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Composition of vitamin K2 and vitamin D3 and application thereof

A technology of vitamins and compositions, applied in the field of medicine, can solve problems such as the reduction of glycolysis of tumor cells, the limitation of anti-tumor research, and the oxidation of mitochondrial metabolic intermediates, so as to eliminate the increase of blood calcium, broaden the treatment methods, and expand the safe use range effect

Active Publication Date: 2021-12-24
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, 1,25(OH) 2 D. 3 It may induce apoptosis by interfering with other signaling pathways (such as tumor necrosis factor TNF-α); (3) It can inhibit the expression of cytoskeletal proteins, resulting in reduced cell motility, thereby producing anti-migration and anti-invasion effects; (4) ) can lead to a decrease in cyclooxygenase 2 and an increase in 15-hydroxyprostaglandin dehydrogenase, resulting in a decrease in prostaglandin synthesis, which plays a key role in the generation of inflammatory responses; (5) with VD 3 Treatment can lead to a decrease in tumor cell glycolysis and can also oxidize mitochondrial metabolic intermediates, which can no longer be used in biosynthetic pathways, limiting the nutrient supply and metabolism of tumor cells
[0009] VD 3 When used as a non-chemotherapy drug to exert anti-tumor effect, it needs to be used in large doses, but the body takes too much VD 3 Later, it will produce side effects of elevated blood calcium, which limits its anti-tumor research in vivo

Method used

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  • Composition of vitamin K2 and vitamin D3 and application thereof
  • Composition of vitamin K2 and vitamin D3 and application thereof
  • Composition of vitamin K2 and vitamin D3 and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1 Vitamin K 2 Preparation of nanoemulsions

[0057] VK 2 Nanoemulsion is an oil-in-water nanoemulsion. VK 2 The recipe for nanoemulsion preparation is shown in Table 1, and the VK of the prescription amount is accurately weighed 2 , MCT, SPC, TPGS, and AP form the oil phase, and weigh the prescription amount of Na 2 S 2 o 5 , CaNa 2 Add appropriate amount of distilled water to EDTA and Gly to form the water phase. The oil phase was stirred and dissolved in a 60°C water bath, and the water phase was stirred and heated at 65°C. After the substances in the oil phase were completely dissolved, the water phase was slowly added to the oil phase under magnetic stirring conditions, and the stirring was continued for 25 minutes to obtain colostrum. The primary emulsion was homogenized four times at 800 bar using a high pressure homogenizer. Finally, the emulsion was filled into vials flushed with nitrogen, sealed with an aluminum cap, and autoclaved at 100 °...

Embodiment 2

[0060] Embodiment 2 Vitamin K 2 Characterization of Nanoemulsions

[0061] (1) Average diameter, polydispersity index (PDI)

[0062] Take the prepared VK 2 Appropriate amount of nanoemulsion, appropriate amount of sample, after diluting with sterile water for injection, put it into the sample pool, and use a laser particle size analyzer based on Nicomp-380 to measure. The results are shown in Table 2.

[0063] Table 2.VK 2 Particle size of nanoemulsion, PDI, (n=3)

[0064]

[0065] (2) Morphological identification under TEM scanning

[0066] Observation of VK by transmission electron microscopy (TEM, JM-1200EX, JEOL Ltd, Japan) 2 The shape of the nanoemulsion. The nanoemulsion was diluted with distilled water and dropped on a copper grid (300 mesh) covered with a carbon film. After the nanoemulsion adhered, phosphotungstic acid solution (2%, w / v) was added for staining for 2 min. Absorb excess liquid with filter paper, air-dry the sample overnight at room temperatur...

Embodiment 3

[0068] Embodiment 3 Oral high-dose vitamin K 2 Pharmacodynamic test of nanoemulsion for prevention and treatment of tumor

[0069] Oral high-dose VK via a xenograft mouse model of S180 tumors 2 (50mg / kg) tumor prevention efficacy research. The mice were randomly divided into 5 groups, 6 in each group, and the route of administration was oral gavage: the control group (0.9% normal saline, 10 mL·kg -1 ), A50 (oral VK before tumor bearing 2 Prevention 15 days 50mg·kg -1 ), B50 (oral VK before tumor bearing 2 Prevention for 15 days, oral VK after tumor bearing 2 15 days of treatment; 50mg·kg -1 ), C50 (no prevention before tumor bearing, oral VK immediately after tumor bearing 2 15 days of treatment; 50mg·kg -1 ), D50 (no prevention before tumor bearing, oral VK three days after tumor bearing 2 15 days of treatment; 50mg·kg -1 ). During the whole pharmacodynamic test period, record tumor volume, tumor mass, and plot the number of days; in order to better reflect the eff...

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Abstract

The invention belongs to the technical field of medicines, and relates to a composition of vitamin K2 and vitamin D3 and application thereof, in particular to application of the combination of vitamin K2 and vitamin D3 in preparation of medicines for preventing or treating tumors, especially application in blood calcium regulation. The invention provides a composition of vitamin K2 and vitamin D3, which comprises vitamin K2 and vitamin D3, and the mass ratio of vitamin D3 to vitamin K2 is (1: 90)-(1: 270). The composition of the vitamin K2 and the vitamin D3 and a pharmaceutically acceptable carrier or excipient can be prepared into clinically acceptable preparations, such as nanoemulsion, liposome and the like. VK2 and VD3 are combined for application, and the anti-tumor effect of the combined VK2 and VD3 is improved than that of independent administration. The VK2 can fully play roles in preventing tumors and reducing blood calcium rise caused by VD3, and cooperates with VD3 to generate an anti-tumor effect, so that the VK2 has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine and relates to vitamin K 2 and vitamin D 3 Compositions and uses thereof, particularly relating to vitamin K 2 Combined Vitamin D 3 The application in the preparation of drugs for the prevention or treatment of tumors, especially in the regulation of blood calcium. Background technique [0002] Cancer is one of the most serious diseases that endanger human health. With environmental pollution, population aging, accelerated pace of life and increasing mental stress, the incidence of malignant tumors is increasing year by year, and the number of patients is increasing. So far, scientists have tried to develop a variety of strategies to prevent and treat cancer. Among them, chemotherapy is often combined with other methods, which is the most widely applicable to patients, but the side effects such as drug resistance, hair loss, and gastrointestinal dysfunction caused by chemotherapy are relative...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/122A61K31/593A61P3/14A61P35/00
CPCA61K31/122A61K31/593A61P3/14A61P35/00A61K2300/00
Inventor 邓意辉胡雅维丁俊强刘梦阳闫娜宋艳志刘欣荣
Owner SHENYANG PHARMA UNIVERSITY