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Placenta targeted delivery system and preparation method and application thereof

A delivery system and targeting technology, applied in the field of medicine, can solve the problems of poor placental tissue specificity, achieve good targeting, improve diagnosis, and ensure the effect of dosing concentration

Pending Publication Date: 2019-04-05
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, SonoVue, a lipid microbubble contrast agent, is commonly used clinically, but clinical practice has found that its specificity for detecting placental tissue is not strong, and most of the microbubble particle sizes are concentrated in the range of 2-10 μm.

Method used

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  • Placenta targeted delivery system and preparation method and application thereof
  • Placenta targeted delivery system and preparation method and application thereof
  • Placenta targeted delivery system and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] A preparation method of a placenta-targeted delivery system, comprising the following steps:

[0085] (1) Dissolve polylactic acid-glycolic acid copolymer (PLGA, the molecular weight is 15000, and the copolymerization ratio of monomeric lactic acid and glycolic acid is 50:50) in acetonitrile to obtain an acetonitrile solution of PLGA, the concentration of PLGA is 2mg / mL ;

[0086] (2) 90 μg of soybean lecithin, 210 μg of DSPE-PEG-COOH (the molecular weight of PEG is 2000), and 750 μg of insulin growth factor 2 were dissolved in 3 mL of 4% ethanol to obtain the first mixed solution;

[0087] (3) Add the acetonitrile solution of 1 mL of PLGA dropwise to the first mixed solution above at a speed of 0.3 mL / min to obtain the second mixed solution;

[0088] Put the above-mentioned second mixed solution in an amount of 3 mL / bottle into a sealed 5 mL vial, pass perfluoropropane into the vial, remove the air in the vial, and shake mechanically for 2 minutes to obtain a drug-loa...

Embodiment 2

[0094] A preparation method of a placenta-targeted delivery system, comprising the following steps:

[0095] (1) 2mg of polylactic acid-glycolic acid copolymer (PLGA, molecular weight 15000, copolymerization ratio of monomeric lactic acid and glycolic acid is 50:50) and 250μg of liquid ultrasound contrast agent - perfluorooctyl ammonium bromide (PFOB ) was dissolved in 1mL of dichloromethane to obtain a hydrophobic polymer solution;

[0096] (2) 40 μg of egg yolk lecithin, 100 μg of DSPE-PEG-NH 2 (The molecular weight of PEG is 3000), 250 μg of indomethacin was dissolved in 3 mL of acetone aqueous solution with a volume fraction of 4%, to obtain the first mixed solution;

[0097] (3) Add 1 mL of the above-mentioned hydrophobic polymer solution dropwise to the above-mentioned first mixed solution at a rate of 0.4 mL / min to obtain a drug-loaded suspension solution;

[0098] The above-mentioned drug-loaded suspension solution was ultrasonically treated at a frequency of 20 kHz ...

Embodiment 3

[0103] A preparation method of a placenta-targeted delivery system, comprising the following steps:

[0104] (1) Dissolve polylactic acid-glycolic acid copolymer (PLGA, the molecular weight is 15000, and the copolymerization ratio of monomer lactic acid and glycolic acid is 50:50) in acetone to obtain an acetone solution of PLGA; wherein, the concentration of PLGA is 2 mg / mL;

[0105] (2) 800 μg egg yolk lecithin, 1600 μg DSPE-PEG-NH 2 (The molecular weight of PEG is 3000), 3000 μg of relaxin peptide was dissolved in 3 mL of 4% ethanol to obtain the first mixed solution;

[0106] (3) Add the acetone solution of 1 mL of PLGA dropwise to the above-mentioned first mixed solution at a speed of 0.5 mL / min to obtain the second mixed solution;

[0107] The above-mentioned second mixed solution is packed in the sealed 5mL vial with the amount of 3mL / bottle, and the perfluoropropane / nitrogen mixed gas (flow ratio is 1:1) is passed into the vial, and the air in the vial is taken out....

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Abstract

The invention provides a placenta targeted delivery system. The placenta targeted delivery system comprises a hydrophobic core, a monolayer lipid molecular layer wrapping the hydrophobic core and a hydrophilic shell. The hydrophobic core comprises a hydrophobic polymer and a targeted delivery object loaded by the hydrophobic polymer, and the targeted delivery object includes at least one of a pregnancy drug and an ultrasound contrast agent. The hydrophilic shell is an amphiphilic macromolecular compound grafted with a polypeptide of targeted placenta-like chondroitin sulfate A, the hydrophobicend of the amphiphilic macromolecular compound is interspersed in the monolayer lipid molecular layer, and the hydrophilic end of the amphiphilic macromolecular compound is linked to the polypeptidethrough an amido bond. The polypeptide is exposed outside the monolayer lipid molecular layer, wherein the amino acid sequence of the polypeptide is selected from one or more of amino acid sequences shown in SEQ ID NO: 1-SEQ ID NO: 3. The invention further provides a preparation method of the placenta targeted delivery system and application of the placenta targeted delivery system to diagnosis and treatment of a pregnancy disorder caused by the placenta.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to a placenta-targeted delivery system and its preparation method and application. Background technique [0002] Pregnancy refers to the physiological process from conception to childbirth, and pregnancy diseases refer to pregnancy-related diseases that occur during this physiological period, which seriously affect the health of pregnant women and the normal development of the fetus, such as fetal intrauterine growth retardation, gestational diabetes and premature birth Wait. The incidence of pregnancy diseases is high, but currently there are no effective means of prevention, early detection and treatment for pregnancy diseases. Studies have shown that pregnancy disorders are mainly caused by abnormal placental development. [0003] Although ultrasonography has the advantages of simple operation, safety and efficiency, non-invasive and radiation-free, real-time detection, and l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K45/00A61P15/00A61P15/06A61K49/22
CPCA61K45/00A61K47/34A61K47/42A61K49/223A61K9/1273
Inventor 范秀军张保珍韩金雨肖天霞张键
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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