WO2014090168A1 - Docétaxel d'échelle nanométrique et son procédé de préparation - Google Patents

Docétaxel d'échelle nanométrique et son procédé de préparation Download PDF

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Publication number
WO2014090168A1
WO2014090168A1 PCT/CN2013/089174 CN2013089174W WO2014090168A1 WO 2014090168 A1 WO2014090168 A1 WO 2014090168A1 CN 2013089174 W CN2013089174 W CN 2013089174W WO 2014090168 A1 WO2014090168 A1 WO 2014090168A1
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docetaxel
nano
sized
silica aerogel
tumor
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PCT/CN2013/089174
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English (en)
Chinese (zh)
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张旭旭
张志安
武超
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清华大学深圳研究生院
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Publication of WO2014090168A1 publication Critical patent/WO2014090168A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0031—Rectum, anus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Definitions

  • the present invention relates to an antitumor drug docetaxel, and more particularly to a nanoscale docetaxel and a process for the preparation thereof.
  • Docetaxel is a taxane compound which can be obtained by semi-synthesis of a non-cytotoxic precursor compound 10-deacetyl gibberellin II extracted from Taxus chinensis. It was approved by the US FDA in 1998. Currently the most effective taxane antitumor drugs are used clinically. The action mechanism of docetaxel is similar to that of paclitaxel, but the antitumor activity is 1.3-12 times that of paclitaxel, and it has a good effect on cancers such as breast cancer, pancreatic cancer, and non-small cell lung cancer.
  • the current clinical use mainly includes frozen powder injection and water injection.
  • the surfactants Tween 80 and ethanol are added to the currently marketed docetaxel injection.
  • the toxic side effects of this injection are serious, and these excipients added for the dissolution are the main factors causing toxic side effects.
  • anti-tumor drugs represented by docetaxel are coping with a rapidly progressing malignant disease, unlike the use of common drugs, they need to be administered in large doses under the conditions of human body tolerability (MTD), and anti-tumor drugs. While killing tumor cells, the effect on normal cells is almost inevitable, so the serious side effects and poor safety are the general characteristics of such drugs.
  • Nanoparticles also known as nanoparticles (including nanospheres and nanoquinones), are nanoscale colloidal drug delivery systems. Drug-loaded nanosystems should meet the following criteria: Can be aggregated and maintained at designated sites, with appropriate release rates, properties Stable and easy to use. The ideal nanoparticle should have a higher drug loading and encapsulation efficiency, suitable preparation conditions and purification methods.
  • the carrier can be biodegradable, low toxicity or non-toxic, and has appropriate particle shape and particle size, and long Body cycle time.
  • a first object of the present invention is to provide a novel nano-sized polyene paclitaxel granule.
  • the present invention provides a nano-sized docetaxel granule characterized by: a silica aerogel as a carrier of docetaxel, a porosity of the silica aerogel
  • the form in the pores of the silica aerogel forms docetaxel particles having a diameter of less than 100 nm.
  • the mass ratio of the docetaxel to the silica aerogel is 1:0.5-20.
  • a pharmaceutically acceptable oral preparation can be prepared from the above-described nano-sized docetaxel granules.
  • the oral preparation is a tablet, a pill, a powder, a capsule, a granule or a suspension.
  • a pharmaceutically acceptable injection or suppository can be prepared from the above nano-sized docetaxel granules.
  • Another object of the present invention is to provide a process for the preparation of the above-described nano-sized docetaxel granules, characterized in that the method comprises the steps of:
  • the silica aerogel described in the step (2) is hydrophobic, it is subjected to heat treatment at 300 to 1000 ° C before the addition of the ethanol solution to cause the alkyl group on the surface to disappear and be hydrophilic.
  • the ratio of the mass of the docetaxel to the volume of the anhydrous ethanol is 1:5 to 200.
  • the drying in the step (3) is natural drying, oven drying or freeze drying.
  • the amount of purified water added in the step (4) is 20 to 200 ml/g of docetaxel.
  • the drying in the step (6) is spray drying.
  • the present invention successfully prepared nano-scale docetaxel for the first time using silica aerogel as a carrier.
  • the nano-sized docetaxel has a diameter below 100 nm, reaching material science.
  • the nanoscale of the category is the true nanoscale docetaxel.
  • particles smaller than ⁇ are called nanoparticles, it is preferred to develop particles with a particle size of less than 100 nm because these particles exhibit some unique physical properties and thus exhibit potentially different and useful biological properties. .
  • the optimal particle size of the drug particles that can enter the blood circulation and be absorbed by the body is 10-100 nm. Therefore, the nano-sized docetaxel of the present invention has a qualitative leap in bioavailability.
  • the drug loading of the nano-sized docetaxel granules of the invention can reach more than 90%, which is unmatched by the existing liposome nanoparticles and polymer nanoparticles, and the drug loading amount can be matched with the nanocrystalline drug. Suspensions are comparable, but the production method is more simple and cheaper.
  • docetaxel is loaded into numerous nano-scale cavities of silica aerogel to form an independent "nano-dispersion" which does not agglomerate, and the structure is extremely stable, directly It has solved the international problem of preparation of micro-nano drug research because agglomeration cannot be made into medicine, and difficult-to-dissolve drugs are difficult to improve bioavailability.
  • the nano-sized docetaxel is an efficient, low-toxic, economical, "targeting function" anti-tumor drug, which solves the problem of dissolution and absorption of docetaxel by a new physical mechanism of "nanodispersion",
  • the full effect of the drug and the unprecedented increase in oral bioavailability have realized the targeted aggregation from systemic toxicity to the tumor site in the treatment of docetaxel antitumor drugs, and solved many problems that have been solved internationally and domestically for decades.
  • the bioavailability of docetaxel injection is low, the toxic side effects are large, the curative effect is poor, and the treatment cost is high.
  • this low toxicity characteristic comes from two aspects: First, the use of the harmful solvent Tween 80 in the injection dosage form is avoided, so that the bioavailability of the drug is increased and the toxicity is greatly reduced; The targeting effect of the systemic action of the docetaxel drug on the tumor site reduces systemic toxicity.
  • nano-level docetaxel provided by the invention realizes a brand new mouth with nano-uptake as the main absorption mode
  • the mechanism of action, and the new structure of "nano-solid dispersion”, the solubility of docetaxel is greatly increased, and it can be absorbed orally. It breaks through the international exclusion zone where docetaxel can not be absorbed orally.
  • oral replacement injection is directly realized at the material level. bioavailability. Because the oral dosage form does not require the use of cosolvent Tween
  • the precursor of the silica aerogel used as a carrier in the nano-level docetaxel of the present invention is inexpensive, readily available, and has been widely used in medicines and foods, and has been used for many years by national and international standards.
  • the silicone-based edible edible material which is also one of the excipients described in the Handbook of Pharmaceutical Excipients, is therefore reliable in the safety of the nano-sized docetaxel of the present invention.
  • the antitumor effect of the nano-sized docetaxel of the present invention is demonstrated below by an anti-tumor mouse experiment : the silica aerogels used in the experiments are each selected from silica aerogels having the following properties: Porosity 95 ⁇ 99%, pore size is 10 ⁇ 50nm, specific surface area is 200 ⁇ 1000m 2 /g, density is 3 ⁇ 300kg / m 3 , and the colloidal particle diameter of the network is l ⁇ 50nm.
  • Experimental nano-polyene paclitaxel is the dry powder obtained in Example 1 of the present invention.
  • mice were 4-6 mm, grouped according to 5/group.
  • dosing regimen the dosing regimen; blank group (only one, for each group reference), Injection of docetaxel group, trade name Taxotere (UK AVENTIS Pharma Dagenham), once daily, intraperitoneal injection; docetaxel raw material group, oral gavage, once a day; nano-polyene paclitaxel group, Oral gavage, 1 time a day.
  • VIR tumor inhibition rate
  • VIR ( 1 RTV treatment group) xl00%
  • the anti-tumor drugs should be used as large as possible in order to quickly kill the characteristics of cancer cells.
  • the dosage is designed according to the maximum tolerance (MTD), and the therapeutic dose of human metastatic tumor-bearing mice is anti-tumor drugs.
  • MTD maximum tolerance
  • Preclinical studies examine the most direct method of drug safety;
  • Docetaxel injection Zhejiang Wanma Pharmaceutical Co., Ltd., batch number: H20051044, specifications: 20mg/0.5ml. Dilute with 2 ml of the diluted solution before use, and then dilute to the desired concentration with physiological saline.
  • Nano-polyene paclitaxel The dry powder obtained in the first embodiment of the present invention is now called ready-to-use. After being mixed with an analytical balance, distilled water is added, and ultrasonically dissolved into a suspension, and then administered by intragastric administration.
  • Source, germline, strain BALB/c mice, provided by the Experimental Animal Center of the Chinese Academy of Military Medical Sciences.
  • Gender Male Number of animals: 6 in each group, a total of 30.
  • the cultured human lung cancer A549 suspension was collected at a concentration of 1 ⁇ 10 7 cells/ml, and each of 0.1 ml was inoculated subcutaneously in the right axilla of the mouse.
  • the diameter of the transplanted tumor was measured with a vernier caliper. After 11 days of inoculation, the animals were randomly divided into groups of 6 animals each growing to 50-75 mm 3 . At the same time, the rats in each group were started to be administered. The dosing regimen and the group were shown in the dosing regimen. The antitumor effect of the test samples was dynamically observed using the method of measuring the tumor diameter. After the end of the administration, the mice were sacrificed and the tumor pieces were surgically removed and weighed.
  • the formula for calculating tumor volume (TV) is:
  • TV l/2 ab 2
  • a and b represent the length and width, respectively.
  • V t V 0 V.
  • V t the tumor volume at each measurement.
  • Evaluation index of antitumor activity Relative tumor growth rate T/C (%), calculated as follows:
  • T/C (%) X 100 T RTV : treatment group RTV; C RTV : model group RTV C RTV
  • Tumor growth inhibition rate (%) Tumor growth inhibition rate (%), the calculation formula is as follows:
  • Model group mean tumor weight - mean tumor weight of the drug-administered group
  • Tumor growth inhibition rate ⁇ 100%
  • Model group mean tumor weight
  • Tumor volume RTV T/C Tumor volume RTV T/C model 3 control group 0.102+0.025 2.066+0.554 - 0.132+0.037 2.665+0.652 - commodity polyene-lOmg/kg 0.044 ⁇ 0.022 0.907+0.540 43.90% 0.055+0.024 1.113 Soil 0.559 41.75% Nanopolyene-50mg/kg 0.069 soil 0.025 1.348 ⁇ 0.360 65.26% 0.067 ⁇ 0.018 1.323+0.296 49.66% Nanopolyene-lOOmg/kg 0.067+0.030 1.348 soil 0.541 65.23% 0.077+0.037 1.545 soil 0.724 57.97% Nanopolyene-200mg/kg 0.063+0.025 1.181 ⁇ 0.481 57.14% 0.073+0.027 1.372+0.534 51.48%
  • Tumor volume RTV T/C Tumor volume RTV T/C model control group 0.180+0.035 3.643+0.609 - 0.232 soil 0.061 4.672 ⁇ 1.045 - commodity multi-women-10mg/kg 0.058+0.020 1.181 ⁇ 0.539 32.61% 0.063+0.019 1.262+0.395 27.02% Nanopolyene-50mg/kg 0.084 ⁇ 0.027 1.660+0.449 45.56% 0.108 ⁇ 0.051 2.125+0.958 45.49% Nanopolyene-100mg/kg 0.085+0.033 1.713+0.646 47.02% 0.109 ⁇ 0.027 2.179+0.436 46.64% Nano Alkene-200mg/kg 0.091+0.030 1.704 ⁇ 0.615 46.77% 0.113+0.040 2.130 soil 0.860 45.60%
  • Figure 1 is an electron micrograph of a silica aerogel of the present invention
  • Figure 2 is an electron micrograph of a docetaxel bulk drug
  • Figure 3 is an electron micrograph of the nano-sized docetaxel of the present invention.
  • Figure 4 is a graph showing the relative tumor inhibition rate of human metastatic rat liver cancer BEL-7402 in an anti-tumor mouse experimental study
  • Figure 5 is a graph showing the relative tumor inhibition rate of human metastatic rat non-small cell lung cancer NCI-1299 in an anti-tumor mouse experimental study
  • Figure 6 is a graph showing the relative tumor inhibition rate of human metastatic mouse breast cancer MCF-7 in the results of an anti-tumor mouse experimental study. detailed description
  • silica aerogels used in the following examples are all selected from silica aerogels having the following characteristics: porosity of 95 to 99%, pore diameter of 10 to 50 nm, and specific surface area of 200 to 1000 m 2 /g.
  • the density of the colloidal particles of the network is 3 ⁇ 300kg / m 3 , and the diameter of the colloidal particles is 1 ⁇ 50nm.
  • nanoscale docetaxel of this example was prepared as follows:
  • Docetaxel bulk drug (Shanghai Zhongxi Dimensional Drug Co., Ltd.) lg, dissolved in anhydrous ethanol 20ml;
  • nanoscale docetaxel of this example was prepared as follows:
  • Docetaxel bulk drug (Shanghai Zhongxi Dimensional Drug Co., Ltd.) lg, dissolved in anhydrous ethanol 5ml;
  • Example 3 The nanoscale docetaxel of this example was prepared as follows:
  • nanoscale docetaxel of this example was prepared as follows:
  • Docetaxel bulk drug (Shanghai Zhongxi Dimensional Drug Co., Ltd.) lg, dissolved in 200 ml of absolute ethanol;
  • nanoscale docetaxel of this example was prepared as follows:
  • step 3 Add the solid after lyophilization in step 3 to the above ethanol solution of PEG-4000, ultrasonic emulsifier Emulsified for 3 min;
  • step 6 The emulsion of step 5 is dried in a thermostatic oven at 60 ° C for 12 hours;
  • nano-sized docetaxel granules obtained in Examples 1 to 5 were uniformly mixed with an appropriate amount of microcrystalline cellulose, starch and magnesium stearate, and then tableted by a tableting machine to obtain a nano-sized docetaxel tablet of the present invention.
  • nano-sized docetaxel granules obtained in Examples 1 to 5 were directly loaded into a hard gelatin shell to obtain a nano-sized docetaxel capsule of the present invention.
  • the nano-sized docetaxel granules obtained in Examples 1 to 5 were added to an aqueous solution, and the mixture was stirred to obtain a nano-sized docetaxel suspension of the present invention.
  • the suspension may be administered orally, or may be prepared as an injection according to the preparation standard of the injection.
  • nano-sized docetaxel granules obtained in Examples 1 to 5 and an appropriate amount of Witepsol were prepared by a hot melt method to obtain a nano-sized docetaxel suppository of the present invention.

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Abstract

L'invention concerne des particules de docétaxel d'échelle nanométrique et leur procédé de préparation. Les particules de docétaxel d'échelle nanométrique utilisent un aérogel de dioxyde de silicium comme vecteur du docétaxel. Le procédé de préparation est le suivant : en premier lieu, dissolution du docétaxel dans de l'éthanol anhydre, puis ajout de l'aérogel de dioxyde de silicium, séchage après adsorption complète, ajout d'eau purifiée, introduction dans une machine d'émulsification pour émulsification, homogénéisation dans un homogénéisateur haute pression, et séchage de l'homogénat obtenu pour obtenir les particules de docétaxel d'échelle nanométrique.
PCT/CN2013/089174 2012-12-13 2013-12-12 Docétaxel d'échelle nanométrique et son procédé de préparation WO2014090168A1 (fr)

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CN201210537237.4A CN102973490B (zh) 2012-12-13 2012-12-13 纳米级多烯紫杉醇及其制备方法
CN201210537237.4 2012-12-13

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CN102973490B (zh) * 2012-12-13 2014-09-17 清华大学深圳研究生院 纳米级多烯紫杉醇及其制备方法
CN103315978B (zh) * 2013-07-12 2014-12-03 上海市第八人民医院 多西紫杉醇干酏剂及其制备方法和应用
CN104337784B (zh) * 2013-08-02 2018-05-11 山东新时代药业有限公司 一种氢溴酸普拉格雷片剂及其制备方法
WO2017075777A1 (fr) * 2015-11-05 2017-05-11 清华大学深圳研究生院 Procédé pour préparer une préparation de pesticide nanométrique à l'aide d'aérogel de silice
CN113304271A (zh) * 2021-03-08 2021-08-27 哈尔滨商业大学 一种基于硅气凝胶的纳米载药系统的构建及评价方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1676125A (zh) * 2004-03-31 2005-10-05 张昊 含有紫杉碱类或难溶药物的纳米级乳剂
CN102973490A (zh) * 2012-12-13 2013-03-20 清华大学深圳研究生院 纳米级多烯紫杉醇及其制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19506141A1 (de) * 1995-02-22 1996-08-29 Hoechst Ag Verwendung von Aerogelen in der Pharmazie, in der Kosmetik und im Pflanzenschutz

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1676125A (zh) * 2004-03-31 2005-10-05 张昊 含有紫杉碱类或难溶药物的纳米级乳剂
CN102973490A (zh) * 2012-12-13 2013-03-20 清华大学深圳研究生院 纳米级多烯紫杉醇及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HU , YANCHEN ET AL.: "Recent Progress of Nano-porous Silica as Drug Carrier", JOURNAL OF SHENYANG PHARMACEUTICAL, vol. 27, no. 12, 2010, pages 933 - 967 *

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