RU2624502C2 - Medical-prophylactic material for dentistry - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: proposed medical and prophylactic dental material in the form of plates includes biologically active substances, miramistin, ascorbic acid and biocompatible polymer. At that, biologically active substances containing chlorophyll-containing compounds are used to make the material, native hyaluronic acid is used as the biocompatible polymer, which is photochemically modified with light at a wavelength of 280 nm using colloidal solutions of Ca, Zn and Mg, with the following ratio of components, wt %: tetracyclic form of native hyaluronic acid 10, colloidal solution of Ca ions 0.1, colloidal solution of Zn ions 0.1, colloidal solution of Mg ions 0.1, miramistin 2, chlorophyll-containing compounds 10, ascorbic acid 0.5, distilled water - the rest.

EFFECT: regenerating, antibacterial and anti-inflammatory effect, ease of use and good tolerability.

2 tbl, 1 dwg

Description

Technical field

The invention relates to medicine, dentistry, and in particular to means for therapeutic and prophylactic care of the gingival mucosa and oral cavity.

State of the art

The development and production of biodegradable materials intended for the effective treatment and prevention of gum disease (periodontal disease and periodontitis) is a new direction in dentistry and the biotechnological industry.

Traditionally, so-called gum dressings are used for these purposes. According to Artyushkevich A.S. ("Periodontal Diseases", Publisher: "Medical Literature", 2006, 328 p.), One of the most commonly used dressings is Soy-Pak, which is prepared by mixing the contents of two tubes to the desired color. One of them contains zinc oxide, oil (as a plasticizer), resin (to improve adhesion to the gums) and fungicide. The second tube contains coconut fatty acid, resin and chlortimol, which gives the dressing antimicrobial properties. Also in clinical practice, cyanoacrylate dressings are used. They are a gel, liquid or aerosol, which are applied immediately to a postoperative wound, previously well dried, and harden for 5-10 seconds. These dressings adhere well to any surface (smooth, rough, uneven) and last from two to seven days. Some manufacturers add antimicrobials (chlorhexidine, nitrofurans) or antibiotics (oxytetracycline, neomycin) to cyanoacrylate dressings, however, to avoid unforeseen complications, it is necessary to carefully collect an allergic history before using them. In order to remove or prevent tooth hypersensitivity, it is recommended that fluoride varnishes be included in dressings immediately before application. Protective gingival dressings are used after curettage, gingivectomy, some mucogingival operations using free autografts, as well as in osteomukingival surgery. The optimal period of presence of the gingival dressing after surgical treatment is up to 7 days, however, during this period it is necessary to change the dressings, for this, the wound is examined again and its antiseptic treatment is performed. Often, when chewing, the bandage can be deformed or broken, in which case pain relief, antiseptic treatment of the gums and its repeated application are necessary.

In connection with these shortcomings of gingival dressings in modern dentistry, the development of plastic materials for directed regeneration is recognized as promising.

In the literature (A. Artyushkevich "Periodontal Diseases", "Medical Literature" Publishing House, 2006, 328 p.) It is indicated that one of the earliest such materials is non-absorbable membranes (Core-Tech, ionomer resin, nylon, polyurethane), which meet the requirements of mechanical plasticity for the specifics of dentistry, but have a significant drawback - these materials do not absorb in the oral cavity.

For this reason, new biodegradable materials are developed, presented in 2 groups (natural and synthetic).

Natural absorbable materials are presented:

1. Derivatives of collagen;

2. Oxidized cellulose;

3. Biological membranes based on the dura mater and intestinal tissue.

These materials have good regenerative properties, but require additional surgical fixation techniques for their use. In addition, the nature of the material may be a source of biological hazard (viral or bacterial contamination).

Along with natural materials, synthetic materials are also being developed, and an example from this group is the Diplen-Dent self-adhesive dental film (the independent portal “Teeth Guide 2011 - 2015” (http://qidpozubam.ru/apteka/1359/Diplen-denta.html ), intended for use in periodontics, therapeutic, surgical and orthopedic dentistry.

Diplen-Denta is a two-layer film consisting of combined hydrophilic and hydrophobic layers, and is intended for topical use. It has a pronounced spectrum of antibacterial action, characteristic of lincomycin hydrochloride. On the hydrophilic (adhesive) side, it is tightly fixed on the surface of the mucous membrane of the oral cavity, wound, burn and other surfaces and persists for 6-8 hours. The outer (hydrophobic) layer prevents the release of film components into the oral cavity and ingress of oral fluid into the film's coverage area. The film is transparent, which allows you to observe the dynamics of the pathological process without removing it from the affected area. The presence of the outer protective layer allows patients during the treatment period to observe oral hygiene in full. The use of the film in the treatment of various infectious and inflammatory diseases of the oral cavity and gums, surgical wounds, burns, etc. leads first of all to the disappearance or significant reduction in the number of aggressive bacteria. Indications for use of the Diplen-Dent film are: gingivitis, chronic periodontitis, generalized moderate, moderate and severe, rapidly progressive severe illness; stomatitis ulcerative necrotic and resulting from wearing dentures; caries prophylaxis and antibiotic therapy in patients with fixed orthodontic appliances; application anesthesia and relieving acute and chronic pain; lesions of the mucous membrane and the red border of the lip, with collagenoses, herpes virus infection, aphthous stomatitis, lichen planus, leptotrichiosis.

However, these films do not have their own adhesion (the ability to adhere), and in order to adhere to the mucous membrane of the gums, it is necessary to introduce additional adhesives into the film, which, as a rule, are synthetic and can cause allergic reactions.

In addition, synthetic materials are not able to absorb in the oral cavity, which necessitates the removal of material after a certain period of time. A flap of synthetic material is dangerous by aspiration into the larynx and trachea.

In addition, there are plates for gums based on the PHARMADONT collagen (independent portal “Teeth Guide 2011-2015”) (http://www.qidpozubam.ru/apteka/1224/Plastiny_dlya_desen_FARMADONT_(Farmadont).html).

PHARMADONT collagen plates for gums contain collagen and extracts of medicinal plants: aloe, plantain, St. John's wort. PHARMADONT collagen plates for gums are used for the treatment and prevention of inflammatory, infectious, necrotic, dystrophic and other diseases of periodontal tissues: gingivitis, periodontitis, periodontal disease, etc. in children and adults at any stage of the pathological process.

PHARMADONT collagen plates for gums have the following effects:

- strengthen weakened gums and relieve bleeding;

- have an antimicrobial effect;

- soothe, relieve soreness;

- contribute to the healing of the mucosa and soft tissues.

PHARMADONT collagen plates for gums are used:

- with bleeding, swelling, hyperemia, sore gums;

- after surgery on the gum and periodontal tissues;

- with trauma to the gums and mucous membranes of the oral cavity and nasopharynx (burns, biting);

- after removal of tartar;

- to strengthen the teeth with their pathological mobility;

- when using removable dentures (rubbing);

- before and after prosthetics to relieve inflammation and strengthen the gums;

- to fill the gum pockets.

Collagen plates are used as follows. Oral hygiene is performed, with clean, dry hands, the collagen plate is removed from the package and gently applied to the gum, gently pressing. The plate itself is fixed to the wet gum and, over time, it partially dissolves itself. Before reapplication, the non-absorbable remnants of the PHARMADONT gum plate must be removed.

However, along with the positive properties, PHARMADONT collagen plates have the following disadvantages.

1. The basis of the plates - collagen - is a protein of animal origin, which is foreign to the human body and often causes allergic reactions. In addition, biotechnological products based on collagen of animal origin are banned in the European Union and the USA in connection with the biological hazard of prion infection, known as the "mad cow virus" [Surguchenko VA, 2011];

2. In these plates, collagen serves as a matrix - a carrier for extracts of medicinal plants (aloe, plantain, St. John's wort) and in the conditions of the oral cavity releases these substances from its structure. As you know, a collagen molecule has a complex heterogeneous tertiary and quaternary structure, which leads to an unregulated time of resorption and yield of extracts of medicinal plants. In practice, this is marked by a peak concentration of drugs in the first hour of application of collagen plates;

3. It is known that the most optimal option for the restoration of the mucosa in gum diseases is the use of dental films at night, since in these conditions there is the possibility of more than 6-hour exposure of drugs to the mucosa. Thus, the prolonged effect of the treatment of gum disease (including periodontal disease) is realized. Due to the fact that PHARMADONT does not completely dissolve (metabolize) on the mucous membrane of the oral cavity, there is a risk of aspiration, therefore, these films have limitations for use at night.

The use of hyaluronic acid in the manufacture of films, plates, and the like for use in dentistry is known in the art; so, in the document CN 1515232 publ. July 28, 2004 describes the preparation of complex film designs. Such films consist of 3 layers. The films contain many chemical compounds and acids (polylactic acid, lactic acid, glycolic acid, caprolactone, beta-hydroxybutyrate, copolymers of polyethylene glycol, chitosan and hyaluronic acid), which prevents the use of these films as a prophylactic agent due to the possible occurrence of allergic reactions.

The prototype of this invention is an antimicrobial dental film for the treatment of the oral cavity (Patent UA 36877, publ. 10.11.2008), including glycerin, sodium carboxymethyl cellulose, miramistin, ascorbic acid, quercetin, vitamin B ₂ , as well as tinctures of marigolds, chamomile alcohol, watering saccharin and purified water.

The disadvantage of this film is the requirement for additional methods of surgical fixation, since these films do not have adhesive properties. In addition, the film does not absorb and its use at night is prohibited, as it is dangerous by aspiration into the larynx and trachea.

Disclosure of invention

The technical result of the invention is a regenerating, bactericidal and anti-inflammatory effect, ease of use and good tolerance.

The problem is solved in that for the manufacture of therapeutic dental material in the form of plates, including biologically active substances, miramistin, ascorbic acid and a biocompatible polymer, biologically active substances containing chlorophyll-containing compounds are used, native hyaluronic acid is used as a biocompatible polymer, which is subjected to photochemical modifications with light with a wavelength of 280 nm using colloidal solutions of Ca, Zn and Mg, in the following ratio NTV, wt.%:

tetracyclic form of native hyaluronic acid 10 colloidal solution of Ca ions 0.1 colloidal solution of Zn ions 0.1 colloidal solution of Mg ions 0.1 miramistin 2 chlorophyll-containing compounds 10 vitamin C 0.5 distilled water rest

The drawing shows the microstructure of the tetracyclic form of hyaluronic acid obtained using colloidal solutions of Ca, Zn and Mg, by photochemical modification of hyaluronic acid with light with a wavelength of 280 nm. Scanning area: 1.7 μm, scale: 1 cm - 150 nm.

The tetracyclic form of hyaluronic acid was obtained using colloidal solutions (Ca, Zn, Mg) using photochemical modification of hyaluronic acid with light with a wavelength of 280 nm, which corresponds to the maximum absorption band of the hydrogel (Rakhmatullin R.R., 2011). The obtained tetracyclic form of hyaluronic acid forms an amphiphilic tetracyclic polymer capable of swelling in water and forming a poorly soluble bulk network. As a result of dissolution, the elements (Ca, Zn, Mg) are released and easily penetrate into the tissues and cells of the body, thereby exerting a therapeutic effect on bone and dental tissue.

The positive properties of the tetracyclic form of hyaluronic acid are:

1. The presence of endogenous (intrinsic) adhesion of thin films of this polymer to the mucous membranes (including the gingival mucosa);

2. Films of a photopolymer under the influence of saliva gradually dissolve on the oral mucosa within 5-6 hours, thereby releasing the drug and elements (Ca, Zn, Mg) that are in their composition;

3. The gradual release of nutrients from the film provides a prolonged therapeutic effect for more effective treatment of gum disease;

4. The complete dissolution of this film in the oral cavity allows it to be used at night, which significantly increases the effectiveness of therapeutic and prophylactic care for gum diseases.

The developed therapeutic and prophylactic material for dentistry (stomaplex) is made on the basis of the native (chemically unmodified) tetracyclic form of hyaluronic acid with the addition of antimicrobial (miramistin) or anti-inflammatory substances (chlorophyll-containing compounds), which is shown in table 1.

The mixing of these components occurs in three separate containers according to the following scheme:

Ca + (C ₁₄ H ₂₁ NO ₁₁ ) _n = Ca (C ₁₄ H ₂₁ NO ₁₁ ) _n

Mg + (C ₁₄ H ₂₁ NO ₁₁ ) _n = Mg (C ₁₄ H ₂₁ NO ₁₁ ) _n

Zn + (C ₁₄ H ₂₁ NO ₁₁ ) _n = Zn (C ₁₄ H ₂₁ NO ₁₁ ) _n

After that, all three cycles are combined and the remaining ingredients are added, which leads to the formation of a viscous hydrocolloid, which is further used in the technology for producing thin plates of the tetracyclic form of hyaluronic acid.

The technology for producing thin plates of therapeutic and prophylactic dental material is based on the principle of distribution of colloidal substance on a hydrophobic surface under conditions of increased atmospheric pressure.

The hyaluronic acid hydrocolloid, which contains the prescription amount of the components listed in Table 1, based on 100 ml of hydrocolloid per 3 dm ² , is carefully poured into the center of the cuvette with a hydrophobic quartz surface of 3 dm ² (the cuvette is in a strictly horizontal position). As a result of this manipulation, an even circle with a diameter of 15 ± 1.5 cm is obtained in the center of the cuvette. Then the cuvette with the hydrocolloid is carefully transferred to the chamber, where 5 atmospheres pressure is created for 1 hour, after one hour the cuvette is removed from the chamber and placed for 6 hours in a laminar a cabinet with a source of ultraviolet radiation at normal atmospheric pressure and a certain microclimate (temperature + 30 ° C, humidity 30-35%, with ventilation at an air flow rate of 0.50 m / s).

As a result, an elastic film of whitish color, 100 microns thick, forms in the cuvette. After 6 hours from the beginning of the ultraviolet exposure, the film is removed from the cuvette and transferred to the apparatus for cutting rectangular plates 5 cm long and 1-1.5 cm wide.

Thin plates of the tetracyclic form of hyaluronic acid due to their high hydrophilicity possess endogenous (intrinsic) adhesion to the mucous membranes of the gums, precisely repeating its anatomical relief. An important advantage of the tetracyclic polymer is the absence of gum-bonding components of a chemical nature, which often cause allergic reactions.

Thus, the novelty of the developed therapeutic and prophylactic dental material is the combination of the tetracyclic polymer of hyaluronic acid with miramistin (antimicrobial substance) and chlorophyll-containing compounds (anti-inflammatory substance), vitamin C (ascorbic acid) and the technology of thin-layer distribution of the obtained tetracyclic hydrocolic hydrochloric acid hyaluronic acid surface its subsequent photopolymerization. After thin-layer distribution on a hydrophobic quartz substrate, the hydrocolloid of hyaluronic acid is subjected to ultraviolet radiation for 6 hours, and subsequently used in the form of rectangular plates for application to the oral mucosa.

In FIG. 1. shows an image of a film obtained using atomic force microscopy (AFM), showing the structure of the tetracyclic polymer of hyaluronic acid.

The therapeutic dental material obtained in this way was clinically tested in volunteers suffering from periodontal disease, according to the following indications:

1. Bleeding gums (20 people, not smokers);

2. Soreness and hypersensitivity of the gums (20 people, not smokers);

3. Periodontal disease in a smoker (20 people).

Volunteers were invited to place plates of therapeutic dental material on the upper and lower gums 2 times a day in between meals for 3 hours, as well as at night. Examination of the oral cavity was carried out by the dentist on the 3rd, 7th and 14th day of application of the material.

The results of the clinical study are presented in table 2.

As can be seen from the table, the best and accelerated result was obtained in the group of volunteers according to the indication “soreness and increased sensitivity of the gums”, and on day 14, all the examined in the group according to the indication “gingival bleeding” showed a marked clinical effect. In the group of smokers with periodontal disease, a positive result was noted in half the cases, which is associated with the continued smoking of volunteers.

All volunteers noted the convenience of using therapeutic and prophylactic dental material: the plates adhered tightly to the mucous membranes, did not interfere with the conversation and did not cause a “feeling of inconvenience” in the oral cavity. In addition, the plates absorbed within 3 hours without the effect of an unpleasant aftertaste. No adverse reactions were noted by dentists and volunteers.

Thus, the studies show that the therapeutic and prophylactic dental material according to the invention has optimal physicochemical properties, has a pronounced clinical effect, is convenient to use and well tolerated.

A distinctive feature of this therapeutic and prophylactic dental material is its composition, high adhesion to the mucous membranes of the gums and prolonged absorption in the oral cavity under the influence of saliva.

Thus, compared with the prototype, the claimed therapeutic and prophylactic dental material provides a regenerative effect, as well as bactericidal and anti-inflammatory effects, in addition, it is convenient to use and provides good tolerance.

Claims (2)

Treatment-and-prophylactic dental material in the form of plates, including biologically active substances, miramistin, ascorbic acid and a biocompatible polymer, characterized in that biologically active substances containing chlorophyll-containing compounds are used to make the material, native hyaluronic acid is used as a biocompatible polymer, which is subjected to photochemical modifications with light with a wavelength of 280 nm using colloidal solutions of Ca, Zn and Mg in the following ratio of comp nents, wt.%: tetracyclic form of native hyaluronic acid - 10 colloidal solution of Ca ions 0.1 colloidal solution of Zn ions 0.1 colloidal solution of Mg ions 0.1 miramistin 2 chlorophyll-containing compounds 10 vitamin C 0.5 distilled water rest

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