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A brain tumor targeted drug delivery system and its preparation method

A drug delivery system and brain tumor technology, applied in antineoplastic drugs, drug combinations, emulsion delivery, etc., can solve brain diseases such as epilepsy and schizophrenia, which are difficult to achieve effective treatment, lack of tumor tissue selectivity, and dose dependence Acute toxicity and other problems, to achieve the effect of improving the efficiency of brain entry, good solubilization effect, uptake and transport rate

Active Publication Date: 2017-10-17
黄山市屯溪区昱城产业投资控股有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, like other cytotoxic antitumor drugs, this type of drug lacks selectivity to tumor tissue, and has serious dose-dependent acute toxicity. Long-term use can cause dose-dependent irreversible cardiomyopathy, thus causing severe cardiotoxicity. and liver damage, at the same time, due to the existence of multidrug resistance, the clinical application is limited
[0003] The blood-brain barrier (BBB) ​​is a special physiological barrier between the brain and the blood, which is composed of brain capillary endothelial cells, intercellular tight junctions, astrocytes, and basement membrane. The dense structure restricts the entry of more than 95% of small molecule drugs and almost all macromolecular drugs, making it difficult for drugs to reach an effective therapeutic concentration in the brain, resulting in brain diseases such as brain tumors, chronic pain, epilepsy, schizophrenia and stroke difficult to achieve effective treatment
Therefore, the current clinical treatment of brain diseases mainly uses brain implants, intracerebroventricular injections and intracerebral injections, which bring great pain to patients.

Method used

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  • A brain tumor targeted drug delivery system and its preparation method
  • A brain tumor targeted drug delivery system and its preparation method
  • A brain tumor targeted drug delivery system and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Dissolve doxorubicin in absolute ethanol, dissolve glucose-modified amphiphilic chitosan derivatives, that is, the drug delivery carrier, in water, and slowly add the doxorubicin solution into the drug delivery carrier solution under rapid stirring. After the solution was mixed, ultrasonicated for 0.5h, ultrasonic power 360w, ultrasonic frequency 28KHz, deionized water dialysis, 0.22μm microporous membrane filtration to remove unencapsulated doxorubicin, and glucose-modified brain tumor-targeted nanomicelle drug delivery was obtained system.

[0051] The concentration of the doxorubicin in absolute ethanol is 10 mg / mL; the concentration of the delivery carrier in water is 15 mg / mL; the weight ratio of the doxorubicin to the delivery carrier is 1:5;

[0052] The weight ratio of doxorubicin to the drug delivery carrier in the prepared drug delivery system is 1:6;

[0053] The drug delivery carrier is synthesized by the following method:

[0054] Dissolve chitosan in 1% ...

Embodiment 2

[0068] Dissolve doxorubicin in dimethyl sulfoxide, dissolve glucose-modified amphiphilic chitosan derivatives, that is, the delivery carrier, in water, slowly add the doxorubicin solution into the delivery carrier solution under rapid stirring, and the two After the two solutions were mixed, sonicate for 0.25h, ultrasonic power 250w, ultrasonic frequency 30KHz, deionized water dialysis, 0.22μm microporous membrane filter to remove unencapsulated doxorubicin, and the glucose-modified brain tumor-targeted nano-micelle delivery was obtained. medicine system.

[0069] The concentration of the doxorubicin in dimethyl sulfoxide is 8 mg / mL; the concentration of the delivery carrier in water is 20 mg / mL; the weight ratio of the doxorubicin to the delivery carrier is 1:7;

[0070] The weight ratio of the drug to the drug delivery carrier in the prepared drug delivery system is 1:8;

[0071] The drug delivery carrier is synthesized by the following method:

[0072] Disperse chitosan i...

Embodiment 3

[0086] Dissolve gambogic acid in dichloromethane, dissolve glucose-modified amphiphilic chitosan derivatives, that is, the delivery carrier, in water, and slowly add the gambogic acid solution into the drug delivery carrier solution under rapid stirring. After the solution was mixed, ultrasonicated for 0.3h, ultrasonic power 400w, ultrasonic frequency 25KHz, deionized water dialysis, 0.22μm microporous membrane filtration to remove unencapsulated gambogic acid, and the glucose-modified brain tumor-targeted nanomicelle drug delivery was obtained system.

[0087] The concentration of the gambogic acid in dichloromethane is 20mg / mL; the concentration of the delivery carrier in water is 35mg / mL; the weight ratio of the gambogic acid to the delivery carrier is 1:6;

[0088] The weight ratio of the drug to the drug delivery carrier in the prepared drug delivery system is 1:7;

[0089] The drug delivery carrier is synthesized by the following method:

[0090] Disperse chitosan in m...

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Abstract

The invention relates to a brain tumor targeted drug delivery system and a preparation method thereof. The brain tumor targeted drug delivery system includes a mediator molecule, a basic carrier and a drug, the mediator molecule is glucose, and the basic carrier is an amphiphilic shell Glycan derivatives, mediator molecules and basic carriers are covalently combined to form drug delivery carriers, and the drug delivery carriers form nanomicelles to entrap drugs. The drug delivery system can significantly increase the accumulation of hydrophobic anti-tumor drugs in the brain and the efficiency of entering the brain, while reducing the damage of drugs to other normal tissues.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a brain tumor targeted drug delivery system and a preparation method thereof. Background technique [0002] Anthracycline antineoplastic drugs are an important class of antineoplastic drugs commonly used in clinical practice. In their structure, there are not only fat-soluble anthraquinone ring ligands and water-soluble eunuchamine, but also acidic phenolic hydroxyl groups and basic amino groups. It enters tumor cells through the cell membrane and acts on DNA to achieve the purpose of anti-tumor. It has a wide anti-tumor spectrum and good curative effect. It is widely used in clinical treatment of various cancers, such as lung cancer, leukemia, breast cancer, liver cancer, brain cancer and others. solid tumors. However, like other cytotoxic antitumor drugs, this type of drug lacks selectivity to tumor tissue, and has serious dose-dependent acute toxicity. L...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/10A61K47/36A61P35/00
Inventor 牛江秀史建俊郑祖彪柯仲成程子洋李伟伟狄蕊
Owner 黄山市屯溪区昱城产业投资控股有限公司
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