Composition for preventing, treating or improving gastroesophageal reflux disease comprising Prunella vulgaris extract and Saururus chinensis extract

Abstract

The composition of the present invention for the prevention, treatment, or improvement of gastroesophageal reflux disease comprises Hagocho extract and Sambakcho extract.

Description

Technology Field

[0001] The present invention relates to a composition for the prevention, treatment, or improvement of gastroesophageal reflux disease comprising extracts of *Hagocho* and *Sambaeckcho*. More specifically, the present invention relates to a pharmaceutical composition, a food composition, and a food additive composition capable of exhibiting preventive, therapeutic, or improvement effects for gastroesophageal reflux disease by utilizing *Hagocho* and *Sambaeckcho*, which are natural medicinal plants. Background Technology

[0003] Gastroesophageal reflux disease (GERD) is a very common condition affecting one in ten South Koreans, and it occurs so frequently that it ranked 11th among the country's most frequent diseases as of 2023. Prior to 2020, the number of GERD patients was relatively low compared to those with gastritis and duodenitis, but it has been increasing rapidly since 2023. Insurance claims for GERD increased from 292.3 billion won in medical expenses in 2019 to 341.2 billion won in 2023, ranking 12th among the country's most frequent diseases. The number of GERD patients is expected to continue rising due to lifestyle habits of modern people, such as the continuous consumption of alcohol, tobacco, greasy foods, and spicy foods.

[0004] Histamine H2 receptor antagonists (H2RAs), one of the major treatments for GERD, are known to suppress gastric acid secretion, thereby reducing acid exposure to the esophagus and helping to alleviate esophageal mucosal damage. However, it has been reported that some patients treated with standard doses of H2RAs still experience persistent GERD symptoms. While H2RAs may provide short-term relief, their efficacy in treating GERD may be limited. In particular, because the effects of H2RAs are not sustained, there is a risk of symptom recurrence if treatment is discontinued. Furthermore, long-term use is known to lead to changes in the balance of gastrointestinal microorganisms or gut bacterial communities due to the suppression of gastric acid secretion, which may result in reduced resistance to intestinal infections. For these reasons, concerns have been raised regarding the long-term use of H2RAs. If treatment is necessary, it is recommended to discontinue use after an appropriate period; consequently, H2RAs play a greater role in the treatment of GERD in terms of symptom control rather than long-term cure. Therefore, there is a need to develop new GERD treatments that can demonstrate superior efficacy with fewer side effects.

[0005] Meanwhile, efforts are being made to utilize natural resources instead of synthetic compounds due to environmental pollution issues and potential harm to the human body. In particular, attempts are being made to develop substances effective for various diseases through research on medicinal plants. In this case, there is an advantage in that natural plant materials that have been previously used on the human body can be utilized, which reduces the possibility of side effects, and active substances can be obtained through relatively easy methods such as extraction and fractionation.

[0006] Accordingly, the inventors of the present invention sought to develop a new treatment that could replace existing GERD treatments through research on medicinal plants, which are natural resources. Prior art literature

[0008] Korean Registered Patent No. 10-2515763 The problem to be solved

[0009] The main objective of the present invention is to provide a new composition that can effectively prevent, treat, or improve gastroesophageal reflux disease by utilizing medicinal plants, which are natural resources. means of solving the problem

[0011] In one aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of GERD according to the following item:

[0012] 1. A pharmaceutical composition for the prevention or treatment of GERD comprising Hagocho extract and Sambakcho extract.

[0013] 2. A pharmaceutical composition according to Item 1, wherein the extract is extracted with a solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.

[0014] 3. A pharmaceutical composition according to Item 1 or Item 2, comprising Hagocho extract and Sambakcho extract in a weight ratio of 1:0.5 to 1.5.

[0015] In another aspect, the present invention provides a food composition for the prevention or improvement of GERD according to the following item:

[0016] 4. A food composition for the prevention or improvement of GERD comprising Hagocho extract and Sambakcho extract.

[0017] 5. A food composition according to Item 4, wherein the extract is extracted with a solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.

[0018] 6. A food composition according to Item 4 or Item 5, comprising Hagocho extract and Sambakcho extract in a weight ratio of 1:0.5 to 1.5.

[0019] In another aspect, the present invention provides a food additive composition for the prevention or improvement of GERD according to the following item:

[0020] 7. A food additive composition for the prevention or improvement of GERD comprising Hagocho extract and Sambakcho extract.

[0021] 8. A food additive composition according to Item 7, wherein the extract is extracted with a solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof.

[0022] 9. A food additive composition according to Item 7 or Item 8, comprising Hagocho extract and Sambakcho extract in a weight ratio of 1:0.5 to 1.5. Effects of the invention

[0024] According to the present invention, a composition is provided that can effectively prevent, treat, or improve GERD by utilizing medicinal plants, which are natural resources. Since the composition of the present invention utilizes medicinal plants, it has the advantage of excluding the possibility of harmful effects associated with the use of synthetic drugs and having a low likelihood of side effects, and also has the advantage of being easy to supply as it can be manufactured by a relatively simple extraction method. Brief explanation of the drawing

[0026] FIG. 1 shows experimental results confirming the effect of the composition of the present invention in an animal model of GERD induction (surgical method). "Normal group", group without GERD induction treatment; "Negative control group", group without any separate treatment other than GERD induction; "Positive control group", GERD induction treatment + ranitidine administration group; "Experimental group 1", GERD induction treatment + 100 mg / kg administration of the composition of the present invention; "Experimental group 2", GERD induction treatment + 300 mg / kg administration of the composition of the present invention. Figure 2 is a graph showing the measurement of bleeding and lesion area on the gastric wall from the experimental results of Figure 1, and the calculation of the inhibition rate based on this. "Normal group", group without GERD induction treatment; "Negative control group", group without separate treatment other than GERD induction; "Positive control group", GERD induction treatment + ranitidine administration group; "Experimental group 1", GERD induction treatment + 100 mg / kg administration of the composition of the present invention; "Experimental group 2", GERD induction treatment + 300 mg / kg administration of the composition of the present invention. Figures 3 and 4 show the experimental results confirming the effect of treatment with the extract alone in an animal model of GERD induction. "Negative control group", group without separate treatment other than GERD induction; "Comparative group 1", GERD induction treatment + Hagocho extract alone administered at 100 mg / kg; "Comparative group 2", GERD induction treatment + Hagocho extract alone administered at 300 mg / kg; "Comparative group 3", GERD induction treatment + Sambakcho extract alone administered at 100 mg / kg; "Comparative group 4", GERD induction treatment + Sambakcho extract alone administered at 300 mg / kg. Specific details for implementing the invention

[0027] The composition for the prevention, treatment, or improvement of GERD according to the present invention is characterized by comprising Hagocho extract and Sambakcho extract.

[0028] According to the present invention, a combination of Hagocho extract and Sambakcho extract can exhibit excellent preventive, therapeutic, or improving effects against GERD, and in particular, there is a synergistic effect resulting from the combination thereof.

[0029] In the present invention, the extract of *Hagocho* is *Dumekkulpul*, which is called *Hagocho* by its medicinal name ( Prunella vulgaris ) or self-heal ( Prunella vulgaris subsp. asiaticaIt is obtained through extraction using ) as an extraction raw material, and Hagocho is a perennial herbaceous plant belonging to the Lamiaceae family, and in the present invention, the flower stalk and above-ground parts of such Hagocho can be used as an extraction raw material.

[0030] In the present invention, the Sambeakcho extract is Sambeakcho ( Saururus chinensis It is obtained through extraction using ) as an extraction raw material, and Sambeakcho is a perennial herbaceous plant belonging to the family Saururaceae, and in the present invention, the above-ground parts of such Sambeakcho can be used as an extraction raw material.

[0031] In the present invention, the term "extract" may refer to a product such as a liquid component obtained by immersing an extract raw material in a solvent and extracting it for a certain period of time, for example, at room temperature or under a heated state, or a solid component obtained by removing the solvent from said liquid component. Furthermore, in addition to said product, it may be comprehensively interpreted to include all of the diluted solutions, concentrates thereof, modified products, purified products, etc. of said product.

[0032] The extract of the present invention can be prepared according to extraction methods commonly used in the field using the relevant material (Hagocho or Sambakcho) as the extraction raw material. For example, extraction can be performed using a polar solvent or a non-polar solvent; the polar solvent may be selected from the group consisting of lower alcohols having 1 to 4 carbon atoms and water, and the non-polar solvent may be selected from the group consisting of chloroform, petroleum ether, ether, butanol, hexane, toluene, and the like. For the desired effect in the present invention, the extract of the present invention is preferably extracted using water, alcohols having 1 to 4 carbon atoms and mixed solutions thereof as solvents, more preferably using water, ethanol, or a mixed solution thereof as solvents, and even more preferably using a mixed solution of water and ethanol as solvents. The above mixed solution of water and ethanol is preferably an aqueous ethanol solution of 5 to 90% (v / v), more preferably an aqueous ethanol solution of 10 to 50% (v / v), more preferably an aqueous ethanol solution of 20 to 40% (v / v), and more preferably an aqueous ethanol solution of 25 to 35% (v / v).

[0033] When extracting, a solvent in a ratio of, for example, 1 to 100 ml per 1 g of dried extract of Hagocho or Sambakcho can be used, and preferably, a solvent in a ratio of 5 to 10 ml per 1 g of dried extract of the extract raw material is used.

[0034] The extraction temperature can be set, for example, to 0 to 120°C, preferably to 50 to 100°C, more preferably to 60 to 90°C, more preferably to 70 to 90°C, and more preferably to 80 to 90°C.

[0035] The extraction time can be set to, for example, 1 to 12 hours, preferably 1 to 10 hours, more preferably 1 to 5 hours, and more preferably 1 to 3 hours.

[0036] According to the extraction conditions described above, an extract exhibiting the effect intended in the present invention can be efficiently produced from Hagocho and Sambakcho when combined.

[0037] In addition, the extract can be obtained by repeating the extraction process, for example, by separating and recovering the extract from the residue after the first extraction, adding a new solvent to the residue to perform a second extraction, and obtaining the extract again. When the extraction is repeated, the number of repetitions can be, for example, 2 to 5 times, preferably 2 to 4 times, more preferably 2 to 3 times, and more preferably 2 times.

[0038] To prepare an extract in the form of a dried product, a drying process can be performed after extraction. Preferably, a method of concentrating under reduced pressure followed by freeze-drying is used.

[0039] When concentrating under reduced pressure, for example, it is performed under conditions of 50 to 70°C and a vacuum of 100 to 200 torr, and when freeze-drying, for example, it is performed for 24 to 48 hours under conditions of -50 to -100°C.

[0040] The composition of the present invention may include Hagocho extract and Sambakcho extract in various proportions. In particular, for the effect intended in the present invention, namely the prevention, treatment, or improvement of GERD, the composition of the present invention preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.1 to 10, more preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.2 to 5, more preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.5 to 2, more preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.7 to 1.5, more preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.8 to 1.3, and more preferably includes Hagocho extract and Sambakcho extract in a weight ratio of 1:0.9 to 1.1.

[0041] The composition of the present invention may contain Hagocho extract and Sambakcho extract to varying degrees. For example, the composition of the present invention may contain Hagocho extract and Sambakcho extract in an amount of 0.1 to 100% by weight as the combined weight thereof, based on the total weight of the composition, but is not limited thereto.

[0042] The pharmaceutical composition of the present invention may be formulated into a conventional pharmaceutical formulation by selecting one or more pharmaceutically acceptable conventional carriers and one or more additives to the active ingredients, which are Hagocho extract and Sambakcho extract. The pharmaceutical composition of the present invention may be used alone or in combination with other pharmaceutically active compounds, as well as in combination with suitable substances.

[0043] The pharmaceutical composition of the present invention may be in various oral or parenteral dosage forms. When formulating, it may be prepared using diluents or excipients such as commonly used fillers, volume expanders, binders, humectants, disintegrants, and surfactants. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and these solid dosage forms may be prepared by mixing at least one excipient. In addition, lubricants may be used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquids, emulsions, and syrups, and may include various excipients, such as humectants, sweeteners, flavorings, and preservatives, in addition to commonly used simple diluents. Preparations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.

[0044] The pharmaceutical composition of the present invention may include other auxiliary components, such as vitamins, in addition to the active ingredients. In addition to the above components, natural flavorings, natural colorings, sweeteners, and acidity agents may be mixed and used as known additives to enhance the taste.

[0045] The organism to which the pharmaceutical composition of the present invention can be applied is a vertebrate, preferably a mammal, and more preferably a human.

[0046] The pharmaceutical composition of the present invention may be administered orally or parenterally. When administered parenterally, external application to the skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dura mater, or intracerebrovascular injection methods may be used, but preferably, it is administered orally.

[0047] The dosage of the pharmaceutical composition of the present invention varies depending on the patient's body weight, age, gender, health condition, diet, time of administration, method of administration, excretion rate, and severity of the disease, but, for example, the daily dosage may be applied in an amount of 0.1 to 10 mg / kg based on the amount of *Hagocho* extract and *Sambaeckcho* extract, and may be administered 1 to 6 times a day.

[0048] The pharmaceutical composition of the present invention may additionally contain one or more active ingredients exhibiting the same or similar functions.

[0049] The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

[0050] The food composition of the present invention may be, for example, various food products such as chewing gum, caramel products, candies, frozen desserts, confectionery, etc., beverage products such as soft drinks, mineral water, alcoholic beverages, etc., or health functional foods containing vitamins or minerals.

[0051] The Hagocho extract and Sambakcho extract of the present invention may be used as they are or together with other foods or food ingredients, and may be used appropriately according to conventional methods. The amount of the active ingredient can be appropriately determined according to the purpose of use. Generally, when manufacturing food or beverages, the active ingredient of the present invention may be added in an amount of 15% by weight or less, preferably 10% by weight or less, relative to the raw material. However, in the case of long-term consumption, the above amount may be less than the above range.

[0052] The food composition of the present invention may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients.

[0053] In addition, the food composition of the present invention may contain various nutritional agents, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the food composition of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination.

[0054] The food additive composition of the present invention may consist only of the active ingredients, Hagocho extract and Sambakcho extract, and may also include other food-grade acceptable additives.

[0056] The present invention will be described in more detail below through examples. These examples are merely illustrative of the present invention, and therefore the scope of the present invention should not be interpreted as being limited by these examples.

[0058] [Example]

[0059] Example 1. Preparation of Composition

[0060] 1-1. Preparation of Extract

[0061] Hagocho and Sambakcho were purchased from Gwangmyeongdang Pharmaceutical and used after verification by the Department of Herbal Medicine at the College of Korean Medicine, Woosuk University. To prepare the respective extracts, 400 ml of 30% (v / v) ethanol was added to 42 g of Hagocho and 400 ml of 30% (v / v) ethanol was added to 70 g of Sambakcho, respectively. The mixtures were then refluxed at 85°C for 2 hours and filtered through filter paper. The filtered extracts were concentrated under reduced pressure and freeze-dried to obtain 18.16 g (yield 8.64%) of Hagocho extract and 8.39 g (yield 11.98%) of Sambakcho extract.

[0063] 1-2. Preparation of Composition

[0064] A composition was prepared by mixing the Hagocho extract and Sambakcho extract of 1-1 above in a weight ratio of 1:1.

[0066] Comparative Example 1. Preparation of Composition

[0067] Only the Hagocho extract of Example 1 above was prepared as a composition for comparison.

[0069] Comparative Example 2. Preparation of Composition

[0070] Only the Sambeakcho extract of Example 1 above was prepared as a composition for comparison.

[0072] Experimental Example 1. Confirmation of effect on gastroesophageal reflux disease

[0073] Six-week-old male Sprague-Dawly rats (DBL, South Korea) weighing approximately 160 to 180 g were purchased as experimental animals and allowed to adapt to the experimental environment by providing sufficient food and water. After allowing a one-week adaptation period, gastroesophageal reflux disease was induced through surgical intervention for the experiment.

[0074] All experimental groups were fasted starting 18 hours before the experiment, and water was stopped 16 hours after fasting.

[0075] For the positive control group, ranitidine, which is used in clinical practice, was orally administered to white rats at a concentration of 50 mg / kg in a volume of 1.0 ml per 100 g of body weight. For experimental group 1, the composition prepared in Example 1 was orally administered at a concentration of 100 mg / kg, and for experimental group 2, at a concentration of 300 mg / kg in a volume of 1.0 ml per 100 g of body weight, dissolved in primary distilled water.

[0076] After 1 hour and 30 minutes of drug administration, all experimental rats were anesthetized by inhalation and then laparotomy was performed to remove the stomach and esophagus, and the fundus and pylorus were ligated using black silk (4-0). The stomach tissue was then returned to the abdominal cavity and the muscle layer and epidermal layer were sutured.

[0077] Four hours and 30 minutes after the above surgical procedure, the white rat was anesthetized by inhalation and the gastroesophageal tissue was removed.

[0078] The excised gastric and esophageal tissue was incised longitudinally, and photographs were taken to expose the inner wall. The area of ​​the lesion on the gastric inner wall was measured using the image analysis program Image J (NIH, USA) from the captured photographs. To evaluate the inhibitory effect on gastroesophageal reflux disease, the lesion area values ​​were statistically analyzed and compared with a control group.

[0079] The results of this are shown in Table 1, Figure 1, and Figure 2 below.

[0080] Figure 1 shows a photograph of the inner wall of the stomach and esophagus, showing that the bleeding area of ​​the inner wall of the stomach and esophagus of the experimental group treated with the composition of the present invention was significantly reduced compared to the bleeding area of ​​the inner wall of the stomach and esophagus of the negative control group and the positive control group.

[0081] In addition, as shown in Table 1 and Figure 2, the bleeding and lesion areas of the gastric wall were measured in an animal model of gastroesophageal reflux disease. In the experimental groups treated with 100 mg and 300 mg of the composition of the present invention, the bleeding and lesion areas were 89.44 ± 14.87 mm² and 99.15 ± 15.56 mm², respectively, which was found to be 52.19% and 47.01% lower than the negative control group of 187.1 ± 21.86 mm².

[0082] army treatment Concentration (mg / kg, po) Lesion area (mm²) M±SEM Suppression rate (%) Normal group - - - - Negative control group disease-causing - 187.1 ± 21.86 - positive control group Disease-causing + Ranitidine treatment 50 75.91 ± 14.63 59.43 Experimental group 1 Disease induction + treatment with the composition of Example 1 100 89.44 ± 14.87 52.19 Experimental group 2 300 99.15 ± 15.56 47.01

[0083] (Number of experimental animals in the normal group = 3, number of experimental animals in each of the remaining groups = 13)

[0084] Separately, for comparison with treatment with the extract alone, the experiment was conducted in the same manner as above, but using the compositions of Comparative Example 1 and Comparative Example 2. As shown in Tables 2 and 3 and Figures 3 and 4 below, the effect when using the compositions of Comparative Example 1 and Comparative Example 2 was found to be inferior to that when the composition of the Example was used in the same amount.

[0085] army treatment Concentration (mg / kg, po) Lesion area (mm²) M±SEM Suppression rate (%) Negative control group disease-causing - 193.3 ± 37.08 - Comparative Experiment Group 1 Disease induction + treatment with the composition of Comparative Example 1 100 138.7 ± 29.27 28.2 Comparative experimental group 2 300 113.1 ± 29.08 41.5

[0086] (Number of experimental animals in each group = 7)

[0087] army treatment Concentration (mg / kg, po) Lesion area (mm²) M±SEM Suppression rate (%) Negative control group disease-causing - 180.6 ± 20.22 - Comparative experimental group 3 Disease induction + treatment with the composition of Comparative Example 2 100 164.5 ± 33.31 8.9 Comparative experimental group 4 300 120.9 ± 39.33 33.1

[0088] (Number of experimental animals in each group = 7)

[0089] The experimental results described above demonstrate that the composition of the present invention has excellent effects in the prevention, treatment, and improvement of gastroesophageal reflux disease, and in particular, there is a synergistic effect resulting from the combination of Hagocho extract and Sambakcho extract.

Claims

Claim 1 A pharmaceutical composition for the prevention or treatment of gastroesophageal reflux disease comprising Hagocho extract and Sambakcho extract. Claim 2 A pharmaceutical composition according to claim 1, wherein the extract is extracted with a solvent selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof. Claim 3 A pharmaceutical composition according to claim 1, comprising Hagocho extract and Sambakcho extract in a weight ratio of 1:0.1 to 10. Claim 4 A food composition for the prevention or improvement of gastroesophageal reflux disease comprising Hagocho extract and Sambakcho extract. Claim 5 A food additive composition for the prevention or improvement of gastroesophageal reflux disease comprising Hagocho extract and Sambakcho extract.

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