PL240165B1 - Herbal preparation that speeds up healing of the mouth cavity mucous membrane injuries - Google Patents

Description

PL 240 165 B1

Description of the invention

The subject of the invention is a herbal preparation for accelerating the healing of damage to the oral mucosa with anti-inflammatory, analgesic and antiseptic properties, used to support the treatment of conditions associated with damage to the mucous membranes (inflammation of the mouth and gums, aphthas, damage caused by wearing mismatched dentures, orthodontic appliances) .

The oral mucosa is constantly exposed to various types of damaging and / or irritating stimuli: mechanical (while chewing food, using orthodontic appliances), physical, thermal or chemical. These factors contribute to the formation of inflammation of the oral mucosa, ulcerations, erosions, bacterial and other infections. The characteristic changes in the oral mucosa also occur in the course of some infectious diseases, such as measles, rubella, scarlet fever, whooping cough, infectious mononucleosis, chicken pox), general diseases, e.g. the hematopoietic system, digestive system, diabetes, vitamin deficiencies or diseases related to the origin allergic. Likewise, the nasal mucosa may be exposed to various types of irritating stimuli that cause nasal dryness, thereby damaging the delicate nasal mucosa.

The changes on the oral mucosa are most often accompanied by symptoms such as spontaneous or stimulating burning (e.g. irritation when consuming foods with spicy or acidic spices), witnessing, disturbances in salivation. Oral mucosa ulcers are a serious clinical problem due to significant sensory innervation in this area, which causes severe pain sensations with difficulty in eating, limiting the functions of the speech apparatus or preventing the maintenance of proper oral hygiene, which leads to an increase in symptoms.

The healing process of this type of mucosal damage is complex due to the chronology of emerging repair phenomena and can be divided into three phases: inflammation, formation of new tissue and its reconstruction. In the inflammatory phase, morphotic elements, including platelets and fibroblasts, containing in their granules numerous peptides stimulating the growth and development of tissues, are supplied with blood to the area of the damaged area, which is one of the key stages of the regeneration process. During this time, a large number of cells and extracellular matrix (collagen and proteoglycans) forming granulation tissue are accumulated, which allows the next phase of healing to begin, which is the reconstruction of normal tissue. The formed basal tissue containing collagen, a proteoglycan matrix, a network of fibroblasts and vessels fills the lesion area. The final stage of repair is tissue reconstruction (remodeling), during which intermembrane connections between cells are created and their spatial arrangement is formed.

The healing process of damaged mucous membranes can be accelerated by the action of various types of synthetic substances, which, in addition to their therapeutic effect, may exhibit a number of side effects.

In the current clinical practice, liquids and gels based on synthetic ingredients (pharmacologically active compounds), herbal extracts or silver nanoparticles have been used to treat damage to the oral mucosa.

The well-known Pyralvex gel of the French company Norgine Pharma, which accelerates the healing of inflammations of the oral mucosa, contains a biologically active ingredient of plant origin in the form of dry rhubarb extract. In addition, it contains sodium carboxymethylcellulose, a humectant such as glycerin and salicylic acid, ethanol, triethanolamine, sodium saccharin, and distilled water. Pyralvex is used to relieve pain and discomfort caused by mouth ulcers and irritation from dentures. It also has antibacterial properties that help prevent irritated areas from becoming infected.

Patent RU2113217 describes an agent in the form of a gel used for the treatment of damage to the oral mucosa with anti-inflammatory, antibacterial and analgesic properties, which contains a biologically active ingredient of plant origin in the form of oak bark extract, sodium carboxymethylcellulose, glycerin, stabilizing ingredient - propylene glycol, cleansing - sodium lauryl sulfate.

Patent RU2351313 describes a gel herbal preparation with anti-inflammatory and antibacterial properties, accelerating the healing of oral diseases, containing dry extract of grape seed Vitis vinifera, sodium alginate, glycerin, germal plus.

From the European patent application EP 154 60 092 a herbal preparation supporting the regeneration of wounds with an anti-inflammatory and astringent effect is known, used to assist in the treatment of conditions related to the disruption of the anatomical continuity of the outer skin or deeper tissues. The herbal preparation contains an alcoholic extract of Melittis melissophyllum, and the organic substrate contains Vaselinum album in an amount of 40% to 70% by weight. or glycerol

PL240 165B1 or 2 wt% propylene glycol, 2 wt% triethylamine, 1 wt% hydroxycellulose, 30-35 wt% aqua purifficata.

The aim of the present invention is to extend the available range of wound healing accelerating products with a preparation based on a herbal extract for the regeneration of damaged oral mucosa.

The essence of the invention is a herbal preparation for accelerating the healing of damage to the oral mucosa, containing as an active ingredient an alcoholic plant extract of Melittis melissophyllum suspended in a hydrogel or glycerol base in an amount of 0.1-10% by weight, analgesics, agents antiseptic characterized in that it contains in an amount from 20 + 99.7 wt. 20% ethanol extract of melissa (Melittis melissophyllum), from 0.1 + 10% by weight. % of an analgesic, from 0.1 + 10 wt. % of an antiseptic and purified water up to 100% by weight.

A herbal preparation for the use of accelerating the healing of mucosal lesions in the oral cavity contains as a base hydroxymethyl cellulose or carboxymethyl cellulose or condensed polyacrylic acid. Preferably, the preparation comprises a 0.1% chlorhexidine solution or a 3% boric acid solution as an antiseptic. Preferably, it comprises a 3% H 2 O 2 solution as antiseptic. Preferably it comprises benzocaine or lidocaine as the analgesic.

Herbal preparation for accelerating the healing of the regeneration of the oral mucosa, containing the ethanol extract of Melittis melissophyllum, accelerates the healing process of ulcers in the mouth and shows anti-inflammatory activity, improving its health.

Male Wistar rats (340-380 g, n = 24) were used in the study. The animals were housed in standard plastic cages, 4 in each, in an air-conditioned room with a temperature of 22-25 ° C, air humidity 40-60% and natural lighting (12/12 day / night cycle). The animals had free access to water and food ad libitum.

The animals were divided into 3 groups - Control (40% ethanol solution), Positive control (agent commonly used in clinical practice) and 20% ethanol extract of Melittis melissophyllum (alcohol concentration was 40 vol%). The animals were subjected to ether anesthesia. Mouth ulcers were induced by a single administration of a 10% acetic acid solution to the inside of the cheek. Immediately after surgery and for two consecutive days, all animals received analgesic metamizole (50 mg / kg / day, i.m.). The resulting mouth ulcers were treated by applying a suitable agent to the wound surface. The procedure was performed under ether anesthesia and repeated until the wounds healed completely. Changes in the size of the healing wounds were assessed macroscopically each day.

Weight changes have been recorded daily as painful mouth ulcers make it difficult to eat, resulting in weight loss. The weight of all animals changed significantly on the 5th day of the experiment compared to the day of starting the study. Only in the control group the changes were noticed on the 10th day of the experiment. There were no significant differences in body weight in the groups of animals receiving the positive control and 20% ethanol plant extract, respectively, during the 10-day observation period. Nevertheless, changes in the body weight of the animals were seen in both the experimental groups and the control group on the 10th day of the experiment (Table 1).

Table 1. Changes in animal body weight over the course of the experiment (n = 8)

Day Control Positive control 20% ethanol extract from the plant 0 353.1 + 4.6 351.3 ± 3.9 350.0 + 3.2 5 335.0 + 3.3 * 340.0 ± 2.8 * 335.0 ± 4.9 * 10 329.4 + 6.3 * 348.8 ± 6.3 # 346.4 ± 5.7 #

* p <0.05 compared to values at day 0 of the experiment (paired Student's t-test);

#p <0.05 compared to control at same follow-up (one-way ANOVA with Dunnet's post hoc test)

PL240 165B1

20% ethanol extract of melissa melissophyllum (Melittis melissophyllum) and the positive control accelerate, in a statistically significant way, the healing of mouth ulcers in rats compared to the control group (15.6 ± 0.7 vs. 12.0 ± 1.1 ; 15.6 ± 0.7 vs. 11.9 ± 0.9 days; positive control 20% ethanol plant extract, respectively). However, no significant differences were found between the groups receiving the positive control and the 20% ethanol extract of Melittis melissophyllum. The size of the lesion area was significantly smaller on the 5th day of the experiment in animals from the test groups compared to the control group.

Table 2. The effect of melissa extract (Melittis melissophyllum) on the healing process of mouth ulcers in rats induced by a single administration of 10% acetic acid (mean ± SEM, n = 8)

Parameter Control Positive control 20% ethanol extract from the plant Lesion area, 5th day, mm ² 23.5 + 0.7 19.7 ± 1.3 * 18.6 ± 0.8 * Complete healing, day 15.6 + 0.7 12.0 ± l, l * ll. 9 ± 0.9 *

* p <0.05 compared to the control group, one-way ANOVA with Tukey's post hoc test

In the control group, the surface of the mucosa was completely covered with fully rebuilt epithelium (reepithelialization). However, some signs of degeneration and exocytosis were observed in the epithelial layer. The surface of the mucosa appeared to be covered with a pseudomembrane. In the lamina propria, inflammatory infiltrates from mononuclear cells were observed compared to undamaged tissues and treatment groups. A slight infiltration of inflammatory cells was observed in the muscle layer. In the treatment groups, the surface of the mucosa was completely covered with fully reconstructed epithelium. Rare inflammatory infiltrates and numerous nerve fibers were observed in the lamina propria. No changes were observed in the muscle layer. There were no significant histological changes between the treatment groups.

The studies used herbal preparations obtained by mixing together the following ingredients in an appropriate amount.

Example I.

20% ethanol extract from Melissa honey (40% by weight)

Hydroxymethylcellulose (3.4 wt.%)

Borasol - 3% solution of boric acid (5% by weight)

Lidocaine (0.5 wt.%)

Aqua purificata ad 100 wt.%

Example II

20% water extract from Melissa honey (50% by weight)

Carboxymethylcellulose (5.5 wt.%)

0.1% chlorhexidine solution (5% by weight)

Benzocaine (0.2 wt.%)

Aqua purificata ad 100 wt.%

Example III

20% ethanol extract from Melissa honey (60% by weight)

Condensed polyacrylic acid - Carbopol (10 wt.%)

3% H2O2 solution (6% by weight)

Lidocaine (1 wt.%)

Aqua purificata ad 100 wt.%

In all of the above examples, the drug substance etched with ethyl alcohol or water is suspended in cold-dissolved hydroxycellulose or carboxycellulose or polyacrylic acid, which constitute a hydrogel base and at the same time are carriers of biological substances.

Claims (6)

PL 240 165 B1 active. Then, appropriate amounts of antiseptic, anti-inflammatory and analgesic agents are added. It is important that the drug substance is suspended in the medium at a concentration below saturation. In all cases, the composition was applied directly to the wounds with an applicator. P r x l a d IV 20% ethanol extract from Melissa honey (70% by weight) Glycerol (10 wt.%) 0.1% chlorhexidine solution (7% by weight) Benzocaine (0.1 wt.%) Aqua purificata ad 100 wt.% The drug substance etched with ethyl alcohol is suspended in glycerol, which is a hydrogel base and at the same time a carrier of biologically active substances. Then, appropriate amounts of antiseptic, anti-inflammatory and analgesic agents are added. It is important that the drug substance is suspended in the medium at a concentration below saturation. The composition was applied directly to the wounds with an applicator. Patent claims 1. A herbal preparation for accelerating the healing of damage to the oral mucosa, containing an active ingredient of an alcoholic plant extract of Melittis melissophyllum suspended in a hydrogel or glycerol base in an amount of 0.1-10% by weight, analgesics, antiseptics % by weight: from 20 to 99.7% by weight. 20% ethanol extract of melissa (Melittis melissophyllum), 0.1 + 10% by weight. % pain reliever, 0.1 + 10 wt. of an antiseptic and purified water to 100% by weight, and the vehicle comprises hydroxymethyl cellulose or carboxymethyl cellulose or condensed polyacrylic acid. 2. The herbal preparation for use according to claim 1 The method of claim 1, wherein the antiseptic is a 0.1% chlorhexidine solution. 3. The herbal preparation for use according to claim 1 The method of claim 1, wherein the antiseptic is a 3% boric acid solution. 4. The herbal preparation for use according to claim 1 The process of claim 1, wherein the antiseptic is a 3% H 2 O 2 solution. 5. The herbal preparation for use according to claim 1 The method of claim 1, wherein the analgesic is lidocaine. 6. The herbal preparation for use according to claim 1 The method of claim 1, wherein the analgesic is benzocaine.