DE1157734B - Process for the production of stable, orally administered poliomyelitis virus preparations - Google Patents

Description

Process for the production of durable, orally administered Poliomyelitis Virus Preparations The invention relates to a method of manufacture from durable poliomyelitis virus preparations to be administered orally attenuated live poliomyelitis viruses.

Poliomyelitis viruses that are ingested orally have been tried should be put into a durable form by placing them in capsules locked. However, this procedure is very cumbersome and time consuming. aside from that Many patients, especially young children, are reluctant to take capsules. Attempts have also been made to mix the poliovirus with sugar and put it in To be administered in sugar syrup or in the form of candy (see U.S. Patent 2 966 443, Academy of Medical Science of the USSR, Inst. For Poliomyelitis Research, Moscow, 1960, Report No. 2 [31. 12. 1959], pp. 66, 72, 73). Sugar syrup is however only difficult to dose, and besides, polioviruses are in both sugar syrup and Can only be kept for a few days in candy at room temperature. In the above, last mentioned Reference is made to the literature that the live Sabin virus is present at -15 to -20 "C has to be stored and at 4 to 8" C it cannot be kept for longer than 30 days. From this it is clear that the Russian authors have no method of making a Longer lasting oral poliovaccine was available as the subject matter of the present invention.

It was also inconvenient, one for oral administration planned poliovirus suspension into a durable form, for example by freeze-drying transferred, as the infectiousness of the virus is a prerequisite for effectiveness of the vaccine would have been affected. So far one had to make do with to freeze the poliomyelitis vaccine as such, to transport it in the frozen state and thaw immediately before application.

It has now been found that durable poliomyelitis virus preparations to be administered orally can be obtained from attenuated live poliomyelitis viruses in a simple manner thereby can that you apply the poliomyelitis viruses to sugar kernels and dry them.

To carry out this process, it is expedient to proceed in Way that an aqueous suspension of live attenuated poliomyelitis viruses, z. B. Type I (Sabin) with an IDso 107 335 applies to sugar cores and preferably let dry under sterile conditions. To accelerate the drying process you can work under reduced pressure or a sterile gas stream, z. B. air flow, use. The drying temperature is between 0 and 37 "C, preferably wise between 20 and 37 ° C. The titer is determined in a known manner in tissue culture.

The present method provides an orally effective polio vaccine obtained of good stability. The shelf life of known orally administered Polio vaccines in the unfrozen state is, as already mentioned, at room temperature z. B. only a few days, during a poliomyelitis virus preparation prepared according to the invention is stable for 6 weeks at room temperature without impairing the effectiveness. These Property is a great advantage for the wide applicability of so-called oral polyol vaccines.

The following examples illustrate the manufacture of vaccine preparations based on sugar nuclei, on the surface of which live weakened polioviruses Type I, II and III as well as a mixture of the three types are dried.

Per sugar nucleus is the amount required to infect a person Dose, about 200,000 to 500,000 TCID50 applied (TCIDso = tissue culture IDso) Of course, sugar cores with a higher dose of polioviruses can also be used for storage. z. B. a multiple of a dose required to infect a human being, be provided. So-called »multidose« preparations for storage can be produced, the z. B. contain 50 or 100 times the above dose. Before administration do you have to be dissolved, as they are for a correspondingly large number of vaccinated persons serve, e.g. B. for 50 or 100 people.

Example 1 500 sugar cores (Globuli sacchari, diameter 8 mm) at 20 ° C in a rotating flask dropwise with 20 ml of a mixture containing part of an aqueous suspension of poliovirus type 1 (Sabin) with an IDSo 107.835 and contains 2 parts of a sugar solution (2 parts of sugar to one part of water), added and dried at 20 ° C. with the aid of a stream of sterile air.

The titre per sugar core is 105.667 ID50 after production = 665 000 after 6 weeks of storage ... 105'375 ID50 = 237 000 Die in this way orally applicable preparations are under 6 weeks at room temperature Consideration of the error limit of the test can be kept with practically no loss of effectiveness.

Example 2 Poliomyelitis virus preparations according to the invention are produced in a corresponding manner made from poliovirus type II (Sabin) with an ID50 107,500.

The titers per sugar core after production are 105.286 ID50 = 193 000 after 6 weeks of storage ... 105-354 ID50 = 225 000 The activity of this The preparation is practically unchanged after 6 weeks of storage at 20 ° C.

Example 3 From poliovirus type III (Sabin) with an ID50 107.714 Poliomyelitis preparations are prepared according to the method of Example 1.

The titre per sugar core is 105,685 ID50 after production = 484,000 after 6 weeks of storage ... 105.417 ID50 = 261,000 The measured titers show that the activity of the stored preparation is within the error limit of the test has been preserved.

Example 4 20 ml poliovirus type I (Sabin) with an ID50 107.836, 20 ml poliovirus type II (Sabin) with an ID 507,600 and 20 ml poliovirus type III (Sabin) with an IDso 107s444 are mixed together and accordingly processed according to the method given in Example 1 to poliovirus preparations.

The titers are per sugar core for all three types together of production 105.806 ID50 = 381,000 after 6 weeks of storage ... 105.715 ID50 = 373 000 As can be seen from the data, the preparation that supports types I, II and III contains, can be stored for 6 weeks without loss of activity.

Claims (1)

PATENT CLAIM: Process for making durable, orally too administering poliomyelitis virus preparations from attenuated live poliomyelitis viruses, characterized in that the poliomyelitis viruses are applied to sugar nuclei and dries. References considered: U.S. Patent No. 2,966 443.