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Oleanolic acid and ursolic acid in the preparation of modulating vitamin D 3 Use in drugs that metabolize enzyme activity

A technology of oleanolic acid and ursolic acid, applied in the field of medicine, can solve problems such as poor water solubility, high toxicity, and fast metabolism

Active Publication Date: 2021-05-25
THE HONG KONG POLYTECHNIC UNIV SHENZHEN RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, many natural compounds have disadvantages such as poor water solubility, rapid metabolism, low bioavailability, and high toxicity, which limit their in vivo applications.

Method used

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  • Oleanolic acid and ursolic acid in the preparation of modulating vitamin D <sub>3</sub> Use in drugs that metabolize enzyme activity
  • Oleanolic acid and ursolic acid in the preparation of modulating vitamin D <sub>3</sub> Use in drugs that metabolize enzyme activity
  • Oleanolic acid and ursolic acid in the preparation of modulating vitamin D <sub>3</sub> Use in drugs that metabolize enzyme activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Cell experiment

[0056] (1) Regulatory effect of mixing different proportions of oleanolic acid (OA) and ursolic acid (UA) on the activity of CYP27B1 promoter:

[0057]HKC-8 cells were used in the experiment (provided by the laboratory of Prof. Racusen of the Department of Pathology of Johns Hopkins University in the United States, the references are as follows: Racusen LC, Monteil C, Sgrignoli A, Lucskay M, Marouillat S, Rhim JG, et al. (1997). Cell lines withextended in vitro growth potential from human renal proximal tubule:characterization, response to inducers, and comparison with established celllines. Journal of Laboratory and Clinical Medicine 129:318-329.), using the inserted CYP27B1 transcription promoter sequence The pGL-3-basic vector (pGL-3-basic vector was provided by the laboratory of Dr. Farzana Perwad, a professor at the University of California San Francisco in the United States: References are as follows: Chanakul A, Zhang MY, Louw A, Armbr...

Embodiment 2

[0062] Example 2 Animal experiment verification (menopausal osteoporosis model)

[0063] In this example, the optimal ratio of oleanolic acid and ursolic acid was mixed (oleanolic acid: ursolic acid = 3:1), fed to 5-month-old ovariectomized female rats, and after 6 weeks of feeding, the in vivo Serum 1,25(OH) 2 D. 3 Level, intestinal calcium absorption and calcium balance, bone density and other indicators, to verify the optimal ratio of oleanolic acid and ursolic acid mixed (oleanolic acid: ursolic acid = 3:1) to regulate vitamin D in the body 3 metabolism, and to improve calcium balance and bone density.

[0064] 1. Materials and methods

[0065] 1.1 Animals and materials

[0066] Animals: 20 5-month-old SPF female ovariectomized SD rats (average body weight 250 g), purchased from the Experimental Animal Center of Purdue University, USA.

[0067] 1.2 Experimental method

[0068] 1.2.1 Experimental grouping and drug treatment: After the animals adapted to the environmen...

Embodiment 3

[0075] Example 3 Animal experiment verification (senile osteoporosis model)

[0076] In this example, the optimal ratio of oleanolic acid and ursolic acid was mixed (oleanolic acid: ursolic acid = 3:1), fed to 11-month-old female rats, and after 12 weeks of feeding, the serum in vivo was detected 1,25(OH) 2 D. 3 Level and serum parathyroid hormone (PTH) level, intestinal calcium absorption and calcium balance, bone density and other indicators, verify the optimal ratio of oleanolic acid and ursolic acid mixed (oleanolic acid: ursolic acid = 3: 1) Regulate vitamin D metabolism in the body, and improve calcium balance and bone density.

[0077] 1. Materials and methods

[0078] 1.1 Animals and materials

[0079] Animals: 24 11-month-old SPF female SD rats (average body weight 389g), and 8 3-month-old SPF female SD rats (average body weight 220g) as a control group were purchased from Guangdong Medical Experimental Animal Center ( Animal certificate number: SCXK (Guangdong) ...

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Abstract

The invention discloses that oleanolic acid and ursolic acid are used in the preparation and regulation of vitamin D 3 Applications in drugs that metabolize enzymatic activity. The present invention has discovered that the natural product oleanolic acid and ursolic acid are mixed with a mass ratio of 3:1, which has the function of regulating vitamin D 3 The role of metabolic enzyme activity, thereby increasing the active vitamin D in the body 3 (1,25(OH) 2 D. 3 ) levels, improve calcium balance and enhance bone density. On this basis, oleanolic acid and ursolic acid are encapsulated with natural high-molecular zein protein to improve their stability under external environmental conditions and increase oral bioavailability. At the same time, the slow-release technology of nanoparticles alleviates the Toxic effects of high-dose oral administration of oleanolic acid and ursolic acid on tissue cells. May be used to treat or prevent active vitamin D 3 Osteoporosis, diabetes, metabolic syndrome, cardiovascular disease, hyperparathyroidism, renal failure, psoriasis, cancer, and immune disease due to decreased synthesis and deficiency.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to the preparation and regulation of vitamin D by oleanolic acid and ursolic acid 3 Applications in drugs that metabolize enzymatic activity. Background technique [0002] Vitamin D, also known as anti-rickets vitamin, is a type of fat-soluble vitamin and belongs to steroid compounds. Among the vitamins required by humans, vitamin D is very special. It is a precursor of a hormone and can be synthesized by the body itself when there is sufficient sunlight (vitamin D 3 ). active vitamin D 3 It plays an irreplaceable role in regulating the body's metabolism and maintaining normal physiological functions. It not only participates in mineral metabolism, but also inhibits the proliferation and differentiation of various tissue cells, inhibits the secretion of parathyroid hormone, improves glucose metabolism and immune regulation, etc. active vitamin D 3 Acting on a variety of target tissues, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/56A61P19/10A61P3/10A61P3/00A61P9/00A61P13/12A61P17/06A61P35/00A61P37/02A61P5/16
Inventor 黄文秀董晓莉曹思思王奕
Owner THE HONG KONG POLYTECHNIC UNIV SHENZHEN RES INST
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