WO2022086127A1 - Composition for preventing or treating inflammatory bowel disease, containing complex herbal medicine extract - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, containing, as active ingredients, herbal medicine extracts of Coptis Rhizome, Schizonepeta tenuifolia Briquet and Ecliptae Herba or Pulsatillae Radix. In addition, the present invention relates to a food composition or feed composition for preventing or alleviating inflammatory bowel disease, containing the herbal medicine extracts as active ingredients.

Description

Composition for preventing or treating inflammatory bowel disease comprising a complex herbal extract

The present invention is hwangryeon (Coptis Rhizome); Hyeonggae ( Schizonepeta tenuifolia Briquet); And it relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a complex herbal extract of Ecliptae Herba or Pulsatillae Radix as an active ingredient. In addition, the present invention relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the complex herbal extract as an active ingredient.

This patent application claims priority to Korean Patent Application No. 10-2020-0137043 filed with the Korean Intellectual Property Office on October 21, 2020, the disclosure of which is incorporated herein by reference.

Inflammatory bowel disease is a chronic intractable disease in which chronic inflammation or ulceration occurs in the mucous membranes of the large intestine and small intestine, causing diarrhea and bloody stools, and the symptoms temporarily improve and then recur. Although inflammatory bowel disease is clinically similar, it is classified into two diseases, ulcerative colitis and Crohn's disease, which are different from each other in histological, endoscopic and immunological aspects.

Ulcerative colitis is a disease in which erosions or ulcers are continuously formed on the mucous membrane of the large intestine. systemic symptoms such as Crohn's disease is a disease in which lesions such as ulcers occur discontinuously in any part of the digestive tract from the mouth to the anus. appears.

Although the exact etiology of inflammatory bowel disease has not been fully elucidated, it is estimated that activation of inflammatory mediators and immune cells due to autoimmune diseases along with environmental or genetic factors is an important etiology. Persistent and inappropriate activation of the intestinal immune system leads to chronic mucositis inflammation, particularly mucosal destruction and ulceration by infiltration of neutrophils, macrophages, lymphocytes and mast cells.

Currently, for the treatment of inflammatory bowel disease, steroids such as glucocorticosteroids, 5-aminosalicylic acid (5-ASA) drugs such as sulfasalazine and mesalazine, TNF- Drugs that suppress excessive immune responses, such as α monoclonal antibodies, are being used, but fundamental treatment is not possible, and a cure cannot be expected. Even these drugs have various side effects reported. For example, sulfasalazine, an aminosalicylic acid product, has reported side effects such as nausea, vomiting, anorexia, rash, headache, liver damage, leukopenia, abnormal red blood cells, proteinuria, and diarrhea. There have been reports of strong side effects such as necrosis of the femoral head. Infliximab, a TNF-α monoclonal antibody, was used to treat Crohn's disease patients after it was approved by the US FDA as a treatment for Crohn's disease in 1998. is appearing Therefore, there is an urgent need to develop a new therapeutic agent for inflammatory bowel disease that is safe and has fewer side effects than the currently used inflammatory bowel disease treatment.

)(Coptis chinensis Franchet), 삼각엽황련(

)(Coptis deltoidea C. Y. Cheng et Hsiao) 또는 운련(雲連)(Coptis teeta Wallich)의 뿌리줄기로서 뿌리를 제거한 것이다. 황련은 열기를 식히고 습기를 말리는 것인 청열조습(淸熱燥濕), 화열(火熱)과 열결(熱結)을 풀어주면서 해독하는 것인 사화해독(瀉火解毒), 사화통강법(瀉火通降法)에 속하는 것으로 심(心)이나 위(胃)의 화열(火熱)을 제거(사심(瀉心))함과 동시에 번조(煩躁)한 것을 제거(제번(除煩))하는 것인 사심제번(瀉心除煩)에 효능이 있다. 또한, 온독(

), 창양열독(瘡瘍熱毒) 등의 병증에 사용하는 방법이 알려져 있고, 항미생물 작용, 혈압 강하 작용, 소염작용 등의 약리효과가 있는 것으로 알려져 있다.On the other hand, Coptis Rhizome is a herbaceous perennial plant of the Ranunculaceae family.

) ( Coptis chinensis Franchet),

) ( Coptis deltoidea CY Cheng et Hsiao) or Unryeon ( Coptis teeta Wallich), with the root removed. Yellow lily is detoxifying by detoxifying heat and heat, releasing heat and heat, and detoxification of fire. It belongs to 通降法, and it is the removal of the fire and heat of the heart or stomach (four heart) and the removal of burnt things (煩躁) at the same time. It is effective in regulating (瀉心除煩). Also, whole reading (

), is known to be used for pathologies such as Changyang fever poison (瘡瘍熱毒), and is known to have pharmacological effects such as antimicrobial action, blood pressure lowering action, and anti-inflammatory action.

Hyeonggae ( Schizonepeta tenuifolia Briquet) is an annual plant belonging to the Lamiaceae ( Labiatae ), and its above-ground part, Hyeonggae (Schizonepetae Herba) or the ear of flower (Schizonepetae Spica), is used medicinally. In oriental medicine, it is used for symptoms of chills, fever, headache and sweating due to external sensitivities. It is used when there is fever and inflammation is spreading in the early stage of Changyang, and when it is roasted black, it has a hemostatic effect on hematemesis, discoloration, nosebleeds, urine bleeding, and uterine bleeding.

Ecliptae Herba is an annual herb of the Compositae family, and is an outpost of Eclipta prostrata Linne. It is also called Aejangcho, Mokhanryun, Mukducho, and Haryuncho. Hanryeoncho is known to have the effects of hemostasis, boeum, bosin, etc., and to strengthen muscles and bones.

Paekduong (Pulsatillae Radix) is called Nogocho, and it is a dried root of a common root plant such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, which is a perennial plant belonging to Ranunculaceae . , have been reported to have antiprotozoan amoeba and antiprotozoal action, cardiotoxicity, sedative, analgesic action, and skin mucosal irritation.

However, it is not known whether the complex herbal extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong can be effectively used for the treatment of inflammatory bowel disease.

As a result of continuous research to develop a method for treating inflammatory bowel disease, the inventors of the present invention showed that when using the complex herbal extracts of H. The present invention was completed by finding an excellent therapeutic effect, particularly at a specific mixing ratio.

Therefore, an object of the present invention is hwangryeon; brother-in-law; And to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.

Another object of the present invention is hwangryeon; brother-in-law; And to provide a food composition or feed composition for the prevention or improvement of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.

Another object of the present invention is hwangryeon; brother-in-law; And to provide a method for preventing, improving or treating inflammatory bowel disease, comprising administering to a subject a pharmaceutical composition or a food composition comprising a herbal extract of orchid or baekduong as an active ingredient.

Another object of the present invention is hwangryeon; brother-in-law; And it is to provide a use for preventing, improving or treating inflammatory bowel disease of the herbal extract of orchid or baekduong.

As a result of continuous research to develop a method for treating inflammatory bowel disease, the inventors of the present invention showed that when using the complex herbal extracts of H. It is effective, and especially in a specific mixing ratio, an excellent therapeutic effect was found.

Therefore, the present invention is hwangryeon; brother-in-law; And it provides a pharmaceutical composition, food composition or feed composition for the prevention, improvement or treatment of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient, and a method for preventing, improving or treating inflammatory bowel disease using the same.

Hereinafter, the present invention will be described in more detail.

According to one aspect of the present invention, the present invention is hwangryeon; brother-in-law; And it provides a pharmaceutical composition for preventing or treating inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.

The herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.

As used herein, the term "crude herbal extract" or "composite herbal extract" refers to an active ingredient of the pharmaceutical composition of the present invention, which includes extracts of Hwangryeon lily, Hyeonggae, Orchidaceae or Baekduong, or extracts extracted from each herbal mixture. it means.

)(Coptis chinensis Franchet), 삼각엽황련(

)(Coptis deltoidea C. Y. Cheng et Hsiao) 또는 운련(雲連)(Coptis teeta Wallich)의 뿌리줄기로서 뿌리를 제거한 것을 지칭한다. "Coptis Rhizome" of the present invention refers to herbal medicines, which are perennial herbaceous plants of the Ranunculaceae , and Coptis japonica Makino, Chinese rhizome (

) ( Coptis chinensis Franchet),

) ( Coptis deltoidea CY Cheng et Hsiao) or Unryeon ( Coptis teeta Wallich) refers to a rhizome from which the root has been removed.

"Hyeonggae ( Schizonepeta tenuifolia Briquet)" of the present invention means an annual plant belonging to the Lamiaceae ( Labiatae ), and its above-ground part, Hyeonggae (Schizonepetae Herba) or ear (flower stalk), Hyeonggae (Schizonepetae Spica) include

"Ecliptae Herba" of the present invention refers to an annual grass of the Compositae family, and is an outpost of Eclipta prostrata Linne, which is also referred to as Aejangcho, Moxa chrysanthemum, Mukducho, Haryeoncho, etc. .

"Baekduong (Pulsatillae Radix)" of the present invention is called Nogocho, and refers to the dried root of a coexisting plant such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, which is a perennial plant belonging to Ranunculaceae . .

Since the extracts of Hwangryeon, Hyeonggae, Orchidaceae, and Baekduong extracts contained in the composition of the present invention are natural plant materials and have been used as food and folk medicine for a long time, the extract of the present invention extracted therefrom is also expected to have no problems such as toxicity and side effects. can do. Therefore, the extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong extract can be used in medicines, foods, feeds, and the like.

As used herein, the term "inflammatory bowel disease" refers to a disease in which inflammation occurs in the intestines, that is, the small intestine and large intestine, and includes diseases in which abnormal chronic inflammation in the intestinal tract repeats improvement and recurrence. It also includes specific enteritis with known etiology, nonspecific enteritis of unknown cause, and enteritis resulting from other diseases, such as entero-Behcet's disease, and the like.

As used herein, the term “treatment” refers to any action in which symptoms of inflammatory bowel disease are improved or cured by administration of the composition according to the present invention.

As used herein, the term “prevention” refers to any action that suppresses or delays symptoms of inflammatory bowel disease by administration of the composition according to the present invention.

As used herein, the term "comprising as an active ingredient" means including an amount sufficient to achieve the efficacy or activity of the extract of the present invention.

The pharmaceutical composition of the present invention may further include extracts of other herbal medicines known in the art to have the same or similar effects as those exhibited by the composition of the present invention.

The pharmaceutical composition of the present invention may further include an active ingredient known to have an inflammatory bowel disease treatment effect in the art. More specifically, the pharmaceutical composition is a glucocorticosteroid, such as steroids, sulfasalazine, mesalazine, such as 5-aminosalicylic acid (5-aminosalicylic acid, 5-ASA) drug, TNF It may further include one or more active ingredients selected from the group consisting of -α monoclonal antibodies.

The pharmaceutical composition of the present invention may further include an active ingredient that has an effect on diseases other than inflammatory bowel disease.

When the herbal extract of the present invention is used together with an additional active ingredient, the herbal extract and the additional active ingredient may be administered simultaneously as one formulation, or may be administered simultaneously or sequentially as separate formulations.

The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, hormone therapy, drug therapy, or a biological response modifier to treat inflammatory bowel disease.

The herbal extract used in the present invention can be obtained using a conventional extraction solvent known in the art. As the extraction solvent, a polar solvent or a non-polar solvent may be used. The polar solvent includes water, a C ₁ to C ₆ alcohol (eg, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol and n-butanol, etc.), acetic acid, or a mixture of the above polar solvents. Non-polar solvents include acetone, acetonitrile, ethyl acetate, methyl acetate, butyl acetate, fluoroalkane, hexane, ether, chloroform, dichloromethane or mixtures of the above non-polar solvents.

In one embodiment of the present invention, the herbal extract is extracted with a solvent selected from the group consisting of water, C ₁ to C ₆ alcohol, acetic acid, and a mixed solvent thereof.

In one embodiment of the present invention, the herbal extract is extracted with 0.01 to 90% ethanol. More specifically, the herbal extract is 0.01 to 90%, 1 to 90%, 10 to 90%, 20 to 90%, 30 to 90%, 40 to 90%, 50 to 90%, 60 to 90%, 0.01 to Extracted with 80%, 1-80%, 10-80%, 20-80%, 30-80%, 40-80%, 50-80% ethanol. Most specifically, the herbal extract is extracted with 60 to 80% ethanol.

In one embodiment of the present invention, the herbal extract is extracted through hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction, or a conventional extraction method known in the art.

As used herein, the term "extract" has a meaning commonly used in the art as a crude extract, but broadly includes a fraction obtained by additionally fractionating the extract. That is, the herbal extract includes not only those obtained using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographs (those prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the herbal extract of the present invention.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers are those commonly used in formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components. Suitable pharmaceutically acceptable carriers and agents are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

In one embodiment of the present invention, the pharmaceutical composition is a powder, granule, tablet, coated tablet, pill, dragee, capsule, liquid, suspension, gel, syrup, slurry, suppository, enema, emulsion, It may be formulated as pastes, ointments, creams, lotions, powders, sprays or suspensions.

In one embodiment of the present invention, the pharmaceutical composition is formulated as a solid preparation such as tablets, pills, powders, granules or capsules for oral administration or liquid preparations such as suspensions, internal solutions, emulsions or syrups. can Alternatively, the pharmaceutical composition may be formulated as a sterile aqueous solution, non-aqueous solution, suspension, emulsion, freeze-drying agent or suppository for parenteral administration.

In one embodiment of the present invention, the pharmaceutical composition may further include an appropriate carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition. For example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, mannitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and response sensitivity of the patient, An ordinarily skilled physician can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 1-100 mg/kg.

In one embodiment of the present invention, the inflammatory bowel disease is Crohn's disease, ulcerative colitis, enteric Behcet's disease, intestinal tuberculosis, hemorrhagic rectal ulcer, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis and ischemic enteritis It may be a disease selected from the group consisting of colitis, but is not limited thereto.

In one embodiment of the present invention, the herbal extract is hwangryeon; brother-in-law; And Hanryeoncho is mixed in a weight ratio of 1.5-15: 1: 0.1-15. More specifically, the herbal extract is Hwangryeon; brother-in-law; and chrysanthemum 1.5-10: 1: 0.1-15, 1.5-7.5: 1: 0.1-15, 1.5-15: 1: 0.1-10, 1.5-10: 1: 0.1-10, 1.5-7.5: 1: 0.1 -10, 1.5-7 : 1 : 0.1-10, 1.5-5 : 1 : 0.1-10, 1.5-4 : 1 : 0.1-10, 1.5-3.5 : 1 : 0.1-10, 1.5-3 : 1 : 0.1 -10, 2-7 : 1 : 0.1-10, 2-5 : 1 : 0.1-10, 2-4 : 1 : 0.1-10, 2-3.5 : 1 : 0.1-10, 2-3 : 1 : 0.1 -10, 1.5-7.5 : 1 : 0.1-8, 1.5-7.5 : 1 : 0.1-6, 1.5-7.5 : 1 : 0.1-4, 1.5-7.5 : 1 : 0.1-3, 1.5-7.5 : 1 : 0.1 -2, 1.5-7.5 : 1 : 0.1-1, 1.5-7.5 : 1 : 0.1-0.8, 1.5-7.5 : 1 : 0.1-0.5, 1.5-7.5 : 1 : 0.1-0.4, 2-7 : 1 : 0.1 -8, 2-7 : 1 : 0.1-6, 2-7 : 1 : 0.1-5, 2-7 : 1 : 0.1-4, 2-7 : 1 : 0.1-3, 2-7 : 1 : 0.1 -2, 2-7: 1: 0.1-1, 2-7: 1: 0.1-0.8, 2-7: 1: 0.1-0.5, 2-7: 1: 0.1-0.4, 2-3: 1: 0.1 -8, 2-3 : 1 : 0.1-6, 2-3 : 1 : 0.1-5, 2-3 : 1 : 0.1-4, 2-3 : 1 : 0.1-3, 2-3 : 1 : 0.1 -2, 2-3: 1: 0.1-1, 2-3: 1: 0.1-0.8, 2-3: 1: 0.1-0.5, or 2-3: 1: 0.1-0.4 by weight.

According to an embodiment of the present invention, the herbal extract is Hwangryeon; brother-in-law; And Hanryeonchoga 2-3: 1: weight ratio of 0.2-0.4, more specifically, the herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho, when mixed in a weight ratio of 2.5: 1: 0.3 (15: 6: 2) shows the most excellent effect.

In one embodiment of the present invention, the herbal extract is hwangryeon; brother-in-law; And Baekduong 1.5-15: 1: It is mixed in a weight ratio of 0.1-15. More specifically, the herbal extract is Hwangryeon; brother-in-law; and Whitehead 1.5-15: 1: 0.1-10, 1.5-15: 1: 0.1-5, 1.5-15: 1: 0.1-2, 1.5-10: 1: 0.1-2, 1.5-9: 1: 0.1 -2, 1.5-7 : 1 :0.1-2, 1.5-5 : 1 : 0.1-2, 1.5-3 : 1 : 0.1-2, 2-10 : 1 : 0.1-2, 2-9 : 1 : 0.1 -2, 2-7: 1: 0.1-2, 2-5: 1: 0.1-2, 2-3: 1: 0.1-2, 1.5-15: 1: 0.1-1.5, 1.5-15: 1: 0.1 -1, 1.5-15: 1: 0.1-0.9, 1.5-15: 1: 0.1-0.7, 1.5-15: 1: 0.1-0.5, 1.5-15: 1: 0.1-0.3, 1.5-10: 1: 0.1 -0.9, 1.5-9: 1: 0.1-0.9, 1.5-7: 1: 0.1-0.9, 1.5-5: 1: 0.1-0.9, 1.5-3: 1: 0.1-0.9, 2-10: 1: 0.1 -0.9, 2-9: 1: 0.1-0.9, 2-7: 1: 0.1-0.9, 2-5: 1: 0.1-0.9, 2-3: 1: 0.1-0.9, 1.5-10: 1: 0.1 -0.5, 1.5-9: 1: 0.1-0.5, 1.5-7: 1: 0.1-0.5, 1.5-5: 1: 0.1-0.5, 1.5-3: 1: 0.1-0.5, 2-10: 1: 0.1 -0.5, 2-9: 1: 0.1-0.5, 2-7: 1: 0.1-0.5, 2-5: 1: 0.1-0.5, 2-3: 1: 0.1-0.5, 1.5-10: 1: 0.1 -0.3, 1.5-9: 1: 0.1-0.3, 1.5-7: 1: 0.1-0.3, 1.5-5: 1: 0.1-0.3, 1.5-3: 1: 0.1-0.3, 2-10: 1: 0.1 -0.3, 2-9: 1: 0.1-0.3, 2-7: 1: 0.1-0.3, 2-5: 1: 0.1-0.3, 1.5-3.5: 1: 0.1-0.3 or 2-3: 1: It is mixed in a weight ratio of 0.1-0.3.

According to an embodiment of the present invention, the herbal extract is Hwangryeon; brother-in-law; And Baekduonggi 2-3: 1: 0.1-0.3 weight ratio, more specifically, the herbal extract is Hwangryeon; brother-in-law; And when Baekduong is mixed in a weight ratio of 2.5: 1: 0.2, the best effect is exhibited.

According to another aspect of the present invention, the present invention is hwangryeon; brother-in-law; And it provides a food composition for preventing or improving inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.

The herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.

As used herein, the term “improvement” refers to any action of reducing a parameter related to a condition to be treated by administration of a composition comprising the extract of the present invention, for example, the severity of symptoms.

The food composition of the present invention may be prepared in the form of powder, granules, tablets, capsules or beverages. For example, there are various foods such as candy, drinks, gum, tea, vitamin complexes, or health supplements.

The food composition of the present invention includes health functional food and health food.

The food composition of the present invention can be taken for a long time.

The food composition of the present invention may include components commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink, citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, licorice root extract, jujube extract, licorice extract, etc. may include

According to another aspect of the present invention, the present invention is hwangryeon; brother-in-law; And it provides a feed composition for preventing or improving inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.

The herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.

Since the contents of extracts of Hwangryeon, hyunggae, chrysanthemum, and baekduong contained in the food composition and feed composition of the present invention are the same as those related to the extraction of the mixed extract contained in the pharmaceutical composition, the content common between the two is In order to avoid excessive complexity of the present specification, description thereof is omitted.

The pharmaceutical composition comprising the mixed herbal extract of the present invention as an active ingredient exhibits excellent therapeutic effects in inflammatory bowel disease, particularly Crohn's disease or ulcerative colitis, and can be used as a novel therapeutic agent.

In addition, the pharmaceutical composition of the present invention can be used as a safe therapeutic agent by reducing the side effects of existing therapeutic agents by including a natural product as an active ingredient.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Example

Throughout this specification, "%" used to indicate the concentration of a specific substance is (weight/weight) % for solid/solid, (weight/volume) % for solid/liquid, and Liquid/liquid is (volume/volume) %.

manufacturing example. Preparation of mixed herbal extracts

Washed and dried Coptis Rhizome, Hyeonggae (Schizonepetae Spica and Schizonepetae Herba), Ecliptae Herba, and Pulsatillae Radix were used in the experiment. After mixing the herbal medicines of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong individually or at the weight ratio (w/w) shown in Table 1 below, 10 times 70% (v/v) aqueous ethanol solution was added and stirred at room temperature for 72 hours. An extract was obtained. Thereafter, each extract was filtered, concentrated under reduced pressure at 50 to 65° C., and freeze-dried to obtain a single herbal extract in a powder state.

division goldthread Hyunggae nasturtium Baek Duong Comparative Example 1 One 0 0 0 Comparative Example 2 0 One 0 0 Comparative Example 3 0 0 One 0 Comparative Example 4 0 0 0 One Preparation 1-1 1.5 One 0.1 0 Preparation 1-2 15 (2.5) 6(1) 2 (0.3) 0 Preparation 1-3 5 One One 0 Preparation Example 1-4 7.5 One 5 0 Preparation 1-5 10 One One 0 Preparation 1-6 15 One 15 0 Comparative Example 5 20 One 15 0 Comparative Example 6 15 One 20 0 Preparation 2-1 1.5 One 0 0.1 Preparation 2-2 2 One 0 1.5 Preparation 2-3 2.5 One 0 0.2 Preparation 2-4 7.5 One 0 0.6 Preparation 2-5 7.5 One 0 2 Preparation Example 2-6 10 One 0 One Preparation 2-7 10 One 0 2 Preparation 2-8 12.5 One 0 One Preparation Example 2-9 15 One 0 One Preparation Example 2-10 15 One 0 2 Comparative Example 7 20 One 0 2

Experimental Example 1. Therapeutic efficacy of mixed herbal extracts in DSS-induced inflammatory bowel disease model

In this example, the efficacy of the mixed herbal extract on inflammatory bowel disease, in particular, ulcerative colitis was confirmed. The DSS-induced inflammatory bowel disease model is known to exhibit morphological changes and symptoms similar to those of human ulcerative colitis. Accordingly, after 8-week-old male mice (C57BL/6) were acclimatized for more than a week, Dextran Sulfate Sodium (DSS; 36,000-50,000 MW, MP Biomedicals, USA) was administered to induce ulcerative colitis. The normal group, the control group and the experimental group were set up as follows to conduct the experiment:

-Normal group: group administered with distilled water only

- (negative) control group: group administered with DSS and distilled water

- Experimental group: group administered with DSS and single herbal extracts or mixed herbal extracts (Hwangryeon, Hyeonggae, Hanryeoncho, and/or Baekduong)

1-1. DAI Assessment

Bowel disease is usually evaluated through clinical symptoms such as weight loss, diarrhea, and bloody stools. The disease activity index (DAI) is a method of analyzing the degree of intestinal disease by measuring weight loss rate, stool condition, and bleeding and assigning a score to each.

Therefore, in this Example, the normal group, the control group, and the experimental group were compared by analyzing the DAI by measuring the weight loss rate, stool status, and bleeding.

The DSS feeding method of the control group and the experimental group was prepared by diluting DSS in negative water to 2.5%, then feeding 100 mL of the DSS to the mice and replacing them every 2 days, DSS was fed for a total of 5 days.

After the start of the experiment, the weight of the mice in each group was measured and calculated as the weight loss rate, and the condition of stool and the presence or absence of bloody stool were checked. For the above three indices, scores were calculated according to the criteria in Table 2 below.

score weight loss rate stool condition bleeding 0 < 1% normal normal One 1-5% - - 2 5-10% loose stools that do not stick around the anus slight bleeding 3 10-15% - - 4 >15% diarrhea that sticks around the anus visible bleeding

1-2. DAI evaluation of the group treated with mixed herbal extracts (Hwangryeon, Hyeonggae, Hanryeoncho)

The normal group was orally administered 0.4 mL of distilled water once/day for 10 days from the start of the experiment.

For the (negative) control group, 0.4 mL of distilled water was orally administered once/day for 10 days from the start date of the experiment.

The experimental group was administered 50 mg/kg of the single and mixed herbal extracts prepared in Preparation Example, and was orally administered once/day for 10 days from the start date of the experiment.

The sum calculated based on the score calculation in Table 2 is shown in Table 3 below as the Disease Activity Index (DAI).

No. Target (weight ratio) Day 10 weight change (%) Day 10 DAI Values normal group 10.10 0 (voice) control group -18.60 5 Comparative Example 1 goldthread -17.40 4.8 Comparative Example 2 Hyunggae -21.50 4.4 Comparative Example 3 nasturtium -24.30 4.2 Preparation 1-2 Yellow lily + hyunggae + chrysanthemum
(15:6:2) -14.03 3.8 Preparation 1-5 Yellow lily + hyunggae + chrysanthemum
(10:1:1) -14.41 3.8

As can be seen in Table 3 above, the mixed herbal extract group of Hwangryeon, Hyeonggae, and Orchid liana of the present invention showed a lower DAI value and less weight change compared to the (negative) control group and the single herbal extract group (Comparative Examples 1 to 3). it was In particular, the mixed herbal extract group of Preparation Example 1-2 (Hwangryeon: Hyeonggae: Hanryeoncho=15:6:2) showed the smallest change in body weight.

1-3. DAI evaluation of the group treated with mixed herbal extracts (Hwangryeon, Hyeonggae, Baekduong)

The normal group was orally administered 0.4 mL of distilled water once/day for 10 days from the start of the experiment.

For the (negative) control group, 0.4 mL of distilled water was orally administered once/day for 10 days from the start date of the experiment.

The experimental group was administered 50 mg/kg of the single and mixed herbal extracts prepared in Preparation Example, and was orally administered once/day for 10 days from the start date of the experiment.

The sum calculated based on the score calculation in Table 2 is shown in Table 4 below as the Disease Activity Index (DAI).

No. Target (weight ratio) Day 10 weight change (%) Day 8 DAI Values Day 10 DAI Values normal group 10.10 0 0 negative control -18.60 7.4 5 Comparative Example 1 goldthread -17.40 3.6 4.8 Comparative Example 2 Hyunggae -21.50 4 4.4 Comparative Example 4 Baek Duong -27.90 7.4 5.6 Preparation 2-3 Hwangryeon + Hyeonggae + Baekduong
(2.5:1:0.2) -10.81 2 2.6 Preparation 2-4 Hwangryeon + Hyeonggae + Baekduong
(7.5:1:0.6) -17.07 3 3.6 Preparation 2-5 Hwangryeon + Hyeonggae + Baekduong
(7.5:1:2) -15.20 4 4 Preparation Example 2-6 Hwangryeon + Hyunggae + Baekduong
(10:1:1) -11.46 3.2 3

As can be seen in Table 4 above, the mixed herbal extract group of Hwangryeon, Hyeonggae and Baekduong of the present invention has a lower DAI value and less weight change compared to the (negative) control group and the single herbal extract group (Comparative Examples 1, 2 and 4). was shown. In particular, the mixed herbal extract group of Preparation Example 2-3 (Hwangryeon:Hyunggae:Baekduong=2.5:1:0.2) showed the lowest DAI value and little change in body weight.

Experimental Example 2. Inhibitory efficacy of mixed herbal extracts measured through NO assay (Griess assay)

To compare the anti-inflammatory efficacy of single and mixed herbal extracts, changes in nitric oxide (NO) content in RAW264.7 cells, a rat macrophage cell line, were measured using Griess assay.

2-1. NO assay (Griess assay)

RAW264.7 cells were cultured in RPMI medium (Corning, USA) containing fetal bovine serum (Fetal Bovine Serum, FBS, Gibco ^TM , USA) and antibiotics (1% Penicillin, Streptomycin [P/S] Gibco-BRL, USA). cultured under Specifically, the incubator was maintained at a temperature of 37° C., and a gas mixed with 95% air and 5% CO ₂ was continuously supplied so that appropriate conditions for cell culture were prepared. Cells were cultured 24 hours before the experiment so as to become 5x10 ⁴ cells/well in a 24-well plate.

2-2. NO evaluation of the group treated with mixed herbal extracts (Hwangryeon, Hyeonggae, Hanryeoncho)

The (negative) control group and the LPS-treated group were pretreated with the cell culture solution for one hour after removing the supernatant of the prepared 24-well plate.

After removing the supernatant of the prepared 24-well plate, the experimental group was pre-treated with the single and complex herbal extracts prepared in Preparation Example for one hour. In the first experiment (1 ^st ), each of the extracts was pretreated at a concentration of 10 μg/ml, and in the second experiment (2 ^nd ), each of the extracts was pretreated at a concentration of 20 μg/ml.

Thereafter, the (negative) control group was treated with the cell culture solution, and the LPS-treated group and the experimental group were treated with LPS at a concentration of 100 ng/ml for 24 hours. Thereafter, the supernatant was taken and the change in the nitric oxide content was evaluated by measuring the absorbance at 520 and 550 nm wavelength values through the Griess assay kit (G2930, Promega, USA). It was measured twice in the same way, and the results are shown in Table 5.

No. Target (weight ratio) Average Standard Deviation 1 ^{st 2nd} 1 ^{st 2nd} (voice) control group 1.28 0.00 0.39 0.00 LPS treatment group 4.31 12.52 0.59 0.15 Comparative Example 1 goldthread 3.90 6.89 0.54 1.02 Comparative Example 2 Hyunggae 3.81 5.69 1.54 0.82 Comparative Example 3 nasturtium 2.98 8.19 0.93 0.55 Preparation 1-1 Yellow lily + hyunggae + chrysanthemum
(1.5 : 1 : 0.1) 2.17 - 0.54 - Preparation 1-2 Yellow lily + hyunggae + chrysanthemum
(15:6:2) 2.09 - 0.30 - Preparation 1-3 Yellow lily + hyunggae + chrysanthemum
(5:1:1) 2.27 - 0.63 - Preparation Example 1-4 Yellow lily + hyunggae + chrysanthemum
(7.5:1:5) 2.78 - 1.04 - Preparation 1-6 Yellow lily + hyunggae + chrysanthemum
(15:1:15) 2.51 - 0.52 - Comparative Example 5 Hangryeon + Hyeonggae + Hanryeoncho
(20:1:15) - 8.05 - 1.30 Comparative Example 6 Yellow lily + hyunggae + chrysanthemum
(15:1:20) - 7.49 - 1.30

As can be seen in Table 5, the mixed herbal extract group of Hwangryeon, Hyeonggae, and Orchid liana of the present invention exhibited lower NO-producing ability compared to the LPS-treated group and the single herbal extract group (Comparative Examples 1 to 3). In particular, the mixed herbal extract group of Preparation Example 1-2 (Hwangryeon: Hyeonggae: Hanryeoncho=15:6:2) showed the lowest NO-producing ability.

2-3. Evaluation of NO content in the group treated with mixed herbal extracts (Hwangryeon, Hyeonggae, Baekduong)

The (negative) control group and the LPS-treated group were pretreated with the cell culture solution for one hour after removing the supernatant of the prepared 24-well plate.

After removing the supernatant of the prepared 24-well plate, the experimental group was pre-treated with the single and complex herbal extracts prepared in Preparation Example for one hour. In the first (1 ^st ) and second (2 ^nd ) experiments, the extracts were pretreated at a concentration of 10 μg/ml, respectively, and in the third (3 ^rd ) experiment, the extracts were pretreated at a concentration of 20 μg/ml, respectively.

Thereafter, the (negative) control group was treated with the cell culture solution, and the LPS-treated group and the experimental group were treated with LPS at a concentration of 100 ng/ml for 24 hours. Thereafter, the supernatant was taken and the change in the nitric oxide content was evaluated by measuring the absorbance at 520 and 550 nm wavelength values through the Griess assay kit (G2930, Promega, USA). It was measured three times in the same way, and the results are shown in Table 6.

No. Target (weight ratio) Average Standard Deviation 1 ^{st 2nd 3rd} 1 ^{st 2nd 3rd} (voice) control group -0.015 1.28 0.00 0.29 0.39 0.00 LPS treatment group 5.92 4.31 12.52 0.32 0.59 0.15 Comparative Example 1 goldthread 2.70 3.90 6.89 0.22 0.54 1.02 Comparative Example 2 Hyunggae 4.47 3.81 5.69 0.21 1.54 0.82 Comparative Example 4 Baek Duong 4.75 3.01 4.45 0.25 0.61 0.41 Preparation 2-1 Hwangryeon + Hyeonggae + Baekduong
(1.5 : 1 : 0.1) - 2.48 - - 0.96 - Preparation 2-2 Hwangryeon + Hyeonggae + Baekduong
(2:1:1.5) - 2.79 - - 0.97 - Preparation 2-3 Hwangryeon + Hyeonggae + Baekduong
(2.5:1:0.2) 1.47 - - 0.14 - - Preparation Example 2-6 Hwangryeon + Hyeonggae + Baekduong
(10:1:1) 1.22 - - 0.11 - - Preparation 2-7 Hwangryeon + Hyeonggae + Baekduong
(10:1:2) - 2.51 - - 0.95 - Preparation 2-8 Hwangryeon + Hyeonggae + Baekduong
(12.5:1:1) 1.24 - - 0.09 - - Preparation Example 2-9 Hwangryeon + Hyeonggae + Baekduong
(15:1:1) 1.09 - - 0.26 - - Preparation Example 2-10 Hwangryeon + Hyeonggae + Baekduong
(15:1:2) - 2.31 - - 0.78 - Comparative Example 7 Hwangryeon + Hyeonggae + Baekduong
(20:1:2) - - 8.05 - - 1.38

As can be seen in Table 6, the mixed herbal extract group of Hwangryeon, Hyeonggae and Baekduong of the present invention exhibited lower NO-producing ability compared to the LPS-treated group and the single herbal extract group (Comparative Examples 1, 2 and 4).

sintering

In the group administered by mixing the herbal extracts of Hwangryeon and Hyeonggae extracts with Baekduong or Hanryeoncho extract, in particular, a weight ratio of 15(2.5): 6(1): 2(0.3) (H. It was confirmed that the extracts mixed with Hwangryeon, Hyeonggae and Baekduong) had an excellent therapeutic effect on inflammatory bowel disease.

Hereinafter, a formulation example of a composition containing the extract of the present invention will be described, but the present invention is not intended to limit the present invention, but to describe it in detail.

Formulation example

Formulation Example 1. Preparation of powder

Yellow lily of the manufacture example; brother-in-law; and 500 mg of mixed extract of baekduong or chrysanthemum

Lactose 100 mg

talc 10 mg

The above ingredients are mixed and filled in an airtight bag to prepare a powder.

Formulation Example 2. Preparation of tablets

Yellow lily of the manufacture example; brother-in-law; and 300 mg of baekduong or chrysanthemum mixed extract

100 mg cornstarch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet manufacturing method.

Formulation Example 3. Preparation of capsules

Yellow lily of the manufacture example; brother-in-law; and 200 mg of baekduong or chrysanthemum mixed extract

3 mg of crystalline cellulose

Lactose 14.8 mg

0.2 mg magnesium stearate

According to a conventional capsule preparation method, the above ingredients are mixed and filled in a gelatin capsule to prepare a capsule.

Formulation Example 4. Preparation of liquid formulation

Yellow lily of the manufacture example; brother-in-law; and 4 g of mixed extract of baekduong or chrysanthemum

10 g isomerized sugar

5 g of mannitol

Purified water appropriate amount

According to a conventional liquid preparation method, each component is added to purified water to dissolve it, an appropriate amount of lemon flavor is added, the above components are mixed, purified water is added, and purified water is added to the total amount to be adjusted to 100 ml, and then filled in a brown bottle. Sterilize to prepare a solution.

Formulation Example 5. Preparation of health food

Yellow lily of the manufacture example; brother-in-law; and 1,000 mg of mixed extract of baekduong or chrysanthemum

appropriate amount of vitamin mixture

70 μg vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture appropriate amount

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

The composition ratio of the above vitamin and mineral mixture is a composition that is relatively suitable for health food in a preferred embodiment, but the mixing ratio may be arbitrarily modified. , to prepare granules, and can be used for preparing health food compositions according to a conventional method.

Formulation Example 6. Preparation of health drinks

Yellow lily of the manufacture example; brother-in-law; and 1,000 mg of mixed extract of baekduong or chrysanthemum

citric acid 1,000 mg

100 g of oligosaccharides

2 g of plum concentrate

1 g taurine

Total 900 ml by adding purified water

After mixing the above ingredients according to the usual health drink manufacturing method, after stirring and heating at 85 ° C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, then refrigerated. It is used to prepare the health drink composition of the invention.

Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use.

The present invention is hwangryeon (Coptis Rhizome); Hyeonggae ( Schizonepeta tenuifolia Briquet); And it relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a complex herbal extract of Ecliptae Herba or Pulsatillae Radix as an active ingredient. In addition, the present invention relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the complex herbal extract as an active ingredient.

Claims (9)

goldthread; brother-in-law; And in the pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient, The herbal extract is Hwangryeon; brother-in-law; And Orchid or baekduong 1.5-15: 1: 0.1-15 of a weight ratio of 0.1-15 is mixed, a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease. The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is extracted with a solvent selected from the group consisting of water, C ₁ to C ₆ alcohol, acetic acid, and mixed solvents thereof. . The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is 0.01% to 90% ethanol extract. The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is a 60% to 80% ethanol extract. According to claim 1, wherein the inflammatory bowel disease is Crohn's disease, ulcerative colitis, enteric Behcet's disease, intestinal tuberculosis, hemorrhagic rectal ulcer, indeterminate colitis (indeterminate colitis), bacterial enteritis, viral enteritis, amoebic enteritis and ischemic colitis consisting of A pharmaceutical composition for preventing or treating inflammatory bowel disease, which is a disease selected from the group. The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis. The method of claim 1, wherein the herbal extract is Hwangryeon; brother-in-law; And Baekduong 1.5-15: 1: 0.1-2 will be mixed in a weight ratio, a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease. goldthread; brother-in-law; And in the food composition for the prevention or improvement of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient, The herbal extract is Hwangryeon; brother-in-law; And Orchids or baekduong 1.5-15: 1: 0.1-15 of a weight ratio of 0.1-15, the food composition for the prevention or improvement of inflammatory bowel disease. goldthread; brother-in-law; And in the feed composition for preventing or improving inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient, The herbal extract is Hwangryeon; brother-in-law; And orchid or baekduong is 1.5-15: 1: 0.1-15 is mixed in a weight ratio of, a feed composition for preventing or improving inflammatory bowel disease.