortive function.The effective ingredient of Radix Scutellariae is flavone compound, mainly has four kinds of compositions such as baicalin (Baicalin), baicalin (Baicalein), wogonin (wogomin), wogonoside (Wogonoside).Baicalin (Baicalin) preparation has been used for the treatment of respiratory tract infection, acute tonsillitis, pharyngitis, chronic obstructive pulmonary disease, infectious hepatitis, acute/chronic gastroenteritis and bacillary dysentery, pyelonephritis etc. clinically.Recent study finds, baicalin has similar pharmacological action with baicalin, but antimicrobial antiviral activity and antimicrobial spectrum are superior to baicalin.
With the phenolic hydroxyl group at three ortho positions in baicalin molecule, it is oxidized easily and becomes quinones, unstable chemcial property.
Research shows, baicalin hydrophilic and lipotropy are the most poor, and dissolubility 0.026mg/ml in water is insoluble in normal hexane, and in soybean oil, dissolubility is 0.33mg/m.
Being limited by physicochemical property, baicalin or wogonin preparation research there is problems in that
1, oral formulations bio-absorbable is poor
Oral formulations needs first disintegrate, dispersion and dissolution (relevant with medicine hydrophilic) after taking, make active component be fully contacted with gastrointestinal mucosa, then utilizes the lipotropy of active component to pass it through mucosa and is rapidly absorbed into body circulation.
For baicalin active component, as being directly prepared into oral formulations, because hydrophilic and lipotropy are the most poor, it is unfavorable for dissolution and absorption.
2, drug administration by injection or mucosa delivery formulation design and the requirement of preparation cannot be met
Baicalin is good in neutrality and stable under acidic conditions, but baicalin dissolubility is extremely low when pH ＜ 7.5, it is impossible to meet dose requirements；When pH >=8.5, drug solubility increases, but almost all is degraded after 72 hours, unstable chemcial property.
For baicalin is made injecting and administering preparations, CN1562147A discloses one " lyophilized powder injection of baikal skullcap root extract and preparation method thereof ", is made up of Radix Scutellariae extract 22～80%, Alkaline solubilization agent 11 ~ 75%, antioxidant, chelating agent 1～12% and filler 1～30%.Dissolubility based on baicalin and stability features, pH value is limited to 7.45～8.0 by this patent, and this requirement is difficult to meet the requirement of industrialization.Additionally, the lyophilized powder made when diluting with normal saline or glucose injection it may happen that compatible change, cause the change of physical property and chemical property.
For improving baicalin physicochemical property, there is document that its liposome is studied.But liposome exists envelop rate storage low, long-term easily to be leaked, is difficult to the defects such as industrialization, makes product development and clinical practice be restricted.
For preparing stable injecting and administering preparations, meeting clinical application demand, the present inventor attempts to baicalin is made oil-in-water (O/W) lipomul, to improve preparation drug loading, to improve the long-term stability stored.Research finds, baicalin lipotropy is poor, dissolubility only 0.3mg/ml in soybean oil, and midchain oil is 1mg/ml, and oleic acid, ethyl oleate, isopropyl myristate and isopropyl palmitate are 0.5mg/ml.Dissolubility relatively low in oil phase is difficult to meet the requirement of Emulsion drug loading, and Emulsion medicine when sterilizing easily occurs phase transfer simultaneously, and baicalin is migrated to outer aqueous phase by interior oil phase, occurs breakdown of emulsion therewith, is layered and separates out the phenomenon of drug crystallization.
In sum, baicalin dissolubility and stability can not meet requirement prepared by injection, prepare freeze-dried powder by control ph, or employing submicron emulsion technology is prepared lipomul and all can not be obtained satisfied result.
The eighties, Italy scholar Bombardelli etc., when studying liposome, finds that many active skull cap components have special affinity with phospholipid.Domestic and foreign literature is reported, active skull cap components is combined under certain condition with phospholipid, obtain active skull cap components phosphatide complexes (phytosomes or phospholipid complex), its physicochemical property and the more former compound of biological nature all have change in various degree, there is stronger lipotropy, active skull cap components absorption in vivo can be effectively improved, significantly change its biological effectiveness.
For this, the present invention uses phosphatide complexes technology to study Radix Scutellariae active component, the lipomul of phase transfer, stable quality after long time storage is there is not, it is achieved drug administration by injection or the purpose of mucosa delivery when preparing drug loading height, sterilizing on the basis of raising is lipophilic.Additionally, phosphatide complexes is while improving Radix Scutellariae active component lipotropy, also can improve its dispersibility in water, therefore, the bioavailability and effectiveness improving oral formulations be had Great significance.
Summary of the invention
It is an object of the invention to provide the phosphatide complexes of a kind of Radix Scutellariae active skull cap components, thus solve above-mentioned Radix Scutellariae active skull cap components water solublity and fat-soluble the most poor, increase along with solution ph rises high-dissolvability, but shortcoming chemical degradation easily occurring in alkalescence condition, improve hydrophilic and the lipotropy of Radix Scutellariae active component, to improving oral formulations bioavailability, or meet injecting and administering preparations and mucosa delivery formulation design requirement.
Another object of the present invention is to provide the preparation method of the phosphatide complexes of this Radix Scutellariae active skull cap components.
A further object of the present invention is to provide the preparation containing Radix Scutellariae active skull cap components phosphatide complexes.
1, Radix Scutellariae active component phosphatide complexes
The phosphatide complexes of Radix Scutellariae active skull cap components of the present invention is to be composited by Radix Scutellariae active skull cap components and phospholipid material, the percentage by weight of Radix Scutellariae active skull cap components is 5-75%, phospholipid percentage by weight is 25-95%, Radix Scutellariae active skull cap components is the baicalin content extracting isolated from baikal skullcap root effective site more than 50% or the baicalin content effective ingredient more than 90% and the wogonin content effective site more than 50% or wogonin content effective ingredient more than 90%, phospholipid material is natural phospholipid or synthetic phospholipid or their mixture.
Test with baicalin effective ingredient (containing baicalin for 92%), soybean phospholipid is carrier material, it is to feed intake at 1: 2 by medicine/phospholipid weight ratio, it is combined under the conditions of uniform temperature, with recombination rate as evaluation criteria, investigate ethanol, acetone, ethyl acetate and the oxolane impact on recombination rate.Result shows, different solvent recombination rates has notable difference, and wherein with oxolane as solvent, recombination rate is up to 99%.
In the phosphatide complexes of preparation, the percentage by weight of Radix Scutellariae active skull cap components is preferred 10-30%, more preferably 15-25%；Phospholipid percentage by weight is preferred 70-90%, more preferably 75-85%.
Preparing Radix Scutellariae active skull cap components phosphatide complexes of the present invention, phospholipid material used is selected from natural phospholipid, it is possible to selected from synthetic phospholipid, be further selected from their mixture.Wherein preferred natural phospholipid, including lecithin, fabaceous lecithin, cholesterol and Cholic acids, sodium alginate, chitosan etc..
Investigating with water, injection soybean oil and midchain oil for solvent, result shows, after baicalin forms phosphatide complexes, can form micellar solution in water, and the dissolubility in soybean oil and midchain oil improves more than 30 times.Therefore, noroxylin phosphatide complexes can be used for the research of all kinds of medicine-releasing system, such as drug administration by injection, oral formulations, mucosa delivery and percutaneous dosing etc..
Prepare the method for Radix Scutellariae active skull cap components phosphatide complexes of the present invention and be selected from following two method:
One of which method includes mixing Radix Scutellariae active skull cap components with phospholipid material, adds organic solvent and dissolves, stirring, and evaporative removal organic solvent is vacuum dried and get final product.
Another kind of method includes taking Radix Scutellariae active skull cap components and phospholipid material, dissolves with different organic solvents respectively, stirs, evaporative removal organic solvent, be vacuum dried and get final product after mixing.
The organic solvent used in said method is selected from ethanol, methanol, benzyl alcohol, acetone, ethyl acetate, oxolane or their mixture.
2, medicine carrying phosphatide complexes injection freeze-dried powder
Present invention also offers the preparation of phosphatide complexes, wherein said preparation is injection freeze-dried powder or oral formulations.
The preparation method of the preparation of described phosphatide complexes includes, by soluble in water for medicine carrying phosphatide complexes, add appropriate proppant, after aseptic filtration and after depyrogenation, freeze-dried can be prepared by injection freeze-dried powder, face the used time with after grape glucose or normal saline dilution quiet.
3, medicine carrying phosphatide complexes oral formulations
Medicine carrying phosphatide complexes can be used for the preparation of all kinds of medicine-releasing system, including percutaneous delivery and oral formulations.The phosphatide complexes of Radix Scutellariae active skull cap components can be mixed with adjuvant conventional on pharmaceutics when preparing oral formulations, use specific preparation technology, make tablet, capsule, granule, drop pill and soft capsule.
Take Radix Scutellariae active skull cap components phosphatide complexes appropriate, place 24 hours for 2-8 DEG C, pulverize, add appropriate diluent mix homogeneously, add the magnesium stearate mixing of full dose 1%, load in hard capsule, to obtain final product.
Take Radix Scutellariae active skull cap components phosphatide complexes to be dissolved in vegetable oil, use pressing or dropping preparation method can prepare soft capsule.
According to clinical application demand, also Radix Scutellariae active skull cap components phosphatide complexes can be made tablet, granule and drop pill etc..
4, medicine carrying phosphatide complexes fat milk and preparation thereof
Radix Scutellariae active component phosphatide complexes not only can be directly prepared into lyophilized powder, percutaneous delivery preparation and all kinds of oral formulations, is also with its lipotropy, is dissolved in oil phase oil-in-water (O/W) fat milk making particle diameter at below 600nm.
Radix Scutellariae active component phosphatide complexes fat milk can be prepared as follows: medicine carrying phosphatide complexes, emulsifying agent and liposoluble constituent is dissolved in vegetable oil as oil phase, and water soluble ingredient is dissolved in water for injection and forms aqueous phase.Oil phase and aqueous phase are heated separately to 60～80 DEG C, and oil phase under agitation gently adds aqueous phase, and high speed shear forms colostrum.After colostrum cools down rapidly, being transferred in high pressure homogenizer carry out homogenizing, control emulsion droplet size, at below 600nm, to obtain final product.
Oil phase in Radix Scutellariae active component phosphatide complexes fat milk and watr-proportion can be controlled in 1: 30 to 1: 3.
Prepare Radix Scutellariae active component phosphatide complexes fat milk of the present invention, oil phase used comprises long-chain, medium-chain fatty acid, long-chain, medium chain fatty acid ester, long-chain fatty alcohol and above-mentioned several mixture, be specifically selected from soybean oil, Oleum Ricini, linoleic acid, Semen Maydis oil, olive oil, Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, oleic acid, glyceryl monostearate, glyceryl monooleate, the glyceride of medium-chain fatty acid, hexadecanol etc.；Emulsifying agent used is nonionic surfactant and natural surfactant, nonionic surfactant is selected from fatty glyceride, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene sorbitan fatty acid ester, sorbitol and sorbitan fatty acid ester, polyoxyethylene fatty acid ester class, Vitamin E derivatives class, polyoxy alkene entirety copolymerization surfactant, and natural surfactant is selected from lecithin, fabaceous lecithin, cholesterol and Cholic acids, sodium alginate, chitosan etc.；Co-emulsifier used is bland Polyethylene Glycol (PEG) class and polyoxy alkene entirety copolymerization surfactant (poloxamer class)；Stabilizer used is oleic acid, PEG class, glycerol, xylitol, sorbitol (sugared) alcohol and mannitol；Other described additives refer to antioxidant and antibacterial.
Fat milk, through pressure sterilizing or aseptic filtration, can prepare injection small-volume injection and transfusion, may also be fabricated which injection dry emulsion after addition proppant is freeze-dried.
Use different devices, fat milk can be distributed into the drop for eye mucosa, nasal mucosa, oral mucosa or respiratory mucosa, spray or aerosol, may also be fabricated which that pulmonary sucks preparation.
Detailed description of the invention
By the preparation technology further illustrating the inventive method and the novelty embodied, spy lists following example, but the rights protection of the present invention is not limited in the content that embodiment describes.
Embodiment 1: medicine carrying phosphatide complexes (I)
Take baicalin effective ingredient 0.6g, soybean phospholipid 3.66g, add oxolane 40ml, after 40 DEG C are combined 1 hour, rotary evaporation removes oxolane, vacuum dried more than 12 hours (20～30 DEG C), obtain medicine carrying phosphatide complexes, airtight package, put into refrigerator cold-storage and preserve.
Embodiment 2: medicine carrying phosphatide complexes (II)
Take baicalin effective ingredient 0.6g, soybean phospholipid 3.62g, add the acetone 40ml being preheated to 40 DEG C, after 40 DEG C are combined 1 hour, rotary evaporation removes solvent, vacuum dried more than 12 hours (20～30 DEG C), obtain medicine carrying phosphatide complexes, airtight package, put into refrigerator cold-storage and preserve.
Embodiment 3: medicine carrying phosphatide complexes (III)
Take baicalin effective ingredient 0.4g, soybean phospholipid 2.43g, add the ethanol acetone 60ml being preheated to 40 DEG C, after 40 DEG C are combined 2 hours, rotary evaporation removes solvent, vacuum dried more than 12 hours (20～30 DEG C), obtains medicine carrying phosphatide complexes, airtight package, puts into refrigerator cold-storage and preserves.
Embodiment 4: medicine carrying phosphatide complexes (IV)
Take baicalin effective ingredient 0.6g, soybean phospholipid 3.65g, add ethyl acetate 40ml, after 40 DEG C are combined 1 hour, rotary evaporation removes solvent, vacuum dried more than 12 hours (20～30 DEG C), obtain medicine carrying phosphatide complexes, airtight package, put into refrigerator cold-storage and preserve.
Embodiment 5: medicine carrying phosphatide complexes recombination rate is investigated
Taking complex prepared by above four kinds of embodiments, use high effective liquid chromatography for measuring recombination rate, result is as follows:
Table 1: phosphatide complexes particle diameter and recombination rate measurement result
| Investigate sample | Recombination rate |
| Medicine carrying phosphatide complexes (I) | 99.3% |
| Medicine carrying phosphatide complexes (II) | 95.4% |
| Medicine carrying phosphatide complexes (III) | 67.4% |
| Medicine carrying phosphatide complexes (IV) | 90.7% |
Embodiment 6: prepared by medicine carrying phosphatide complexes capsule
The medicine carrying phosphatide complexes 8.5g (being equivalent to baicalin effective ingredient 1200mg) of Example 1 preparation, pulverize, cross 60 mesh sieves, separately took the lactose 2g of 80 mesh sieves, magnesium stearate 120mg, mix homogeneously, load in No. 2 hard capsules, every seed lac capsule loading amount is 265.5mg, is 30mg containing baicalin active component.
Embodiment 7: prepared by medicine carrying phosphatide complexes tablet
The medicine carrying phosphatide complexes 8.5g (being equivalent to baicalin effective ingredient 1200mg) of Example 1 preparation, pulverizes, and crosses 60 mesh sieves, separately taking the lactose 5g of 80 mesh sieves, microcrystalline Cellulose 3g, polyvinylpolypyrrolidone 1g, mix homogeneously, with 75% ethanol soft material, 14 mesh sieves are pelletized, 30 DEG C are dried, and 18 mesh sieve granulate add magnesium stearate 180mg, mix homogeneously, tabletting, every theoretical tablet weight is 442mg, the every active component 30mg Han baicalin.
Embodiment 8: prepared by medicine carrying phosphatide complexes soft capsule
The medicine carrying phosphatide complexes 8.5g (being equivalent to baicalin effective ingredient 1200mg) of Example 1 preparation, α vitamin E 10mg, add 15ml soybean oil, it is heated to 30 DEG C, it is stirred to dissolve, with soybean oil to 20ml, is sub-packed in soft capsule, every theoretical loading amount is 0.5ml, containing baicalin active component 30mg.
Embodiment 9: prepared by medicine carrying phosphatide complexes freeze-dried powder
Take mannitol 10g, the 150ml that adds water makes to be dissolved to clarification, add the medicine carrying phosphatide complexes 4.3g (being equivalent to baicalin effective ingredient 600mg) of embodiment 1 preparation, 40 DEG C of stirrings make to be uniformly dispersed, add the activated carbon of 0.02%, stir 30 minutes, coarse filtration, then with 0.22 μm filtering with microporous membrane, it is sub-packed in 30ml cillin bottle, every bottled amount 10ml ,-40 DEG C of pre-freezes 4 hours ,-25 DEG C of distillations remove moisture removal in 10 hours,-10 DEG C are dried 5 hours, 20 DEG C are dried 5 hours again, obtain injection freeze-dried powder, and containing active component in every cillin bottle is 30mg.
Embodiment 10: prepared by medicine carrying phosphatide complexes fat milk (I)
Medicine carrying phosphatide complexes 4.3g (being equivalent to baicalin effective ingredient 600mg), the lecithin 12g and oleic acid 2.4g of Example 1 preparation, adds injection soybean oil 100g, is heated to 60 DEG C, forms oil phase；Separately take glycerol 25g and Pluronic (F68) 20g, add in about 700-800ml water, be heated to 60 DEG C, form aqueous phase.Oil phase being slowly added into aqueous phase, injects water to 1000ml, at 60 DEG C, high-shear emulsifying 8min under the conditions of 16000r/min, cooling prepares colostrum rapidly.By emulsifying 6 times under the conditions of 650Mpa of colostrum high pressure homogenizer, obtaining uniform off-white color lipomul, drug loading is 0.6mg/ml.Through 0.8 μm membrane filtration, it is sub-packed in primary infusion bottle, every bottled amount 100ml, sterilizing 15min at 121 DEG C, obtains sterilizing transfusion, every bottle of baicalin 60mg Han active component.
Particle diameter is investigated: the lipomul before taking sterilizing and after sterilizing, uses MALVERN Mastersizer 2000 type particle size determination instrument to investigate particle diameter and distribution, and result shows, before sterilizing, mean diameter is 173nm, it is 182nm after sterilizing, both no significant differences, and particle diameter distribution is basically identical.
Content and chemical property are investigated: the lipomul before taking sterilizing and after sterilizing, add ethanol to dissolve, measure according to HPLC method in accordance with the law, investigate sterilization process to active component content and the impact of baicalin chemical purity, result shows, before and after sterilizing, baicalin drug loading is respectively 0.58mg/ml and 0.56mg/ml, and chemical purity is respectively 96.2% and 96.3%, and both compare and significant change does not occurs.
Embodiment 11: prepared by medicine carrying phosphatide complexes fat milk (II)
Medicine carrying phosphatide complexes 7.1g (being equivalent to baicalin effective ingredient 1000mg), the lecithin 20g and oleic acid 3g of Example 1 preparation, adds injection soybean oil 100g, is heated to 60 DEG C, forms oil phase；Separately take glycerol 25g and Pluronic (F68) 20g, add in about 700-800ml water, be heated to 60 DEG C, form aqueous phase.Oil phase being slowly added into aqueous phase, injects water to 1000ml, at 60 DEG C, high-shear emulsifying 8min under the conditions of 16000r/min, cooling prepares colostrum rapidly.By emulsifying 6 times under the conditions of 650Mpa of colostrum high pressure homogenizer, obtaining uniform off-white color lipomul, drug loading is 1mg/ml.Through 0.8 μm membrane filtration, it is sub-packed in primary infusion bottle, every bottled amount 100ml, sterilizing 15min at 121 DEG C, obtains sterilizing transfusion, every bottle of active component 100mg Han baicalin.
Embodiment 12: prepared by medicine carrying phosphatide complexes fat milk (III)
Medicine carrying phosphatide complexes 7.1g (being equivalent to baicalin effective ingredient 1000mg), the lecithin 15g and oleic acid 3g of Example 1 preparation, adds injection soybean oil 50g, injection midchain oil 50g, is heated to 60 DEG C, forms oil phase；Separately take glycerol 25g and Pluronic (F68) 20g, add in about 700-800ml water, be heated to 60 DEG C, form aqueous phase.Oil phase being slowly added into aqueous phase, injects water to 1000ml, at 60 DEG C, high-shear emulsifying 8min under the conditions of 16000r/min, cooling prepares colostrum rapidly.By emulsifying 6 times under the conditions of 650Mpa of colostrum high pressure homogenizer, obtaining uniform off-white color lipomul, drug loading is 1mg/ml.Through 0.8 μm membrane filtration, it is sub-packed in primary infusion bottle, every bottled amount 100ml, sterilizing 15min at 121 DEG C, obtains sterilizing transfusion, every bottle of active component 100mg Han baicalin.
Embodiment 13: prepared by medicine carrying phosphatide complexes fat milk (IV)
On the basis of embodiment 12 prescription, add α vitamin E 0.05g, operate by embodiment 9 preparation method in accordance with the law, preparation 100ml sterilizing transfusion, every bottle of 100mg Han active component.
Embodiment 14: prepared by medicine carrying phosphatide complexes fat milk (V)
Medicine carrying phosphatide complexes 0.85g (being equivalent to baicalin effective ingredient 120mg), the lecithin 2.0g and oleic acid 0.3g of Example 1 preparation, adds injection soybean oil 2g, injection midchain oil 2g, is heated to 60 DEG C, forms oil phase；Separately take glycerol 2.5g and Pluronic (F68) 2.0g, add in about 30ml water, be heated to 60 DEG C, form aqueous phase.Oil phase being slowly added into aqueous phase, injects water to 40ml, at 60 DEG C, high-shear emulsifying 8min under the conditions of 16000r/min, cooling prepares colostrum rapidly.By emulsifying 6 times under the conditions of 650Mpa of colostrum high pressure homogenizer, obtain uniform off-white color lipomul.Through 0.8 μm membrane filtration, being sub-packed in 10ml ampulla, sterilizing 15min at 121 DEG C, obtain sterile solution for injection, drug loading is 3mg/ml, every 30mg Han active component.
Embodiment 15: prepared by medicine carrying phosphatide complexes fat milk (VI)
Medicine carrying phosphatide complexes 0.71g (being equivalent to baicalin effective ingredient 100mg), the lecithin 2.0g and oleic acid 0.3g of Example 1 preparation, adds and uses midchain oil 2g, be heated to 60 DEG C, forms oil phase；Separately taking glycerol 2.5g, Pluronic (F68) 2.0g, α vitamin E 10mg and mud moor gold ethyl ester 4mg, add water about 15ml water for injection, is heated to 60 DEG C, forms aqueous phase.Oil phase being slowly added into aqueous phase, injects water to 20ml, at 60 DEG C, high-shear emulsifying 8min under the conditions of 16000r/min, cooling prepares colostrum rapidly.By emulsifying 6 times under the conditions of 650Mpa of colostrum high pressure homogenizer, obtain uniform off-white color lipomul, through 0.22 μm membrane filtration, it is sub-packed in the spray bottle of 5ml band proportional valve device, drug loading is 5mg/ml, every bottle of 25mg Han active component, can be used for lung mucosa or nasal mucosa spray delivery.
Embodiment 16: medicine carrying phosphatide complexes dry breast preparation
The uniform off-white color fat milk of Example 14 preparation, concentration by 5% adds mannitol and makees proppant, through 0.22 μm microporous filter membrane aseptic filtration, it is sub-packed in the cillin bottle of 30ml,-40 DEG C of pre-freezes 4 hours ,-25 DEG C of distillations remove moisture removal for 10 hours, and-10 DEG C are dried 5 hours, 20 DEG C are dried 5 hours again, obtain dry emulsion.Every cillin bottle is 30mg containing active component.
Claims (11)
1. a phosphatide complexes for Radix Scutellariae active skull cap components, by Radix Scutellariae natural activity
Composition and phospholipid material are composited, and the percentage by weight of Radix Scutellariae active skull cap components is
5-75%, phospholipid percentage by weight is 25-95%, and Radix Scutellariae active skull cap components is therefrom
Medicine Radix Scutellariae extracts the baicalin content of the isolated effective site more than 50%,
Or the effective site that wogonin content is more than 50%, phospholipid material is natural phosphorus
Fat or synthetic phospholipid or their mixture.
Phosphatide complexes the most according to claim 1, wherein said Radix Scutellariae is natural
Active component be the baicalin content extracting isolated from baikal skullcap root 90% with
On effective ingredient or wogonin content effective ingredient more than 90%.
Phosphatide complexes the most according to claim 1 and 2, it is characterised in that its
The percentage by weight of middle Radix Scutellariae active skull cap components is 10-30%；Phospholipid percentage by weight
For 70-90%.
Phosphatide complexes the most according to claim 3, it is characterised in that wherein
The percentage by weight of Radix Scutellariae active skull cap components is 15-25%；Phospholipid percentage by weight is
75-85%.
Phosphatide complexes the most according to claim 1 and 2, it is characterised in that described
One or more in lecithin and fabaceous lecithin of phospholipid material.
6. the method for preparation phosphatide complexes according to any one of claim 1-5,
It includes mixing Radix Scutellariae active skull cap components with phospholipid material, adds organic solvent and dissolves,
Stirring, evaporative removal organic solvent, it is vacuum dried and get final product.
7. the method for preparation phosphatide complexes according to any one of claim 1-5,
It includes taking Radix Scutellariae active skull cap components and phospholipid material, respectively with different organic molten
Agent is dissolved, and stirs, evaporative removal organic solvent, be vacuum dried and get final product after mixing.
8. according to the preparation method described in claim 6 or 7, it is characterised in that You Jirong
Agent selected from ethanol, methanol, benzyl alcohol, acetone, ethyl acetate, oxolane or it
Mixture.
9. contain the preparation of phosphatide complexes according to any one of claim 1-5,
It is characterized in that it is oral formulations or injection freeze-dried powder.
Preparation the most according to claim 9, it is characterised in that Radix Scutellariae is natural
The phosphatide complexes of active component mixes with adjuvant conventional on pharmaceutics, uses specific
Preparation technology, make tablet, capsule, granule or drop pill.
11. preparations according to claim 9, it is characterised in that by natural for Radix Scutellariae work
Property composition phosphatide complexes be dispersed in water, add proppant and antioxidant, warp
0.22 μm filtering with microporous membrane, uses freeze drying process to be prepared injection lyophilizing
Powder pin.
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| CN1748706A (en) * | 2004-09-13 | 2006-03-22 | 上海凯曼生物科技有限公司 | Compositions of lecithin and flavonoid small molecule, preparing method and their use |
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| CN1748706A (en) * | 2004-09-13 | 2006-03-22 | 上海凯曼生物科技有限公司 | Compositions of lecithin and flavonoid small molecule, preparing method and their use |
Non-Patent Citations (1)
| Title |
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| 黄芩苷磷脂复合物制备工艺的研究;吴建梅等;《中国中药杂志》;20010325;第26卷(第03期);166-169 * |
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