TUBERKULYN (Tuberculinum) — the general name of the drugs received from cultures of mycobacteria of tuberculosis of different types and applied to statement of allergy diagnostic tests and also with the medical purposes.
T. it was for the first time received in 1890 by Koch in the form of «glyceric extract of pure growth of tubercular bacilli». Old tuberculine of Koch — ATK (Alt-tuberculinum Koch) is a filtrate 6 — 8 weeks culture of mycobacteria of tuberculosis for beef-extract 5% glitserinovokhm the broth condensed to Vm of volume. It represents transparent siropoobrazny liquid of brown color with aromatn-cheskikhm a smell. ATK can be received from bacteria of a human, bull or bird's look, and also from a strain of BTsZh. A lack of ATK is existence along with specific active agents of ballast substances of a medium, to-rye can cause side reactions. Further various methods of cleaning of T were developed., and with their help drugs of the same type, as ATK, but exempted from ballast impurity are received. The first T., free from proteins of the environment, it was prepared on synthetic medium with sparaginy (see Soton Wednesday).
In 1934 Seybert (F. Century of Seibert) and sotr. received T. mammals — PPD (Purified Protein Derivative) representing the derivative of a protein of mycobacteria of tuberculosis possessing biol. activity, stability and deprived of the sensibilizing properties. Drug was received by ultrafiltration (see) or an uljtratsentrifugirovaniye (see), sedimentation trichloroacetic to - that or ammonium sulfate and drying in vacuum from the frozen state.
(PPD-L) was prepared in 1939 for M. A. Linnikova, and since 1954 the mass production of this drug began. In a crust, time in the USSR the following tuberculines are produced: ATK,
PPD (the dry purified tuberculine), PPD-L (the purified tuberculine in standard cultivations). The last is drug of mass use.
In many countries drugs of T type are marketed. — the so-called sensitin representing allergens from atypical mycobacteria. They are applied to differential diagnosis of tuberculosis and mikobakterioz since usual T., according to Edwards (L. Century of Edwards, 1965), cause cross-reactions at statement of skin tests to the people and animals infected with atypical mycobacteria. The manufacturing techniques of sensitin are similar to manufacturing techniques of PPD.
By researches of Longum (E. R. Long) and Seybert (1926) it is established that specific active substance T., causing skin reaction of the slowed-down type, represents the protein of mycobacteria which is allocated in culture medium at their deep autolysis. Further studying of the chemical nature of T. showed that proteins (tuberkuloproteina And, In, C) about a pier are a part it. it is powerful (weighing) 17 000 — 18 Ltd companies, carbohydrates (polysaccharides I and II) and nucleinic to - that. Gupta and Landi (K. S. of Gupta, S. Landi, 1978) emitted from cultural filtrates of mycobacteria high cleaning tuberkulinovy peptides about a pier. weighing 3000 — 12 000, causing the increased specificity of T., and Nagai (S. Nagai, 1980) et al. — about a pier. weighing 5800.
Before release drugs T. undergo control, in process to-rogo their physical properties, sterility, harmlessness, protein content, specific activity are estimated, and also tests for lack of live mycobacteria and the sensibilizing action are carried out (see Control of bacteritic drugs). In the USSR state control of T. it is entered in 1928. Preparation and release of AT K and G1PD-L are regulated by the special instructions approved by M3 of the USSR. Domestic T. strictly conform to national standards and requirements of WHO.
Inadequacy of results during the work with various commercial series T. caused need of creation of the corresponding standards for production of standard drugs (see Standardization). The first AT K international standard was issued by the State
institute of serums in Copenhagen in 1928 and approved in 1931. The organization of health care at the League of Nations, the second — is claimed in 1935, the third — in
1965 by WHO; 1 ml of this standard supports 90 Ltd companies of the international units (IU).
Basis of the international standard for PPD of mammals approved in 1951 was the PPD-S series prepared Seybert in 1941. The international unit for this drug is approved in 1952 and there correspond 0,00002 mg of substance (taking into account buffer salts of 0,000028 mg). Standard drug is produced in the ampoules containing 10 mg of PPD and 4 mg of buffer salts that makes 50 000 IU.
The international standard for PPD of a bird's look is approved in 1954. Its international unit is defined as 0,0000726 mg of substance. Standard drug is produced in the ampoules containing 10 mg of PPD and 26,3 mg of buffer salts (500 000 IU).
In many countries the RT-23 series of the Danish PPD prepared State in-volume of serums in Copenhagen in a large number is widely used. Its biological activity is approximately twice higher than activity of PPD-S. In the USSR there are national standards T., conforming to the international standards on biol. activities. Specific activity of commercial series domestic T. it is expressed in the tuberkulinovy units (TU).
The majority of the countries for a tuberculinodiagnosis generally use ready standard solutions T. For prevention of sorption of active agent T. on a surface of glass tanks add 0,005% to its solutions solution tvi - on - 80 as detergent and 0,01% solution of Chinosolum as preservative.
Skin reaction to T. is reaction of hypersensitivity of the slowed-down type. T. has no full antigenic properties, i.e. does not sensibilize a healthy organism and does not cause antibody formation, and the organism works only on previously sensibilized with mycobacteria of tuberculosis. In these cases it causes local, focal and general reaction (temperature increase, an indisposition), degree of manifestation to-rykh depends on a dose of T., route of administration and specific allergic mood of an organism.
In practice of T. widely apply for diagnosis to definition of contamination of the population, selection of persons, the subject antitubercular vaccination, studying of its efficiency, assessment of forms and the course of tubercular process, at the combined antitubercular therapy, at experimental studying of an immunogenesis of tuberculosis, vaccinal process, cellular immunity in reactions of in vitro.
See also Mycobacteria, Tuberculosis, the Tuberculinodiagnosis.
Bibliography: Linnikova M. A. The cleared protein derivative, Probl. tube., No. 12, page 3, 1939; The Guide to vaccinal and serumal business, under the editorship of N. I. Vlasyevsky, etc., page 480, M. — JI., 1934; Gupta K. Page a. L a n d i S-Isolation, characterization, and biological properties of a tuberculin — active pepti-doglycan isolated from the culture filtrate of mycobacterium tuberculosis, Infect. Immun., v. 27, p. 344, 1980; Koch R. Weitere Mittheilungen tiber ein Heilmittel gegen Tuberculose, Zbl. Bact., Bd 8, S. 673, 1890; it, Weitere Mitt-heilung tiber das Tuberkulin, Dtsch. med. Wschr., S. 1189, 1891; Nagai S., M a-tsumoto J. N agasuga T. Specific skin-reactive protein from culture filtrate of mycobacterium bovis BCG, Infect. Immun., v. 31, p. 1152, 1981; Seibert F. B. Isolation and properties of purified protein derivative of tuberculin, Amer, Rev. Tuberc., v. 30, p. 713, 1934.
T. B. Yablokova.