A kind of bone targeting salmon calcitonin and its preparation method

A salmon calcitonin, bone targeting technology, applied in the field of biomedicine, can solve problems such as reduced biological efficiency, achieve the effect of less difficulty in operation, improve treatment effect, and repair bone tissue

Active Publication Date: 2021-07-27
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Modification of Lys-11 and Lys-18 of salmon calcitonin (sCT) by acetylation leads to a significant reduction in biopotency, so derivatization of sCT by amino groups is not possible (see S.M.Ryan, etc., Journal of Controlled Release 149( 2) (2011) 126-132; G. Andreotti, etc., Journal of Biological Chemistry 281 (34) (2006) 24193-203.)
Studies have demonstrated that Gln-14 can derivatize transglutaminase without loss of activity, however this method is not a general method

Method used

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  • A kind of bone targeting salmon calcitonin and its preparation method
  • A kind of bone targeting salmon calcitonin and its preparation method
  • A kind of bone targeting salmon calcitonin and its preparation method

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Experimental program
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Effect test

Embodiment 1

[0037] In this embodiment, a preparation method of bone-targeted salmon calcitonin is provided, and the steps are as follows:

[0038] (1) Preparation of bone-targeting conjugated molecules

[0039] ①Synthesis of the first intermediate

[0040] Dissolve dithiophenylmaleimide and N-methylmorpholine in ethyl acetate at a molar ratio of 1:1 so that the concentration of dithiophenylmaleimide is 3 mg / mL, and add in the dark Methyl chloroformate in an equimolar amount with dithiophenylmaleimide was stirred and reacted at room temperature for 1 h. After the reaction was completed, the crude product was separated by rotary evaporation, and the crude product was dissolved in dichloromethane and washed with deionized water. Three times, then remove the aqueous phase, keep the organic phase, add desiccant anhydrous MgSO to the organic phase 4 Remove water from organic phase, then filter to remove MgSO 4 , spin to remove dichloromethane to obtain the first intermediate 3,4-dithiophenyl...

Embodiment 2

[0055] In this embodiment, a preparation method of bone-targeted salmon calcitonin is provided, and the steps are as follows:

[0056] (1) Preparation of bone-targeting conjugated molecules

[0057] ①Synthesis of the first intermediate

[0058] Dibromomaleimide and N-methylmorpholine were dissolved in ethyl acetate at a molar ratio of 1:1.2 so that the concentration of dibromomaleimide was 4 mg / mL, and methyl chloroformate was added in the dark , the addition of methyl chloroformate is 1.2 times of the equimolar amount of dibromomaleimide, stirred and reacted at room temperature for 2h, and the crude product was separated by rotary evaporation after the reaction was completed, and the crude product was dissolved in dichloromethane, and used Wash three times with deionized water, then remove the water phase, keep the organic phase, add desiccant anhydrous MgSO to the organic phase 4 Remove water from organic phase, then filter to remove MgSO 4 , and the dichloromethane was s...

Embodiment 3

[0069] In this embodiment, a preparation method of bone-targeted salmon calcitonin is provided, and the steps are as follows:

[0070] (1) Preparation of bone-targeting conjugated molecules

[0071] ①Synthesis of the first intermediate

[0072]Dissolve dithiophenylmaleimide and N-methylmorpholine in ethyl acetate at a molar ratio of 1:1 so that the concentration of dithiophenylmaleimide is 2 mg / mL, and add in the dark Methyl chloroformate in an equimolar amount with dithiophenylmaleimide was stirred and reacted at room temperature for 1 h. After the reaction was completed, the crude product was separated by rotary evaporation, and the crude product was dissolved in dichloromethane and washed with deionized water. Three times, then remove the aqueous phase, keep the organic phase, add desiccant anhydrous MgSO to the organic phase 4 Remove water from organic phase, then filter to remove MgSO 4 , and the dichloromethane was removed by spinning to obtain the first intermediate,...

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Abstract

The invention provides a bone-targeted salmon calcitonin, which is formed by opening the disulfide bond in the salmon calcitonin molecule and covalently coupling it with a bone-targeted coupling molecule. The preparation method is as follows: (1) To prepare bone-targeting coupling molecules, (2) dissolving salmon calcitonin in a water-soluble solvent with a pH value of 5 to 7, adding a reducing agent to reduce the disulfide bonds of salmon calcitonin to form free sulfhydryl groups, and then adding The bone-targeting coupling molecule is stirred and reacted at 0-40° C. for 0.5-12 hours, the crude product is separated, and purified by preparative liquid chromatography to obtain the bone-targeting salmon calcitonin. The bone-targeted salmon calcitonin provided by the invention has no cytotoxicity and immunogenicity, can improve the bone tissue enrichment ability of the calcitonin, can effectively repair the bone tissue, and has broad application prospects.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a bone-targeted salmon calcitonin and a preparation method thereof. Background technique [0002] Salmon calcitonin (sCT) is a single-chain polypeptide hormone containing 32 amino acids, which can regulate the calcium ion concentration in the blood, reduce bone resorption, and has a clear analgesic effect. With the growth of age, human organs gradually aging, the ability to secrete calcitonin and other related hormones will be greatly reduced, resulting in bone loss, bone structure disorder, decreased ability to inhibit bone resorption, and gradually develop into osteoporosis . Most of the drugs currently used to treat osteoporosis in postmenopausal women are calcitonin-like protein and polypeptide drugs, and long-term medication is required. [0003] During the treatment of exogenous calcitonin, since the half-life of calcitonin is very short, it will be quickly cleared from the body,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/585C07K1/06
CPCC07K14/585
Inventor 李建树刘衍朋俞鹏谢婧李安琦
Owner SICHUAN UNIV
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