DE1617648A1 - Antitetanus vaccine and process for its preparation - Google Patents

Description

Antitetanus vaccine and method of making it has been effective against tetanus for more than forty years (Tetanus), which is a particularly dreadful disease of the nervous system.

However, a considerable number of tetanus cases are still complained today, and possibly more than at the time the vaccination was not yet known This fact is based essentially on the fact that according to the current state vaccinated with antigen three times at an interval of several weeks using the tetanus vaccination technique will must in order to achieve effective immunization, and that be re-vaccinated regularly at intervals of several years to refresh got to.

For this reason, in numerous cases the vaccinations are not carried out satisfactorily, particularly among the populations of developing countries; here it is difficult or even impossible to prescribe a vaccination for all people, which must be carried out several times and at certain time intervals.

The present invention therefore relates to a new vaccine against Tetanus and a new method of making the vaccine that already existed after the first injection offers an effective vaccination protection and also with very simple aids can be administered, e.g. with a vaccination gun or with a multi-pointed scarification ring.

The inventive method for producing a vaccine against tetanus, with which an effective vaccination protection in a single injection is achieved, is characterized in that one is first on a nutrient solution cultivates a culture of P-Tetani, detoxifies this culture solution, the one obtained in this way Anatoxin cleanses and finally the anatoxin on a salary concentrated in antigen from 300 to 1000 IU / cm3 vaccine.

It should be remembered that the IE (International Unity) defines is considered to be the weakest vaccine dose that a number of guinea pigs have yet to immunize. For testing four to six weeks after vaccination is 10 times the minimum lethal dose injected; 80% of the guinea pigs should survive here. One The unit defined in this way represents the usual vaccination dose for humans.

According to a particular embodiment of the invention, for production of the culture solution of strain 141 Toronto from P-Tetani used and the culture in drawn in a meat-liver medium. The culture solution is then filtered sterile and detoxified with formula.

According to a preferred embodiment of the invention, the vaccine concentrated by counter dialysis and then stabilized in glycerol.

The new vaccine according to the invention itself is thus characterized by that it is purified and has a high antigen content «e.g. B. 300 to 1000 times more than contained in the currently used vaccines is, d. H. z. B. 300 to 1000 IU / cm3.

The vaccine according to the invention provides effective vaccination protection scored against tetanus when present in an amount of 0.10 to 0.50 cm3 in the human Organism is injected.

This vaccine is so effective that it can be obtained with the help of 6 vaccination guns can be administered; these are devices with which a jet of liquid is introduced into the body under high pressure and penetrates the skin without it to hurt.

With the currently commercially available vaccination guns, doses can be easily removed Inject of at least 0.10 cm3, with some types even up to 1 cm3.

The inventive vaccine against tetanus can also with With the help of scarification rings, which a certain number of Have tips impregnated with the vaccine, provided that one make a sufficient number - generally five or six skatifications, to get the necessary amount of vaccine into the organism to achieve vaccination protection to introduce.

Such scarification rings can also be used to refresh the Vaccinations to be carried out, sur which requires a lower amount of vaccine will.

Of course, the vaccine according to the invention can also be used in conventional Injected with a hypodermic needle, with the injections intramuscular, subcutaneous or hypodermic.

Numerous studies, first with animals and then with humans made: were confirmed that contrary to previous fears injecting tetanus vaccine into the human organism in a concentration that is 500 to 1000 times stronger than usual, none at all produced an abnormal reaction and the patient tolerated this dose excellently will.

Furthermore, in a series of experiments it was found that that a dose of 0.10 to 0.50 cm3 is sufficient to achieve with a single injection of the vaccine according to the invention an effective immunization against tetanus to achieve.

To further explain the invention, a method is provided below for the production of the vaccine against tetanus described according to the invention, as well as the way it can be administered and the results it will produce will.

Example First, a tetanus anatoxin was produced in a known manner, outgoing. from a culture broth of MP-Tetani (strain 141 Toronto) in meat liver Medium that was kept in the incubator at 340 for 10 days and then sterile filtered. Hierafu was detoxified the nutrient solution by keeping it at a temperature of 1 month 38 ° in formula, concentration 6: 1,000. The anatoxin thus obtained was purified up with metaphosphoric acid to remove the foreign proteins.

The precipitate obtained in this purification was washed with a buffer solution from an aqueous solution of glycocolla / sodium chloride, added, the Anatoxin content was 50 to 100 IU / cm3.

This anatoxin, which e.g. has a 50 to 100 times higher concentration compared to the tetanus vaccines currently used, was then counter-dialyzed concentrated and then stabilized in glycerine according to that of PLAN (R.) and FAYET (M.TH.), in the article "Concentration des solutions proteiques par les polyéthylènes-glycoles et polyvin ylpyrrolidones "in" Bulletin des Travaux de la Société de Pharmacie de Lyon "- 1960 - Vol. 4, No. 2, pp. 35 to 40 described procedure.

The tetanus vaccine thus obtained shows a 400-fold higher concentration of anatoxin than the common vaccine, i.e. a content of around 400 IU / cm3.

With the received vaccine against tetanus was already at the first vaccination an immunization achieved if 3. a vaccination gun 0.30 cm3 were administered intracutaneously.

To explain the effectiveness of the vaccine obtained according to the invention the results of an effectively conducted experiment are listed below.

14 children were given 0.30 cm3 of the vaccine obtained intracutaneously vaccinated against tetanus with the help of a vaccination gun (trade name "Dermo-Jet"), whereby it had been ensured beforehand that the children had one at the time of vaccination Had antigen levels less than 0.005 IU / cm3.

Ten weeks later the mirror was checked again: had 1 child a level above 0.20 '6 children had a level above 0.10 4 children had a level above 0.05 3 children had a level equal to or. about 0.02 this shows that uniform, effective vaccination protection had been achieved.

Another vaccination was administered subcutaneously / intramuscularly with the help of the made available under the trade name "Pedojet" vaccination gun. Here were nine children each injected 0.50 cm3 of the vaccine against tetanus according to the invention; the children had an antitoxin level of less than at the time of vaccination 0.005 IU / cm3.

10 weeks later the level was determined again: 1 child had one Mirror 0.20 3 children had a mirror greater than or equal to 0.10 2 children had a level 0.50 1 child had a level 0.05 1 child had a level 0.02 Booster vaccinations continued to be given; there were scarification rings with 9 tips used with the vaccine obtained according to the invention against Tetanus with a content of 1 000 IU / cm3 impregnated goods; every vaccinee received 4 impressions with the scarification ring.

This booster vaccination was carried out on 10 vaccinees and raised the antibody level to a level that would allow effective immunization guaranteed.

Claims (9)

Claims i, tetanus vaccine, with the when People are immunized with the first injection, g e k This is indicated by a tetanus anatoxin level of about 300 to about 1000 IU / cm3 2. Vaccine according to claim 1, g e k e n n z e i c h n e t by a Glycerine content as a stabilizing agent. 3. A method for producing a vaccine according to the claims 1 - 2, by the fact that a culture solution of P-Tetani produces, detoxifies this nutrient solution, cleanses the anatoxin obtained in this way and up concentrated to an antigen level of about 300 to about 1000 IU / cm3. 4. The method according to claim 3, characterized in that g e k e n n z e i c hn e t, that for the preparation of the culture solution of P-Tetani the strain 141 Toronto in A meat-liver medium is cultured in an incubator at 34o for 10 days, after which the solution is cultured sterile filtered. 5. The method according to claims 3 or 4, characterized g e k e n nz e i n e t that one detoxifies the culture solution with formol. 6. The method according to claim 5, characterized in that one detoxifies the culture solution with formol in a concentration of 6: 1000 approx Performs 1 month at a temperature of 380. 7. The method according to claims 3 to 6, characterized g e k e n nz e i c h.n e t that one cleans the anatoxin with metaphosphoric acid and the obtained Precipitate with a buffer from an aqueous solution of glycocolla / sodium chloride records. 8. The method according to claims 3 to 7, characterized g e k e n nz e i It is not possible to purify the anatoxin by counter-dialysis. 9. The method according to claims 3 to 8, characterized g e k e n nz e i c h n e t that the vaccine obtained is stabilized in glycerol.