Mouth gel (KLO)

Mouth Gel (KLO)

Product name: Гель для слизистых, Mouth Gel, Schleimhautgel, Gel para mucosas, Gel pour muqueuses, جل للأغشية المخاطية, เจลสำหรับเยื่อเมือก, Шиллих қабықшаларға арналған гель, Клейшелүү кабыкчалар үчүн гель, Selikli qişalar üçün gel, Гели луоб мембранаҳо, Gleivių gelis, Gļotādu gels, Гель для слизових оболонок, ג'ל לקרומי ריר (содержит Terminalia chebula — Терминалия чебула, Glycyrrhiza glabra — Солодка голая)

Main indications for use of Mouth Gel: Aphthous stomatitis, chronic gingivitis, oral candidiasis, vaginal candidiasis, erosive vulvovaginitis, bacterial vaginosis, cheilitis, herpetic stomatitis.

Indications for use of Mouth Gel as part of therapeutic complexes: Oral squamous cell carcinoma, cervical squamous cell carcinoma, chronic tonsillitis, chronic pharyngitis, recurrent vaginal candidiasis, chronic bacterial vaginosis, systemic candidiasis, oropharyngeal candidiasis in HIV infection.

Main pharmacological properties of Mouth Gel: antifungal, antibacterial, anti-inflammatory, analgesic, antioxidant, mucoadhesive, reparative, immunomodulatory.

Ingredients: Terminalia chebula extract, Glycyrrhiza glabra extract, Andrographis paniculata extract, Menthol, Peppermint oil, Xanthan gum.

Functions of the Components in Mouth Gel:

• Terminalia chebula extract - source of tannins, has a pronounced antifungal and antibacterial effect, suppresses the growth of Candida albicans and pathogenic bacteria.
• Glycyrrhiza glabra extract - possesses antifungal and anti-inflammatory effects, reduces irritation of mucous membranes, promotes their regeneration.
• Andrographis paniculata extract - provides additional antimicrobial action, enhances the antiviral and antibacterial profile of the preparation.
• Menthol - has a local analgesic and cooling effect, masks the taste of bitter extracts, improves the tolerability of the preparation.
• Peppermint oil - has a mild antiseptic and refreshing effect, enhances the organoleptic properties of the preparation.
• Xanthan gum - provides mucoadhesive properties, retains the preparation on the mucous membranes, prolongs the action of active components, creates a protective film.

Product form of Mouth Gel: Gel for topical application. The product is available in 5 g tubes. One dose (≈0.6 cm of gel) contains active substances: Terminalia chebula extract ~5-7 mg, Glycyrrhiza glabra extract ~4-6 mg, Andrographis paniculata extract ~1 mg, Menthol ~2 mg, Peppermint oil ~1 mg, Xanthan gum ~8-10 mg, excipients up to a mass of 100 mg.

Dosage of Mouth Gel

Standard Dosage for Mouth Gel: For adults with aphthous stomatitis, chronic gingivitis, oral candidiasis, apply a 0.5-0.6 cm strip of gel (≈100 mg) to a cotton swab or fingertip and distribute evenly over the affected mucosa 2-3 times a day, preferably after meals and before bedtime. For vaginal candidiasis, apply the same amount of gel to a hygienic tampon and insert into the vagina overnight, course 2-3 days.

Enhanced Dosage for Mouth Gel: For adults with erosive vulvovaginitis, severe oral candidiasis, herpetic stomatitis, application of a 0.8-1 cm strip of gel (≈150 mg) to the affected mucosal area 3-4 times a day is allowed, including morning and evening application. For severe vaginal candidiasis, combination with systemic antifungal therapy is possible.

Maximum Dosage for Mouth Gel: For adult patients with oropharyngeal candidiasis due to immunodeficiency and recurrent vaginal candidiasis, application of up to a 1.2 cm strip of gel (≈200 mg) to the affected mucosal area up to 4 times a day is allowed. The maximum duration of use at the increased dosage is 7 consecutive days.

Pediatric Dosage for Mouth Gel: Recommended for children over 6 years of age with a body weight of at least 20 kg. For aphthous stomatitis or gingivitis, apply a 0.2-0.3 cm strip of gel (≈40-60 mg) to the affected mucosa 1-2 times a day after meals. Use in children under 6 years of age, as well as in children with body weight less than 20 kg, has not been studied.

Preventive Dosage for Mouth Gel: For adults with chronic recurrent vaginal candidiasis, chronic gingivitis and a tendency to aphthous ulcers, apply a 0.5 cm strip of gel (≈80-100 mg) once a day at night to the mucous membrane for 5-7 days monthly. Use is recommended for patients with immunodeficiency conditions and women during periods of frequent candidiasis recurrences.

Contraindications for Mouth Gel: Individual intolerance to components, severe allergic reactions to plants of the Terminaliaceae, Fabaceae or Acanthaceae families, presence of open bleeding ulcers of the mucosa. Scientifically registered data on contraindications during pregnancy, lactation and use in children under 6 years of age are not available.

Side Effects of Mouth Gel: Overdose may cause burning of the mucosa, irritation, increased salivation, very rarely - allergic reaction (rash, itching, angioedema).

Dosage adjustment based on patient body weight: Patients with body weight below 60 kg are recommended to use no more than the standard dosage (0.5-0.6 cm of gel per application). Patients with body weight over 90 kg and severe candidiasis may use the enhanced dosage (0.8-1 cm) up to 3 times a day.

Storage conditions: Store at temperatures from +8 °C to +25 °C, in a dry, dark place, protected from direct sunlight and sources of electromagnetic radiation. Shelf life – 24 months. After opening the tube, use within 30 days, close the cap tightly after each use.

Method of Vaginal Application for Mouth Gel

For intravaginal application, it is recommended to use a small or medium-sized hygienic tampon without fragrances or impregnations. Before use, wash hands thoroughly, remove the tampon from the package and prepare a clean surface. Squeeze a strip of gel 0.8-1 cm long, corresponding to approximately 150-200 mg, onto the upper third of the tampon, i.e., the part that is inserted first. Distribute the gel evenly in a thin layer over the surface; applying an excessive amount is not recommended to avoid leakage. Insert the tampon into the vagina in the usual way. The optimal time for insertion is in the evening, just before bedtime, which ensures contact of the preparation with the mucosa for 6-8 hours. Remove the tampon in the morning.

For mild forms of vaginal candidiasis, one application is sufficient. For severe manifestations, the course can be two or three consecutive nights. Use for more than five consecutive nights is not advisable, as the active substances have a cumulative effect and the mucosa has the ability to regenerate on its own.

The product is not used during menstruation. Simultaneous use with vaginal suppositories or other forms of local therapy is not recommended; courses should be separated. If burning or worsening of symptoms occurs, remove the tampon and rinse the vagina with warm water. For the prevention of recurrent candidiasis, the product can be used once a month for one night, preferably after courses of antibiotic therapy or during periods of immune exhaustion.

Toxicity and Biosafety — Mouth Gel

Data on the toxicity of Mucosal Gel (Mouth Gel) are based on a cumulative assessment of the safety of individual components included in the preparation. Terminalia chebula extract has low toxicity, acute toxicity upon oral administration to animals exceeds LD₅₀ 5 g/kg body weight, no cases of lethal dose in clinical practice have been registered. Glycyrrhiza glabra extract also has a high safety profile, LD₅₀ in rats is more than 14 g/kg upon oral administration, toxic effects are observed only with long-term systemic use in very high doses. Andrographis paniculata extract is characterized by moderate toxicity, LD₅₀ in mice is about 4 g/kg upon oral administration, while local use as part of the gel is not accompanied by systemic action. Menthol has an LD₅₀ in rats of about 3.3 g/kg upon oral administration; when applied topically to mucous membranes, it shows minimal absorption. Peppermint oil has an LD₅₀ in rats of 2.4 g/kg upon oral administration. Xanthan gum is a non-toxic substance, LD₅₀ in rats exceeds 45 g/kg.

The modeled aggregate toxicity of the complex of components of Mucosal Gel (Mouth Gel) for topical application is estimated as extremely low. The calculated indicator of acute toxicity for the combined composition upon oral administration extrapolatively exceeds LD₅₀ 5 g/kg body weight, which indicates the high biosafety of the preparation. When applied topically to mucous membranes, systemic absorption is minimal, which further reduces the risk of toxic reactions.

Synergy — Mouth Gel

The pharmacological synergy of the components of Mucosal Gel (Mouth Gel) is determined by the combination of phenolic compounds, flavonoids, tannins, terpenoids and polysaccharides with an overlapping spectrum of biological activity. Terminalia chebula extract, rich in gallic, ellagic and chebulagic acids, forms the basis of antimicrobial action. These polyphenols, in combination with glycyrrhizic acid and liquiritoside from Glycyrrhiza glabra, demonstrate a potentiating effect regarding the inhibition of microorganism and fungal growth, confirmed both in vitro and in in vivo models. The synergy of these compounds is predominantly additive-potentiating in nature: tannins of terminalia cause denaturation of microbial cell wall proteins, and saponins of licorice increase membrane permeability, enhancing the penetration of phenolic acids. Simultaneously, a modulating effect on inflammatory mediators is observed due to glycyrrhizin, which complements the anti-inflammatory activity of terminalia.

The inclusion of Andrographis paniculata in low concentration expands the spectrum of action of the composition. Andrographolide and its derivatives have the ability to inhibit the expression of pro-inflammatory cytokines, which, in combination with licorice flavonoids and terminalia tannins, forms a pronounced anti-inflammatory cascade with additive and partially potentiating effects. This has been confirmed in cellular models of inflammation, where the combined use of extracts demonstrated a more pronounced reduction in TNF-α and IL-6 production compared to isolated substances.

Menthol and peppermint essential oil play a predominantly modulating role. Their local analgesic effect due to the activation of cold TRPM8 receptors complements the anti-inflammatory and protective effect of polyphenols. Menthol also reduces the sensory reactivity of the mucosa, providing a protective background for the prolonged action of active substances. Xanthan gum, although it does not have pharmacological activity, provides important technological synergy: by creating a mucoadhesive matrix, it prolongs the contact time of terminalia, licorice and andrographis with the cells of the mucous membrane, which increases the bioavailability of polyphenols and saponins.

Thus, the composition demonstrates multi-vector synergy: potentiation of antimicrobial action through the combination of tannins and saponins, complementation of the anti-inflammatory effect through co-inhibition of cytokines, modulation of sensory signals by menthol, and prolongation of activity with the help of a polysaccharide base. This interaction can be classified as predominantly additive and potentiating, with a systemic focus at the tissue level of the mucous membranes.

References: PubMed ID 19425184, PubMed ID 21878063, PubMed ID 23970999, PMC3659612, ScienceDirect doi:10.1016/j.jep.2011.02.038.

Pharmacodynamics of Mouth Gel

The pharmacodynamic properties of Mucosal Gel (Mouth Gel) are due to the interaction of polyphenols, saponins, terpenoids and essential oils, acting primarily on the mucous membranes of the oral cavity and vagina. Terminalia chebula extract provides local antimicrobial and antifungal action due to the high concentration of tannins capable of binding to proteins of the microorganism cell wall and causing their denaturation. An additional effect is associated with the inhibition of bacterial enzymes and disruption of metabolic processes in cells.

Glycyrrhiza glabra acts through glycyrrhizic acid and flavonoids, which exhibit anti-inflammatory properties by suppressing NF-κB activation and reducing the production of pro-inflammatory cytokines. Licorice saponins increase the permeability of microorganism cell membranes, enhancing the action of terminalia tannins. Simultaneously, glycyrrhizin stabilizes the cell membranes of the epithelium, providing a protective effect for host tissues.

Andrographis paniculata contributes additionally through andrographolide, which inhibits pro-inflammatory mediators and exhibits antioxidant properties. On the immune system, it acts as a modulator, reducing the hyperactivity of inflammatory cascades. Menthol activates TRPM8 receptors of sensory nerve endings, providing a local cooling and analgesic effect, and also partially reduces the reactivity of mucosal nociceptors. Peppermint oil has a mild antiseptic effect and enhances local microcirculation.

Xanthan gum plays a key role in pharmacodynamics as a carrier: it forms a biopolymer matrix that holds the extracts on the mucosal surface, prolongs their contact with epithelial cells and ensures the gradual release of active substances. This creates a prolonged effect and increases local bioavailability.

Collectively, the pharmacodynamic profile of the preparation is characterized as locally directed, tissue-specific, possessing antimicrobial, antifungal, anti-inflammatory, antioxidant and analgesic action, with elements of immunomodulation. The main action is realized at the level of mucous membranes and epithelial cells, with minimal systemic influence.

References: PubMed ID 15707769, PubMed ID 23261812, PMC4003790, ScienceDirect doi:10.1016/j.phymed.2010.11.007, Wiley doi:10.1002/ptr.2930.

Pharmacokinetics of Mouth Gel

The active substances of Mucosal Gel (Mouth Gel) enter the body primarily through the mucous membranes of the oral cavity and vagina. Polyphenols of terminalia under conditions of local application have low systemic absorption, however, upon local contact they form stable complexes with proteins of epithelial cells, which ensures their prolonged local action. Glycyrrhizin saponins from licorice have a moderate ability for transmembrane penetration, but most of their activity is realized at the mucosal level, due to interaction with microorganism membranes and modulation of the local inflammatory response.

Flavonoids and phenolic acids are partially metabolized by the microflora of the mucosa and intestine upon accidental ingestion, where they undergo breakdown with the formation of metabolites possessing antioxidant activity. Andrographolide and related diterpenoids from andrographis have limited absorption through the mucous membranes, but their lipophilicity ensures penetration into the superficial layers of the epithelium. Menthol and essential oils penetrate through the mucous membranes faster due to high lipophilicity, reaching nociceptors and TRP receptors of sensory nerve endings, where they exhibit local action.

The distribution of active components is predominantly tissue-specific and limited to the site of application. Systemic action is possible only with repeated and massive ingestion. The metabolism of polyphenols and saponins is carried out in the liver, with the formation of conjugated forms (glucuronides, sulfates), which are excreted in urine and bile. Terpenoids of menthol are partially excreted through the lungs and skin, which explains the characteristic odor upon systemic absorption. Excretion of all components occurs mainly by the kidneys and liver; accumulation in tissues with local use is uncharacteristic.

References: PubMed ID 20884343, PubMed ID 30544558, ScienceDirect doi:10.1016/j.phymed.2016.12.009, Wiley doi:10.1002/ptr.4973.

Mechanisms of Action and Scientific Rationale: Mouth Gel

Liver and Gastrointestinal Tract. Polyphenols of terminalia and flavonoids of licorice exhibit lipotropic and antioxidant effects through the activation of antioxidant defense enzyme systems, including superoxide dismutase and catalase, as well as suppression of lipid peroxidation. Glycyrrhizic acid stabilizes hepatocyte cell membranes, and andrographolide reduces the expression of inflammatory cascade enzymes in the liver. The joint action can be characterized as modulating and membrane-stabilizing.
Reference: PubMed ID 18417164, ScienceDirect doi:10.1016/j.fct.2011.07.061

Immune System. Andrographolide and tannins of terminalia suppress the activation of NF-κB and JAK/STAT signaling cascades, reducing the expression of pro-inflammatory cytokines. Licorice saponins modulate the activity of macrophages and neutrophils, increasing phagocytic activity and regulating the release of interleukins. In aggregate, a potentiating effect on innate immune mechanisms and a modulating influence on inflammatory cascades are formed.
Reference: PMC4003790, Wiley doi:10.1002/ptr.2930

Nervous System. Menthol and peppermint essential oils activate TRPM8 receptors of sensory neurons, causing a cooling effect and local analgesia. They reduce the sensitivity of nociceptors and decrease the conduction of pain signals. Simultaneously, flavonoids and terpenoids exhibit neuroprotective action through antioxidant mechanisms and reduction of oxidative stress. The nature of the interaction is additive and modulating.
Reference: PubMed ID 21232571, ScienceDirect doi:10.1016/j.neuro.2017.06.002

Endocrine and Metabolic Regulation. Phenolic acids of terminalia and licorice saponins modulate the level of corticosteroid mediators through influence on the enzyme 11β-hydroxysteroid dehydrogenase, and also regulate the activity of glucose and lipid metabolism. Andrographolide interacts with MAPK and AMPK cascades, exerting a modulating effect on metabolism. These effects are tissue-specific and manifest in the regulation of the metabolic response to inflammation and stress.
Reference: PubMed ID 21878063, SpringerLink doi:10.1007/s11010-013-1900-1