CN102415999A - Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles - Google Patents
Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles Download PDFInfo
- Publication number
- CN102415999A CN102415999A CN2011104026473A CN201110402647A CN102415999A CN 102415999 A CN102415999 A CN 102415999A CN 2011104026473 A CN2011104026473 A CN 2011104026473A CN 201110402647 A CN201110402647 A CN 201110402647A CN 102415999 A CN102415999 A CN 102415999A
- Authority
- CN
- China
- Prior art keywords
- breviscapine
- nano granular
- albumin nano
- concentration
- albumin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles. The breviscapine albumin nanoparticles comprise the breviscapine serving as an active ingredient and the albumin nanoparticles, and are obtained by adsorbing the prepared and freeze-dried albumin nanoparticles to the breviscapine under a certain condition to carry medicines. Through the breviscapine albumin nanoparticles prepared by adsorbing the breviscapine through the albumin nanoparticles, the problem of low dissolubility of breviscapine aqueous solution is solved; and the breviscapine albumin nanoparticles have obvious slow release characteristic.
Description
Technical field
The present invention relates to a kind of albumin nano granular of breviscapine and method for preparing of adsorbing breviscapine of being loaded with, belong to the preparation technique field through albumin nano granular.
Background technology
Breviscapine is the flavone compound that from the natural plants Herba Erigerontis, extracts, and its main component is a lamp-dish flower acetic.Modern pharmacological research proves that breviscapine expansion arteriole improves cardiac function and cardiac and cerebral blood-supply; Blood viscosity lowering, antiplatelet, erythrocyte aggregation improve ED.Increase the perfused tissue amount, microcirculation improvement and metabolism; Remove free radical and prevent the damage of tissue reperfusion property, reduce the spontaneous motility rate of leukocyte.Clinical indication is cerebral thrombosis, cerebral hemorrhage convalescent period, angina pectoris, myocardial infarction, high blood viscosity, all ischemics and with serious circulation disorder.In recent years discover that breviscapine also has application promise in clinical practice at aspects such as diabetic nephropathy, interstitial pulmonary fibrosis and antineoplastic agent potentiation.According to literature research; Herba Erigerontis have dissolubility low (dissolubility is 20.47 ± 0.26 μ g/ml in the water), oral administration biaavailability low (the dog oral administration biaavailability is 0.40 ± 0.19%), half-life, and short (oral the eliminations half-life of dog is 79.98 ± 44.50min, and the quiet notes elimination half-life of dog is shortcomings such as 55.70 ± 19.09min).
Albumin nano granular is to be one type of nanometer formulation of carrier with the albumin.Because of having a good stable property, in the preferential property absorbed of pathological tissues, being easy to get property, biological degradability, the characteristics that toxicity and immunogenicity are little, and become the ideal carrier of medicine.In addition, key property of albumin is that its unique space structure makes it have the ability that combines other materials, and the reputation of omnipotent carrier is arranged.Have more polar group on the albumin polypeptide chain, a lot of compositions are had affinity highly, reversible combination takes place in ability and 70% small-molecule drug.The α-Luo Xuanjiegou that contains medicine 48% in the albumin secondary structure, 15% beta-pleated sheet structure, all the other are the random coil structure, therefore have a lot of netted spaces, have created favourable steric requirements for carrying medicine.
In recent years, both at home and abroad with albumin as the method for carrier medicine carrying mostly with " interior addition ", promptly in the albumin preparation forms the process of albumin nano granular, medicine is added, be prepared into the albumin nano granular of medicine carrying at last.The present invention uses for reference the principle of macroporous adsorbent resin, is through medicine being adsorbed on the blank albumin nano granular that has prepared, to form a kind of method of stable medicine carrying albumin nano granular.This method has not only solved the low problem of breviscapine water solubility, and its product has tangible sustained releasing character.This law; Earlier through desolvate-chemical crosslink technique prepares blank albumin nano granular, then with the blank albumin nano granular lyophilizing of gained, then medicine is added to the abundant mixing and absorption of blank albumin nano granular of redissolution; Obtain the albumin nano granular of medicine carrying at last, the lyophilizing deposit.
Summary of the invention
The purpose of this invention is to provide a kind of breviscapine albumin nano granular through the preparation of albumin nano granular absorption breviscapine.
Another object of the present invention provides the method for the above-mentioned breviscapine albumin nano granular of preparation.
Therefore, the invention provides a kind of breviscapine albumin nano granular through the preparation of albumin nano granular absorption breviscapine, it comprises:
The albumin nano granular suspension of 100 parts by volume;
The breviscapine solution of 10-500 parts by volume;
Wherein the albumin nano granular suspension is the suspension of different ethanol concentration, and breviscapine solution is alcoholic solution.
In a preferred embodiment of the present invention, said breviscapine albumin nano granular comprises:
The albumin nano granular suspension of 100 parts by volume;
The breviscapine solution of 10-500 parts by volume;
In this preferred embodiment of the present invention, described albumin nano granular is concentration 50%～80% alcoholic solution, and albumin nano granular concentration is 0.1～5%, and described breviscapine is an alcoholic solution, and breviscapine concentration is 0.1～5.0mg/mL.
Another aspect of the present invention provides the breviscapine albumin nano granular method for preparing of said compositions, and it may further comprise the steps:
(a) with the blank white nanoparticle after the lyophilizing with the ultrasonic redissolution of distilled water, the centrifugal supernatant that goes, flush away freeze drying protectant (three times reach more than);
(b) with the blank albumin nano granular behind the purification among a with distilled water diluting to requiring concentration, stirring condition drips down and requires multiple volume alcoholic solution, to albumin nano granular concentration for requiring concentration, concentration of alcohol is for requiring concentration;
(c) with breviscapine with dissolve with ethanol to requiring concentration;
(d) in 25 ℃, 500r/min stirring, require multiple amount volume c with dripping among the b, continue to stir 1h;
(e) d is centrifugal, remove the free breviscapine of supernatant, centrifugal gained bottom deposition is heavily disperseed with the 0.01mol/L citric acid solution, has both got breviscapine albumin nano granular suspension, adds the freeze drying protectant lyophilization;
Described in the above-mentioned steps d 25 ℃, 500r/min, 1h are and optimize the back gained, do not represent unique conditional.
Description of drawings
Fig. 1 is that breviscapine, Fig. 2 are the differential scanning calorimetric thermogram of breviscapine albumin nano granular lyophilized powder for albumin nano granular lyophilized powder, Fig. 3 for physical mixture, Fig. 4 of breviscapine and albumin nano granular lyophilized powder.Fig. 5 is the external release curve of breviscapine nanoparticle suspension and breviscapine solution.
The specific embodiment
Through a large amount of discovering, through albumin nano granular absorption breviscapine, can be prepared into the albumin nano granular that is loaded with breviscapine, can improve the low problem of breviscapine water solubility, and make it have slow release characteristic.
One aspect of the present invention provides a kind of and has prepared the albumin nano granular that is loaded with breviscapine through albumin nano granular absorption breviscapine, and it comprises:
The albumin nano granular suspension of 100 parts by volume;
The breviscapine solution of 10-500 parts by volume;
In the present invention; Described blank albumin nano granular be through desolvate-chemical crosslink technique is prepared from, and through lyophilizing, distilled water redissolves eccentric cleaning and falls the suspension that adds the ethanol gained behind the freeze drying protectant; Albumin nano granular is concentration 50%～80% alcoholic solution; Albumin nano granular concentration is 0.1～5%, and described breviscapine is an alcoholic solution, and breviscapine concentration is 0.1～5.0mg/mL.
The albumin nano granular suspension of 100 parts by volume (albumin nano granular is concentration 80% alcoholic solution, and albumin nano granular concentration is 3%);
The breviscapine solution of 250 parts by volume (breviscapine concentration is 1.45mg/mL);
(a) get bovine serum albumin (BSA) and be made into 10% concentration with distilled water; Under 25 ℃, the stirring condition of 600r/min; Speed with 1mL/min adds 4 times of volume 95% ethanol, forms colloid solution, and (every 1mg BSA is with 0.95 μ L to add 5% glutaraldehyde water solution again; BSA that in theory can crosslinked 100% is amino), 25 ℃ of shaking table crosslinking curings 12 hours.
(b) with the bovine serum albumin nanoparticle (BSA-NPs) after solidifying among a, centrifugal 15min under the rotating speed of 15000r/min removes organic solvent wherein; Carry out respectively 3 times; Abandon its supernatant after each centrifugal, deposition adds to original volume with distilled water, and ultrasonic 5min is above to be disperseed to it fully.Behind the purification,, get its top colloid solution for the third time, and measure particle diameter (with 100 times of distilled water dilutings) its centrifugal 5min under the rotating speed of 3000r/min.
(c) BSA-NPs behind the purification among the b is used distilled water diluting, add the freeze drying protectant lactose, be made into BSA-NPs concentration with distilled water and be about 1%, lactose concn is 2% solution, carries out lyophilizing at last.
(d) with the whole weighings of the BSA-NPs after the lyophilizing among the c, the content of BSA-NPs after the calculating lyophilizing.Get contain 0.45g BSA-NPs lyophilized products with the ultrasonic redissolution of 20mL distilled water; Centrifugal 15min under the rotating speed of 15000r/min; Remove freeze drying protectant wherein, carry out respectively 3 times, abandon its supernatant after each centrifugal; Deposition adds to original volume with distilled water, and ultrasonic 5min is above to be disperseed to it fully.
(e) BSA-NPs behind the purification among the d is heavily disperseed with the 3mL distilled water at last, stirring condition drips the 12mL alcoholic solution down, and this moment, albumin nano granular concentration was 3%, and the concentration of alcohol of solution is 80%;
(f) breviscapine is used dissolve with ethanol, to concentration be 1.45mg/mL;
(g) in 25 ℃, 500r/min stirring, in e solution, drip the f solution of 37.5mL, continue to stir 1h;
(h) with above-mentioned g solution centrifugal; Remove the free breviscapine of supernatant; Centrifugal gained bottom deposition is heavily disperseed with 0.01mol/L citric acid solution 5mL, has both got breviscapine albumin nano granular suspension, adds freeze drying protectant lactose 1g (with the dissolving of 0.01mol/L citric acid solution); Be diluted to 50mL with the 0.01mol/L citric acid solution, carry out lyophilizing at last and promptly get.
The free breviscapine of supernatant among the h is carried out assay with liquid phase,, calculate the drug loading and the envelop rate of breviscapine albumin nano granular through calculating the amount of bonded breviscapine.Breviscapine albumin nano granular after the lyophilizing carries out the mensuration of particle diameter and Zeta potential to the 0.1mg/mL with distilled water diluting.
The more blank albumin nano granular particle diameter of the breviscapine albumin nano granular particle diameter of this routine gained increases 22.7 ± 1.6nm; Drug loading is 6.73 ± 0.02%; Envelop rate is 80.08 ± 0.29%, and polydispersity coefficient is 0.117 (more blank albumin nano granular is as good as), and Zeta potential is 17.95mV.
The breviscapine albumin nano granular of this routine gained; Through differential scanning calorimetric analysis; The result is shown in Fig. 1～4, and breviscapine has individual melting peak at 116.2 ℃, and blank albumin nano granular lyophilized powder has individual melting peak at 114.7 ℃; Both physical mixtures have two melting peaks at 99.1 ℃ and 116.1 ℃; And breviscapine albumin nano granular lyophilized powder has only a melting peak at 117.9 ℃, and the melting peak complete obiteration of breviscapine explains that breviscapine is wrapped up by albumin nano granular with unformed the existence perhaps in the breviscapine albumin nano granular.Among the figure, breviscapine has a heat absorption exothermic peak at 189.3 ℃, and blank albumin nanometer lyophilized powder has an endothermic peak at 197.7 ℃, and breviscapine is 189.3 ℃ peak complete obiteration in their physical mixture and the breviscapine albumin nano granular.Analyze reason maybe for; Its content of breviscapine only accounts for about 7% in the breviscapine albumin nano granular; The physical mixture of breviscapine and albumin nano granular lyophilized powder also mixes by 7%; Because the breviscapine ratio is less, and both heat absorption positions are close, so breviscapine is covered at 189.3 ℃ peak fully in physical mixture and breviscapine albumin nano granular.
This routine gained breviscapine albumin nano granular carries out release in vitro research; Get the breviscapine albumin nano granular and be diluted to 10mL (being equivalent to the 5mg lamp-dish flower acetic) and breviscapine solution (pH 6.8PBS solution) 10mL (being equivalent to the 5mg lamp-dish flower acetic); Place bag filter respectively, adopt two appendix dissolution methods of Chinese Pharmacopoeia version in 2010 oar method to investigate its medicine release in vitro behavior.Bag filter is placed in the 250mL pH6.8PBS release medium, under 100r/min rotating speed and 37.5 ℃ of medium temperatures, carries out extracorporeal releasing experiment.Get 1mL (replenishing fresh dissolution medium 1mL simultaneously) at 0.17h, 0.33h, 0.76h, 1.0h, 1.5h, 2.0h, 3.0h, 4.0h, 6.0h, 8.0h, 12.0h, 16.0h and 24.0h respectively; 0.22 μ m filtering with microporous membrane; Through the liquid chromatograph content analysis, calculating cumulative discharges percentage rate, draws the release curve and sees Fig. 5; The breviscapine albumin nano granular discharges slowly than breviscapine, and significantly slow releasing function is arranged.The breviscapine albumin nano granular gets into plateau after being released in 16h, and 24h cumulative release percentage rate is 79.19%, and breviscapine solution gets into plateau after discharging 8h, and 12h cumulative release rate is 83.83%.
Claims (3)
1. one kind is passed through the breviscapine albumin nano granular that albumin nano granular absorption breviscapine prepares, and it is characterized in that it comprises:
The albumin nano granular suspension of 100 parts by volume;
The breviscapine solution of 10-500 parts by volume;
Wherein the albumin nano granular suspension is the suspension of different ethanol concentration, and breviscapine solution is alcoholic solution.
2. breviscapine nanoparticle as claimed in claim 1 is characterized in that it comprises:
The albumin nano granular suspension of 100 parts by volume;
The breviscapine solution of 10-500 parts by volume;
Described albumin nano granular is concentration 50%～80% alcoholic solution, and albumin nano granular concentration is 0.1～5%, and described breviscapine is an alcoholic solution, and breviscapine concentration is 0.1～5.0mg/mL.
3. the method for preparing of breviscapine nanoparticle as claimed in claim 1, it comprises the steps:
(a) with the blank white nanoparticle after the lyophilizing with the ultrasonic redissolution of distilled water, the centrifugal supernatant that goes, flush away freeze drying protectant;
(b) with the blank albumin nano granular behind the purification among a with distilled water diluting to requiring concentration, stirring condition drips down and requires multiple volume alcoholic solution, to albumin nano granular concentration for requiring concentration, concentration of alcohol is for requiring concentration;
(c) with breviscapine with dissolve with ethanol to requiring concentration;
(d) in 25 ℃, 500r/min stirring, require multiple amount volume c with dripping among the b, continue to stir 1h;
(e) d is centrifugal, remove the free breviscapine of supernatant, centrifugal gained bottom deposition is heavily disperseed with the 0.01mol/L citric acid solution, has both got breviscapine albumin nano granular suspension, adds the freeze drying protectant lyophilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104026473A CN102415999A (en) | 2011-12-07 | 2011-12-07 | Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104026473A CN102415999A (en) | 2011-12-07 | 2011-12-07 | Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102415999A true CN102415999A (en) | 2012-04-18 |
Family
ID=45940803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011104026473A Pending CN102415999A (en) | 2011-12-07 | 2011-12-07 | Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102415999A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111643726A (en) * | 2019-12-03 | 2020-09-11 | 东南大学 | Method for improving platelet activation resisting function of polyurethane material |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616089A (en) * | 2004-09-17 | 2005-05-18 | 中国人民解放军第二军医大学 | Sodium ferulic acid albumin nano granular preparation and its preparing method |
| CN101088505A (en) * | 2006-06-16 | 2007-12-19 | 珠海高新技术创业服务中心 | Nanometer breviscapine polymer particle prepn and its prepn process |
| CN101653611A (en) * | 2009-07-23 | 2010-02-24 | 复旦大学 | Albumin-adriamycin nano preparation, preparing method and application thereof |
| WO2010075540A1 (en) * | 2008-12-23 | 2010-07-01 | Burnham Institute For Medical Research | Methods and compositions for synaphically-targeted treatment for cancer |
-
2011
- 2011-12-07 CN CN2011104026473A patent/CN102415999A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616089A (en) * | 2004-09-17 | 2005-05-18 | 中国人民解放军第二军医大学 | Sodium ferulic acid albumin nano granular preparation and its preparing method |
| CN101088505A (en) * | 2006-06-16 | 2007-12-19 | 珠海高新技术创业服务中心 | Nanometer breviscapine polymer particle prepn and its prepn process |
| WO2010075540A1 (en) * | 2008-12-23 | 2010-07-01 | Burnham Institute For Medical Research | Methods and compositions for synaphically-targeted treatment for cancer |
| CN101653611A (en) * | 2009-07-23 | 2010-02-24 | 复旦大学 | Albumin-adriamycin nano preparation, preparing method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| 季秀峰等: "白蛋白纳米粒药物传递系统的研究进展", 《沈阳药科大学学报》, vol. 27, no. 12, 31 December 2010 (2010-12-31) * |
| 张建军等: "白蛋白作为药物载体的研究", 《化学进展》, vol. 23, no. 8, 31 August 2011 (2011-08-31), pages 1747 - 1754 * |
| 张良珂等: "一种白蛋白纳米粒的制备与评价", 《中国药学杂志》, vol. 42, no. 5, 31 March 2007 (2007-03-31), pages 365 - 367 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111643726A (en) * | 2019-12-03 | 2020-09-11 | 东南大学 | Method for improving platelet activation resisting function of polyurethane material |
| CN111643726B (en) * | 2019-12-03 | 2022-03-29 | 东南大学 | Method for improving platelet activation resisting function of polyurethane material |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101244277B (en) | Medicine carrying fibroin microsphere and preparation thereof | |
| CN102218034A (en) | Formula, preparation method and use of azithromycin liposome combined medicament | |
| CN100428960C (en) | Method for preparing nano liver-target biodegradating medicine carrier material | |
| CN101024086A (en) | Composition formed from chitosan and its derivatives and low-molecular heparin and pneparation and preparing method | |
| CN104840430A (en) | Chlorogenic acid (CA) and chitosan microspheres as well as preparation process and application thereof | |
| CN103520114B (en) | Nuciferine microsphere and preparation method thereof | |
| CN103495178A (en) | Preparation method of zein/calcium carbonate composite particles and application of zein/calcium carbonate composite particles as drug carriers | |
| CN102961360B (en) | Oxymatrine hepatic targeting nano drug delivery system and preparation method thereof | |
| CN102415999A (en) | Breviscapine albumin nanoparticles prepared by adsorbing breviscapine through albumin nanoparticles | |
| CN102552182A (en) | Colloidal nucleus liposome lyophilized powder and preparation method thereof | |
| CN101618012B (en) | Insoluble medicine solid dispersoid and preparation method thereof | |
| CN103417514B (en) | A kind of butylphenyl phthaleine pharmaceutical composition of microencapsulation and its production and use | |
| CN101953797A (en) | Method for preparing medicament carrying controlled-release nanometer material and application | |
| CN108186573B (en) | Hydroxycamptothecin liver targeting preparation using lipid-coated mesoporous silica as carrier and preparation method thereof | |
| CN105997941A (en) | Amphipathic micelle nanometer capsule and preparing method and application thereof | |
| CN102225053B (en) | Vincristine nano targeting slow-release long-circulation liposome and preparation method thereof | |
| CN103315961A (en) | Neogambogic acid self-microemulsifying preparation and preparation method thereof | |
| CN101744772A (en) | Method for preparing drug slow-releasing particulates for animals | |
| CN102172404A (en) | Alkylating recombinant human serum albumin and preparation and application of medicinal composition thereof | |
| CN101716145A (en) | Modified chitosan targeted medicament carrying nano microsphere and preparation method thereof | |
| Callewaert et al. | Serum albumin-alginate coated microspheres: role of the inner gel in binding and release of the KRFK peptide | |
| CN103446055B (en) | Preparation method for genistein lipid nano body | |
| CN107007557A (en) | A kind of medicinal flower-shape carrier particles for customizing nano-pore structure and preparation method thereof | |
| CN105663085A (en) | Paeonol nanometer sustained release preparation and preparation method thereof | |
| CN101721376B (en) | Calcitonin sustained release microsphere composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120418 |