KR102430797B1 - pharmaceutical composition for preventing or treating xerostomia - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of dry mouth and periodontitis, and the like, comprising extracts of lichen and lactic acid bacteria as active ingredients. It promotes the secretion and activity of amylase, increases the amount of salivation, inhibits endoplasmic reticulum stress activation and reduces oxidative stress, and has the effect of suppressing alveolar bone loss due to periodontitis, improvement, prevention, and treatment of dry mouth and periodontitis It is expected to be used in various fields such as pharmaceuticals, quasi-drugs, and food for

Description

A pharmaceutical composition for preventing or treating dry mouth and periodontitis, comprising extracts of sagebrush and lactic acid bacteria as active ingredients TECHNICAL FIELD

The present invention relates to a pharmaceutical composition for the prevention or treatment of dry mouth and periodontitis, and the like, comprising an extract of sagebrush and lactic acid bacteria as active ingredients.

Xerostomia is a disease in which the oral mucosa becomes dry due to a decrease in saliva secretion due to various causes. You will experience severe pain from burning of the membrane or ulceration of the oral mucosa.

Saliva plays an important role in the maintenance of the oral environment and oral function. That is, saliva has two functions: food intake and oral environment maintenance. As for the food intake function of saliva, saliva is responsible for maintaining taste through digestion, such as the formation of food mass and the action of digestive enzymes, or the solubilization of taste stimulants or secretion of gastin (a carbonate dehydrogenase). shows action. In the oral environment maintenance function, saliva exhibits an effect of cleaning teeth and mucous membranes, a remineralizing action of teeth, an antibacterial action, an immune action, an action of promoting tissue repair by growth factors and the like, and an anti-inflammatory action.

Recently, the number of patients complaining of a decrease in salivation caused by various factors is increasing. Therefore, the social demand for his treatment is increasing. Decreased salivation is accompanied by abnormalities of the salivary gland itself caused by radiation therapy or parotitis, and metabolic diseases (eg, Basedow's disease, diabetes, etc.), or other diseases such as collagen diseases. It can also be triggered by stressors or the side effects of various medications. With the recent aging of the population, the function of the salivary glands decreases with aging, and the number of patients complaining of decreased salivation as a result of various drug therapies for various complex diseases that occur in the elderly is expected to increase in the future. is becoming

Hyposalivation, as a result of dry mouth, causes the tongue to turn red and sometimes crack. Patients with hyposalivation complain of pain when eating, and difficulty chewing or swallowing. In addition, decreased salivation is known to cause uncomfortable feeling in the oral cavity, or taste disorders and pronunciation disorders, and denture instability, tooth decay, onset of periodontitis, stomatitis, pneumonia, and digestive dysfunction.

Although topical application of artificial saliva is used as a treatment for decreased salivation, its effect is limited and time-limited. As salivation promoters, anetol trithione, known as a muscarinic receptor agonist, and cevimeline hydrochloride are used, which are unstable in their effect and have problems with possible side effects of the digestive system such as nausea, vomiting, loss of appetite, abdominal discomfort, etc. There are several disadvantages. Under these circumstances, the development of a new therapeutic agent for the treatment of decreased salivation is desired.

Accordingly, the present inventors made research efforts to find a substance that is easy to ingest, safe for the human body, and can treat dry mouth. During simultaneous treatment, it promotes amylase secretion, reduces the expression of endoplasmic reticulum stress-related proteins, as well as reduces oxidative stress and suppresses the loss of alveolar bone in an animal model of periodontitis by confirming that it exhibits therapeutic and preventive effects on dry mouth and periodontitis. The present invention has been completed.

For the prevention and treatment of dry mouth and periodontitis accompanied by severe pain as described above, there is an urgent need to develop a composition for promoting salivation of natural ingredients without side effects other than compounds known to have a salivation promoting effect.

KR 10-1601778

The technical problem to be achieved by the present invention is to provide a composition for improving, preventing, or treating dry mouth and periodontitis, which includes a complex extract of sagebrush and lactic acid bacteria.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

In order to solve the above problems, the present invention provides a food composition for preventing or improving dry mouth and periodontitis, which includes an extract of the larvae and lactic acid bacteria complex as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of dry mouth and periodontitis, comprising the extract of the complex extract of sagebrush and lactic acid bacteria as an active ingredient.

In addition, the present invention provides a method for preventing or treating dry mouth and periodontitis, comprising administering to the subject a complex extract of lichen and lactic acid bacteria.

In addition, the present invention provides the use of the extract of the complex extract of sagebrush and lactic acid bacteria for the preparation of a medicament for the prevention or treatment of dry mouth and periodontitis.

As an embodiment of the present invention, the extract of sagebrush may be one extracted using water, a C ₁ to C ₄ lower alcohol, or a mixture thereof as a solvent.

As another embodiment of the present invention, the lactic acid bacteria may be Lactobacillus gasseri ( Lactobacillus gasseri ).

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In another embodiment of the present invention, the composition can increase the activity and secretion of amylase secreted from salivary gland cells.

As another embodiment of the present invention, the composition can increase the expression of aquaporin 5 (aquaporin-5: AQP-5) and NHE-1 (Na ⁺ -H ⁺ exchanger1) of salivary gland cells.

In another embodiment of the present invention, the composition may inhibit ER stress activation.

As another embodiment of the present invention, the composition may be to suppress the production of reactive oxygen species (ROS) in salivary gland cells, and to eliminate the already generated ROS.

As another embodiment of the present invention, the composition may inhibit alveolar bone loss in an animal model of periodontitis.

The extract of the present invention is derived from natural products, is safe for the human body, and has no side effects, and is easy to consume, promotes the secretion and activity of amylase, increases the amount of salivation, suppresses endoplasmic reticulum stress activation and reduces oxidative stress. As it is effective, it is expected to be used in various fields such as medicines, quasi-drugs, and food for the improvement, prevention, and treatment of dry mouth and periodontitis.

1 is a view comparing and confirming the amount of saliva and the rate of salivation according to the administration of extracts of sagebrush and / or lactic acid bacteria.
Figure 2 is a view comparing and confirming the amount of amylase secretion and its activity according to the administration of extracts of sagebrush and / or lactic acid bacteria.
3 is a view comparing and confirming the expression levels of Aquaporin 5 and NHE-1 according to the administration of extracts of sagebrush and / or lactic acid bacteria.
Figure 4 is a view comparing and confirming the expression level of ER stress protein according to the administration of the larvae and / or lactic acid bacteria extract.
Figure 5 is a view comparing the ROS production amount and the expression level of the ROS scavenging protein according to the administration of the extract of sagebrush and / or lactic acid bacteria.
6 is a view comparing and confirming the effect on the recovery of alveolar bone loss according to the administration of alveolus and / or lactic acid bacteria extract.

As a result of research efforts to find a substance that is easy to ingest, safe for the human body, and that can treat dry mouth and periodontitis, in an experiment using streptozotocin-induced diabetic rats, the complex extract of St. The present invention was completed by confirming that the effect of promotion, increase of salivation secretion, inhibition of endoplasmic reticulum stress activation, and oxidative stress reduction effect appears.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating dry mouth and periodontitis, comprising an extract of the lichen and lactic acid bacteria complex as an active ingredient.

Ixeris dentata of the present invention is a perennial herb belonging to the Compositae family, including Ixeris dentata NAKAI, Ixeris chinensis NAKAI, or Ixeris debilis A. GARY.

The pharmaceutical composition of the present invention may further include suitable carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions.

In addition, the pharmaceutical composition for the prevention or treatment of dry mouth including the composition according to the present invention, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., and sterile injection solutions according to conventional methods, respectively. It may be formulated and used in the form of, but preferably formulated in a solid form and administered orally.

Carriers, excipients and diluents that may be included in the composition comprising the composition include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose ) or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. may be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the suppository base, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

In addition, the present invention provides a food composition for preventing or improving dry mouth, comprising maekmundong, creation, licorice, health, dermis, longanyuk, fresh ginseng, and darasu flower extract as active ingredients. In addition, the composition may be added to food for the purpose of preventing dry mouth. When the composition of the present invention is used as a food additive, the composition may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, in the production of food or beverage, the composition of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all foods in the ordinary sense.

The health beverage composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, as in a conventional beverage. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumatine and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01-0.20 g, preferably about 0.04-0.10 g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may contain a carbonation agent used for carbonated beverages, and the like. In addition, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.

As used herein, the term “prevention” refers to any action that suppresses or delays the onset of dry mouth by administration of the pharmaceutical composition according to the present invention.

As used herein, the term “treatment” refers to any action in which symptoms for dry mouth are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.

As used herein, the term “improvement” refers to any action that reduces a parameter related to dry mouth, for example, the severity of symptoms by administering the composition according to the present invention.

The present invention can apply various transformations and can have various embodiments. Hereinafter, specific embodiments are illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.

[Experimental materials and methods]

1 reagent

They were provided as extracts of sagebrush (Yonsei University), lactic acid bacteria (Myongji University), and streptozotocin (S0130, sigma-aldrich), respectively. For the plant extract, dried and pulverized plant extract, about 40 g was extracted using an ultrasonic device at 50 °C for 3 h at 300 mL of water or 20%, 40%, 60%, 80% and 100% ethanol. These extracts were suspended in water before use to obtain a desired concentration.

Lactobacillus extract ( lactobacillus gasseri ) was isolated from human saliva and stored in 20% glycerol at -80°C. After activation on DeMan-Rogosa-Sharpe (MRS) agar plates at 37° C. for 24 hours, cells were re-cultured in MRS medium at 37° C. for 16 hours. After that, 0.5 mL of culture medium was inoculated in 0.5 L MRS broth and incubated at 37 °C for 24 hours. After fermentation, the supernatant was extracted with an equal volume of ethyl acetate (EtOAc), and the extract was concentrated to dryness on a rotary evaporator under vacuum.

2. Measurement of amylase activity

Amylase activity was measured using an amylase assay kit (BioVision Co., K711-100) at a wavelength of 405 nm at 25° C. and then ELISA.

3. Western Blot Analysis

After collecting salivary gland cells from mice, RIPA Buffer buffer (20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM Na ₂ EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5 mM Sodium pyrophosphate, 1 mM β-glycerophosphate, 1 mM Na ₃ VO ₄ ) was treated with a protease inhibitor (P3100-001, GenDEPOT) to extract proteins. Each sample is mixed with buffer and boiled for 5 minutes, then electrophoresed on sodium dodecyl sulfate-polyacrylamide gel (0227, AMRESCO) to separate proteins by size, block with blocking buffer (REF232100, BD Difco), and amylase, aquaporin 5, NHE-1, in order to check the expression of the endoplasmic reticulum stress-related antibody, the reaction was carried out at 4 ° C. overnight, and then the secondary antibody was reacted for 1 hour at room temperature ECL solution (Dae Myung Science Co., Ltd, Korea) was used. Membrane was reacted with the actin antibody again to check whether a certain amount of protein was used.

4. Measurement of Protein Oxidation

The amount of carbonyl in the protein was measured using the Protein oxidation detection kit (OxyBlot ^TM Chemical International, Temecula, CA). After protein extraction, the protein is separated using 10% SDS-PAGE. After attaching dinitrophenyl, a primary antibody, to Immno-blot ^TM PVDF transfer membranes (162-0177, bio-rad), and leaving it overnight at 4°C, the secondary antibody rabbit (sc-2004) , santa cruz) and reacted at room temperature for 1 hour. Then, the expression of the protein is checked using SuperDetect ^TM ECL solution (Dae Myung Science Co., Ltd, Korea).

5. Dry Mouth Animal Model Preparation

Dry mouth is one of the main outcomes of diabetes and is known to cause salivary gland dysfunction. Therefore, a diabetic model was selected as a dry mouth animal (Bhattarai, K.R.; Junjappa, R.; Handigund, M.; Kim, H.R.; Chae, H.J. The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmune. Rev. 2018 .)

7-week-old male Sprague-Dawley rats weighing 200 to 230 g were bred in a general breeding environment (22±2°C, 55-60% relative humidity, and 12 hours day/night cycle lighting), and one week before use in the experiment. It was made to adapt to the laboratory environment. Water and feed were allowed to be freely fed during the period of the experiment.

In group 1 of reared rats, 6.5 mg/kg streptozotocin (STZ) was dissolved in 0.1 M citrate buffer (pH 4.5) and injected intraperitoneally (IP), followed by breeding for 2 weeks to induce dry mouth did.

6. Immunohistochemistry (IHC)

After fixing the rat salivary gland tissue in 10% formaline, cut it to a thickness of 5 μm to inactivate endogenous peroxidase present in the tissue. The primary antibody related to the water channel was appropriately diluted in a diluted solution of 0.05% sodium azide and 0.5% BSA, respectively, left overnight at 4°C, and then biotinylated anti-rabbit IgG of the secondary antibody solution was again 1:200 Dilute and react at room temperature for 1 hour. After the ABC kit reaction, it was washed 3 times for 3 minutes with 0.05M PBS, and then colored for 5 minutes at room temperature using a coloring agent for color development. After the reaction, the tissue was washed 3 times with 0.05M PBS for 10 minutes and mounted. . The expression of the water channel-related protein in the salivary gland tissue is observed under an optical microscope and a photograph is taken.

7. Periodontitis Experimental Model Induction and Sample Processing

Experimental animals were a normal control group that did not induce periodontitis (NL, non-ligatured and non-treated), a negative control group that induced periodontitis (L, ligatured and vehicle-treated), and a sample treated group that was treated with periodontitis induced periodontitis and wormwood extract ( IXD-treated), lactic acid bacteria-treated sample-treated group (Lac.B), or co-treated sagebrush and lactic acid bacteria extract (IXD+Lac.B) were divided into 5 groups with 7 mice per group. White papers of all groups except the normal control group were general anesthetized with a ketamine/zolazepam mixture (Zoletil 50, Virbac Lab, Carroscedex, France) and then ligated to the maxillary second molar with a sterile suture (5-0, nylon thread) to induce periodontitis. did. On the other hand, in the normal media control group, only the cervical part of the incisor was checked and ligation was not performed. Afterwards, to the sample treatment group, 10 mg/kg of sagebrush alone, 0.5 mg/kg of lactic acid bacteria alone, and a lichen/lactic acid bacteria extract were simultaneously administered to the same site where periodontitis was induced. A single dose of sagebrush and/or lactic acid bacteria extract was administered as a spray. Distilled water containing 1% carboxymethyl cellulose was equally applied to the normal control group and the negative control group after administration of 00 g/l and rearing for 00 days. Sample treatment and control treatment were treated once a day for 8 days. After 8 days, the histomorphological and molecular indicators were analyzed in the alveolar bone obtained by sacrificing white paper.

8. Assessment of alveolar bone loss

The left maxilla separated from the white paper was cleaned after soaking the surrounding tissues, and the tissues were fixed in 10% paraformaldehyde for 24 hours. After the fully fixed maxilla was completely dried, it was stained with 1% aqueous methylene blue (Sigma, USA) for 5 minutes. The stained left maxilla was photographed with a smart microscope (Canon digital camera, 100mm macro lens). For the evaluation of alveolar bone loss (ABL), the boundary between the cementum and enamel of the teeth ( The distance from the cementoenamel junction, CEJ) to (alveolar bone crest, ABC) was measured with Image J (NIH, Bethesda, USA).

9. Statistical Treatment

Results are expressed as mean ± standard error, and analysis of variables was performed using Duncan's test. When the P value was less than 0.05, it was judged to be statistically significant, and all experiments were independently performed three or more times for statistical processing.

[Experiment result]

Example 1. Confirmation of changes in blood sugar according to administration of sagebrush and lactic acid bacteria complex extract

In the dry mouth animal model prepared by administering streptozotocin, 10 mg/kg Lactobacillus alone, 0.5 mg/kg Lactobacillus alone, and Lactobacillus/Lactobacillus extract were simultaneously administered. After administering 00 g/l single administration as a spray and bred for 00 days, blood glucose was measured by collecting the tail of the rats. As a result, it was confirmed that high blood sugar of 300 mg/dl or more was maintained in the group treated with the sagebrush and lactic acid bacteria complex extract than the animals treated with the sagebrush extract or the lactic acid bacteria extract.

Example 2. Confirmation of increase in salivary volume and salivation rate according to administration of the extract

After the simultaneous administration of 10 mg/kg of Lactobacillus alone, 0.5 mg/kg of Lactobacillus alone, and Calcifera/lactobacillus extract in a dry mouth animal model prepared by administering streptozotocin, 00 g/l of Siberian oleracea and/or lactic acid bacteria extract was administered and administered for 00 days. After breeding, the amount of saliva and the rate of salivation were measured.

As a result, it was confirmed that the amount of saliva and the rate of salivation decreased according to the treatment of streptozotocin, and the tendency of the decreased amount of saliva and the rate of salivation to be recovered according to the treatment of the sagebrush extract and/or lactic acid bacteria extract. On the other hand, it could be confirmed that the treatment of the extract of serrata and lactic acid bacteria significantly increased the amount of saliva and the rate of salivation compared to the single treatment group (FIG. 1).

Example 3. Confirmation of increase in amylase activity according to the administration of the extract of S. serrata and lactic acid bacteria

In a dry mouth animal model prepared by administering streptozotocin, after simultaneous administration of Streptoid and/or Lactobacillus extract at 10 mg/kg, Lactobacillus alone 0.5 mg/kg, and Lactobacillus/Lactobacillus extract at the same time, 00 g/l was administered and for 00 days After breeding, the amount and activity of amylase secreted from the salivary glands were measured.

As a result, it was confirmed that the amylase secretion was decreased according to the treatment with streptozotocin, and the amylase secretion ability was increased according to the treatment with the Swallowtail extract and/or the lactic acid bacteria extract. On the other hand, it was confirmed that the treatment with the extract of serrata and lactic acid bacteria complex extract was significantly higher in amylase secretion compared to the single treatment group, and the activity of amylase was recovered to a similar degree as the untreated control group with streptozotocin (FIG. 2).

Example 4. Confirmation of the effect of increasing the expression of aquaporin 5 and NHE-1 according to the administration of the extract

After simultaneous administration of 10 mg/kg Lactobacillus alone, 0.5 mg/kg of Lactobacillus alone, and Lactobacillus/Lactobacillus extract to a dry mouth animal model prepared by administering streptozotocin, 00 g/l of Siberian oleracea and/or lactic acid bacteria extract was administered and administered for 00 days. After breeding, the salivary gland cells of the rats were separated and the expression levels of aquaporin 5 (aquaporin-5: AQP-5) and NHE-1 (Na ⁺ -H ⁺ exchanger1) of the acupuncture cells were analyzed.

As a result, it was confirmed that the expression levels of AQP-5 and NHE-1 decreased according to the treatment with streptozotocin, and the expression of AQP-5 and NHE-1 was increased according to the treatment with the sagebrush extract and/or lactic acid bacteria extract. On the other hand, it could be confirmed that the treatment of the extract of serrata and lactic acid bacteria remarkably increased the expression levels of AQP-5 and NHE-1 compared to the single treatment group (FIG. 3).

Example 5. Confirmation of the endoplasmic reticulum stress activation inhibitory effect according to the administration of the extract

In the salivary gland tissue, activation of the ER stress response and decreased secretion of saliva and the like are correlated. The endoplasmic reticulum is involved in the transport and secretion of secreted proteins within the cell, and when the function of this organelle does not work smoothly, the secretion of saliva is reduced. Therefore, in this experiment, after the simultaneous administration of 10 mg/kg of Lactobacillus alone, 0.5 mg/kg of Lactobacillus alone, and lactobacilli/lactic acid bacteria extract in the dry mouth animal model, 00 g/l of A. After breeding for 00 days, rat salivary gland cells were isolated and the expression levels of endoplasmic reticulum stress proteins GRP78, CHOP, p-IRE1α α, and p-eIF2α α were analyzed.

As a result, it was confirmed that the expression of the ER stress protein increased according to the treatment with streptozotocin, and the increased amount of the ER stress protein expression was decreased according to the administration of the Swallowtail extract and/or the lactic acid bacteria extract. On the other hand, it was confirmed that the treatment of the extract of serrata and lactobacilli significantly decreased the expression level of the endoplasmic reticulum stress protein as compared to the single treatment group, and recovered to a similar extent to the untreated control group with streptozotocin (FIG. 4).

Example 6. Confirmation of the oxidative stress reduction effect according to the administration of the extract

In order to confirm the expression of oxidative stress in salivary gland tissues, the degree of ROS induction according to the administration of streptozotocin and the inhibitory effect of ROS generation of wormwood and/or lactic acid bacteria extracts were investigated using DHE staining.

As a result, it was confirmed that the amount of ROS production increased according to the treatment with streptozotocin, and the treatment with the sagebrush extract and/or the lactic acid bacteria extract inhibited the increase in ROS production by streptozotocin. On the other hand, it was confirmed that the treatment of the extract of serrata and lactic acid bacteria can more strongly inhibit the generation of ROS compared to the single treatment group ( FIG. 5A ).

Example 7. Confirmation of the antioxidant effect of sagebrush and lactic acid bacteria complex extract

As a result of this experiment, as shown in FIG. 5D , intracellular damage caused by streptozotocin occurs, and in order to confirm whether intracellular damage is recovered through sturgeon or lactic acid bacteria, as a result of confirming the expression of lipid peroxidation, streptozotocin alone treatment While the expression of lipid peroxidation was increased compared to the control group, it was confirmed that the expression of lipid peroxidation was decreased when the sagebrush or lactic acid bacteria were simultaneously treated with streptozotocin compared to the group treated with streptozotocin alone. In addition, it was confirmed that the expression of lipid peroxidation was more reduced when the lichen and lactic acid bacteria were simultaneously treated with streptozotocin compared to the group treated with Streptococcus or lactobacilli at the same time.

As a result of checking the activity of the GSH / GSSG ratio, GPx or SOD in order to confirm the antioxidant effect of the sagebrush and / or lactic acid bacteria extract, when treated with streptozotocin, the GSH / GSSG ratio, GPx or SOD activity decreased compared to the control group, Simultaneous treatment with Streptococcus or Lactobacillus extract was confirmed to increase the activity of the GSH/GSSG ratio, GPx or SOD compared to the group treated with streptozotocin alone. In addition, it was confirmed that the GSH / GSSG ratio, GPx or SOD activity increased to a remarkably high level compared to the single-treated group when co-treated with streptozotocin complex extract of sagebrush and lactic acid bacteria.

Example 8. Confirmation of the alveolar bone loss recovery effect of alveolar and lactic acid bacteria complex extract

As a result of confirming the alveolar bone damage to confirm the alveolar bone loss recovery effect of the alveolar bone loss and recovery effect of the alveolar bone marrow extract, the periodontitis-inducing group increased alveolar bone damage compared to the control group. It was confirmed that the alveolar bone damage was significantly inhibited compared to the single treatment group. In addition, it was confirmed that when the combination extract of sagebrush and lactic acid bacteria was simultaneously treated in the periodontitis model group, alveolar bone damage was significantly inhibited compared to the single treatment group. (Fig. 6)

As described above in detail a specific part of the content of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

A pharmaceutical composition for the prevention or treatment of dry mouth and periodontitis, comprising an extract of sagebrush and lactic acid bacteria complex as an active ingredient. The method of claim 1,
The extract is water, C ₁ to C ₄ A lower alcohol, or a mixture thereof as a solvent, the extracted pharmaceutical composition. The method of claim 1,
The lactic acid bacteria is Lactobacillus gasseri ( Lactobacillus gasseri ), the pharmaceutical composition. The method of claim 1,
The lactic acid bacteria extract is obtained by separating Lactobacillus gasseri from human saliva, a pharmaceutical composition. delete The method of claim 1,
The composition is characterized in that it increases the activity and secretion amount of amylase secreted from the salivary gland cells, a pharmaceutical composition. The method of claim 1,
The composition is characterized in that to increase the expression of aquaporin 5 (aquaporin-5: AQP-5) and NHE-1 (Na ⁺ -H ⁺ exchanger1) of the salivary gland cells, a pharmaceutical composition. The method of claim 1,
The composition is characterized in that inhibiting the ER stress (ER stress) activation, a pharmaceutical composition. The method of claim 1,
The composition is characterized in that it has the ability to inhibit and eliminate active oxygen (ROS) production in salivary gland cells, a pharmaceutical composition. A food composition for the prevention or improvement of dry mouth and periodontitis, comprising an extract of sagebrush and lactic acid bacteria as an active ingredient.

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