WO2018128481A1 - Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant comme principe actif de l'indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci - Google Patents

Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant comme principe actif de l'indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci Download PDF

Info

Publication number
WO2018128481A1
WO2018128481A1 PCT/KR2018/000304 KR2018000304W WO2018128481A1 WO 2018128481 A1 WO2018128481 A1 WO 2018128481A1 KR 2018000304 W KR2018000304 W KR 2018000304W WO 2018128481 A1 WO2018128481 A1 WO 2018128481A1
Authority
WO
WIPO (PCT)
Prior art keywords
muscle
indole
carbinol
active ingredient
composition
Prior art date
Application number
PCT/KR2018/000304
Other languages
English (en)
Korean (ko)
Inventor
박태선
Original Assignee
연세대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 연세대학교 산학협력단 filed Critical 연세대학교 산학협력단
Publication of WO2018128481A1 publication Critical patent/WO2018128481A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/132—Heterocyclic compounds containing only one nitrogen as hetero atom
    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles

Definitions

  • the present invention relates to a composition for preventing or treating muscle diseases, comprising indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the elderly population accounted for 7.2% of the total population in 2000 and entered an aging society.
  • the aged population is expected to enter an aging society (more than 20%).
  • Muscle mass in humans decreases with age (10-15% at 50-70 years, and more than 30% at 70-80 years), thereby weakening muscle strength and muscle function, called sarcopenia. do.
  • Geriatric muscular dystrophy is a major cause of limiting the independent living of the elderly by inducing activity disorder and gait disorder.
  • myopathy lowers metabolic rate, increases insulin resistance, promotes type 2 diabetes, and increases the risk of hypertension and cardiovascular disease by three to five times.
  • drug repositioning technology is being developed to apply myostatin inhibitor or other FDA-approved drugs to myopathy.
  • Muscles are divided into skeletal muscles, cardiac muscles, and smooth muscles, and skeletal muscles are the most abundant tissues in the human body, accounting for 40 to 45% of body weight. Skeletal muscles attach to bones through the tendons, creating bone movement or force.
  • One muscle is made up of numerous myofibers, which in turn are made up of numerous myofibers composed of actin and myosin. When actin and myosin overlap each other, they shorten or lengthen the muscles, causing the entire muscle to contract and relax.
  • An increase in myofibril size means an increase in myofiber thickness, resulting in an increase in muscle.
  • Type I muscle fibers that make up muscle are classified into Type I, Type IIA and Type IIB by the metabolic process and contraction rate that produce ATP.
  • Type I muscle fibers are slow in contraction and contain a large number of myoglobin and mitochondria, making them suitable for continuous, low-intensity aerobic activity.
  • Type II muscle fibers have a red color and are also called red muscles, and soleus is typical.
  • 'Type IIB muscle fibers' are very short but have high strength for anaerobic exercise due to their high contraction speed. They are white due to the low content of myoglobin, and the gastrocnemius is one of them.
  • Type IIA muscle fibers have the intermediate characteristics of the two muscle fibers mentioned above, and the rectus femoris. As the body ages, not only the composition of Type I and II muscle fibers varies by muscle area, but all types of muscle fibers decrease.
  • Skeletal muscles have the characteristics of being regenerated and maintained according to the environment, but these characteristics are lost with age, and consequently, as aging progresses, muscle mass is reduced and muscle strength is also lost.
  • Signaling systems involved in the growth and regeneration of muscle include signaling mediated by insulin like growth factor 1 (IGF-1) / AKT to regulate protein synthesis.
  • IGF-1 receptor IGF-1R
  • the activation of IGF-1 receptor (IGF-1R) in the muscle cell membrane increases AKT phosphorylation through IRS1 and PI3K phosphorylation, and the latter activates mTORC phosphorylation.
  • Activation of mTORC increases the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K1), which increases mRNA translation and increases the activity of eukaryotic translation initiation factor 4 G (eIF4G), and eukaryotic translation initiation factor 4E binding protein Phosphorylate 1 (4E-BP1) protein.
  • eIF4G and 4E-BP1 are involved in the formation of the eIF4F complex, that is, eIF4G binds to eIF4A and eIF4E to form the eIF4F complex, while phosphorylation of 4E-BP1 inhibits its binding to eIF4E, leading to an increase in free eIF4E. do.
  • Akt / mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.Nature cell biology, 3, 1014-1019, 2001).
  • AKT phosphorylation stimulates muscle fiber growth by increasing eIF2B expression through glycogen synthase kinase 3 (GSK3) and also inhibits muscle loss by inhibiting the expression of forkhead box O (FOXO), a proteolytic transcription factor.
  • Muscle loss is regulated by signaling mediated by receptors of the TGF- ⁇ family, including myostatin, transforming growth factor beta (TGF- ⁇ ), and activin. Binding of the ligand to the TGF- ⁇ type II receptor phosphorylates the type I receptor, the latter phosphorylates the smad 2/3 complex and eventually activates FOXO.
  • the latter increases gene expression of muscle-specific ubiquitin-ligase, muscle RING-finger protein-1 (MURF1) and Muscle Atrophy F-Box (MAFbx) / atrogin-1, which attach ubiquitin to the lysine site of the target protein. Promote proteolysis and eventually induce muscle loss (Gumucio et al., Atrogin-1, MuRF-1, and sarcopenia. Endocrine, 43, 12-21, 2013).
  • MURF1 muscle RING-finger protein-1
  • MAFbx Muscle Atrophy F-Box
  • An object of the present invention is to prevent or treat muscle diseases, including indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient, to promote muscle differentiation, muscle regeneration or muscle enhancement To provide a composition.
  • Still another object of the present invention is to provide a cosmetic composition for improving muscle function, including indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is a method for preventing or treating muscle diseases, comprising administering to or administering to a subject a pharmaceutical composition comprising indole-3-carbinol or a salt thereof as an active ingredient, It is to provide a method for promoting muscle differentiation, muscle regeneration or muscle strengthening.
  • Another object of the present invention to provide a method for preventing or treating muscle diseases, promoting muscle differentiation, muscle regeneration or muscle strengthening of a composition comprising indole-3-carbinol or a salt thereof as an active ingredient. will be.
  • the composition may increase the expression of p-4E-BP1 or p-p70S6K1 protein.
  • the composition may reduce the expression of a MuRF1 (Muscle Ring-Finger Protein) or MaFbx (Muscle atrophy F-box).
  • MuRF1 Muscle Ring-Finger Protein
  • MaFbx Muscle atrophy F-box
  • the muscle disease may be a muscle disease due to muscle function decline, muscle reduction, muscle wasting or muscle degeneration.
  • the muscle disease is atony, muscular atrophy, muscular dystrophy, myasthenia, cachexia, rigid spinesyndrome, muscular dystrophy At least one selected from the group consisting of sclerosis (amyotrophic lateral sclerosis), Charcot-Marie-Tooth disease, and sarcopenia.
  • the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention also provides a health functional food composition for preventing muscle diseases or improving muscle function, including indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention also provides a health functional food composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, including indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a composition for animal feed for preventing or improving muscle diseases, which comprises indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a cosmetic composition for improving muscle function, comprising indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a method for preventing or treating muscle diseases, comprising administering to or administering to a subject a pharmaceutical composition comprising indole-3-carbinol or a salt thereof as an active ingredient. .
  • the present invention provides a method for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising administering to or administering to a subject a composition comprising indole-3-carbinol or a salt thereof as an active ingredient. to provide.
  • the present invention provides a use for preventing or treating muscle diseases of a composition comprising indole-3-carbinol or a salt thereof as an active ingredient.
  • the present invention provides the use of indole-3-carbinol or a salt thereof as an active ingredient to promote muscle differentiation, muscle regeneration or muscle strengthening.
  • the present invention relates to a composition for preventing or treating muscle diseases or improving muscle function, which comprises indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • 3-carbinol can increase the expression of proteins involved in muscle protein synthesis and muscle mass in muscle cells, and the expression of enzymes involved in muscle protein degradation can be suppressed from the mRNA level, thus reducing muscle function, muscle wasting or muscle degeneration
  • muscle diseases caused by muscle differentiation, muscle regeneration, muscle mass increase effect can be exhibited, and can inhibit muscle loss, bar disease prevention or treatment, muscle differentiation, muscle regeneration and muscle mass increase or It can be used to improve muscle function.
  • FIG. 1 shows the thickness change of myotube in mouse myoblasts.
  • FIG. 1A is a microscopic image of Giemsa-wright stained root canal cells
  • FIG. 1B is a result of measuring the diameter of the root canal cells, and each value is the mean ⁇ standard error of three crystals in three independent wells. P ⁇ 0.05 indicates statistical significance.
  • FIG. 2 shows the expression changes of proteins involved in protein degradation and synthesis in mouse myoblasts treated with indole-3-carbinol.
  • FIG. 2A shows the protein levels of p-4E-BP1, Total 4E-BP1, p-p70S6K1, and Total p70S6K1, and
  • FIG. 2B shows gene expression levels of MaFbx and MuRF1. Each value is the mean ⁇ standard error of three determinations in three independent wells. P ⁇ 0.05 indicates statistical significance.
  • Figure 3 shows the changes in body weight (A), hanging time (B) and grip force (C) of the normal diet (Chow), high fat diet (HFD) and indole-3-carbinol mice This is a result of confirming the increase in muscle strength by indole-3-carbinol intake.
  • muscle refers to tendons, muscles, and tendons in general
  • muscle function means the ability to exert a force by contraction of muscles, muscles can exert maximum contraction force to withstand resistance Muscle strength, which is the ability to be present, muscle endurance, which is how long or how many times a muscle can repeat contraction and relaxation, and quickness, which is the ability to exert a strong force in a short time.
  • Muscle functions are subjective to the liver, proportional to muscle mass, and “muscle improvement” means better muscle function.
  • the indole-3-carbinol is a grayish white solid, which is an indole compound which is extremely unstable under acidic solution and is changed to another derivative by biological activity when exposed to gastric acid.
  • C 9 H 9 NO molecular weight is 147.17 g / mol.
  • Indole-3-carbinol may be represented by Formula 1 below, and the IUPAC name is 1H-Indol-3-ylmethanol.
  • composition according to the invention can increase the expression of p-4E-BP1 or p-p70S6K1 protein.
  • the pharmaceutical composition for preventing or treating muscle diseases according to the present invention is not particularly limited as long as it contains indole-3-carbinol or a pharmaceutically acceptable salt thereof, preferably the indole-3-carbinol
  • the dose may include, but is not limited to, a concentration of 0.1 ⁇ M to 1000 ⁇ M.
  • the indole-3-carbinol is less than the concentration range, there is a problem that the protein synthesis and degradation activity in muscle cells is lowered, it is difficult to exhibit the effect of preventing or treating muscle disease, indole-3-carbinol in the concentration range If exceeded, there may be toxicity concerns, including cytotoxicity.
  • the carrier or excipient or diluent may be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicide, cellulose, methyl cellulose, undetermined. And various compounds or mixtures including vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin and the like can be used.
  • the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening comprising indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient. Specific details of the indole-3-carbinol are as described above.
  • Muscle growth can occur by increasing the fiber size and / or by increasing the number of fibers.
  • the growth of the muscle can be measured by A) increase in wet weight, B) increase in protein content, C) increase in number of muscle fibers, and D) increase in diameter of muscle fibers.
  • An increase in muscle fiber growth can be defined as an increase in diameter when the diameter is defined as the shortening of the ellipsoid in cross section.
  • Useful therapeutic agents include, but are not limited to, wetting gain, protein content, and / or in animals with muscle degeneration at least 10% compared to control animals previously treated similarly (ie, animals with degenerated muscle tissue not treated with muscle growth compounds). Increasing the diameter by at least 10%, more preferably at least 50%, and most preferably at least 100%.
  • Compounds that increase growth by increasing the number of muscle fibers are useful as therapeutic agents when they increase the number of muscle fibers in diseased tissues by at least 1%, more preferably at least 20%, and most preferably at least 50%. These percentage values are relative to the basal level in untreated and disease-free comparative mammals or when the compound is administered locally and in contrast to disease-free muscle.
  • Muscle regeneration refers to the process by which new muscle fibers are formed from myoblasts.
  • Useful therapeutic agents for regeneration increase the number of new fibers at least about 1%, more preferably at least 20%, and most preferably at least 50%, as described above.
  • Myocyte differentiation refers to the induction of muscle developmental programs that specify components of muscle fibers such as contractile organs (myofibril).
  • Useful therapeutic agents for differentiation may comprise at least about 10%, more preferably at least 50%, and most preferably at least 100% of all myofiber components in diseased tissues, as compared to equivalent tissues in similarly treated control animals. Increase.
  • indole-3-carbinol when indole-3-carbinol was treated to mouse myoblasts reduced by dexamethasone, myotubes of the mouse myoblasts were significantly increased. can confirm. That is, the indole-3-carbinol of the present invention can suppress muscle loss and promote muscle growth by increasing the thickness of myotubes in mouse myoblasts.
  • the present invention also provides a health functional food composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, including indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient. Specific details of the indole-3-carbinol are as described above.
  • the indole-3-carbinol when used as an additive for the health functional food, it may be added as it is or used together with other foods or food ingredients, Can be used accordingly.
  • the mixed amount of the active ingredient can be appropriately determined depending on the purpose of use, such as prevention, health or treatment.
  • Formulations of dietary supplements may be in the form of powders, granules, pills, tablets, capsules, as well as in the form of general foods or beverages.
  • the indole-3-carbinol may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of the raw material.
  • the amount may be below the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. The above amount can also be used.
  • the beverage in the health functional food according to the present invention may contain various flavors or natural carbohydrates, etc. as an additional ingredient, as in general drinks.
  • the above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol.
  • sweetening agent natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.
  • the present invention provides a composition for animal feed for preventing or improving muscle diseases, which comprises indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a composition for animal feed for preventing or improving muscle diseases which comprises indole-3-carbinol or a pharmaceutically acceptable salt thereof as an active ingredient. Specific details of the indole-3-carbinol are as described above.
  • the livestock is preferably one kind of livestock selected from the group consisting of cattle, pigs, chickens, ducks, goats, sheep and horses, but is not limited thereto.
  • the feed composition may include a feed additive.
  • the feed additive of the present invention corresponds to a feed supplement in the Feed Control Act.
  • feed may refer to any natural or artificial diet, one meal, or the like, or a component of the one meal, for the animal to eat, ingest, and digest.
  • the present invention provides a cosmetic composition for improving muscle function comprising indole-3-carbinol (Indole-3-carbinol) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • indole-3-carbinol indole-3-carbinol
  • a pharmaceutically acceptable salt thereof as an active ingredient.
  • the excipients include, but are not limited to, emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents.
  • fragrances, pigments, fungicides, antioxidants, preservatives and moisturizing agents may be further included, and may include thickeners, inorganic salts, synthetic polymer materials and the like for the purpose of improving the properties.
  • the indole-3-carbinol may be easily added to the face wash and the soap base.
  • the cream When the cream is prepared, it may be prepared by adding indole-3-carbinol or a salt thereof to a cream base of a general oil-in-water type (O / W). To this, synthetic or natural materials, such as proteins, minerals, vitamins, etc., for the purpose of improving physical properties, such as flavors, chelating agents, pigments, antioxidants, and preservatives, may be added.
  • the content of indole-3-carbinol contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight based on the total weight of the composition. If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect may not be expected, and when the content is more than 10% by weight, there may be difficulty in preparing a safety or formulation.
  • the present invention is a method for preventing or treating muscle diseases comprising the step of administering to or administering to a subject a pharmaceutical composition comprising indole-3-carbinol or a salt thereof as an active ingredient, muscle differentiation Provide methods of palpation, muscle regeneration, or muscle strengthening.
  • the present invention also provides a use for preventing or treating muscle diseases, promoting muscle differentiation, muscle regeneration or muscle strengthening of a composition comprising indole-3-carbinol or a salt thereof as an active ingredient.
  • Mouse myoblast cell lines (C2C12 cells) were purchased from ATCC (Manassas, VA, USA), and the cells were purchased at 37 ° C., 5% CO using 10% fetal bovine serum media (Gibco-BRL). Incubated in 2 incubators. When the cultured cells became 80% confluent, they were differentiated into myotubes using 2% horse serum media (Gibco-BRL).
  • the stained myotubes were taken at X20 magnification using a fluorescence microscope (IX 71, Olympus) and analyzed using image J software (USA). Six sections of each well were randomly selected and micrographed, and at least 100 myoblast thicknesses were analyzed from each well (3 replicates / Group).
  • Example 1 in Comparative Example 1, the thickness of the myotube was significantly reduced compared to that of normal cells, and in Example 1 treated with indole-3-carbinol, it was decreased by dexamethasone. Visually, the myotube thickness was increased again. In addition, as shown in Figure 1B, it was confirmed that even when treated with indole-3-carbinol quantified using the image J software, the myotube thickness reduced by dexamethasone increased 56% significantly. From this, it can be seen that indole-3-carbinol increases the thickness of myotube in mouse myoblasts, thereby inhibiting muscle loss and promoting muscle growth.
  • RNA samples extracted from mouse myoblasts were synthesized by reverse transcription using oligo dT primers and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA). PCR was performed using 5 'and 3' flanking sequences of the gene cDNA to be amplified as a template and cDNA obtained through reverse transcription, and the primer sequences used are shown in Table 1 below. 1 ⁇ l of the amplified PCR product was electrophoresed on a 1% agarose gel to confirm the DNA band.
  • p70S6K1, phopho-p70S6K1 (p-p70S6K1), 4E-BP1, phospho-4E-BP1 (p-4E-BP1) and GAPDH were used as primary antibodies.
  • the proteins were visualized on an X-ray film using an ECL Western blot detection kit (RPN2106, Amersham, Arlington Heights, IL, USA). Bands visualized on the X-ray film were scanned and quantified using Quantity One analysis software (Bio-Rad).
  • Figure 2 is a graph showing the change in expression of protein degradation and synthesis in mouse myoblasts treated with indole-3-carbinol.
  • FIG. 2A in Comparative Example 1, the amount of p-4E-BP1 and p-p70S6K1 proteins related to protein synthesis was significantly reduced compared to normal cells (Basal) (FIG. 2A). Genes MaFbx / atrogin1 and MuRF1 expression can be seen to increase significantly (Fig. 2B).
  • FIG. 2A shows that the amount of p-4E-BP1 and p-p70S6K protein reduced by dexamethasone was again significantly increased (FIG.
  • mice Twenty five-week-old male C57BL / 6N mice (mating, Korea) were adapted to a laboratory environment for one week on a commercial rodant chow, and then in three groups (Chow, HFD, and Indole-) according to the ovary method. 8 animals per group were randomly placed in 3-carbinol group for 10 weeks.
  • the obesity induction diet used in this experiment was a high fat diet (HFD: 40% fat calorie, 17 g lard + 3% corn oil / 100 g diet) and an indole-3-carbinol supplement (Indole) -3-carbinol-supplemented high fat diet (Indole-3-carbinol) had the same composition as HFD but contained 0.2% of indole-3-carbinol (Table 2). Chow fed a commercial rodent chow. Indole-3-carbinol was purchased from Sigma-Aldrich.
  • HFD High fat Control diet
  • Indole-3-carbinol Supplementary diet g / kg diet
  • Casein 200 200 DL-Methionine 3 3
  • Corn starch 111 109 Sucrose 370 370 cellulose 50 50
  • Corn oil 30
  • Mineral complex 42 Choline Bitartrate 2
  • cholesterol 10
  • tert-butyhydroquinone 0.04 0.04 Test substance (Indole-3-carbinol) - 2 Total (g) 1,000 1,000 1,000
  • grip strength was measured using the four feet of the mouse at 10 weeks of breeding.
  • the grip force measuring device equipped with a wire mesh (20 x 10 cm) (Daejong Equipment Industry, Korea) measured the force (N) of the wire mesh of the mouse a total of five times, and at least 1 minute rest between measurements. Gave time.
  • the experimental results were obtained by dividing the measured force (N) and weight (kg).
  • the muscle tissue of the mouse was extracted, fixed in 10% formalin, and then stained with Hematoxylin and eosin (H & E) by a Korean CFC (Gyeonggi-do, Korea) and observed using an optical microscope (IX71, Olympus, JPN). Pictures were taken using a camera (DP71, Olympus, JPN).
  • indole-3-carbinol was significantly reduced by 36% than the weight of the mice fed the high fat diet (Fig. 3A).
  • Indole-3-carbinol also significantly increased the holding impulse (FIG. 3B) and grip strength (FIG. 3C) of mice fed high fat diets by 169% and 38%, respectively. From these results, indole-3-carbinol was found to have a very good strength enhancing effect in high fat diet induced muscle loss animal model.
  • indole-3-carbinol was found in the rectus femoris (6%, FIG. 4A) and soleus (6%, FIG. 4B) of high-fat diet mice.
  • the fiber diameter was significantly increased. Therefore, it was found that indole-3-carbinol showed a very good skeletal muscle increase effect in the high fat diet induced muscle loss animal model.
  • the above ingredients were mixed and filled in an airtight cloth to prepare a powder.
  • tablets were prepared by tableting according to a conventional method for producing tablets.
  • the above components are dissolved in purified water according to a conventional preparation method, dissolved in purified water, and then lemon juice is added in an appropriate amount. After adjusting to 100 mL in total, sterilized and filled in a brown bottle to prepare a liquid formulation.
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored Used to prepare the healthy beverage composition of the invention.
  • composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • the compounding ratio is mixed with a component suitable for nutritional longevity in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is mixed composition of a component suitable for a flexible softener in a preferred embodiment, but the blending ratio may be arbitrarily modified, it can be prepared according to the manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for nourishing cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the compounding ratio is mixed with a component suitable for a massage cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for a pack in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for a gel in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the blending ratio is a relatively suitable composition for the cosmetic composition in a preferred embodiment, but can be applied to cosmetics of various uses, including other color cosmetics, according to the efficacy that can be applied to a thin coating on the human body, that is, Ointment may be used for manufacturing, and the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • composition 0.1-10%
  • Vitamin E 0.01 ⁇ 0.1%
  • a feed was prepared as follows.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Husbandry (AREA)
  • Birds (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une composition servant à prévenir ou à traiter des maladies musculaires ou à améliorer la fonction musculaire, qui comprend comme principe actif de l'indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci.
PCT/KR2018/000304 2017-01-06 2018-01-05 Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant comme principe actif de l'indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci WO2018128481A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020170002505A KR20180081361A (ko) 2017-01-06 2017-01-06 인돌-3-카비놀 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근육 질환 예방 또는 치료용 조성물
KR10-2017-0002505 2017-01-06

Publications (1)

Publication Number Publication Date
WO2018128481A1 true WO2018128481A1 (fr) 2018-07-12

Family

ID=62789500

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2018/000304 WO2018128481A1 (fr) 2017-01-06 2018-01-05 Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant comme principe actif de l'indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci

Country Status (2)

Country Link
KR (1) KR20180081361A (fr)
WO (1) WO2018128481A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001008637A2 (fr) * 1999-08-02 2001-02-08 Designed Nutritional Products, Inc. Traitement du syndrome premenstruel et de la menopause
WO2009103754A2 (fr) * 2008-02-19 2009-08-27 Dsm Ip Assets B.V. Nouvelle utilisation de 3,3'-diindolylméthane
US20140056862A1 (en) * 2011-04-18 2014-02-27 Nestec S.A. Nutritional compositions having alpha-hica and alpha-ketoglutarate
WO2016149277A1 (fr) * 2015-03-17 2016-09-22 Specialty Nutrition Group, Inc. Compositions nutritionnelles pour améliorer la production d'énergie mitochondriale

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001008637A2 (fr) * 1999-08-02 2001-02-08 Designed Nutritional Products, Inc. Traitement du syndrome premenstruel et de la menopause
WO2009103754A2 (fr) * 2008-02-19 2009-08-27 Dsm Ip Assets B.V. Nouvelle utilisation de 3,3'-diindolylméthane
US20140056862A1 (en) * 2011-04-18 2014-02-27 Nestec S.A. Nutritional compositions having alpha-hica and alpha-ketoglutarate
WO2016149277A1 (fr) * 2015-03-17 2016-09-22 Specialty Nutrition Group, Inc. Compositions nutritionnelles pour améliorer la production d'énergie mitochondriale

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GUN CLUB, BOOST YOUR TESTOSTERONE WITH INDOLE-3-CARBINOL, 20 June 2015 (2015-06-20), Retrieved from the Internet <URL:https://www.aimtowin.com/shooting-range/boost-your-testosterone-with-indole-3-carbinol> *

Also Published As

Publication number Publication date
KR20180081361A (ko) 2018-07-16

Similar Documents

Publication Publication Date Title
WO2018070707A1 (fr) Composition pour la prévention ou le traitement de maladie musculaire, contenant comme principe actif decanal ou un sel pharmaceutiquement acceptable de celui-ci
WO2018124508A1 (fr) Composition pour la prévention et le traitement de maladies musculaires ou pour l&#39;amélioration de la fonction musculaire, contenant de l&#39;acide 3,5-dicaféoylquinique ou de l&#39;extrait de chrysanthème
WO2019135637A1 (fr) Procédé de préparation d&#39;un extrait de feuille de gynostemma pentaphyllum contenant une quantité accrue de saponine efficace de faible masse moléculaire et une quantité réduite de benzopyrène, et extrait de feuille de gynostemma pentaphyllum préparé selon ledit procédé
WO2018128479A1 (fr) Composition pour la prévention ou le traitement de maladies musculaires, comprenant comme principe actif de l&#39;acide subérique ou un sel pharmaceutiquement acceptable de celui-ci
WO2018128483A1 (fr) Composition pour la prévention ou le traitement de maladies musculaires, comprenant de l&#39;ocimène, de l&#39;eugénol ou un sel pharmaceutiquement acceptable de ceux-ci en tant que principe actif
WO2018236186A1 (fr) Composition comprenant un dérivé de sesquiterpène en tant que principe actif pour la prévention ou le traitement de maladies musculaires
WO2022035115A1 (fr) Composition pour la prévention et le traitement des troubles musculo–squelettiques contenant un extrait d&#39;alnus japonica ou un composé isolé à partir de celui-ci et utilisation de celle-ci
WO2020218720A1 (fr) Composition pour la prévention ou le traitement de troubles musculaires ou l&#39;amélioration de la fonction musculaire, contenant un extrait de leonurus japonicus ou de la léonurine
WO2010087577A2 (fr) Utilisation d&#39;extrait de thymus capitatus, d&#39;extrait de satureja hortensis, ou de carvacrol pour traiter des maladies métaboliques
WO2018070705A1 (fr) Composition pour prévenir ou traiter des maladies musculaires, contenant, en tant que principe actif, de la diosmine ou un sel pharmaceutiquement acceptable de cette dernière
WO2018186640A1 (fr) Composition pour réduire les rides de la peau, hydrater la peau, améliorer son élasticité, l&#39;exfolier, inhiber l&#39;érythème ou réduire le photovieillissement cutané, contenant de l&#39;ocimène ou un sel de celui-ci à titre de substance active
WO2019231150A1 (fr) Composition comprenant un extrait d&#39;aster sphathulifolius maxim pour la prévention, l&#39;amélioration ou le traitement des maladies musculaires ou pour l&#39;amélioration des fonctions musculaires
WO2018062820A1 (fr) Composition visant à prévenir la chute des cheveux et à en favoriser la pousse, comprenant un phytoœstrogène en tant que principe actif
WO2019017677A2 (fr) Composition comprenant du citral utilisé comme principe actif pour présenter un effet de raffermissement musculaire, de renforcement musculaire, de différenciation musculaire, de régénération musculaire ou de suppression de sarcopénie
WO2018186641A1 (fr) Composition pour réduire les rides de la peau, hydrater la peau, améliorer son élasticité, l&#39;exfolier, inhiber l&#39;érythème ou réduire le photovieillissement de la peau, contenant du pipéronal ou l&#39;un de ses sels à titre de principe actif
WO2018128482A1 (fr) Composition, comprenant un cymène ou un sel pharmaceutiquement acceptable de celui-ci comme principe actif, pour la prévention ou le traitement de maladie musculaire
WO2020085826A1 (fr) Composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane
WO2018128481A1 (fr) Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant comme principe actif de l&#39;indole-3-carbinol ou un sel pharmaceutiquement acceptable de celui-ci
WO2020032435A1 (fr) Composition de prévention de la perte des cheveux ou de promotion de la restauration capillaire contenant du yarayara en tant qu&#39;ingrédient actif
WO2018128478A1 (fr) Composition, comprenant comme principe actif de l&#39;ionone ou un sel pharmaceutiquement acceptable de celle-ci, destinée à la prévention ou au traitement de troubles musculaires
WO2018128480A1 (fr) Composition destinée à la prévention ou au traitement de maladies musculaires, comprenant de l&#39;acide géranique ou un sel pharmaceutiquement acceptable de celui-ci en tant que principe actif
WO2019172566A1 (fr) Agent anti-stress, composition d&#39;agent anti-anxiété ou antidépresseur contenant de l&#39;ionone en tant que principe actif
WO2019017676A9 (fr) Composition comprenant de l&#39;éthylvanilline en tant que principe actif pour conférer un effet de renforcement musculaire, d&#39;amélioration musculaire, de différenciation musculaire, de régénération musculaire ou de suppression de sarcopénie
WO2015037855A1 (fr) Composition comprenant un extrait d&#39;herbes combinées comprenant de l&#39;acanthopanax koreanum naka et du crinum asiaticum var. japonicum présentant une activité de prévention de la calvitie et une activité de stimulation de la croissance capillaire
WO2016190689A2 (fr) Composition permettant de prévenir, de soulager ou de traiter les maladies musculaires ou d&#39;améliorer la fonction musculaire

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18736767

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18736767

Country of ref document: EP

Kind code of ref document: A1