KR20160028423A - A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia - Google Patents

Abstract

The present invention relates to a composition for preventing and treating xerostama, containing a compound isolated from an Ixeris dentata (Thunb.) Nakai. extract as an active ingredient. According to the present invention, the Ixeris dentata (Thunb.) Nakai. extract promotes amylase secretion when co-treating high-concentration glucose and Ixeris dentata (Thunb.) Nakai. together, in an experiment using human salivary gland (HSG) cells, and decreases expression of proteins associated with endoplasmic reticulum stress. In addition, an oxidation-reduction environment in an endoplasmic reticulum associated with protein synthesis is well maintained after short-term and long-term co-treatment of high-concentration glucose. Thus, the composition of the present invention can be useful as a pharmaceutical composition for preventing and treating xerostama and a functional health food.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing and treating dry mouth syndrome, which contains, as an active ingredient, a compound (ID-56D2)

The present invention relates to a composition for the prevention and treatment of dry mouth syndrome containing, as an active ingredient, a compound (ID-56D2) isolated from scarab extract.

[Document 1] Metabolism of Information Extracts, Young Lim, p1057-1058, 1998

[2] Hwa-Young Lee, Geum-Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyungpyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata- induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food and Chemical Toxicology. 62 2013. 739-749.

[Literature 3] J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola. Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. Phytochemistry. 36 (3) 1994. 725-729.

[Document 4] Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from Ixeris debilis and Ixeris repens . Phytochemistry. 29 (10) 1990. 3217-3224.

[Literature 5] Keiichi Nishimura, Toshio Miyase, Akira Ueno, Tadataka Noro, Masanori Kuroyanagi, Seigo Fukushima. Sesquiterpene lactones from Ixeris stolonifera A. Gray. Chemical and Pharmaceutical Bulletin. 33 (8) 1985, 3361-3368.

[Literature 6] W. Kisiel, B. Barszcz. Sesquiterpene lactone glycosides from Crepis pyrenaica. Phytochemistry. 39 (6) 1995. 1395-1397.

[Literature 7] Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3 (2) 2008. e1648.

[Literature 8] Benjamin P. Tu and Jonathan S. Weissman. Oxidative protein folding in eukaryotes: mechanisms and consequences, The Journal of Cell Biology. 164 (3) 2004. 341-346.

Xerostomia is a disease in which saliva secretion is reduced due to various causes and causes dry mouth mucosa. It usually complains of dysfunction of chewing function and language function. It causes severe bad breath and tooth decay, Or burning of the mucous membranes or ulcers of the oral mucosa.

Saliva plays an important role in maintaining oral environment and oral function. In other words, saliva has two functions: food intake function and oral environment maintenance function. In the food intake function of saliva, the saliva maintains the taste through the formation of the food mass and the digestion such as the digestive enzymatic action, or the solubilization of the taste stimulant substance or the secretion of gastin (which is a carbonate dehydrogenase) Lt; / RTI > In the oral environment maintenance function, the saliva shows a midnight effect of the teeth and mucous membranes, a rejuvenation effect of the teeth, an antibacterial effect, an immune function, a tissue restoration enhancing action by growth factors and the like, and an anti-inflammatory action.

Recently, there are increasing numbers of patients who complain of decreased salivation caused by various factors. Therefore, the social demand for his treatment is increasing. The lowering of saliva secretion is accompanied by abnormality of the salivary gland itself caused by radiotherapy or mumps, and other diseases such as metabolic diseases (for example, bassadoesitic disease, diabetes mellitus) or collagen diseases, Or by side effects of various medicines. As the population ages in recent years, the number of patients who complain of salivary gland function decline due to aging and the decrease of saliva secretion as a result of various medications for various diseases that accompany to the elderly will increase in the future .

Decreased saliva secretion, as a result of oral dryness, reddened tongue, sometimes cracked, salty fluid secretion patients suffer pain at the time of appeal, chew or swallow difficulty. In addition, lowering of saliva secretion has been known to cause uncomfortable feeling in the oral cavity, or taste disorder and pronunciation disorder, causing dental instability, cavities, periodontal disease, stomatitis, pneumonia, and digestive dysfunction.

Topical application of artificial saliva is used as a treatment for saliva secretion reduction, but the effect is temporary and limited. Anitol trithione, known as muscarinic receptor agonists, and sevimeline hydrochloride, are used as salivary secretagogues. They are unstable in their effectiveness and have a possibility of adverse gastrointestinal side effects such as nausea, vomiting, loss of appetite and abdominal discomfort There are some disadvantages. In this situation, the development of a new therapeutic agent for the treatment of salivation deficiency is desired.

For the prevention and treatment of dry mouth accompanied by severe pain as described above, development of a composition for promoting the saliva secretion of a natural ingredient without adverse effect, which is different from a compound already known to have saliva secretion promoting effect, is desperately needed.

Ixeris dentata NAKAI) is a perennial herb that belongs to the Compositae, and refers to the outpost as a mountain stop, and Ixeris chinensis NAKAI), I xeris debilis A. GARY) have been used in the treatment of urinary stone, pneumonia, bruises, and the like.

However, there is no mention or teaching in the literature of the therapeutic efficacy of dry extract or compounds isolated therefrom on oral dryness.

As a result of efforts to find a substance which is easy to ingest, safe for human body and can treat dry mouth, the present inventors have found that a compound isolated from the extract of Zygomycetum is (1) an experiment using human salivary gland cells (HSG cells) (6) the oxidation-reduction of endoplasmic reticulum (ER) associated with protein synthesis during simultaneous treatment with glucose at a high concentration for a short period of time and a long period of time, as well as to reduce amylase secretion during simultaneous treatment of scabies and high- And confirming that the environment is well maintained, it shows the treatment and prevention effect of dry mouth, thereby completing the present invention.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating dry mouth, which comprises a compound isolated from the extract of Zygomycis koreana as an active ingredient.

In addition, the present invention provides a health functional food for preventing or ameliorating dry mouth symptoms containing as an active ingredient, a compound isolated from an extract of Ascarians.

The conspiracy defined here is the Ixeris dentata NAKAI), Ixeris chinensis NAKAI, or I xeris debilis A. GARY.

The extract as defined herein is an extract which is soluble in a solvent selected from water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably a water and ethanol mixed solvent, more preferably 30 to 100% (v / v) And extracts soluble in water and ethanol mixed solvent.

The compound isolated from the scabbard extract as defined herein is 11,13-dihydrointegrifolin 3-O- beta -D-glucopyranoside (ID-56B2), (2) ixerisoside A, (ID-56D2), (3) ixerin M, (ID-56D1B), and (4) epiisolipidiol-3-ss-glucopyrano Glucopyranoside, (ID-57D).

As defined herein, the dry mouth syndrome is characterized by a dry mouth syndrome caused by a metabolic disease such as radiotherapy, mumps, bassedodiosis, diabetes, collagen diseases, stress, aging, or side effects of medicines.

The compounds of the present invention may be prepared into pharmaceutically acceptable salts and solvates by methods conventional in the art.

Pharmaceutically acceptable salts include acid addition salts formed by free acids. The acid addition salt is prepared by a conventional method, for example, by dissolving the compound in an excess amount of an acid aqueous solution, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The same molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be filtered by suction.

As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid Citric acid, lactic acid, glycollic acid, gluconic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid and hydroiodic acid can be used.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving a compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt in particular, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

Pharmaceutically acceptable salts of the compounds of the present invention include, unless otherwise indicated, salts of acidic or basic groups that may be present in the compounds of the present invention. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of hydroxy groups, and other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate rate, methane sulfonate (mesylate) and p - toluene sulfonate (tosylate) and a salt, the salt manufacturing method or manufacturing process known in the art ≪ / RTI >

Compounds isolated from the scabious extract of the present invention can be obtained by the following production method.

For example, the present invention will be described in detail below.

The scarab extract of the present invention can be prepared as follows. After drying and shredding the dried scabbard, the scabbard is washed with water containing purified water, a solvent selected from lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol and butanol, or a mixed solvent thereof, preferably water and ethanol mixed solvent, more preferably 30 Followed by ultrasonic extraction, hot water extraction, room temperature extraction or the like at a temperature of 30 ° C to 150 ° C, preferably 50 ° C to 100 ° C for 30 minutes to 48 hours, preferably 1 hour to 12 hours, The extract obtained by repeatedly performing the reflux extraction method, preferably the ultrasonic extraction method, about 1 to 20 times, preferably 2 to 10 times, is filtered, concentrated under reduced pressure, and dried to obtain the crude extract of the present invention.

Compounds isolated from the crude extract are obtained by adding water of about 0.0005 to 0.005 times, preferably 0.05 to 0.5 times the volume (v / w%) of the crude extract, preferably 10 to 90% ethanol crude extract, , Ethyl acetate and butanol to obtain non-polar solvent-soluble extract fractions which are used in non-polar solvents such as n-hexane, methylene chloride and ethyl acetate; And a polar solvent-soluble fraction extracted in a polar solvent such as butanol and water; The polar solvent-extractable fraction, preferably the water-soluble fraction, obtained in the above-mentioned polar solvent such as butanol and water is subjected to flash column chromatography, RP C18 column chromatography or silica gel open column chromatography, Diaion HP-20 column chromatography Or the like can be selectively and repeatedly carried out several times to purify and obtain the compound of the present invention, corrillazine.

The present invention provides a pharmaceutical composition and a health functional food for the treatment or prevention of dry mouth syndrome containing the compound as an active ingredient, the compound being separated from the extract of Zygomycethe sp. Obtained by the above production method and the production process.

(1) In experiments using human salivary gland cells (HSG cells), it was found that the simultaneous treatment of scabbard and high glucose concentration promotes the secretion of amylase, and the expression of endoplasmic reticulum stress-related proteins (6) It is confirmed that the oxidation-reduction environment in the endoplasmic reticulum associated with protein synthesis is maintained well during the simultaneous treatment with glucose at a high concentration for a short period of time and for a long period of time.

The pharmaceutical composition of the present invention contains 0.01 to 80% by weight, preferably 10 to 50% by weight of the above compound, based on the total weight of the composition.

The pharmaceutical compositions comprising the compounds of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the compounds of the present invention may also be used in the form of their pharmaceutically acceptable salts and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set.

The composition may be formulated into various formulations, such as oral or parenteral formulations. When formulating the composition, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant may be used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose, Sucrose), lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The compound according to the present invention is preferably contained in an amount of 0.1 to 50% by weight based on the total weight of the composition. However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

The preferred dosage of the compound according to the present invention varies depending on the condition and body weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, in order to obtain the desired effect, it is preferable to administer it at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The composition according to the present invention may be used alone or in combination with methods for the treatment and / or treatment of an objective disease or using surgery, hormone therapy, drug therapy and biological response modifiers.

The herbal extract according to the present invention has little toxicity and side effects, and therefore can be safely used for long-term administration for preventive purposes.

The present invention also provides a health functional food for improving and preventing dry mouth symptoms, which comprises a compound isolated from the extract of Zygomycota as an active ingredient.

The health functional food containing the compound of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of dry mouth symptoms. Examples of the foods to which the compound of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, leach tea, health supplements and the like, and they are in the form of powder, granule, tablet, capsule or beverage Can be used.

Accordingly, the present invention also provides a health supplement or a food additive containing, as an active ingredient, a compound isolated from an extract of Zygomycetum having an effect of preventing and improving dry mouth.

Food forms to which the compounds of the present invention can be added include various foods of candy, beverages, gums, tea, vitamin complexes, or foods that are health supplement foods.

The compounds of the present invention may be added to foods or beverages for the purpose of preventing and improving oral dryness. At this time, the amount of the compound in the food or beverage may generally be from 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition is preferably 0.02 to 10 g based on 100 ml, Can be added at a ratio of 0.3 to 1 g.

The health beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional ingredient, such as ordinary beverages, in addition to containing a mixture of the above-mentioned compounds as essential ingredients in the indicated ratios, have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

(1) In experiments using animal models with human salivary gland cells (HSG cells), it was found that the compounds of the present invention inhibit the secretion of amylase during the simultaneous treatment of the high-concentration glucose and the high- It was confirmed that not only the expression of the ER stress related protein was reduced but also the oxidative-reductive environment in the endoplasmic reticulum associated with protein synthesis was maintained well during the simultaneous treatment with glucose at a high concentration of short and long term, Can be usefully used as a functional food.

Figure 1 shows the results of an assay for the secretion of amylase from high glucose:
FIG. 2 is a graph showing the result of UPLC analysis of the crude extract (FIG. 2A is a chromatogram of 8-epiisolipidiol-3-.beta.-D-glucopyranoside of 0.1 mg / mL and FIG. 2B is of 8-epiisolipidiol-3-.beta.-D-glucopyranoside FIG. 2C is a chromatogram of Ixerin M 0.05 mg / mL; FIG. 2D is a chromatogram of ethanol extract of Ixerin M and Zygomycetum; FIG. 2C is a chromatogram of Ixerin M 0.05 mg / Lt; / RTI >
FIG. 3 is a graph showing the results of experiments on the secretion effect of amylase due to ethanol extract and methanol extract on the high concentration glucose treatment in salivary gland cells; FIG. 3B shows the results of the secretion effects of amylase on 0, 20, 40, 60, 80 and 100% of ethanol extracts of Amaranthus japonicus);
FIG. 4 is a graph showing the results of time-dependent secretion of amylase from 100% ethanol extract of rosemary extract during long-term high-concentration treatment in salivary gland cells (FIGS. 4A and 4B show 40 mM glucose alone and the simultaneous treatment of 100% ethanol extract with high concentration of glucose and amylase secretion)
FIG. 5 is a time-dependent secretion effect study of amylase by ID-56D1B (Ixerin M), which is an effective ingredient for scavenging in high concentration treatment in salivary gland cells (FIGS. 5A and 5B are 0, 1, 2, 3, The result of amylase secretion in the simultaneous treatment of Ixerin M active ingredient extract and high glucose at 40 mg / day for 7 days);
FIG. 6 shows the results of the time-dependent secretion effect of amylase secreted by ID-57D, which is an effective component of the secretion in short-term high-concentration treatment in salivary gland cells (FIG. 6A shows 0.005, 0.001, 0.002, 0.004 mg / mL ID- 6B and C show the results of single cell treatment of 40 mM glucose, and simultaneous treatment of ID-57D and glucose at 0, 12, 24, 36, and 48 hours FIG. 6D shows the expression of stress-related proteins in the endoplasmic reticulum when treating high glucose and ID-57D simultaneously);
FIG. 7 shows the results of time-dependent secretion of amylase in the saline-germ cells treated with ID-57D, which is the active component of the secretion in high concentration treatment (FIGS. 7A and 7B show results of 40 mM glucose and the secretion of amylase in the simultaneous treatment of ID-57D and high concentration glucose in the case of treatment with high glucose and ID-57D at the same time, stress in the endoplasmic reticulum FIG. 7D shows the result of confirming the degree of Oxydation after treating high glucose at 0, 1, 2, 3, 5 and 7 days in salivary gland cells and ID-57D at high glucose concentration simultaneously being);
FIG. 8 is a graph showing the results of blood sugar change experiments due to scurvy during treatment with streptozotocin in an animal model; FIG.
FIG. 9 shows experimental results on the salivary gland weight, amount of protein and secretion effect of amylase in the animal model when treated with streptozotocin;
FIG. 10 shows the results of an assay for the secretion of amylase in saliva and salivary glands due to scurvy during streptozotocin treatment in animal models;
Figure 11 shows the results of saliva fraction ratios due to scurvy during streptozotocin treatment in animal models;
FIG. 12 is a graph showing the results of histological analysis of salivary glands due to scabies during streptozotocin treatment in an animal model. FIG.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

COMPARATIVE EXAMPLE 1 < tb >

Literature (Hwa-Young Lee, Geum- Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyung pyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata- induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. (Korea Plant Extract Bank, http://extract.pdre.re.kr , Daejeon) from Korea Biotechnology Research Institute in Korea, Food and Chemical Toxicology, Pages 11, Model 5G, 4, Were used. In order to compare the contents of the active ingredients according to the extraction solvent, the dried scabbard was extracted with 100% methanol.

EXAMPLES Example 1. Ethanol extract of horseradish

The dried Ixeris dentata used in the experiment was purchased from Jeung Woo ( http://www.herbseoul.com/ , Seoul, Korea). 30 ~ 40g of the pulverized sample was extracted with 200 mL of 100% ethanol solution for HPLC by using an ultrasonic pulverizer (BRAONSON Ultrasonication corporation, ultrasonic cleaner, BRANSON) at 50 ° C, and the extract was filtered using a cotton pad and concentrated. After the sample was lyophilized, the dried material was used in the following experiment.

Example 2. Determination of active ingredient of extract

In order to confirm the component content and the component phase of the extracts of the above Comparative Examples and Examples, component analysis was performed under the HPLC analysis conditions as shown in Table 1 below.

The active ingredient content in the extract was measured at 210 nm using a Waters ACQUITY UPLC H-Class System and INNOPIA Inno C18 (4.6 x 150 mm, 5 μm) column.

2-1. Selection of analysis conditions

○ Analytical instrument: Waters ACQUITY UPLC H-Class System

Column temperature and flow rate: 30 ° C, 1 mL / min, 10 μL injection

○ Fixed phase, mobile phase and detection conditions: INNOPIA Inno C18 (4.6 × 150 mm, 5 μm), 210 nm

Time Soln. A (water) Soln. B (acetonitrile) 0.0 95.0 5.0 20.0 75.0 25.0 20.1 95.0 5.0 30.0 95.0 5.0

2-2. result

As a result of the above experiment, in terms of the active ingredient content of Ixerin M and ID-57D (8-epiisolipidiol-3-β-D-glucopyranoside) which are the index components of scarab, the 100% methanol extract contained 0.0507 mg / 100 mg (ID-56D1B) and 0.1266 mg / 100 mg (Ixerin M) and 0.0675 mg / 100 mg (ID-56D1B), respectively, , And Ixeris M and ID-56D1B were found to be the most abundant in 100% ethanol extracts, and the content of indomethacin in the ethanol extracts of 0, 20, 40, 60, 80 and 100% Ixeris M and 8-EI-3G were the most abundant in the ethanol extracts (see FIG. 2 and Table 2).

Evaluation of content of indomethacin extract mg / 100 mg 0% EtOH 20% EtOH 40% EtOH 60% BEtOH 80% EtOH 100% EtOH 100% MeOH
(Yonsei University) Ixerin M 0.0694 0.0676 0.0612 0.0614 0.0644 0.1266 0.0507 8-EI-3-G 0.0 0.0 0.1289 0.1921 0.2675 0.5388 0.0

Example 3. Scutellariae Extract Isolation Compound.

(1) 11,13-dihydrointegrifolin 3-O-? -D-glucopyranoside (hereinafter referred to as ID-56B2, reference: J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola, Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. (2) ixerisoside A (referred to as ID-56D2, reference: Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from I xeris debilis and Ixeris repens . Phytochemistry, Compound 9, 1990), (3) ixerin M, (ID-56D1B, reference: Keiichi Nishimura, Toshio Miyase, Akira Ueno, Tadataka Noro, Masanori Kuroyanagi, Seigo Fukushima, Sesquiterpene lactones from Ixeris stolonifera A. Gray. (ID-57D, referenced by W. Kisiel, B. Barszcz, Sesquiterpene lactone glycosides, and the like), (4) 8-epiisolipidiol-3-D- glucopyranoside from Crepis pyrenaica. Phytochemistry, Page 1396, Compound 4, 1995) were separated, and the compound structures were identified by comparing their physical properties with those described in the existing literature.

In order to separate the compounds, 5 kg of dried scallops were ultrasonically extracted with 100% MeOH three times for 4 hours. The extract was filtered and concentrated under reduced pressure to obtain 700 g of MeOH extract. The fractions were fractionated in chloroform (CHCl ₃ ), ethyl acetate (EtOAc) and H ₂ O in the order of 53.3 g, 17 g and 550 g, respectively. The H ₂ O fraction was passed through HP-20 resin, which was divided into five fractions (3A-3E) using Water: MeOH (0: 1 → 1: 0) as the solvent. 3B fraction was purified by silica gel column chromatography (30 × 40 cm). ID-56B2 (15.0 mg) was obtained by eluting with CHCl ₃ -MeOH = 4: 1. Running a prep-LC to 15% Acetonitrile in H ₂ O as eluent with respect to the 3D fraction to obtain the ID-56D2 (7.0 mg), ID-56D1B (4.6 mg) and ID-57D (10.3 mg).

(a) 11,13-dihydrointegrifolin 3-O-? -D-glucopyranoside (ID-56B2)

- Molecular _{weight: C 21 H 30 O 9 (} MW: 426.46)

- ¹ H- NMR & ^C-13 NMR (Table 3)

¹ H-NMR < ¹³ > C-NMR of ID-56B2 Pos ? _C (*) δ _C 隆_H One 44.9 46.09 2.94 (dd, 8.5, 17.2) 2 37.3 38.60 1.93 (m)
2.30 (m) 3 80.7 81.23 4.6 (t, 6.2) 4 148.5 151.10 - 5 51.2 52.37 2.65 (m) 6 78.1 79.75 4.44 (dd, 9.6, 11.0) 7 52.7 55.18 2.08 (ddd, 2.8, 9.6, 12.0) 8 67.2 65.61 3.93 (m) 9 39.6 43.38 2.45 (m) 10 141.8 145.02 11 36.6 37.62 2.82 (m)
2.60 (m) 12 177.8 181.21 13 13.5 13.34 1.16 (d, 6.8) 14 117.7 116.60 4.89 (s)
5.06 (s) 15 114.4 113.56 5.30 (s)
5.37 (s) 3- O- Glc One' 99.5 102.97 4.43 (d, 7.8) 2' 75.23 3.20 3 ' 78.07 3.32 4' 71.72 3.24 5 ' 77.85 3.23 6 ' 62.81 3.64 (dd, 5.4, 11.6)
3.85 (d, 11.6)

(b) ixerisoside A (ID-56D2)

- Molecular weight: C ₂₉ H ₃₄ O ₁₁ (MW: 558.57)

^{- 1 H- NMR & 13 C-} NMR ( Table 4)

≪ ¹ > H-NMR < ¹³ > C-NMR of ID-56D2 Pos ? _C (*) δ _C 隆_H One 44.4 45.31 2.93 (m) 2 38.4 38.55 1.92 (m)
2.33 (m) 3 80.7 81.54 4.60 (m 4 150.6 150.77 - 5 50.1 50.99 2.77 (m) 6 78.8 80.19 4.45 (m) 7 48.3 49.00 3.20 (m) 8 68.2 69.28 5.46 9 40.6 41.40 2.48 (m) 10 143.5 144.43 - 11 136.1 136.72 - 12 169.4 171.34 - 13 121.4 122.27 5.41 (s)
6.01 (s) 14 117.1 117.73 5.03 (s)
4.75 (s) 15 111.9 112.51 5.31 (s)
5.46 (s) 3- O- Glc One' 104.7 103.90 4.38 (d, 7.2) 2' 75.4 75.29 3.23 3 ' 78.7 78.16 3.33 4' 71.8 71.74 3.26 5 ' 78.5 77.89 3.24 6 ' 62.9 62.79 3.64 (dd, 4.6, 11.6)
3.85 (d, 11.6) 8- O- Ester alpha 171.6 172.90 - beta 40.4 41.20 3.45 * One'' 124.9 126.07 - 2 ", 6 " 131.1 131.40 6.97 (d, 8.0) 3 ", 5 " 116.3 116.27 6.67 (d, 8.0) 4'' 158.2 157.58 -

(c) ixerin M, (ID-56D1B)

- Molecular weight: C ₂₆ H ₃₈ O ₁₁ (MW: 526.57)

^{- 1 H- NMR & 13 C-} NMR ( Table 5)

≪ ¹ > H-NMR < ¹³ > C-NMR of ID-56D1B2 Pos ? _C (*) δ _C 隆_H One 44.9 45.8 3.02 (m) 2 38.4 38.77 2.00 (m)
2.37 (m) 3 80.7 81.67 4.64 4 150.3 150.98 - 5 50.4 51.46 2.83 6 78.9 80.33 4.64 7 48.1 49.00 3.80 (m) 8 68.4 69.76 5.63 (m) 9 40.3 41.00 2.49 (dd, 5.1, 14.1)
2.64 (dd, 5.6, 14.1) 10 143.7 144.67 - 11 136.2 137.00 - 12 169.1 171.35 - 13 121.3 122.39 5.58 (d, 3.5)
6.19 (d, 3.5) 14 117.2 117.98 4.91 (s)
5.15 (s) 15 112.3 113.04 5.37 (s)
5.47 (s) 14- O- Glc One' 104.1 103.88 4.45 (d, 7.8) 2' 75.2 75.30 3.22 (m) 3 ' 78.2 78.20 3.37 (m) 4' 71.9 71.74 3.28 5 ' 78.2 77.93 3.26 6 ' 63.0 62.83 3.64 (dd, 5.4, 11.6)
3.86 (d, 11.6) 8-O-Ester One" 174.1 174.62 - 2" 76.1 76.65 3.85 3 " 32.5 33.11 1.98 4" 17.2 17.10 0.87 (d, 6.5) 5 " 19.2 19.31 0.94 (d, 6.5)

(d) 8-epiisolipidiol-3 -? - D-glucopyranoside, (ID-57D)

- Molecular _{weight: C 21 H 32 O 9 (} MW: 428.47)

^{- 1 H- NMR & 13 C-} NMR ( Table 6)

≪ ¹ > H-NMR < ¹³ > C-NMR of ID- Pos ? _C (*) δ _C 隆_H Aglycone One 43.3 43.79 2.79 2 38.5 38.67 1.82
2.25 3 87.3 88.34 3.65 4 45.5 45.99 1.96 5 51.7 52.34 1.76 6 80.7 82.21 4.22 (t, 10.2) 7 56.3 57.25 3.80 8 63.7 64.69 3.92 (s) 9 45.2 44.96 2.26
2.58 (dd, 2.8, 13.2) 10 144.3 144.46 - 11 37.0 37.88 2.78 12 178.9 181.50 - 13 13.2 13.11 1.15 (d, 7.2) 14 115.4 116.23 4.91 (s)
5.05 (s) 15 18.6 18.79 1.17 (d, 6.8) 3- O- Glc One' 105.8 105.37 4.33 (d, 7.8) 2' 75.4 75.23 3.17 (t, 8.4) 3 ' 78.5 77.98 3.33 4' 71.8 71.60 3.26 5 ' 78.3 77.72 3.26 6 ' 63.0 62.72 3.65 (dd, 5.0, 11.6)
3.85 (d, 11.6)

Experimental Example  One. In salivary gland cells  Measurement of time-dependent secretion of amylase, expression of endoplasmic reticulum stress and effects on oxidative-reductive environment in high glucose treatment

In order to confirm the time-dependent increase of amylase secretion in human salivary gland cells (HSG cells) of the samples, the method described in the literature was applied as follows to confirm the effect of the stress on the endoplasmic reticulum. (Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3 (2) (2008) e1648.)

1.1 Reagents

(Sigma, T9033), tunicamycin (sigma, T7765) and RPMI Medium 1640 medium (gibco life technologie, 31800-022), respectively.

1.2 Cell culture

Human salivary gland (HSG) cells were cultured in RPMI 1640 medium supplemented with antibiotics (antibiotics, 15140, gibco) and 10% fetal bovine serum (FBS, gibco, 10437028). Cells were cultured in a constant temperature humidified incubator at 37 ° C while supplying a mixed gas of air (95%) and CO ₂ (5%) and subcultured every 2 to 3 days.

1.3 Measurement of amylase activity

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

1.4 Western Blot Analysis

HSG cells were treated with 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, -Glycerophosphate, 1 mM Na ₃ VO ₄ ) was treated with a protease inhibitor (P3100-001, GenDEPOT) to extract the protein. Each sample was boiled for 5 minutes and then electrophoresed on sodium dodecyl sulfate-polyacrylamide gel (0227, AMRESCO). Proteins were separated by size, blocked with blocking buffer (REF232100, BD Difco) Was incubated overnight at 4 ° C and reacted with secondary antibody for 1 hour at room temperature to confirm protein expression using ECL solution (Dae Myung Science Co., Ltd., Korea). Re-reacted with antibody to confirm that a certain amount of protein was used.

1.5 Reverse transcription PCR

To separate the RNA from the cultured HSG cells, 1 mL of Trizol (15596-026, life technologies) was added and lysate was incubated at room temperature for 5 minutes. 200 [mu] L of chloroform was added, vortexed for 15 seconds, and incubated at room temperature for 10 minutes. Then centrifuge at 13000 rpm, 4 캜 for 15 minutes. Transfer the supernatant to a tube and add 500 μL of isopropyl alcohol into the transferred supernatant, vortex, mix and incubate at room temperature for 10 minutes. Centrifuge at 13000 rpm at 4 ° C for 15 minutes. RNA is deposited on the bottom. The sample was dissolved in 60 占 폚 water (D5758, Sigma-aldrich) prepared in advance and quantified.

1.6 cDNA synthesis procedure: Reverse Transcription

PrimeScript ^TM RT reaction kit (Perfect Real Time, TaKaRa) for 3 minutes at 95 ° C, 35 cycles for 1 minute at 95 ° C, 1 minute at 72 ° C for 1 minute, 72 ° C C for 51 minutes and then stored at 4 ° C. PCR (20 μL), cDNA (2.5 μL), double-distilled H ₂ O (10.5 μL), Universal PCR Master Mix (5 μX), reverse primer (0.5 μL) and forward primer After adding DMSO (2 μL), PCR cDNA is synthesized using Primus 96 (PeQLab) instrument.

1.7 Protein oxidation measurement

The amount of carbonyl in the protein was measured using a protein oxidation detection kit (OxyBlot ^TM Chemical International, Temecula, Calif.). After protein extraction, proteins are separated using 10% SDS-PAGE. Dinitrophenyl, a primary antibody, was added to Immno-blot ^™ PVDF transfer membranes (162-0177, bio-rad) and incubated overnight at 4 ° C. The secondary antibody rabbit (sc-2004 , santa cruz) and allowed to react at room temperature for 1 hour. Then SuperDetect ^TM ECL solution (Dae Myung Science Co., Ltd., Korea).

1.8 Statistical processing

Results were expressed as mean ± standard error, and Duncan's test was used for analysis of variables. P values less than 0.05 were considered to be statistically significant, and all experiments were performed three times or more independently and statistically.

1.9 Experimental Results

1) Secretion of amylase from active ingredient due to long-term high glucose concentration

As shown in FIG. 1, in order to investigate the secretion ability of amylase from high-concentration glucose in the active component of salivary gland cells, a culture medium containing 40 mM glucose for a long period of time was used as the active ingredient (ID-56B2, ID-56D2, Ixerin M and ID- And the amylase secretion was increased in ID-56D1B2 and ID-57D, respectively. The secretion of amylase from the culture medium and intracellular amylase was increased in the salivary gland cells (IXD) extract and its components (ID-56B2, ID-56D2, Ixerin M and ID-57D) were transplanted into salivary gland cells and then secreted in culture medium and intracellular amylase (IDx-56D1B2 (Ixerin M) and ID-57D), and the results showed that the secretion of amylase was increased in ID-56D1B2 (Ixerin M) and ID-57D.

2) In salivary gland cells  Effects of ethanol and methanol extract on the secretion of amylase during long-term high glucose treatment

As shown in FIG. 3A, the secretion of amylase from the extracts of 100% ethanol and 100% methanol showed that the secretion of amylase during the simultaneous treatment of 100% ethanol extract and high concentration of glucose (G8270, sigma-aldrich) As shown in FIG. 3B, when amylase secretion was observed at 0, 20, 40, 60, 80 and 100% ethanol extracts, the extracts of 100% ethanol and high concentration of glucose were simultaneously treated The secretion of cyamylase was increased by 78%.

3) In salivary gland cells  Time-dependent secretion of amylase from 100% ethanol extract of rosemary extract

As shown in FIGS. 4A and 4B, the secretion of amylase was observed when 40 mM glucose alone, 0, 1, 2, 3, 5 and 7 days, and 100% Amylase secretion was decreased after 3 days when high concentration was treated alone. However, when 100% ethanol extract and high concentration of glucose were simultaneously treated, the secretion of amylase was increased by 95.3% even after 3 days.

4) In salivary gland cells  At high-concentration treatment for a long time Ingredients ID- 56D1B2  ( Ixerin  M) to  Time-dependent secretion effect of amylase

As shown in FIGS. 5A and 5B, the secretion of amylase was observed when 40 mM glucose alone was treated at 0, 1, 2, 3, 5 and 7 days and when Ixrin M active ingredient extract and high glucose were simultaneously treated As a result, the secretion of amylase was decreased from 3 days after the high concentration treatment, whereas the secretion of amylase was increased by 92.8% even after 3 days when the extract of Ixrin M and the high concentration of glucose were simultaneously treated.

5) In salivary gland cells  Time-dependent secretion effect of amylase in ID-57D

As shown in FIG. 6A, the cell viability of ID-57D was determined by treatment with 0.005, 0.001, 0.002, and 0.004 mg / mL of the active ingredient, In FIG. 6B and FIG. 6C, amylase secretion was observed when 40 mM glucose alone was treated at 0, 12, 24, 36 and 48 hours and when ID-57D and high glucose were simultaneously treated. As a result, ID- At the same time, it was confirmed that the secretion of amylase was increased by 77% more. In FIG. 6D, the expression of stress-related proteins in the endoplasmic reticulum was not observed when the high glucose concentration and ID-57D were simultaneously treated. As shown in FIG. 6D, when ID-57D was simultaneously treated with glucose at a high concentration (40 mM) for 0, 12, 24, 36 and 48 hours in salivary gland cells and at high concentration of glucose, And the expression of Oxyblot was confirmed to confirm the reduction reaction. As shown in the chart, it was confirmed that the intracellular oxidation-reduction environment was better maintained at the same time in the time-dependent manner.

6) In salivary gland cells  Time-dependent secretion effect of amylase due to ID-57D, an effective ingredient of the scavenger during long-term high-concentration treatment

As shown in FIG. 7A and FIG. 7B, when 40 mM glucose alone was treated at 0, 1, 2, 3, 5 and 7 days, the secretion of amylase during the simultaneous treatment of ID-57D and high- As a result, the secretion of amylase was decreased by 99.5% from 3 days after the treatment of high concentration, whereas the secretion of amylase was increased by 97.8% even after 3 days of simultaneous treatment of ID-57D and high glucose. FIG. 4C shows the expression of stress-related proteins in the endoplasmic reticulum when treating high glucose and ID-57D simultaneously. As a result, when high glucose was treated, expression of protein of ER stress (GRP78, CHOP, p-eIF2 ?, XBP -1), but the simultaneous treatment of ID-57D decreased the expression of ER stress-related proteins. As shown in FIG. 7D, the expression of Oxyblot was observed in saline cells treated with glucose at a high concentration of 0, 1, 2, 3, 5, or 7 days and ID-57D at a high glucose concentration, , The endoplasmic reticulum oxidation and reduction environment were destroyed, whereas the simultaneous treatment of ID-57D showed that the environment of the endoplasmic reticulum was maintained.

7) Experimental study of blood glucose change by streptozotocin treatment in animal model

As shown in FIG. 8, in the control group, it was confirmed that the blood glucose level remained constant within the normal range. However, when the streptozotocin (S0130, sigma-aldrich) was treated alone and the glucose level change As a result, it was confirmed that hyperglycemia was maintained at a blood glucose level of 300 mg / dl or more.

8) In animal models Streptozotocin  Experiments on salivary gland weight, protein amount and secretion effect of amylase due to umbagus during treatment

As shown in FIG. 9, when the streptozotocin alone was treated, and the amount of salivary gland and protein was simultaneously measured at the same time, the weight of the salivary glands was reduced compared with the control group In contrast, the amount of protein increased while the weight of the salivary gland was increased by simultaneous treatment of scutellum and streptozotocin. However, the amount of protein was increased compared to the control group, but decreased compared with the group treated with streptozotocin. The secretion of amylase in saliva and salivary glands was measured at the same time. The secretion of amylase was decreased in the single treatment of streptozotocin compared to that of control, whereas the treatment of streptozotocin alone and the treatment of streptozotocin Secretion of amylase compared to Increase of 98% was confirmed that.

9) Experimental study on secretion of amylase in saliva and salivary glands due to scabies during treatment with Streptozotocin in animal models

As shown in FIG. 10, when the streptozotocin alone treatment and the secretion of amylase in the saliva and salivary glands were examined at the same time, the treatment of streptozotocin alone showed amylase activity in the saliva and salivary glands While the secretory capacity of amylase was decreased by 97.5% compared with that of the control group compared with that of the control group.

10) Experiments on the ratio of saliva in the animal model for the treatment of streptozotocin

As shown in FIG. 11, when the streptozotocin was treated alone, and the streptozotocin was simultaneously treated with streptozotocin, the salivary ratio was decreased in the case of streptozotocin treatment alone, whereas the ratio of salivary and streptozotocin Simultaneous treatment showed that the saliva fraction was decreased by 72% as compared with the control group, but compared with the group treated with streptozotocin.

11) Histological analysis of the salivary glands due to scabies during streptozotocin treatment in animal models

As shown in FIG. 12, histological analysis of the treatment of streptozotocin alone and simultaneous treatment of scorpion and streptozotocin showed that the structure of the salivary gland was lost and deteriorated upon treatment with streptozotocin alone, while that of scorpion and streptozotocin It was confirmed that the salivary gland structure was maintained better than the single treatment group with streptozotocin. In addition, amylase expression was confirmed by immunohistochemical staining. As a result, amylase expression was decreased when streptozotocin alone was treated, whereas amytase expression of streptozotocin was increased when streptozotocin was co-treated with streptozotocin alone Respectively.

Hereinafter, formulation examples of the composition containing the compound of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

≪ Formulation Example 1 > Preparation of powders

Compound ID-56B2 ---------------------------------------- 20 mg

Lactose ------------------------------------------------- 100 mg

Talc ------------------------------------------------- - 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

≪ Formulation Example 2 > Preparation of tablet

Compound ID-56D2 ---------------------------------------- 10 mg

Corn starch ------------------------------------------- 100 mg

Lactose ------------------------------------------------- 100 mg

Magnesium stearate ------------------------------------ 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

≪ Formulation Example 3 > Preparation of capsules

Compound ID-56D1B ---------------------------------------- 10 mg

Crystalline cellulose --------------------------------------- 3 mg

Lactose --------------------------------------------- 14.8 mg

Magnesium stearate 0.2 mg < RTI ID = 0.0 >

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

≪ Formulation Example 4 > Preparation of injection

Compound ID-ID-57D --------------------------------------- 10 mg

Mannitol ------------------------------------------------ 180 mg

Sterile sterile distilled water used - 297 mg

Na ₂ HPO _4, 12H ₂ O ------------------------------------------ - 26 mg

(2 ml) per 1 ampoule according to the usual injection preparation method.

≪ Formulation Example 5 > Preparation of liquid agent

Compound ID-56B2 ---------------------------------------- 20 mg

Issa Party ----------------------------------------------- 10 g

Mannitol ------------------------------------------------- - 5 g

Purified water ------------------------------------------------- Suitable amount

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

≪ Formulation Example 6 > Preparation of health food

Compound ID-56D2 - 1000 mg

Vitamin mixture -------------------------------------------

Vitamin A Acetate ----------------------------------- 70 [mu] g

Vitamin E --------------------------------------------- 1.0 mg

Vitamin B1 ------------------------------------------- 0.13 mg

Vitamin B2 - 0.15 mg

Vitamin B6 -------------------------------------------- 0.5 mg

Vitamin B12 ------------------------------------------- 0.2 g

Vitamin C ---------------------------------------------- 10 mg

Biotin ------------------------------------------------ 10 G

Nicotinic acid amide 1.7 mg

Folic acid ------------------------------------------------- - 50 [mu] g

Calcium pantothenate ---------------------------------------- 0.5 mg

Inorganic mixture --------------------------------------------------------------------------

Ferrous sulfate 1.75 mg < RTI ID = 0.0 >

Zinc oxide - 0.82 mg

Magnesium carbonate ---------------------------------------- 25.3 mg

Potassium phosphate monohydrate 15 mg

Secondary Calcium Phosphate - 55 mg

Potassium citrate -------------------------------------------- 90 mg

Calcium carbonate - 100 mg

Magnesium chloride ---------------------------------------- 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

≪ Formulation Example 7 > Preparation of health drink

Compound ID-ID-57D ------------------------------------ 1000 mg

Citric acid ---------------------------------------------- 1000 mg

Oligosaccharides ---------------------------------------------- 100 g

Plum concentrate ---------------------------------------------- 2 g

Taurine ------------------------------------------------- - 1 g

Purified water 900 ml total

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (6)

A pharmaceutical composition for the prevention or treatment of dry mouth disease, which comprises ixerisoside A, (ID-56D2) compound as an active ingredient. The pharmaceutical composition according to claim 1, wherein the dry mouth disease is dry mouth disease caused by radiation therapy, mumps, baclofen, diabetes, collagen diseases, stress, aging, or side effects of medicines. (Ixerisoside A), (ID-56D2) as an active ingredient. The health functional food according to claim 3, wherein the health functional food form is powder, granule, tablet, capsule, beverage, gum, vitamin complex or health supplement food. Ixerisoside A, (ID-56D2) compound having the effect of improving oral dryness as an active ingredient. Food additive containing ixerisoside A, (ID-56D2) compound as an active ingredient having the effect of improving oral dryness.

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