What is blood?
Blood is a red, opaque, viscous liquid that flows through the blood vessels and heart of a person. The blood is composed of plasma and blood cells. One liter of plasma contains 900–910 grams of water, 65–85 grams of protein and 20 grams of low molecular substances. There are many electrolytes and organic compounds in low molecular substances. Blood cells include red blood cells and white blood cells. And platelet three types of cells. The average life span of red blood cells is 120 days, the life span of white blood cells is 9–13 days, and the lifespan of platelets is 8–9 days. In general, 40 ml of blood cells die every day. At the same time, there are also a corresponding number of cell newborns. The function of blood includes blood cell function and plasma function. It has four functions of transporting, regulating body temperature, defense, regulating human osmotic pressure and acid-base balance.
The composition of the blood: plasma and blood cells
Plasma
Plasma can be understood as blood without blood cells. Corresponding to the interstitial tissue of connective tissue, it is a pale yellow translucent liquid. In addition to containing a large amount of water, there are inorganic salts, fibrinogen, albumin, globulin, enzymes, hormones, various nutrients, metabolites, etc. These substances have no specific form but have important physiological functions.
1L of plasma contains 900 to 910 g of water (90% to 91%), 65 to 85 g of protein (6.5% to 8.5%), and 20 g of low molecular substance (2%). There are many electrolytes and small molecule organic compounds in low molecular substances, such as metabolites and other hormones. The electrolyte content in plasma is basically the same as that of the tissue fluid, and therefore, the chemical stability of plasma is high.
Serum is a pale yellow liquid that precipitates after blood coagulation. The biggest difference from plasma is that it does not contain fibrinogen, and serum stability assay can be performed.
Blood cells
During the life of the body, blood cells are constantly metabolizing. The average life span of red blood cells is about 120 days, and the survival time of granular white blood cells and platelets generally does not exceed 10 days. The life span of lymphocytes varies from a few hours to a few years. Blood cells and platelets are produced from hematopoietic organs. Red blood cells, white blood cells and platelets are produced by red bone marrow, while non-granulated white blood cells are produced by lymph nodes and spleen.
Blood cells are divided into three categories: red blood cells, white blood cells, and platelets.
Adults have about 5 liters of blood. Blood cells account for about 45% of the blood by volume. Each liter of blood has: 5×10 ^ 12 red blood cells (about 45% of the blood volume): in mammals, mature red blood cells have no nuclei and organelles. They contain heme to deliver oxygen. The glycoprotein on the red blood cells determines which type of blood type. The proportion of red blood cells in the blood is called hematocrit. The total surface area of all red blood cells in the human body is about 2000 times the skin area outside the human body. 9×10 ^ 9 white blood cells (about 1.0% of the blood volume): they are part of the immune system, responsible for destroying and removing old or abnormal cells and cell debris, and attacking pathogens and foreign objects. 3 x 10¹¹ platelets (about 1% of the blood volume): they are responsible for blood clotting, turning fibrinogen into fibrin. Fibrin forms a network of red blood cells that form a blood clot that prevents more blood loss and helps prevent bacteria from entering the body.
When there is a problem with blood components or circulation, it can cause downstream tissues to not function effectively. “Ischemia” means that some parts of the body do not have enough blood to circulate. The pumping function of the heart causes blood to flow through the lungs and other organs. Gravity and muscle activity also help the blood flow back to the heart for recirculation. In mammals, blood forms a balance with lymph, which is formed by ultrafiltration of blood through the capillaries and back from the thoracic duct.
Blood function:
1. To deliver oxygen to all parts of the body, mainly responsible for red blood cells.
2. Delivery of nutrients such as glucose, amino acids, fatty acids, etc.
3. Take away waste, such as carbon dioxide, uric acid, lactic acid, etc.
4. Provide immune function, which is responsible for white blood cells and antibodies.
5. Information functions such as hormone and tissue damage signals.
6, regulate the body’s pH value.
7, adjust body temperature.
8, hydraulic function.
What is safe blood?
Safe blood refers to blood that does not contain any viruses, parasites, drugs, alcohol, chemicals or other foreign substances that can cause damage, danger or disease to the recipient. Blood donors must be healthy and have not had any serious illnesses. The recipient should not be harmed by the blood, and the blood donor should not be exposed to the risk of blood donation.
Plasma stability
The basic principle of plasma stability: plasma contains a variety of hydrolases, such as cholinesterase, aldolase, lipase, dehydropeptidase, alkaline and acid phosphatase. If a compound has an affinity for one of these enzymes and has a hydrolyzable group at a suitable position, it can be broken down in the plasma, thereby affecting the accuracy of the biological test conclusion or making it in vivo. No effective therapeutic concentration is reached.
Common groups that are easily decomposed in plasma: esters, amides, carbamates, lactams, lactones, sulfonamides.
Structural modification strategy for improving plasma stability
The ester is substituted with an amide (for the hydrolysis of plasma, the amide is more stable than the ester at the same position).
Increased steric hindrance (increasing the steric hindrance near the hydrolysable group reduces its affinity for hydrolases, thereby increasing the plasma stability of the compound).
Adding a power-absorbing group to reduce the stability of the soft drug (soft drugs are intentionally modified to reduce plasma stability, allowing them to be quickly cleared from the body, reducing toxic side effects).
The group that can be hydrolyzed is removed.
Application of plasma stability data
Poor properties of a compound in vivo (such as small area under the curve, short half-life, and high clearance) are sometimes not due to poor metabolic stability. If the compound contains a group that is susceptible to hydrolysis, low plasma stability may be a partial cause of its clearance. Plasma stability data can be used as a routine identification to retrospectively analyze possible causes of poor in vivo properties of compounds.
Plasma instability data can indicate the unstable structure of the research team’s compounds, allowing researchers to determine the next step in the study as soon as possible. By identifying the structure of the plasma degradation products, it was determined that the terminal carbamate was unstable in the molecule, while the cyclic carbamate was stable. Through structural modification, the researchers finally obtained a stable terminal carbamate. The compounds are prioritized for in vivo testing in animals. Information on the stability of the compound’s plasma improves the comprehensiveness of the data and helps the research team make informed decisions. This information is used to prioritize the pharmacokinetic and pharmacological studies of compounds in vivo. Prodrugs with optimal properties were selected by measuring in vitro plasma stability.