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CN-121987575-A - Soxhlet Ma Lutai nano-particle preparation and preparation method thereof

CN121987575ACN 121987575 ACN121987575 ACN 121987575ACN-121987575-A

Abstract

The invention relates to a cable Ma Lutai nanoparticle preparation, and relates to the field of pharmaceutical preparations. A rope Ma Lutai nanoparticle preparation, wherein the nanoparticle is used for encapsulating an active component rope Ma Lutai-carboxylated dextran-40 compound, and the rope Ma Lutai-carboxylated dextran-40 compound is obtained by blending rope Ma Lutai and carboxylated dextran-40 in an aqueous solvent. The nano preparation is used for preparing a rope Ma Lutai-pC-DEX 40 compound by means of electrostatic compression, so that the capacity of the rope Ma Lutai for tolerating adverse factors in the preparation forming process is improved, in addition, sml-pC-DEX40 is coated in nano particles by taking water-in-oil-in-water compound emulsion as a drug delivery system, and the oral delivery efficiency and bioavailability of the nano particle lifting rope Ma Lutai for loading the Sml-pC-DEX40 are obtained.

Inventors

  • GOU JINGXIN
  • TANG XING
  • HE HAIBING
  • ZHANG YU
  • YIN TIAN
  • GUO MINGBO

Assignees

  • 沈阳药科大学

Dates

Publication Date
20260508
Application Date
20260212

Claims (10)

  1. 1. A cable Ma Lutai nanoparticle preparation, which is characterized in that the nanoparticle is used for encapsulating an active component cable Ma Lutai-carboxylated dextran-40 compound, wherein the cable Ma Lutai-carboxylated dextran-40 compound is obtained by blending cable Ma Lutai and carboxylated dextran-40 in an aqueous solvent.
  2. 2. The cord Ma Lutai nanoparticle formulation according to claim 1, wherein the molar ratio of cord Ma Lutai to carboxylated dextran-40 is 1:20 to 10:1, preferably 1:5 to 2:1.
  3. 3. The rope Ma Lutai nanoparticle formulation of claim 1, wherein the aqueous solvent is water.
  4. 4. The cable Ma Lutai nanoparticle preparation according to claim 1, wherein the cable Ma Lutai-carboxylated dextran-40 complex is prepared by dispersing the cable Ma Lutai in an aqueous phase solvent under the condition of heating and stirring at 5-50 ℃, adding a stabilizer I, stirring uniformly at 25-40 ℃ to obtain a cable Ma Lutai solution, regulating the cable Ma Lutai solution to be acidic, dropwise adding the carboxylated dextran-40 solution, stirring uniformly to obtain a cable Ma Lutai-carboxylated dextran-40 complex solution, wherein the stabilizer I is at least one of poloxamer 188, tween 80 and PEG6000, and the concentration is 0.5-50 mg/ml.
  5. 5. The rope Ma Lutai nanoparticle formulation of claim 1, wherein the rope Ma Lutai nanoparticle formulation encapsulates the rope Ma Lutai-carboxylated dextran-40 complex with a medium chain triglyceride.
  6. 6. The rope Ma Lutai nanoparticle formulation of claim 1, wherein the nanoparticle formulation is an oral formulation.
  7. 7. A method for preparing a cable Ma Lutai nanoparticle preparation according to any one of claims 1 to 6, characterized in that the preparation method is a multiple emulsion method, Taking a rope Ma Lutai-pC-DEX 40 complex solution as an internal water phase; the medium chain triglyceride containing a stabilizer II is used as an oil phase, wherein the stabilizer II is one or more of polyglycerol ricinoleate (PGPR), span 80, glycerol monooleate and glycerol monostearate; An aqueous solution of a stabilizer III with the concentration of 10mg/ml to 50mg/ml is taken as an external aqueous phase, wherein the stabilizer III is one or more of poloxamer 188, tween 80 and Briji.
  8. 8. The method of claim 7, wherein the inner aqueous phase and the oil phase are mixed at a volume ratio of 0.1-0.4:1, the colostrum is prepared by ultrasonic emulsification, the colostrum is dried to remove water to obtain S/O-type colostrum, the obtained S/O-type colostrum is mixed with the outer aqueous phase at a volume ratio of 1:2-5, the compound emulsion is prepared by ultrasonic emulsification, and the compound emulsion is freeze-dried.
  9. 9. The method according to claim 7, wherein the stabilizer II is PGPR, span 80 or a combination of PGPR and span 80 in a mass ratio of 10:1 in the oil phase, When the stabilizer II is PGPR, the concentration of the PGPR is 20mg/ml to 500mg/ml, preferably 40mg/ml to 400mg/ml, further preferably 60mg/ml to 300mg/ml, and most preferably 80mg/ml to 200mg/ml; when the stabilizer II is PGPR and span 80, the concentration of the span 80 is 5mg/ml to 15mg/ml, preferably 5mg/ml to 10mg/ml.
  10. 10. The method of claim 7, wherein the external aqueous phase, When the stabilizer III is poloxamer 188, the concentration of the poloxamer is 18810 mg/ml-40 mg/ml, preferably 20 mg/ml-40 mg/ml, and further preferably 30 mg/ml-40 mg/ml; When the stabilizer III is poloxamer 188 and Briji, the concentration of Briji is 5 mg/ml-15 mg/ml, preferably 5-10 mg/ml, the concentration of poloxamer 188 is 18810 mg/ml-40 mg/ml, preferably 20 mg/ml-40 mg/ml, and more preferably 30 mg/ml-40 mg/ml.

Description

Soxhlet Ma Lutai nano-particle preparation and preparation method thereof Technical Field The invention relates to a cable Ma Lutai nanoparticle preparation, and relates to the field of pharmaceutical preparations. Background Diabetes mainly includes type I diabetes (insulin hyposecretion) and type II diabetes (insulin resistance). In modern society life, population aging is aggravated, living standard of people is improved, the proportion of obese people is increased, the number of diabetics worldwide is increased year by year, wherein the proportion of type II diabetics exceeds 90%. The exact pathogenesis of type II diabetes is still unclear, mainly the secretion of insulin is reduced or the human body can not effectively utilize the insulin, the regulating capacity of the human body on blood sugar is reduced, the blood sugar is maintained at a higher level for a long time, and the blood sugar causes changes of blood vessels, nerves and the like, so that complications of heart, kidney, eyes and the like are caused, and serious patients can become disabled or even fatal. Cord Ma Lutai (Sml) is a novel long acting glucagon-like peptide-1 (GLP-1) analog developed based on liraglutide, with structural modification of the liraglutide to give cord Ma Lutai a longer half-life. Known pharmacological actions of cable Ma Lutai include glucose concentration dependence promoting insulin secretion, inhibiting glucagon secretion, decreasing islet beta cell apoptosis and increasing beta cell number, promoting urination and diuresis, reducing appetite in patients, delaying gastric emptying, reducing feeding, improving fasting and postprandial blood glucose levels in type II diabetics, and the like. The cable Ma Lutai is clinically applied to two dosage forms, namely injection and oral tablet at present, and the cable Ma Lutai subcutaneous injection which is marketed in the United states in 2017 and used for controlling the blood sugar of adult type 2 diabetics has the trade name of Ozempic. Cord Ma Lutai injection for chronic weight management of obese or overweight adults is formally obtained in 2021, has the trade name of Wegovy, is marketed in the United states in 2019 by taking exercise and diet control as auxiliary means, and is a global first oral GLP-1 analog hypoglycemic agent for controlling blood sugar of type 2 diabetics, namely a cord Ma Lutai oral tablet, and has the trade name of Rybelsus. The existing clinical administration modes of the cable Ma Lutai comprise injection administration and oral administration, the injection is required to be subcutaneously injected, the compliance of patients is poor, the patients need to be fasting before and after tablet administration, the compliance of the patients is poor, the oral bioavailability is low, the burden of the patients is only 0.5-1%, the economic pressure is high, and the medicine waste is serious. Therefore, in order to expand the clinical application of the cable Ma Lutai preparation, development of a cable Ma Lutai oral preparation with long administration period, more convenient administration, strong patient medication compliance, weak burst effect and high bioavailability is urgently needed. Disclosure of Invention The invention aims to provide an oral nanoparticle preparation with strong patient compliance and high bioavailability and a preparation method thereof, wherein the cable Ma Lutai nanoparticle is prepared by coating cable Ma Lutai-carboxylated dextran-40 (abbreviated as cable Ma Lutai-pC-DEX 40, abbreviated as Sml-pC-DEX 40) in Nanoparticles (NPs) and utilizing the good sustained and controlled release medicine of the NPs, enzyme stability, gastrointestinal epithelial permeability and low toxicity, so as to solve the problems of rapid burst release, long drug release delay period and large steady-state blood concentration fluctuation of the existing product. A rope Ma Lutai nanoparticle preparation, wherein the nanoparticle is used for encapsulating an active component rope Ma Lutai-carboxylated dextran-40 compound, and the rope Ma Lutai-carboxylated dextran-40 compound is obtained by blending rope Ma Lutai and carboxylated dextran-40 in an aqueous solvent. In the above technical scheme, the molar ratio of the cable Ma Lutai to the carboxylated dextran-40 is 1:20-10:1, preferably 1:5-2:1. In the above technical solution, preferably, the aqueous phase solvent is water. Further, the concentration of the cord Ma Lutai in the aqueous phase solvent is 2.5 mg/ml to 10 mg/ml. The carboxylated dextran-40 (pC-DEX 40) is prepared by using sodium periodate as an oxidant to prepare aldehyde DEX, controlling the hydroformylation proportion through the feed ratio, and then further oxidizing aldehyde groups into carboxyl groups by adopting potassium permanganate to obtain the carboxylated dextran-40. In the technical scheme, the cable Ma Lutai-carboxylated dextran-40 compound is prepared according to the following method: The cable Ma Lutai-carboxylate