KR20200083370A - Pharmaceutical composition and health functional food for prevention or treatment of salivation - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and a dietary supplement comprising alpha-lipoic acid or a salt thereof, by improving the damage of the salivary glands, it is possible to achieve a prophylactic or therapeutic effect of salivary hypoplasia, more specifically, due to irradiation It has an excellent effect on improving the damage of salivary glands.

Description

Pharmaceutical composition and health functional food for prevention or treatment of salivation

The present invention relates to a pharmaceutical composition and health functional food for preventing or treating salivation.

Acupuncture is a secretion liquid that is secreted from the acupuncture into the oral cavity. In normal people, saliva averages 1 to 1.5 L per day. About 99.5% of saliva is water and the remaining 0.5% is composed of electrolytes, mucus, glycoproteins, enzymes, and antimicrobial substances. Acupuncture lubricates the oral mucosa, protects oral tissue, and is involved in digestion, taste, and remineralization of teeth. In particular, several proteins present in saliva have a profound effect on the oral microbiota due to antibacterial, antiviral and antifungal action.

The salivation mechanism can be divided into protein secretion and liquid and electrolyte secretion. In the case of protein secretion, the sympathetic neurotransmitter norepinephrine binds to the β-adrenergic receptor present in the cell membrane at the bottom of the secretory terminal cell, resulting in heterotrimeric G-protein. G-protein) and adenylyl cyclase are activated. This catalyzes the formation of high-cyclic adenosine monophosphate and activates protein kinase A, whereby secreted granules present in the cell membrane secrete proteins toward the lumen through an extracellular outflow method. On the other hand, the secretion of liquid and electrolyte is mainly caused by the binding of the parasympathetic neurotransmitter acetylcholine to the muscarinic receptor. When an agonist binds to the muscarinic receptor, the heterotrimeric G-protein and phospholipase C are sequentially activated, ultimately inositol triphosphate. , IP₃). IP₃ releases the Ca ²⁺ stored in the cell, and the increased concentration of Ca ²⁺ opens the Cl ^- passage on the lumen side and the K ⁺ passage on the bottom side Na ⁺ /K ⁺ /2Cl ^- co- The co-transporter is activated. In addition, the aquaporin 5 (AQP5) protein present in the vesicle moves to the luminal cell membrane. Cl ^- on the increased lumen side balances along Na ⁺ moving to the lumen through a closed junction, resulting in an osmotic gradient. The osmotic gradient shifts water from the cell to the lumen through closed contact with AQP5.

Meanwhile, aquaporin is a water channel protein found in the cornea, kidney, liver, and skin. Aquaporin (Aquaporin), AQP0 ~ 12 subfamily (subfamily) is present in a variety, AQP5 is a major biomarker (biomarker) for saliva secretion. In particular, a study has reported that saliva secretion was reduced by more than 60% in AQP5 knockout mice.

Xerostomia is the most common clinical symptom associated with acupuncture. If the amount of saliva secreted during non-irritation is 0.1 ml or less per minute, it is diagnosed as dry mouth. The causes of dry mouth are mainly side effects caused by drugs such as anti-depression, anti-diabetes, and anti-allergy. Dry mouth caused by natural aging is caused by a decrease in the parenchymal parenchyma, replacement with adipose tissue, or a decrease in the volume of the axillary. When the amount of saliva in the oral cavity decreases, tooth decay, acid erosion, oral candidiasis, dysgeusia, dysphagia, oral dysesthesia, and intraoral halitosis It is accompanied.

Typical treatments for dry mouth syndrome currently in use include parasympathomimetic pilocarpine, cevimeline, and bethanechol. However, these treatments have the disadvantage of causing side effects such as sweating, vomiting, vasodilation, diarrhea, and bronchospasm. Therefore, it is very important to prevent and treat dry mouth syndrome based on natural products with low side effects and high safety.

On the other hand, when irradiated, the salivary glands are damaged, and accordingly, the amount of saliva secretion is reduced. Accordingly, there is a need for a composition capable of restoring the amount of saliva secretion as the damage to the salivary glands is improved.

An object of the present invention is to provide a pharmaceutical composition for preventing or treating salivary hypoplasia comprising alpha-Lipoic acid or a pharmaceutically acceptable salt thereof.

In addition, an object of the present invention is to provide a health functional food for preventing or improving salivary hypocytosis, which includes alpha-lipoic acid or a food-acceptable salt thereof.

1. Alpha-lipoic acid (α-Lipoic acid) or a pharmaceutical composition for the prevention or treatment of hypothalamus comprising a pharmaceutically acceptable salt thereof.

2. In the above 1, wherein the salivary gland hypothyroidism is caused by damage to the salivary glands, the pharmaceutical composition.

3. In the above 2, the salivary gland damage is caused by irradiation, pharmaceutical composition.

4. Alpha-lipoic acid (α-Lipoic acid) or a health functional food for preventing or improving salivation, including food-acceptable salts thereof.

5. In the above 4, the salivary gland hypothyroidism is caused by damage to the salivary glands, health functional food.

6. In 5 above, the salivary gland damage is caused by irradiation, health functional food.

The pharmaceutical composition comprising alpha-lipoic acid of the present invention can achieve the prevention or treatment effect of salivation hypoplasia by improving the damage of the salivary glands, and the health functional food of the present invention can achieve the prevention or improvement effect of salivation hypoplasia Can.

1 is a view showing that ALA improves SG weight loss and impaired saliva secretion caused by irradiation.
2 and 3 are diagrams showing that administration of ALA improves radiation-induced AQP5 expression.
4 to 6 are diagrams showing that ALA preserves the parasympathetic nerve in SG.
7 and 8 are diagrams showing that ALA maintains neurotrophic factor levels in SG.
9 is a view showing that ALA preserves Hh signaling in SG after irradiation.
10 is a view showing improving the radiation-induced damage of stem cells.

Hereinafter, the present invention will be described in detail.

Alpha-lipoic acid (α-Lipoic acid) or a pharmaceutical composition for preventing or treating salivary hypoplasia comprising a pharmaceutically acceptable salt thereof.

The alpha lipoic acid is a compound represented by the following Chemical Formula 1, the chemical formula is C ₈ H ₁₄ O ₂ S ₂ , the molar mass is 206.33 g/mol, and the name of IUPAC is 5-(1,2-dithiolan-3-yl)pentanoic acid to be:

[Formula 1]

.

.

The alpha lipoic acid may be derived from nature, or may be synthesized using a known organic synthetic method.

The alpha lipoic acid may be a product obtained by culturing non-protein compounds, peptides, plant-derived tissue or cell extracts, and microorganisms (eg, bacteria or fungi, and especially yeast).

The pharmaceutical composition according to the present invention may include an active ingredient alone or may be provided as a pharmaceutical composition including one or more pharmaceutically acceptable carriers, excipients, or diluents.

"Pharmaceutically acceptable" in the present invention means that it exhibits properties that are not toxic to cells or humans exposed to the composition.

The term "pharmaceutically acceptable salt" of the present invention means a salt prepared by using a specific compound according to the present invention and a relatively non-toxic acid or base. When the compounds of the present invention contain relatively acidic functional groups, base addition salts can be obtained by contacting a sufficient amount of the base with a neutral form of such a compound in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amines, or salts of magnesium or similar salts. When the compounds of the present invention contain relatively basic functional groups, acid addition salts can be obtained by contacting a sufficient amount of acid in a neat solution or in a suitable inert solvent with the neutral form of these compounds. Pharmaceutically acceptable acid addition salts are salts of inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, hydrogen carbonate ion, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, hydrogen sulfate ion, hydroiodic acid or phosphorous acid, And salts of organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid Examples thereof include salts of amino acids (for example, arginine) and salts of organic acids such as glucuronic acid.

The pharmaceutically acceptable salt of the present invention can be synthesized by a conventional chemical method from a parent compound containing an acidic or basic moiety. Generally, these salts are prepared by reacting the form of the free acid or base of these compounds with a stoichiometrically appropriate base or acid in water or in an organic solvent or in a mixture of the two. In general, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile are preferred.

Furthermore, the pharmaceutical composition of the present invention may be provided by mixing with a composition for preventing or treating hypoxia. That is, the pharmaceutical composition of the present invention can be administered in parallel with a known compound having a prophylactic or therapeutic effect on salivation.

In the present invention, "administration" refers to the introduction of a predetermined substance to an individual by an appropriate method, and "individual" refers to all living things, such as rats, mice, and livestock, including humans, capable of retaining hypocytosis. As a specific example, it may be a mammal, including a human.

If necessary, the pharmaceutical composition of the present invention may further include a composition having a known effect of preventing or treating salivation.

Examples of the composition for preventing or treating salivation hypothyroidism include, but are not limited to , the extract of Curcuma ( Curcumaxanthorrhiza ), polyglutamic acid, and Aspalathus-linearis, Aspenathus linearis extract, squirrel extract, and stalk extract. no.

In the present invention, the route of administration of the pharmaceutical composition is, but is not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, Topical, sublingual or rectal.

The composition of the present invention may be administered orally or parenterally, and when parenterally administered, it is preferable to select an external injection or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection injection method. , But is not limited thereto.

The preferred dosage of the composition of the present invention depends on the patient's condition and body weight, the degree of disease, the drug form, the route and duration of administration, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition is preferably administered at 0.01 to 1000 mg/kg/day, preferably 0.1 to 500 mg/kg/day, but is not limited thereto. The administration may be administered once a day, or may be divided into several times. The above dosage does not limit the scope of the present invention in any way.

In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose. Or it is prepared by mixing lactose, gelatin, and the like. In addition, lubricants such as magnesium stearate and talc are used in addition to simple excipients. Liquid preparations for oral use include suspensions, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, can be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

The salivation secretion may be caused by various causes, for example, may be caused from salivary gland damage, but is not limited thereto. In addition, the salivary gland damage may also be caused by various causes, for example, it may be caused by irradiation, specifically, it may be caused by damage to the parasympathetic nerve due to radiation, but is not limited thereto.

The alpha-lipoic acid may increase saliva secretion by restoring damage to the salivary glands, specifically increase the reduced weight of salivary glands due to damage to the salivary glands, and specifically decrease the salivary gland-related factor of aquaporin 5 Expression may be increased, but is not limited thereto.

In addition, the alpha lipoic acid can restore damaged parasympathetic nerves, and specifically, increase the expression of glial cell-derived neurotrophic factor family receptor 2 (GFR2), which is a marker of the parasympathetic nerve. There is, and may increase the expression of brain-derived neurotrophic factor (BDNF) and neurturin associated with parasympathetic nerves, but is not limited thereto.

In addition, the alpha-lipoic acid can regenerate the salivary glands, specifically, Sonic Hedgehog (Shh) and its receptor patched (Ptch) related to hedgehog (Hh) signaling related to regeneration of the salivary glands. Gene expression may be increased, and expression of Sca-1, a stem cell-related marker associated with regeneration of salivary glands, may be increased, but is not limited thereto.

In addition, the present invention relates to a health functional food for preventing or improving salivation syndrome, including alpha-lipoic acid or a food-acceptable salt thereof.

The salivary gland hypothyroidism may be caused by salivary gland damage, and the salivary gland damage may be caused by irradiation, but is not limited thereto.

The efficacy and mechanism of action of the alpha lipoic acid may be within the above-described range.

In the present invention, "food-tolerant" means that it exhibits non-toxic properties to cells or humans exposed to the compound.

In the present invention, "food-acceptable salt" means a salt prepared by using a specific compound according to the present invention and a relatively non-toxic acid or base, and may be within the above-mentioned range for "salt".

The health functional food of the present invention may be formulated as one selected from the group consisting of tablets, pills, powders, granules, powders, capsules, and liquid formulations, further comprising one or more of carriers, diluents, excipients, and additives. Foods to which the extract of the present invention can be added include various foods, powders, granules, tablets, capsules, syrups, drinks, gums, teas, vitamin complexes, and health functional foods.

Additives that may be further included in the present invention include natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), coloring agents, fillers (cheese, chocolate, etc.), Factic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonizing agents and one or more components selected from the group consisting of flesh can be used. .

Examples of the natural carbohydrates described above include monosaccharides, such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, etc.; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents (taumatine, stevia extract (for example, rebaudioside A, glycyrrhizine, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid And salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonic acid used in carbonated beverages, and the like. In addition, the composition according to the present invention may contain natural fruit juice and pulp for the production of vegetable drinks. These ingredients can be used independently or in combination.

Specific examples of the carrier, excipients, diluents and additives include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium phosphate, calcium Silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methylcellulose, methyl hydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate And it is preferred that one or more selected from the group consisting of mineral oil is used.

When formulating the health functional food of the present invention, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are usually used.

Hereinafter, examples will be described in detail to specifically describe the present invention.

Example

1. Experimental method

(1) Radiation exposure

We assigned Sprague-Dawley (SD) mice to the group as follows: control, n =12 (Con); Alpha-Lipoic Acid (ALA) alone administration, n =12 (ALA); Irradiation alone, n =16 (RT); And ALA administration prior to irradiation, n =16 (ALA+RT). We administered ALA (100 mg/kg intraperitoneally; Bukwang Pharmaceutical Co., Seoul, Korea) 30 minutes or 24 hours prior to irradiation and selected doses and frequencies based on previous studies. The neck area was irradiated with 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator (21EX; Varian, Palo Alto, CA, USA). Lucite's 3 cm block was placed over the head and neck to provide adequate accumulation and even to uniformize the radiation distribution. Each rat was exposed to a single dose of radiation and was sacrificed 2, 6, 8 or 12 weeks after irradiation.

(2) Salivary gland (SG) function

SG was homogenized in lysis buffer. The resulting protein (50 μg) was loaded onto sodium dodecyl sulfate-polyacrylamide gel and electroblotting. Blots were examined with primary antibodies against polyclonal anti-AQP5 (Abcam, Cambridge, MA, USA) and anti-GFR2 (Abcam) overnight at 4°C. The primary antibody was visualized by a secondary antibody and an enhanced chemiluminescence kit (Amersham Pharmacia Biotech, Piscataway, NJ, USA).

(3) Immunoblotting

After deparaffinization, sections are incubated with primary antibodies against polyclonal anti-AQP5 (Abcam), anti-GFR2 (Abcam) and anti-AchE (Elabscience, Houston, TX, USA), followed by biotin binding. Secondary IgG (diluted at 1:200; Vector Laboratories, Burlingame, CA, USA), avidin-biotin-peroxidase complex (ABC Elite Kit; Vector Laboratories) and Incubated with diaminobenzidine tetrahydrochloride. Next, we visualized the sections with an optical microscope, and took and analyzed digital photos.

(4) Enzyme-linked immunosorbent assay (ELISA)

To confirm the effect of ALA on saliva regeneration, ELISA was performed on neurotrophic factors. Fresh tissue and serum were collected and stored at -80°C. It was measured according to the manufacturer's instructions of BDNF (Quantikine ELISA kit; R&D Systems, Minneapolis, MN, USA) and neurturin (ELISA kit; Elabscience).

(5) Quantitative real-time polymerase chain reaction (qPCR)

The transcription levels of Shh and Ptch, important proteins involved in Hh signaling, were measured by qPCR. Salivary gland tissue was resuspended in TRIzol Reagent (Invitrogen Life Technologies, Carlsbad, CA, USA) and all RNA was extracted. The purified RNA was then reverse transcribed into cDNA using the iScript cDNA synthesis kit (Bio-Rad Laboratories, Hercules, CA, USA). After reverse transcription, quantitative cDNA was amplified using the TaqMan gene expression assay mix (Shh; Rn00568129; Ptch: Rn01527980) on the Applied Biosystems qPCR system (Applied Biosystems Inc., Foster City, CA, USA). The thermal cycling conditions are as follows: after denaturation at 95°C for 3 minutes, 50 cycles of deformation at 95°C for 10 seconds, unwinding and extension at 60°C for 30 seconds. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as an internal control for standardization of RNA quantification. The relative gene expression level of each sample was quantified using the 2 ^-ΔΔCt method.

(6) Reverse-transcription PCR

All RNA was extracted from salivary gland tissue using the TRIzol method (GIBCO BRL, Grand Island, NY, USA). RNA (5 μg) was converted to cDNA, and the resulting cDNA (2.0 μL) was PCR amplified. Primer sequences were as follows: 5'-AACCATATTTGCCTTCCCGTC-3' (sense) for Sca-1 (SEQ ID NO: 1) and 5'-GAGATCTGAAAGCCCTAGAG-3' (antisense) (SEQ ID NO: 2), 5'for GAPDH TCCCTCAAGATTGTCAGCAA-3' (sense) (SEQ ID NO: 3) and 5'-AGATCCACAACGGATACATT-3' (antisense) (SEQ ID NO: 4).

(7) Statistical analysis

Statistical analysis was performed using Graph Pad Prism 5 (Graph Pad Software Inc., La Jolla, CA, USA). The Mann-Whitney U test was used to test the differences between the two groups. P -value <0.05 was considered significant.

2. Experimental results

(1) Irradiation significantly caused loss of body weight and SG weight, but ALA improved radiation-induced SG weight loss and reduced saliva levels.

Radiation caused significant weight loss at all time points. No regeneration after ALA treatment was observed in the irradiation group (FIG. 1A ). At 6 and 8 weeks after irradiation, loss of wet weight was significantly induced. However, the administration of ALA significantly restored the gland weight at 8 weeks after irradiation compared to the irradiated control group (FIG. 1B ). In addition, irradiation significantly reduced salivary gland secretion, partially recovered by ALA (FIG. 1C ). These data suggest that ALA may be involved in the recovery of radiation-induced salivation.

(2) ALA restores radiation-induced AQP5 expression.

Saliva secretion occurs through aquaporin 5 (AQP5) during SG water discharge. Irradiation significantly reduced the expression of AQP5 protein at 2, 6, 8 and 12 weeks after irradiation, but ALA significantly increased AQP5 expression level to the same level every week after irradiation as indicated by immunoblotting analysis. (Figure 2). The preservation of AQP5 by ALA administration was further confirmed by immunohistochemical staining. Consistently, the number of AQP5-positive acinar cells was significantly reduced at each time point in the irradiation group, but was significantly recovered by ALA, which is confirmed by immunoblotting (FIG. 3 ). These data indicate that ALA contributes to the recovery of impaired salivary gland function by irradiation.

(3) ALA preserves the parasympathetic nerve.

Radiation affects the parasympathetic nerves in the SG, and parasympathetic stimulation improves the regeneration of the SG after irradiation. To test the effect of ALA on the damage of radiation-induced parasympathetic nerves in SG, we tested the glial cell-derived neurotrophic factor family receptor 2 (GFR2), a marker of glial cells in the SG. Protein levels were investigated. Radiation-induced disorder of GFR 2 protein expression was significantly improved by ALA administration (FIG. 4 ). Immunohistochemical staining of GFR 2 was significantly recovered by ALA treatment (Figure 5), which was confirmed by immunohistochemical staining of another marker of the parasympathetic nerve, acetylcholinesterase (AchE) (Figure 6). These data suggest that ALA protects SG from radiation-induced dysfunction by preserving parasympathetic nerves in SG.

(4) ALA enhances neurotrophic factor levels in SG.

Radiation-induced damage of parasympathetic nerves in SG is remedied by increased production of neurotrophic factors. Brain-derived neurotrophic factor (BDNF) and neuroturin levels in SG were significantly reduced by radiation at each time point, but BDNF levels were 2 weeks after irradiation in the ALA treated radiation group And significantly increased at 8 weeks, and the level of Neuturin increased at 8 and 12 weeks (Fig. 7). Serum BDNF levels increased significantly 2 weeks after irradiation, but there was no significant difference with other groups at any time point. There was no significant difference in serum Neuturin levels (Fig. 8). These data indicate that ALA preserves parasympathetic nerves by maintaining neurotrophic factor levels in SG after irradiation.

(5) ALA increases SG regeneration.

Hedgehog (Hh) signaling was activated during functional regeneration of adult SG after vascular connection. In addition, the temporary activation of the Sonic Hedgehog (Shh) gene improves radiation-induced hypothalamus. We investigated the effect of ALA on radiation-induced Hh signaling. The mRNA expression levels of Shh and its receptor Patched, Ptch, Hh signaling and regeneration related factors were measured by qPCR. Shh and Ptch mRNA levels were reduced in the irradiation group; However, in the ALA treated radiation group, the mRNA level of Shh increased at 2 and 6 weeks and the level of Ptch increased at 2, 6 and 8 weeks (Fig. 9). This means that ALA is involved in SG regeneration through Hh signaling after irradiation.

(6) ALA rescues endogenous resident stem cell population

To test the effect of ALA on the regenerative potential of SG, we evaluated the production of stem cells in ALA treated irradiated glands. Rat SG stem cells/progenitor cells express well established stem cell markers including Sca-1. However, the number of Sca-1 positive cells was extremely small in vivo. Therefore, we performed reverse transcription PCR to evaluate Sca-1 expression. Single irradiation significantly reduced Sca-1 mRNA expression at 6, 8 and 12 weeks after irradiation, indicating a lack of resident SG stem/progenitor cells compared to unirradiated controls. Rats receiving ALA showed significantly increased Sca-1 mRNA expression compared to the irradiated group (FIG. 10 ). These data indicate that ALA can rescue resident stem cells in an irradiated SG environment.

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Claims (6)

Alpha-lipoic acid (α-Lipoic acid) or a pharmaceutical composition for preventing or treating salivary hypoplasia comprising a pharmaceutically acceptable salt thereof. The method according to claim 1, wherein the salivary glands are caused by salivary gland damage, pharmaceutical composition. The pharmaceutical composition of claim 2, wherein the salivary gland damage is caused by irradiation. Alpha-lipoic acid (α-Lipoic acid) or a health functional food for preventing or improving salivation, including food-acceptable salts thereof. The method according to claim 4, The salivary gland hypothyroidism is caused by damage to the salivary glands, health functional food. The method according to claim 5, The salivary gland damage is caused by irradiation, health functional food.

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