CN102949344A - Application of curcumin solid lipid nano-particle serving as medicament for treating asthma - Google Patents
Application of curcumin solid lipid nano-particle serving as medicament for treating asthma Download PDFInfo
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Abstract
The invention belongs to the technical field of biomedical materials, and relates to application of curcumin solid lipid nano-particles. After traditional Chinese medicament curcumin is loaded with solid nano-lipisome, the syringeability of curcumin can be improved, the bioavailability of curcumin can be improved by about 30 times, and the lung targeting of curcumin can be improved. The SLN-curcumin can be used for effectively treating asthma to recover the airway resistance to a normal level, is safe, does not have remarkable toxic or side effect, and has great market developing potentials. The reaction system related in the invention is relatively stable, the technical operation is simple, the product treatment is especially convenient and convenient, and industrialization can be favored.
Description
Technical field
The invention belongs to biological medicine material technology field, relate to a kind of application of curcumin solid lipid nanoparticle.
Background technology
Curcumin is Chinese medicine commonly used, safety non-toxic, asthma had obvious curative effect, but curcumin is water insoluble, is insoluble in oil, only is only soluble in some organic solvents, organism is very low to the degree of absorbing of curcumin, be less than 1% of administration, and the availability individual variation is very big, brings very large restriction also for the application of curcumin.Solve the problem that the curcumin bioavailability is poor, administration is difficult, with its new drug that develops into treatment and Control of asthma, will introduce suitable medicine-carried system, this also is comparatively popular to a curcumin research in recent years field.The more medicine-carried system that is applicable to curcumin of research has microsphere, polymer, liposome, solid lipid nanoparticle (SLN) etc. both at home and abroad at present, the document of this respect often all is for oncotherapy and overcomes the research of other tumour medicine drug resistance aspect, perhaps only limit to how to improve stability and the bioavailability of curcumin, and there is not yet report both at home and abroad in the research aspect treating asthma and the control.
Summary of the invention
The object of the invention is to provide for the defective of prior art the application of a kind of curcumin solid lipid nanoparticle (SLN-Curcumin) as the treatment asthmatic medicament.
In order to achieve the above object, the present invention is by the following technical solutions:
The present invention adopts the solid lipid nanoparticle (SLN) of the comparatively ripe safety of present research, degradable in vivo as the medicine-carried system of curcumin.And have very strong pulmonary's targeting, be fit to very much be applied to pulmonary disease.
A kind of curcumin solid lipid nanoparticle is as the application for the treatment of asthmatic medicament.
The administering mode of described curcumin solid lipid nanoparticle is oral, injection or atomized medicine introducing.
Described curcumin solid lipid nanoparticle is each 5mg/kg～20mg/kg to the scope of the effective dose of rat, once a day.
Described curcumin solid lipid nanoparticle was two weeks to the administration cycle of rat, on every Fridays the sky.
Described curcumin solid lipid nanoparticle, every 100mg comprises following component and content thereof:
Lecithin 8～20mg,
Surfactant 10-30mg.
Described lipidic matrix is selected from fatty acid, glyceride or triglyceride, preferred stearic acid, Palmic acid, docosanoic acid, glyceryl tristearate or cholesterol.
Described surfactant is selected from Myrj53 (polyoxyethylene (50) stearate), Tween-20 (Tween-20), Tween-80 (Tween 80) or sodium dehydrocholate.
The particle diameter of described curcumin solid lipid nanoparticle is 50-200nm, and mean diameter is 65nm.
Calculate according to every rat 250g, take by weighing among the PBS (0.01M, pH 7.4) that SLN-curcumin 1.25～5mg is dissolved in 1mL, fully mix pneumoretroperitoneum injection/oral administration, be administered once every day, and the sky continued medication for 2 weeks on every Fridays.
Improve the syringeability of curcumin, improve the in vivo blood drug level of curcumin and to the targeting of pulmonary, be applied to first treating asthma, obtained the curative effect suitable with dexamethasone sodium phosphate DSP at Rat Asthma Model, the air flue level returns to PBS negative control group level, and does not have obvious toxic-side effects.
A kind of preparation method of above-mentioned curcumin solid lipid nanoparticle comprises following steps:
(1) take by weighing lipidic matrix 15～40mg, lecithin 8～20mg, curcumin 15～40mg is dissolved in the 10-30m1 organic solvent, forms organic facies;
(2) accurately take by weighing the 10-30mg surfactant, the ultrasonic 30-90ml deionized water that is dissolved in forms water, and water is poured in 3 mouthfuls of flasks, and heating is stirred;
(3) organic facies at the uniform velocity is injected into aqueous phase, 800-2000rpm is stirred to system residue 3-8ml under the 68-78 ℃ of condition, and namely system presents glue, removes water-bath, pours rapidly ready 4 ℃ of deionized waters into, under the room temperature, continues 1200rpm and stirs 2 hours;
(4) collect product in the there-necked flask, 12000-20000rpm, centrifugal 6-18h removes supernatant, and deionized water is resuspended, 12000-20000rpm, centrifugal 6h removes supernatant, precipitated product lyophilization powdered.
The organic solvent of described step (1) is selected from the mixed system of chloroform, cyclohexane extraction, the tert-butyl alcohol, dichloromethane and methanol mixed system or acetone and ethanol etc.
The heating-up temperature of described step (2) is 68-78 ℃, and mixing speed is 800-2000rpm, and mixing time is 1h.
The nanocurcumin of 50～60nm of the present invention's preparation by the mice therapeutic drug monitoring, finds that the SLN-curcumin can improve the blood drug level (AUC) of simple medicine up to 29.4 times.On this basis, carried out SLN-curcumin, curcumin blood drug level relatively, traditional glucocorticoid medicine DSP to the drug effect of SD experimental rat model of asthma relatively, result of study shows, the SLN-curcumin not only can make the rat airway resistance return to PBS matched group level, and rat body weight maintenance onset level (DSP group rat body weight has descended 20%), show that it has good safety.Experiment on Asthmatic Rats confirms that also the SLN-curcumin is without any obvious toxic-side effects, and only adopt very little dosage just to have than the better curative effect of dexamethasone sodium phosphate (DSP) for experimental rat model of asthma, the SLN-curcumin is safe and effective, toxic and side effects is little, is the asthma new drug that the medical use potentiality are arranged very much.
The present invention has the following advantages:
1, after the present invention uses solid nano liposome medicine carrying with the Chinese medicine curcumin, improved the syringeability of curcumin, the bioavailability that improves curcumin reaches about 30 times, improves pulmonary's targeting of curcumin.
2, SLN-curcumin of the present invention can effectively be treated asthma, recover airway resistance to normal level, and safety has very large market development potential without obvious toxic-side effects.
3, the reaction system that the present invention relates to is relatively stable, and technical operation more simply, particularly the product processing is convenient simple and direct, is easy to industrialization.
Description of drawings
Fig. 1 is SLN-curcumin TEM granularmetric analysis.
Fig. 2 is the analysis of SLN-curcumin surface potential.
Fig. 3 is XRD figure analysis of spectrum (a) curcumin; (b) SLN nanoparticle empty carrier; (c) SLN-curcumin nano medicine-carried system.
Fig. 4 is the external elution profiles of SLN-curcumin (PBS (0.01M, pH 7.4,1%Tween (tween) 80)).
Fig. 5 is blood drug level change curve in the Mice Body.(▲) SLN-curcumin administration group; (■) curcumin administration group.
Fig. 6 is Mice Body giving drugs into nose fabric texture scattergram.
Fig. 7 is SD rat airway resistance.(▲) curcumin administration group; (■) SLN-curcumin administration group; (◆) asthma positive controls () PBS negative control group.Data are expressed as means ± SEM (mean+/-standard error).
Fig. 8 is IL-4 expression in the SD Rat Asthma Model pulmonary washing liquid.(
*P＜0.05;
*P＜0.01, and the OVA positive controls is relatively).
The specific embodiment
Embodiment 1
Take by weighing stearic acid 40mg, lecithin 20mg, curcumin 40mg is dissolved in the 10ml chloroform;
Organic facies at the uniform velocity is injected into the 10# syringe needle contains being preheated among 75 ℃ the water 30ml of 30mg Myrj53,1200rpm stirred about 1 hour, by the time system remains 5ml, remove water-bath, pour rapidly ready 4 ℃ of deionized waters into, continue 1200rpm under the room temperature and stirred 2 hours, the abundant centrifugal sample of collecting, PBS cleans twice, and lyophilization gets the medicine finished product.
SLN-curcumin particle diameter is 50-200nm, rounded (such as Fig. 1), and surface band negative charge, surface potential are-20mV (such as Fig. 2).Show that by XRD analysis the SLN-curcumin has all characteristic peaks of SLN, have simultaneously the Partial Feature peak of curcumin, show that SLN is wrapped in curcumin in the lipid, the two combination (such as Fig. 3).
By Bag filter method the SLN-curcumin is carried out the medicament slow release experiment external, the result shows that in the PBS of 1%Tween 80 solution, the drug release of SLN-curcumin can reach more than 5 days, and the release of 2 days left and right sides medicines reaches 50% (such as Fig. 4).In the blood drug level experiment, adopt the BALB/C experiment mice to amount to 3 groups, every group 3, be respectively the PBS group, SLN-curcumin administration group and curcumin administration group, take contained curcumin as metering, intraperitoneal administration, 200mg/kg, respectively at the different time points blood sampling, get tissue in 1 hours point, blood drug level and tissue distribution are calculated respectively in the HPLC quantitative analysis, discovery is in curcumin administration group, curcumin concentration can be surveyed hardly in the blood, and in SLN-curcumin group, blood drug level AUC can reach 29.4 times (such as Fig. 5) of simple medicine.According to the drug level based on albumen, the SLN-curcumin has very strong pulmonary's targeting (such as Fig. 6).
Adopt ovalbumin to set up the allergic asthma model of SD rat, on the basis of successfully setting up SD bronchus of rat asthmatic model, divide at random 4 groups, every group 10, be made as respectively positive controls, curcumin administration group, SLN-curcumin administration group, the administration metering is 10mg/kg, intraperitoneal injection; Set up simultaneously negative control group.2 weeks of successive administration (5 days/week), the airway resistance of test rat pulmonary.SLN can significantly improve the therapeutic effect of curcumin, so that the airway resistance of experimental rat model of asthma returns to negative control group level (as shown in Figure 7).Simultaneously the relative asthma positive control of IL-4 expression makes up simple drug administration group and all has the significance difference opposite sex in the rat pulmonary irrigating solution of SLN-curcumin administration group, basically returns to negative control group level (such as Fig. 8).
Take by weighing stearic acid 40mg, lecithin 20mg, curcumin 20mg is dissolved in the 10ml chloroform; At the uniform velocity be injected into organic facies among the water 30ml that contains 30mg Myrj53 with the 10# syringe needle, 75 ℃, 1200rpm stirred about 1 hour, and system remains about 5ml by the time, removes water-bath, pour rapidly ready 4 ℃ of deionized waters into, continue 1200rpm under the room temperature and stirred 2 hours, the abundant centrifugal sample of collecting, PBS cleans twice, lyophilization gets the medicine finished product.
SLN-curcumin particle diameter is 50-200nm, and is rounded, the surface band negative charge, and surface potential is-25mV.In the PBS of 1%Tween80 solution, the drug release of SLN-curcumin can reach more than 7 days, and the release of 2 days left and right sides medicines reaches 45%.
In the blood drug level experiment, adopt the BALB/C experiment mice to amount to 3 groups, every group 3, be respectively the PBS group, SLN-curcumin administration group and curcumin administration group, take contained curcumin as metering, intraperitoneal administration, 200mg/kg, respectively at the different time points blood sampling, get tissue in 1 hours point, blood drug level and tissue distribution are calculated respectively in the HPLC quantitative analysis, discovery is in curcumin administration group, curcumin concentration can be surveyed hardly in the blood, and in SLN-curcumin group, blood drug level AUC can reach 26.8 times of simple medicine.
Adopt ovalbumin to set up the allergic asthma model of SD rat, divide at random 4 groups, 10 every group, be made as respectively positive controls, curcumin administration group, SLN-curcumin administration group, the administration metering is 20mg/kg, intraperitoneal injection; Set up simultaneously negative control group.2 weeks of successive administration (5 days/week), the airway resistance of test rat pulmonary.SLN can significantly improve the therapeutic effect of curcumin, so that the airway resistance of experimental rat model of asthma returns to the negative control group level.
Embodiment 3
Take by weighing stearic acid 20mg, lecithin 10mg, curcumin 15mg is dissolved in the 10ml chloroform; At the uniform velocity be injected into organic facies among the water 30ml that contains 20mg Myrj53 with the 10# syringe needle, 75 ℃, 1200rpm stirred about 2 hours, and system remains about 5ml by the time, removes water-bath, pour rapidly ready 4 ℃ of deionized waters into, continue 1200rpm under the room temperature and stirred 2 hours, the abundant centrifugal sample of collecting, PBS cleans twice, lyophilization gets the medicine finished product.
SLN-curcumin particle diameter is 50-200nm, and is rounded, the surface band negative charge, and surface potential is-25mV.In the PBS of 1%Tween80 solution, the drug release of SLN-curcumin can reach more than 5 days, and the release of 2 days left and right sides medicines reaches 48%.
In the blood drug level experiment, adopt the BALB/C experiment mice to amount to 3 groups, every group 3, be respectively the PBS group, SLN-curcumin administration group and curcumin administration group, take contained curcumin as metering, intraperitoneal administration, 200mg/kg, respectively at the different time points blood sampling, get tissue in 1 hours point, blood drug level and tissue distribution are calculated respectively in the HPLC quantitative analysis, discovery is in curcumin administration group, curcumin concentration can be surveyed hardly in the blood, and in SLN-curcumin group, blood drug level AUC can reach 27 times of simple medicine.
Adopt ovalbumin to set up the allergic asthma model of SD rat, divide at random 4 groups, 10 every group, be made as respectively positive controls, curcumin administration group, SLN-curcumin administration group, the administration metering is 5mg/kg, and the nebulizer inhalation is set up negative control group simultaneously.2 weeks of successive administration (5 days/week), the airway resistance of test rat pulmonary.SLN can significantly improve the therapeutic effect of curcumin, so that the airway resistance of experimental rat model of asthma returns to the negative control group level.
Embodiment 4
Take by weighing stearic acid 20mg, lecithin 15mg, curcumin 20mg is dissolved in the 10ml chloroform; At the uniform velocity be injected into organic facies among the water 30ml that contains 30mg Myrj53 with the 10# syringe needle, 70 ℃, 1200rpm stirred about 3 hours, and system remains about 5ml by the time, removes water-bath, pour rapidly ready 4 ℃ of deionized waters into, continue 1200rpm under the room temperature and stirred 2 hours, the abundant centrifugal sample of collecting, PBS cleans twice, lyophilization gets the medicine finished product.
SLN-curcumin particle diameter is 50-200nm, and is rounded, the surface band negative charge, and surface potential is-20mV.In the PBS of 1%Tween80 solution, the drug release of SLN-curcumin can reach more than 5 days, and the release of 2 days left and right sides medicines reaches 50%.
In the blood drug level experiment, adopt the BALB/C experiment mice to amount to 3 groups, every group 3, be respectively the PBS group, SLN-curcumin administration group and curcumin administration group, take contained curcumin as metering, intraperitoneal administration, 200mg/kg, respectively at the different time points blood sampling, get tissue in 1 hours point, blood drug level and tissue distribution are calculated respectively in the HPLC quantitative analysis, discovery is in curcumin administration group, curcumin concentration can be surveyed hardly in the blood, and in SLN-curcumin group, blood drug level AUC can reach 28.4 times of simple medicine.
Adopt ovalbumin to set up the allergic asthma model of SD rat, divide at random 4 groups, 10 every group, be made as respectively positive controls, curcumin administration group, SLN-curcumin administration group, the administration metering is 20mg/kg, and negative control group is set up in the oral administration gavage administration simultaneously.2 weeks of successive administration (5 days/week), the airway resistance of test rat pulmonary.SLN can significantly improve the therapeutic effect of curcumin, so that the airway resistance of experimental rat model of asthma returns to the negative control group level.
The above-mentioned description to embodiment is can understand and apply the invention for ease of those skilled in the art.The person skilled in the art obviously can easily make various modifications to these embodiment, and needn't pass through performing creative labour being applied in the General Principle of this explanation among other embodiment.Therefore, the invention is not restricted to the embodiment here, those skilled in the art are according to announcement of the present invention, and not breaking away from the improvement that category of the present invention makes and revise all should be within protection scope of the present invention.
Claims (8)
1. a curcumin solid lipid nanoparticle is as the application for the treatment of asthmatic medicament.
2. application according to claim 1 is characterized in that: the administering mode of described curcumin solid lipid nanoparticle is oral, injection or atomized medicine introducing.
3. application according to claim 1 is characterized in that: described curcumin solid lipid nanoparticle is each 5mg/kg～20mg/kg to the scope of the effective dose of rat, once a day.
4. application according to claim 1 is characterized in that: described curcumin solid lipid nanoparticle was two weeks to the administration cycle of rat, on every Fridays the sky.
5. arbitrary described curcumin solid lipid nanoparticle as the treatment asthmatic medicament among the claim 1-4, it is characterized in that: every 100mg curcumin solid lipid nanoparticle comprises following component and content thereof:
Curcumin 15～40mg,
Lipidic matrix 15～40mg,
Lecithin 8～20mg,
Surfactant 10-30mg.
6. curcumin solid lipid nanoparticle according to claim 5, it is characterized in that: described lipidic matrix is selected from fatty acid, glyceride or triglyceride, preferred stearic acid, Palmic acid, docosanoic acid, glyceryl tristearate or cholesterol.
7. curcumin solid lipid nanoparticle according to claim 5, it is characterized in that: described surfactant is selected from polyoxyethylene (50) stearate, Tween-20, Tween 80 or sodium dehydrocholate.
8. curcumin solid lipid nanoparticle according to claim 5, it is characterized in that: the particle diameter of described curcumin solid lipid nanoparticle is 50-200nm, mean diameter is 65nm.
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Cited By (8)
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| CN103446055A (en) * | 2013-08-22 | 2013-12-18 | 合肥工业大学 | Preparation method for genistein lipid nano body |
| CN103655519A (en) * | 2013-12-24 | 2014-03-26 | 哈尔滨医科大学 | Curcumin solid lipid nanoparticle with P-gp inhibiting effect and preparation method thereof |
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| CN104415016A (en) * | 2013-08-22 | 2015-03-18 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Application of dry curcumin nano-powder inhalant in treatment of acute lung injury |
| CN105919973A (en) * | 2016-04-26 | 2016-09-07 | 同济大学 | Application of solid lipid nanoparticles as antidepressant drug carrier |
| RU2726193C2 (en) * | 2014-10-09 | 2020-07-09 | Дистретто Текнолоджико Сицилия Микро Э Нано Системи С.К.А.Р.Л. | Nanostructured compositions for delivery of silibinin and other active ingredients for treating eye diseases |
| CN113041233A (en) * | 2021-03-22 | 2021-06-29 | 深圳大学 | Curcumin-loaded bovine serum albumin-mannuronic acid oligosaccharide Maillard reaction graft nanoparticle and preparation method thereof |
| CN114259473A (en) * | 2021-09-16 | 2022-04-01 | 海南医学院 | Galangin nano lipid assembly and preparation method thereof |
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Cited By (13)
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| CN103446055A (en) * | 2013-08-22 | 2013-12-18 | 合肥工业大学 | Preparation method for genistein lipid nano body |
| CN103446055B (en) * | 2013-08-22 | 2015-02-11 | 合肥工业大学 | Preparation method for genistein lipid nano body |
| CN104415016A (en) * | 2013-08-22 | 2015-03-18 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Application of dry curcumin nano-powder inhalant in treatment of acute lung injury |
| CN103655519A (en) * | 2013-12-24 | 2014-03-26 | 哈尔滨医科大学 | Curcumin solid lipid nanoparticle with P-gp inhibiting effect and preparation method thereof |
| CN103784421A (en) * | 2014-02-27 | 2014-05-14 | 哈尔滨医科大学 | Curcumin and piperine carried solid lipid nanoparticles and preparation method thereof |
| RU2726193C2 (en) * | 2014-10-09 | 2020-07-09 | Дистретто Текнолоджико Сицилия Микро Э Нано Системи С.К.А.Р.Л. | Nanostructured compositions for delivery of silibinin and other active ingredients for treating eye diseases |
| US11253526B2 (en) | 2014-10-09 | 2022-02-22 | Distretto Tecnologico Sicilia Micro E Nano Sistemi S.C.A.R.L. | Nanostructured formulations for the delivery of silibinin and other active ingredients for treating ocular diseases |
| US11266659B2 (en) | 2014-10-09 | 2022-03-08 | Distretto Tecnologico Sicilia Micro E Nano Sistemi S.C.A.R.L. | Nanostructured formulations for the delivery of silibinin and other active ingredients for treating ocular diseases |
| US11633356B2 (en) | 2014-10-09 | 2023-04-25 | Distretto Tecnologico Sicilia Micro E Nano Sistemi S.C.A.R.L. | Nanostructured formulations for the delivery of silibinin and other active ingredients for treating ocular diseases |
| CN105919973A (en) * | 2016-04-26 | 2016-09-07 | 同济大学 | Application of solid lipid nanoparticles as antidepressant drug carrier |
| CN113041233A (en) * | 2021-03-22 | 2021-06-29 | 深圳大学 | Curcumin-loaded bovine serum albumin-mannuronic acid oligosaccharide Maillard reaction graft nanoparticle and preparation method thereof |
| CN114259473A (en) * | 2021-09-16 | 2022-04-01 | 海南医学院 | Galangin nano lipid assembly and preparation method thereof |
| CN114259473B (en) * | 2021-09-16 | 2023-07-25 | 海南医学院 | Galangin nanometer lipid assembly and preparation method thereof |
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Application publication date: 20130306 |