RU2181583C1 - Agent for treatment and prophylaxis of diseases of maxillofacial region organs - Google Patents

Abstract

FIELD: medicine, phytotherapy. SUBSTANCE: invention relates to medicinal agents based on vegetable materials. Agent has lavender essential oil and/or bergamot essential oil, film-forming agent based on a mixture of polyvinyl alcohol aqueous solutions, potato starch, glycerol and water. Components are taken in definite quantitative ratios. Agent is used as a film, it shows good adhesion, prolonged effect, antibacterial and sedative action. EFFECT: enhanced effectiveness of agent, significant decreased time of treatment. 1 cl, 24 ex

Description

 The invention relates to medicine, namely to medicines based on plant materials with a prolonged action and intended for use in otolaryngology and dentistry.

 Known drugs for the treatment of acute and chronic (acute) inflammatory diseases of the maxillofacial region - the nose, pharynx and larynx, including anti-inflammatory and antiseptic agents that provide pharmacological effects and obtained from plant materials (for example, G. V. Lavrenova. Treatment of diseases ear, throat, nose. Series “Healing herbs.” St. Petersburg: SMIO Press, Diamant, 1997).

 It is known and in medical practice that the drug "KAMETON" Aerosolum ("Cametonun" aerosolum) is used, containing chlorobutane anhydrate, camphor, menthol, eucalyptus oil, liquid paraffin, and freon in predetermined concentrations (Medicines used in medical practice in the USSR. Reference. Edited by A.M. Klyuyev, Moscow: Medicine, 1990, p. 152). An indication for the use of an antimicrobial agent is acute and chronic diseases of the nasopharynx and larynx. The drug is used by spraying in the mouth and nose 3-4 times a day for 1-2 s, while the duration of inhalation is 1-2 minutes. The tool is not prescribed for children under 5 years of age, it is sensitive to ambient temperature, mechanical stress on the container in which the product is stored. The known product has insufficient impact effectiveness due to its short duration, the consumption of the product is high, and, in addition, the freon-containing product has a known effect on the environment, since freons accumulate in the atmosphere, almost without destruction.

 Known agent for the treatment of inflammatory diseases of the nasopharynx (acute rhinitis, pharyngitis, pharyngolaryngitis) - "KAMFOMEN" Aerosol ("Camphomenum" aerosolum), which has antimicrobial and emollient action, which contains alcoholic solution of furacilin, menthol, eucalyptus oil, castor oil, camphor oil, camphor oil, camphor oil olive oil, freon (Medicines used in medical practice in the USSR. Reference book. Edited by A.M. Klyuyev. M: Medicine, 1990, p. 153). The tool has a good therapeutic effect, due to the properties of components of plant origin, is applied by spraying in the mouth and nose 3-4 times a day for 1-3 sprays per procedure. The drug is not prescribed for children under the age of 5 years, as well as for patients working in conditions of significant dustiness of the air. A disadvantage of the known means can be considered the low effectiveness of its impact, due to its short duration, high consumption of funds, limited use, relatively extended treatment periods, as well as the effect of freon on the environment.

 A known tool for the treatment and prevention of diseases of the oral cavity, containing a biologically active substance of plant origin - coniferous sodium chlorophyllin, film former - gelatin or agar-agar and water at a given ratio of components (patent application N 98105696/14 of 03/26/98, A 61 K 7/26, 35/78, publ. 01/27/2000). The tool, the therapeutic component of which is included in the gelatin film (agar-agar), has a prolonged action, which increases its therapeutic effect, allows you to optimize the therapeutic dose of the active substance, to individualize the treatment regimen.

 Stabilized pharmaceutical compositions of a wide spectrum of action are also known, including biologically active substances, in particular antibiotics, in the composition of a solid dispersion of moderately water-soluble medicinal substances, converted to an amorphous state by joint heat treatment with stabilizing agents such as polyvinyl alcohol (PVA), or starch, or polyvinyl acetate, or gelatin, etc. (application PCT / JP 96/02246 from 08.08.96, A 61 K 9/00). However, the use of such compositions, including antibiotics, can cause allergic reactions, inhibition of the body's immune system, as well as the multi-resistance of pathogens to antibiotics, despite the fact that the choice of a stabilizing agent allows you to control the solubility of drugs (their composition).

 A known tool for the treatment and prevention of diseases of the organs of the maxillofacial region, in particular the oral cavity, including a biologically active substance of plant origin and a film former, is selected as the closest analogue of the claimed invention.

 The objective of the invention is to expand the range of prolonged therapeutic effects for the treatment and prevention of diseases of the organs of the maxillofacial region.

The problem is solved in that in the known tool for the treatment and prevention of diseases of the organs of the maxillofacial region, including a biologically active substance of plant origin, a film former and water, in accordance with the invention as a biologically active substance of plant origin it contains lavender oil and / or bergamot oil , and as a film-forming agent - a mixture of aqueous solutions of polyvinyl alcohol and potato starch with glycerin in the following ratio of components, wt.%:
Polyvinyl alcohol - 7.0-9.0
Food potato starch - 7.0-9.0
Glycerin - 3.5-4.5
Lavender oil and / or bergamot oil - 0.9-1.1
Water - Else
The technical result of the invention is to obtain resistant to mechanical stress and a plastic polymer film containing essential oils in its volume, which has good adhesion to the mucosa of the maxillofacial region and satisfactory organoleptic properties, has the ability to dissolve with the gradual release of an active therapeutic agent, as which uses volatile essential oils, which include at least 100 organic and inorganic substances with ntisepticheskimi, sedative and antispasmodic properties of the nervous system and exhibiting antiviral properties.

 Upon receipt of the film, potato starch is used, which has good water absorption and swelling, acceptable taste, low cost, and gives the films good mechanical properties. LAN and starch are polymers that structure the film, glycerin gives it elasticity. The formation of the film and its properties are due to the structure and properties of the components of the film former. The starch polymer contains amylose, an unbranched molecule of a spiral structure with six monosaccharide units in each turn, connecting suitable-sized molecules into the internal channel of the spiral, and amidopectin, a branched starch fraction with a cluster structure, in which individual sections of the polyglycoside chains are helical like. During the formation of the film, starch and PVA form a polymer matrix network structure, in the micropores of which essential oils are included. The use of lavender or bergamot oils is due to their volatility, the absence of fatty traces after evaporation, which ensures complete cleansing of the surface of the mucous membrane of the maxillofacial region from a therapeutic agent after the film is dissolved.

The inventive tool is obtained as follows. The initial film-forming solution is prepared by preparing an aqueous PVA solution of a predetermined concentration, which is heated on a magnetic stirrer to 40 ^{° C.} , into which an aqueous starch solution of a predetermined concentration and a predetermined amount of glycerol are then poured. The resulting mixture is heated with constant stirring until a gel-like homogeneous mass is obtained, to which the calculated amount of lavender or bergamot oil (or a mixture thereof) is added dropwise in a predetermined ratio to the volume of the aqueous film-forming solution. The mixture is poured into Petri dishes of 25 ml each in a thin layer, dried in a dry oven at a temperature of 45-50 ^o C in a closed Petri dish for 3-5 hours, cooled in air in an open cup for 1 hour, then ready to the use of the film is separated from the walls of the Petri dishes.

 The properties of the obtained films with an immobilized therapeutic agent are sensitive to maintaining the given ratios of the components. To study the mechanical properties of the films, they were obtained by varying the quantitative composition of the components. The therapeutic effect was assessed by the results of microbiological studies in the test system - by the diameter of the zone of inhibition of bacteria of the standard strain of Staphylococcus aureus Golden staphylococcus aureus 809 on standard-sized disks cut from films (disk method).

 Example 1. Received a film according to the above scheme. To prepare 50 g of the composition, 4 g of PVA was added to a container with preheated distilled water with a volume of 20 ml (weight 20 g), which was dissolved with continuous stirring, preventing the formation of large conglomerates. In distilled water with a volume of 19.5 ml (weight 19.5 g), 4 g of starch was dissolved under heating and continuous stirring, after which the aqueous solutions of PVA and starch were mixed and 2 g of glycerol were added to the resulting mixture, and then the solution was thickened to a gel-like consistency homogeneous mass with continuous stirring and heating. 0.5 g of lavender or / and bergamot essential oil was added dropwise, mixed and poured into Petri dishes for drying in an oven.

 In terms of 100% mass of the mixture, the indicated amounts of the components provide the following ratios of the components, wt.%: PVA 8.0, potato starch 8.0, glycerin 4.0, lavender oil and / or bergamot oil 1.0, water - the rest.

 After drying in a dry oven, we got a dense, elastic, homogeneous film with the smell of essential (lavender) oil.

 According to microbiological studies, the diameter of the zones of inhibition of bacteria in the test system was 13-15 mm.

 Example 2. A film was obtained, as in example 1, by dissolving 4.5 g of LAN in 19.5 ml of distilled water (content of 9.0 wt.% LAN in the mixture). The obtained films had satisfactory mechanical and organoleptic properties, the diameter of the zones of inhibition of bacteria coincided with the results of example 1.

 Example 3. A film was obtained, as in example 1, using a solution of PVA at a concentration of 5 g of PVA per 19 ml of distilled water (content of 10 wt.% PVA in the mixture). After drying in a dry oven, a solid, dense, poorly soluble film was obtained in water. Lavender oil practically did not stand out, because according to microbiological studies of zones of inhibition of bacteria was not observed.

 Example 4. A film was obtained, as in example 1, using a solution of PVA at a concentration of 3.5 g of PVA per 20.5 ml of water, which gives a concentration of 7.0 wt.% PVA in the mixture. The obtained films had satisfactory mechanical and organoleptic properties, the diameter of the zones of inhibition of bacteria coincides with the results of example 1.

 Example 5. A film was obtained, as in example 1, using a solution of PVA at a concentration of 3 g of PVA per 21 ml of water, which gives a content of 6.0 wt.% PVA in the mixture. After drying, the mixture remained gelatinous; no films were obtained.

 Thus, the optimal PVA content in the mixture is 7.0-9.0 wt.%.

 Then films were obtained, as in example 1, with an average PVA content of 8 wt.%, Varying the content of potato food starch in the composition.

 Example 6. A film was obtained, as in example 1, using a solution of 4.5 g of potato starch in 19 ml of water, which gives a content of 9.0 wt.% Starch in the composition. The obtained films had satisfactory mechanical properties, the diameter of the zones of inhibition of bacteria coincided with the results of example 1.

 Example 7. A film was obtained, as in example 1, using a solution of 5 g of potato starch in 18.5 ml of water, which corresponds to 10.0 wt.% Starch in the mixture. The resulting films had satisfactory mechanical properties, however, the diameter of the zones of inhibition of bacteria decreased on average to 10 mm, which is associated with a decrease in the diffusion of essential oils into the polymer structure and a decrease in the effectiveness of the film.

 Example 8. The obtained film, as in example 1, using a solution of 3.5 g of potato starch in 20 ml of water, which corresponds to 7.0 wt.% Starch in the mixture. The obtained films were suitable for use, although they turned out to be more loose than in example 1, but the diameter of the oppression zones almost coincided with the results of example 1.

 Example 9. The obtained film, as in example 1, using a solution of 3 g of potato starch in 20.5 ml of water, which is 6 wt.% Starch in the mixture. The resulting films were loose, crumbled and could not be used for their intended purpose.

 Thus, it was found that the optimal concentration of potato starch in the mixture is 7.0-9.0 wt.%.

 Then films were obtained, as in example 1, at average concentrations of PVA 4.0 wt.% And potato starch 4.0 wt.%, Varying the glycerol content in the mixture.

 Example 10. The obtained film, as in example 1, adding to the mixture of aqueous solutions of PVA and starch of potato glycerin in an amount of 2.5 g, which is a concentration of 5.0 wt.% In the mixture. Received films of satisfactory quality, elastic. The diameter of the zones of inhibition of bacteria coincided with the results of example 1.

 Example 11. The obtained film, as in example 1, adding to the mixture of aqueous solutions of PVA and starch of potato glycerin in an amount of 3 g, which corresponds to a content of 6.0 wt.% In the mixture. The resulting films were sticky, wet, inhomogeneous and could not be used for their intended purpose.

 Example 12. Films were obtained, as in example 1, adding to the mixture of aqueous solutions of PVA and starch potato glycerin in an amount of 1.5 g, which corresponds to a content of 3.0 wt.% In the mixture. Despite the increase in fragility, the obtained films nevertheless possessed acceptable mechanical properties; the diameter of the zone of inhibition of bacteria is close to the results of Example 1.

 Example 13. The obtained film, as in example 1, adding to a mixture of aqueous solutions of PVA and starch of potato glycerin in an amount of 1 g, which corresponds to a content of 2.0 wt.% The mixture. The resulting films crumbled, were brittle and brittle, not suitable for use.

 Thus, it was found that the optimal concentration of glycerol in the mixture is 3.0-5.0 wt.%.

 Given the mutual influence of the content of the components of the film former in the mixture on the quality of the films, it should be recognized as preferable to maintain the concentrations of the components of the mixture near the average values from the indicated intervals of their change.

 Then films were obtained, as in example 1, with average interval concentrations of the components of the film former in the mixture, varying the content of lavender essential oil and / or bergamot oil.

 Example 14. The obtained film, as in example 1, adding to the mixture of the component of the film former lavender oil at a concentration of 0.45 g per 50 g of the mixture, which is about 0.9 wt. % in the mixture. Films with antibacterial properties close to those of Example 1 were obtained.

 Example 15. Films were obtained, as in example 1, adding lavender oil at a concentration of 0.4 g per 50 g of the mixture to the mixture of the film-forming component, which is about 0.8 wt.% In the mixture. Films with a weakened antibacterial effect were obtained; the diameter of the zones of inhibition decreased to 5–9 mm, i.e. one and a half to two times compared with example 1.

 Example 16. Films were obtained, as in example 1, by adding to the mixture the film-forming component of lavender oil in an amount of 0.55 g per 50 g of the mixture, which is about 1.1 wt.% In the composition. Films with a good antibacterial effect were obtained, the size of the zones of inhibition of bacteria coincided with the results of example 1.

 Example 17. Films were obtained, as in example 1, adding lavender oil in the amount of 1.0 g per 50 g of the mixture to the mixture of the film-forming component, which is 2.0 wt.% In the composition. The resulting films had an antibacterial effect comparable to the results of example 1, and therefore, an increase in the content of essential lavender oil is not justified from the point of view of optimizing the process of obtaining films.

 Example 18. Films were obtained, as in example 1, adding lavender oil in the amount of 1.5 g per 50 g of the mixture to the mixture of the film-forming component, which is 3 wt.% In the mixture. The resulting mixture is characterized by instability of the structure, an oil-water separation occurs, the oil is poorly fixed in the polymer matrix.

 Example 19. Films were obtained, as in example 1, using bergamot oil, at identical concentrations of the components of the mixture. The quality of the film and its antibacterial properties are equivalent to the properties of lavender oil, which allows them to be used both separately and in combination.

 Thus, it was found that the optimal concentration of lavender and / or bergamot oil in the mixture is 0.9-1.1 wt.%.

 The obtained films of prolonged action of the therapeutic component were tested for therapeutic and prophylactic purposes in diseases of the organs of the maxillofacial region.

 Example 20. Patient A., 23 years old, complaints of difficulty in nasal breathing. Sick for 1 year, a history of surgery for curvature of the nasal septum (sectum surgery). With anterior rhinoscopy, the nasal mucosa is pink, there is no discharge, on the right - in the posterior sections there are synechia between the middle nasal concha and the nasal septum, on the left - a small synechia between the lower nasal concha and the nasal septum.

 Under local anesthesia (lidocaine solution 10% - 1.0), a synechia was dissected, and cut pieces of a polymer film with lavender oil were introduced into the nasal cavity, which remained in the nose for 4-6 hours until complete resorption. The procedure was repeated daily for 3-5 days.

 The films did not cause negative subjective sensations; their tolerance to patients was noted. After the course of treatment, the nasal mucosa is pink, shiny, moist, breathing free, there are no synechiae. A follow-up examination after 2 months confirmed a complete cure - free nasal breathing, the nasal mucosa is normal, there is no discharge, there are no adhesions and synechia.

 Example 21. Patient N., 32 years old, complaints of difficulty in nasal breathing. Sick for 3 children due to a nose injury. Surgical treatment was performed - rhinoseptoplasty with bilateral tamponade after surgery. Two days later, the tampons were removed, after which there was moderate bleeding stopped by the introduction of cotton filters, after removal of which strips cut from a polymer film containing bergamot oil were introduced into both halves of the nose. The films dissolved after 4 hours, the bleeding did not recur, and nasal breathing was satisfactory. Films were injected daily for three days, while the patient lacked crusts typical of the early postoperative period with blood-purulent discharge, and the mucous membrane regenerated very quickly. Discharged on the 5th day after surgery in satisfactory condition.

 Example 22. Patient L., 34 years old, complaints of congestion and frequent profuse mucous discharge from the nose, especially after hypothermia. Sick for 5 years with an increasing frequency of exacerbation of rhinitis. I used vasoconstrictor drops as a counter-current agent constantly, but with a short-term effect.

 On examination, it was found that the mucous membrane of the nasal cavity is swollen, in the nasal passages a large amount of mucous discharge, the mucous membrane of the nasal concha is stagnantly hyperemic with areas of ischemia. There is a slight crest of the nasal septum on the left, nasal breathing is difficult. After anemization of the nasal mucosa with a solution of adrenaline, a temporary restoration of nasal breathing occurs and the discharge from the nose stops.

 Under local anesthesia (novocaine solution 1% - 10.0), bilateral lower submucosal vasotomy was performed, and the front loop tamponade was performed according to Volchek. After removing the tampons after 2 days, the bleeding is insignificant, the bleeding stops spontaneously, after which strips cut from a polymer film containing lavender oil are introduced into both halves of the nose. The films were in the nose for 4 hours until complete resorption, and the patient did not notice any unpleasant sensations. After daily use of the films (within 3 days), the nasal mucosa acquired a normal color, there were no discharge from the nose, and nasal breathing was not difficult. The patient’s hospital stay in the postoperative period is reduced from 7 to 4 days with a noticeable improvement in the course of this period for the patient.

 Example 23. Patient N., 57 years old, was admitted to the clinic in a planned manner with jabods for lack of nasal breathing on the left and difficulty in nasal breathing on the right. The patient was repeatedly removed polyps in an outpatient and inpatient setting. A history of bronchial asthma is of allergic genesis (allergen is house dust).

 In front rhinoscopy, light gray polyps were found in both halves of the nose, which were removed from both halves of the nose under local anesthesia using a tear loop. Restored free nasal breathing. After removing the tampons on the second day after the operation, minor bleeding was noted, which was stopped with cotton filters with a vasoconstrictor ointment. After removing the filters and the toilet of the nasal cavity, applications of a polymer film with bergamot oil were introduced, which were in the nasal cavity for 4-5 hours, resolving with the release of the active substance. The patient's condition is satisfactory, there were no complaints, no asthma attacks during this period. When observing the patient in dynamics (over 6 months), there were no relapses of polyps, nasal breathing was satisfactory. The postoperative period showed good tolerance of films of prolonged action even by patients with increased sensitivity to environmental factors.

 Example 24. Patient K., 52 years old, was undergoing treatment for periodontitis. The patient complained of swelling and bleeding of the gums, loose teeth, frequent rashes on the mucous membrane of the oral cavity. After the main course of treatment, it is recommended additionally monthly, preventively, for 3-4 days, daily application of films with lavender oil on the surface of the gums. Further examination showed an improvement in the patient's subjective assessment of the state of the oral cavity, the prolonged effect of the antibacterial and anti-inflammatory components of the film with increased humidity in the oral cavity, and the possibility of lengthening the period of remission.

 Thus, the results of clinical and outpatient tests show the high efficiency of the use of films in which essential oils diffuse slowly from the micropores of the polymer base, compared with a short-term single exposure to a therapeutic agent. The antibacterial properties of essential oils and the possibility of fixing films on the mucous membrane of the oral cavity, nose and nasopharynx make them promising for the treatment of diseases of the maxillofacial region associated with lesions of the mucous membrane, the treatment of which requires its reparative and physiological regeneration.

 The inventive tool is characterized by low cost, manufacturability, its use can be shown to any age group, since it does not contain allergens, which significantly expands the arsenal of therapeutic and prophylactic drugs for a similar purpose.

Claims (1)

A tool for the treatment and prevention of diseases of the organs of the maxillofacial region, including a biologically active substance of plant origin, a film former and water, characterized in that it contains lavender oil and / or bergamot oil as a biologically active substance of a plant, and a mixture as a film former aqueous solutions of polyvinyl alcohol and potato starch food with glycerin, in the following ratio, wt. %:
Polyvinyl alcohol - 7.0-9.0
Food potato starch - 7.0-9.0
Glycerin - 3.5-4.5
Lavender oil and / or bergamot oil - 0.9-1.1
Water - Else