Medical News

 Breast cancer is a common malignancy in women, and multidrug resistance is one of the main reasons affecting the efficacy of chemotherapy and patient survival in breast cancer. A tumor drug resistance-associated protein, BCRP, has been reported in breast cancer drug-resistant cell lines.  Also, BCRP is a transporter, mainly responsible for the excretion of endogenous and exogenous substances outside the cell, and has a vital role in drug metabolism research. The BCRP gene of human breast cancer resistance protein (BCRP) is located in the chromosome 4q22 region. It encodes 655 amino acids, which are present in several vital organs in the body, such as the small intestine, placenta, liver, and kidney. It is essential for drug absorption, distribution, metabolism, and excretion. Drug transport proteins play a vital role in drug metabolism kinetics. According to the drug transport mode, drug transport proteins can be divided into drug uptake proteins and drug efflux proteins....

 Isatis Radix, also known as the big blue heel, is the dried root of the plant woad or big blue-green, which can be used clinically for influenza, mumps, chickenpox, and measles.  The liver is the leading site of drug metabolism , and applying the liver microsomal model allows for metabolite analysis studies of drugs. Drug metabolite analysis has evolved rapidly to become an essential part of pharmacokinetic studies . According to a study reported on the internet, it was found that based on the systematic screening of the active antiviral ingredients of radix isatidis, straight heliotropin B was the most abundant compound among the 31 compounds isolated from the aqueous extract of radix isatidis, and compound activity testing studies showed that it had significant antiviral and antioxidant activities. Therefore, the lignan compound Gibberellin B contained in Isatidis Radix no toginseng is one of the critical active substance bases of Isatidis Radix no toginseng against viruses...

 Mass spectrometry is an essential technique for performing drug metabolite analysis , which is characterized by high detection sensitivity, a wide range of molecular masses analyzed, and a large amount of molecular structure information provided. Moreover, mass spectrometry is often used in conjunction with other analytical methods, such as chromatography and electrophoresis, which further expands the application of mass spectrometry. For example, some researchers have used ultra-high pressure liquid chromatography-time-of-flight mass spectrometry for metabolite analysis of drugs in rats to investigate the substances that exert drug effects. 1. Mass spectrometry can be used for drug metabolite analysis Drug metabolites are derived from the metabolic reactions of drugs, and the structure of metabolites is closely related to the type of metabolic reactions and the structural properties of precursor compounds. After the metabolic transformation of a drug in vivo, only some structural...

 In drug development, many compounds often die in clinical trials because of the toxicity or safety of their metabolites, among which the active metabolites formed by drug molecules activated by human liver metabolism are more likely to be an important cause of toxicity.  In vivo or in vitro metabolite analysis of drugs can be used to determine an early stage whether a compound is toxic and suitable for further development, thus minimizing unnecessary losses. In preclinical drug metabolite analysis and metabolite structure identification to evaluate the safety of a drug metabolite, one can identify an animal species in a routine toxicology test in which adequate exposure levels of that metabolite can be formed, which is comparable to or higher than human exposure, and then study the drug toxicity in that animal species. Alternatively, if a relevant animal species cannot be identified that forms the metabolite, the metabolite can be synthesized, and further safety evaluations ...

 Drugs are bound to plasma proteins to varying degrees in plasma, and the degree of binding can affect the drug's absorption, distribution, metabolism, and excretion in vivo, which in turn can affect the pharmacodynamic behavior of the drug. In general, after absorption into the bloodstream, only free drug reaches the site of action and produce pharmacological activity.  Equilibrium dialysis is one of the most commonly used method to determine the free concentration of medicines based on the equilibrium principle of drug binding. It is the classical method to study drug plasma protein binding rate. It has been found that the critical physiological and pharmacological functions of proteins require the participation of small drug molecules, which can promote or inhibit the protein functions through their interaction with proteins. The binding of drugs to plasma proteins can affect the biological activity of drugs. Therefore, determining the drug plasma protein binding rate is m...

 Natural products and their derivatives are essential for various drug lead compounds. Finding new drugs from active natural product skeletons and optimizing lead compounds is critical to drug development. Some chemical components of Chinese medicines are of great interest to pharmaceutical R&D workers because they may have multiple pharmacological activities .  Understanding the metabolism of natural products isolated from plants or synthesized using chemical methods in vivo can provide an individual material basis for pharmacodynamic and pharmacological studies of the drug. Rats or mice are usually used as animal models for the analysis of metabolites of compounds in vivo. Drug metabolism is one of the critical factors affecting the action of drugs. Studying the pathways and stability of drug metabolism, the enzymes and kinetic parameters involved in metabolism, and the drug interaction problems caused by metabolism are necessary to find efficient and less toxic drugs. T...

 Usually, good pharmacokinetics properties are one of the criteria for judging a good or bad drug. Pharmacokinetics can explore the absorption, distribution, metabolism, and excretion of drugs in the body, as well as the pharmacological and toxicological significance, brought about in this process, to ensure the safe dose of rational clinical use of drugs, reduce the incidence of adverse reactions in the process of clinical use, and ultimately ensure the safety of human drug use. Among them, drug excretion is an essential component of drug elimination in vivo and is part of the pharmacokinetic study. Generally, drugs are excreted through the kidneys, bile, lungs, breast milk, salivary glands, bronchial glands, sweat glands, and intestines. 1、Renal The kidney is an essential organ for drug excretion. The basic structure of the kidney is the renal unit, which consists of the glomerulus and the renal tubules, and there are about one million renal units in a kidney. The blood flow thr...

 A large number of candidate compounds is the basis for drug development, and compound activity screening and testing are critical to obtaining candidate compounds with clinical safety data. In screening candidate compounds, pharmacokinetic parameters are another important screening metric to examine potential compounds in addition to their efficacy, which can be used to better control drug development time and reduce drug development costs by excluding candidates with suboptimal pharmacokinetic parameters early in drug development. Image from pixabay Modern advances in science and technology have greatly accelerated the rate of drug candidate discovery, with thousands of new compounds requiring screening each year. When a candidate compound enters the clinical phase, it is usually studied in healthy volunteers to obtain the kinetic parameters of the drug in humans.  A large number of candidate compounds are often eliminated for pharmacokinetic reasons. Important pharmacokine...

People may take medicine when they catch a cold daily; some take tablets, and some take capsules; these tablets and capsules are pharmaceutical preparations. Pre-prescription study of drug formulation is the understanding, analysis, utilization, or improvement of a series of fundamental physical, chemical, and formulation properties of a drug before designing a formulation prescription to make the drug stable, effective, and in line with the requirements of formulation prescription and formulation process in industrial production. Medicilon can provide professional pre-prescribing services and uncover valuable information to lead the compound into late-stage development for tiny quantities of active pharmaceutical ingredients or candidate compounds with drug-forming properties. The impact of physical properties of active pharmaceutical ingredients (APIs) on pre-prescription studies of injectables is one of the main points of pre-prescription studies of injectables, which are mainly re...

 Pharmaceutical R&D outsourcing CRO refers to pharmaceutical companies using the purchase of new drug clinical or preclinical research and other services from a third party, and the contractor is responsible for the work tasks of drug development trials and declaration of registration within the scope of the contract, mainly serving the stage of new drug launch and before.  The pressure of new drug R&D has led to the rise of new drug R&D outsourcing services and has also driven the global CRO industry to take off. Consistency evaluation of generic drugs, self-checking and verification of drug clinical trials, and acceleration of drug trials are driving the domestic CRO market to the 100 billion level. The current high cost of pharmaceutical R&D, the reduced success rate of R&D, and massive patent expiration have prompted pharmaceutical companies to be more eager to improve the efficiency and speed of R&D, which has accelerated the development of the ...

  Metformin is a biguanide compound that reduces blood sugar mainly by reducing hepatic glucose output, improving insulin resistance, and reducing glucose absorption in the small intestine. It is currently one of the world's most widely used oral hypoglycemic drugs. Drug safety evaluation studies have found that Metformin has a good safety profile, no carcinogenic or mutagenic effects, and no evidence that Metformin can increase the risk of lactic acidosis. Medicilon has a professional team and experience in preclinical drug safety evaluation services, providing high-quality data and a fast turnaround time to support all drug safety evaluation studies. Many patients are concerned about the effects of long-term metformin use on the kidneys. The drug does not directly damage the kidneys but can lead to drug accumulation when taken by patients with existing kidney damage. Both the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2017 edition) and the Expert C...

 SPR biosensors have a wide range of applications in life sciences, drug residues, food detection, disease mechanisms, etc. due to their advantages of no labeling, online detection, reproducibility, no sample pre-treatment, etc. In the fields of protein network regulation and cellular signal transduction, it is often necessary to search for the unknown factors interacting with a known protein to discover the whole regulatory network. Surface plasmon resonance (SPR) technology is a biosensing analysis technique for analyzing interactions between biomolecules and is now commonly used in the Biacore, a biomolecular interaction analysis system. The Biacore assay can be used for the analysis of binding specificity between biomolecules, concentration quantification, binding kinetics and affinity analysis, and thermodynamic analysis, enabling real-time detection of biomolecular interactions between DNA and proteins, between protein molecules, between drugs and proteins, be...

化合物的代谢性质是关系到其能否成药，并真正的运用到临床的重要影响因素，因此在药物研发中需要对新合成的化合物进行药物代谢动力学研究。其中肝微粒体体外孵育法、基因重组CYP450酶系技术、肝细胞体外孵育法等是比较常见的体外药物代谢研究方法。 1、肝微粒体体外孵育法 候选化合物在不同种属的肝微粒体中的代谢稳定性和代谢表型研究对于化合物体内的代谢性质具有很好的预测作用，是药物开发前期评估候选化合物的有效手段。通过药代动力学的研究，并开展 药理学 研究，从而了解药物的临床用途。肝微粒体包括大鼠肝微粒体、人肝微粒体、犬肝微粒体、猴肝微粒体、小鼠肝微粒体等。在新化学实体的药物发现、药物的代谢特征及药物的相互作用研究中，肝微粒体体外孵育法是体外药物代谢的“金标准”，是目前临床和临床前药物代谢动力学研究中采用较广的方法。美迪西在药物代谢动力学的体外研究方面拥有丰富的经验，体外研究是指代谢稳定性、P450诱导和抑制、代谢途径研究、代谢产物鉴定等研究项目，涉及的动物有大鼠、小鼠、兔、狗、猴子等。 微粒体是通过匀浆经超速离心得到的内质网碎片形成的小泡，包含了CYPs的全部组分，具有制备技术简单、代谢过程快、结果重现性好、易于大批量操作、在-80℃条件下能长期保持稳定等优点而广为采用。 有研究者考察了两色金鸡菊在人肝微粒体的体外代谢，将肝微粒体空白对照、两色金鸡菊醇提物乙醇溶液、灭活肝微粒体加两色金鸡菊醇提物及肝微粒体加两色金鸡菊醇提物进行体外共孵育，采用高效液相色谱法测定，通过对比色谱峰，阐明两色金鸡菊在肝微粒体的体外代谢规律[1]。结果发现两色金鸡菊醇提物在人肝微粒体药物代谢酶作用下，各成分含量均降低，其中4种物质被代谢而未被检出，两色金鸡菊醇提物在人肝微粒体药物代谢酶作用下可较快地代谢消除。 2、基因重组CYP450酶系技术 细胞色素P450（CYP450）酶系有基因超家族编码的酶蛋白所组成，参与许多内源性和外源性物质的生物转化。药物对细胞色素P450酶活性的影响是导致药物相互作用的主要原因之一。重组酶由于其成分单一、药物代谢表征明确，是对研究CYPs代谢表征的可靠方法，基因重组的P450酶系在药物的体外肝代谢研究中得到越来越广泛的应用。 基因重组P450酶系即利用基因工程及细胞工程，将调控P450酶系表达的基因整合到大肠杆菌或昆虫细胞，经细胞培养，表达高水平的P450酶系，纯化后可获...