RU2775939C1 - Method for activating tissue regeneration of the wound surface of the oral mucosa - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dentistry and maxillofacial surgery, and can be used to stimulate the process of regeneration of wound defects of the oral mucosa. To do this, the photosensitizer "Geleophor" is applied to the wound areas with an exposure of 30 minutes, which is then washed off. Next, exposure to ultra-bright semiconductor LEDs is performed for 37.5±0.5 s at a wavelength of 660 nm with a power density of 0.2 W/cm², then for 75 seconds at a wavelength of 400 nm with a power density of 0.1 W/cm².

EFFECT: method allows to reduce the period of complete recovery of wound surface tissues without pronounced cicatricial changes while reducing the risk of tissue heating during photodynamic therapy due to low power density and radiation energy density, sequential exposure to light with the specified wavelengths, which contributes to the activation of the photosensitizer at different depths of light absorption by tissues, which in turn ensures a favorable course of the postoperative period.

1 cl, 2 ex

Description

The present invention relates to medicine, namely to dentistry and maxillofacial surgery, and can be used to stimulate the process of regeneration of wound defects of the oral mucosa.

Currently, in dental clinical practice, a large number of surgical interventions in the oral cavity are performed in conditions of soft tissue deficiency with the formation of extensive open wounds. In the postoperative period, it is not possible to completely isolate the wound surface from the influence of mechanical, chemical and physical factors. The patient begins to experience discomfort, the normal course of the regenerative process is disturbed with an increase and resynchronization of the timing of epithelialization and maturation of granulation tissue. At the same time, the risk of replacing lost tissues with cicatricial deforming tissues increases significantly, which prevent the achievement of not only aesthetic, but also functional results from the treatment. A favorable outcome is the replacement of the defect with tissue similar in structure and functions.

Despite the accumulated practical experience and active research into the processes of tissue regeneration of the oral mucosa, the urgency of the problem of reducing the recovery period of tissues in the area of the wound surface with the formation of authentic tissues still remains. As a result, it is of interest to search for and develop new methods of influencing regenerative processes, the use of which would ensure the most favorable course of the wound process for the patient and reduce the postoperative period.

Photodynamic therapy (PDT), which has a pronounced cytotoxic effect on tissue cells, is actively used in a wide range of diseases as an antitumor, antimicrobial, and anti-inflammatory treatment. This type of therapy helps to reduce the drug load on the body, which in turn prevents its allergization, the development of toxic, immunosuppressive and other side effects.

A known method of photodynamic therapy of diseases of the oral cavity, namely for the prevention and treatment of inflammatory diseases of the oral cavity, in particular periodontitis (RU 2728108). The method is based on carrying out photodynamic therapy of the oral cavity with the application of a dental gel-photosensitizer on the treated areas with an exposure of 8 to 20 minutes and exposing the treated areas to light radiation with a wavelength of 660 nm and an radiation intensity of 5 to 11 mW/cm ² through an inserted into mouth cap. The cap is made of transparent silicone with built-in LEDs, taking into account the structural features of the patient's oral cavity, and is equipped with a connector for connecting the LED power source.

This method eliminates the possibility of sequential use of light radiation with different wavelengths in order to improve the density gradient of absorbed photons, which ensures the activation of the photosensitizer at different depths of light absorption by the tissue. It is intended for use in the treatment of patients with inflammatory diseases of the maxillofacial region and is aimed at increasing the efficiency and accelerating the elimination of the inflammatory process in tissues due to the pronounced cytotoxic, bactericidal action of the photosensitizer activated by light, and not at stimulating the regenerative processes of wound defects in intact mucosal tissues. in the oral cavity.

A known method for the treatment of inflammatory diseases of the maxillofacial region (RU 2690414) by applying a photosensitizer to the inflamed tissue of the mucous membrane with an exposure of 3-5 minutes and exposure through a bispectral nozzle with continuous radiation with a wavelength of 405 nm, radiation power of 1.5-1.9 W and pulsed radiation with a wavelength of 650±10 nm, a pulse power of 20 W, with a pulse repetition rate of 28-30 kHz, a radiation dose of 130 J/cm ² , an exposure of 2.5-3 minutes.

This invention is intended for use in the treatment of patients with inflammatory diseases of the maxillofacial region. It is aimed at increasing the efficiency and accelerating the elimination of the inflammatory process in tissues due to the pronounced cytotoxic, bactericidal action of the photosensitizer activated by light, and not at stimulating the regenerative processes of wound defects in intact tissues of the oral mucosa. The high power and dose of light radiation used in this case with a wavelength of 660-650±10 nm have an additional thermal damaging effect, which excludes the use of these inventions in order to restore authentic tissues.

The objective of the proposed invention is to develop a method of photodynamic therapy in order to activate the process of tissue regeneration and reduce the period of complete restoration of authentic tissues in the area of the wound surface of the oral mucosa.

The technical result achieved in this case is to increase the effectiveness of treatment, reduce the period of complete restoration of authentic tissues in the area of the wound surface.

The technical result is achieved by the fact that in a method involving exposure to radiation of ultra-bright semiconductor LEDs, a photosensitizer made on the basis of a natural product of chlorophyll derivative chlorin e6 is applied to the wound areas with an exposure of 30 minutes, which is then washed off and exposure to radiation of ultra-bright semiconductor LEDs is performed for 37 .5 ± 0.5 seconds at a wavelength of 660 nm with a power density of 0.2 W / cm², then for 75 seconds at a wavelength of 400 nm with a power density of 0.1 W / cm².

The method is carried out as follows.

On the first day of the postoperative period, a photosensitizer made on the basis of a natural product of a chlorophyll derivative, chlorin e6, is applied to the wound surface of the oral mucosa for 30 minutes, after which it is washed off with saline (0.9% NaCL). The phototherapy LED device "Harmony" is installed on a hard, flat surface and connected to the mains, turned on by pressing the power switch button on the rear panel of the control unit. After starting the device on its front panel, press the control enable button. In the main mode menu, set the necessary parameters by pressing the wavelength button. For radiation with a wavelength of 660 nm, set the output power level (intensity) 0.2 W/cm ² equal to 2 positions and a timer for 1 minute, with a wavelength of 400 nm - the output power level (intensity) 0.1 W/cm ² equal to 1 position and a timer for 2 minutes. A nozzle is screwed into the emitter corresponding to a wavelength of 660 nm, introduced into the oral cavity with a cut to the wound surface and kept at a distance of 1-2 mm from the defect. Then, the radiation mode is switched on by pressing the red start button, and light exposure is performed for 37.5 ± 0.5 s. By pressing again, the emitter is turned off and the nozzle is removed from the oral cavity. Then it is reinstalled in the emitter corresponding to a wavelength of 400 nm, introduced into the oral cavity with a cut to the wound surface and kept at a distance of 1-2 mm from the wound. Then, the radiation mode is switched on by pressing the blue start button, and the light exposure is performed for 75 s. By pressing again, the emitter is turned off, the nozzle is removed from the oral cavity and unscrewed from the emitter. The device is turned off by pressing the button on the rear panel of the control unit, after which it is disconnected from the mains.

The advantages of using this method lie in the influence of the method of photodynamic therapy on the course of the wound process in the oral cavity, namely on regenerative processes. A decrease in the power density and energy density of radiation allows you to increase the proliferative activity of cells, stimulate the processes of neoangiogenesis and collagen formation. These effects have been confirmed in an in vivo experiment on laboratory animals (outbred specimens of Wistar drain rats).

During the study, defects with a diameter of 3 mm were formed on the mucous membrane of the cheeks of animals. All individuals were divided into control and experimental groups. In all groups, the wounds healed by secondary intention. In the experimental group, on the next day, a photosensitizer of the chlorine series "Geleophor" was locally applied, which was washed off after 30 minutes, and a single light exposure was performed on a two-wave phototherapy LED apparatus "Harmony" (Russia). In the experimental group, sequential radiation with wavelengths of 660 nm, power density of 0.2 W/cm ² and exposure time of 37.5 ± 0.5 s, and 400 nm, power density of 0.1 W/cm ² and exposure time was used. 75 s. The total radiation energy density was 15 J/cm ² . In the postoperative period, a histological study of the experimental material (standard hematoxylin-eosin stain), an immunohistochemical study to determine the content of markers of neoangiogenesis CD-31 and proliferative activity of Ki-67 cells, and a histochemical study according to Masson, verifying the content of type I collagen, were performed. The terms of postoperative control were 3, 7 and 14 days.

The main processes of tissue regeneration occur approximately on the 14th day of the course of the wound process. In the experimental group, on day 14, there was an increase in the processes of neoangiogenesis, expressed in a positive reaction of CD-31 compared with the control group, where the immunohistochemical reaction with this antibody was not traced. There was an increase in the Ki-67 index by 1.7 times compared with the control group, which indicated the proliferative activity of the cells. There was also an increase in the synthesis of type 1 collagen by 20% compared with the control group.

Also, in the course of using the proposed method, the risk of tissue heating under the influence of photodynamic therapy is reduced due to low power density and radiation energy density, which eliminates additional negative thermal effects on the tissues of the wound surface. In turn, successive complementary exposure to light at different wavelengths, 660 nm and 400 nm, promotes the activation of the photosensitizer at different depths of light absorption by biological tissues. The safety of its use in the oral cavity is dictated by the low invasiveness of the intervention.

The effectiveness of our proposed method is demonstrated by the following clinical examples.

Clinical example 1

Patient N., 22 years old, came to the dental clinic with complaints about the exposure of the neck of tooth 32, with a referral from an orthodontist for plastic surgery of the vestibule of the oral cavity before orthodontic treatment. During a dental examination in the anterior part of the lower jaw, there was a decrease in the level of attached keratinized gingiva with the formation of a Miller class 1 recession in the area of the tooth 32 to 2 mm, the initial stage of recessions in the area of teeth 43,42, 41, 31, the height of the periodontal papilla was preserved. The level of attached gingiva ranged from 1 to 2 mm in the area of teeth 35-45 with pronounced muscle bands. The frenulum of the lower lip is short, attached high; when the lip is pulled, pronounced ischemia of the marginal gum is determined. The diagnosis was made: gingival recession in the area of tooth 32, class 1 according to Miller (K06.0); small vestibule of the lower jaw (K13.7).

The patient underwent surgery in the scope of the operation of vestibuloplasty in the region of the lower jaw using a free gingival graft from the palate.

During the control examination on the next day, the procedure of photodynamic therapy of the oral cavity according to the proposed method was carried out. The photosensitizer "Geleophor" was applied from a syringe to the wound surface in the region of the hard palate for 30 minutes, after which it was washed off with saline (0.9% NaCl). The necessary parameters were set in the menu of the main mode of the phototherapeutic LED device "Harmony". For radiation with a wavelength of 660 nm, an output power level (intensity) of 0.2 W/cm ² was chosen equal to position 2 and a timer was set for 1 minute, with a wavelength of 400 nm - an output power level (intensity) of 0.1 W/cm ² equal to 1 position and a timer for 2 minutes. A nozzle was screwed into the emitter corresponding to a wavelength of 660 nm, brought into the oral cavity with a cut to the wound surface and kept at a distance of 1 mm from the defect. Then the radiation mode was switched on by pressing the red start button, and the light exposure was performed for 37 s. By repeated pressing, the emitter was turned off and the nozzle was removed from the oral cavity. Then it was reinstalled in the emitter corresponding to a wavelength of 400 nm, introduced into the oral cavity with a cut to the wound surface and kept at a distance of 1 mm from the wound. Then, the radiation mode was switched on by pressing the blue start button, and the light exposure was performed for 75 s. By repeated pressing, the emitter was turned off, the nozzle was removed from the oral cavity and unscrewed from the emitter.

After the photodynamic therapy procedure, the patient noted the absence of pain and bleeding in the palate. Macroscopic examination of the wound surface revealed hyperemia and edema of the surrounding soft tissues. The edges of the wound are clear, even and raised.

On the 3rd day, the patient complained of pain in the vestibule of the oral cavity. The wound in the palate did not bother the patient. There was no swelling of the surrounding soft tissues. The wound surface was clean. The edges are smooth, not raised, clear. There were small areas of hyperemia without signs of bleeding.

On the 7th day the patient had no complaints. The area of the newly formed mucous membrane of pale pink color was determined. The edges of the defect are smooth and not raised, sometimes fuzzy, hyperemic, the wound does not bleed during probing.

2 weeks after surgery, the entire area of the wound surface was covered with a pale pink mucosa, smooth and shiny, without visible changes.

Analysis of the results of dynamic observation showed that this method allows to reduce the period of complete recovery of the tissues of the wound surface without pronounced cicatricial changes and provides a favorable postoperative period.

Clinical example 2

Patient A., 74 years old, was referred by an orthopedic dentist for plastic surgery of the vestibule in the lateral section of the upper jaw on the right. A temporary bridge is fixed in the oral cavity supported by implants installed in the area of teeth 1.5, 1.4, 1.3, 2.2. During the dental examination, the absence of attached gums in the area of teeth 1.4-2.1 was noted, pronounced bucco-alveolar bands were determined. The frenulum of the upper lip is massive, the level of its attachment is under the intermediate part of the prosthesis, when the lip is pulled back, pronounced gingival ischemia is determined. The diagnosis was made: small vestibule of the upper jaw on the right (K13.7).

The patient underwent surgical intervention in the scope of the operation of vestibuloplasty in the region of the upper jaw on the right.

During the control examination on the next day, the procedure of photodynamic therapy of the oral cavity according to the proposed method was carried out. On the wound surface in the vestibule of the upper jaw on the right, the photosensitizer "Geleophor" was applied from a syringe for 30 minutes, after which it was washed off with saline (0.9% NaCl). In the menu of the main mode of the phototherapeutic LED device "Harmony", the necessary parameters were set by pressing the button with the inscription of the wavelength. For radiation with a wavelength of 660 nm, an output power level (intensity) of 0.2 W/cm ² was chosen equal to position 2 and a timer was set for 1 minute, with a wavelength of 400 nm - an output power level (intensity) of 0.1 W/cm ² equal to 1 position and a timer for 2 minutes. A nozzle was screwed into the emitter corresponding to a wavelength of 660 nm, brought into the oral cavity with a cut to the wound surface and kept at a distance of 2 mm from the defect. Then, the radiation mode was switched on by pressing the red start button, and the light exposure was performed for 38 s. By repeated pressing, the emitter was turned off and the nozzle was removed from the oral cavity. Then it was reinstalled in the emitter corresponding to a wavelength of 400 nm, introduced into the oral cavity with a cut to the wound surface and kept at a distance of 2 mm from the wound. Then, the radiation mode was switched on by pressing the blue start button, and the light exposure was performed for 75 s. By repeated pressing, the emitter was turned off, the nozzle was removed from the oral cavity and unscrewed from the emitter. The device was turned off by pressing the button on the rear panel of the control unit, after which it was disconnected from the mains.

After the procedure of photodynamic therapy, the patient noted the absence of pain. Macroscopic examination of the wound surface revealed hyperemia and edema of the surrounding soft tissues. The edges of the wound are clear, even and not raised.

On the 3rd day the patient had no complaints. There was no swelling of the surrounding soft tissues. The wound surface is clean, without signs of fibrinous plaque. The edges are smooth, not raised, clear. There were small areas of hyperemia without signs of bleeding.

On the 7th day, when examining the wound surface, an area of the newly formed mucous membrane of a pale pink color was determined. The edges of the defect are smooth and not raised, sometimes indistinct, hyperemic, with no sign of bleeding on probing.

2 weeks after surgery, the entire area of the wound surface was covered with a pale pink mucosa, smooth and shiny, without visible changes.

Analysis of the results of dynamic monitoring also showed that this method allows to reduce the period of complete recovery of the tissues of the wound surface without pronounced cicatricial changes and provides a favorable postoperative period.

Claims (1)

A method for activating tissue regeneration of the wound surface of the oral mucosa, including exposure to ultra-bright semiconductor LEDs, characterized in that the photosensitizer "Geleophor" is applied to the wound areas, made on the basis of a natural product of the chlorophyll derivative chlorin e6, with an exposure of 30 minutes, which is then washed off and perform exposure to radiation of ultra-bright semiconductor LEDs for 37.5±0.5 seconds at a wavelength of 660 nm with a power density of 0.2 W/cm ² , then for 75 seconds at a wavelength of 400 nm with a power density of 0.1 W/cm ² .