Protein nanometer granules wrapped with taxane medicaments and preparation method for nanometer granules

A taxane and nanoparticle technology, which is applied in the field of protein nanoparticle preparation, can solve the problems of loss of curative effect, unfavorable tumor targeting, easy failure of drugs, etc., and achieves improved convenience and safety of medication, good in vitro and in vivo Effects of stability, good pharmacodynamic properties

Active Publication Date: 2014-05-21
CHINA PHARM UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] However, through the direct chemical coupling of HSA and drugs, there are the following problems: 1) The range of drug selection is narrow: the drug needs to have a certain reactive group, and the drug is prone to failure during the chemical coupling process; 2) The curative effect is uncertain Performance: The ease of breaking the chemical bond between the drug and HSA determines the efficacy of the drug. If it breaks too fast, HSA will lose its advantage as a carrier material. If it breaks too slowly, the drug will not be able to exert its curative effect; 3) High cost and low drug loading : In the coupling process, the drug dosage is much larger than HSA, and the coupling drug amount is limited, resulting in high preparation costs (especially the high price of anti-tumor drug raw materials) and low drug loading in the system.
Because HSA is highly water-soluble, the prepared nanoparticles need to be cured, that is, add a chemical cross-linking agent to cross-link albumin or heat to denature the protein. The former is more toxic, and it is easy for the drug to cross-link at the same time and lose its efficacy , the latter is not suitable for the loading of temperature-sensitive drugs; in addition, some people think that the method of cross-linking or heat curing will reduce the hydrophilicity of the surface of HSA nanoparticles, thereby reducing the circulation time in the blood, which is not conducive to tumor targeting;
[0020] 3) The post-processing process is complex
Due to the use of toxic additives such as surfactants, oils, and chemical cross-linking agents in the process, a large amount of organic solvents are required to clean and purify, but a small amount of residue will still bring hidden dangers to drug safety; high-speed centrifugation (16000-20000g) is used to collect nano Particles, not only have high requirements for instruments, but also have poor redispersibility in water;
[0021] 4) The scope of applicable drugs is small
But the precipitation of nanoparticle occurs very soon, it is more difficult when carrying out described microporous membrane filtration (1.2um, 0.8um, 0.45um and 0.22um), and the situation of clogging occurs easily in filter membrane, and its freeze-dried product is in The nanosuspension formed after reconstitution in physiological solution is unstable, with macroscopic precipitation appearing within about 8 hours, which is completely different from the results claimed in the patent that the stability is greater than 24 hours

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Protein nanometer granules wrapped with taxane medicaments and preparation method for nanometer granules
  • Protein nanometer granules wrapped with taxane medicaments and preparation method for nanometer granules
  • Protein nanometer granules wrapped with taxane medicaments and preparation method for nanometer granules

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Example 1 Preparation of Paclitaxel Albumin Nanoparticles by Melting Method

[0081] Dissolve 500 mg of paclitaxel in 9.0 mL of ethanol. After 1200 mg of polyethylene glycol was heated and completely melted in an oil bath at 60°C, the paclitaxel solution was added thereto, and stirred by magnetic force until it was completely mixed evenly. After the ethanol was removed by rotary evaporation, it was rapidly cooled under vigorous stirring conditions. After vacuum drying overnight, the solid dispersion was added to 85 ml of human serum albumin aqueous solution (4.5% w / v, g / ml, the same below). The mixture was premixed by a high-speed disperser (XHF-1, Shanghai Jinda Biochemical Instrument Factory) for 1 minute to form a coarse milk, and then transferred to a high-pressure homogenizer (EmulsiFlex-05, Avestin, Canada). High pressure homogenization at 5000-30,000 psi 2 Under certain conditions, the emulsion is repeatedly circulated at least 5 times to obtain a suspension of...

Embodiment 2

[0083] Example 2 Preparation of paclitaxel albumin nanoparticles by melting-solvent evaporation method

[0084]Dissolve 300 mg of paclitaxel in 6.0 mL of ethanol. Dissolve 900 mg of polyethylene glycol in 1.5 ml of absolute ethanol, heat and completely melt in an oil bath at 45°C, add the paclitaxel solution into it, stir magnetically until it is completely mixed, and remove the ethanol by rotary evaporation, quickly under vigorous stirring conditions cool down. After drying under vacuum overnight, the solid dispersion was added to 65 ml of aqueous human serum albumin (4.5% w / v). The mixture was premixed by a high-speed disperser (XHF-1, Shanghai Jinda Biochemical Instrument Factory) for 1 minute to form a coarse milk, and then transferred to a high-pressure homogenizer (EmulsiFlex-05, Avestin, Canada). Emulsified at 5000-30,000 lbs / in 2 Carried out under the conditions of the above conditions, the emulsion was repeatedly circulated at least 6 times to obtain a protein nano...

Embodiment 3

[0086] Example 3 Preparation of Paclitaxel Albumin Nanoparticles Sterile Filterable Less than 200 Nanometers

[0087] Dissolve 500 mg of paclitaxel in 9.0 mL of ethanol. Dissolve 800 mg of polyethylene glycol in 1.5 ml of absolute ethanol, heat and completely melt in an oil bath at 45°C, add paclitaxel solution into it, stir magnetically until it is completely mixed evenly, and remove ethanol by rotary evaporation, rapidly under vigorous stirring conditions cool down. After drying under vacuum overnight, the solid dispersion was added to 97 ml of aqueous human serum albumin (4.5% w / v). The mixture was premixed by a high-speed disperser (XHF-1, Shanghai Jinda Biochemical Instrument Factory) for 1 minute to form a coarse milk, and then transferred to a high-pressure homogenizer (EmulsiFlex-05, Avestin, Canada). Emulsified at 10,000-40,000 lbs / in 2 Carried out under the conditions of the above conditions, the emulsion was repeatedly circulated at least 6 times to obtain a prot...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
particle sizeaaaaaaaaaa
particle sizeaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of pharmacy, and discloses protein nanometer granules wrapped with taxane medicaments and a preparation method for the nanometer granules. In a formula, the granules comprise the following substances in percentage by weight: 0.1 to 10 percent of taxane medicaments, 0.1 to 40 percent of water-soluble carrier material and 50 to 90 percent of protein substances. The method comprises the following steps of: preparing water-soluble carrier solid dispersion containing the taxane medicaments from the taxane medicaments and the water-soluble carrier material; adding the obtained solid dispersion into an aqueous medium containing the protein substances, mixing uniformly, and performing high-shear treatment on the mixture to obtain suspension of the protein nanometer granules wrapped with slightly-soluble medicaments; and further preparing required formulations. The protein nanometer granules have the advantages of large medicine-carrying quantity, uniform grain diameters, high stability and safety and the like; and by the method, toxic organic solvent residues are avoided, the safety of clinical administration is improved, and a process is simple, low in cost and high in operability.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a preparation method of protein nanoparticle encapsulating taxane drugs. Background technique [0002] Taxane drugs (such as paclitaxel, docetaxel, etc.) are one of the most effective anti-tumor drugs currently used clinically. Paclitaxel is a natural product isolated from the bark or needles of Taxus or its species discovered in the 1970s. Docetaxel is a semi-synthetic product, which was later discovered to be a class of anti-tumor agents with a special anti-tumor mechanism of action . [0003] The anti-tumor mechanism of taxane drugs is to promote microtubule polymerization and reduce the depolymerization speed of microtubules, so that the microtubules are in a stable non-functional state, thereby achieving the purpose of preventing tumor cell mitosis and proliferation. And preclinical studies have shown that compared with paclitaxel, docetaxel has stronger affinity for microtubules, lo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K47/42A61K31/337A61P35/00
Inventor 周建平霍美蓉崔蓓
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products