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Application of 23-HBA for preparing drug to reduce cardiotoxicity caused by adriamycin

A technology for cardiotoxicity and doxorubicin, applied in drug combinations, anti-toxins, pharmaceutical formulations, etc., can solve problems such as aggravating the bone marrow suppression effect of doxorubicin and reducing the anticancer effect of doxorubicin

Inactive Publication Date: 2012-01-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has been reported in the literature that this drug may reduce the anticancer effect of doxorubicin and aggravate the inhibitory effect of doxorubicin on bone marrow (Nat Clin Pract Oncol, 2004; 1(1): 16-17)

Method used

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  • Application of 23-HBA for preparing drug to reduce cardiotoxicity caused by adriamycin
  • Application of 23-HBA for preparing drug to reduce cardiotoxicity caused by adriamycin
  • Application of 23-HBA for preparing drug to reduce cardiotoxicity caused by adriamycin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Example 1: Histopathological examination of tumor mouse heart tissue

[0012] Experimental Materials:

[0013] Human breast cancer cell MCF-7 / ADR was provided by Tianjin Institute of Blood Diseases at 37°C, 5% CO 2 Under conventional conditions, the medium was RPMI-1640 (Gibco) containing 10% calf serum (PAA). Female SCID mice aged 4-6 weeks were purchased from the Experimental Animal Center of the Academy of Military Medical Sciences, and the animal feeding and all experiments were completed in the SPF mouse breeding room of the Institute of Pharmacology, Jiangsu Provincial Hospital of Traditional Chinese Medicine. Fresh human breast tissue was obtained from normal subjects (20-40 years old) after mammoplasty, provided by the First Affiliated Hospital of Nanjing Medical University. 23-Hydroxybetulinic acid was provided by Professor Ye Wencai (Jinan University). After dissolving in DMSO, it was diluted with 0.5% CMC-Na to form a homogeneous suspension with a concentra...

Embodiment 2

[0021] Example 2: Detection of cardiac function in tumor mice

[0022] Experimental Materials:

[0023] Same as Example 1

[0024] experimental method:

[0025] The method for establishing the tumor mouse model and the administration regimen are the same as in Example 1.

[0026] After 3-4 weeks of administration, mice were anesthetized with avertin at a dose of 0.15ml / 10g body weight. After anesthesia, the mice were detected and recorded under the high-resolution small animal ultrasound imaging system (vevo770), and M-mode echocardiograms were recorded, and LVPW (left ventricular posterior wall thickness), LVID (left ventricular diastolic diameter), LVS (left ventricular systolic inner diameter), EF% (left ventricular ejection fraction), FS% (left ventricular short-axis contraction rate) and other cardiac function indicators.

[0027] Experimental results:

[0028] M-mode echocardiogram as figure 2 As shown, the quantitative results of left ventricular ejection fractio...

Embodiment 3

[0032] Example 3: Determination of Doxorubicin Concentration in Heart Tissue of Tumor Mice

[0033] Experimental Materials:

[0034] Same as Example 1

[0035] experimental method:

[0036] The method for establishing the tumor mouse model and the administration regimen are the same as in Example 1.

[0037]After the administration period, the tumor mice were sacrificed, and the heart tissue was washed with PBS and placed under the CRi in vivo imaging system for fluorescence imaging to detect the enrichment degree of doxorubicin in the myocardial tissue.

[0038] Take 200mg of myocardial tissue, add 1ml of ultrapure water, and homogenate. Take 80 μl of homogenate and add 30 μl of RIPA lysate for sonication, then add 30 μl of 10% perchloric acid, vibrate and centrifuge at high speed to measure the drug concentration of adriamycin in myocardium by HPLC-FLD.

[0039] Experimental results:

[0040] The effect of 23-hydroxybetulinic acid on the distribution of doxorubicin in t...

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Abstract

The invention relates to the field of natural drugs, in particular to the application of 23-hydroxybetulinic acid (23-HBA) for preparing a drug to reduce cardiotoxicity caused by adriamycin. When being combined with adriamycin, the 23-hydroxybetulinic acid can reduce the consistency of the adriamycin in heart tissues of tumor mice, reverse eardiotoxieity caused by the adriamycin and improve cardiac function, thereby being capable of being used as a myocardial protecting agent of the adriamycin as an antitumor drug.

Description

technical field [0001] The invention relates to the field of natural medicines, in particular to the application of 23-hydroxybetulinic acid (23-HBA) in the preparation of medicines for reducing cardiotoxicity caused by doxorubicin. Background technique [0002] Doxorubicin (adriamycin, ADR, or doxorubicin, DOX) is a classic anthraquinone antineoplastic drug, which acts on a variety of tumors by inhibiting the synthesis of RNA and DNA. Tumor cells of various growth cycles have a strong killing effect. Since the drug was used in the clinical treatment of cancer in 1970, it is considered to be an efficient and broad-spectrum anticancer drug for the treatment of solid tumors, especially for leukemia, lymphoma, breast cancer, etc. The treatment effect is remarkable. However, Lefrak reported the cardiotoxicity caused by doxorubicin for the first time in 1973 (Cancer, 1973; 32(2):302-14). Afterwards, in the course of long-term clinical use, it was further found that doxorubicin c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/56A61P39/02A61P9/00
Inventor 王广基郝刚周芳吴晓兰郑媛婷叶文才朱萱萱阿基业张经纬刘林生张筱璇周颖孙渊罗丹季玮
Owner CHINA PHARM UNIV
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