Background and overview[1][2]
The Chinese alias of diphenyl acid is 2-Aminoethoxydiphenyl borate (2-APB). 2-APB is a new type of membrane-permeable inositol trisphosphate (IP3) receptor calcium antagonist, thereby inhibiting the activation of calcium store-regulated channels (SOC) induced by calcium stores and inhibiting the calcium ion influx mediated by it. , IC50 is 42μM, but does not affect the binding of IP3 to its receptor. Its effect on inhibiting calcium ion release can be enhanced accordingly as the concentration of 2-APB increases (>90μM). 2-APB inhibits the phenotypic conversion and proliferation of rat vascular smooth muscle cells under serum stimulation. It is a potential anti-vascular proliferation drug and plays a very important role in preventing and reversing the phenotypic conversion and proliferation of vascular smooth muscle cells. 2-APB regulates TRP ion channels and blocks TRPC1, TRPC3, TRPC5, TRPC6, TRPV6, TRPM3, TRPM7, TRPM8 and TRPP2. In vivo intervention of 2-APB can downregulate the expression of TRPM7 and inhibit the progression of its related cardiac hypertrophy; in the absence of Among other stimulating factors, 2-APB can stimulate TRPV1, TRPV2 and TRPV3; 2-APB selectively and specifically blocks certain gap junction channel subtypes. Compared with existing drug-coated stents, 2-APB can directly inhibit vascular smooth muscle proliferation and smooth muscle phenotype conversion.
Structure
Apply[1-3]
Diphenyl acid (2-APB) is a chemical that acts by inhibiting IP3 receptors and TRP channels (although it activates TRPV1, TRPV2, and TRPV3 at higher concentrations), inhibiting IP3-induced Ca2+ release . The endoplasmic reticulum is a highly sensitive organelle with numerous functions in eukaryotes. Under normal circumstances, the endoplasmic reticulum can perform normal physiological functions to maintain the stability of the intracellular environment. However, once the body is exposed to physical and chemical conditions such as hypoxia, When factors affect it, it will cause homeostasis in cells and induce endoplasmic reticulum stress (ERS). ERS is a self-protection mechanism produced by the body when stress occurs. Excessive stress may cause cells to produce Apoptosis phenomenon.
Endoplasmic reticulum stress in mammalian cells mainly includes two calcium channel proteins, IP3R and RyR. The release of intracellular calcium ions mainly relies on the effective regulation of calcium channel proteins IP3R and RyR. 2-APB, as an IP3R inhibitor, can regulate calcium release from IP3R calcium channels, inhibit or activate calcium ion signal transduction, and affect the flow of calcium ions in calcium pools. In research, it has been used to manipulate the intracellular release of calcium ions (Ca2+) and alter TRP channel activity, although its lack of specific effects makes it less than ideal in some situations. In addition, there is evidence that 2-APB acts directly to inhibit gap junctions composed of connexin26 or connexin32. Increasing evidence suggests that 2-APB is a powerful modifier of store-operated calcium channel (SOC) function, with low concentrations of 2-APB enhancing SOC, whereas high concentrations induce a transient increase followed by complete inhibition.
In addition, 2-APB is also used in endovascular coated stents. The cardiac stent, also known as the coronary stent, is a commonly used medical device in cardiac interventional surgery. The cardiac stent has gone through the development process of metal stents, coated stents, and soluble stents. The main materials are stainless steel, nickel-titanium alloy, or cobalt-chromium alloy. A new technology for implanting cardiac stents to improve myocardial blood supply deficiency and cardiac artery blockage caused by coronary heart disease. The surgical treatment only requires puncturing the blood vessel under local anesthesia, allowing the catheter to advance through the blood vessel, reaching the opening of the coronary artery, and using a special delivery system The stent is delivered to the site where it needs to be placed, the catheter is placed and withdrawn, and the operation is completed.
An intravascular drug-coated stent containing 2-aminoethyl diphenylboronic acid is provided to provide a drug-coated stent that inhibits vascular smooth muscle proliferation, including a stent body and a coating, and the coating is coated on On the surface of the stent body, the coating includes at least one layer of 2-aminoethyl diphenylboronic acid on the stent body and a polymer layer covering the outermost layer of the coating. The polymer layer is at least one chitosan layer, gelatin layer or heparin layer. When the number of layers of 2-aminoethyl diphenylboronic acid is greater than 1, an intervening layer can be provided between two layers containing 2-aminoethyl diphenylboronic acid. The intercalated layer includes a chitosan layer and a heparin layer. layer. The number of layers of 2-aminoethyl diphenylboronic acid is 10-12 layers, preferably 11 layers. The coating also includes coating on the surface of the stent body and the 2-aminoethyl esterThe polymer bottom layer between the diphenylboronic acid layers is at least one chitosan layer or heparin layer. The stent body is titanium alloy, titanium stent or stainless steel stent. At least one layer containing 2-aminoethyl diphenylboronic acid is inserted into the above intravascular coating, so that the stent can selectively inhibit the proliferation of intravascular smooth muscle cells. At the same time, the polymer coated on the 2-aminoethyl diphenylboronic acid layer can play a role in sustained release of the drug and prolong the action time of the stent to release the drug in the human body.
In addition, diphenyl acid can also be used to prepare a durable interior wall paint, which is made of the following raw materials in parts by weight: 1.5-3.7 parts of nano-titanium oxide, 5-10 parts of titanium dioxide , 20-30 parts of white latex, 6-10 parts of DL-1,4-dithiothreitol, 15-20 parts of deionized water, 2.5-6.3 parts of lauric aldehyde, 2.5-3.6 parts of secondary octylphenol polyoxyethylene ether parts, methyl methacrylate 2.5-3.7 parts and diphenylboronic acid-2-aminoethyl ester 3.5-4.2 parts. Compared with existing latex paints, in formula design, in addition to selecting low-VOC and low-odor latex, the main invention is to extract distilled lauric aldehyde from vegetable oil as a film-forming aid, avoiding the need for conventional film-forming aids. The organic volatile matter that is harmful to the human body can be truly healthy, environmentally friendly, and harmless to the human body. The invention is suitable for decoration in public places such as hospitals, schools, office buildings, shopping malls, hotels, etc., especially in places where personnel and equipment cannot be evacuated.
Main reference materials
[1[ CN201620641544.0 Intravascular coated stent containing 2-aminoethyl diphenylboronic acid layer
[2] CN201511029816.8 Durable interior wall paint and preparation method thereof
[3] CN201710695313.7 Application of endoplasmic reticulum Ca2+ blockers in the preparation of drugs for the treatment of cranial nerve arsenic poisoning
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