The method of producing microcapsules containing living microorganisms

 

The invention relates to medicine. The method consists in the fact that the freeze-dried Lactobacillus cover shell, which contains polyvinylpyrrolidone, tanned tannin. In the production process is the formation of aggregates of macromolecules agent. The method provides the best survival of microorganisms in the process through the use of safe for macroorganisms and microorganisms ingredients. Microencapsulated Lactobacillus can then be placed in a variety of dosage forms and used in combination with other drugs. table 1.

The invention relates to medicine, namely to the technology of medicinal forms with bacterial drugs.

For the correction of dysbiotic conditions in medical practice widely used a variety of drugs, created on the basis of live strains of microorganisms that are part of the normal flora.

Recently, various researchers pay much attention to the use of microencapsulated forms of bacterial preparations. Substances used as encapsulating coating for microorganisms need both the NII in the wet environment of the organism.

Of particular interest in microencapsulated form of lactobacilli derived from polyvinylpyrrolidone. This polymer is non-toxic, not harmful to humans and microorganisms that are allowed for medical purposes. He has good solubility in inorganic solvents, including water, and its solubility depends on pH of the medium, it can be used to obtain microencapsulated forms of lactobacilli, intended for dissolution in a variety of environments, including for the production of microcapsules for topical use (in the form of powders).

A method of obtaining microencapsulated forms of lactobacilli using aqueous solutions of crosslinked or linear polyvinylpyrrolidone (U.S. patent 5733568, NPK 424-422, 1998). Its essence consists in the following: freeze-dried Lactobacillus is dispersed at a temperature of about 0oWith the solution crosslinked or linear polyvinylpyrrolidone with constant stirring, and then perform the cross-linking of the polymer divinylbenzene. When this bacteria take so that in the finished microcapsules was not less than 103bacteria in the same microcapsule.

When playing this sposobstvovanie and certain after the destruction of the membrane phosphate buffer, is less than 1041.0 gram of microcapsules.

The disadvantages of this method include the high loss rate of microorganisms in a process that achieves 104cells and more, and use as an agent for cross-linking of the polymer divinylbenzene, which is toxic organic reagent. The use of this substance leads, on the one hand, to a significant loss of microorganisms during the course of the production process, on the other - is dangerous to humans because it is a moderately toxic substance.

The invention was reduced losses of living organisms and increased process safety due to elimination of toxic reagents.

The task was solved by using as the curing agent of such natural substances as tannin obtained from vegetable raw materials (Sumy, cotinus and others) and represent the sum of polysaccharides rich in polyphenolic groups.

For the manufacture of microcapsules taken dried Lactobacillus containing 108cells in 1.0 gram.

The essence of the invention lies in the fact that the freeze-dried culture of microorganisms (customerinformation with molecular weight of 15000 (see table) in a ratio of from 1:10 to 1: 15 by weight with stirring to a suspension containing individual particles of the desired size. To the resulting suspension was added a solution of crosslinking agent (tanning agent) - 10%-30% aqueous solution of tannin (GFK, senior 658). The mixture is stirred for 30-180 minutes, then cured microcapsules are collected by filtration, washed and dried. The obtained microcapsules are particles of gray-yellow in size from 10 to 200 microns, depending on the rheological parameters of the technological mix.

The invention is illustrated by specific examples are set forth below.

EXAMPLE 1.

For the manufacture of microcapsules taken the culture of lyophilized Lactobacillus strains L. fermentum 90TS4 containing 108living cells in 1.0 gram.

Prepare 100.0 g of 50% aqueous solution of the polyvinylpyrrolidone, the process is carried out with constant stirring. Then in the specified solution for 30 minutes is dispersed 10.0 g of lyophilized lactobacilli until a homogeneous, stable suspension (process temperature 4oC). In parallel with the heating (water bath to about 80o(C) prepare a 30% aqueous solution of tannin in the amount of 140 ml to obtain a clear rest is pensio with a rate of 1.8 ml/min The system is left under stirring for 30 minutes, and cured microcapsules are then harvested by filtration, washed and dried. The obtained microcapsules are particles of gray-yellow color with a size of 50-150 μm. The yield of microcapsules was 70.5%. The number of viable lactic acid bacteria was determined after the destruction of the polymer shell microcapsules in phosphate buffer at pH of 7.6 to 7.8 with subsequent titration of culture and seeding of lactic acid bacteria on agar medium small ruminants. As control was used standard culture in the same dilutions. The number of viable lactobacilli in this example was 1.5104cells in 1.0 gram of microcapsules.

EXAMPLE 2 For the manufacture of microcapsules taken the culture of lyophilized Lactobacillus strains L. fermentum 90TS4 containing 108living cells in 1.0 gram.

Prepare to 120.0 g of 40% aqueous solution of polyvinylpyrrolidone, cooled to 4oFrom then to this solution was added 10.0 g of lyophilized lactobacilli and stirred until a homogeneous, stable suspension. After 30 minutes in this system a squirt serves 50 ml of a 10% aqueous solution of tannin, cooled to 4oC. the System axis of the microcapsules, they are collected by filtration, washed and dried. The obtained microcapsules are rounded particles of gray-yellow color size 50-120 μm. The output of the microcapsules was 67.8%. The number of viable lactobacilli was determined by the method described above. The number of viable lactobacilli in this case amounted to 4,5104cells in 1.0 gram of microcapsules.

EXAMPLE 3 For the manufacture of microcapsules taken the culture of lyophilized Lactobacillus strains L. fermentum 90TS4 containing 10 living cells in 1.0 gram.

Prepare 100.0 g of 50% aqueous solution of polyvinylpyrrolidone and cool it down to 4oC. 5.0 g of the freeze-dried lactic acid bacteria mixed with 5.0 g of inert carrier polysaccharide structure and then within 30 minutes is dispersed in a solution of PVP until a homogeneous, stable suspension. Further, in this system a squirt serves 50 ml of a 10% aqueous solution of tannin, cooled to 4oC. the System is left under stirring for 60 minutes. Cured microcapsules are collected by filtration, washed and dried. The obtained microcapsules are spherical particles of gray-yellow color size of 10-150 μm. The output was 75,9%. The amount of life the m was 5.3104cells in 1.0 gram of microcapsules.

EXAMPLE 4 For the manufacture of microcapsules taken the culture of lyophilized Lactobacillus strains L. fermentum 90TS4 containing 108living cells in 1.0 gram.

Prepare 75,0 g of 30% aqueous solution of polyvinylpyrrolidone cool his 4oC. the resulting solution for 30 minutes was dispersed in 5.0 g of freeze-dried lactobacilli until a homogeneous, stable suspension. Then the system through a separating funnel serves 70 ml of 30% aqueous solution of tannin, cooled to 4oWith a rate of 1.8 ml/min the System is left under stirring at 180 minutes, and then cured microcapsules are collected by filtration, washed and dried. The obtained microcapsules are rounded particles of gray-yellow color with a size of 80-200 μm. The yield of microcapsules amounted to 64.7%. The number of viable lactobacilli was determined by the method described above. The number of viable lactobacilli when it was 3.7104cells in 1.0 gram of microcapsules.

Claims

The method of producing microcapsules containing living microorganisms, based on polyvinylpyrrolidone, atherolitin in the ratio 1:10 - 1:15 by weight with stirring until the formation of a stable suspension, add 10-30% aqueous solution of tannin, the mixture is stirred until the formation of microcapsules.

 

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