WO2021111983A1 - Agent for preventing or ameliorating functional somatic syndromes and composition including the same - Google Patents

Agent for preventing or ameliorating functional somatic syndromes and composition including the same Download PDF

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Publication number
WO2021111983A1
WO2021111983A1 PCT/JP2020/044056 JP2020044056W WO2021111983A1 WO 2021111983 A1 WO2021111983 A1 WO 2021111983A1 JP 2020044056 W JP2020044056 W JP 2020044056W WO 2021111983 A1 WO2021111983 A1 WO 2021111983A1
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agent
syndrome
ameliorating
lactic acid
functional somatic
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PCT/JP2020/044056
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French (fr)
Japanese (ja)
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勝太郎 永田
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株式会社ライフ・クオリティ研究所
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Priority to JP2021562612A priority Critical patent/JP7072966B2/en
Publication of WO2021111983A1 publication Critical patent/WO2021111983A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
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Definitions

  • the present invention relates to agents and compositions for preventing, treating or ameliorating functional somatic syndrome, and more specifically, preventing, treating or treating functional somatic syndrome containing lactic acid bacteria and / or lactic acid bacteria-derived ingredients as active ingredients.
  • the present invention relates to an improving agent and a composition containing the same.
  • FSS Functional Somatic Syndromes
  • Non-Patent Document 1 a pathological condition that cannot be clearly explained
  • Non-Patent Document 2 More specifically, FSS is defined as follows and is treated as one syndrome (Non-Patent Document 2). 1) Complain of various physical symptoms (mainly chronic fatigue, chronic pain); 2) Lack of pathological abnormalities or laboratory findings that can explain the symptoms; 3) Often accompanied by mental illness (prone to be mistaken for mental illness); 4) There are few effective treatments.
  • MUS medically unexplained symptoms
  • the main symptoms are chronic fatigue and chronic pain (headache, joint pain, muscle pain, abdominal pain, etc.).
  • Others palpitations, dizziness, diarrhea, constipation, etc.
  • the frequency of such symptoms of unknown etiology in daily practice is said to be arthralgia 37%, back pain 32%, fatigue 25%, headache 25%, abdominal pain 24%, and dizziness 23% (Non-Patent Document 3). Since some of these symptoms have organic diseases, sufficient tests are required for diagnosis, but the symptoms in which no abnormalities are found even after the tests are called MUS. In recent years, it has been referred to as the above-mentioned FSS.
  • FSS specifically includes the following diseases. Irritable bowel syndrome (IBS) in the digestive system, functional dyspeptia; hyperventilation syndrome in the respiratory system, bronchial asthma-like bronchitis; angina, arrhythmia, hypotension in the circulatory system; chronic headache in the nervous system, Chronic low back pain, complex local pain syndrome (CRPS), cervical-shoulder-arm syndrome; fibromyalgia (FMS) in rheumatic systems, myopathic encephalopathy / chronic fatigue syndrome (ME / CFS), chronic fatigue syndrome (CFS); allergic system Chemical hypersensitivity (MCS); premenstrual syndrome (PMS) in gynecology; menopausal disorders; jaw arthritis in dentistry. And these are generically called FSS.
  • FSS includes various diseases, but it is regarded as one disease concept for the following reasons. 1.
  • the diagnostic criteria for each disease are similar and there are many common symptoms. 2.
  • Some diseases with FSS meet the diagnostic criteria for other diseases of FSS. 3.
  • In FSS there are complications between diseases. For example, 60% of CFS is associated with IBS and 75% of FMS is associated with temporomandibular disorders. 4. High rate of psychiatric symptoms such as depression and anxiety. 5. Most patients are women. 6. Relationships with doctors are difficult. 7. Respond to the same treatment.
  • FSS which includes such various diseases, conventional drug therapy with autonomic nerve agonists, psychotropic drugs (antidepressants, antidepressants), Chinese herbs, etc.; Life to improve lifestyle Therapy: Psychotherapy / physical therapy such as counseling, stress control, exercise therapy, acupuncture and moxibustion therapy, hot spring therapy, etc. has been performed, but at present, sufficient improvement effect has not been obtained and sufficient effect on FSS. There is a need for safe preventive or ameliorating agents.
  • Lactis KLAB-4 strain KLAB-4 is a strain isolated from fermented milk, and is a novel lactic acid bacterium belonging to the genus Lactobacillus delbricky subspecies lactis. Deposited with the Independent Administrative Institution Product Evaluation Technology Infrastructure Organization (2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan) (Deposit No. NITE BP-394; Original Deposit Date August 9, 2007 Domestic Deposited Strains Was transferred to an international deposit based on the Budapest Treaty (September 22, 2008). It is known that this lactic acid bacterium has an excellent anti-allergic function, and further has an anti-autoimmune disease function, a diabetes improving function and a hypoglycemia improving function (Patent Documents 1 and 2 and Non-Patent Document 4).
  • An object of the present invention is to provide an agent for preventing or ameliorating functional somatic syndrome, which is highly safe and effective, has few side effects, and can be used continuously for a long period of time.
  • a drug for preventing or ameliorating functional somatic syndrome containing lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium as an active ingredient;
  • Drugs for preventing or ameliorating syndrome [3] The agent for preventing or ameliorating functional somatic syndrome according to the above [1] or [2], which further contains a water-soluble dietary fiber component or is used in combination with a water-soluble dietary fiber component; [4]
  • the water-soluble dietary fiber component is glucomannan, pectin, guar gum, alginic acid, polydextrose, ⁇ -glucan, fructan, inulin, levan, laminan, arabic gum, martitol, psyllium, indigestible oligosaccharide, indigestible
  • the agent for preventing or ameliorating the functional physical syndrome according to the above [3] which is selected from the group consisting of sex dextrin, agarose, sodium alginate, carrageenan, fucoidan, porphyran, laminarin, seaweed, and agar; [5] The agent for preventing or ameliorating the functional somatic syndrome according to the above [4], wherein
  • cervicobrachial syndrome fibromyalgia, myopathic encephalopathy / chronic fatigue syndrome, chronic fatigue syndrome, multiple chemical sensitivity, premenstrual syndrome, menopausal disorder, and temporomandibular joint disease.
  • the agent for preventing or improving functional somatic syndrome of the present invention and the composition containing the same can effectively improve functional somatic syndrome. Since the agent for improving functional somatic syndrome and the composition containing the same of the present invention contain highly safe lactic acid bacteria or a component derived from the lactic acid bacteria as an active ingredient, there is concern about side effects even if they are administered or ingested for a long period of time. There is no such thing and it is highly safe. In addition, a water-soluble dietary fiber component such as glucomannan is also a beneficial component having many years of eating experience for humans and is highly safe. Therefore, the agent for improving functional somatic syndrome of the present invention and the composition containing the same can be used prophylactically or therapeutically.
  • FIG. 1 is a diagram comparing changes before and after administration of fatigue VAS. “**” represents p ⁇ 0.01 with respect to the previous value, and “***” represents p ⁇ 0.001 with respect to the previous value.
  • FIG. 2 is a diagram comparing the rate of change before and after administration of fatigue VAS. “**” represents p ⁇ 0.01 for the P group, and “***” represents p ⁇ 0.005 for the P group. “**” represents p ⁇ 0.01 for the L group.
  • FIG. 3 is a diagram comparing changes before and after administration of pain VAS. “**” represents p ⁇ 0.01 with respect to the previous value, and “***” represents p ⁇ 0.001 with respect to the previous value.
  • the agent for preventing or ameliorating functional somatic syndrome of the present invention contains the lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium as an active ingredient. Therefore, the agent of the present invention can consist only of the lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium, and can also contain other active ingredients.
  • Lactobacillus delbricky subspecies lactis used in the present invention can be isolated from fermented milk or fermented foods such as cheese, or the isolated strain can be obtained and used. it can.
  • the lactic acid bacteria used in the present invention include a group consisting of Lactobacillus delbrueckii subsp. Lactis KLAB-4 (hereinafter also referred to as "KLAB-4 strain") and variants thereof. It is desirable to include lactic acid bacteria selected from.
  • the KLAB-4 strain is a strain described in detail in Patent Document 1 (Patent No. 5554994). Since it was confirmed that the sequence from the 5'-terminal base of the 16s rRNA gene to the 544th base of this strain has 90% or more homology with the lactobacillus delbricky subspecies lactis standard strain, lacto It was identified as Lactis, a subspecies of the genus Delbricky.
  • the preferred lactic acid bacterium for use in the present invention is not only the KLAB-4 strain but also a mutant thereof.
  • Such mutants are not particularly limited, and are those obtained by spontaneous mutation, those obtained by artificially inducing mutation by a known method such as exposure to radiation or a mutation-inducing substance, and the like. Can be done.
  • the mutant can be used in the present invention as long as it has the same characteristics as KLAB-4 lactic acid bacteria (particularly, a preventive or ameliorating effect on functional somatic syndrome).
  • Lactobacillus lactobacillus delbricky subspecies lactis for example, KLAB-4 strain or a mutant thereof, can be cultured by a known general medium and method.
  • These lactic acid bacteria are cultured in a medium in which these bacteria can grow, for example, MRS medium, in a container such as a fermentation jar, a test tube, a bottle, or a flask, which is usually used under general culture conditions. Can be cultivated by performing.
  • the lactic acid bacterium used in the present invention may be a live bacterium or a dead bacterium.
  • Live bacteria refer to live cells
  • dead bacteria refer to cells that have been sterilized by heating, pressurizing, or treating with drugs.
  • the lactic acid bacterium-derived component obtained from the lactic acid bacterium can also be used in the present invention in the same manner as the bacterial cell as long as it has the same function.
  • the lactic acid bacterium-derived component refers to a part or component of a bacterial cell, or a component containing any of them.
  • lactic acid bacterium is ground, crushed, extracted, fractionated, dried, heated, frozen, cooled, concentrated, diluted, etc.
  • the lactic acid bacterium-derived component may be in any form such as liquid, paste, powder, and granules.
  • the residue after extracting some component from the cells may be used, and for example, the residue after hot water extraction may be used.
  • the KLAB-4 strain lactic acid bacterium powder is commercially available under the trade name "lactic acid bacterium LAB4" (manufactured by Kaneka Corporation), so that it may be used.
  • the agent for preventing or ameliorating functional somatic syndrome of the present invention may contain a water-soluble dietary fiber component in addition to the above-mentioned lactic acid bacteria or components derived from lactic acid bacteria. It has been found that the effect of the agent of the present invention is enhanced by further containing such a component.
  • the water-soluble dietary fiber component refers to a water-soluble dietary fiber or a food / pharmaceutical product or a food / pharmaceutical material containing the same.
  • Specific examples of the water-soluble dietary fiber component include glucomannan, pectin, guar gum, alginic acid, polydextrose, ⁇ -glucan, fructan, inulin, levan, graminan, arabic gum, maltitol, psyllium, and indigestible oligosaccharides.
  • Examples include natural or synthetic water-soluble or synthetic fiber-containing materials such as refractory dextrin, agarose, sodium alginate, carrageenan, fucoidan, porphyran, laminaran, and seaweed and agar.
  • the water-soluble dietary fiber component may be contained in the agent of the present invention, or may be combined with lactic acid bacteria or a component derived from lactic acid bacteria at the time of administration or ingestion. Alternatively, they can be administered or ingested as separate preparations containing each, in which case both may be administered or ingested simultaneously or at back and forth in time.
  • the agent or composition of the present invention is not only when the lactic acid bacterium or the component derived from the lactic acid bacterium and the water-soluble dietary fiber component are contained in the same composition, but also as separate agents or compositions at the same time or before and after. May be administered or ingested.
  • the agent of the present invention in the form of being encapsulated can be taken in a beverage containing a water-soluble dietary fiber component.
  • the ratio is not particularly limited, but for example, lactic acid bacteria or a component derived from lactic acid bacteria.
  • About 0.1 to 2 parts of the water-soluble dietary fiber component is preferable with respect to 1 part.
  • glucomannan is highly hydrophilic and can absorb about 100 times the weight of glucomannan, so that the volume of glucomannan increases about 100 times by absorbing water in the stomach. Then, it is considered that a thin film is stretched on the gastric mucosa. Therefore, one possibility is that the presence of a water-soluble dietary fiber component can regulate the absorption of lactic acid bacteria.
  • the agent for preventing or ameliorating functional somatic syndrome of the present invention contains lactic acid bacteria or components derived from lactic acid bacteria as described above as the only essential component, but contains or uses other active ingredients such as a water-soluble dietary fiber component. be able to.
  • the composition containing the agent for preventing or ameliorating functional somatic syndrome of the present invention contains one or more other ingredients in addition to the agent of the present invention.
  • the composition of the present invention may be a pharmaceutical composition, a food or drink composition, an animal feed composition, an animal pharmaceutical composition, or the like, and the specific form thereof is not particularly limited.
  • the composition of the present invention when used as a pharmaceutical composition, as its form or dosage form, capsules, tablets, pills, powders, granules, drinks, syrups, injections, infusions, nasal drops , Eye drops, suppositories, patches, sprays and the like.
  • the composition of the present invention when used as a food or drink composition, it may be in the form of a general food together with various food raw materials or ingredients, or it may be a functional food such as a supplement in the form of a capsule or a tablet. You can also.
  • any component contained in the composition of the present invention can be appropriately selected according to the properties, form, production method, etc. of the composition, and various components and additives known in the industry such as pharmaceuticals, foods, and cosmetics. Can be.
  • Additives that may be included in the compositions of the present invention include excipients, disintegrants, and lubricants that are pharmaceutically acceptable or routinely used in industries such as pharmaceuticals, foods and cosmetics. Examples include swamps, binders, surfactants, fluidity promoters, colorants, solvents, thickeners, dispersants, pH regulators, moisturizers, stabilizers, preservatives, fragrances and the like.
  • the excipients used are lactose, sucrose, glucose.
  • binders disintegrants, surfactants, lubricants, fluidity promoters, antioxidants, anti-aggregation agents, absorption promoters, dissolution aids, stabilizers, preservatives, moisture proofing agents. , Colorants, fragrances and the like can be used as appropriate.
  • binder examples include starch, dextrin, arabic gum powder, gelatin, hydroxypropyl starch, carboxymethyl cellulose / sodium salt, methyl cellulose, crystalline cellulose, ethyl cellulose, and polyvinylpyrrolidone.
  • Disintegrants include starches, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium salt, polyvinylpyrrolidone and the like.
  • Surfactants include soybean lecithin and sucrose fatty acid esters, talc, wax, sucrose fatty acid esters, hydrogenated vegetable oils, calcium stearate, magnesium stearate and the like as lubricants, and anhydrous as fluidity promoters. Examples thereof include silicic acid, dry aluminum hydroxide, and magnesium silicate.
  • composition of the present invention is used as an animal feed or an animal pharmaceutical composition
  • various feed raw materials or pharmaceutically acceptable ingredients are used to prepare feeds, supplements, pharmaceuticals and the like. It can be in the desired form or dosage form.
  • agent or composition of the present invention may be administered or used alone or in combination with other agents.
  • agent or composition of the present invention when used in combination with another agent, both may be used at the same time, or both may be used before and after.
  • the administration (or ingestion or application) route of the agent for preventing or ameliorating the functional somatic syndrome of the present invention or the composition can be appropriately selected from, for example, oral, transdermal, enteral, rectal routes and the like.
  • the daily dose (or ingestion or application) of the agent or composition of the present invention effective for the prevention or amelioration of functional physical syndrome is the formulation form, the method and route of administration, the age and body weight of the subject, and the subject's age and body weight.
  • the amount of the active ingredient lactic acid bacteria or lactic acid bacteria-derived component is generally about 0.1 mg to about 1000 mg / kg body weight / day, preferably about 1 mg.
  • About 500 mg / kg body weight / day, most preferably about 2 mg to about 300 mg / kg body weight / day can be administered or ingested at once or in divided portions.
  • the timing of administration or ingestion is not particularly limited, and may be, for example, at the same time as a meal, immediately after a meal, immediately before a meal, before sleep, or the like.
  • the agent or composition of the present invention is extremely safe, it can be given not only to patients but also to healthy subjects.
  • the agent or composition of the present invention can be similarly administered (or ingested or applied) to a subject, specifically a human and a non-human animal, preferably a mammal.
  • non-human animals include domestic animals such as cows, horses, pigs and sheep, and companion animals such as dogs and cats.
  • the dose can be adjusted according to the characteristics of the animal based on the same amount as described above.
  • the amount of lactic acid bacteria or components derived from lactic acid bacteria is about 0.01 to about 1000 mg / kg body weight / day, more preferably about 0.1 to about 30 mg / kg body weight / day. It can be adjusted and given.
  • Whether or not the agent or composition of the present invention has improved the functional somatic syndrome is determined after the time before and after the administration or ingestion, or at different time points such as during or after the administration or ingestion, as compared with the previous time point. At this time, for example, it can be evaluated based on whether or not the values of pain VAS or fatigue VAS, which will be described later, have increased or decreased.
  • Production Example 1 Per capsule, 100 mg of lactic acid bacteria powder, 50 mg of glucomannan powder, 17.5 mg of crystalline cellulose powder, 2 mg of calcium stearate powder, and 0.5 mg of silicon dioxide powder are mixed and stirred to make them uniform, and then a commercially available capsule (trade name "Pig"). It was filled in "Gelatin Clear No. 3" (manufactured by Qualicaps Co., Ltd.).
  • Production example 2 One capsule contains 100 mg of lactic acid bacteria powder, 50 mg of lactose, 17.5 mg of crystalline cellulose powder, 2 mg of calcium stearate powder, and 0.5 mg of silicon dioxide powder. Was filled into capsules. Comparative example: Instead of the lactic acid bacteria powder and the glucomannan powder, the same capsules as in Production Example 1 were produced except that they contained 150 mg of lactose.
  • ⁇ Subject> 99 patients (33 males and 66 females) diagnosed with FSS were divided into three groups, a placebo (P) group, a lactic acid bacterium (L) group, and a lactic acid bacterium + glucomannan (M) group, by the envelope method.
  • P placebo
  • L lactic acid bacterium
  • M lactic acid bacterium + glucomannan
  • Table 1 shows the breakdown of the subjects that make up each group.
  • Group P, L, or M were allowed to take the capsules of Comparative Example, Production Example 2, or Production Example 1 as described above in an amount of 3 capsules (1 capsule at a time) immediately after meals, respectively. It was. The administration period was 3 months.
  • VAS visual analogue scale
  • FIG. 1 is a diagram comparing changes before and after administration of fatigue VAS. There was no significant difference in fatigue VAS values between the groups before administration. For group P, there was no significant difference before and after administration. On the other hand, in the L group and the M group, there was a significant difference after the administration as compared with before the administration. The significant difference was larger in the M group. “**” represents p ⁇ 0.01 with respect to the previous value, and “***” represents p ⁇ 0.001 with respect to the previous value.
  • FIG. 2 is a diagram comparing the rate of change before and after administration of fatigue VAS.
  • the rate of change was calculated as [(Fatigue VAS after administration-Fatigue VAS before administration) / Fatigue VAS before administration] ⁇ 100 (%).
  • the fatigue VAS value was significantly lower than that in the P group.
  • the M group decreased more significantly.
  • “**” represents p ⁇ 0.01 for the P group
  • “***” represents p ⁇ 0.005 for the P group
  • **” represents p ⁇ 0.01 for the L group. Represents.
  • FIG. 3 is a diagram comparing changes before and after administration of pain VAS. There was no significant difference in pain VAS values between the groups before administration. For group P, there was no significant difference before and after administration. On the other hand, in the L group and the M group, there was a significant difference after the administration as compared with before the administration. The significant difference was larger in the M group. “**” represents p ⁇ 0.01 with respect to the previous value, and “***” represents p ⁇ 0.001 with respect to the previous value.
  • FIG. 4 is a diagram comparing the rate of change before and after administration of pain VAS.
  • the rate of change was calculated as [(Pain VAS after administration-Pain VAS before administration) / Pain VAS before administration] ⁇ 100 (%).
  • the pain VAS value was significantly lower than that in the P group.
  • the M group decreased more significantly.
  • “**” represents p ⁇ 0.01 for the P group
  • “***” represents p ⁇ 0.005 for the P group
  • **” represents p ⁇ 0.01 for the L group. Represents.
  • ⁇ Consideration of safety> blood and urine samples were collected before the start of administration and after the end of administration, and blood counts (erythrocytes, leukocytes, hemoglobin, hematocrit, platelets), Alb, GOT, GPT, LDH, AlP, ⁇ -GTP, amylase, BUN, creatinine, blood glucose level, hemoglobin A1c, and urine (protein, sugar, urobilinogen) were tested and the results were compared.

Abstract

The purpose of the present invention is to provide a highly safe and effective agent for preventing or ameliorating functional somatic syndromes, the agent causing few adverse effects and being able to be continuously used for a long term.　One embodiment of the present invention is an agent for preventing or ameliorating functional somatic syndromes, the agent including, as an active ingredient, a lactic acid bacterium Lactobacillus delbrueckii subsp. lactis or a lactic acid bacterium component ingredient therefrom.

Description

機能性身体症候群の予防又は改善用剤及びそれを含む組成物Agents for preventing or ameliorating functional somatic syndrome and compositions containing them
　本発明は、機能性身体症候群を予防、治療又は改善するための剤及び組成物に関し、さらに具体的には、乳酸菌及び／又は乳酸菌由来成分を有効成分とする機能性身体症候群の予防、治療又は改善用剤及びそれを含む組成物に関する。 The present invention relates to agents and compositions for preventing, treating or ameliorating functional somatic syndrome, and more specifically, preventing, treating or treating functional somatic syndrome containing lactic acid bacteria and / or lactic acid bacteria-derived ingredients as active ingredients. The present invention relates to an improving agent and a composition containing the same.
　機能性身体症候群（Functional Somatic Syndromes、以降、ＦＳＳとも記載する）は、新しい疾患概念であり、適切な診察や検査を行っても、器質的疾患（病理学的所見の認められる疾患）の存在を明確に説明できない病態と定義されている（非特許文献１）。ＦＳＳは、より具体的には、下記のように定義されており、一つの症候群として扱われている（非特許文献２）。
１）多彩な身体症状を訴える（主に、慢性疲労、慢性疼痛）；
２）その症状を説明できる病理学的異常や検査所見を欠く；
３）精神疾患を併発することが多い（精神疾患に誤認されやすい）；
４）効果的な治療法に乏しい。 Functional Somatic Syndromes (hereinafter also referred to as FSS) is a new disease concept, and even with proper medical examination and examination, the existence of organic diseases (diseases with pathological findings) can be detected. It is defined as a pathological condition that cannot be clearly explained (Non-Patent Document 1). More specifically, FSS is defined as follows and is treated as one syndrome (Non-Patent Document 2).
1) Complain of various physical symptoms (mainly chronic fatigue, chronic pain);
2) Lack of pathological abnormalities or laboratory findings that can explain the symptoms;
3) Often accompanied by mental illness (prone to be mistaken for mental illness);
4) There are few effective treatments.
　従来は、医学的に説明できない身体症状は、medically unexplained symptoms（ＭＵＳ）として知られており、その症状の主なものとしては、慢性疲労、慢性疼痛（頭痛、関節痛、筋肉痛、腹痛など）、その他（動悸、めまい、下痢、便秘など）が挙げられている。日常診療でこうした病因不明の症状の頻度は、関節痛３７％、背部痛３２％、疲労感２５％、頭痛２５％、腹痛２４％、めまい２３％といわれている（非特許文献３）。こうした症状の中には器質的疾患を有している人もいるため診断には十分な検査が必要であるが、検査をしてもどこにも異常が見つからない症状をＭＵＳと称していた。近年は、上述のＦＳＳと称している。 Conventionally, physical symptoms that cannot be explained medically are known as medically unexplained symptoms (MUS), and the main symptoms are chronic fatigue and chronic pain (headache, joint pain, muscle pain, abdominal pain, etc.). , Others (palpitations, dizziness, diarrhea, constipation, etc.) are listed. The frequency of such symptoms of unknown etiology in daily practice is said to be arthralgia 37%, back pain 32%, fatigue 25%, headache 25%, abdominal pain 24%, and dizziness 23% (Non-Patent Document 3). Since some of these symptoms have organic diseases, sufficient tests are required for diagnosis, but the symptoms in which no abnormalities are found even after the tests are called MUS. In recent years, it has been referred to as the above-mentioned FSS.
　ＦＳＳには、具体的には以下の各疾患が含まれる。消化器系では過敏性腸症候群（ＩＢＳ）、機能性ディスペプチア；呼吸器系では過換気症候群、気管支喘息様気管支炎；循環器系では、狭心症、不整脈、低血圧；神経系では慢性頭痛、慢性腰痛、複合性局所疼痛症候群（ＣＲＰＳ）、頸肩腕症候群；リウマチ系では線維筋痛症（ＦＭＳ）、筋痛性脳症/慢性疲労症候群（ＭＥ／ＣＦＳ）、慢性疲労症候群（ＣＦＳ）；アレルギー系では化学物質過敏症（ＭＣＳ）；婦人科系では月経前症候群（ＰＭＳ）、更年期障害；歯科では顎関節症などである。そして、これらをＦＳＳと総称している。 FSS specifically includes the following diseases. Irritable bowel syndrome (IBS) in the digestive system, functional dyspeptia; hyperventilation syndrome in the respiratory system, bronchial asthma-like bronchitis; angina, arrhythmia, hypotension in the circulatory system; chronic headache in the nervous system, Chronic low back pain, complex local pain syndrome (CRPS), cervical-shoulder-arm syndrome; fibromyalgia (FMS) in rheumatic systems, myopathic encephalopathy / chronic fatigue syndrome (ME / CFS), chronic fatigue syndrome (CFS); allergic system Chemical hypersensitivity (MCS); premenstrual syndrome (PMS) in gynecology; menopausal disorders; jaw arthritis in dentistry. And these are generically called FSS.
　このようにＦＳＳは多様な疾患を包含するが、以下の理由から一つの疾患概念として捉えられている。
１．各疾患の診断基準が類似し、共通する症状が多い。
２．ＦＳＳのある疾患は、ＦＳＳの他の疾患の診断基準を満たす。
３．ＦＳＳでは、疾患の間に合併が認められる。例えばＣＦＳの６０％はＩＢＳを合併し、ＦＭＳの７５％は顎関節症を合併する。
４．抑うつ、不安などの精神症状を高率に伴う。
５．患者は女性に多い。
６．医師との人間関係が難しい。
７．同じ治療に反応する。 In this way, FSS includes various diseases, but it is regarded as one disease concept for the following reasons.
1. 1. The diagnostic criteria for each disease are similar and there are many common symptoms.
2. Some diseases with FSS meet the diagnostic criteria for other diseases of FSS.
3. 3. In FSS, there are complications between diseases. For example, 60% of CFS is associated with IBS and 75% of FMS is associated with temporomandibular disorders.
4. High rate of psychiatric symptoms such as depression and anxiety.
5. Most patients are women.
6. Relationships with doctors are difficult.
7. Respond to the same treatment.
　ＦＳＳの診断に際しては、十分な問診と一般的な検査により器質的疾患を除外し、更に問診、行動観察、心理検査により精神疾患を除外する。更に、自律神経検査、内分泌検査、免疫検査により、ホメオスタシス状態を評価し、生活習慣やストレス状態を詳細に検討する必要があり、特に慢性疲労、慢性疼痛、不眠状態を評価する。 When diagnosing FSS, organic diseases are excluded by thorough interviews and general examinations, and mental illnesses are excluded by interviews, behavioral observations, and psychological tests. Furthermore, it is necessary to evaluate homeostatic status by autonomic nerve test, endocrine test, and immunological test, and to examine lifestyle and stress status in detail, especially chronic fatigue, chronic pain, and insomnia.
　このように多様な疾患を包含するＦＳＳに対しては、従来は自律神経作動薬、向精神薬（抗うつ剤、抗不安剤）、漢方方剤等による薬物療法；ライフスタイルの改善を図る生活療法；カウンセリング、ストレスコントロール、運動療法、鍼灸療法、温泉療法等などの心理療法・物理療法が行われているが、現在、十分な改善効果は得られておらず、ＦＳＳに対して十分な効果を有すると共に安全な予防又は改善用剤が求められている。 For FSS, which includes such various diseases, conventional drug therapy with autonomic nerve agonists, psychotropic drugs (antidepressants, antidepressants), Chinese herbs, etc.; Life to improve lifestyle Therapy: Psychotherapy / physical therapy such as counseling, stress control, exercise therapy, acupuncture and moxibustion therapy, hot spring therapy, etc. has been performed, but at present, sufficient improvement effect has not been obtained and sufficient effect on FSS. There is a need for safe preventive or ameliorating agents.
　近年、健康の維持及び改善において機能性乳酸菌が注目されており、多数の菌株が単離され、それらの有用性が検討されている。ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス　ＫＬＡＢ－４株（Lactobacillus delbrueckii subsp. lactis KLAB-4）は、発酵乳から分離された菌株であり、ラクトバチルス属デルブリッキー種亜種ラクティスに属する新規な乳酸菌として、独立行政法人製品評価技術基盤機構（日本国千葉県木更津市かずさ鎌足２－５－８）に寄託されている（受託番号ＮＩＴＥ　ＢＰ－３９４；原寄託日２００７年８月９日の国内寄託株をブダペスト条約に基づく国際寄託へ移管（２００８年９月２２日））。この乳酸菌は、優れた抗アレルギー機能を有し、さらに抗自己免疫疾患機能、糖尿病改善機能及び低血糖改善機能を有することが知られている（特許文献１及び２、非特許文献４）。 In recent years, functional lactic acid bacteria have been attracting attention in maintaining and improving health, and many strains have been isolated and their usefulness is being investigated. Lactobacillus delbrueckii subsp. Lactis KLAB-4 strain KLAB-4 is a strain isolated from fermented milk, and is a novel lactic acid bacterium belonging to the genus Lactobacillus delbricky subspecies lactis. Deposited with the Independent Administrative Institution Product Evaluation Technology Infrastructure Organization (2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan) (Deposit No. NITE BP-394; Original Deposit Date August 9, 2007 Domestic Deposited Strains Was transferred to an international deposit based on the Budapest Treaty (September 22, 2008). It is known that this lactic acid bacterium has an excellent anti-allergic function, and further has an anti-autoimmune disease function, a diabetes improving function and a hypoglycemia improving function (Patent Documents 1 and 2 and Non-Patent Document 4).
特許第５５５４９９４号公報Japanese Patent No. 5554994 特許第６７４７７２４号公報Japanese Patent No. 6747724
　本発明は、安全性及び有効性が高く、副作用が少なく、長期連用の可能な機能性身体症候群の予防又は改善用剤を提供することを目的とする。 An object of the present invention is to provide an agent for preventing or ameliorating functional somatic syndrome, which is highly safe and effective, has few side effects, and can be used continuously for a long period of time.
　本発明者は、上記課題を解決すべく鋭意研究した結果、特定の乳酸菌が、優れたＦＳＳの予防又は改善作用を示すことを見出し、本発明を完成した。
　本発明によれば、
〔１〕　乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス又はその乳酸菌由来成分を有効成分とする機能性身体症候群の予防又は改善用剤；
〔２〕　前記乳酸菌が、ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティスＫＬＡＢ－４株（ＮＩＴＥ　ＢＰ－３９４）及びその変異体からなる群から選択される乳酸菌を含む、前記〔１〕記載の機能性身体症候群の予防又は改善用剤；
〔３〕　水溶性食物繊維成分をさらに含有する、又は水溶性食物繊維成分と併用される、前記〔１〕又は〔２〕記載の機能性身体症候群の予防又は改善用剤；
〔４〕　前記水溶性食物繊維成分が、グルコマンナン、ペクチン、グアーガム、アルギン酸、ポリデキストロース、βグルカン、フルクタン、イヌリン、レバン、グラミナン、アラビアガム、マルチトール、サイリウム、難消化性オリゴ糖、難消化性デキストリン、アガロース、アルギン酸ナトリウム、カラギーナン、フコイダン、ポルフィラン、ラミナラン、海藻、及び寒天からなる群から選択される、前記〔３〕記載の機能性身体症候群の予防又は改善用剤；
〔５〕　前記水溶性食物繊維成分が、グルコマンナンである、前記〔４〕記載の機能性身体症候群の予防又は改善用剤；
〔６〕　前記機能性身体症候群が、過敏性腸症候群、機能性ディスペプチア、過換気症候群、気管支喘息様気管支炎、狭心症、不整脈、低血圧、慢性頭痛、慢性腰痛、複合性局所疼痛症候群、頸肩腕症候群、線維筋痛症、筋痛性脳症/慢性疲労症候群、慢性疲労症候群、化学物質過敏症、月経前症候群、更年期障害、及び顎関節症からなる群から選択される、前記〔１〕～〔５〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤；
〔７〕　前記〔１〕～〔６〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、組成物；
〔８〕　前記〔１〕～〔６〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、医薬品組成物；
〔９〕　前記〔１〕～〔６〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、飲食品組成物；
〔１０〕　前記〔１〕～〔６〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、動物用飼料又は動物用医薬品組成物；
〔１１〕　前記〔１〕～〔６〕のいずれか１項記載の機能性身体症候群の予防又は改善用剤、あるいは前記〔７〕～〔１０〕のいずれか１項記載の組成物を、対象に投与することを含む、機能性身体症候群の予防又は改善方法；
が提供される。 As a result of diligent research to solve the above problems, the present inventor has found that a specific lactic acid bacterium exhibits an excellent preventive or ameliorating effect on FSS, and has completed the present invention.
According to the present invention
[1] A drug for preventing or ameliorating functional somatic syndrome containing lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium as an active ingredient;
[2] The functional body according to the above [1], wherein the lactic acid bacterium contains a lactic acid bacterium selected from the group consisting of Lactobacillus delbricky Subspecies Lactis KLAB-4 strain (NITE BP-394) and a mutant thereof. Drugs for preventing or ameliorating syndrome;
[3] The agent for preventing or ameliorating functional somatic syndrome according to the above [1] or [2], which further contains a water-soluble dietary fiber component or is used in combination with a water-soluble dietary fiber component;
[4] The water-soluble dietary fiber component is glucomannan, pectin, guar gum, alginic acid, polydextrose, β-glucan, fructan, inulin, levan, laminan, arabic gum, martitol, psyllium, indigestible oligosaccharide, indigestible The agent for preventing or ameliorating the functional physical syndrome according to the above [3], which is selected from the group consisting of sex dextrin, agarose, sodium alginate, carrageenan, fucoidan, porphyran, laminarin, seaweed, and agar;
[5] The agent for preventing or ameliorating the functional somatic syndrome according to the above [4], wherein the water-soluble dietary fiber component is glucomannan;
[6] The functional somatic syndrome includes irritable bowel syndrome, functional dyspeptia, hyperventilation syndrome, bronchial asthma-like bronchitis, angina, arrhythmia, hypotension, chronic headache, chronic lower back pain, and complex local pain syndrome. It is selected from the group consisting of cervicobrachial syndrome, fibromyalgia, myopathic encephalopathy / chronic fatigue syndrome, chronic fatigue syndrome, multiple chemical sensitivity, premenstrual syndrome, menopausal disorder, and temporomandibular joint disease. -The agent for preventing or ameliorating functional somatic syndrome according to any one of [5];
[7] A composition containing a prophylactic or ameliorating agent for functional somatic syndrome according to any one of the above [1] to [6];
[8] A pharmaceutical composition containing the agent for preventing or ameliorating the functional somatic syndrome according to any one of the above [1] to [6];
[9] A food or drink composition containing the agent for preventing or ameliorating the functional somatic syndrome according to any one of the above [1] to [6];
[10] An animal feed or an animal pharmaceutical composition containing the agent for preventing or ameliorating the functional somatic syndrome according to any one of the above [1] to [6];
[11] The subject is the agent for preventing or ameliorating the functional somatic syndrome according to any one of the above [1] to [6], or the composition according to any one of the above [7] to [10]. Methods of prevention or amelioration of functional somatic syndrome, including administration to
Is provided.
　本発明の機能性身体症候群の予防又は改善用剤及びそれを含む組成物は、機能性身体症候群を有効に改善することができる。本発明の、機能性身体症候群の改善用剤及びそれを含む組成物は、安全性が高い乳酸菌又はその乳酸菌由来成分を有効成分とするため、長期的に投与又は摂取しても、副作用の心配がなく安全性が高い。また、水溶性食物繊維成分、例えばグルコマンナンもまた、人間にとって長年の食経験がある有益成分であり、安全性が高い。したがって、本発明の機能性身体症候群の改善用剤及びそれを含む組成物は、予防的に使用することも可能であり、治療に使用することも可能である。 The agent for preventing or improving functional somatic syndrome of the present invention and the composition containing the same can effectively improve functional somatic syndrome. Since the agent for improving functional somatic syndrome and the composition containing the same of the present invention contain highly safe lactic acid bacteria or a component derived from the lactic acid bacteria as an active ingredient, there is concern about side effects even if they are administered or ingested for a long period of time. There is no such thing and it is highly safe. In addition, a water-soluble dietary fiber component such as glucomannan is also a beneficial component having many years of eating experience for humans and is highly safe. Therefore, the agent for improving functional somatic syndrome of the present invention and the composition containing the same can be used prophylactically or therapeutically.
図１は、疲労ＶＡＳの投与前後での変化を比較した図である。「＊＊」は、前値に対しｐ＜０．０１、「＊＊＊」は、前値に対しｐ＜０．００１を表す。FIG. 1 is a diagram comparing changes before and after administration of fatigue VAS. “**” represents p <0.01 with respect to the previous value, and “***” represents p <0.001 with respect to the previous value. 図２は、疲労ＶＡＳの投与前後での変化率を比較した図である。「＊＊」は、Ｐ群に対しｐ＜０．０１、「＊＊＊」は、Ｐ群に対しｐ＜０．００５を表す。「※※」は、Ｌ群に対しｐ＜０．０１を表す。FIG. 2 is a diagram comparing the rate of change before and after administration of fatigue VAS. “**” represents p <0.01 for the P group, and “***” represents p <0.005 for the P group. "**" represents p <0.01 for the L group. 図３は、疼痛ＶＡＳの投与前後での変化を比較した図である。「＊＊」は、前値に対しｐ＜０．０１、「＊＊＊」は、前値に対しｐ＜０．００１を表す。FIG. 3 is a diagram comparing changes before and after administration of pain VAS. “**” represents p <0.01 with respect to the previous value, and “***” represents p <0.001 with respect to the previous value. 図４は、疼痛ＶＡＳの投与前後での変化率を比較した図である。「＊＊」は、Ｐ群に対しｐ＜０．０１、「＊＊＊」は、Ｐ群に対しｐ＜０．００５を表す。「※※」は、Ｌ群に対しｐ＜０．０１を表す。FIG. 4 is a diagram comparing the rate of change before and after administration of pain VAS. “**” represents p <0.01 for the P group, and “***” represents p <0.005 for the P group. "**" represents p <0.01 for the L group.
　本発明の機能性身体症候群の予防又は改善用剤は、乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス又はその乳酸菌由来成分を有効成分とする。したがって、本発明の剤は、乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス又はその乳酸菌由来成分のみからなることができ、他の有効成分を含むこともできる。 The agent for preventing or ameliorating functional somatic syndrome of the present invention contains the lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium as an active ingredient. Therefore, the agent of the present invention can consist only of the lactic acid bacterium Lactobacillus delbricky subspecies lactis or a component derived from the lactic acid bacterium, and can also contain other active ingredients.
＜乳酸菌＞
　本発明において使用される乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティスは、発酵乳又はチーズなどの発酵食品などから単離することができ、あるいは、単離された菌株を入手して使用することもできる。本発明において使用される乳酸菌としては、ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス　ＫＬＡＢ－４株（Lactobacillus delbrueckii subsp. lactis KLAB-4、以下「ＫＬＡＢ－４株」ともいう）及びその変異体からなる群から選択される乳酸菌を含むことが望ましい。 <Lactic acid bacteria>
The lactic acid bacterium Lactobacillus delbricky subspecies lactis used in the present invention can be isolated from fermented milk or fermented foods such as cheese, or the isolated strain can be obtained and used. it can. The lactic acid bacteria used in the present invention include a group consisting of Lactobacillus delbrueckii subsp. Lactis KLAB-4 (hereinafter also referred to as "KLAB-4 strain") and variants thereof. It is desirable to include lactic acid bacteria selected from.
　ＫＬＡＢ－４株は、特許文献１（特許第５５５４９９４号公報）に詳細に記載されている菌株である。この菌株は、その１６ｓ　ｒＲＮＡ遺伝子の５'末端の塩基より５４４番目の塩基までの配列が、ラクトバチルス属デルブリッキー種亜種ラクティス標準株と９０％以上の相同性を有することが確認されたため、ラクトバチルス属デルブリッキー種亜種ラクティスと同定された。 The KLAB-4 strain is a strain described in detail in Patent Document 1 (Patent No. 5554994). Since it was confirmed that the sequence from the 5'-terminal base of the 16s rRNA gene to the 544th base of this strain has 90% or more homology with the lactobacillus delbricky subspecies lactis standard strain, lacto It was identified as Lactis, a subspecies of the genus Delbricky.
　本発明における使用に関して好ましい乳酸菌は、ＫＬＡＢ－４株だけでなく、その変異体であってもよい。このような変異体は、特に限定されず、自然突然変異によるもの、放射線や突然変異誘導物質への曝露などの公知の方法で人為的に突然変異を誘導させて得られたものなどであることができる。変異体は、ＫＬＡＢ－４乳酸菌と比較して同等の特性（特に、機能性身体症候群の予防又は改善作用）を有するものであれば、本発明において使用することができる。 The preferred lactic acid bacterium for use in the present invention is not only the KLAB-4 strain but also a mutant thereof. Such mutants are not particularly limited, and are those obtained by spontaneous mutation, those obtained by artificially inducing mutation by a known method such as exposure to radiation or a mutation-inducing substance, and the like. Can be done. The mutant can be used in the present invention as long as it has the same characteristics as KLAB-4 lactic acid bacteria (particularly, a preventive or ameliorating effect on functional somatic syndrome).
　乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス、例えばＫＬＡＢ－４株又はその変異体は、公知の一般的な培地及び方法により培養することができる。これらの乳酸菌は、これらの菌が生育可能な培地、例えば、ＭＲＳ培地を用い、一般的な培養条件下で、通常使用される発酵ジャー、試験管、ボトル、フラスコ等の容器で通常の乳酸菌培養を行うことにより、培養することができる。 Lactobacillus lactobacillus delbricky subspecies lactis, for example, KLAB-4 strain or a mutant thereof, can be cultured by a known general medium and method. These lactic acid bacteria are cultured in a medium in which these bacteria can grow, for example, MRS medium, in a container such as a fermentation jar, a test tube, a bottle, or a flask, which is usually used under general culture conditions. Can be cultivated by performing.
　本発明において使用される乳酸菌は、生菌であってもよく、死菌であってもよい。生菌とは、生きている菌体を指し、死菌とは、加熱、加圧、薬物などによる処理で殺菌された菌体を指す。 The lactic acid bacterium used in the present invention may be a live bacterium or a dead bacterium. Live bacteria refer to live cells, and dead bacteria refer to cells that have been sterilized by heating, pressurizing, or treating with drugs.
　さらに、乳酸菌から得られる乳酸菌由来成分も、同等の機能を有する限り、菌体と同様に本発明において使用することができる。乳酸菌由来成分とは、菌体の部分又は成分、あるいはそれらのいずれかを含むものをいい、例えば、乳酸菌に磨砕、破砕、抽出、分画、乾燥、加熱、凍結、冷却、濃縮、希釈などの処理の少なくとも一つを施して得られる菌体処理物などをいう。乳酸菌由来成分は、液体、ペースト、粉末、顆粒など、いずれの形態であってもよい。菌体から何らかの成分を抽出した後の残渣を使用してもよく、例えば、熱水抽出後の残渣を使用してもよい。 Furthermore, the lactic acid bacterium-derived component obtained from the lactic acid bacterium can also be used in the present invention in the same manner as the bacterial cell as long as it has the same function. The lactic acid bacterium-derived component refers to a part or component of a bacterial cell, or a component containing any of them. For example, lactic acid bacterium is ground, crushed, extracted, fractionated, dried, heated, frozen, cooled, concentrated, diluted, etc. Refers to a cell-treated product obtained by performing at least one of the above treatments. The lactic acid bacterium-derived component may be in any form such as liquid, paste, powder, and granules. The residue after extracting some component from the cells may be used, and for example, the residue after hot water extraction may be used.
　ＫＬＡＢ－４株乳酸菌粉末は、商品名「乳酸菌ＬＡＢ４」（株式会社カネカ製）として市販されているので、これを使用してもよい。 The KLAB-4 strain lactic acid bacterium powder is commercially available under the trade name "lactic acid bacterium LAB4" (manufactured by Kaneka Corporation), so that it may be used.
＜水溶性食物繊維成分＞
　本発明の機能性身体症候群の予防又は改善用剤には、上記のとおりの乳酸菌又は乳酸菌由来成分に加えて、水溶性食物繊維成分を含ませることができる。このような成分をさらに含むことにより、本発明の剤の効果が増強されることが見出された。 <Water-soluble dietary fiber component>
The agent for preventing or ameliorating functional somatic syndrome of the present invention may contain a water-soluble dietary fiber component in addition to the above-mentioned lactic acid bacteria or components derived from lactic acid bacteria. It has been found that the effect of the agent of the present invention is enhanced by further containing such a component.
水溶性食物繊維成分とは、水溶性食物繊維、又はそれを含む食品／医薬品もしくは食品／医薬品素材をいう。水溶性食物繊維成分の具体例としては、例えば、グルコマンナン、ペクチン、グアーガム、アルギン酸、ポリデキストロース、βグルカン、フルクタン、イヌリン、レバン、グラミナン、アラビアガム、マルチトール、サイリウム、難消化性オリゴ糖、難消化性デキストリン、アガロース、アルギン酸ナトリウム、カラギーナン、フコイダン、ポルフィラン、ラミナラン、ならびに海藻及び寒天などの、天然又は合成の水溶性食物繊維又は水溶性食物繊維含有材料が挙げられる。 The water-soluble dietary fiber component refers to a water-soluble dietary fiber or a food / pharmaceutical product or a food / pharmaceutical material containing the same. Specific examples of the water-soluble dietary fiber component include glucomannan, pectin, guar gum, alginic acid, polydextrose, β-glucan, fructan, inulin, levan, graminan, arabic gum, maltitol, psyllium, and indigestible oligosaccharides. Examples include natural or synthetic water-soluble or synthetic fiber-containing materials such as refractory dextrin, agarose, sodium alginate, carrageenan, fucoidan, porphyran, laminaran, and seaweed and agar.
　水溶性食物繊維成分は、本発明の剤に含有させておいてもよく、投与又は摂取時に乳酸菌又は乳酸菌由来成分と一緒にしてもよい。あるいは、それぞれを含有する別々の調製物として投与又は摂取することもでき、その場合、両方を同時に、又は時間的に前後して投与又は摂取してもよい。言い換えれば、本発明の剤又は組成物は、乳酸菌又は乳酸菌由来成分と、水溶性食物繊維成分とを同一の組成物中に含む場合だけでなく、別々の剤又は組成物として、同時又は前後して投与又は摂取してもよい。例えば、カプセルに封入された形態の本発明の剤を、水溶性食物繊維成分を含む飲料で服用させることができる。 The water-soluble dietary fiber component may be contained in the agent of the present invention, or may be combined with lactic acid bacteria or a component derived from lactic acid bacteria at the time of administration or ingestion. Alternatively, they can be administered or ingested as separate preparations containing each, in which case both may be administered or ingested simultaneously or at back and forth in time. In other words, the agent or composition of the present invention is not only when the lactic acid bacterium or the component derived from the lactic acid bacterium and the water-soluble dietary fiber component are contained in the same composition, but also as separate agents or compositions at the same time or before and after. May be administered or ingested. For example, the agent of the present invention in the form of being encapsulated can be taken in a beverage containing a water-soluble dietary fiber component.
　本発明の剤に水溶性食物繊維成分を含有させる場合又は本発明の剤と水溶性食物繊維成分とを併用する場合、その割合（重量比）は、特に限定されないが、例えば乳酸菌又は乳酸菌由来成分１部に対し、水溶性食物繊維成分０．１～２部程度が好ましい。 When the agent of the present invention contains a water-soluble dietary fiber component or when the agent of the present invention and a water-soluble dietary fiber component are used in combination, the ratio (weight ratio) is not particularly limited, but for example, lactic acid bacteria or a component derived from lactic acid bacteria. About 0.1 to 2 parts of the water-soluble dietary fiber component is preferable with respect to 1 part.
　水溶性食物繊維成分によって乳酸菌の効果が増強される作用機序は不明であり、本発明は、特定の作用機序に拘束されるものではない。例えば、グルコマンナンは、親水性が高く、グルコマンナンの重量に対して約１００倍の重量の水を吸収することができるため、グルコマンナンは胃内で吸水することにより約１００倍に体積が増加して、胃粘膜に薄い膜が張られた状態となると考えられる。したがって、一つの可能性として、水溶性食物繊維成分が存在することにより乳酸菌の吸収を調節することができると考えられる。 The mechanism of action in which the effect of lactic acid bacteria is enhanced by the water-soluble dietary fiber component is unknown, and the present invention is not bound by a specific mechanism of action. For example, glucomannan is highly hydrophilic and can absorb about 100 times the weight of glucomannan, so that the volume of glucomannan increases about 100 times by absorbing water in the stomach. Then, it is considered that a thin film is stretched on the gastric mucosa. Therefore, one possibility is that the presence of a water-soluble dietary fiber component can regulate the absorption of lactic acid bacteria.
＜その他の成分＞
　本発明の機能性身体症候群の予防又は改善用剤は、上記のとおりの乳酸菌又は乳酸菌由来成分を唯一の必須成分とするが、水溶性食物繊維成分のような他の有効成分を含有又は併用することができる。本発明の機能性身体症候群の予防又は改善用剤を含む組成物は、本発明の剤に加えて、一以上の他の成分を含む。 <Other ingredients>
The agent for preventing or ameliorating functional somatic syndrome of the present invention contains lactic acid bacteria or components derived from lactic acid bacteria as described above as the only essential component, but contains or uses other active ingredients such as a water-soluble dietary fiber component. be able to. The composition containing the agent for preventing or ameliorating functional somatic syndrome of the present invention contains one or more other ingredients in addition to the agent of the present invention.
　本発明の組成物は、医薬品組成物、飲食品組成物、動物用飼料組成物又は動物用医薬品組成物などであることができ、それらの具体的な形態は、特に限定されない。例えば、本発明の組成物を医薬品組成物として用いる場合は、その形態又は剤型として、カプセル剤、錠剤、丸剤、散剤、顆粒剤、ドリンク剤、シロップ剤、注射剤、輸液、点鼻剤、点眼剤、座薬、貼付剤、噴霧剤などが挙げられる。本発明の組成物を飲食品組成物として用いる場合は、各種の食品原材料又は成分と共に一般食品の形態にしてもよく、また、カプセル剤又は錠剤などの形態のサプリメントなどの機能性食品とすることもできる。 The composition of the present invention may be a pharmaceutical composition, a food or drink composition, an animal feed composition, an animal pharmaceutical composition, or the like, and the specific form thereof is not particularly limited. For example, when the composition of the present invention is used as a pharmaceutical composition, as its form or dosage form, capsules, tablets, pills, powders, granules, drinks, syrups, injections, infusions, nasal drops , Eye drops, suppositories, patches, sprays and the like. When the composition of the present invention is used as a food or drink composition, it may be in the form of a general food together with various food raw materials or ingredients, or it may be a functional food such as a supplement in the form of a capsule or a tablet. You can also.
　本発明の組成物に含まれる任意の成分は、組成物の性質、形態、製造方法などに応じて適宜選択することができ、製薬、食品、化粧品などの業界で公知の種々の成分や添加剤であることができる。本発明の組成物が含んでいてもよい添加剤としては、薬剤学的に許容される、又は製薬、食品、化粧品などの業界で日常的に使用されている、賦形剤、崩壊剤、滑沢剤、結合剤、界面活性剤、流動性促進剤、着色剤、溶剤、増粘剤、分散剤、ｐＨ調整剤、保湿剤、安定化剤、保存料、香料などを挙げることができる。 Any component contained in the composition of the present invention can be appropriately selected according to the properties, form, production method, etc. of the composition, and various components and additives known in the industry such as pharmaceuticals, foods, and cosmetics. Can be. Additives that may be included in the compositions of the present invention include excipients, disintegrants, and lubricants that are pharmaceutically acceptable or routinely used in industries such as pharmaceuticals, foods and cosmetics. Examples include swamps, binders, surfactants, fluidity promoters, colorants, solvents, thickeners, dispersants, pH regulators, moisturizers, stabilizers, preservatives, fragrances and the like.
　これらの添加剤は、所望の剤型などに応じて、適宜選択される。例えば、本発明の医薬品組成物又は飲食品組成物などの組成物が、粉末剤、顆粒剤、錠剤、カプセル剤などの形態である場合には、用いる賦形剤としては、乳糖、蔗糖、グルコース、ソルビトール、ラクチトールなどの単糖又は二糖類、コーンスターチ、ポテトスターチのような澱粉類、結晶セルロース、無機物としては軽質シリカゲル、合成珪酸アルミニウム、メタ珪酸アルミン酸マグネシウム、リン酸水素カルシウム、二酸化ケイ素などがある。また、必要に応じ、結合剤、崩壊剤、界面活性剤、滑沢剤、流動性促進剤、酸化防止剤、凝集防止剤、吸収促進剤、溶解補助剤、安定化剤、防腐剤、防湿剤、着色料、香料などを適宜使用することができる。 These additives are appropriately selected according to the desired dosage form and the like. For example, when the composition such as the pharmaceutical composition or the food or drink composition of the present invention is in the form of powder, granules, tablets, capsules, etc., the excipients used are lactose, sucrose, glucose. , Monosaccharides or disaccharides such as sorbitol and lactose, starches such as corn starch and potato starch, crystalline cellulose, light silica gel as inorganic substances, synthetic aluminum silicate, magnesium aluminometasilicate, calcium hydrogen phosphate, silicon dioxide and the like. is there. Also, if necessary, binders, disintegrants, surfactants, lubricants, fluidity promoters, antioxidants, anti-aggregation agents, absorption promoters, dissolution aids, stabilizers, preservatives, moisture proofing agents. , Colorants, fragrances and the like can be used as appropriate.
　結合剤としては、例えば、澱粉、デキストリン、アラビアガム末、ゼラチン、ヒドロキシプロピルスターチ、カルボキシメチルセルロース・ナトリウム塩、メチルセルロース、結晶性セルロース、エチルセルロース、ポリビニルピロリドンが挙げられる。 Examples of the binder include starch, dextrin, arabic gum powder, gelatin, hydroxypropyl starch, carboxymethyl cellulose / sodium salt, methyl cellulose, crystalline cellulose, ethyl cellulose, and polyvinylpyrrolidone.
　崩壊剤としては、澱粉類、カルボキシメチルセルロース（ＣＭＣ）、ヒドロキシプロピルセルロース（ＨＰＣ）、カルボキシメチルセルロース・ナトリウム塩、ポリビニルピロリドンなどがある。 Disintegrants include starches, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium salt, polyvinylpyrrolidone and the like.
　界面活性剤としては、大豆レシチン、蔗糖脂肪酸エステルなどが、滑沢剤としては、タルク、ロウ、蔗糖脂肪酸エステル、水素添加植物油、ステアリン酸カルシウム、ステアリン酸マグネシウムなどが、流動性促進剤としては、無水ケイ酸、乾燥水酸化アルミニウム、ケイ酸マグネシウムなどが、それぞれ挙げられる。 Surfactants include soybean lecithin and sucrose fatty acid esters, talc, wax, sucrose fatty acid esters, hydrogenated vegetable oils, calcium stearate, magnesium stearate and the like as lubricants, and anhydrous as fluidity promoters. Examples thereof include silicic acid, dry aluminum hydroxide, and magnesium silicate.
　本発明の組成物を動物用飼料又は動物用医薬品組成物として用いる場合も、上記と同様であり、各種飼料原材料又は薬剤学的に許容される成分を使用して、飼料、サプリメント、医薬などの所望の形態又は剤型にすることができる。 The same applies to the case where the composition of the present invention is used as an animal feed or an animal pharmaceutical composition, and various feed raw materials or pharmaceutically acceptable ingredients are used to prepare feeds, supplements, pharmaceuticals and the like. It can be in the desired form or dosage form.
　本発明の剤又は組成物は、単独で投与又は使用してもよく、他の薬剤と併用してもよい。また、本発明の剤又は組成物を他の薬剤と併用する場合は、両者を同時に用いてもよく、前後して用いてもよい。 The agent or composition of the present invention may be administered or used alone or in combination with other agents. When the agent or composition of the present invention is used in combination with another agent, both may be used at the same time, or both may be used before and after.
　本発明の機能性身体症候群の予防又は改善用剤、あるいは組成物の投与（又は摂取もしくは適用）経路は、例えば、経口、経皮、経腸、直腸内経路などから適宜選択することができる。機能性身体症候群の予防又は改善に有効な本発明の剤又は組成物の１日当たりの投与（又は摂取もしくは適用）量は、その製剤形態、投与などの方法や経路、対象者の年齢及び体重、疾患の重症度などによって異なるが、例えば経口経路の場合、ヒトでは、一般的には、有効成分の乳酸菌又は乳酸菌由来成分量として約０．１ｍｇ～約１０００ｍｇ／ｋｇ体重／日、好ましくは約１ｍｇ～約５００ｍｇ／ｋｇ体重／日、最も好ましくは約２ｍｇ～約３００ｍｇ／ｋｇ体重／日を、一度に又は分割して、投与又は摂取することができる。投与又は摂取のタイミングは、特に限定されず、例えば、食事と同時、食直後、食直前、睡眠前などであることができる。 The administration (or ingestion or application) route of the agent for preventing or ameliorating the functional somatic syndrome of the present invention or the composition can be appropriately selected from, for example, oral, transdermal, enteral, rectal routes and the like. The daily dose (or ingestion or application) of the agent or composition of the present invention effective for the prevention or amelioration of functional physical syndrome is the formulation form, the method and route of administration, the age and body weight of the subject, and the subject's age and body weight. Although it depends on the severity of the disease, for example, in the case of the oral route, in humans, the amount of the active ingredient lactic acid bacteria or lactic acid bacteria-derived component is generally about 0.1 mg to about 1000 mg / kg body weight / day, preferably about 1 mg. ~ About 500 mg / kg body weight / day, most preferably about 2 mg to about 300 mg / kg body weight / day can be administered or ingested at once or in divided portions. The timing of administration or ingestion is not particularly limited, and may be, for example, at the same time as a meal, immediately after a meal, immediately before a meal, before sleep, or the like.
　本発明の剤又は組成物は、非常に安全性が高いので、患者だけでなく健常者に与えることもできる。また、本発明の剤又は組成物は、対象、具体的にはヒト及びヒト以外の動物、好ましくは哺乳類に同様に投与（又は摂取もしくは適用）することができる。ヒト以外の動物の例としては、ウシ、ウマ、ブタ、ヒツジなどの家畜、及びイヌ、ネコなどのコンパニオン動物が挙げられる。投与量については上記と同様の量を基準として、動物の特性に応じて調整することができる。例えば、小動物の場合、乳酸菌又は乳酸菌由来成分量として、約０．０１～約１０００ｍｇ／ｋｇ体重／日、より好ましくは約０．１～約３０ｍｇ／ｋｇ体重／日に相当する投与又は摂取量になるよう調整して与えることができる。 Since the agent or composition of the present invention is extremely safe, it can be given not only to patients but also to healthy subjects. In addition, the agent or composition of the present invention can be similarly administered (or ingested or applied) to a subject, specifically a human and a non-human animal, preferably a mammal. Examples of non-human animals include domestic animals such as cows, horses, pigs and sheep, and companion animals such as dogs and cats. The dose can be adjusted according to the characteristics of the animal based on the same amount as described above. For example, in the case of small animals, the amount of lactic acid bacteria or components derived from lactic acid bacteria is about 0.01 to about 1000 mg / kg body weight / day, more preferably about 0.1 to about 30 mg / kg body weight / day. It can be adjusted and given.
　本発明の剤又は組成物により、機能性身体症候群が改善されたか否かは、投与又は摂取の前と後、又は投与又は摂取中もしくは後などの異なる時点において、前の時点と比較して後の時点において、例えば後述する疼痛ＶＡＳ又は疲労ＶＡＳの値が増減したか否か等により、評価することができる。 Whether or not the agent or composition of the present invention has improved the functional somatic syndrome is determined after the time before and after the administration or ingestion, or at different time points such as during or after the administration or ingestion, as compared with the previous time point. At this time, for example, it can be evaluated based on whether or not the values of pain VAS or fatigue VAS, which will be described later, have increased or decreased.
　以下に例を示し、本発明をより具体的に説明するが、本発明はこれらの実施例に何ら限定されるものではない。 The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
１．カプセル剤の製造
　乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティスとして、ＫＬＡＢ－４乳酸菌粉末（商品名「乳酸菌ＬＡＢ４」（株式会社カネカ製））を、水溶性食物繊維成分としてグルコマンナン（商品名「レオレックスＲＳ」（清水化学株式会社製））を使用し、以下の３種のカプセル剤を製造した。 1. 1. Manufacture of Capsules Lactobacillus del Bricky Subspecies Lactis, KLAB-4 lactic acid bacterium powder (trade name "Lactobacillus LAB4" (manufactured by Kaneka Co., Ltd.)) The following three types of capsules were manufactured using "Rex RS" (manufactured by Shimizu Chemical Co., Ltd.).
　製造例１：
　１カプセル当たり、乳酸菌粉末１００ｍｇ、グルコマンナン粉末５０ｍｇ、結晶セルロース粉末１７．５ｍｇ、ステアリン酸カルシウム粉末２ｍｇ、二酸化ケイ素粉末０．５ｍｇを混合、撹拌して均一にした後、市販のカプセル（商品名「ブタゼラチンクリア３号」（クオリカプス株式会社製））に充填した。
　製造例２：
　１カプセル当たり、乳酸菌粉末１００ｍｇ、乳糖５０ｍｇ、結晶セルロース粉末１７．５ｍｇ、ステアリン酸カルシウム粉末２ｍｇ、二酸化ケイ素粉末０．５ｍｇを混合、撹拌して均一にした後、製造例１で使用したものと同じ市販のカプセルに充填した。
　比較例：
　乳酸菌粉末及びグルコマンナン粉末の代わりに、乳糖１５０ｍｇを含む以外は製造例１と同じカプセル剤を製造した。 Production Example 1:
Per capsule, 100 mg of lactic acid bacteria powder, 50 mg of glucomannan powder, 17.5 mg of crystalline cellulose powder, 2 mg of calcium stearate powder, and 0.5 mg of silicon dioxide powder are mixed and stirred to make them uniform, and then a commercially available capsule (trade name "Pig"). It was filled in "Gelatin Clear No. 3" (manufactured by Qualicaps Co., Ltd.).
Production example 2:
One capsule contains 100 mg of lactic acid bacteria powder, 50 mg of lactose, 17.5 mg of crystalline cellulose powder, 2 mg of calcium stearate powder, and 0.5 mg of silicon dioxide powder. Was filled into capsules.
Comparative example:
Instead of the lactic acid bacteria powder and the glucomannan powder, the same capsules as in Production Example 1 were produced except that they contained 150 mg of lactose.
　これら３種のカプセル剤は、外見、味、匂いともに差がなく、区別がつかないものであった。 These three types of capsules had no difference in appearance, taste, and odor, and were indistinguishable.
２．ＦＳＳに対する効果の試験
　本研究は、（公財）国際全人医療研究所の倫理委員会の承認のうえで、十分なインフォームド・コンセントを得て実施した（２０１７年）。 2. Test of effect on FSS This study was conducted with sufficient informed consent with the approval of the Ethics Committee of the International Institute for All-Personal Medicine (2017).
＜被験者＞
　ＦＳＳと診断された患者９９例（男性３３例、女性６６例）を、封筒法によって、プラセボ（Ｐ）群、乳酸菌（Ｌ）群、及び乳酸菌＋グルコマンナン（Ｍ）群の３群に分け、二重盲検法により、本発明の剤のＦＳＳに対する改善効果を検討した。 <Subject>
99 patients (33 males and 66 females) diagnosed with FSS were divided into three groups, a placebo (P) group, a lactic acid bacterium (L) group, and a lactic acid bacterium + glucomannan (M) group, by the envelope method. The improvement effect of the agent of the present invention on FSS was examined by a double-blind method.
　各群の被験者の年齢及び性別に統計学的有意差はなかった。各群を構成する被験者の内訳を表１に示す。 There was no statistically significant difference in the age and gender of the subjects in each group. Table 1 shows the breakdown of the subjects that make up each group.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　Ｐ群、Ｌ群、又はＭ群に、それぞれ、上記のとおりの比較例、製造例２、又は製造例１のカプセルを、１日３カプセル（１回１カプセル）の量で食直後に服用させた。投与期間は、３カ月であった。 Group P, L, or M were allowed to take the capsules of Comparative Example, Production Example 2, or Production Example 1 as described above in an amount of 3 capsules (1 capsule at a time) immediately after meals, respectively. It was. The administration period was 3 months.
＜ＦＳＳの評価＞
　得られた結果の評価は、国際的に一般的に用いられているＶＡＳ（visual analogue scale）法、すなわち１００mmの線分を用い、最大の疼痛・疲労を１００mmとし、まったく疼痛・疲労のない状態を０mmとして、測定日の状態を被験者に線分に記入してもらう方法によって行った。本法は、疼痛・疲労など客観的指標のない症状の評価によく用いられる方法である。 <Evaluation of FSS>
The evaluation of the obtained results uses the VAS (visual analogue scale) method, which is generally used internationally, that is, a line segment of 100 mm, the maximum pain / fatigue is 100 mm, and there is no pain / fatigue at all. Was set to 0 mm, and the state of the measurement date was entered by the subject in a line segment. This method is often used to evaluate symptoms without objective indicators such as pain and fatigue.
　統計数字は、平均値±標準偏差で表現し、ＭＡＣ版、統計ソフトＳＳＭＣにより解析した。 Statistical figures were expressed as mean ± standard deviation and analyzed by MAC version and statistical software SSMC.
　結果を図１～４に示す。
　図１は、疲労ＶＡＳの投与前後での変化を比較した図である。投与前の各群間の疲労ＶＡＳ値には有意差はなかった。Ｐ群については、投与前後に有意差はなかった。一方、Ｌ群及びＭ群では、投与前と比較して投与後において有意差があった。Ｍ群のほうが、有意差は大きかった。「＊＊」は、前値に対しｐ＜０．０１、「＊＊＊」は、前値に対しｐ＜０．００１を表す。 The results are shown in FIGS. 1 to 4.
FIG. 1 is a diagram comparing changes before and after administration of fatigue VAS. There was no significant difference in fatigue VAS values between the groups before administration. For group P, there was no significant difference before and after administration. On the other hand, in the L group and the M group, there was a significant difference after the administration as compared with before the administration. The significant difference was larger in the M group. “**” represents p <0.01 with respect to the previous value, and “***” represents p <0.001 with respect to the previous value.
　図２は、疲労ＶＡＳの投与前後での変化率を比較した図である。変化率は、［（投与後の疲労ＶＡＳ－投与前の疲労ＶＡＳ）／投与前の疲労ＶＡＳ］×１００（％）として算出した。Ｌ群、Ｍ群では、Ｐ群に比し、疲労ＶＡＳ値は有意に低下した。Ｌ群とＭ群の比較では、Ｍ群のほうがより有意に低下した。「＊＊」は、Ｐ群に対しｐ＜０．０１、「＊＊＊」は、Ｐ群に対しｐ＜０．００５を表し、「※※」は、Ｌ群に対しｐ＜０．０１を表す。 FIG. 2 is a diagram comparing the rate of change before and after administration of fatigue VAS. The rate of change was calculated as [(Fatigue VAS after administration-Fatigue VAS before administration) / Fatigue VAS before administration] × 100 (%). In the L group and the M group, the fatigue VAS value was significantly lower than that in the P group. In the comparison between the L group and the M group, the M group decreased more significantly. “**” represents p <0.01 for the P group, “***” represents p <0.005 for the P group, and “**” represents p <0.01 for the L group. Represents.
　図３は、疼痛ＶＡＳの投与前後での変化を比較した図である。投与前の各群間の疼痛ＶＡＳ値には有意差はなかった。Ｐ群については、投与前後に有意差はなかった。一方、Ｌ群及びＭ群では、投与前と比較して投与後において有意差があった。Ｍ群のほうが、有意差は大きかった。「＊＊」は、前値に対しｐ＜０．０１、「＊＊＊」は、前値に対しｐ＜０．００１を表す。 FIG. 3 is a diagram comparing changes before and after administration of pain VAS. There was no significant difference in pain VAS values between the groups before administration. For group P, there was no significant difference before and after administration. On the other hand, in the L group and the M group, there was a significant difference after the administration as compared with before the administration. The significant difference was larger in the M group. “**” represents p <0.01 with respect to the previous value, and “***” represents p <0.001 with respect to the previous value.
　図４は、疼痛ＶＡＳの投与前後での変化率を比較した図である。変化率は、［（投与後の疼痛ＶＡＳ－投与前の疼痛ＶＡＳ）／投与前の疼痛ＶＡＳ］×１００（％）として算出した。Ｌ群、Ｍ群では、Ｐ群に比し、疼痛ＶＡＳ値は有意に低下した。Ｌ群とＭ群の比較では、Ｍ群のほうがより有意に低下した。「＊＊」は、Ｐ群に対しｐ＜０．０１、「＊＊＊」は、Ｐ群に対しｐ＜０．００５を表し、「※※」は、Ｌ群に対しｐ＜０．０１を表す。 FIG. 4 is a diagram comparing the rate of change before and after administration of pain VAS. The rate of change was calculated as [(Pain VAS after administration-Pain VAS before administration) / Pain VAS before administration] × 100 (%). In the L group and the M group, the pain VAS value was significantly lower than that in the P group. In the comparison between the L group and the M group, the M group decreased more significantly. “**” represents p <0.01 for the P group, “***” represents p <0.005 for the P group, and “**” represents p <0.01 for the L group. Represents.
＜安全性の検討＞
　各群について、投与開始前及び投与終了後に、血液及び尿検体を採取し、血算（赤血球、白血球、ヘモグロビン、ヘマトクリット、血小板）、Ａｌｂ、ＧＯＴ、ＧＰＴ、ＬＤＨ、ＡｌＰ、γ－ＧＴＰ、アミラーゼ、ＢＵＮ、クレアチニン、血糖値、ヘモグロビンＡ１ｃ、尿（蛋白、糖、ウロビリノーゲン）の検査を行って、結果を比較した。 <Consideration of safety>
For each group, blood and urine samples were collected before the start of administration and after the end of administration, and blood counts (erythrocytes, leukocytes, hemoglobin, hematocrit, platelets), Alb, GOT, GPT, LDH, AlP, γ-GTP, amylase, BUN, creatinine, blood glucose level, hemoglobin A1c, and urine (protein, sugar, urobilinogen) were tested and the results were compared.
　投与の前後にわたって、これらの血液及び尿検査の異常は、どの群にも認められなかった。副作用としては、軟便がＰ群に１例、Ｌ群に３例、Ｍ群に３例、観られた。 No abnormalities in these blood and urine tests were observed in any of the groups before and after administration. As side effects, loose stools were observed in 1 case in the P group, 3 cases in the L group, and 3 cases in the M group.
　本研究の結果によれば、本発明の機能性身体症候群の予防又は改善用剤を投与された群では、Ｌ群及びＭ群のいずれにおいても、疲労ＶＡＳ及び疼痛ＶＡＳが改善され、その改善効果は、Ｍ群、すなわち、乳酸菌ＬＡＢ４及びグルコマンナンを投与された群において特に顕著であった。いずれの群においても、副作用としては少数の被験者に若干の軽微な軟便が見られただけであり、本発明の剤及び組成物は非常に安全性が高いことが確認された。 According to the results of this study, in the group to which the preventive or ameliorating agent for functional somatic syndrome of the present invention was administered, fatigue VAS and pain VAS were improved in both the L group and the M group, and the improving effect thereof. Was particularly prominent in the M group, that is, the group to which the lactic acid bacteria LAB4 and glucomannan were administered. In each group, only a few slight loose stools were observed as side effects in a small number of subjects, confirming that the agent and composition of the present invention are extremely safe.
　この出願は、２０１９年１２月２日出願の日本特許出願、特願２０１９－２１８２１９に基づくものであり、特願２０１９－２１８２１９の明細書及び特許請求の範囲に記載された内容は、すべてこの出願明細書に包含される。 This application is based on the Japanese patent application filed on December 2, 2019, Japanese Patent Application No. 2019-218219, and the description of Japanese Patent Application No. 2019-218219 and the contents described in the claims are all in this application. Included in the specification.

Claims (11)

  1. 　乳酸菌ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティス又はその乳酸菌由来成分を有効成分とする機能性身体症候群の予防又は改善用剤。 A drug for preventing or ameliorating functional somatic syndrome containing lactic acid bacterium Lactobacillus delbricky subspecies lactis or its lactic acid bacterium-derived ingredient as an active ingredient.
  2. 　前記乳酸菌が、ラクトバチルス・デルブリッキー・サブスピーシーズ・ラクティスＫＬＡＢ－４株（ＮＩＴＥ　ＢＰ－３９４）及びその変異体からなる群から選択される乳酸菌を含む、請求項１記載の機能性身体症候群の予防又は改善用剤。 The prevention of functional somatic syndrome according to claim 1, wherein the lactic acid bacterium includes a lactic acid bacterium selected from the group consisting of Lactobacillus delbricky Subspecies Lactis KLAB-4 strain (NITE BP-394) and a mutant thereof. Improvement agent.
  3. 　水溶性食物繊維成分をさらに含有する、又は水溶性食物繊維成分と併用される、請求項１又は２記載の機能性身体症候群の予防又は改善用剤。 The agent for preventing or ameliorating functional somatic syndrome according to claim 1 or 2, which further contains a water-soluble dietary fiber component or is used in combination with a water-soluble dietary fiber component.
  4. 　前記水溶性食物繊維成分が、グルコマンナン、ペクチン、グアーガム、アルギン酸、ポリデキストロース、βグルカン、フルクタン、イヌリン、レバン、グラミナン、アラビアガム、マルチトール、サイリウム、難消化性オリゴ糖、難消化性デキストリン、アガロース、アルギン酸ナトリウム、カラギーナン、フコイダン、ポルフィラン、ラミナラン、海藻、及び寒天からなる群から選択される、請求項３記載の機能性身体症候群の予防又は改善用剤。 The water-soluble dietary fiber component is glucomannan, pectin, guar gum, alginic acid, polydextrose, β-glucan, fructan, inulin, levan, graminan, arabic gum, martitol, psyllium, indigestible oligosaccharide, indigestible dextrin, The agent for preventing or ameliorating functional physical syndrome according to claim 3, which is selected from the group consisting of agarose, sodium alginate, carrageenan, fucoidan, porphyran, laminaran, seaweed, and agar.
  5. 　前記水溶性食物繊維成分が、グルコマンナンである、請求項４記載の機能性身体症候群の予防又は改善用剤。 The agent for preventing or ameliorating functional somatic syndrome according to claim 4, wherein the water-soluble dietary fiber component is glucomannan.
  6. 　前記機能性身体症候群が、過敏性腸症候群、機能性ディスペプチア、過換気症候群、気管支喘息様気管支炎、狭心症、不整脈、低血圧、慢性頭痛、慢性腰痛、複合性局所疼痛症候群、頸肩腕症候群、線維筋痛症、筋痛性脳症/慢性疲労症候群、慢性疲労症候群、化学物質過敏症、月経前症候群、更年期障害、及び顎関節症からなる群から選択される、請求項１～５のいずれか１項記載の機能性身体症候群の予防又は改善用剤。 The functional somatic syndromes are irritable bowel syndrome, functional dyspeptia, hyperventilation syndrome, bronchial asthma-like bronchitis, angina, arrhythmia, hypotension, chronic headache, chronic low back pain, complex local pain syndrome, cervicobrachial syndrome. , Fibromyalgia, Myopathic Encephalopathy / Chronic Fatigue Syndrome, Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Premenstrual Syndrome, Menopausal Disorder, and Temporomandibular Disorders, any of claims 1-5. The agent for preventing or ameliorating functional somatic syndrome according to item 1.
  7. 　請求項１～６のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、組成物。 A composition comprising a preventive or ameliorating agent for functional somatic syndrome according to any one of claims 1 to 6.
  8. 　請求項１～６のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、医薬品組成物。 A pharmaceutical composition comprising a preventive or ameliorating agent for functional somatic syndrome according to any one of claims 1 to 6.
  9. 　請求項１～６のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、飲食品組成物。 A food or drink composition containing a preventive or ameliorating agent for functional somatic syndrome according to any one of claims 1 to 6.
  10. 　請求項１～６のいずれか１項記載の機能性身体症候群の予防又は改善用剤を含む、動物用飼料又は動物用医薬品組成物。 A veterinary feed or veterinary drug composition containing a prophylactic or ameliorating agent for functional somatic syndrome according to any one of claims 1 to 6.
  11. 　請求項１～６のいずれか１項記載の機能性身体症候群の予防又は改善用剤、あるいは請求項７～１０のいずれか１項記載の組成物を、対象に投与することを含む、機能性身体症候群の予防又は改善方法。 Functionality comprising administering to a subject the agent for preventing or ameliorating the functional somatic syndrome according to any one of claims 1 to 6, or the composition according to any one of claims 7 to 10. How to prevent or improve physical syndrome.
PCT/JP2020/044056 2019-12-02 2020-11-26 Agent for preventing or ameliorating functional somatic syndromes and composition including the same WO2021111983A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009066681A1 (en) * 2007-11-19 2009-05-28 Kaneka Corporation Lactic acid bacterium-containing preparation
CN107259575A (en) * 2017-05-31 2017-10-20 华子昂 A kind of health care ferment with anti-oxidation function and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009066681A1 (en) * 2007-11-19 2009-05-28 Kaneka Corporation Lactic acid bacterium-containing preparation
CN107259575A (en) * 2017-05-31 2017-10-20 华子昂 A kind of health care ferment with anti-oxidation function and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WU WEN-TZU, CHENG HAN-CHUNG, CHEN HSIAO-LING: "Ameliorative effects of konjac glucomannan on human faecal beta-glucuronidase activity, secondary bile acid levels and faecal water toxicity towards Caco-2 cells", BRITISH JOURNAL OF NUTRITION, vol. 105, no. 4, 28 February 2011 (2011-02-28), pages 593 - 600, XP055831999, ISSN: 0007-1145, DOI: 10.1017/S0007114510004009 *

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