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Human calcitonin-cucurbituril compound preparation and preparation method thereof

A technology of human calcitonin and compound preparations, which is applied in the direction of pharmaceutical formulas, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., which can solve the problem of decreased biological activity, affecting the therapeutic effect, and easily causing thyroid tumors, etc. problem, to achieve the effect of inhibiting fibrosis and improving biological activity

Active Publication Date: 2016-05-11
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the amino acid sequence of calcitonin from non-human sources is quite different from that of human calcitonin, for example, the homology between sCT and hCT is only 50%. Chlorin is an immune reactant, and the human body's immune response to it will affect its clinical application value
Although sCT is often used in the clinical treatment of osteoporosis and hypercalcemia, due to its poor homology with hCT, the immune response and antibodies generated during application will affect the therapeutic effect
[0004] Although hCT is used to treat osteoporosis and hypercalcemia, the human body will not have an immune response to it, but hCT is more prone to fibrosis than sCT. In aqueous solvents, hCT molecules are easily aggregated and fibrosis occurs, forming Long-fiber precipitates, long-fiber precipitates of calcitonin can easily cause thyroid tumors (HazardJB, HawkWA, CrileG.JClinEndocrMetab.1959; 19:152-61.); the mutual aggregation of calcitonin molecules can also reduce its biological activity
The above problems lead to great difficulties in the clinical application of hCT, and hCT has not yet achieved clinical application

Method used

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  • Human calcitonin-cucurbituril compound preparation and preparation method thereof
  • Human calcitonin-cucurbituril compound preparation and preparation method thereof
  • Human calcitonin-cucurbituril compound preparation and preparation method thereof

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Effect test

Embodiment 1

[0028] Add 2.0mg of human calcitonin (hCT) and 6.9mg of cucurbituril 7 (CB[7]) into the 1# control bottle equipped with a stirring bar, add 2.0mg of hCT and 17.4mg of CB[7] into the already equipped Add 2.0mg of hCT and 34.8mg of CB[7] to the 2# control bottle with stirring bar in the 3# control bottle already equipped with the stirring bar. In the 1~3# control bottle, the molar ratio of hCT to CB[7] They are 1:10, 1:25, 1:50 respectively.

[0029] Add 3mL of PBS buffer solution with a pH value of 7.4 to 1~3# vials, put them in an ice bath and sonicate until hCT and CB[7] are completely dissolved and mixed to obtain the hCT-CB[7] compound preparation. Then place the 1~3# control bottles in a water bath at 40°C, use a constant temperature magnetic stirrer to stir at a speed of 200r / min, take samples at intervals of 0.5h from the 0th to 4h when the stirring starts, and start stirring Sampling was carried out every 1h from the 4th to 20h, and the stirring was stopped after stirr...

Embodiment 2

[0038] Measure hCT and CB[7] according to the molar ratio of hCT and CB[7] = 1:10, add hCT and CB[7] into the vial equipped with a stirring bar, add deionized water into the vial at room temperature , Shake the control bottle to completely dissolve hCT and CB[7]. Stir at a speed of 1 / min for 20 minutes, and freeze-dry to obtain the hCT-CB[7] compound preparation.

Embodiment 3

[0040] Measure hCT and CB[7] according to the molar ratio of hCT and CB[7] = 1:30, add hCT and CB[7] into the control bottle equipped with a stirring bar, add pH value to the control bottle at room temperature 7.4 PBS buffer solution, shaking the control bottle to completely dissolve hCT and CB[7], the amount of PBS buffer solution should be such that the concentration of hCT is 100 μmol / L and the concentration of CB[7] is 3 mmol / L, and then the control bottle The vial was placed in a water bath at 40°C using a constant temperature magnetic stirrer at a speed of 100r / min to stir the vial for 30min, and freeze-dried to obtain the hCT-CB[7] compound preparation.

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Abstract

The invention provides a human calcitonin-cucurbituril compound preparation. The compound preparation is prepared from human calcitonin-cucurbituril supermolecular complex, human calcitonin and cucurbituril. A preparation method of the human calcitonin-cucurbituril compound preparation comprises the steps that human calcitonin and cucurbituril are dissolved in a water-borne solvent with the pH value of 7-8 at the temperature of 0 to 40 DEG C and evenly mixed, and the human calcitonin-cucurbituril compound preparation is obtained; or human calcitonin and cucurbituril are dissolved in a water-borne solvent with the pH value of 7-8 at the temperature of 0 to 40 DEG C and evenly mixed, then freeze drying is carried out, and the human calcitonin-cucurbituril compound preparation is obtained. The human calcitonin-cucurbituril compound preparation is not prone to fibrosis in the use process, the biological activity of the compound preparation is higher than that of independent human calcitonin, and the human calcitonin is beneficial for promoting clinical application of human calcitonin.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a human calcitonin-cucurbitacin compound preparation and a preparation method thereof. Background technique [0002] Calcitonin (CT) is a linear polypeptide hormone containing 32 amino acids, which is secreted by the parafollicular cells (parafollicular cells, also known as C cells) of the hindbranch body of vertebrates and the thyroid gland of mammals. , has its corresponding receptors in bone and kidney, has the function of regulating calcium and phosphorus metabolism, and is currently mainly used for the treatment of diseases related to low bone mass. The secretion of calcitonin is related to the calcium concentration in the blood flowing through the thyroid gland, so the increase of blood calcium concentration can cause the increase of calcitonin secretion and inhibit bone resorption, and reduce the blood calcium concentration of patients with hypercalcemia. [0003] The amino aci...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K38/23A61K47/69
CPCA61K38/23
Inventor 李建树商惠丁春梅刘衍朋陈星羽
Owner SICHUAN UNIV
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