CN103301090B - Preparation method of genistein targeted nanometer particle - Google Patents
Preparation method of genistein targeted nanometer particle Download PDFInfo
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- CN103301090B CN103301090B CN201310263358.9A CN201310263358A CN103301090B CN 103301090 B CN103301090 B CN 103301090B CN 201310263358 A CN201310263358 A CN 201310263358A CN 103301090 B CN103301090 B CN 103301090B
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Abstract
The invention discloses a preparation method of a genistein targeted nanometer particle, which belongs to the technical field of pharmacy. The preparation method comprises the following steps of: mixing trisodium citrate dehydrate, sodium hydroxide, ferrous sulfate heptahydrate, sodium tripolyphosphate and deionized water; adding a polyethylene glycol 400 solution of genistein; adding chitosan under stirring; centrifuging and separating after 2 hours to obtain the yellowish-brown genistein targeted nanometer particle. The product prepared by the preparation method disclosed by the invention can be used for changing the distribution of the drug in the human body and the dynamic characteristic of the drug, so that the drug is prevented from distributing broadly in the body and diffusing quickly; the targeted orientation of the drug can be used for reducing the drug exposure of the normal tissue, so that the side and toxic effect is lowered, and the treatment effect of the drug is improved.
Description
Technical field
The invention belongs to pharmaceutical technology sectors.
Background technology
The science of the various Chemical Problem of nanochemistry (nanochemistry) mainly more than research atom, in the Nanometer World of below 100nm is science of the chemical preparation of research nanometer system, chemical property and application.Attempt is understood and is used in the main focus that various surprising complex steps that life system runs into and process are nanochemistrys.
Chitosan (chitosan writes a Chinese character in simplified form CS) is that the chitin (chitin) extensively existed by nature obtains through deacetylation, and chemical name is Chitosan (1-4)-2-amino-B-D glucose.The natural biologic material with good biocompatibility and degradability is not only by chitosan, be also the cationic polymer that occurring in nature uniquely exists in a large number, cheap due to its distinctive character, become novel nano-medicament carrier.At present, the method utilizing chitosan to prepare drug microcapsule for bag ancient piece of jade, round, flat and with a hole in its centre material has covalent cross-linking method, ion induction method and self-assembly method etc., wherein, covalent cross-linking method is one of conventional method, it utilizes the amino of chitosan molecule chain and chemical cross-linking agent to react, but because cross-linking agent such as the Organic substance such as formaldehyde, glutaraldehyde often used contains certain toxicity, therefore cannot vivo medicine-feeding be applicable to; Though self-assembly method has certain advantage to the release controlling macromolecular drug, its test method is comparatively loaded down with trivial details; And ion induction method prepares chitosan nano method the most general, it occurs intermolecular and to be intramolecularly cross-linked to form nanoparticle by protonated amino positively charged on electronegative ion and chitosan, this method mild condition, technique is simple, condition controllability is higher, but this method is generally applicable to hydrophilic medicament, bring difficulty to the preparation of hydrophobic drug nanoparticle.
Genistein (Genistein) is the main component of soybean isoflavone, also known as genistein, genistein, is the isoflavonoid coming from bean and dentation plant, its chemistry genistein by name.Genistein has multiple physiology or pharmacologically active, to Several Kinds of Malignancy as breast carcinoma, gastric cancer, hepatocarcinoma, colon cancer, the esophageal carcinoma etc. have stronger inhibitory action.The structure of genistein and relative molecular mass and estradiol similar.But genistein is not soluble in water, therefore significantly limit its use in aqueous phase, direct oral bioavailability rate is lower.
Summary of the invention
The object of the invention is to propose a kind of easy and simple to handle, condition is easily controlled, be easy to the preparation method of industrialized genistein targeted nano-particle.
Technical solution of the present invention is: after two citric acid monohydrate trisodiums, sodium hydroxide, green vitriol, sodium tripolyphosphate and deionized water being mixed, add the PEG400 solution of genistein, under agitation add chitosan.After 2 hours, centrifugalize, obtains yellowish-brown genistein targeted chitosan nanoparticle.
These 8 kinds of raw materials of two citric acid monohydrate trisodiums, sodium hydroxide, green vitriol, sodium tripolyphosphate, chitosan, genistein, PEG400 and deionized water account for 0.20 ~ 0.36%, 0.3 ~ 0.7%, 0.7 ~ 1.1%, 0.2 ~ 0.6%, 1.6 ~ 2.0%, 4.0 ~ 8.0%, 20% ~ 25% and 62.5 ~ 68.5% of the gross mass that feeds intake respectively.
The present invention with chitosan ion induction legal system for genistein targeted nano-particle emulsion, be that ion crosslinking agent carries out physical crosslinking packaging medicine formation nanoparticle to it with sodium tripolyphosphate, the Penetration ration of hydrophobic drug by cell membrane is improved with chitosan, with magnetisable material ferriferrous oxide nano-particle for pharmaceutical carrier, disposablely make genistein targeted nano-particle emulsion.This product changes the distribution of medicine in human body and the dynamics of medicine, avoids medicine to distribute in vivo extensively, spreads soon, and the targeting location of medicine decreases the drug exposure of normal structure, reduces toxic and side effects, improves curative effect of medication; Again because the magnetisable material ferriferrous oxide nano-particle wherein comprised is under the magnetic navigation function of external high-frequency alternating magnetic field, arrive tumor locus, by regulating the intensity of externally-applied magnetic field, making the nano-particle temperature in body increase and killing tumor cell.
Accompanying drawing explanation
Fig. 1 is the infrared spectrum qualification figure of the genistein targeted nano-particle adopting the present invention to make.
Detailed description of the invention
One, preparation technology: two citric acid monohydrate trisodiums, sodium hydroxide, green vitriol, sodium tripolyphosphate are joined in deionized water.Each thing adds the PEG400 solution of genistein, under agitation adds chitosan after dissolving mixing.After 2 hours, under 5000 ~ 10000 r/min conditions, adopt centrifugal separation method, obtain yellowish-brown genistein targeted chitosan nanoparticle.
In kind, adopt following five kinds of different mix proportion schemes, five parts of genistein targeted nano-particles can be prepared respectively:
Scheme 1: two citric acid monohydrate trisodium 0.2kg, sodium hydroxide 0.3 kg, green vitriol 0.8 kg, sodium tripolyphosphate 0.6 kg, chitosan 1.6 kg, genistein 5.0 kg, Polyethylene Glycol 23 kg, deionized water 68.5 kg.
Scheme 2: two citric acid monohydrate trisodium 0.2 kg, sodium hydroxide 0.4 kg, green vitriol 0.8 kg, sodium tripolyphosphate 0.5 kg, chitosan 1.7 kg, genistein 6.0 kg, Polyethylene Glycol 23 kg, deionized water 67.4 kg.
Scheme 3: two citric acid monohydrate trisodium 0.28 kg, sodium hydroxide 0.5 kg, green vitriol 0.9 kg, sodium tripolyphosphate 0.5 kg, chitosan 1.8 kg, genistein 7.5kg, Polyethylene Glycol 25 kg, deionized water 63.52kg.
Scheme 4: two citric acid monohydrate trisodium 0.35 kg, sodium hydroxide 0.7 kg, green vitriol 1.0 kg, sodium tripolyphosphate 0.3 kg, chitosan 1.6 kg, genistein 8.0 kg, Polyethylene Glycol 21 kg, deionized water 67.05 kg.
Scheme 5: two citric acid monohydrate trisodium 0.35 kg, sodium hydroxide 0.5 kg, green vitriol 1.1 kg, sodium tripolyphosphate 0.6 kg, chitosan 2.0 kg, genistein 7.0 kg, Polyethylene Glycol 22 kg, deionized water 66.54 kg.
Two, product infrared spectrum is identified:
Infrared spectrum is recorded by Fourier infrared spectrograph (NEXUS-670F-IR).
As shown in Figure 1, wherein, the infrared spectrogram of the genistein targeted nano-particle that curve 1 is prepared for the present invention, curve 2 is the infrared spectrogram of genistein nanoparticle, curve 3 is the infrared spectrogram of magnetic ferroferric oxide, curve 4 is the infrared spectrogram of genistein, and curve 5 is the infrared spectrogram of chitosan.Genistein targeted nano-particle is the infared spectrum superposition of chitosan, genistein and ferroso-ferric oxide, but peak intensity is again than strong a lot, this is because ferroso-ferric oxide and genistein is less is adsorbed on particle surface, and be wrapped in chitosan inside together, and relative amount is less, and the absworption peak of genistein targeted nano-particle has the superposition compared with multimodal, therefore, peak intensity is stronger.
Ferroso-ferric oxide is at 585cm
-1there is characteristic absorption peak at place, also embodies in the infared spectrum of genistein targeted nano-particle; At 3350cm
-1there is larger absworption peak in left and right genistein targeted nano-particle, chitosan and genistein also have absorption herein; At 800cm
-1to 1750cm
-1near there is comparatively many peaks, at 1600cm
-1and 1500cm
-1there is the peak that more genistein is similar in place's medicament nano particle, on the whole, genistein targeted nano-particle is the infared spectrum superposition of chitosan, genistein and ferroso-ferric oxide.Infared spectrum, to the sign of medicament nano particle, chitosan and genistein, proves that genistein and ferroso-ferric oxide are wrapped up by chitosan, containing genistein effective ingredient in genistein targeted nano-particle.
Three, the process of extracorporeal releasing test and result:
Adopt dynamic dialysis method, by the in-vitro simulated releasing effect of contrast genistein reference substance, genistein chitin nanometer and tool magnetic genistein targeted nano-particle, almost all discharge in genistein reference substance 7h, after genistein chitin nanometer 60h, burst size is 96.07%, and the burst size after genistein targeted nano-particle 60h only reaches 78.35%, prove that genistein targeted nano-particle has good slow releasing function.
Claims (1)
1. the preparation method of a genistein targeted nano-particle, it is characterized in that: after two citric acid monohydrate trisodiums, sodium hydroxide, green vitriol, sodium tripolyphosphate and deionized water are mixed, add the PEG400 solution of genistein, under agitation add chitosan, after 2 hours, centrifugalize, obtains genistein targeted chitosan nanoparticle; When feeding intake, described two citric acid monohydrate trisodiums, sodium hydroxide, green vitriol, sodium tripolyphosphate, chitosan, genistein, PEG400 and deionized water account for 0.20 ~ 0.36%, 0.3 ~ 0.7%, 0.7 ~ 1.1%, 0.2 ~ 0.6%, 1.6 ~ 2.0%, 4.0 ~ 8.0%, 20% ~ 25% and 62.5 ~ 68.5% of the gross mass that feeds intake respectively.
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| CN110384684B (en) * | 2019-08-26 | 2021-04-06 | 安徽农业大学 | Monocarboxyl chitosan/alkannin composite nano-particles and preparation method thereof |
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| 5-氟尿嘧啶磁性壳聚糖纳米微囊的制备及特性;周孙英等;《海峡药学》;20091231;第21卷(第7期);第35-38页 * |
| 三羟基异黄酮壳聚糖纳米体的制备及其体内吸收、抗氧化研究;谢玄;《中国优秀硕士学位论文全文数据库工程科技I辑》;20130615(第6期);第12页 * |
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