Method of combination dehydratation of high-disperse biologically active materials

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a method of combination dehydratation of high-disperse biologically active materials containing active substances in a liquid phase, implemented in stages and differing by the fact that the liquid phase with the active substance in a microdrop state stabilised by a dry high-disperse hydrophobic disconnector in ratio 1:3-1:22, is dehydrated initially at atmospheric pressure and then by mixing with a high-absorbency sorbent with residual moisture less than 1% and dried up if needed.

EFFECT: invention provides higher activity of the active substances.

9 ex, 1 tbl

 

The invention relates to medicine and the pharmaceutical industry and relates to a method of obtaining dry biologically active materials dehydration by a combination of methods.

A known method of drying biological materials, in accordance with which the dehydration is carried out in two stages: the first stage partial dehydration of the material is carried out by mixing with anhydrous lactose, lactose is converted into crystalline, which subsequently facilitates the process of removing the moisture to the desired residual moisture content of from 2 to 4%); at the second stage, the final drying of the material by vacuum evaporation under vacuum, excluding samozatachivanie, when heated not higher than 25C (EN, application 93027480 A, F26B 5/16, 27.10.1996).

The main disadvantage of analog is the impossibility of its use for dewatering fine-grained materials.

The closest to the technical nature of the claimed is a method for freeze-dried bacterial drugs, according to which a suspension of microorganisms is mixed with sorbent - dry fine powder of silicon oxide, in a ratio of 2:1, drying is carried out in thermostat at 27-32C or in air and the resulting mixture was dispersed to fine condition (RU, patent 2104299 C1, C12N 1/04, 10.02.1998).

Essentially know the private method involves a combination of dehydration of the suspension of microorganisms: in the first stage, the removal of part of the moisture adsorbent - a powder of silicon dioxide, the second to remove the remaining moisture from the material (sorbent) in thermostat at 27-32C or in the air.

The main disadvantage of the prototype is a large loss of activity of active substances in the dehydration process of biologically active materials.

The basis of the claimed invention is the task of increasing the activity of active substances in the dehydration process of biologically active materials.

The problem is solved by the fact that the liquid phase sequentially dehydrated from drip condition, stable dry finely dispersed hydrophobic disconnector with nano particles, initially at atmospheric pressure and then mixed with absorbent sorbent at a ratio of 1:3-1:22.

As a result of our research for the first time shows that the benefit of the dehydration of liquids containing biologically active substances from drip condition, stable dry finely dispersed hydrophobic disconnector with nano particles, is that this condition generates the expanded surface of the liquid in the powder component, according to our data, 0,04-0,09 m21 cm3powder that provides a large area of moisture evaporation, and consequently the short duration of the removal of the free mass is the lag in the surrounding space, since the process is carried out from the total volume of dried powder. This allowed for the first stage of drying to apply air (at atmospheric pressure) dehydration of the material to a moisture content of 20-25%, still does not have a negative impact on the activity of active substances contained in the materials.

Since the removal of the remaining moisture from the materials under such conditions (atmospheric drying) is not practicable without significant loss of activity of the bio-component, then in the second stage, we applied the method of sorption-pin dehydration absorbent sorbents, which is not only the most effective for the removal of bound water, but also allows changing the number of used sorbent handling residual moisture in dried materials, and hence their biological activity.

High absorption rate of moisture sorbents allows you to quickly place the segment relative humidity drip powder in the mixture in the range of "critical" moisture 7-8%, corresponding 22-28% relative humidity biologically active substances (e.g., microorganisms) and determine their mass inactivation [Monk G.W., McCaffrey P.A., Davies M.S. Studies on the mechanism of sorbed water killing of bacteria // J.Bacteriol. - 1957. - V.73. - P.661-672], which leads to increased activity of the active substances is involved in a process of dehydration labile biologically active materials.

According to the invention, the increase of activity of active substances in the dehydration process of biologically active materials is ensured by the fact that the liquid phase sequentially dehydrated from drip condition, stable dry finely dispersed hydrophobic disconnector with nano particles, initially at atmospheric pressure and then mixed with absorbent sorbent at a ratio of 1:3-1:22.

The inventive method combined dehydration high dispersion of the biologically active material is new and are not described in literature.

The technical result of the claimed invention is the increased activity of the active substances in the dehydration process of biologically active materials.

The invention is illustrated in the following examples, showing the increase of activity of active substances in the dehydration process of biologically active materials during implementation of the method.

The content in the preparations of viable aerobic microorganisms Serratia marcescens was determined by the method of Pasteur-Koch on solid nutrient media. The content of viable anaerobic microorganisms Bifidobacterium bifidum was determined in a liquid nutrient medium by the method of limiting dilutions. Biological activity of antibodies preparations characterized protional hellesnes activity (in the credits TPHA) [FS 42-3347-97]. Sterilization of sorbents with simultaneous dehydration was performed in a dry-heat Cabinet SUP-4 at a temperature of 120C with exposure to steady-state thermal conditions for at least 2 hours.

Example 1. The object of dehydration were prepared by mixing a suspension of the microorganism Serratia marcescens pieces VKM-851 with lactase protective environment in the ratio of 2:1 and translated it into drip condition in the electromagnetic dispersant. Drip powder culture test to check air filters with the liquid phase in drip condition, stable dry finely dispersed hydrophobic disconnector with nanosized particles with concentration of viable microorganisms 56109CFU/g initially dried at atmospheric pressure at room temperature to a moisture content of 60%, and then mixed with sorbent KB-4P-2 with a residual humidity of less than 1% and a temperature of minus 10-15C for 5 min with a ratio of the liquid phase and the sorbent was 1:3 in a screw mixer. The mixture was loaded into a metal canisters and placed on final drying at a temperature of 2-8C for 6-12 hours.

The biological activity of the finished dry product test culture for inspection of air filters and its moisture content are presented in the table.

Example 2. The implementation of the method of dewatering a suspension of the microorganism Serratia marcescens pieces VKM-851 with La is tonneu protective environment was carried out, as described in example 1, but to an intermediate moisture content of 20% and with a ratio of liquid phase to the adsorbent 1:22.

Moisture content and biological activity of the finished dry product of the culture test to check air filters, consisting of dry particles (bacterial cells with components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

Example 3. The implementation of the method of dewatering a suspension of the microorganism Serratia marcescens pieces VKM-851 with lactase protective environment was carried out as described in example 1, but to an intermediate moisture content of 35% and with a ratio of liquid phase to the adsorbent 1:10.

Moisture content and biological activity of the finished dry product of the culture test to check air filters, consisting of dry particles (bacterial cells with components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

Example 4. The object of dehydration were prepared by mixing suspensions of microorganisms Bifidobacterium bifidum pieces 1C with Saharsa-breast protective environment in the ratio of 2:1 and translated it into drip condition in the disk disperser. Drip powder probiotic preparation with the liquid phase in mi is rockapella condition, stable dry finely dispersed hydrophobic disconnector with nanosized particles with concentration of viable microorganisms of 3.2109CFU/g initially dried at atmospheric pressure at room temperature to a moisture content of 60%, and then mixed with sorbent dispersed alumina with residual moisture less than 1% and a temperature of minus 10-15C for 5 min with a ratio of the liquid phase and the sorbent was 1:3 in a drum mixer. The mixture was loaded into a metal canisters and placed on final drying at a temperature of 2-8C for 6-12 hours.

The biological activity of the finished dry probiotic drug and its moisture content are presented in the table.

Example 5. The implementation of the method of dewatering a suspension of microorganisms Bifidobacterium bifidum was carried out as described in example 4, but to an intermediate moisture content of 20% and with a ratio of liquid phase to the adsorbent 1:22.

Moisture content and biological activity of the finished dry probiotic preparation, consisting of dry particles (bacterial cells with components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

Example 6. The implementation of the method of dewatering a suspension of microorganisms Bifidobacterium bifidum was carried out as described in the example is 4, but to an intermediate moisture content of 35% and with a ratio of liquid phase to the adsorbent 1:10.

Moisture content and biological activity of the finished dry probiotic preparation, consisting of dry particles (bacterial cells with components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

Example 7. The object of dehydration were prepared by mixing a solution of immunoglobulins IgG, IgA, IgM with glycine (2%) as a protective environment and translated it into drip condition in the disk disperser. Drip powder immunobiological preparation of liquid phase in drip condition, stable dry finely dispersed hydrophobic disconnector with nanosized particles with protivoallergennoy activity 1:640 in the credits TPHA was initially dried at atmospheric pressure at room temperature to a moisture content of 60%, and then mixed with sorbent alumina with residual moisture less than 1% and a temperature of minus 15-20C for 5 min with a ratio of the liquid phase and the sorbent was 1:3 in a drum mixer. The mixture was loaded into a metal canisters and placed on final drying at a temperature of 2-8C for 6-12 hours.

The biological activity of the finished dry immunobiological preparation and vlahos is the actual content presented in the table.

Example 8. The implementation of the method of dehydration of the solution of immunoglobulins IgG, IgA, IgM was carried out as described in example 7, but to an intermediate moisture content of 20% and with a ratio of liquid phase to the adsorbent 1:22.

Moisture content and biological activity of the finished dry immunobiological preparation, consisting of dry particles (a mixture of antibodies to components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

Example 9. The implementation of the method of dehydration of the solution of immunoglobulins IgG, IgA, IgM was carried out as described in example 7, but to an intermediate moisture content of 35% and with a ratio of liquid phase to the adsorbent 1:10.

Moisture content and biological activity of the finished dry immunobiological preparation, consisting of dry particles (a mixture of antibodies to components of a protective environment), stable dry finely dispersed hydrophobic disconnector with nano particles and sorbent presented in the table.

The dry preparation basedThe ratio of liquid phase to the sorbentThe biological activity of the drug Veloster-content, %
before dehydrationafter dehydration
Serratia marcescensprototype1:1273109CFU/gof 6.7109CFU/g13,0
declare1:356109CFU/g19,6109CFU/gof 17.0
1:1056109CFU/g24,0109CFU/g6,5
1:2256109CFU/g20,3109CFU/g3,5
Bifidobacterium bifidumprototype1:10of 4.2109CFU/gthe 5.7108CFU/g10,8
declare1:3of 3.2109CFU/gthe 9.7108CFU/g16,6
1:10of 3.2109CFU/g8,4108CFU/g7,0
1:22of 3.2109CFU/g7,3108CFU/g4,0
immunoglobulins IgG, IgA, IgMprototype1:121:6401:16012,2
declare1:31:6401:32015,8
1:101:6401:3206,2
1:221:6401:3204,1

As follows from the analysis of the data presented in the table, the materials obtained in implementing the inventive method of dehydration, at the same moisture content have a 1.3-3.5 times higher activity compared with products prepared in accordance with the prototype, which is provided for dewatering the liquid phase of the drip condition, stable dry the highly dispersed hydrophobic disconnector with nano particles and combination of methods in atmospheric and sorption of dehydration.

The method combined dehydration 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 drip from the state, stable dry finely dispersed hydrophobic disconnector in the ratio of 1:3-1:22, dehydrated initially at atmospheric pressure and then mixed with absorbent sorbent with residual moisture less than 1% and, if necessary, be dried.



 

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