TRYPSIN — one of the main enzymes of digestion. Cosecretes a pancreas in the form of the inactive predecessor — trypsinogen, belongs to peptide - gidrola - deputy (KF 18.104.22.168), hydrolyzes proteins and peptides. Emergence active T. in tissue of a pancreas (see) is one of the main pathogenetic factors of development acute and hron. pancreatitis (see). Definition of activity of T. and nek-ry other enzymes in duodenal contents it is used for assessment of a functional condition of a pancreas and serves for differential diagnosis of pancreatitis. Use of drug of trypsin in medicine as medicine is based on ability of T. to selectively destroy nekrotizirovanny fabrics, to liquefy a phlegm and other viscous secrets, exudate, clots, and also on its antiinflammatory and antiedematous action and on ability of this enzyme to reduce resistance of pyogenic microflora to antibiotics. In this regard trypsin accelerates process of regeneration of purulent wounds. At pathological reduction of vneshnesekretorny function of a pancreas trypsin as a part of Pancreatinum (see) use for replacement therapy. Key situation T. in system of digestive enzymes is explained by the fact that he not only participates in splitting of food proteins, but also activates all proferments formed in a pancreas i.e. trypsinogen, chymotrypsinogens A and B (see Chymotrypsin), use rboks ipeptidaza
And yes In (see Karboksipeptidaza), pro-elastase (page of m. Elastases), professional wasps-folipazu (see Lipases). At hit in a blood channel and at insufficiency of the corresponding inhibitors T. can activate Hageman's factor, plasminogen, pre-kallikrein and to start thus the cascade of reactions of coagulant system of blood (see. Coagulant system of blood), fibrinolitpchesky (see the Fibrinolysis) and kinin (see. To ii-pins) systems.
T. it was open in 1857. Zh. The visa rum, and in 1867 W. Kiihne the name «trypsin» was offered to box. In 1931 Northrop (J. The N of Northrop), etc. enzyme was received in a crystal look.
T. it is found in vertebrate animals; enzyme similar to T., it is found at nek-ry invertebrates, microorganisms and the higher plants. In a pancreas of the person and a number of mammals so-called anion T are found., but to properties similar to T., but an isoelectric point (see) these enzymes is at lower pH values. Along with peptide bonds of T. splits also ester and amide links, catalyzes reaction of a transiyeptp-dprovaniye. Enzyme is characterized by narrow substrate specificity and selectively hydrolyzes the bonds formed by carboxyl (SOON-) groups of the main amino acids of arginine (see) and a lysine (see). Optimum pH values for action of T. 7,8 — 8,0.
Pier. weight (weight) of T. cattle it is equal to 23 800; the isoelectric point is at pH 10,5. The molecule T consists of one polypeptide chain constructed of 223 amino-acid remains and containing 6 disulfide bridges. Tertiary structure of T. it is also established. T. the protea naz belongs to a subclass serpnovy, the remains of serine (see), a histidine (see) and aspartic acid enter an active center of enzyme (see) in situation 183, 46 and 89 respectively. High specificity of T. is defined by presence in the sub-stratsvyazyvayushchem site of an active center of the rest asparaginic to - you in situation 177.
Activity of T. it is oppressed diiso-propilftorfosfatom, fenilmetil-sulfonilftoridy, hlormetilke-tone] Ch-tozil-lpzina, leypepti-iy, nek-ry metals, 4-amino-benzamidine, etc., and also a large number of the natural proteinaceous inhibitors called sometimes by antitrypsins to-rye are present at tissues of animals, plants, microorganisms and protect them from destruction of T. Main inhibitors T. in a blood plasma are ai-proteinazny inhibitor (and \-антнтрипенн), a2-macroglobulin and inter - and - inhibitor T. The pancreas contains two inhibitors T., one of to-rykh cosecretes in a duodenum together with trypsinogen and protects it from premature activation. Similar secretory inhibitors T. about a pier. it is powerful apprx. 6000 are found in secrets of nek-ry glands. Drugs of such inhibitors T., allocated from a pancreas or lungs — counter p kcal, Trasylolum (see) — use in medical practice as remedies. With deficit or defect of nek-ry inhibitors T. (e.g., ai-proteinazny inhibitor) development of a row patol is connected. states.
T. it is synthesized (3 cells of a pancreas in the form of inactive proferment to a tripa of a nnogen (the outdated and seldom found name — pretrppsin), to-ry in
intestines turns into T. under the influence of enzyme of enterokinase (see), and also T. V process and kt and Bail and and from the N-trailer site of a tripeinogen is chipped off hexapeptide. At the same time it is formed so-called (3 trypsin, to-ry as a result of hydrolysis of one more peptide bond turn in and - the trypsin consisting of two peptide chains. In the neutral and alkalescent environment T. easily is exposed to an autolysis (samoperevarivanpyu) that leads to pollution of drug inactive products. Ions of Sa2 + promote activation of trypsinogen and stabilize T., protecting it from an autolysis. In alkaline condition of T. it is irreversible it is denatured, in acid medium it is stable. T. termoustoychiv: activity of enzyme
remains after boiling in 0,01 M salt to - those.
T., received from a pancreas, clear by means of a chromatography (see).
For definition of activity of T. numerous methods are offered. Were widely adopted Kunitts's method based on splitting of T. casein (see Kazenna) with the subsequent definition in a protein-free filtrate of content of tyrosine (with - m), and Erlanger's method, to-rogo is the cornerstone use of synthetic substrate/g nitroanilide N-6eH3oim-D, L-argpshsha (BAPN). Often for definition of activity of T. use the hydrolysis of N-replaced L-argnnina ethers controlled spektrofo-tometrichesk. Activity of T., determined by this method in the duodenal contents of the person received by a stylet, on an empty stomach without use of special irritants, normal makes 100 — 150 milliyedinitsa (take its such activity for an activity unit of enzyme, at a cut there is a splitting of 1 µmol of substrate in 1 min.). At acute and chronic pancreatitis the delay of allocation of a secret is resulted by intraorganic activation of pancreatic enzymes and, first of all, trypsin, to-ry activates then other proferments; it, eventually, leads to an autolysis of a parenchyma of gland.
Trypsin as drug. As drug in medical practice the hl is used. obr. T. crystal, received from a pancreas of cattle. Besides, T. together with himo-tr and to dogs (see) is a part of drugs of Pancreatinum and chemical opsin (see).
Trypsin crystal (Tgur-sinum of crystallisatum) represents powder, white or with a subtle yellowish shade, inodorous. Let's easily dissolve in water and isotonic solution of sodium of chloride; pH of 0,2% of aqueous solution 3,0 — 5,5. In neutral and caustic solutions drug quickly collapses.
In surgery of T. crystal is used for treatment of purulent and it is long not healing wounds (see Wounds, wounds), osteomyelitis (see), trophic ulcers (see), decubituses (see) and burns (see). For this purpose drug is used locally and intramusculary. Locally drug is used in the form of 1 — 2,5% of solutions in isotonic solution of sodium of chloride for wetting of the gauze tampons entered into a wound. In the presence of liquid purulent separated the drug can be administered in a wound in the form of powder (from 0,03 to 0,2 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. Just before introduction drug is dissolved in 1 — 2 ml of sterile isotonic solution of sodium of chloride or 0,5 — 2% of solution of novocaine. Solutions of drug need to be entered deeply into an upper outside quadrant of a buttock. Use of T. at treatment of purulent wounds allows to perform plastic surgeries in case of need widely. At treatment hron. osteomyelites after opening of paraossalny phlegmon of T. apply locally, and also use its solutions for washing of bone cavities and fistulas.
Treatment of trophic ulcers is also long not healing wounds using T. carry out by the same technique, as treatment of purulent wounds. After clarification of a surface of ulcers and wounds from it is purulent - necrotic masses topical treatment of T. stop, and continue parenteral administration of drug during several (to 10) days.
At purulent diseases of lungs solutions T. enter it is inhalation (0,005 — 0,01 g of drug in 2 — 3 ml of isotonic solution of sodium of chloride) and intramusculary, and if necessary — by endotracheal injection (0,025 — 0,05 g of drug in 2 — 5 ml of isotonic solution of sodium of chloride). T. as the expectorant (see) direct like action is appointed usually in inhalations and sometimes intramusculary at bronchitis, pneumonia and other diseases of the lungs proceeding with education by knitting, difficult separating phlegm. At pleurisy and an empyema of a pleura intraplevralno
1 time a day is entered on 0,01 — 0,02 g of the drug dissolved in 20 — 50 ml of isotonic solution of sodium of chloride.
Sometimes T. use in complex therapy of thrombophlebitises (see) together with anticoagulants (see), for this purpose appoint it intramusculary in the doses stated above.
At periodontosis (see) and a periodontal disease in addition to intramuscular injections the drug is administered podnadkostnichno (to the area of defeat).
In ophthalmology of T. crystal appoint intramusculary and locally (in the form of eye drops and trays) at irites, iridocyclites (see), hemorrhage in an anterior chamber of an eye, posttravmatpchesky and postoperative hypostasis of okologlaz-ny fabrics. For trays solutions of drug, and as eye drops — 0,25 — 1% solutions use 0,2%, to-rye appoint 3 — 4 times a day within 2 — 3 days.
Apply to intramuscular introduction only T. crystal. For topical administration except it also the T can be used. amorphous.
Side effect of T. it is shown unequally depending on ways of introduction. So, after intramuscular introduction it can cause local morbidity and a hyperemia. After inhalations of T. emergence of signs of irritation of upper respiratory tracts is possible (hoarseness of a voice, etc.). At parenteral use of T. can cause allergic reactions, tachycardia and fever. At emergence of allergic reactions use antihistaminic substances
Drug is contraindicated at heart failure, dekompensi-rovanny forms of a pulmonary tuberculosis, emphysema of lungs with respiratory insufficiency, cirrhosis, a viral hepatitis, pancreatitis, diseases of kidneys and hemorrhagic diathesis. The drug cannot be administered in a vein and to apply on ulcerated surfaces of malignant tumors.
Form of release: the ampoules or bottles containing 0,005 and 0,01 g of trypsin crystal. Store in the dry, protected from light place 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; Geytman I. Ya., Card sh B. E. and Kivman G. Ya. Change of factors of hemocoagulation under the influence of exogenous proteinases, Probl. gematol. and modulation, blood, t. 27, No. 10, page 38, 1982; Clinical pharmacology, under the editorship of V. V. Zakusov, page 421, M., 1978; Mashkovsky M. D. Pharmaceuticals, p. 2, page 20, M., 1977; M about-solov V. V. Proteolytic enzymes, M., 1971; Northrop D., To at - N and t of c of M. and X e p r and about t of t of River. Crystal enzymes, the lane with English, M.,
TRYPTOPHANE 273 1950; Pods In * And» and d river. Pro-tzolitichesky enzymes in purulent surgery, M5jj 1970; Enzymes in otorhinolaryngology, under the editorship of K. N. Veremeenko, Kiev, 1980; Townes P. L. Trypsinogen deficiency disease, J. Pediat., v. 66, p. 275, 1965; Townes P. L., In of y s o n M. F. a. Miller G. Further observations on trypsinogen deficiency disease, ibid., v. 71, p. 220, 1967.
L. A. Lokshina; V. K. Muratov (pharm.).