RU2075965C1 - Agent for mouth cavity illness treatment - Google Patents

Abstract

FIELD: medicine, stomatology. SUBSTANCE: agent is made as a film that consists of the combined hydrophobic and hydrophilic layers. Hydrophobic layer consists of polyvinylbutyral and plasticizer TWEEN at their ratio = 9:1 and hydrophilic layer consists of polyvinyl alcohol and plasticizer polyethylene glycol at their ratio = 9:1. Molecular mass of polyethylene glycol is 400-4000. Film has antibiotics and/or sulfanilamide preparations, and/or imidazole derivatives, and/or cationic surface-active substances, and/or medicinal plant extracts in combination with the indicated bioactive substances or in mixture with vitamins, essential oils. EFFECT: enlarged assortment of medicinal agents. 6 cl

Description

 The invention relates to medicine, namely dentistry, and specifically relates to the creation of a dosage form of prolonged action.

 Antibacterial drugs are known and used in the treatment of diseases of the oral cavity. So, for example, the ointment based on metronidozole "Kliostom" is used in the treatment of gingivitis, periodontitis, stomatitis. In this case, the ointment is recommended to be applied to the gum and between the teeth and kept in the mouth for at least 15 minutes. The procedure is repeated 2-4 times a day for 1-2 weeks. (Kliostom. Reference Drugs of foreign firms in Russia, 1992, Moscow, Asfafarmservis, p. 329).

 In medical practice, currently in the treatment of diseases of the oral cavity, drugs are used in a convenient prolonged-release dosage form.

So, the finished dosage form in the form of plates is known, which is used for taking medicines by children and the elderly. The plate consists of gelatin and mannitol, easily absorbed in the mouth. In water at 37 ^o C, the plate disintegrates in 5 s (Arch. Pharm. 1989-322, N 10, p. 753 German).

 The closest in technical essence and the achieved result is a composition for drug delivery in the treatment of diseases of the oral cavity.

 The composition includes a solid hydrocolloid substance, for example gelatin, pectin, sodium salt of carboxymethyl cellulose, or preferably a mixture thereof, and as a base, in particular, mineral oil containing dispersed polyethylene (Plastibase). The moisture content of the hydrocolloid substance is 5% and its content is 500. Such compositions are suitable for delivery of active components, for example steroids, antifungal and antibacterial agents, to the oral mucosa (European Patent No. 0291838, 1989, MKI A 61 K 47/00).

 The aim of the invention is to expand the arsenal of drugs of prolonged action used in the treatment of various diseases of the oral cavity. An agent for treating oral diseases is a film made of combined hydrophobic and hydrophilic layers, with a hydrophobic layer of polyvinyl butyral and TWIN plasticizer at a ratio of 9: 1, and a hydrophilic layer of polyvinyl alcohol and polyethylene glycol plasticizer mol. masses 400-4000 with a ratio of 9: 1 and includes antibiotics and / or sulfonamide preparations, and / or imidazoles and / or cationic surfactants, and / or extracts of medicinal plants using these biologically active substances or in combination with vitamins, essential oils.

 All these films are grouped under the general name "Diplen-Dent." They have a pronounced antibacterial property with an action spectrum characteristic of the drug included in the film. At the same time, they have a hemostatic and analgesic effect.

 Obtaining films is as follows.

 Source materials.

1. Plasticizers for the hydrophilic layer were used polyethylene glycols (PEG) mol. masses from 400 to 6000. Before use, the samples were freed from volatile components by keeping the residual mercury in a vacuum at 2 mm at 45 ^o C for 2 hours. The presence of heavy metals in the samples is unacceptable.

2. Plasticizers for the hydrophobic layer were used TWIN 20, 21, 40, 60, 65, 80-81, 85. In all initial samples, the pH should fluctuate from 6 to 8. The presence of heavy metals is unacceptable. Samples that meet these requirements were kept in a vacuum of 2 mm residual mercury at 45 ^° C. for 2 hours before use.

 3. The antibiotic stabilizers used sodium, calcium, magnesium salts, formaldehyde sulfonic acids (rongalite-Na, -Ca and Mg), sodium sulfate thiosulfate, disodium salt of ethylenediaminetetraacetic acid (2 a EDTA), benzyl alcohol, etc.

 4. Substances used to prolong the action of drugs. For this purpose, polyvinylpyrrolidone, vinyl acetate-vinylpyrrolidone copolymers, polyvinyl acetate and other polymers were used.

 5. The limits of acidity and alkalinity of the solutions for casting films were regulated within such limits that the maximum activity of the preparation used appears. Regulation of pH was carried out with hydrochloric acid or monoethanolamine.

 6. Polymer bases.

a) polyvinyl alcohol was used for the hydrophilic layer after two reprecipitation of ethyl alcohol from aqueous solutions. The polymer was then dried in a vacuum of 2 mm sp. Hg at 45 ^o C for two hours, the presence of heavy metals in the polymer is unacceptable;
b) for the hydrophobic layer, polyvinyl butyral was used, twice precipitated with water from an alcohol solution. The reprecipitated polymer was kept in a vacuum of 2 mm sp. Hg at 45 ^o C to free from residues of free organic acids, aldehydes and other volatile products. The presence of heavy metals in the original polymer is unacceptable, the mass fraction of chlorine ions is not more than 0.002%
The films are cast onto pre-siliconized glass plates with an area of 400 cm ² . First, a hydrophobic layer is cast, and then, after drying, a hydrophilic layer is cast on its surface.

a) Casting a hydrophobic layer: prepare a 10% alcohol solution of polyvinyl butyral with TWINOS (9: 1 ratio). 16 cm ^{3 of the} resulting solution is cast on a glass surface, the solution is evenly distributed over the entire surface and dried at 40 ^o C for four hours.

 b) a solution for casting a hydrophilic layer of 9 g of НВС and 1 g of PEG is dissolved in 60 ml of distilled water and filtered.

 PRI me R 1. Obtaining films with an antibiotic.

0.1 g of monomycin, 10.1 g of polyvinylpyrrolidone are dissolved in 6 cm ^{3 of} distilled water, the pH of monoethanolamine is adjusted to 9, 0.004 g of rongalite is added. The resulting solution is mixed with 14 cm ³ of plasticized polyvinyl alcohol solution. 10 cm ³ are taken from the resulting mixture and evenly distributed over the surface of the hydrophobic layer. After drying for 12-20 hours at 40 ^° C., the film is removed from the glass surface.

The content of monomycin in the finished film is 0.075 mg / cm ² .

 Similarly, films were prepared with lincomycin, gentamicin, clindamycin, neomycin, bacitracin, natamycin, josamycin, ofloxacin, mediomycin and sodium fusidate. In addition, these films were prepared with antibiotics of the cephalosporin series (especially generation III), the fluoroquinone group, etc.

In all cases, the antibiotic content in the finished film should be at least 0.03 mg / cm ² .

 PRI me R 2. Obtaining films with drugs from the group of imidazoles and with drugs of similar effect.

To 10 ml of an aqueous solution of medonidazole (soda 0.05 g of the basic substance), 0.005 g of sodium benzoate is added and the resulting solution is mixed with 10 ml of a solution for casting a hydrophilic layer. From the resulting mixture, 10 cm ^{3 are} evenly distributed on the previously prepared surface of the hydrophobic layer and dried at 40 ^o C for 12-20 hours

In the resulting film, the content of metronidazole is 0.08-0.1 mg / cm ² .

 Films with tinidazole, nitrofural, miconazole, clotrimazole, pronidome, dexpanthenal, and films in which metronidazole is combined with other drugs with herbal extracts, essential oils, etc. are prepared in a similar manner.

In all cases, the content of the main substance in the films should not be lower than 0.07 mg / cm ² .

 PRI me R 3. Obtaining films with cationic surfactants and with preparations having similar antimicrobial properties.

To 10 ml of an aqueous solution of benzalkonium chloride (soda. 0.05 g of the basic substance) is added 10 ml of a solution for casting a hydrophilic layer. From the resulting mixture, 10 cm ^{3 are} evenly distributed on the previously prepared and dried surface of the hydrophobic layer and dried at 40 ^° C. for 12-20 hours. In the resulting film, the content of benzalkonium chloride is 0.08-0.1 mg / cm ² .

 Films with chlorhexidine, decavinium chloride, cetrimide, desicam, diamine 10x, vagik, sulfanilamide preparations, as well as films with a combination of the active substance with corticosteroids, vitamin C, lysozyme, extracts of medicinal plants, essential oils and other drugs and excipients are prepared in the same way.

In all cases, the content of the main substance in the films should not be lower than 0.06 mg / cm ² surface.

 PRI me R 4. Obtaining films with extracts of medicinal plants and similar preparations.

 To 10 ml of a solution of insadol (soda. 0.025 g of extract in 1 ml of a solution containing no saponins) is added 10 ml of a solution for casting a hydrophilic layer. The film is prepared analogously to example 3.

The content of active substance in the resulting film is 0.5-0.8 mg / cm ² .

Similarly, films are prepared with helepin, alpizarin, propolis extract and other drugs and excipients. In all cases, the content of the active substance in the film should not be lower than 0.2 mg / cm ² .

 The resulting films can be used for inflammatory and infectious diseases of the oral cavity (stomatitis, gingivitis, periodontitis), in particular for the treatment of various forms of periodontitis, characterized by bleeding and suppuration from the periodontal pockets with hyperemia, pathological periodontal pockets of various depths, as well as acute herpetic and recurrent aphthoses stomatitis, decubital ulcers, etc.

 Mode of application.

 Before use, it is necessary to cut off a strip of film 10 × 50 mm in size and place it on the gum with the adhesive side or insert into the interdental space. The film immediately adheres to the gum surface. In the event that special supervision by a doctor is not required, patients can independently apply a film on the gum (more convenient at night). After 8-12 hours, the rest of the film is removed.

 The course of treatment is 12-20 sessions with daily film application. In severe cases of the disease, it is recommended to apply a film up to three times a day. On the recommendation of a doctor, the course can be repeated.

 After the accepted course of treatment, the patients experience a cessation of bleeding, suppuration, the mucous membrane acquires a healthy pale pink color, and the marginal gum is attached to the teeth. Radiological compression of the bone structure of the interalveolar septa is noted.

The use of films has several advantages compared to traditional methods, in particular, the injection of antibiotics into the gums and, accordingly, has the advantages of:
It is painless superimposed on the gum and is removed after the expiration of the term;
excludes mechanical injury to the soft tissue of the gums;
eliminates the need for bulky, unaesthetic and functionally inconvenient periodontal dressings;
allows for a long (up to 24 hours) active and selective effect of the treatment factor on the lesion site or on the postoperative wound;
the presence of an external protective layer in the film prevents the distribution of film components throughout the oral cavity, their entry into the stomach and the appearance of discomfort in the mouth.

 In addition, when using films, oral hygiene is observed, the affected area or wound is isolated from the oral fluid by the film.

 Films have high therapeutic efficacy after 5-6 sessions of application, the patient stops bleeding and suppuration, hypersthesia and begins the process of stabilization of the teeth.

 It should also be noted that the treatment process is facilitated, patients can independently apply a film, which is especially important for remote areas. The visit to the clinic is reduced, the consumption of drugs, aids, syringes, etc. is reduced.

 There are no contraindications and is usually well tolerated by patients.

 Clinical observations were carried out on volunteers, on samples of films prepared by the standard method on the basis of Central Research Institute of Dentistry of Dentistry, at the Department of Therapeutic Dentistry of Yerevan Medical Institute. Tver Medical Academy and VNIIMT. There are positive conclusions from these organizations.

Claims (6)

 1. An agent for treating diseases of the oral cavity in the form of a film, comprising a medicinal substance, characterized in that the film is made of combined hydrophobic and hydrophilic layers, the hydrophobic layer of polyvinyl butyral and TWIN plasticizer at their ratios of 9 1 and the hydrophilic layer of polyvinyl alcohol and plasticizer of polyethylene glycol mol.m. 400 4000 with a ratio of 9 to 1 and includes antibiotics, and / or sulfa drugs, and / or drugs of the imidazole group, and / or cationic surfactants and / or antibacterial substances, and / or extracts of medicinal plants using these biologically active substances or in combination with vitamins, essential oils. 2. The tool according to claim 1, characterized in that the antibiotic content is not lower than 0.03 mg / cm ² . 3. The tool according to claim 1, characterized in that the content of sulfa drugs is not lower than 0.07 mg / cm ² . 4. The tool according to claim 1, characterized in that the content of surface-active and antibacterial substances is not less than 0.06 mg / cm ² . 5. The tool according to claim 1, characterized in that the content of extracts of medicinal plants is not lower than 0.2 mg / cm ² . 6. The tool according to claim 1, characterized in that the content of the drug from the group of imidazoles is not lower than 0.07 mg / cm ² .