KR20210019894A - Composition for prevention, treatment or improvement of colitis comprising steamed and dryed ginger as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing, treating or alleviating colitis containing a steamed and dried ginger as an active component. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating colitis, and a food composition for preventing or alleviating colitis containing the steamed and dried ginger obtained by repeatedly steaming and drying ginger under specific conditions, or an extract thereof as an active component. The composition of the present invention contains the steamed and dried ginger obtained by repeatedly steaming and drying ginger under specific conditions, or the extract thereof as the active component, thereby being able to effectively prevent, alleviate or treat colitis.

Description

Composition for prevention, treatment or improvement of colitis comprising steamed and dryed ginger as an active ingredient}

The present invention relates to a composition for preventing, treating, or improving colitis containing a steamed ginger dried product as an active ingredient, and specifically, a steamed ginger dried product obtained by repeatedly steaming and drying ginger under specific conditions; Or an extract thereof; It relates to a pharmaceutical composition for the prevention or treatment of colitis containing as an active ingredient and a functional food composition for the prevention or improvement of colitis.

Colitis is a state of inflammation in the large intestine and is largely classified into infectious colitis and non-infectious colitis depending on the cause. Infectious colitis is caused by damage to the colonic mucosa due to infection with viruses or bacteria, or the balance of the colonic flora due to toxins from infectious bacteria.Unlike infectious colitis, non-infectious colitis is caused by a cause other than microbial infection Colitis includes inflammatory bowel disease (ulcerative colitis, Crohn's disease), radioactive colitis, and ischemic colitis.

Inflammatory bowel disease is a disease in which abnormal chronic inflammation in the intestine repeats improvement and recurrence, and ulcerative colitis and Crohn's disease are typical, and a clear pathogenesis has not been established yet. Among them, ulcerative colitis has a close relationship with the onset of colon cancer, and it is known that the risk of developing colon cancer increases as the degree and duration of colitis increases.

Agents such as dexamethasone are mainly used to treat colitis, but there are side effects such as dehydration, so it is necessary to develop a safer and more effective treatment for colitis. Therefore, to develop new treatments for colitis or functional foods that can help improve colitis by using natural products that have been applied to humans for the purpose of improving food or other diseases and have been verified for safety, especially natural products with known anti-inflammatory effects. Research is being done.

The present inventors have tried various studies to develop safe and effective anti-colitis agents or functional foods using ginger, which has been known for various physiological activities and has been used as a food ingredient for a long time, and has proven its safety, and as a result, steaming and drying under specific conditions. It was confirmed that the steamed dried ginger, which was repeatedly performed, can exhibit an excellent anti-colitis effect, and the present invention was completed.

Journal of Nutrition and Health (J. Nutr. Health) 2019; 52(2): 139-148. Korean journal of plant resources (Korean J. Plant Res.) 2014; 27(5): 421-428.

Therefore, the main object of the present invention is to provide a composition excellent in preventing, treating and improving colitis using ginger.

According to one aspect of the present invention, the present invention is by steaming whole ginger at 90 to 95°C for 3 to 5 hours, drying at 88 to 92°C for 20 to 40 minutes, and then drying at 58 to 62°C to a moisture content of 20% or less. The first steam-dried, the first steam-dried ginger was steamed at 90 to 95°C for 2 to 4 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 20% or less. After the second steaming and drying, the second steamed and dried ginger was steamed at 90 to 95°C for 1 to 3 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 10% or less. 3rd steam-dried ginger steam-dried product; Or its extract; provides a pharmaceutical composition for the prevention or treatment of colitis containing as an active ingredient.

In the pharmaceutical composition of the present invention, the extract is preferably extracted by adding a mixed solution of alcohol and water to the pulverized product of the steamed ginger and heating at 87 to 93°C for 8 to 12 hours.

According to another aspect of the present invention, the present invention is by steaming whole ginger at 90 to 95°C for 3 to 5 hours, drying at 88 to 92°C for 20 to 40 minutes, and then drying at 58 to 62°C to a moisture content of 20% or less. The first steam-dried, the first steam-dried ginger was steamed at 90 to 95°C for 2 to 4 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 20% or less. After the second steaming and drying, the second steamed and dried ginger was steamed at 90 to 95°C for 1 to 3 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 10% or less. 3rd steam-dried ginger steam-dried product; Or its extract; provides a functional food composition for preventing or improving colitis containing as an active ingredient.

In the functional food composition of the present invention, the extract is preferably extracted by adding a mixed solution of alcohol and water to the pulverized product of the steamed ginger and heating at 87 to 93°C for 8 to 12 hours.

The composition of the present invention is a ginger steam dried product obtained by repeatedly steaming and drying ginger under specific conditions; Or its extract; by containing as an active ingredient can effectively prevent, treat and improve colitis.

1 shows the results of a cytotoxicity experiment of steamed ginger according to an embodiment of the present invention. A: Cytotoxicity test result of general ginger extract (control group), B: Cytotoxicity test result of steamed ginger of the present invention, each graph expressed as mean±standard deviation.
Figure 2 shows the experimental results of the ability to inhibit the production of nitrogen monoxide (NO) of steamed dried ginger according to an embodiment of the present invention. A: Experimental results of inhibiting nitrogen monoxide production of general ginger extract (control), B: Experimental results of inhibiting nitrogen monoxide production of steamed dried ginger of the present invention, CON: untreated group, each graph expressed as mean ± standard deviation.
3 shows the experimental results of PEG2 production inhibitory ability of steamed dried ginger according to an embodiment of the present invention. SG: Ginger steamed dried product of the present invention, each graph is represented by mean ± standard deviation, *P<0.05, **P<0.01 vs #(Student t-test), #: LPS only treatment group.
Figure 4 is a result of an experiment on the expression of iNOS, COX2 and inflammatory cytokines (IL-1β, IL-6, TNFα) of the steam dried ginger according to an embodiment of the present invention. A: RT-PCR results, B: graphs showing numerical results of A, SG: steamed dried ginger of the present invention, each graph expressed as mean ± standard deviation, *P<0.05, **P<0.01, ** *P<0.001 vs #(Student t-test), #: Group treated with LPS only.
Figure 5 is a MAP kinase and NF-KB pathway-related factors (p-IKB, pNF-KB, p-JNK, p-p38, p-ERK, ERK, COX) of the dried ginger according to an embodiment of the present invention. -2, iNOS) expression or phosphorylation of the effect of the experiment. SG: steamed dried ginger of the present invention
6 is a result of an experiment on the effect of the change in the length of the colon in an animal model of colitis of steamed ginger according to an embodiment of the present invention. Induced control group: DSS administration group, general ginger administration group: sample administration group prepared with an extract in the same manner as in Example 2, processed ginger administration group: extract administration group of Example 2.
7 is a graph showing the results of FIG. 6 numerically. Normal: Normal group, Induced: Induced control group, General: General ginger administration group, Processing: processed ginger administration group, 6-Gingerol: 6-gingerol administration group, 6-Shogaol: 6-shogaol administration group, *** ~ ** **: It means that there is a statistically significant difference between the control groups.
8 is a result of experimentation of the effect of the steamed dried ginger according to an embodiment of the present invention on the occurrence of blood stool in an animal model of colitis. Induced control group: DSS administration group, general ginger administration group: sample administration group prepared with an extract in the same manner as in Example 2, processed ginger administration group: extract administration group of Example 2.
9 is a graph showing the numerical results of FIG. 8. Normal: Normal group, Induced: Induced control group, General: General ginger administration group, Processing: processed ginger administration group, 6-Gingerol: 6-gingerol administration group, 6-Shogaol: 6-shogaol administration group, ** ~ *** *: It means that there is a statistically significant difference between the control groups.

The present invention was conceived based on new research results supporting that the steamed dried ginger, which was performed by repeatedly steaming and drying ginger under specific conditions, can effectively prevent, treat and improve colitis.

In the present invention, ginger refers to the root of the ginger plant (Zingiber officinale).

Ginger steam-dried product, an active ingredient of the present invention, steamed whole ginger at 90 to 95°C for 3 to 5 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 20% or less. Tea steam-dried, the first steam-dried ginger was steamed at 90 to 95°C for 2 to 4 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 20% or less. The second steam-dried ginger was steamed at 90 to 95°C for 1 to 3 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 10% or less. Tea can be obtained by steam drying.

At this time, a conventional steaming device may be used for the steaming, and a conventional drying device such as a hot air dryer may be used for drying.

The steamed ginger of the present invention is more preferably obtained by using the steamed dry without a separate pretreatment other than the operation of removing water after washing whole ginger, and using whole ginger in an unpeeled state. It is preferably obtained by.

In addition, more preferably, the steaming time in the first steaming drying is 220 to 260 minutes, the steaming time in the second steaming drying is 160 to 200 minutes, and the steaming time in the third steaming drying is 100 to 140 minutes. It is preferably obtained by.

In addition, more preferably, the drying time of 88 to 92°C in the first, second and third steaming drying is 25 to 35 minutes, and the moisture of ginger when drying at 58 to 62°C in the first and second steaming drying It is preferred that the content is dried to be 18 to 20% (w/w), and dried so that the moisture content of ginger is 8 to 10% (w/w) when dried at 58 to 62° C. in the third steam drying. Do.

In the present invention, the extract of the steamed ginger can be obtained by adding a mixed solution of alcohol and water to the pulverized product of the steamed ginger and heating it at 87 to 93°C for 8 to 12 hours to extract.

In this case, the pulverized product may be obtained by pulverizing the steamed dried ginger in a conventional pulverizing device, and a conventional extraction device equipped with a heating device may be used for the extraction.

The extract of the steamed dried ginger of the present invention is more preferably a solution obtained by mixing alcohol with an alcohol content of 90 to 99% (v/v) and water in a volume ratio of 7: 2 to 7: 4 as a solvent, and 9 to 11 It is preferably obtained by time extraction.

Further, more preferably, it is an extract obtained by filtration after the extraction, or it is preferable that the extract is freeze-dried.

According to the present invention, as a result of investigating the anti-colitis effect of the steamed ginger, using a model in which DSS is administered to a mouse, which is an animal model most widely used for confirming the anti-colitis effect, Therefore, it was found that the effect of suppressing the phenomenon of shortening the colon length and the occurrence of bloody stool was very excellent. Through these research results, it was confirmed that the steamed dried ginger of the present invention is very effective in preventing, treating and improving colitis.

The composition of the present invention is preferably used for the prevention, improvement or treatment of inflammatory bowel disease among colitis, and more preferably, it is preferably used for the prevention, improvement or treatment of ulcerative colitis.

In the pharmaceutical composition of the present invention, the content of the steamed dried ginger or extract thereof of the present invention, which is an active ingredient, can be applied in various ranges depending on the use or administration method, but is usually 0.1 to 90 weight based on the total weight of the pharmaceutical composition of the present invention It may contain in %.

The pharmaceutical composition of the present invention can be administered orally or parenterally during clinical administration, and when administered parenterally, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine dural injection, cerebrovascular injection or It may be administered by intrathoracic injection, and may be used in the form of a general pharmaceutical formulation.

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

The daily dosage of the pharmaceutical composition of the present invention may be 1,000 to 2,000 mg for an adult with a body weight of 60 kg based on the steamed dried ginger of the present invention or an extract thereof contained in the composition, and may be administered once to several times a day. The range will vary depending on the weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease. The preferred daily dose of the pharmaceutical composition of the present invention calculated based on the experimental results using a mouse model is determined to be about 1,440 mg for an adult weighing 60 kg based on the steamed dried ginger of the present invention or an extract thereof contained in the composition.

In actual clinical administration, it can be administered in various parenteral formulations.In the case of formulation, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.

The pharmaceutical composition of the present invention may contain one or more active ingredients showing the same or similar function in addition to the steamed dried ginger or an extract thereof of the present invention.

The functional food composition of the present invention may be a composition mixed with a steamed dried ginger or an extract thereof of the present invention itself or a food pharmaceutically acceptable carrier based on the effective amount. Functional food composition of the present invention is processed meat products, fish products, tofu, jelly, porridge, noodles such as ramen or noodles, seasoned foods such as soy sauce, miso, red pepper paste, mixed sauce, sauces, sweets, dairy products such as fermented milk or cheese, Pickled foods such as kimchi and pickles, and beverages such as fruits, vegetables, soy milk, and fermented drinks are expected to be available. In addition, the pharmaceutically acceptable carrier may also be used as a food pharmaceutically acceptable carrier.

Hereinafter, the present invention will be described in more detail through examples. Since these examples are for illustrative purposes only, the scope of the present invention is not to be construed as being limited by these examples.

[Example]

1. Manufacture of steamed ginger dry matter

The ginger used in this example is whole ginger in a state that is not peeled, and was purchased from Wanjubongsang Ginger Association in Wanju-gun, Jeollabuk-do, and its origin is Wanju-gun. Prior to steam drying, the ginger was washed three times with clean water to remove impurities on the surface of the ginger, and then washed once additionally with distilled water and dried with a paper towel.

1-1. 1st steaming and drying

Whole ginger was put in a steamer and set at 90 to 95°C, and steamed for 4 hours (4 hours from the time it reached 90 to 95°C). Thereafter, the steamed ginger was taken out, put in a dryer set at 90°C, dried for 30 minutes, and then transferred to a dryer set at 60°C, and dried until the moisture content of the ginger reached 15 to 20% (w/w).

1-2. 2nd steaming and drying

Ginger, which had undergone the first steaming and drying step, was put into the steamer again and set to 90 to 95°C, followed by steaming for 3 hours (3 hours from the time reaching 90 to 95°C). Then, it was dried in the same manner as in the first step.

1-3. 3rd steaming and drying

Ginger, which had undergone the second steaming and drying step, was put into the steamer again and set to 90 to 95°C, followed by steaming for 2 hours (2 hours from the time reaching 90 to 95°C). Thereafter, it was dried in the same manner as in the first step, but dried until the moisture content of ginger was 5 to 10% (w/w) in a dryer set at 60°C.

In this way, a steamed dried ginger was prepared through three steaming and drying steps.

2. Extract preparation

2 kg of the steamed ginger prepared in Example 1 was put into a grinder and pulverized, and then all of the pulverized product was put into an extractor, and purified water and alcohol [alcohol content 95% (v/v)] were 30:70 by volume. 30 L of the mixed solution was added.

After circulating extraction at 90°C for 10 hours in an extractor, it was filtered through an 80-100 mesh filter, and the extract was added to a concentrator and concentrated under reduced pressure at 60°C until the sugar content of the extract reached 20 brix.

Thereafter, the concentrate was put into a freeze dryer, freeze-dried, and then pulverized into 80-100 mesh in a grinder to form powder. At this time, the yield was 26.5%.

3. Cytotoxicity assessment

The extract of Example 2 was added to the medium of RAW264.7 cells at various concentrations, cultured for 24 hours, 10 µl of CCK-8 reagent was added, and a microplate reader (Biotek, USA) was used after 2 hours. Cell viability was measured by measuring the absorption rate at 450nm wavelength.

As a control, a sample prepared as an extract from general ginger in the same manner as in Example 2 was used.

As a result, as shown in FIG. 1, the cell viability of the treated group of steamed ginger extract of the present invention was slightly lowered than that of the group treated with general ginger extract, but it was found that there was no cytotoxicity at most concentrations.

4. Evaluation of anti-inflammatory efficacy in cell models

4-1. Evaluation of inhibitory ability to produce nitrogen monoxide and PEG2

Nitrogen monoxide (NO) and PGE2 were added to the medium of RAW264.7 cells by adding LPS (0.5µg/ml) and the extract of Example 2 at various concentrations, and cultured for 24 hours, using Griess Reagent System kit and PGE2 ELISA kit. The production amount of (Prostaglandin E2) was measured.

As a control, a sample prepared as an extract from general ginger in the same manner as in Example 2 was used.

As a result, as shown in FIGS. 2 and 3, the extract of steamed ginger according to the present invention was found to significantly lower the production of nitrogen monoxide due to inflammatory reactions and significantly lower the production of PGE2 compared to general ginger.

4-2. Evaluation of the effect on the expression of iNOS, COX2 and inflammatory cytokines

The extract of Example 2 was added to the medium of RAW264.7 cells at various concentrations, cultured for 1 hour, LPS (0.5 μg/ml) was added, and cultured for 24 hours, and then iNOS, COX2, IL- through RT-PCR. The mRNA levels of 1β, IL-6, and TNFα were measured. Each result was quantified using Image J software.

As a result, as shown in FIG. 4, the extract of steamed ginger of the present invention was found to be capable of reducing the expression of iNOS, COX2 and inflammatory cytokines due to the inflammatory reaction in a concentration-dependent manner.

4-3. Assessment of effects on MAP kinase and NF-KB pathways

The extract of Example 2 was added to the medium of RAW264.7 cells at various concentrations, incubated for 1 hour, and then LPS (1 μg/ml) was added and incubated for 30 minutes, 6 hours or 12 hours, and then MAP through Western blot. Expression or phosphorylation of kinase and NF-KB pathway-related factors (p-IKB, pNF-KB, p-JNK, p-p38, p-ERK, ERK, COX-2, iNOS) were measured.

As a result, as shown in FIG. 5, the extract of steamed ginger of the present invention inhibited the expression of p-IKB and p-NF-KB in a concentration-dependent manner, whereas it was large in inhibiting the expression of p-JNK, p-p38 and p-ERK. It does not affect the expression of iNOS and COX-2, so it is thought that it exhibits anti-inflammatory effects through the NF-KB pathway, not the MAP kinase.

5. Evaluation of anti-colitis efficacy in animal models

5-1. Evaluation of the effect of changes in colon length caused by colitis induction

Experimental animals, 6-week-old female C57BL/6 mice (20±5g) were placed in cages and reared under a cycle of 23±3°C, 50±20% humidity, 12 hours light and 12 hours dark conditions. All mice were allowed to have an adaptation period for a week (DAY 0 ~ 7) before the experiment. Afterwards, standard feed was supplied to all mice, and in order to induce ulcerative colitis in the normal group and all other administration groups, DSS (Dextran Sulfate Sodium) was diluted in sterile water at a concentration of 5% for 5 days (Day 8 ~ 12). ) Was supplied. Afterwards, sterile water was supplied to all groups for 7 days for recovery (Day 13 ~ 19). The sample was orally administered at a predetermined concentration for 12 days (Day 8 ~ 19). After the animal was sacrificed, the intestine from the cecum to the anus was excised and the intestine length was measured.

The extract of Example 2 or the general ginger extract sample was administered according to the dosage as shown in Table 1.

group gender Number of animals Dosage (mg/kg) Dosing liquid volume (ml/kg) Normal



female



8 animals/group 0



10 Triggered control 0 General ginger administration group 100 100 General ginger administration group 200 200 General ginger administration group 300 300 Processed ginger administration group 100 100 Processed ginger administration group 200 200 Processed ginger administration group 300 300

* Induced control group: DSS administration group, general ginger administration group: sample administration group prepared with an extract in the same manner as in Example 2, processed ginger administration group: extract administration group of Example 2.

As a result, as shown in Table 2, Fig. 6 and Fig. 7, both the steamed dried ginger extract and the general ginger extract of the present invention did not have any significant effect at the doses of 100 mg/kg and 200 mg/kg, but steamed ginger of the present invention In the case of the dried extract, the effect of suppressing the shortening of the colon length due to the induction of colitis was excellent at a dose of 300 mg/kg.

group Average (cm) Standard deviation (cm) Normal 7.65 0.32 Triggered control 5.64 0.59 General ginger administration group 100 5.69 0.61 General ginger administration group 200 5.14 0.72 General ginger administration group 300 6.18 0.57 Processed ginger administration group 100 5.65 0.84 Processed ginger administration group 200 5.81 0.35 Processed ginger administration group 300 7.21 0.74

5-2. Evaluation of the effect on blood stool caused by colitis induction

In the same manner as in Example 5-1, the blood stool of a mouse model to which colitis induction and the sample was administered was measured.

At this time, the condition of the feces was visually checked to measure the induction and remission of colitis, and the degree of colitis symptoms was quantified by performing a fecal occult blood test using a hema-screen kit.

As a result, as shown in Table 3, FIGS. 8 and 9, the extract of steamed ginger according to the present invention was shown to have an excellent effect of inhibiting the occurrence of bloody stool caused by colitis-induced unlike general ginger extract at a dose of 300 mg/kg.

group Average (score) Deviation (score) Normal 1.50 0.53 Triggered control 3.50 0.76 General ginger administration group 100 3.38 0.52 General ginger administration group 200 3.88 0.83 General ginger administration group 300 3.63 0.74 Processed ginger administration group 100 3.38 0.74 Processed ginger administration group 200 3.50 0.53 Processed ginger administration group 300 2.25 0.46

Claims (4)

Whole ginger is steamed at 90 to 95°C for 3 to 5 hours, dried at 88 to 92°C for 20 to 40 minutes, then dried at 58 to 62°C to a moisture content of 20% or less, followed by first steam drying, and the first steam drying Steamed ginger at 90 to 95°C for 2 to 4 hours, dried at 88 to 92°C for 20 to 40 minutes, then dried at 58 to 62°C to a moisture content of 20% or less, followed by second steam drying, and the second steam drying Steamed ginger at 90 to 95°C for 1 to 3 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 10% or less, followed by a third steam drying of ginger; or
Its extract; a pharmaceutical composition for the prevention or treatment of colitis containing as an active ingredient. The method of claim 1,
The extract is a pharmaceutical composition for preventing or treating colitis, characterized in that the extract is extracted by adding a mixed solution of alcohol and water to the pulverized product of the steamed ginger and heating at 87 to 93°C for 8 to 12 hours. Whole ginger is steamed at 90 to 95°C for 3 to 5 hours, dried at 88 to 92°C for 20 to 40 minutes, then dried at 58 to 62°C to a moisture content of 20% or less, followed by first steam drying, and the first steam drying Steamed ginger at 90 to 95°C for 2 to 4 hours, dried at 88 to 92°C for 20 to 40 minutes, then dried at 58 to 62°C to a moisture content of 20% or less, followed by second steam drying, and the second steam drying Steamed ginger at 90 to 95°C for 1 to 3 hours, dried at 88 to 92°C for 20 to 40 minutes, and then dried at 58 to 62°C to a moisture content of 10% or less, followed by a third steam drying of ginger; or
Its extract; functional food composition for preventing or improving colitis containing as an active ingredient. The method of claim 3,
The extract is a functional food composition for preventing or improving colitis, characterized in that the extract is extracted by adding a mixed solution of alcohol and water to the pulverized product of the steamed ginger and heating at 87 to 93°C for 8 to 12 hours.

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