Application of miltipolone or pharmaceutically acceptable salts thereof in pharmacy

A pharmacy and drug technology, applied in the field of medicine and biology, can solve problems such as no "activity", "active" activity, and differences in sensitivity

Inactive Publication Date: 2011-11-09
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Those skilled in the art know that the treatment methods and drugs used for different cancers are often very different, because the gene level and epigenetic level of different cancers will be very different, and their sensitivity to the same drug may be different. There will be a big difference, even the difference between "with" activity and "without" activity; The sensitivity to the same drug will also vary greatly. Although the existing public documents have introduced the cytotoxicity of Miltipolone to B16F10 (murine melanoma) and HCT-116 (human colon cancer), but It cannot therefore be concluded that Miltipolone is useful for the treatment of other human cancers based on current knowledge or similar trials

Method used

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  • Application of miltipolone or pharmaceutically acceptable salts thereof in pharmacy
  • Application of miltipolone or pharmaceutically acceptable salts thereof in pharmacy
  • Application of miltipolone or pharmaceutically acceptable salts thereof in pharmacy

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Experimental program
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Effect test

Embodiment 1

[0020] The present invention finds the cycloheptatrienone compound Miltipolone with good and extensive anti-tumor cell activity (see figure 1 ).

[0021] Salvia miltiorrhiza or other traditional Chinese medicines such as Yunnan salvia miltiorrhiza and Tibetan salvia miltiorrhiza are extracted 3-8 times at room temperature with 8 times the volume of petroleum ether (including other alkanes), ethyl acetate, methylene chloride, chloroform, methanol or ethanol (to The color of the extract is very light), 24h / time, the solvent is recovered under reduced pressure at room temperature or the extract sample is obtained by freeze-drying. The extract sample was dissolved in ethyl acetate and divided into six parts through normal phase preparative high-performance liquid chromatography (HPLC), figure 2 The fourth part in a detects that it has the best anti-tumor cell proliferation activity, and then uses normal phase preparative HPLC to separate and purify multiple times to obtain Milti...

Embodiment 2

[0024] Cancer cells were inoculated in 96-well plates according to the number in Table 1, and Miltipolone was added after the cells were adhered or stabilized (the drug Miltipolone was first dissolved in DMSO and diluted with PBS before adding the drug), the solvent control group and the drug-dosing group (including the positive drug ) The final concentration of DMSO in the cell culture solution is 0.1%, each concentration has 3 duplicate wells. After adding the drug and continuing to cultivate for 96 hours, add 20 μl MTT (5.0 mg / ml) to each well, and then incubate at 37°C, 5% CO 2 Continue to incubate for 4 hours under the same conditions, then aspirate the cell culture medium, add 100 μl DMSO analytical reagent to each well to dissolve the product of MTT reduction - blue-purple Formazan crystals, and read at 570nm on a super microplate reader. The reading of the super microplate reader is the absorbance value of Formazan (OD 570 ), which reflects that the reductase activity...

Embodiment 3

[0029] Ultraviolet / Visible (UV / Vis) scanning and measurements were performed on a Lambda 35 UV / Vis spectrophotometer (PerkinElmer) with a scanning slit of 2 nm and a 1 cm pathlength for a 50 microliter cuvette. The DMSO concentration for all experiments was 0.2% and zeroed using 0.2% DMSO in water. Scanning range 200 to 800 nm ( Figure 6 given range 200-550 nm), Miltipolone and FeCl 2 , Fe(NO 3 ) 3 、CoCl 2 , MnSO 4 and ZnCl 2 The final concentration was 100 micromolar.

[0030] Ultraviolet / visible spectroscopy (UV / Vis) studies (see Figure 6 ) showed that Miltipolone and Fe 2+ Able to undergo obvious complexation, adding Fe 2+ The position and shape of the maximum absorption peak of UV / Vis changed significantly; Fe 3+After complexing with Miltipolone, the UV / Vis absorption intensity increased significantly, and its basic peak shape and maximum absorption position did not change significantly at around 244nm, but the peak shape at the position of 300-400nm changed ob...

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Abstract

The invention discloses an application of miltipolone or pharmaceutically acceptable salts thereof in the preparation of medicines for preventing or curing diseases related to Fe2+. A cancer cell inhibiting effect of the medicines prepared by the miltipolone or the pharmaceutically acceptable salts thereof realizes the purpose of anticancer through inhibiting cancer cell proliferation ; and particularly, the invention provides new choices of the medicines for curing or preventing human lung cancer, human liver cancer, human cervical carcinoma, human breast carcinoma, leukocythemia, fibrosarcoma, or gastric cancer.

Description

technical field [0001] The invention belongs to the field of medical biology, and in particular relates to a new application of Miltipolone or a pharmaceutically acceptable salt thereof in pharmacy. Background technique [0002] Salvia miltiorrhiza is the most commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis. Its efficacy is recorded in "Shenlong Materia Medica" and it has the effects of "breaking diseases and removing lumps". Due to its special efficacy, danshen appears in many compound Chinese medicines. Modern pharmacological studies have confirmed that Salvia miltiorrhiza has certain antitumor activity. The tropotrienone compound Miltipolone with the following structural formula is also isolated from Salvia miltiorrhiza the earliest, reported in the literature (Haro, G.; Mori, M.; Ishitsuka, M.O.; Kusumi, T.; Inouye, Y.; Kakisawa, H. .Bull.Chem.Soc.Jpn.1991, 64, 3422-3426.) is an active compound with cytotoxic effects ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/352A61P35/00A61P35/02
Inventor 周国春杨俊芸刘英学陈少鹏刘劲松
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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