RU2761303C1 - Method for obtaining a pharmaceutical composition and a pharmaceutical composition for the treatment and prevention of periodontal diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely dentistry, and concerns a method for obtaining a pharmaceutical composition for the treatment and prevention of periodontal diseases and a composition obtained in such a way that can be used for the treatment and prevention of periodontitis, gingivitis and periodontal disease, as well as for any infections of the oral cavity with the phenomena of inflammation and edema. The method consists in adding a mixture of chondroitin 4-6 sulfate to deionized water cooled to 0-4.0 degrees Celsius and a mixture of hydroxypropylmethylcellulose and hydroxyethylcellulose cooled to -18 degrees Celsius, stirred for 1 hour, heated to boiling, glycerin is added, in which the flavor in the form of essential oil or menthol is previously dissolved, stirred and the solution is brought to the required volume with deionized water, chlorhexidine bigluconate is added, stirred, the solution is kept for 24 hours. The pharmaceutical composition is characterized by the fact that it is obtained by the above method and contains a mixture of chondroitin 4-6 sulfates, chlorhexidine bigluconate, glycerin, flavor in the form of essential oil or menthol, hydroxyethyl cellulose, hydroxypropylmethylcellulose and deionized water at the following ratio, g/100 ml: chondroitin 4-6 sulfate 0.0005-0.01, chlorhexidine bigluconate 0.001, glycerin 4.5-7.5, flavor 0.004 2.0, hydroxypropylmethylcellulose 0.1-1.0, hydroxyethylcellulose 0.1-1.0, deionized water up to 100.0. At the same time, the total content of hydroxyethylcellulose and hydroxypropylmethylcellulose is at least 1.0 g/100 ml.

EFFECT: use of the group of inventions provides a more uniform distribution of components throughout the entire volume of the composition, as well as an increase in the effectiveness of treatment by increasing the exposure time and deeper penetration of active components into the tissues of the oral cavity.

2 cl, 2 dwg, 2 tbl, 4 ex

Description

The invention relates to medicine, more specifically to dentistry, and can be used for the treatment and prevention of periodontitis, gingivitis and periodontal disease, as well as for any infections of the oral cavity with symptoms of inflammation and edema.

A known method of obtaining a pharmaceutical composition for the treatment of periodontitis, which is obtained by mixing components, in particular methylcellulose, glycerin and water (US Pat. No. 4251507, 1981).

There is also known a method of obtaining a pharmaceutical composition for the treatment of periodontitis (RF Patent No. 2304427 dated 20.08.2007), which includes mixing a water-soluble derivative of cellulose, glycerin, water, while the water is heated and a mixture of chondroitin 4-6-sulfates is added to it, then the derivative is added cellulose, mix and add glycerin, in which peppermint oil is dissolved, mix and make up to the required volume with water and add chlorhexidine bigluconate and then settle for 24 hours. The composition contains a mixture of chondroitin 4-6 sulfates, chlorhexidine bigluconate, glycerin, peppermint oil, a water-soluble cellulose derivative and water. This method is closest to the proposed technical solution and therefore is chosen as a prototype.

The disadvantage of this method is that the mixing of the main components with a solution of methylcellulose is carried out while boiling purified water, which greatly complicates the dissolution of some of the components and their uniform distribution throughout the volume of the solution.

In addition, the obtained pharmaceutical composition for the treatment of periodontitis, made on the basis of one water-soluble cellulose derivative, has a weak anti-inflammatory and anti-edema effect and does not have a pronounced antimicrobial effect on periodontal tissues due to the rapid elimination of glycosaminoglycans and antiseptics from the solution composition. In particular, the use of hydroxyethyl cellulose does not provide a sufficient time exposure to the active components of the solution.

The objective of the invention, in terms of the method of obtaining a pharmaceutical composition for the treatment and prevention of periodontal diseases, is to improve the mixing quality of the components of the solution in order to distribute them more evenly throughout the volume, as well as to obtain an anti-inflammatory and anti-edema effect, to accelerate the processes of periodontal tissue repair and osseointegration, for by increasing the exposure time and deeper penetration into the tissues and oral cavity of the active components of the solution, in particular sulfated glycosaminoglycans (sGAG), namely chondroitin 4-6 sulfates and chlorhexidine bigluconate.

The technical result, according to the invention, is achieved in part of the method in that the method for producing a pharmaceutical composition for the treatment and prevention of periodontal diseases consists in the fact that a mixture of chondroitin 4-6 sulfates and cooled to -18 degrees Celsius, a mixture of hydroxypropyl methylcellulose and hydroxyethyl cellulose, stir for 1 hour, heat to a boil, add glycerin, in which a flavoring agent is previously dissolved, for example, peppermint oil, menthol or other essential oils, mix and bring the solution to the required volume with deionized water , add chlorhexidine bigluconate, mix, settle the solution for 24 hours. The resulting mixture is poured into vials.

According to the invention, a mixture of chondroitin 4-6 sulfates is used as the main active ingredient for preparing a pharmaceutical composition for the treatment and prevention of periodontal diseases. These substances are complex polysaccharides and belong to the class of sulfated glycosaminoglycans.

The introduction of a mixture of chondroitin 4-6 sulfates into the pharmaceutical composition is due to their stimulating effect on the processes of tissue repair and the ability to inhibit the process of fibrosis and the development of granulations (Waddington RJ, Embery G. 1994. Characterization of proteoglycan metabolites in human gingival crevicular fluid during orthodontic tooth movement. Archives of Oral Biology, 39, 361-368).

In addition, the introduction of chondroitin 4-6 sulfates into the composition is due to their stimulating effect on the processes of osteoreparation, which is especially important, since with advanced periodontitis, bone tissue is often damaged (Ivanov S. Yu., Larionov E. V. - New in dentistry. - M., 1999, issue 2).

It has been experimentally established that it is a mixture of chondroitin 4-6 sulfates that is capable of positively affecting the repair of a layered gum wound and inhibiting the germination of epithelium into the gingival pocket in experimental animals.

When using chondroitin 4 sulfate alone, stimulation of the gingival epithelium and fibroblasts was noted.

When using chondroitin 6 sulfate alone, only inhibition of epithelial migration was noted without a direct positive effect on periodontal tissue fibroblasts.

According to the invention, chondroitin 4-6 sulfates are introduced into the composition of the material as long as it is this combination that achieves a synergistic and adequate effect of these substances on pathologically altered periodontal tissues.

Chondroitin 4-6 sulfates are complex polysaccharides and are part of proteoglycans. In turn, proteoglycans, being one of the main components of the extracellular matrix of gum and bone tissue, are complex compounds of polysaccharides with protein. The polysaccharides included in their composition are linear polymers built from different disaccharide subunits formed by uronic acids (glucuronic, galacturonic and iduronic), N-acetylhexosamines (N-acetylglucosamine, N-acetylgalactosamine) and neutral saccharides (galactose and xylose). It is these polysaccharide chains that are called glycosaminoglycans. At least one of the sugars in the disaccharide has a negatively charged sulfate group. Periodontal tissues contain sulfated glycosaminoglycans such as chondroitin-4- and chondroitin-6-sulfates and a small amount of dermatan sulfate. The biosynthesis of proteoglycans in periodontal tissues and bone tissue is carried out mainly by activated gingival fibroblasts, osteoblasts and, to a small extent, by mature osteocytes of the alveolar bone.

Chondroitin 4-6 sulfates are introduced in the form of a powder into cooled deionized, depyrogenated water, which provides a more uniform swelling of powder particles, which finally dissolve after boiling deionized water, since at the boiling point they finally quickly and completely dissolve without destruction.

Chondroitin 4-6 sulfates are obtained as a mixture according to the method described in RF Patent No. 2162331 from various sources - trachea, bone or cornea, which does not exclude the possibility of using commercial substances chondroitin 4-6 sulfates, for example, from Sigma USA or Structum »Firm Pierre-Fabre France, it is possible to use chondroitin sulfate obtained from shark cartilage.

In the method for preparing the composition, deionized, deprirogenated water is used, which does not contain pyrogens, heavy metal salts, harmful impurities or other mechanical inclusions and has a maximum dissolving effect on chondroitin sulfate and a combination of hydroxypropyl methylcellulose and hydroxyethyl cellulose, as well as other components of the composition.

The effectiveness of the action of chondroitin 4-6 sulfates depends on the time of exposure of this substance to the tissues and oral cavity. To increase the ability for a longer exposure of the components of the composition for dissolving chondroitin 4-6 sulfates, they are added to deionized water cooled to 0-4 degrees Celsius, and powdered hydroxyethyl cellulose and hydroxypropyl methyl cellulose cooled to -18 degrees are added to the resulting solution. Cooled to -18 degrees hydroxyethyl cellulose and hydroxypropyl methyl cellulose do not stick together in water to form lumps that are difficult to dissolve in water, which improves the rheological properties of the composition and accelerates the formation of a homogeneous gel when heated to boiling. The combination of hydroxypropyl methylcellulose and hydroxyethyl cellulose, introduced into the pharmaceutical composition, gives it optimal rheological properties, which increase the exposure time of the main active ingredients, namely, a mixture of chondroitin 4-6 sulfate and chlorhexidine bigluconate.

The solution is stirred for 1 hour, since this time is sufficient for the distribution of hydroxypropyl methylcellulose and hydroxyethylcellulose throughout the volume of the solution. This time has been established experimentally.

After stirring the cellulose and heating, glycerin is added to the solution, in which the flavoring agent is previously dissolved in the form of one of the essential oils, for example, peppermint oil. The preliminary dissolution of the fragrance is a prerequisite, since otherwise, its dissolution in water will be difficult, and with large volumes of solution, it is simply impossible.

Glycerin is included in the composition in order to soften the mucous membranes of the oral cavity, as well as to impart a sweet taste and maintain the necessary viscosity. In addition, it is a solvent for peppermint oil.

A fragrance in the form of an essential oil is introduced into the solution not only as an aromatic additive, but also as a component to reduce inflammation or edema, as well as to make the solution better tolerated. The positive effect of the fragrance is also enhanced by the longer exposure time when using a viscous base of a mixture of hydroxypropyl methylcellulose and hydroxyethylcellulose.

After stirring, the solution is brought to the required volume with deionized water and added to the chlorhexidine digluconate solution.

Chlorhexidine bigluconate is currently a generally recognized highly effective antiseptic, widely used in many composite solutions for the treatment of periodontitis. Unlike other compositions, the concentration of chlorhexidine bigluconate is 0.001 g.

It has been experimentally established that this concentration is sufficient for the manifestation of the antiseptic properties of this substance. In addition, chlorhexidine bigluconate is a strong cation, and with an increase in its concentration, binding and a decrease in the healing properties of chondroitin 4-6 sulfates, which are polyanions, can occur.

After adding chlorhexidine bigluconate to the solution, the solution is stirred and defended for 24 hours at a temperature of 4 degrees Celsius.

This settling time is necessary for the final distribution of all components throughout the volume of the solution and the acquisition of its final viscosity. This time has been established experimentally.

After settling, the solution is heated to room temperature and poured into vials.

Brief technology for obtaining a pharmaceutical composition.

50.0 ml of deionized water is cooled to 0-4 degrees Celsius, 0.0005 g of chondroitin 4-6 sulfate powder is added to cooled deionized water, 0.5 g of hydroxypropyl methylcellulose in powder form and 0.5 g of hydroxyethyl cellulose (Natrosol "Hercules" Holland ) cooled to -18 degrees Celsius and placed in a cooled mixture of chondroitin 4-6 sulfate, stirred for 1 hour, heated to a boil, added from 5.0 g of glycerin, in which 0.004 g of flavoring was previously dissolved, mix and adjust the volume of the solution to 100.0 ml with deionized water, add chlorhexidine bigluconate 0.001 g, mix, settle the solution for 24 hours at 4.0 degrees Celsius and pour it into vials.

Known pharmaceutical composition for the treatment of periodontal disease, containing a water-soluble derivative of cellulose, glycerin and water (RF Patent No. 2304427 dated 20.08.2007).

However, due to the lack of optimal rheological properties of a viscous base made from a water-soluble cellulose derivative, the action of the active ingredients does not have a sufficient anti-inflammatory, anti-edema and antimicrobial effect.

The technical result, in terms of a pharmaceutical composition for the treatment and prevention of periodontal diseases, is an increase in anti-inflammatory, reparative, antimicrobial and anti-edema properties due to the introduction into the composition of a combination of hydroxypropyl methylcellulose (dispersive viscoelastic component) and hydroxyethyl cellulose (cohesive viscoelastic component).

The technical result, in terms of a pharmaceutical composition for the treatment and prevention of periodontal diseases, is achieved by the fact that it is obtained by the above method and contains chondroitin 4-6 sulfates, chlorhexidine, glycerin, a fragrance in the form of essential oil or menthol, hydroxypropyl methylcellulose, hydroxyethyl cellulose and depyrogenated water, with deionized the following ratio of components, wt. g / 100 ml:

Chondroitin 4-6 sulfates 0.0005 to 0.01 Chlorhexidine bigluconate 0.001 Glycerol 4.5 to 7.5 Flavoring 0.004 to 2.0 Hydroxypropyl methylcellulose 0.1-1.0 Hydroxyethyl cellulose 0.1-1.0 Deionized water Up to 100.0,

while the total content of hydroxyethyl cellulose and hydroxypropyl methyl cellulose is not less than 1.0 g / 100 ml.

The pharmaceutical composition according to the invention contains a mixture of chondroitin 4-6 sulfates, from 0.0005 to 0.01 g, which is optimal for the manifestation of anti-inflammatory, reparative and anti-edema effect.

The concentration of chondroitin 4-6 sulfates less than 0.0005 g does not have a pronounced stimulating effect on the process of periodontal tissue repair, and a concentration of more than 0.01 g may cause an allergic reaction.

Chlorhexidine bigluconate is currently recognized as a highly effective antiseptic, widely used in many composite solutions for the treatment of periodontitis. Unlike other compositions, the concentration of chlorhexidine bigluconate is 0.001 g.

It has been experimentally established that this concentration, in combination with all other components, is sufficient for the manifestation of the antiseptic properties of this substance. In addition, chlorhexidine bigluconate is a strong cation, and with an increase in its concentration, binding and a decrease in the healing properties of chondroitin 4-6 sulfates, which are polyanions, can occur.

According to the invention, glycerin is added to the composition from 4.5 to 7.5 g. The concentration of glycerol less than 4.5 g does not have a softening effect and does not maintain the viscosity of the solution, and a concentration of more than 7.5 g makes it unnecessarily sweet.

Essential oils in a concentration of 0.004 to 2.0 weight percent are used as a flavoring additive in the composition.

The concentration of the flavoring agent is limited by sanitary standards.

As a substance imparting viscosity and prolonging properties to the composition, a combination of hydroxypropyl methylcellulose in a concentration of 0.1 to 1.0 wt. % and hydroxyethyl cellulose in a concentration of 0.1 to 1.0 wt. %. Moreover, the total concentration of this combination is not less than 1.0 wt. %.

The use of a combination of hydroxypropyl methylcellulose and hydroxyethylcellulose allows you to optimize the colloidal state of the protective film that forms on the surface to be healed. The dispersive nature of hydroxypropyl methylcellulose makes it possible to form a protective film on the surface, which covers the surface very well, but at the same time is capable of partially blocking the action of the active components of the composition (Fig. 1). And cohesive hydroxyethyl cellulose has a structure in the form of spherical formations, which provides a greater penetrating ability of the solution into the niches of biological structures, but having a lower protective ability (figure 2). The combination of hydroxypropyl methylcellulose and hydroxyethylcellulose provides good protective properties and provides sufficient penetration and exposure of the active substances of the composition, which enhances the anti-inflammatory, reparative and antiseptic effect of the latter.

Fig. 1. Protective film of hydroxypropyl methylcellulose (electron scanning microscopy, magnification X250).

Fig. 2. Spherical structure of hydroxyethyl cellulose macromolecules (scanning electron microscopy, magnification X250)

The total concentration below 1.0 g does not impart viscosity to the solution, and at a concentration above 2.0 g, difficulties arise in the distribution of the basic substance and other components throughout the volume of the solution.

The preparation of a solution during the preparation of a pharmaceutical composition is controlled at each stage of its preparation and includes the main methods for assessing its characteristics, adopted for GOST R 51577-2000.

Chondroitin 4-6 sulfates were determined spectrophotometrically by staining with 1,9-dimethylene blue at a wavelength of 735 nm according to the Farndel method.

The control of the remaining components of the composition is done according to the State Pharmacopoeia of the XI edition.

The anti-inflammatory and reparative effect of the proposed composition was studied on experimental animals - Wistar rats, which were inflicted layer-by-layer wounds on the skin under local anesthesia.

Studies of the effect of the composition on the wound process were carried out on rats (a total of 20 animals), which under local anesthesia with a 0.5% solution of novocaine were made layer-by-layer gum wounds and intraoral baths of the drug were carried out on days 1, 3, 5 and 7 after the operation.

Control animals were given baths with the composition according to the prototype.

The results of these experiments are set out in Table 1.

Table 1 Effect of a pharmaceutical composition on full-thickness wound healing in rats. The size of a full-thickness wound (in% of the original) days after surgery 7 10 14 eighteen 21 24 27 control 75 ± 15 59 ± 12 35 ± 7 19 ± 3 8 ± 2 3 ± 2 0 0.005 mg / ml 60 ± 10 48 ± 17 23 ± 7 9 ± 3 0 0 0 0.01 mg / ml 63 ± 7 45 ± 7 29 ± 8 14 ± 3 3 ± 2 0 0

It can be seen that the healing of a full-thickness gum wound in the experimental animals proceeds one week faster than in the control animals.

The antimicrobial effect of a 0.001% solution of chlorhexidine bigluconate was studied on cultures from the collection of GKTSINILS (State Control Institute of Medicines).

The antimicrobial effect of the drug was determined according to the method specified in the State Fund of the XI ed., Issue 2, p. 188. The results of the determination are presented in table 2.

table 2 Dilution of the drug in a nutrient medium 1 ml of the drug, diluted with Sabouraud's medium in 10 ml of nutrient medium: Thioglycolic Test micro-organisms B. Subtilis S.aureus E.coli C.albicans ATCC 6633 ATCC 6538-P ATCC 25922 NCTC 885-653 1/10 ml - - - - 1/20 ml - - - - 1/50 ml - - - - 1/100 ml - - - - Control + + + + cultures of microorganisms + - the presence of growth of test microorganisms
- - no growth of test microorganisms

Conclusion: the pharmaceutical composition has antimicrobial effect under the conditions of the sterility test. When using the pharmaceutical composition for the treatment and prevention of periodontal diseases, according to the invention, the healing processes of periodontal tissues are accelerated, which ensures a reduction in the time of treatment and rehabilitation of patients. The components included in the composition provide pathogenetically targeted therapy for periodontal diseases.

For a better understanding of the essence, the invention is illustrated by examples of specific execution.

Example 1.

50.0 ml of deionized water is cooled to 3 degrees Celsius and powder 0.0005 g of chondroitin 4-6 sulfate ("Sigma" USA Cat. No. C 4384) is added to it, stirred and cooled to -18 degrees Celsius 1.0 g is added hydroxyethyl cellulose (Natrosol 250 Pharm "Hercules" Holland) and 0.1 g of hydroxypropyl methyl cellulose, stirred for 1 hour, heated to boiling, add 4.5 g of glycerin (grade PK-94, GOST 6824-96), in which 0 , 004 g of peppermint oil (FS 42-2804-01), stir and bring the solution volume to 100.0 ml with deionized water, add 0.001 g chlorhexidine digluconate (ND 42-3821-95), stir, settle the solution for 24 hours and poured into vials. Received a pharmaceutical composition with the following ratio of components g / 100 ml:

chondroitin 4-6 sulfate - 0.0005 (Sigma USA Cat. No. C 4384);

hydroxyethyl cellulose (Natrosol 250 Pharm "Hercules" Holland) - 1.0;

hydroxypropyl methylcellulose -0.1;

glycerin (grade PK-94, GOST 6824-96) - 4.5;

peppermint oil (FS 42-2804-01) - 0.004;

chlorhexidine bigluconate (ND 42-3821-95) - 0.001,

deionized water - up to 100.0 ml.

The pharmaceutical composition according to the invention is used as a therapeutic and prophylactic agent in the treatment of periodontitis, gingivitis, periodontal disease, as well as for any infections of the oral cavity with symptoms of inflammation and edema.

Example 2.

50.0 ml of deionized water is cooled to 0 degrees Celsius and powder of 0.005 g of chondroitin 4-6 sulfate, cooled to -18 degrees Celsius, is added to it, mixed and 1.5 g of hydroxyethyl cellulose and 0.5 g of hydroxypropyl methylcellulose, cooled to -18 degrees Celsius, are added , stirred for 1 hour, heated to boiling, added 5.0 g of glycerin, in which 2.0 g of Messina lemon essential oil was previously dissolved, stirred and the volume of the solution was adjusted to 100.0 with deionized water, 0.001 g of chlorhexidine bigluconate was added, stirred , the solution is defended for 24 hours and poured into vials. A pharmaceutical composition was obtained with the following ratio of components g / 100.0 ml: chondroitin 4-6 sulfate ("Sigma" USA Cat. No. C 4384) - 0.005 g, hydroxyethyl cellulose (Natrosol 250 Pharm "Hercules" Holland) - 1.5 g and hydroxypropyl methylcellulose - 0.5 g,

glycerin (grade PK-94, GOST 6824-96) - 5.0 g,

essential oil lemon messina - 2.0 g,

chlorhexidine bigluconate (ND 42-3821-95) - 0.001 g,

deionized water - up to 100.0 ml.

The pharmaceutical composition is used as a therapeutic and prophylactic agent in the treatment of periodontitis, gingivitis, periodontal disease, as well as for any infections of the oral cavity with symptoms of inflammation and edema.

Example 3.

50.0 ml of deionized water is cooled to 1 degree Celsius and 0.01 g chondroitin 4-6 sulfate powder cooled to -18 degrees Celsius is added to it, mixed and cooled to -18 degrees Celsius 0.5 g of hydroxyethyl cellulose and 0.5 g of hydroxypropyl methylcellulose, stirred for 1 hour, heated to boiling, 7.5 g of glycerin was added, in which 1.0 g of menthol was previously dissolved, mixed and the volume of the solution was adjusted to 100.0 ml with deionized water, chlorhexidine bigluconate 0.001 g was added, stirred , the solution is defended for 24 hours and poured into vials. Received a pharmaceutical composition with the following ratio of components by weight g / 100.0 ml:

chondroitin 4-6 sulfate ("Sigma" USA Cat. No. C 4384) - 0.01 g,

hydroxyethyl cellulose (Natrosol 250 Pharm "Hercules" Holland) - 0.5 g, hydroxypropyl methyl cellulose - 0.5 g,

glycerin (grade PK-94, GOST 68.24-96) 7.5 g,

menthol -1.0 g,

chlorhexidine bigluconate (ND 42-3821-95) - 0.001,

deionized water - up to 100.0 ml.

The pharmaceutical composition is used as a therapeutic and prophylactic agent in the treatment of periodontitis, gingivitis, periodontal disease, as well as for any infections of the oral cavity with symptoms of inflammation and edema.

Example 4.

50.0 ml of deionized water is cooled to 4 degrees Celsius and 0.01 g chondroitin 4-6 sulfate powder cooled to -18 degrees Celsius is added to it, mixed and 1.0 g of hydroxyethyl cellulose and 1.0 g cooled to -18 degrees Celsius are added g of hydroxypropyl methylcellulose, stirred for 1 hour, heated to boiling, add 7.5 g of glycerin, in which 0.5 g of sweet red orange essential oil is previously dissolved, mix and bring the volume of the solution to 100.0 ml with deionized water, add chlorhexidine bigluconate 0.001 g, stir, settle the solution for 24 hours and pour into vials. Received a pharmaceutical composition with the following ratio of components by weight g / 100.0 ml:

chondroitin 4-6 sulfate ("Sigma" USA Cat. No. C 4384) - 0.01 g,

hydroxyethyl cellulose (Natrosol 250 Pharm "Hercules" Holland) - 1.0 g, hydroxypropyl methyl cellulose - 1.0 g,

glycerin (grade PK-94, GOST 6824-96) - 7.5 g,

essential oil sweet red orange - 0.5 g,

chlorhexidine bigluconate (ND 42-3821-95) - 0.001,

deionized water - up to 100.0 ml.

The pharmaceutical composition is used as a therapeutic and prophylactic agent in the treatment of periodontitis, gingivitis, periodontal disease, as well as for any infections of the oral cavity with symptoms of inflammation and edema.

Claims (4)

1. A method of obtaining a pharmaceutical composition for the treatment and prevention of periodontal diseases, which consists in the fact that a mixture of chondroitin 4-6 sulfates and a mixture of hydroxypropyl methylcellulose and hydroxyethyl cellulose cooled to -18 degrees Celsius is added to deionized water cooled to 0-4.0 degrees Celsius, mixed for 1 hour, heated to a boil, add glycerin, in which the fragrance in the form of essential oil or menthol is previously dissolved, mix and bring the solution to the required volume with deionized water, add chlorhexidine digluconate, mix, settle the solution for 24 hours. 2. A pharmaceutical composition for the treatment and prevention of periodontal diseases, characterized in that it is obtained according to claim 1 and contains a mixture of chondroitin 4-6 sulfates, chlorhexidine bigluconate, glycerin, a fragrance in the form of an essential oil or menthol, hydroxyethyl cellulose, hydroxypropyl methylcellulose and deionized water at the following ratio, g / 100 ml: Chondroitin 4-6 sulfates 0.0005 to 0.01 Chlorhexidine bigluconate 0.001 Glycerol 4.5 to 7.5 Flavoring 0.004 to 2.0 Hydroxypropyl methylcellulose 0.1-1.0 Hydroxyethyl cellulose 0.1-1.0 Deionized water Up to 100.0, while the total content of hydroxyethyl cellulose and hydroxypropyl methyl cellulose is not less than 1.0 g / 100 ml.

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