RU2659685C1 - Method of sorption-vacuum drying of liquid thermolabile biologically active materials - Google Patents

Abstract

FIELD: technological processes.

SUBSTANCE: invention relates to the field of drying various substances, in particular to the drying of liquid thermolabile biologically active materials (hereinafter referred to as BM), the quality of which is determined by the achievement of the required value of the indicator of the residual mass during drying and preservation of the specific activity of the biological agent, and can be used in food, medical, microbiological, chemical and related industries for the production of multicomponent dry preparations. Essence of the proposed method consists in the implementation of drying due to the two main sorption processes of adsorption and desorption of moisture flowing between the BM and lactose-filler-dehydrator simultaneously in one stage, that is, one technological stage in one technological apparatus at a vacuum of 670–680 mm Hg and a temperature of 2 to 20 °C. To intensify drying, it is produced by continuous mechanical mixing of the mixture and transferring it to the pseudo-boiling state by rotating the rotor-mixer.

EFFECT: invention makes it possible to intensify the drying process of thermolabile biologically active materials.

1 cl, 2 tbl

Description

The invention relates to the field of drying various substances, in particular to drying liquid thermolabile biologically active materials (hereinafter referred to as BM), the quality of which is determined by achieving the desired value of the residual mass during drying and maintaining the specific activity of the biological agent, and can be used in food, medical, microbiological, chemical and related industries for the production of multicomponent dry preparations.

A known method of combined dehydration of highly dispersed biologically active materials containing active substances in the liquid phase, carried out in several stages, characterized in that the liquid phase with the active substance from a microdrop state stabilized by a dry highly dispersed hydrophobic uncoupling in a ratio of 1: 3-1: 22, dehydrate initially at atmospheric pressure and then mixing with a moisture-absorbing sorbent with a residual moisture content of less than 1% and, if necessary, dried [1].

A known method of obtaining a dry probiotic preparation by mixing the culture with a protective medium followed by contact-sorption dehydration and drying of the target product, characterized in that the contact-sorption dehydration of the target product is carried out by a sorbent cooled to minus 8-10 ° C, for example, aluminum oxide with residual humidity of less than 1% with a mass ratio of 1:10, 1:12, respectively, and drying is carried out for 18-20 hours at a temperature of 0-5 ° C in a closed volume [2].

As a prototype, the method of drying biological materials [3] was selected, consisting in the fact that wet BM is mixed in a paddle mixer with anhydrous lactose in the ratios 1: (2, 3, 4 or more) for partial dehydration at a temperature of 4 to 25 ° С . Then the resulting wet biomass is removed from the mixer and packaged in a ditch with a thickness of 10-12 mm. The cuvettes are placed in a laboratory drying unit without preliminary cooling and heating, but with a refrigerated condenser-freezer. The drying unit is closed, the vacuum pump and the heating of the drying chamber are turned on. The amount of vacuum in the drying chamber is from 400 to 600 mm Hg. The temperature in the drying zone is not higher than 25 ° C, the drying time is 30-180 minutes.

The disadvantages of the prototype method include the following.

1. The multi-stage process. The process consists of two stages: the first is partial dehydration of BM, which occurs due to its mixing with lactose, the second is the vacuum drying of the resulting wet biomass to the desired value of the residual mass during drying.

2. The complexity of the process. The method involves the following sequence of technological operations: loading lactose into a paddle mixer, dosing BM, mixing BM with lactose to obtain a homogeneous wet biomass, unloading the biomass from the mixer and filling it into cuvettes, placing cuvettes with wet biomass in the drying chamber, drying the biomass to a predetermined values of the indicator of residual mass during drying.

3. The use of several technological devices. For the drying of BM, two technological apparatuses are required: the first is a paddle mixer, in which lactose and dried BM are mixed for its partial dehydration, the second is a drying unit in which the wet biomass is dried at a given vacuum and temperature.

4. High probability of contamination of wet biomass by extraneous microflora during operations in which the biomass is in the open state (unloading biomass from a paddle mixer, packaging it in cuvettes and placing them in a drying chamber).

5. The duration of the process of drying the biomass (up to 180 min), due to its being in an agglomerated state, stationary in a layer 10-12 mm thick.

6. Large technological losses. When BM and lactose are mixed, the resulting material is a biomass, the moisture of which does not allow to unload it without large technological losses due to sticking on the inner surface of the mixer body and the blades of the mixing device. Manipulations with biomass in the process of its unloading from the mixer and packaging in the cells are also accompanied by significant irretrievable losses of material.

The objectives of the invention are:

intensification of the drying process;

reduction in the number of technological stages and production operations;

reducing the complexity of the hardware of production and the complexity of the process;

elimination of the danger of contamination of dried biomass by extraneous microflora;

elimination of technological losses of biomass.

The problem is solved due to the fact that in the method of sorption-vacuum drying of liquid thermolabile biologically active materials by mixing them with a dehydrating filler, which is used as dehydrated lactose in mass ratios of 1: 5 or more, according to the invention, the ingredients are mixed and the resulting biomass is dried at the same time when it is transferred to a pseudo-boiling state with a vacuum of 670-680 mm Hg and temperature from 2 ° C to 20 ° C for one technological stage in one device.

Drying the BM to a condition characterized by the required values of the residual mass during drying and the specific activity of the bioagent is carried out in one technological stage.

For drying BM, one unit of technological equipment is used - a dryer of thermolabile materials (STM) [4], which provides optimal conditions for simultaneously mixing the dried BM with filler-dehydrator (lactose) and for removing moisture from the dried biomass.

The optimality of the conditions for drying BM created in STM is ensured by transferring the resulting wet biomass to a pseudo-boiling state with a vacuum of 670-680 mm Hg. and temperature from 2 ° C to 20 ° C [5].

To destroy the agglomerates formed by mixing BM and lactose, grinding bodies - metal balls - are introduced into the dried biomass.

Production operations involving the open storage of BM are excluded from the technological scheme of the drying process.

Technological losses of material in the implementation of the proposed method of drying are absent.

The essence of the proposed method consists in drying BM due to sorption processes occurring simultaneously in one technological stage in one technological apparatus with a vacuum of 670-680 mm Hg and at a temperature of 2 to 20 ° C. Sorption processes are:

- adsorption due to the redistribution of moisture between the dried BM and the moisture-intensive filler-dehydrator when they are dosed in STM;

- desorption is the reverse adsorption process in which moisture leaves the biomass from the surface of its particles and is removed from the drying zone.

To intensify sorption processes, drying is carried out with continuous mechanical mixing of the biomass due to the rotation of the paddle rotor-mixer in the STM, the speed of which ensures the biomass is transferred to the pseudo-boiling state [5]. Moreover, to disaggregate the agglomerates formed when BM is combined with lactose, metal balls are introduced into the dried biomass as grinding media.

The presence of a causal relationship between the totality of the essential features of the claimed object and the achieved technical result is shown in table 1.

The possibility of carrying out the claimed invention is shown by the example of the preparation of a dry preparation of a vaccine virus (SPVB). A liquid virus-containing material (LCM), which is a homogenate prepared from chorion-allantoic membranes and the fruit of 12-13-day-old chicken embryos infected with the vaccine virus, with the addition of a stabilizer, is used as BM for obtaining SPVV.

By analogy with example No. 1 of the prototype method, 100 g of HPM were subjected to drying with a specific activity index (8.7 ± 0.2) lg OOE⋅ml ^-1 . Mixing HPM and lactose was carried out in a mass ratio of 1:15, respectively.

1500 g of sterile dehydrated lactose cooled to a temperature of (4 ± 2) ° C in an amount of 1,500 g and grinding media (metal balls) were placed in a STM cooled to a temperature of (4 ± 2) ° C. By means of a sterile flexible conduit, a container with an HPM cooled to a temperature of (4 ± 2) ° C was connected to STM. STM was evacuated to a vacuum level of 670-680 mm Hg. The rotation of the rotor-mixer in the STM was turned on and 100 g of the liquid was dispensed. After the dosing, the STM was put into the temperature mode (18 ± 2) ° C.

The drying time after completion of the dosing of the HPM until the value of the indicator of the residual mass when drying less than 3% was 15 minutes The total duration of the drying process was 20 minutes Obtained after drying, the HPMV of SPVV was a powdered biologically active substance containing the vaccine virus.

The results of evaluating the impact of the proposed drying method and the prototype method on the stability of the vaccine virus in the preparation and storage of SPVV are shown in table 2.

The invention allows to significantly intensify the process of drying BM, to reduce the number of technological stages and production operations, to reduce the amount of technological equipment used and the complexity of the technological process; eliminate the danger of contamination of the dried biomaterial with extraneous microflora and completely eliminate technological losses of biomass.

The proposed method of drying is applicable on an industrial scale for large-scale production of multicomponent dry (powder) preparations.

List of sources used

1. Patent 2440099 RU, IPC A61K 009/14, A61K 035/74, A61K 049/16, A61K 047/04, F26B 005/16. The method of combined dehydration of highly dispersed biologically active materials / V.Yu. Davydkin, I.Yu. Davydkin, V.A. Aleshkin, A.V. Melikhova (RU); Federal budgetary institution of science "Moscow Research Institute of Epidemiology and Microbiology named after G.N. Gabrichevsky of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being" (Federal State Budgetary Institution of Medicine and Science named after G.N. Gabrichevsky Rospotrebnadzor) (RU). No. 2009101095/15; Claim 01/15/2009; Publ. 01/20/2012.

2. Patent 2067114 RU, IPC 6 C12N 1/20. A method of obtaining a dry probiotic preparation / I.M. Nakhabin, V.V. Perelygin, Yu.S. Birkina, A.V. Startsev (RU); State Research Institute of Applied Microbiology (GNII Applied Microbiology) (RU). No. 5016135/13; Claim 12/05/1991; Publ. 09/27/1996.

3. Pat. 2044239 RU, INC F26B 5/16. The method of drying biological materials / A.I. Grigorenko, V.P. Krasnyansky, V.N. Podkuyko, V.V. Mikhailov, A.M. Kurlov (RU); "Virology Center of the Scientific Research Institute of Microbiology" (CC NIIM) (RU). No. 93027480/06; Claim 05/11/1993; Publ. 09/20/1995.

4. Pat. 2607148 RU, INC F26B 11/14. Device for the preparation of dry thermolabile biological materials / I.V. Shmalko, N.G. Vlasov, A.Ya. Shelemetyev, V.V. Osin, S.V. Borisevich; Federal State Budgetary Institution “48 Central Research Institute” of the Ministry of Defense of the Russian Federation (FSBI “48 Central Research Institute” of the Ministry of Defense of Russia) (RU). No. 2015149573; Claim 11/18/2015; Publ. 01/10/2017.

5. Goncharovich I.F. Vibration technology in the food industry / I.F. Goncharovich, N.B. Uryev, M.A. Talisnik. - The food industry. - M .: 1977. - S. 32-34.

Claims (1)

A method of sorption-vacuum drying of liquid thermolabile biologically active materials by mixing them with a dehydrating filler, which is used dehydrated lactose in mass ratios of 1: 5 or more, characterized in that the mixing of the ingredients and drying of the resulting biomass is carried out simultaneously when it is converted to pseudo-boiling state with a vacuum of 670-680 mm RT.article and temperature from 2 to 20 ° C for one technological stage in one device.