JP2011148710A - Prophylactic and/or therapeutic agent for inflammatory bowel disease and/or irritable bowel syndrome - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a prophylactic and/or therapeutic agent for inflammatory bowel diseases and/or irritable bowel syndrome that is daily ingestible and highly safe even when ingested over a long period of time unlike pharmacotherapy or nutritional therapy liable to accompany with a side effect, and a food and drink and fodder each containing the prophylactic and/or therapeutic agent for inflammatory bowel diseases and/or irritable bowel syndrome. <P>SOLUTION: The prophylactic and/or therapeutic agent for inflammatory bowel diseases and/or irritable bowel syndrome contains cheese as an effective ingredient. The food and drink and the fodder each contains the prophylactic and/or therapeutic agent for inflammatory bowel diseases and/or irritable bowel syndrome. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention contains a prophylactic and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome, a prophylactic and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome, comprising cheese as an active ingredient. It relates to food and drink and feed. Since the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome of the present invention can prevent and / or treat inflammatory bowel disease by ingesting it, Crohn's disease and ulcerative Prevents and treats inflammatory bowel diseases such as colitis and intestinal Behcet's disease, and various symptoms such as bloody stool, melena, abdominal pain, anemia, leukocyte increase, fever, weight loss and loss of appetite associated with these diseases Or can be in remission. Furthermore, according to the present invention, irritable bowel syndrome can be prevented, and any symptoms such as constipation, diarrhea, gas, abdominal pain and mucus excretion associated with these diseases can be prevented, treated or ameliorated.

Inflammatory bowel disease (IBD) is a chronic disease that causes inflammation of the gastrointestinal tract and ulcerative colitis (UC)
Crohn's disease (CD) is a representative example. It is a disease that has been designated as a specific disease (intractable disease) in Japan, and is a disease that is refractory and has a prolonged disease that is difficult to treat clinically. Although the number of patients in Japan was small compared to the West, it is now rapidly increasing to over 100,000. For UC and CD, no fundamental treatment method has been established, and nutritional therapy (complete parenteral nutrition, enteral nutrition, diet) and drug therapy (sulfasalazine, S-ASA (mesalazine) Sulfa drugs, steroid drugs centered on prednisolone, immunosuppressive drugs such as azathioprine, 6-MP, etc. are used stepwise depending on the disease stage). UC and CD have different treatment methods, UC is pharmacotherapy, and CD is nutrition therapy. On the other hand, in severe cases such as resistance to medical treatment, bleeding, and the possibility of canceration, surgical treatment is performed, but the application rate is 10% of all patients even with UC alone. Up to 15%.
Behcet's disease has a smaller number of patients than UC and CD, but is refractory and is treated with the same pharmacotherapy, nutritional therapy and surgical treatment as UC and CD. In addition, most IBD can be treated medically, and depending on the symptoms, drug therapy (antibacterial administration) and nutritional therapy (fasting, dietary restriction, ingredient nutrition, high calorie infusion), etc. Has been done.
Irritable bowel syndrome is a disease with chronic abdominal pain or fecal abnormalities such as abdominal discomfort and diarrhea. In addition to social stress and mental anxiety, the cause of the disease is also known to develop after inflammation due to gastrointestinal infection, and many patients have irritable bowel syndrome and IBD. As for the treatment of irritable bowel syndrome, psychological stress is controlled, and step-by-step pharmacological treatments are performed according to symptoms from intestinal and laxatives to antipsychotics.

  On the other hand, cheese is a food that human beings have eaten on a daily basis since ancient times, and it can be said that there is no problem with safety, but recently, the health function of cheese has attracted attention. Effects of promoting the reduction of blood triglyceride concentration by ingesting cheese and improving cholesterol metabolism have been reported (Patent Documents 1 and 2). Furthermore, it has been invented that the components contained in cheese have a visceral fat accumulation-inhibiting action, which is expected as a preventive / therapeutic agent for metabolic syndrome (Patent Document 3). In addition, a preventive or therapeutic agent for gastrointestinal ulcer comprising a cheese enzyme degradation product as an active ingredient is disclosed (Patent Document 4).

Japanese Patent Laid-Open No. 2003-300890 Japanese Patent Laid-Open No. 2003-144090 JP 2007-223926 JP 2009-120519 JP

As problems of pharmacotherapy, allergic reactions caused by sulfa drugs, cataracts caused by long-term use of steroids, osteoporosis, impaired glucose tolerance, susceptibility to infection, leukopenia caused by immunosuppressants, hair loss, and hyperamylaseemia have been pointed out. In addition, liver damage caused by antipsychotic drugs and skin rashes are known. Also in nutritional therapy, the transition of enteric pathogens into the blood due to intestinal mucosal atrophy due to long-term use is regarded as a problem in complete parenteral nutrition and enteral nutrition therapy.
Thus, current drug therapy and nutritional therapy involve side effects and require prescription. Therefore, for the treatment and prevention of inflammatory bowel disease (IBD) and / or irritable bowel syndrome, treatment of IBD and / or irritable bowel syndrome that can be taken on a daily basis and is safe even if taken for a long time.・ An ingredient effective for prevention is desired.

On the other hand, Patent Documents 1 to 3 do not disclose anything about the effects of cheese itself on the prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome.
Patent Document 4 is a cheese enzyme degradation product (EMC) used as an antihypertensive agent and a peptide found from EMC as a new use as a gastrointestinal ulcer preventive agent. Moreover, in order to produce | generate an active ingredient, it is necessary to process cheese with protease derived from microorganisms, and what was used as a comparison which confirms the effect of EMC is only undegraded Danish skim cheese. Cheese is a complex containing a wide variety of ingredients, and it is by no means the main component of peptides and amino acids that are produced by protein degradation by proteases. In other words, it is a complex that contains substances that are further converted from peptides and amino acids, lipid / fatty acid degradation products / metabolites, vitamins, minerals, lactic acid bacteria, lactic acid bacteria metabolites, and unexplained components. . Therefore, it is considered that these multiple components are also involved in the prevention and / or treatment effects of inflammatory bowel disease and / or irritable bowel syndrome, but such effects are verified using cheese itself. There is no example.
Therefore, the present invention is useful for the suppression of inflammatory bowel disease by ingesting this, and is also an inflammatory bowel disease and / or irritable bowel syndrome comprising cheese which can be taken daily It is an object of the present invention to provide a preventive and / or therapeutic agent.

In view of whether various abnormalities of the living body can be prevented or improved by food materials that can be ingested on a daily basis, the present inventors have focused on cheese and confirmed its physiological function. We found an action to improve / suppress disease symptoms. And it discovered that inflammatory bowel disease was suppressed by providing the preventive and / or therapeutic agent of inflammatory bowel disease using these physiological functions, and came to complete this invention. That is, the problem is solved by providing a preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome using cheese as an active ingredient, utilizing the action of cheese to suppress inflammatory bowel disease. I was able to.
In addition, cheese is a food that has been eaten since ancient times, and it can be said that there is no problem with safety even if it is taken daily, but the consumption of cheese in Japan is about 5 to 6 g per day Few.

Accordingly, the present invention is an invention having any of the following configurations.
(1) A preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome comprising cheese as an active ingredient.
(2) A food and drink containing the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome according to (1).
(3) A feed containing the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome according to (1).

  The preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome comprising the cheese of the present invention as an active ingredient suppresses inflammatory bowel disease by ingesting these, thereby causing Crohn's disease and ulcerative Prevents and treats inflammatory bowel diseases such as colitis and intestinal Behcet's disease, and various symptoms such as bloody stool, melena, abdominal pain, anemia, leukocytosis, fever, weight loss and loss of appetite associated with these diseases It is effective for. Furthermore, according to the present invention, irritable bowel syndrome is prevented, and constipation, diarrhea, gas, abdominal pain and mucus excretion associated with these diseases are effective in preventing and treating various symptoms.

The rate of weight change of colitis model mice induced by DSS (dextran sodium sulfate) is shown. The amount of food intake of DSS-induced colitis model mice is shown. The result of having scored the stool property of the colitis model mouse induced by DSS is shown. The result of having scored the state of the bloody stool of the colitis model mouse induced by DSS is shown. The result of integrating | accumulating the weight change rate of the colitis model mouse induced by DSS, the characteristic of stool, and the score of the state of bloody stool is shown. The colon length of the DSS-induced colitis model mouse is shown.

  The cheese that can be used in the present invention is a cheese that is usually eaten, for example, gouda cheese, cheddar cheese, emmental cheese, edam cheese, camembert, stilton cheese, blue cheese, natural cheese, or these natural cheeses. Processed cheese processed as a raw material, these cheeses themselves can be used, or after suspending cheese in a solvent, degreasing, insoluble material removal, protein removal, etc. Can also be used. Moreover, the fraction which refine | purified these fractions by various chromatography, such as a dialysis membrane, gel filtration, and ion exchange, can also be used. These fractions can also be used after being concentrated or dried. Moreover, it can also be used in powder form.

  The preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome of the present invention prevents inflammatory bowel diseases such as Crohn's disease, ulcerative colitis, and intestinal Behcet's disease, and accompanies these diseases Symptoms such as bloody stool, melena, abdominal pain, anemia, leukocytosis, fever, weight loss and anorexia can be prevented, treated or ameliorated. Furthermore, irritable bowel syndrome can be prevented, and symptoms such as constipation, diarrhea, gas, abdominal pain and mucus excretion associated with these diseases can be prevented, treated or ameliorated.

As a dosage form of a preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome, a stabilizer, an excipient, a binder, a disintegrant, a lubricant, a flavoring agent, a suspending agent for cheese Examples thereof include tablets, capsules, granules, powders, powders, syrups and the like, which are mixed with coating agents and other arbitrary drugs. These can be administered orally.
In addition, as a mixture with cheese itself or other food materials, or foods and beverages in which cheese is blended with bread, snack confectionery, cakes, puddings, beverages, fermented milk, noodles, sausages, various milk powders, baby foods, etc. .

Since the prophylactic and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome can be achieved by orally administering a prophylactic and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome It can also be used as a food, drink, or feed for prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome. As a form of food and drink for the prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome, what kind of form does not interfere with the prevention and / or treatment action of inflammatory bowel disease and / or irritable bowel syndrome? It may be anything, it may be cheese, used as bread, snacks, cakes, puddings, beverages, fermented milk, noodles, sausages and other foods and drinks, as well as various types of powdered milk, infant food, nutrition It can also be blended in compositions, feeds and the like.

In addition, the dose of the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome of the present invention may be appropriately determined in consideration of the purpose of treatment and prevention, symptoms, weight, age, sex, etc. Usually, it is desirable to be able to ingest about 20 to 200 g of cheese itself.
When using a fraction that has been defatted, insoluble matter removed, or protein removed after suspending cheese in a solvent, 20 to 200 g per serving for adults, taking into account its concentration rate, etc. The active ingredient corresponding to the cheese of the degree can be ingested.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples. However, these are merely illustrative and the present invention is not limited thereto.

[Example 1]
(Preparation of bacteria ripening type cheese)
The raw milk was sterilized by heating (75 ° C., 15 seconds), cooled to 30 ° C., and 0.01% calcium chloride was added. Furthermore, commercially available lactic acid bacteria starter for cheese production (Christian Hansen) 1.5% and polysaccharide-producing lactic acid bacteria Lactobacillus helveticus SBT2171 strain (FERM BP-5445) 3%, and rennet 0.003% Added to coagulate milk. The curd thus obtained was cut, stirred until the pH was 6.2 to 6.1, and whey was discharged to obtain curd grains. Then, the curd grains were packed and pressed, further salted, and aged at 10 ° C. to prepare gouda cheese type hard natural cheese. This hard natural cheese (aged for 6 months) was minced using a mincing machine (GM-DX, manufactured by Nippon Carrier Co., Ltd.) and freeze-dried. Then, it refined | miniaturized with the coffee mill and obtained cheese powder. The resulting cheese powder can be used as a preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome.

[Test Example 1]
Effect on Ulcerative Colitis Model Using the cheese powder obtained in Example 1, the effect of suppressing ulcerative colitis was confirmed. Thirty six-week-old male C57BL / 6J mice (Charles River Japan) were divided into two groups (20 control food groups and 10 cheese food groups) according to body weight after 5 days of pre-breeding with AIN-76 standard diet. Divided into. The cheese meal group was provided with a cheese powder blended with only protein and lipid ingredients. In the control food group, based on the results of cheese component analysis (see Table 1), the content of general ingredients, main minerals, and vitamin E (α-tocopherol) are the same as the cheese powder combination food. A feed using milk casein as a protein source and butter oil as a lipid source was given.
The intake of each experimental feed was started from the time of grouping and allowed to freely take for 5 weeks. Drinking water was deionized water ad libitum. After ingesting the experimental feed for 5 weeks, the control diet group was further divided into 2 groups according to body weight (10 animals per group), one side with deionized water (no treatment group) and the other side with dextran sulfate (MP Biomedicals, MW = 36,000-50,000) in 2% (w / v) dissolved in deionized water (2% DSS water) was allowed to drink freely for 7 days (control group). The cheese group was also allowed to drink 2% DSS water freely for 7 days. The experimental feed was ad libitum during the DSS water administration period. During DSS water administration, body weight and food intake were measured daily. On days 0, 1, 3, 5, and 7 after DSS administration, stool properties and bloody stool status were observed and scored together with the rate of change in body weight (see Table 2). Seven days after the administration of DSS water, it was dissected and the length of the colon was measured. Fig. 1 shows the rate of weight change, Fig. 2 shows the amount of food intake, Fig. 3 shows the characteristics of stool, Fig. 4 shows the state of bloody stool, Fig. 5 shows the total score of symptoms, and Fig. 6 shows the length of the colon. Shown in
In the control group, body weight began to decrease after day 4, and the food intake decreased significantly, but in the cheese diet group, these fluctuations were significantly reduced (FIGS. 1 and 2). Fecal characteristics and bloody stool status continued to increase from the day after DSS water administration, but the cheese diet group showed reduced symptoms compared to the control group (FIGS. 3 and 4). The total score integrated value was significantly lower in the cheese diet group than in the control group, confirming the pathologic condition improving effect of colitis (FIG. 5). In addition, the length of the colon in the control group was significantly shorter than that in the non-treated group, but the value in the cheese diet group was longer than that in the control group, and an effect of reducing colon shortening was observed (Fig. 6). From these results, it was confirmed that the cheese diet has an excellent protective effect against the pathogenesis of colitis induced by DSS.

[Example 2]
Mixing 0.5 kg of Gouda cheese and 0.5 kg of cheddar cheese obtained in Example 1, adding 20 g of molten salt sodium polyphosphate and 110 ml of water, and blowing steam while rotating with a kettle emulsifier (rotation speed 120 rpm), 85 The temperature was raised to 0 ° C. to emulsify. Then, the emulsified cheese was filled in a carton and stored refrigerated at 5 ° C. to obtain a process cheese for prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome.

[Example 3]
10 kg of Gouda cheese obtained in Example 1 is shredded with a meat chopper, and hot water at 90 ° C. with molten salt (1.2% Na phosphate, 1% polyphosphate Na) and emulsifier (0.6% sugar ester). After being charged into a dissolution tank containing 5 kg and adjusted to pH 6.2, an emulsion was prepared by stirring and blowing with steam. This emulsion was homogenized, filtered through a filter, and spray-dried to obtain a powdered cheese for prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome.

[Example 4]
100 g of powdered cheese for prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome obtained in Example 1, 40 g of vitamin C, 100 g of granulated sugar, and 60 g of an equal mixture of corn starch and lactose are mixed in a bag. 100 bags of stuffed, stick-like nutritional health foods for prevention and / or treatment of inflammatory bowel disease and / or irritable bowel syndrome were produced.

[Example 5]
Soybean cake 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, cellulose 2.8 kg, mineral mixture 2 kg, 120 ℃, 4 Sterilize for a minute, blend 10 kg of cheese powder obtained in Example 1,
A feed for preventing and / or treating inflammatory bowel disease and / or irritable bowel syndrome was produced.

Claims (3)

  A preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome, comprising cheese as an active ingredient.   A food or drink containing the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome according to claim 1.   A feed comprising the preventive and / or therapeutic agent for inflammatory bowel disease and / or irritable bowel syndrome according to claim 1.