CN105147640A - Total bufogenin PLGA nanoparticle freeze-drying preparation and preparation method thereof - Google Patents
Total bufogenin PLGA nanoparticle freeze-drying preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a total bufogenin PLGA (poly-(lactic-co-glycolic acid)) nanoparticle freeze-drying preparation and a preparation method thereof and belongs to the field of PLGA nanoparticle freeze-drying preparations and preparation thereof. At first, the invention discloses total bufogenin PLGA nanoparticles which comprise the components of total bufogenin, PLGA and a freeze-drying protective agent. The preparation method comprises the following steps: total bufogenins and PLGA are dissolved in an organic solvent to serve as a dispersion phase; an F68 water solution serves as a continuous phase; the dispersion phase is slowly injected into the continuous phase in an ultrasonic environment to form an O/W emulsion; then the O/W emulsion is transferred onto a magnetic stirrer to be stirred; after the organic solvent is fully volatilized, stirring is performed under the ice-bath condition to obtain a nanoparticle solution; and centrifugal treatment is conducted to obtain the total bufogenin PLGA nanoparticles. According to the total bufogenin PLGA nanoparticle freeze-drying preparation, the measured particle diameter of the particles is 150-210 nm, and the encapsulation efficiency is 50-90 percent. The total bufogenin PLGA nanoparticle freeze-drying preparation can effectively improve the tumor cell target ability of the total bufogenins, improves the medical bioavailability, achieves the slow-release curative effect and reduces toxic and side effects.
Description
Technical field
The present invention relates to lyophilized formulations, particularly relate to total bufogenin PLGA Nano microsphere lyophilized formulations, the invention still further relates to the preparation method of described total bufogenin PLGA Nano microsphere lyophilized formulations, belong to PLGA Nano microsphere lyophilized formulations and preparation field thereof.
Background technology
The cinobufacin taking from Chinese medicine Bufo siccus skin zone can detoxify, detumescence, pain relieving.In being applicable to, late tumor, the treatment of chronic hepatitis B etc.But find after deliberation, total bufogenin class (bufotalin class of tool anti-tumor activity in HUACHANSU ZHUSHEYE, bufotoxin class) component content is extremely low, be mainly water solublity indoles alkaloid (as 5-hydroxy tryptamine, bufotenine, the special Buddhist nun of Bufo siccus, Bufo siccus sulfur etc.) class, the compositions such as aminoacid, and a large amount of lactone loss of effective components totally, alkaloid component is not yet had to have the research of anti-tumor activity to report at present, and cinobufacin untoward reaction arrhythmia is thought in clinical research, local venous stimulation reaction, dermoreaction, asthma, allergy etc. are caused by the pharmacological action of water solublity indoles alkaloid composition.The major defects such as to sum up, it is low that cinobufacin has effective component content, and impurity is many, and quality and clinical efficacy are unstable, toxic and side effects is large, therefore, enrichment play anti-tumor activity lactone composition, remove the center of gravity that alkaloid and other impurity become us to study.
Separation and purification is carried out to cinobufacin extracting solution, obtain cinobufacin effective site---total bufogenin, mainly containing lactone compositions such as bufotalin (resibufogenin), cinobufagin (cinobufagin), Toadpoison Medicine (bufalin), bufotalien (Bufotalin), Gamabufotalin-3-half suberate (Gamabufotalin-3-hydrogenSuberate), bufalin-3-succinyl arginine ester, cinobufacin-3-succinyl arginine esters.For the ubiquitous problems of Chinese medicine injection on market, develop technique advanced person, steady quality, curative effect is high, toxic and side effects is few traditional medicine Injectio be very necessary, in view of total bufogenin has unique technical advantage, we carry out secondary deep exploitation to HUACHANSU ZHUSHEYE, have developed total bufogenin lyophilized formulations---and " injection China toad lactone ".
PLGA has good biocompatibility, slow release characteristic, degradability; be widely used in the preparation of microsphere; this microsphere system has protection medicine and exempts from destruction; targeted drug is to some particular tissues; delay/Drug controlled release; prolong drug action time, reduce the advantage such as drug toxicity and zest.FDA approval is used as the material of pharmaceutical carrier, and become a kind of carrier of the antitumor drug be widely used, comparatively many-sided advantages such as having anti-tumor neovascularization generation compared by classic chemotherapy preparation.And we can specifically adjust suitable particle diameter according to clinical demand, utilize the various ways such as intravenous injection, interstitial administration, oral administration.
Nano microsphere (nanospheres, NSs) be a kind of novel drug-supplying system that 20 century 70s rise, it is the spherical microgranule of the spherical or class that utilizes the macromolecular material of suitable natural or synthesis carrier parcel or Drug absorbability to be formed.The major advantage of nano microsphere preparations: (1) solves the route of administration of oral hydrolysis medicine.(2) select suitable carrier material and optimized fabrication technique, medicine a few weeks or months slow releasing in vivo can be realized, reduce or administration number of times.(3) realize target administration, as microsphere is modified, drug effect is in target site.(4) improve dissolubility and the dissolution of insoluble drug, play slow releasing function.(5) Nano microsphere discharges with given pace, a year a variety of medicine can be wrapped to maintain effective blood drug concentration microsphere, as chemical classes medicine, protein medicaments, polypeptide, DNA, RNA, natural drug, and microsphere can make help medicine realize the diversification of administering mode, can by oral, pulmonary, nasal-cavity administration.Therefore Nano microsphere is the very promising carrier format of one, is worth our further research and extension.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of total bufogenin PLGA Nano microsphere;
Another technical problem to be solved by this invention is to provide a kind of total bufogenin PLGA Nano microsphere lyophilized formulations;
Another technical problem to be solved by this invention is to provide the preparation method of a kind of total bufogenin PLGA Nano microsphere and total bufogenin PLGA Nano microsphere lyophilized formulations.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
First the present invention discloses a kind of total bufogenin PLGA Nano microsphere, comprises following component: total bufogenin, PLGA, freeze drying protectant.
The weight of each component is: total bufogenin 1 ~ 5 part, PLGA5 ~ 50 part, freeze drying protectant 0.5-5 part
Preferably, the weight of each component is: total bufogenin 1 part, PLGA10 part, freeze drying protectant 0.5 part.
Wherein, the molecular weight of described high molecular polymer PLGA is 0.5-50000, its lactic acid: the molar ratio of hydroxyacetic acid monomer is one or several material mixing in 75:25,50:50,25:75.
The invention also discloses a kind of preparation method of described total bufogenin PLGA Nano microsphere, comprise the following steps:
(1) take each component according to described proportioning, total bufogenin, PLGA are added in organic solvent, as decentralized photo;
(2) F68 aqueous solution is continuous phase;
(3) under ultrasound environments, decentralized photo is slowly injected continuous phase, forms O/W Emulsion,
(4) be transferred to immediately on magnetic stirring apparatus and stir, after organic solvent is fully volatilized, stir to obtain Nano microsphere solution under condition of ice bath, centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
(5) added in F68 water by total toadpoison lactone PLGA Nano microsphere, add freeze drying protectant, lyophilization obtains total bufogenin PLGA Nano microsphere lyophilized formulations.
Wherein, step (1) described organic solvent to be selected from dichloromethane, ethyl acetate, acetone or dehydrated alcohol any one or the two or more mixture according to arbitrary proportion composition; Be preferably the mixture that dichloromethane and ethyl acetate form according to arbitrary proportion; Most preferably be, the mixture that dichloromethane and ethyl acetate form according to volume ratio 1:1;
Stir speed (S.S.) in the solvent volatilization process of step (4) is 300 ~ 15000rpm, and temperature controls at 4 DEG C ~ 40 DEG C, and solvent volatilization adopts room temprature evaporation; Stir under condition of ice bath after obtaining Nano microsphere solution, centrifugal, centrifugal speed is 3000 ~ 12000rpm.
Step (5) freeze drying protectant be selected from glucose, sucrose, trehalose, mannitol, sodium chloride, lactose, sorbitol, xylitol, glucosan, Polyethylene Glycol, polyvinylpyrrolidone, dextran, glycerol or glycine any one or two or more according to arbitrary proportion composition mixture
Total bufogenin PLGA Nano microsphere particle diameter prepared by the present invention is 150-210nm, and envelop rate is 50%-90%.
The PLGA of high molecular polymer described in the present invention different molecular weight, its lactic acid: the different mol ratio of hydroxyacetic acid monomer, the variety classes of organic solvent and different amounts thereof play important influence to total bufogenin PLGA Nano microsphere mean diameter, envelop rate.Wherein, high molecular polymer PLGA molecular weight 40000, its lactic acid: mol ratio 75:25, the total bufogenin PLGA Nano microsphere mean diameter of organic solvent obtained by dichloromethane and ethyl acetate 1:1 of hydroxyacetic acid monomer are 168.5nm, and envelop rate is 89.8%, and quality evaluation is best.Because the particle diameter of total bufogenin PLGA Nano microsphere is less, the targeting of its obtained freeze-dried powder preparation medicine is better; Unit dosage envelop rate is larger, and its dose that can act on tumor cell is larger, and effect is better.
Technical solution of the present invention compared with prior art, has following beneficial effect:
1. use a kind of total toadpoison lactone PLGA Nano microsphere of preparing of this method to have higher envelop rate under the condition ensureing total toadpoison lactone stability, drug level that can be best in holder, and the time of prolong drug effect.Therefore, the slow release of medicine, target administration can be realized, there is important theory value and actual application prospect.
2. this preparation method has simple process, preparation cost is low, technique favorable reproducibility, sample requirement are few, and the prescription of experiment sieving and technique also can be amplified to production application, thus have directive significance to the application of industrialization.
Detailed description of the invention
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.It should be understood that described embodiment is only exemplary, any restriction is not formed to scope of the present invention.It will be understood by those skilled in the art that and can modify to the details of technical solution of the present invention and form or replace down without departing from the spirit and scope of the present invention, but these amendments or replacement all fall into protection scope of the present invention.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 1
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 168.5nm, and envelop rate is 89.8%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 2
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:2) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 179.3nm, and envelop rate is 80.7%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 3
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 2:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 185.3nm, and envelop rate is 85.2%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 4
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 50:50 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 201.8nm, and envelop rate is 66.5%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 5
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 25:75 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 201.8nm, and envelop rate is 59.7%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 6
By total for 2mg bufogenin, 15mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 170.8nm, and envelop rate is 59.5%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 7
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 30000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 175.9nm, and envelop rate is 63.8%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 8
By total for 2mg bufogenin, 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer), 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 50:50 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 173.3nm, and envelop rate is 72.9%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 9
By total for 2mg bufogenin, 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer), 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 25:75 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 180.9nm, and envelop rate is 66.5%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 10
By total for 2mg bufogenin, 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 50:50 of hydroxyacetic acid monomer), 10mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 25:75 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 185.4nm, and envelop rate is 53.6%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 11
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 70:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 177.4nm, and envelop rate is 72.6%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 12
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 50000, its lactic acid: the mol ratio 75:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 800rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 201.4nm, and envelop rate is 70.7%.
The preparation of the total bufogenin PLGA Nano microsphere of embodiment 13
By total for 2mg bufogenin, 20mgPLGA (high molecular polymer PLGA molecular weight 40000, its lactic acid: the mol ratio 70:25 of hydroxyacetic acid monomer) be dissolved in 2mL dichloromethane and ethyl acetate (volume ratio 1:1) mixed solution, as decentralized photo (oil phase), F68 aqueous solution is continuous phase (aqueous phase), under 400rpm stirring at room temperature, decentralized photo is slowly injected 10ml continuous phase, form O/W Emulsion, be transferred to 1000rpm on magnetic stirring apparatus immediately to stir, continue to stir 4h, after organic solvent is fully volatilized, Nano microsphere solution is stirred to obtain under condition of ice bath, 10000rpm centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
Total toadpoison lactone PLGA Nano microsphere prepared by this method is even sized by observed result under Electronic Speculum, profile rounding, smooth surface.The particle diameter recording microsphere is 185.6nm, and envelop rate is 85.5%.
The preparation of the total bufogenin PLGA Nano microsphere lyophilized formulations of embodiment 14
Get total bufogenin PLGA Nano microsphere 11g of preparation to embodiment 1, add in 1LF68 water, add freeze drying protectant glucose 0.5g, lyophilization, obtain total bufogenin PLGA Nano microsphere lyophilized formulations.
Dissolve obtained total bufogenin PLGA Nano microsphere lyophilized formulations water for injection, do quality evaluation with Nano microsphere size and envelop rate, total bufogenin PLGA Nano microsphere mean diameter measured after redissolving is 170.1nm, and envelop rate is 88.8%.
The preparation of the total bufogenin PLGA Nano microsphere lyophilized formulations of embodiment 15
Get total bufogenin PLGA Nano microsphere 11g of preparation to embodiment 3, add in 1LF68 water, add freeze drying protectant mannose 0.5g, lyophilization, obtain total bufogenin PLGA Nano microsphere lyophilized formulations.
Dissolve obtained total bufogenin PLGA Nano microsphere lyophilized formulations water for injection, do quality evaluation with Nano microsphere size and envelop rate, total bufogenin PLGA Nano microsphere mean diameter measured after redissolving is 188.1nm, and envelop rate is 82.5%.
The preparation of the total bufogenin PLGA Nano microsphere lyophilized formulations of embodiment 16
Get total bufogenin PLGA Nano microsphere 11g of preparation to embodiment 13, add in 1LF68 water, add freeze drying protectant polyvinylpyrrolidone 0.5g, lyophilization, obtain total bufogenin PLGA Nano microsphere lyophilized formulations.
Dissolve obtained total bufogenin PLGA Nano microsphere lyophilized formulations water for injection, do quality evaluation with Nano microsphere size and envelop rate, total bufogenin PLGA Nano microsphere mean diameter measured after redissolving is 186.1nm, and envelop rate is 80.8%.
Claims (8)
1. a total bufogenin PLGA Nano microsphere lyophilized formulations, is characterized in that, comprise following component: total bufogenin, PLGA, freeze drying protectant.
2. according to total bufogenin PLGA Nano microsphere lyophilized formulations according to claim 1, it is characterized in that, the weight of each component is: total bufogenin 1 ~ 5 part, PLGA5 ~ 50 part, freeze drying protectant 0.5-5 part.
3. according to total bufogenin PLGA Nano microsphere lyophilized formulations according to claim 2, it is characterized in that, the weight of each component is: total bufogenin 1 part, PLGA10 part, freeze drying protectant 0.5 part.
4. total bufogenin PLGA Nano microsphere lyophilized formulations according to claim 1-3, it is characterized in that, the molecular weight of described high molecular polymer PLGA is 0.5-50000, its lactic acid: the molar ratio of hydroxyacetic acid monomer is one or several material mixing in 75:25,50:50,25:75.
5. Claims 1-4 total bufogenin PLGA Nano microsphere lyophilized formulations preparation method described in any one, is characterized in that, comprise the following steps:
(1) take each component according to described proportioning, total bufogenin, PLGA are dissolved in organic solvent, as decentralized photo;
(2) F68 aqueous solution is continuous phase;
(3) under ultrasound environments, decentralized photo is slowly injected continuous phase, forms O/W Emulsion,
(4) be transferred to immediately on magnetic stirring apparatus and stir, after organic solvent is fully volatilized, stir to obtain Nano microsphere solution under condition of ice bath, centrifugal treating, obtain total toadpoison lactone PLGA Nano microsphere.
(5) added in F68 water by total toadpoison lactone PLGA Nano microsphere, add freeze drying protectant, lyophilization obtains total bufogenin PLGA Nano microsphere lyophilized formulations.
6. according to preparation method described in claim 5, it is characterized in that: step (1) described organic solvent to be selected from dichloromethane, ethyl acetate, acetone or dehydrated alcohol any one or the two or more mixture according to arbitrary proportion composition; Be preferably the mixture that dichloromethane and ethyl acetate form according to arbitrary proportion; Most preferably be, the mixture that dichloromethane and ethyl acetate form according to volume ratio 1:1.
7., according to preparation method described in claim 5, described in it is characterized in that: the stir speed (S.S.) in the solvent volatilization process of step (4) is 300 ~ 15000rpm, temperature controls at 4 DEG C ~ 40 DEG C; Solvent volatilization adopts room temprature evaporation, and stir under condition of ice bath after obtaining Nano microsphere solution, centrifugal, centrifugal speed is 3000 ~ 12000rpm.
8., according to total bufogenin PLGA Nano microsphere lyophilized formulations according to claim 5, it is characterized in that: described freeze drying protectant be selected from glucose, sucrose, trehalose, mannitol, sodium chloride, lactose, sorbitol, xylitol, glucosan, Polyethylene Glycol, polyvinylpyrrolidone, dextran, glycerol or glycine any one or two or more according to arbitrary proportion composition mixture.
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| CN115068429A (en) * | 2022-06-16 | 2022-09-20 | 遵义医科大学 | Mulberry root ketone C PLGA microspheres and preparation method of dry powder inhalation thereof |
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