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Drug composition for targeted release of trace elements and preparation method and application thereof

A technology of trace elements and compositions, applied in the field of anti-tumor pharmaceutical compositions and inducing tissue regeneration, can solve the problems of low content and intake, restricted, and difficult to achieve therapeutic concentration and biophysiological effects of trace elements.

Active Publication Date: 2010-12-29
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Any trace element must be subject to the "trace" requirements for the body. Although this type of metal element is very important to the body, the body content and intake are extremely low, which often leads to The body's uptake and utilization of such elements is inefficient, and it is prone to trace metal element poisoning
2. Contradictions between the non-specificity of routine intake and distribution in the body and the specific concentration requirements of disease sites
However, such methods are still subject to the functional status of specific organs. For example, if the function of related organs has been damaged, it is still difficult to achieve the therapeutic concentration and biophysiological effect of trace elements even through a large amount of dietary supplementation.

Method used

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  • Drug composition for targeted release of trace elements and preparation method and application thereof
  • Drug composition for targeted release of trace elements and preparation method and application thereof
  • Drug composition for targeted release of trace elements and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Example 1 Confirmation of the physiological effects of copper ions in vitro stimulation of cell regeneration and stem cell mobilization experiments and the controlled release of copper ions in vivo

[0096] In vitro cell experiments confirmed that the trace element-copper ion can effectively enhance the proliferation and differentiation of human umbilical vein endothelial cell (HUVEC). HUVEC was cultured and passaged in vitro. Convert HUVEC to 5×10 3 Cells / well density was seeded in 96-well plates, and the cells were randomly divided into 3 groups according to the concentration of the solution added to the well plates, group A was 5μmol / L CuSO 4 , Group B 25μmol / L CuSO 4 , C group is a blank control, each group has 4 multiple wells, the basic medium is MCDB131, and the MTT method is used to detect cell proliferation and draw a growth curve. Take HUVEC to 2×10 5 The density of each hole was inoculated in a 6-well plate, and the grouping was the same as before. The expressio...

Embodiment 2

[0100] Example 2 confirmed the physiological effects of copper ions in vitro stimulation of cell regeneration and stem cell mobilization experiments and the controlled release of copper ions in vivo.

[0101] In order to determine the local effect of copper ions in the activation of injury scars and stimulating the regeneration of blood vessels in the scars, a copper ion gel was applied to the animal model of local myocardial infarction to verify the physiological effects of local slow release of copper ions.

[0102] 1. Preparation of calcium alginate + CuSO 4 Film. With 2% mass fraction of sodium alginate solution 10ml and containing 10mg CuSO 4 Mix the solution thoroughly, add 5ml CaCl dropwise 2 Film formation after solution.

[0103] 2. Preparation of myocardial infarction model: under anesthesia, open the chest and ligate the left anterior descending coronary artery of the rabbit heart to prepare a rabbit left myocardial infarction model. With the chest open, attach the film f...

Embodiment 3

[0107] Example 3 Copper ion and albumin binding experiment (preparation of copper ion chelated albumin microbubbles)

[0108] The solution used in the experiment was prepared with deionized water, using 0.1mol·L -1 To maintain the ionic strength of NaCl, use Tris-HCl as a buffer solution, with a pH of 7.4, prepare HSA and copper sulfate solutions, the concentration is 8.76×10 -6 mol·L-1 and 6.48×10 -4 mol·L-1. Using a 1cm cuvette, measured (1) fixed excitation wavelength of 280nm, copper sulfate titrated HSA, and observed the change of HSA's fluorescence emission peak. It can be seen from the figure that Cu 2+ The addition of sulphate did not significantly change the positions of the excitation peak and the maximum fluorescence peak, but the fluorescence intensity decreased to varying degrees as the amount of copper sulfate increased. Since the volume of the HSA solution is much larger than the volume of the dropped metal ion solution, the dilution effect can be ignored.

[0109] ...

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Abstract

The invention discloses a drug composition with a function of ultrasonic targeted release of the trace elements. The drug composition comprises hollow microspheres the concentration of which is greater than 1*106 / ml and the particle size of which is less than 10 mu m, at least one trace element the dosage of which is less than or equal to ten times higher than that of the physiological dose of human body and pharmaceutically acceptable carriers or auxiliaries, wherein the trace element and the hollow microspheres exist in the form of combination or dissociation; and the hollow microspheres are prepared by a pharmaceutically acceptable film-forming material. The drug composition of the invention is stable and safe; and the trace element ions can be directionally introduced into the body under the ultrasonic irradiation effect so as to effectively realize the biological effects of regeneration of blood vessels of the tissue, regeneration of the tissue or tumor resistance for the parts irradiated by the ultrasound, thereby having wide clinical prospect.

Description

Technical field [0001] The invention discloses a pharmaceutical composition for directional and controlled release of trace elements, especially a pharmaceutical composition that can be oriented and controlled by ultrasound, and can induce tissue regeneration and anti-tumor. technical background [0002] Trace elements play a basic role in maintaining human health. The main physiological function is to play a catalytic role in various enzyme systems, play a role with essential components or cofactors of hormones or vitamins, and form metalloproteins with special functions. The physiological role of trace elements can be compared with vitamins, but the body can synthesize some vitamins on its own but cannot synthesize any elements. From this point of view, essential trace elements are more important to the human body than vitamins. The basic definition of essential trace elements refers to those elements that have obvious nutritional and physiological functions, and are essential ...

Claims

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Application Information

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IPC IPC(8): A61K33/00A61K33/04A61K33/16A61K33/18A61K33/22A61K33/24A61K33/26A61K33/30A61K33/32A61K47/48A61K47/42A61K47/30A61K47/24A61K9/19A61K35/00
CPCA61K9/0019A61K33/00A61K9/1275A61K9/1658A61K9/0009A61K9/127A61K9/5052A61K41/0028A61P9/00A61P35/00
Inventor 周翔解慧琪康裕建
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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