Composition for preventing, improving or treating gastritis or peptic ulcer comprising extract of cinnamomum cassia, fraction or isolate of the extract, or compound isolated therefrom

Abstract

To provide a substance useful for prevention, improvement or treatment of gastritis and peptic ulcer, which exhibits excellently improved pharmacological effects without causing side effects to the human body.SOLUTION: The present invention uses a component selected from the group consisting of a Cinnamomum cassia extract, a fraction of the extract, and an isolate of the fraction. The component may be, for example, ferulic acid, 4-hydroxycinnamaldehyde, 3-(2-hydroxyphenyl)propanoic acid, 3,4-dihydroxybenzaldehyde, syringic acid, or vanillic acid.SELECTED DRAWING: Figure 7

Description

[Technical Field]

[0001] The present invention relates to a composition that contains a cinnamon extract, a fraction of the extract, an isolate of the fraction, or a compound isolated and purified therefrom, and that exhibits improved pharmacological or phytological effects and can prevent, improve, or treat gastritis or peptic ulcers such as gastric ulcers. [Background technology]

[0002] The stomach, a part of the digestive tract, is a pouch-like organ located between the esophagus and the small intestine (duodenum). It stores food and drink that enters through the esophagus, breaks it down into small pieces for easy digestion, and regulates its delivery to the duodenum, thereby balancing the secretion of digestive enzymes and ensuring efficient digestion and absorption. The factors that adversely affect the function of the human gastrointestinal system are extremely diverse and can occur in the upper gastrointestinal tract, the lower gastrointestinal tract, or both. There is a wide range of causes for gastrointestinal disorders, including genetic, physiological, environmental, and psychological factors. Typical diseases of the upper gastrointestinal tract include gastritis, gastric ulcers, and peptic ulcers, commonly known as duodenal ulcers. Gastritis refers to damage and inflammation of the gastric mucosa, while gastric ulcers occur when such damage penetrates the mucosa and extends to the submucosa and muscle layer. Duodenal ulcers are ulcers that occur in the duodenum, and both gastric and duodenal ulcers are commonly referred to as peptic ulcers. Gastritis and peptic ulcers are known to occur due to an imbalance between attacking factors such as gastric acid, anti-inflammatory agents, and bacterial infection, and defensive factors such as mucus, cell regeneration, and alkaline secretion.

[0003] Treatments for gastritis and peptic ulcers primarily include antacids, which neutralize excess gastric acid; histamine antagonists, proton pump inhibitors, and anticholinergics, which suppress acid secretion; and gastric mucosal protectants, which increase the gastric lining's resistance to digestive juices and aid recovery. Recently, a new drug treatment has emerged that combines stomach medications with antibiotics to eliminate Helicobacter pylori. Antacids are characterized by their fast-acting properties and neutralize gastric acid by raising the intragastric pH, thereby protecting the gastric mucosa from damage caused by gastric acid. However, the administration of inorganic substances can affect the smooth muscle of the gastrointestinal tract, causing constipation, diarrhea, or allergic rejection.

[0004] Cimetidine is a representative histamine receptor blocker widely used in the treatment of peptic ulcers. Its derivatives, ranitidine, famotidine, and roxatidine, work by blocking histamine receptors in the gastric mucosa, preventing histamine molecules from secreting acid from gastric cells. While these drugs have demonstrated excellent anti-ulcer effects in clinical trials, they have the disadvantage of a high recurrence rate, as the regenerated mucosa and submucosa are structurally weaker than normal tissue and are susceptible to damage from factors such as gastric acid after drug administration has been discontinued. Ranitidine also has the disadvantage of being ineffective in treating conditions such as acute ethanol-induced gastritis and of poor gastric mucosal protection. Furthermore, the US Food and Drug Administration recently announced that ranitidine is no longer used because the nitrite and dimethylamine groups contained in ranitidine decompose and combine over time to form a carcinogenic substance called NMDA (N-nitrosodimethyl).

[0005] Relatively recently developed proton pump inhibitors include omeprazole and lansoprazole, which are known to have a strong acid secretion suppressing effect by inhibiting acid secretion in gastric parietal cells at the final stage, but they have been reported to have a high recurrence rate and side effects such as diarrhea, fever, headache, and fatigue.

[0006] Gastric mucosal protective agents generally have the disadvantage of requiring long-term treatment and high dosages, but unlike agents that suppress attacking factors, they are known to result in the regenerated mucosa recovering to a state similar to normal.

[0007] Helicobacter pylori, a type of bacteria that lives in the stomach, is known to be a major cause of recurrent peptic ulcers. Helicobacter pylori is a gram-negative bacillus that lives in the junctions between gastric mucosal epithelial cells and causes chronic gastric ulcers. Treatments aimed at eradicating it have been performed, and while many successes have been achieved to date, there are issues with efficacy, side effects, and the emergence of resistant strains, and a safe and reliable eradication method has not yet been established. Summary of the Invention [Problem to be solved by the invention]

[0008] Therefore, the present inventors have made extensive efforts to find a substance that is useful for preventing, improving or treating gastritis and peptic ulcers, which has an excellent and improved pharmacological effect without inducing side effects to the human body. As a result, they have found that cinnamon extract, fractions of the extract, isolates of the fractions, or compounds isolated and purified therefrom can be used effectively for preventing, improving or treating gastritis and peptic ulcers, and have thus completed the present invention.

[0009] Therefore, an object of the present invention is to provide a pharmaceutical or food composition for preventing, ameliorating or treating gastritis or peptic ulcer, which comprises, as an active ingredient, a cinnamon extract, a fraction of the extract, an isolate of the fraction, an active ingredient isolated therefrom or a pharmaceutically acceptable salt thereof. [Means for solving the problem]

[0010] To achieve the above object, the present invention provides a pharmaceutical or food composition for preventing, ameliorating or treating gastritis or peptic ulcer, comprising, as an active ingredient, a cinnamon extract, a fraction of the extract, an isolate of the fraction, an active ingredient isolated therefrom or a pharmaceutically acceptable salt thereof.

[0011] For example, the cinnamon extract, a fraction of the extract, or an isolated product of the fraction may contain one or more isolated active ingredients selected from the group consisting of compounds represented by the following chemical formulas 1 to 6:

[0012] For example, the isolated active ingredient may be selected from the group consisting of compounds represented by the following chemical formulas 1 to 6.

[0013] (Chemical Formula 1) Ferulic acid

[0014] [ka]

[0015] (Formula 2) 4-Hydroxycinnamaldehyde

[0016] [ka]

[0017] (Formula 3) 3-(2-Hydroxyphenyl)propanoic acid

[0018] [ka]

[0019] (Formula 4) 3,4-Dihydroxybenzaldehyde

[0020] [ka]

[0021] (Chemical formula 5)Syringic acid

[0022] [ka]

[0023] (Formula 6) Vanillic acid

[0024] [ka]

[0025] The present invention has been described in detail above.

[0026] In one aspect, the present invention relates to a pharmaceutical or food composition for preventing, ameliorating, or treating gastritis or peptic ulcer, comprising, as an active ingredient, a cinnamon extract, a fraction of the extract, an isolate of the fraction, an active ingredient separated and purified from the extract, or a pharmaceutically acceptable salt thereof.

[0027] In the present invention, the term refers to the branches or bark of the cinnamon tree (Cinnamomum cassia, Chinese cinnamon), an evergreen broad-leaved tree of the Lauraceae family in the Ranunculaceae order belonging to the dicotyledonous plants, native to China and distributed in Sri Lanka, Indochina, and Korea (Jeju), which grows to a height of about 8 m in its native habitat.

[0028] In the present invention, the term "cinnamon extract" refers to an extract obtained by extracting cinnamon. As a specific example, the cinnamon extract is prepared by drying cinnamon or cutting or crushing it into a size suitable for extraction using a conventionally known method, and extracting it using an appropriate extraction solvent. Pretreatment may be performed before extraction.

[0029] The extraction method may be any known method for extracting herbs, such as hot water extraction, cold maceration extraction, reflux cooling extraction, or ultrasonic extraction, but is not limited thereto. The extract may include not only the extract itself, but also a diluted or concentrated extract, or a dried product obtained by drying the extract.

[0030] In one embodiment, the cinnamon extract of the present invention may be an extract that has undergone pretreatment before being extracted with a polar solvent (i.e., a pretreated polar solvent extract of cinnamon).

[0031] In one embodiment, the pretreatment may involve treating the cinnamon with a non-polar solvent. As a specific example, the non-polar solvent may be ethyl acetate. The non-polar solvent can be used in a volume that is 0.5 to 5 times, 0.7 to 4 times, or 1 to 3 times the weight (preferably dry weight) of the cinnamon, but is not limited thereto. As a specific example, the pretreatment can be performed by immersing and stirring cut or crushed cinnamon in a non-polar solvent such as ethyl acetate for 10 minutes to 5 hours, 20 minutes to 4 hours, or 30 minutes to 3 hours at a temperature of 20 to 35°C or room temperature. In one embodiment, after the pretreatment is complete, the cinnamon may be washed before being extracted with a polar solvent.

[0032] Furthermore, the cinnamon extract according to the present invention may be a polar solvent, preferably a water extract, of the cinnamon pretreated as described above. The polar solvent used during extraction can be used in a volume that is 5 to 12 times, 6 to 10 times, or 8 times the weight (preferably dry weight) of cinnamon, but is not limited thereto. As a specific example, the cinnamon pretreated with the non-polar solvent may be extracted at a temperature of 70 to 100°C, or 80 to 100°C, for 1 to 7 hours, 2 to 6 hours, or 5 hours. Such extraction may be performed once to several times, once to three times, or once to twice. The extracted pre-treated extract may be additionally filtered, concentrated, and / or dried. In this case, the methods used may be the same as those for filtering, concentrating, and drying that are commonly used in the production of extracts, without any restrictions.

[0033] In one embodiment of the present invention, cinnamon is dried and shredded, and then 2 volumes of ethyl acetate are added to the cinnamon, followed by immersion and stirring at room temperature for at least 1 hour. After removing the ethyl acetate, the pretreated cinnamon herb is washed off with water, and then water equivalent to 8 times the volume of the cinnamon herb is added and extracted at about 90°C for 5 hours. This process is repeated twice. The extract obtained is filtered, concentrated under reduced pressure, and vacuum-dried or spray-dried to produce a water extract of cinnamon pretreated with ethyl acetate.

[0034] In the present invention, the term "fraction" refers to a product obtained by a fractionation method for separating a specific component or group from a mixture containing various components. The fractions of the cinnamon extract of the present invention can be obtained by fractionating the cinnamon extract using polar solvents such as water, methanol, ethanol, or butanol, or nonpolar solvents such as hexane, ethyl acetate, or chloroform as fractionation solvents, resulting in polar solvent fractions and nonpolar solvent fractions, respectively. As a specific example, the cinnamon extract fraction may be an ethyl acetate fraction of the cinnamon extract.

[0035] In one embodiment, the fractionation solvent is used in an amount of 1 to 5, 1 to 10, or 1 to 20 times the volume of 1 kg of cinnamon extract with a polar or nonpolar solvent such as water, C1-C4 alcohol, chloroform, ethyl acetate, hexane, butanol, or a mixture thereof, and the polar or nonpolar solvent-soluble layer is extracted and separated 1 to 10 times, preferably 2 to 5 times. Alternatively, such solvent fractionation may be performed sequentially.

[0036] In one embodiment of the present invention, the aqueous extract of cinnamon (1 kg) pretreated with ethyl acetate obtained above was subjected to solvent fractionation using 800 ml each of HO / n-hexane, HO / chloroform, HO / ethyl acetate, and HO / n-butanol, and the solvents were then removed using a concentrator and a vacuum dryer to prepare cinnamon solvent fractions (n-hexane, chloroform, ethyl acetate, and n-butanol fractions).

[0037] In one embodiment, the fraction of the cinnamon extract exhibits NO inhibition of 4% or more, 7% or more, 19% or more, 50% or more, or 60% or more. In a preferred embodiment, the fraction exhibits NO inhibition of 60%-70%, 60-80%, or 65-85%.

[0038] In the present invention, the term "isolated product" means a product obtained by additionally performing a conventional separation step on the fraction. For example, such isolates can be obtained by passing a fraction of the cinnamon extract of the present invention through an ultrafiltration membrane with a certain molecular weight cut-off value, or by various purification methods further performed, such as separation by various chromatographies (designed for separation by size, charge, hydrophobicity, or affinity).

[0039] In one embodiment, such an isolate is a fraction having higher physiological activity or the like separated from the fraction, and is also referred to as an active fraction or effective fraction.

[0040] In one embodiment, the chromatography may be, but is not limited to, column chromatography, thin layer chromatography (TLC), or high performance liquid chromatography (HPLC), and may be performed using various chromatography methods known in the art. The column chromatography may be performed using a packing material selected from the group consisting of silica gel, Sephadex, LH-20, ODS gel, C-18 (RP-18), polyamide, Toyopearl, and XAD resin to separate and purify compounds. Column chromatography may be performed several times as needed, using an appropriate packing material, but is not limited to this. When using the chromatography, the elution solvent, elution rate, and elution time may be those commonly used in the art.

[0041] In one embodiment of the present invention, the cinnamon extract was fractionated with ethyl acetate, and the ethyl acetate solvent fraction was eluted using silica gel (normal phase) with chloroform:methanol as an elution solvent, and the separated product was concentrated and dried.

[0042] In one embodiment, the cinnamon extract isolate exhibits NO inhibition of at least 4%, at least 7%, at least 15%, at least 20%, at least 50%, or at least 60%. In a preferred embodiment, the fraction exhibits NO inhibition of 60-100%, 70-100%, or 75-100%.

[0043] Furthermore, specific active ingredients can be isolated from the cinnamon isolate by the above-mentioned chromatography. The isolated and purified active ingredients refer to single substances that exhibit physiological activity.

[0044] In one embodiment, the isolated and purified active ingredient according to the present invention can be obtained by subjecting the isolated material to chromatography and / or preparative high performance liquid chromatography (Prep-HPLC). In this case, a C-8 reversed phase column can be used as the HPLC column, and acetonitrile and water can be used as the elution solvent, but this is not limited thereto.

[0045] In one embodiment, the isolated and purified active ingredient according to the present invention may be selected from the group consisting of compounds represented by the following chemical formulas 1 to 6.

[0046] [ka]

[0047] The cinnamon extract, a fraction of the extract, or an isolate of the fraction contained in the composition according to the present invention may contain one or more, two or more, three or more, four or more, five or more, six, one to two, one to three, one to four, one to five, one to six, two to three, two to four, two to five, two to six, three to four, three to five, three to six, four to five, four to six, or five to six compounds selected from the group consisting of compounds represented by chemical formulas 1 to 6.

[0048] The composition of the present invention may also contain a pharmaceutically acceptable salt of the isolated and purified active ingredient. Acid addition salts formed with pharmaceutically acceptable free acids are useful as such salts. The term "pharmaceutically acceptable salt" as used herein refers to any and all organic or inorganic addition salts of the compound, which have a relatively non-toxic and harmless effective effect on patients, and whose side effects do not diminish the beneficial efficacy of the compound according to the present invention.

[0049] Acid addition salts are prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid and precipitating the salt with a water-miscible organic solvent, such as methanol, ethanol, acetone, or acetonitrile. Equal molar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water are heated, and the mixture is then evaporated to dryness or the precipitated salt can be filtered off with suction.

[0050] In this case, the free acid may be an organic acid or an inorganic acid. Examples of inorganic acids that may be used include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and tartaric acid. Examples of organic acids that may be used include, but are not limited to, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, and hydroiodic acid.

[0051] Pharmaceutically acceptable metal salts can also be prepared using bases. Alkali metal salts or alkaline earth metal salts can be obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, sodium, potassium, or calcium salts are particularly suitable for pharmaceutical use, but are not limited to these. Corresponding silver salts can also be obtained by reacting an alkali metal or alkaline earth metal salt with an appropriate silver salt (e.g., silver nitrate).

[0052] Pharmaceutically acceptable salts of the compounds of the present invention, unless otherwise indicated, include salts of acidic or basic groups which may be present in the compounds of Formulas 1-6 above.

[0053] The composition of the present invention contains an active ingredient selected from the group consisting of the compounds of formulas 1 to 6, or a cinnamon extract containing such an active ingredient, a fraction of the extract, or an isolate of the fraction, and is therefore highly effective in preventing, improving, or treating gastritis or peptic ulcers such as gastric ulcers and duodenal ulcers.

[0054] In one embodiment, the composition of the present invention may be a pharmaceutical composition.

[0055] The pharmaceutical composition of the present invention may contain 10 to 90% by weight of the cinnamon extract, a fraction of the extract, or an isolate of the fraction, based on the total weight of the composition.

[0056] Meanwhile, the pharmaceutical composition may contain, as an active ingredient, one or more selected from the group consisting of ferulic acid, 4-hydroxycinnamaldehyde, 3-(2-hydroxyphenyl)propanoic acid, 3,4-dihydroxybenzaldehyde, syringic acid, and vanillic acid, which are represented by Chemical Formulas 1 to 6, respectively.

[0057] The content of the extract, fraction, isolate or active ingredient in the composition may be increased or decreased depending on the type of formulation, route of administration and other factors when the composition is formulated.

[0058] The pharmaceutical composition of the present invention can be administered orally or parenterally and can be used in the form of a common pharmaceutical preparation.Preferred pharmaceutical preparations include oral preparations such as tablets, pills, powders, granules, hard or soft capsules, liquids, suspensions, etc., and these pharmaceutical preparations can be prepared using pharmaceutically acceptable common carriers, for example, in the case of oral preparations, excipients, binders, disintegrants, lubricants, solubilizers, suspending agents, preservatives, or fillers.

[0059] The dosage of the pharmaceutical composition of the present invention can be determined by an expert based on various factors such as the patient's condition, age, weight, and stage of disease progression, but generally, 9.7 to 2,919 mg of the extract can be administered once or in divided doses per day, preferably 29.2 to 2,919 mg, and more preferably 68.1 to 2,919 mg. However, in the case of long-term ingestion, the amount may be less than the above range, and since there are no safety issues with the active ingredient, amounts greater than the above range can also be used.

[0060] The composition of the present invention may also be a food composition. The food may be, but is not limited to, a health supplement, a functional health food, or a functional food. It may also include natural foods, processed foods, or general food ingredients to which the pre-treated cinnamon extract of the present invention is added. Here, "functionality" refers to the ability to regulate nutrients for the structure and function of the human body, or to achieve a physiological effect, which is useful for health purposes.

[0061] The health supplement, health functional food, or functional food of the present invention can be prepared by methods commonly used in the art, and can be prepared by adding raw materials and ingredients commonly used in the art. Unlike conventional medicines, the health functional food of the present invention is made from currently consumed herbal medicines, which have the advantage of being free of side effects that can occur with long-term drug use. It is also highly portable, and can be taken as an adjuvant to promote the prevention or improvement of gastritis or gastric ulcers. The amount of active ingredient can be appropriately determined depending on the intended use (prevention, health, or therapeutic treatment). Generally, the food product can contain 10 to 90% by weight of the fraction or isolate of the fraction according to the present invention.

[0062] Meanwhile, the food composition may contain, as an active ingredient, one or more selected from the group consisting of ferulic acid, 4-hydroxycinnamaldehyde, 3-(2-hydroxyphenyl)propanoic acid, 3,4-dihydroxybenzaldehyde, syringic acid, and vanillic acid, which are represented by Chemical Formulas 1 to 6, respectively.

[0063] When the composition is formulated into a food product, the content of the extract, fraction, isolate or active ingredient in the composition can be increased or decreased depending on the type of food, route of administration, etc.

[0064] The effective dose can be the same as that of the pharmaceutical composition, but in the case of long-term intake for the improvement or maintenance of gastritis or gastric ulcer, it may be less than the above range, and since cinnamon is also used in conventional foods, there is no problem in terms of safety as an ingredient, so it can also be used in an amount greater than the above range.

[0065] The type of food is not particularly limited. Food compositions containing the cinnamon extract, a fraction of the extract, an isolate of the fraction, or an active ingredient selected from the group consisting of Formulas 1-6 can be used in the form of oral dosage forms such as tablets, hard or soft capsules, liquids, and suspensions. These dosage forms can further contain acceptable conventional food supplement additives. The term "food supplement additive" refers to additives added to prepare functional health foods in various dosage forms and can be appropriately selected and used by those skilled in the art. Examples of food supplement additives include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and fillers, pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonation agents used in carbonated beverages. However, the types of food supplement additives of the present invention are not limited by these examples.

[0066] The food composition of the present invention can be used by adding the composition as is or together with other foods or food compositions, and can be used appropriately by conventional methods. The amount of active ingredient to be mixed can be suitably determined depending on the purpose of use (prevention, improvement, or therapeutic treatment).

[0067] Examples of such foods include, but are not limited to, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gum, dairy products including ice cream, various soups, drinking water, tea, energy drinks, alcoholic beverages, vitamin complexes, and other nutritional supplements.

[0068] According to one embodiment of the present invention, the cinnamon extract, a fraction of the extract, or an isolated product of the fraction, and the active ingredients of Formulas 1 to 6 separated and purified therefrom reduce NO production and inhibit PGE2, thereby exhibiting excellent anti-inflammatory effects and also excellent gastric ulcer inhibitory effects. [Effects of the Invention]

[0069] The cinnamon extract, fractions of the extract, or isolates of the fractions according to the present invention, and the active ingredients of Formulas 1 to 6 separated and purified therefrom have excellent anti-inflammatory and anti-gastric ulcer effects, and are therefore very useful as agents for preventing, improving or treating gastritis or peptic ulcer, or as functional foods. [Brief explanation of the drawings]

[0070] [Figure 1] 1 is a graph showing HPLC data of the cinnamon extract contained in the composition according to the present invention. [Figure 2] 1 is a graph showing the NO inhibition rate of each type of cinnamon solvent fraction contained in the composition according to the present invention. [Figure 3] 1 is a graph showing the NO inhibition rate of each type (N1 to N6) of isolates contained in the composition according to the present invention. [Figure 4] 1 is a graph showing the NO inhibition rate of isolated substances contained in the composition according to the present invention by type (N2-1 to N2-6). [Figure 5] 1 is a graph showing the NO inhibition rate of isolated substances contained in the composition according to the present invention by type (R2-1 to R2-8). [Figure 6] 1 is a graph illustrating the method for fractionating, separating and purifying a cinnamon extract according to the present invention. [Figure 7] 1 is a graph comparing the gastric ulcer inhibitory rates of cinnamon extract, fractions, and active ingredients ferulic acid, p-coumaraldehyde, and 3,4-dihydroxybenzaldehyde contained in the composition of the present invention with those of mugwort leaf extract and rebamipide. DETAILED DESCRIPTION OF THE INVENTION

[0071] The present invention will be described in more detail below through examples. These examples are merely for the purpose of illustrating the present invention, and the scope of the present invention is not to be construed as being limited by these examples.

[0072] Example 1. Preparation of extracts and solvent fractions according to the present invention

[0073] 1) Preparation of pre-treated cinnamon extract The cinnamon pre-treated extract according to the present invention was prepared as follows. Specifically, 2 volumes of ethyl acetate were added to the cinnamon herb, and the mixture was soaked and stirred at room temperature for at least 1 hour. After removing the ethyl acetate and rinsing the cinnamon herb with water, 8 volumes of water were added and extracted at approximately 90°C for 5 hours (repeated twice). The extract was filtered, concentrated under reduced pressure, and vacuum-dried or spray-dried to prepare the cinnamon ethyl acetate pre-treated water extract (extract yield: 16-26 → 1).

[0074] 2) Production of cinnamon solvent fraction The cinnamon solvent fraction according to the present invention was prepared as follows. Specifically, 1 kg of the cinnamon pre-treated extract of Example 1 was subjected to solvent fractionation using 800 ml each of HO / n-Hexane, HO / Chloroform, HO / Ethyl acetate, and HO / n-Butanol, and the solvent was then removed using a concentrator and a vacuum dryer to prepare the cinnamon solvent fraction.

[0075] [Table 1]

[0076] Example 2. Separation and purification of physiologically active substances according to the present invention 1

[0077] 1) Separation of physiologically active substances by silica gel column chromatography

[0078] Physiologically active substances were isolated by silica gel column chromatography according to the present invention as follows. Specifically, among the cinnamon solvent fractions in Examples 1-2, the resin used for the ethyl acetate solvent fraction and the open column was silica gel (normal phase). The ethyl acetate solvent fraction was packed into a silica gel column and separated due to its adsorption properties. The elution solvent was chloroform:methanol = 5:1, and the degree of separation of spots was confirmed on TLC, followed by concentration and drying.

[0079] [Table 2]

[0080] 2) Separation of physiologically active substances by silica gel column chromatography

[0081] Physiologically active substances were isolated by silica gel column chromatography according to the present invention as follows. Specifically, in the column chromatography of Example 2-1, silica gel (normal phase) was used as the resin for the isolated substance N2 and the open column. Isolated substance N2 was separated by its adsorption properties after being packed into a silica gel column. The elution solvent was hexane:ethyl acetate = 1:3, and the degree of separation of spots was confirmed on TLC, followed by concentration and drying.

[0082] [Table 3]

[0083] 3) Purification of single physiologically active substances by Prep-HPLC

[0084] The bioactive substances were separated by Prep-HPLC according to the present invention as follows. Specifically, the silica gel column chromatography of Example 2-2 was used with Prep-HPLC equipped with a C18 column. N2-1 was separated into PH2-1-1 and PH2-1-2 depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying. PH2-1-1 was purified into compound A depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying. PH2-1-2 was purified into compound B and compound C depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying.

[0085] [Table 4]

[0086] Example 3. Separation and purification of physiologically active substances according to the present invention 2

[0087] 1) Separation of physiologically active substances by C18 column chromatography

[0088] Physiologically active substances were isolated by C18 column chromatography according to the present invention as follows. Specifically, in the column chromatography of Example 2-1, the resin used for the isolated substance N2 and the open column was C18 (reverse phase). Isolated substance N2 was separated by its adsorption properties after being packed into the C18 column. The elution solvent was methanol:HO = 1:1, and the degree of separation of spots was confirmed on TLC, followed by concentration and drying.

[0089] [Table 5]

[0090] 2) Purification of single physiologically active substances by Prep-HPLC

[0091] The physiologically active substances were separated by Prep-HPLC according to the present invention as follows. Specifically, using Prep-HPLC equipped with a C18 column, as in Example 3-1, the separated substance R2-2 was separated into PH2-2-1 and PH2-2-2 depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying. PH2-2-1 was purified into compound D depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying. PH2-2-2 was purified into compound E and compound F depending on the properties of the C18 column. The elution solvent was acetonitrile:HO, and the degree of separation of the spots was confirmed by TLC, followed by concentration and drying.

[0092] [Table 6]

[0093] Example 4. Identification of the structure of purified compounds according to the present invention by physical and chemical properties

[0094] Nuclear Magnetic Resonance (NMR) spectrum measurement The NMR spectrum was measured using 1H-NMR (400 MHz) and 13C-NMR (100 MHz) by dissolving 10 mg of the purified product in each solvent.

[0095] Mass spectrum measurement After separation and purification, 1 mg of the dried powder solid sample was measured by chemical analysis using negative ion FAB-mass spectrum under reduced pressure (10 mmHg). At this time, thioglycerol was used as the measurement solvent, and the measurement conditions were an emitter current of 22-28 eV and an accelerating voltage of 6-7 kV.

[0096] The structure of the purified substance was identified by the above method, and the results are as follows:

[0097] 1) Compound A As a result of structural identification of Compound A, C 10 H 10 It has the molecular structure of O4, and the positive FAB-MS molecular weight was determined to be 194.18. 1 H-NMR (CD3OD, 400 MHz) spectrum is δ H 7.57 (1H, d, J = 16.0 Hz), 7.17 (1H, d, J= 2.0 Hz), 7.05 (1H, dd, J = 8.0, 2.0 Hz), 6.80 (1H, d, J = 8.0 Hz), 6.30 (1H, d, J = 16.0 Hz), 3.88 (3H, s) ppm, 13 C-NMR (CD3OD, 100 MHz) spectrum is δ CCompound A was identified as ferulic acid at 170.2, 149.1, 148.0, 144.2, 128.0, 121.6, 116.6, 114.6, 110.3, and 54.4 ppm.

[0098] 2) Compound B The structural identification of Compound B revealed that it had a molecular structure of C9H8O2 and a positive FAB-MS molecular weight of 148.16. 1 H-NMR (CDCl3, 400 MHz) spectrum is δ H 9.63 (1H, d, J = 7.8 Hz), 9.09 (1H, br s), 7.62 (2H, d, J = 8.7 Hz), 7.58 (1H, d, J = 15.8 Hz), 6.94 (2H, d, J = 8.6 Hz), 6.61 (1H, dd, J = 15.8, 7.7 Hz) ppm, 13 C-NMR (CDCl3, 100 MHz) spectrum is δ C The concentrations were 193.9, 161.3, 153.7, 131.6, 127.0, 126.8, and 116.8 ppm, and compound B was identified as 4-hydroxycinnamaldehyde.

[0099] 3) Compound C The structure of Compound C was identified and it was found to have a molecular structure of C9H8O3, with a positive FAB-MS molecular weight of 164.16. 1 H-NMR (DMSO-d6, 400 MHz) spectrum is δ H 7.0 (4H, m), 2.78 (2H, t, J = 7.0 Hz), 2.50 (2H, t, J = 7.0 Hz) ppm, 13 C-NMR (DMSO-d6, 100 MHz) spectrum is δ CThe concentrations were 174.6, 155.6, 130.1, 127.6, 127.3, 119.3, 115.3, 34.1, and 25.9 ppm, and compound C was identified as 3-(2-hydroxyphenyl)propanoic acid.

[0100] 4) Compound D The structural identification of Compound D revealed that it had a molecular structure of C7H6O3 and a positive FAB-MS molecular weight of 138.12. 1 H-NMR (CD3OD, 400 MHz) spectrum is δ H 9.68 (1H, s), 7.30 (1H, dd, J = 9.48, 1.70 Hz), 7.28 (1H, d, J = 1.41 Hz), 6.90 (1H, d, J = 8.1 Hz) ppm, 13 C-NMR (CD3OD, 100 MHz) spectrum is δ C Compound D was identified as 3,4-dihydroxybenzaldehyde at 193.8, 154.5, 148.0, 131.6, 127.2, 117.0, and 116.2 ppm.

[0101] 5) Compound E The structure of Compound E was identified as C9H 10 It has the molecular structure of O5, and its positive FAB-MS molecular weight was measured to be 198.17. 1 H-NMR (CD3OD, 400 MHz) spectrum is δ H 7.31 (2H, s), 3.87 (6H, s) ppm, 13 C-NMR (CD3OD, 100 MHz) spectrum is δ C Compound E was identified as syringic acid at 167.2, 147.4, 140.1, 120.6, 106.8, and 55.9 ppm.

[0102] 6) Compound F The structure of Compound F was identified and it was found to have a molecular structure of C8H8O4, with a positive FAB-MS molecular weight of 168.15. 1 H-NMR (CD3OD, 400 MHz) spectrum is δ H 7.55 (2H, m), 6.84 (d, J=8.8 Hz), 3.89(3H, s) ppm, 13 C-NMR (CD3OD, 100 MHz) spectrum is δ C Compound F was identified as vanillic acid at 170.1, 152.6, 148.7, 125.3, 123.2, 115.8, 113.9, and 56.4 ppm.

[0103] [Measurement of anti-inflammatory effects in Raw264.7 cells] Experimental Example 1: Confirmation of Nitric Oxide Production Inhibitory Activity

[0104] Nitric oxide (NO) was measured in the cell supernatant as nitrite and nitrate. The safe form of NO after oxidation from nitrite to nitrate was measured using Griess reagent (Sigma, USA). 3 × 10 cells were placed in a 2-well plate. 5 The cells were cultured for 24 hours. After 24 hours, each well was treated with various concentrations of solvent fractions, column-isolated products, and prep-HPLC purified products. All wells, except for the normal group, were stimulated with 100 ng / ml lipopolysaccharide (LPS). After 5 minutes of incubation with Griess reagent, the absorbance at 540 nm was measured. A calibration curve was prepared using sodium nitrite solution, and the nitrite concentration was calculated based on the absorbance. The NO inhibition rate was evaluated by comparing with a group treated with LPS only using the following formula 1. The results are shown in Tables 7, 8, 9, 10, 11, and 12 and Figures 2, 3, 4, and 5.

[0105] (Equation 1) NO inhibition rate (%) = 100 - [(NO production amount in sample-added group* × 100) / sample-free group* NO production] *Lipopolysaccharide (LPS) treated group

[0106] [Table 7]

[0107] [Table 8]

[0108] [Table 9]

[0109] [Table 10]

[0110] [Table 11]

[0111] [Table 12]

[0112] [Measurement of gastric ulcer inhibitory effect in animals] Experimental Example 2: Confirmation of gastric ulcer inhibition rate Gastric ulcer index evaluation in indomethacin-induced animal models

[0113] The test animals were 7-week-old specific pathogen-free (SPF) male rats. After a 7-day acclimation period, they were randomly assigned to groups of 10 rats each to maximize the uniformity of mean body weight distribution. The mugwort leaf extract, rebamipide and cinnamon ethyl acetate pre-treated aqueous extract, fraction (N2-1), 3,4-dihydroxybenzaldehyde, ferulic acid, and 4-hydroxycinnamaldehyde were administered orally in a single dose. The administration volume was calculated at 10 mL / kg based on the body weight measured on the day of administration. All animals were fasted 48 hours prior to administration of the test and control drugs, and then each test and control drug was orally administered. 30 minutes after administration, a pre-prepared dose of indomethacin was administered orally at a dose of 80 mg / kg. Five hours after administration, the animals were anesthetized with diethyl ether, and the stomach was removed and the gastric mucosa was photographed with a digital camera. The area of ​​the injured area was analyzed using ImageJ software (NIH, Bethesda, MD). The gastric ulcer index was calculated using the following formula: The results are shown in Table 13 and FIG.

[0114] (Equation 2) Gastric ulcer index (%) = (injury area / total area) x 100

[0115] [Table 13]

[0116] As can be seen from Figure 7 and Table 13, the cinnamon extract and fractions according to the present invention, as well as 3,4-dihydroxybenzaldehyde, ferulic acid, and 4-hydroxycinnamaldehyde separated and purified from these extracts, exhibited superior gastric ulcer inhibition rates compared to styrene in conventional mugwort leaf extract preparations and rebamipide, a commercially available anti-gastric ulcer drug. In particular, 3,4-dihydroxybenzaldehyde, ferulic acid, and p-coumaraldehyde exhibited extremely high gastric ulcer inhibition rates despite being present in very small amounts, demonstrating that preparations containing these active ingredients are highly effective in treating gastritis and peptic ulcers.

[0117] The technology may be as follows: [1] cinnamon extract, a fraction of said extract, and an isolate of said fraction. Contains ingredients, The extract, fraction or isolate is a pharmaceutical composition for preventing, ameliorating or treating gastritis or peptic ulcer, characterized in that it contains one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1 to 6: [Chemical formula 1~6] JPEG2025122663000022.jpg176170 [2] A pharmaceutical composition for preventing, ameliorating, or treating gastritis or peptic ulcer, comprising one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1 to 6, or pharmaceutically acceptable salts thereof: [Chemical formula 1~6] JPEG2025122663000023.jpg180170 [3] The pharmaceutical composition described in [1], wherein the cinnamon extract is a polar solvent extract of cinnamon pretreated with a non-polar solvent. [4] The pharmaceutical composition according to [3], wherein the non-polar solvent is ethyl acetate and the polar solvent is water. [5] The pharmaceutical composition according to [1], wherein the fraction is fractionated using a solvent selected from the group consisting of water, methanol, ethanol, butanol, hexane, ethyl acetate, and chloroform. [6] The pharmaceutical composition according to [5], wherein the fraction of the cinnamon extract is an ethyl acetate fraction. [7] The pharmaceutical composition according to [1], wherein the isolate is separated by ultrafiltration or chromatography. [8] The pharmaceutical composition according to [7], wherein the chromatography is silica gel column chromatography or C-18 column chromatography. [9] The pharmaceutical composition according to [1], wherein one or more active ingredients selected from the group consisting of the chemical formulas 1 to 6 are obtained by separating and purifying the isolated product by Prep-HPLC.

[10] The pharmaceutical composition according to [1] or [2] above, further comprising a pharmaceutically acceptable carrier.

[11] comprising an ingredient selected from the group consisting of a cinnamon extract, a fraction of said extract, and an isolate of said fraction; A food composition for preventing or improving gastritis or peptic ulcer, wherein the extract, fraction, or isolate contains one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1 to 6: [Chemical formula 1~6] JPEG2025122663000024.jpg187170

[12] A food composition for preventing or improving gastritis or peptic ulcer, comprising one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1 to 6, or pharmaceutically acceptable salts thereof: [Chemical formula 1~6] JPEG2025122663000025.jpg184170

Claims

1. comprising an ingredient selected from the group consisting of a cinnamon extract, a fraction of said extract, and an isolate of said fraction; The extract, fraction or isolate is a pharmaceutical composition for preventing, ameliorating or treating gastritis or peptic ulcer, characterized in that it contains compounds represented by chemical formulas 1, 2 and 4: 【Chemical 1】

2. A pharmaceutical composition for preventing, improving or treating gastritis or peptic ulcer, comprising compounds represented by chemical formulas 1, 2 and 4: 【Chemistry 2】

3. The pharmaceutical composition according to claim 1 or 2, further comprising one or more active ingredients selected from the group consisting of compounds represented by chemical formulas 3, 5, and 6, or pharmaceutically acceptable salts thereof: 【Chemistry 3】

4. The pharmaceutical composition of claim 1, wherein the cinnamon extract is a polar solvent extract of cinnamon pretreated with a non-polar solvent.

5. 5. The pharmaceutical composition of claim 4, wherein the non-polar solvent is ethyl acetate and the polar solvent is water.

6. 2. The pharmaceutical composition according to claim 1, wherein the fraction is fractionated using a solvent selected from the group consisting of water, methanol, ethanol, butanol, hexane, ethyl acetate, and chloroform.

7. 7. The pharmaceutical composition of claim 6, wherein the fraction of cinnamon extract is an ethyl acetate fraction.

8. 10. The pharmaceutical composition of claim 1, wherein the isolate is separated by ultrafiltration or chromatography.

9. 9. The pharmaceutical composition according to claim 8, wherein the chromatography is silica gel column chromatography or C-18 column chromatography.

10. 3. The pharmaceutical composition according to claim 1, wherein the active ingredient is obtained by separating and purifying the isolated product by Prep-HPLC.

11. 3. The pharmaceutical composition of claim 1 or 2, further comprising a pharmaceutically acceptable carrier.

12. comprising an ingredient selected from the group consisting of a cinnamon extract, a fraction of said extract, and an isolate of said fraction; A food composition for preventing or improving gastritis or peptic ulcer, wherein the extract, fraction, or isolate contains compounds represented by chemical formulas 1, 2, and 4: 【Chemistry 4】

13. A food composition for preventing or improving gastritis or peptic ulcer, comprising compounds represented by chemical formulas 1, 2 and 4: 【Chemistry 5】

14. The food composition according to claim 12 or 13, further comprising one or more active ingredients selected from the group consisting of compounds represented by chemical formulas 3, 5, and 6, or pharmaceutically acceptable salts thereof: 【Chemistry 6】

15. The isolated fraction of the cinnamon extract is separated from the ethyl acetate fraction of the cinnamon extract by silica gel column chromatography or C-18 column chromatography; 14. A food composition for preventing or improving gastritis or peptic ulcers according to claim 12 or 13, wherein the cinnamon extract is a polar solvent extract of cinnamon pretreated with a non-polar solvent, the non-polar solvent being ethyl acetate and the polar solvent being water.

16. The present invention comprises a component selected from the group consisting of a fraction of cinnamon extract and an isolate of said fraction, The cinnamon extract is an aqueous extract of cinnamon pretreated with ethyl acetate, and the fraction is fractionated using ethyl acetate; The fraction or isolate contains one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1, 2 and 4. A pharmaceutical composition for preventing, improving or treating gastritis or gastrointestinal ulcer: 【Chemistry 7】

17. A pharmaceutical composition for preventing, improving or treating gastritis or gastrointestinal ulcer, comprising one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1, 2 and 4, or pharmaceutically acceptable salts thereof: 【Chemistry 8】

18. The pharmaceutical composition according to claim 16 or 17, further comprising one or more active ingredients selected from the group consisting of compounds represented by chemical formulas 3, 5, and 6, or pharmaceutically acceptable salts thereof: 【Chemistry 9】

19. 10. The pharmaceutical composition of claim 1, wherein the isolate is separated by ultrafiltration or chromatography.

20. 20. The pharmaceutical composition according to claim 19, wherein the chromatography is silica gel column chromatography or C-18 column chromatography.

21. The pharmaceutical composition according to claim 16 or 17, wherein the isolated active ingredient is obtained by separating and purifying the isolated product by Prep-HPLC.

22. 18. The pharmaceutical composition of claim 16 or 17, further comprising a pharmaceutically acceptable carrier.

23. The present invention comprises a component selected from the group consisting of a fraction of cinnamon extract and an isolate of said fraction, The cinnamon extract is a water extract of cinnamon pretreated with ethyl acetate, and the fraction is fractionated using ethyl acetate; A food composition for preventing or improving gastritis or gastrointestinal ulcer, wherein the fraction or isolate contains one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1, 2, and 4: 【Chemistry 10】

24. A food composition for preventing or improving gastritis or gastrointestinal ulcers, comprising one or more isolated active ingredients selected from the group consisting of compounds represented by chemical formulas 1, 2 and 4, or pharmaceutically acceptable salts thereof: 【Chemistry 11】

25. The food composition according to claim 23 or 24, further comprising one or more active ingredients selected from the group consisting of compounds represented by chemical formulas 3, 5 and 6, or pharmaceutically acceptable salts thereof: 【Chemistry 12】

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