CHYMOTRYPSIN — the proteolytic enzyme cosecreted by a pancreas. Peptide-hydrolases concerns to group (see); splits proteins and peptides. Together with trypsin (see) participates in the proteolysis of food in a small bowel (see Digestion). The optimum of effect of chymotrypsin is at pH 7,6 — 8,2.
Chymotrypsin as medicine is applied at treatment of a number of diseases. Use of chymotrypsin in medicine is based on ability of enzyme to selectively split proteins of a не-кротизированных of fabrics, to liquefy various exudates, purulent masses. Besides, chymotrypsin has antiinflammatory and antiedematous effect, accelerates processes of regeneration in wounds. At acute and hron. pancreatitis as a result of intraorganic activation of proferments chymotrypsin is released, to-ry promotes an autolysis of a parenchyma of a pancreas. At hit in a blood channel and a lack of the corresponding inhibitors chymotrypsin can destroy nek-ry components of a blood plasma and fabrics.
Chymotrypsin is synthesized by Ii-cells of a pancreas (see) in the form of inactive proferment of chymotrypsinogen. At the person and the majority of mammals two types of chymotrypsinogen (And yes In) differing on physical are produced. - to chemical properties. Also chymotrypsinogen C is found in some mammals. The chymotrypsin C which is formed at its activation differs on specificity from chymotrypsins A and B a little.
Activation of chymotrypsinogens happens in a duodenum under the influence of trypsin. The remains of a histidine, serine and asparaginic to - you,
the 57th, 195th and 102nd positions holding respectively are a part of an active center of chymotrypsin. Activity of chymotrypsin is oppressed dpizopropil-ftorfosfaty, phenyl metileulfo-nilftoridy, hlormetilke-tone of N-tozil-L-phenylalanine, himostati-iy N by some other inhibitors. At a blood plasma and fabrics there are proteinaceous inhibitors of chymotrypsin protecting proteins from splitting. Mnegne from them, e.g. a2-makroglobul in, a number of inhibitors of trypsin (so-called antitrypsins), are the polyvalent inhibitors oppressing also activity of other proteinases; specific inhibitor of a himo-trinsin of a blood plasma — ai - anti-XII mo trip a synonym
in the course of activation of a himotrip-siiogen And can be formed several active forms of enzyme [l, and, and, (And), P, 7] differing in a form of crystals, solubility and the size of specific activity. The main and the most well studied form is chymotrypsin A. Its pier. the weight (weight) apprx. 25 Ltd companies, an isoelectric point is at pH 8,6, the maximum stability at pH about 3, in the alkalescent environment is exposed to an autolysis. The molecule of chymotrypsin A contains 245 amino-acid remains and consists of 3 polypeptide chains connected by disulfide bridges. Three-dimensional structure of molecules of enzyme is deciphered. The molecule of chymotrypsin A represents a compact globule, in a cut there is a hydrophobic cavity where it is located with at with t r and t with in I z y in and yu shch and y
the site of an active center.
The chymotrypsin B which is formed at activation of chymotrypsinogen B is homologous on structure to chymotrypsin A, is characterized by the same activity and specificity.
For definition of activity of chymotrypsin a number of the methods based on the proteolysis and synthetic substrates is offered. The hydrolysis of ethers of the N-replaced tyrosine controlled spektrofotometrichesk is widely used (Shvert's method — Takenaki).
Chymotrypsin as drug. As drug in medical practice the hl is used. obr.
chymotrypsin A, to-ry in the USSR is produced under the name Chymotrypsinum crystal-lisatum. It is received from a pancreas of cattle in the form of chymotrypsinogen, to-ry later recrystallization subjected to activation by trypsin. It represents brilliant scales or white powder, we will dissolve in water and isotonic solution of sodium chloride; pH of 0,2% of water solution makes 4,5 — 6,5. In a dry form it is resistant; in water solutions it is quickly inactivated (especially at high temperature).
In surgical practice chymotrypsin is applied to treatment of purulent and it is long not healing wounds, trophic ulcers, decubituses, burns, hron. osteomyelitis. For this purpose drug is appointed locally and intramusculary. Locally use 1 — 2,5% solution of drug on isotonic solution of sodium chloride for wetting of the tampons entered into a wound. In a wound (in the presence of separated) the drug can be administered in the form of powder in doses from 0,03 to 2 g. Intramusculary the drug is administered the adult on 0,005 — 0,01 g of 1 — 2 time a day, to children — on 0,0025 g once a day, dissolving necessary amount of drug just before the use in 1 — 2 ml of sterile isotonic solution of sodium chloride or 0,5 — 2% of solution of novocaine. At osteomyelitis solutions of enzyme wash out bone cavities and fistulas.
Routes of administration and doses of chymotrypsin at treatment of trophic ulcers, decubituses and burns same, as at treatment of purulent wounds.
At pleurisy and an empyema of a pleura chymotrypsin is entered vnutriplevral-but 1 time a day in a dose of 0,01 — 0,02 g, dissolving drug before introduction to 20 — 50 ml of isotonic solution of sodium chloride.
At purulent diseases of lungs solutions of chymotrypsin enter is inhalation (on 0,005 — 0,001 g of drug in 2 — 3 ml of isotonic solution of sodium chloride once a day), by endotracheal injections (on 0,025 — 0,05 g of drug in 2 — 5 ml of isotonic solution of sodium chloride) or intramusculary.
As an expectorant chymotrypsin is applied at bronchitis, pneumonia and other diseases of the lungs proceeding with formation of a viscous, trudnootde-lyaemy phlegm. For this purpose chymotrypsin is appointed it is inhalation or intramusculary.
In Ophthalmolum. to practice chymotrypsin is applied at irites, irido-tsik litas, hemorrhages in an anterior chamber of an eye, postoperative and posttraumatic hypostasis of okologlazny fabrics, appointing drug intramusculary and locally in the form of eye drops or trays. As eye drops use 0,25 — 1% solution, and for trays — 0,2% solution of drug. Drops and trays appoint 3 — 4 times a day within 2 — 3 days. Besides, drug of enzyme is often used at intrakapsulyarny extraction of a cataract for processing of front and back chambers of the eye. For this purpose use solutions of chymotrypsin in concentration 1:2500 or 1:5000. In 2 — 3 min. after use of chymotrypsin front and back chambers of the eye are washed out solutions of a pantripin (see) for braking of excess effect of chymotrypsin.
Use of chymotrypsin can be followed by the same side effects as use of trypsin. E.g., at intramuscular introduction enzyme is capable to cause a hyperemia and morbidity in the field of an injection, and at inhalation introduction — hoarseness of a voice and other signs of irritation of upper respiratory tracts. At parenteral administration allergic reactions, fever, tachycardia can be observed.
Chymotrypsin is contraindicated in the same cases, as trypsin (at heart failure, cirrhosis, a dekompensirovanny pulmonary tuberculosis and emphysema of lungs with respiratory insufficiency, pancreatitis, infectious hepatitis, diseases of kidneys, hemorrhagic diathesis). Chymotrypsin cannot be entered into a vein and to apply on ulcerated surfaces of malignant tumors.
Form of release: hermetically the corked bottles containing 0,005 and 0,01 g of drug. Storage: in the place protected from light at a temperature not over 10 °.
Bibliography: Antonov V. K. Chemistry
of proteolysis, M., 1983; Bogush JI. To. and Schwarzman JI. Ya. Use of proteolytic enzymes at a pulmonary tuberculosis, M., 1970; Veremeenko K. N. Enzymes of proteolysis and their inhibitors in medical practice, Kiev, 1971; Clinical pharmacology, under the editorship of V. V. Zakusov, page 423, M., 1978;
Mashkovsky M. D. Pharmaceuticals, p. 2, page 50, M., 1984; M about-solov V. V. Proteolytic enzymes, M., 1971; Northrop D., To at-nitts M. and Herr and Ott R. Crystal enzymes, the lane with English, M., 1950; V. I. Pods, etc. Proteolytic enzymes in purulent surgery, M., 1970.
JI. A. Lokshina; V. K. Muratov (pharm.).