JP2002338464A - Muscular atrophy inhibitor - Google Patents
Muscular atrophy inhibitorInfo
- Publication number
- JP2002338464A JP2002338464A JP2001143602A JP2001143602A JP2002338464A JP 2002338464 A JP2002338464 A JP 2002338464A JP 2001143602 A JP2001143602 A JP 2001143602A JP 2001143602 A JP2001143602 A JP 2001143602A JP 2002338464 A JP2002338464 A JP 2002338464A
- Authority
- JP
- Japan
- Prior art keywords
- muscular atrophy
- group
- proanthocyanidin
- atrophy
- muscle
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 201000000585 muscular atrophy Diseases 0.000 title claims abstract description 33
- 239000003112 inhibitor Substances 0.000 title claims abstract description 10
- JPFCOVZKLAXXOE-XBNSMERZSA-N (3r)-2-(3,5-dihydroxy-4-methoxyphenyl)-8-[(2r,3r,4r)-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2h-chromen-4-yl]-3,4-dihydro-2h-chromene-3,5,7-triol Chemical compound C1=C(O)C(OC)=C(O)C=C1C1[C@H](O)CC(C(O)=CC(O)=C2[C@H]3C4=C(O)C=C(O)C=C4O[C@@H]([C@@H]3O)C=3C=CC(O)=CC=3)=C2O1 JPFCOVZKLAXXOE-XBNSMERZSA-N 0.000 claims abstract description 13
- 229920001991 Proanthocyanidin Polymers 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 239000000284 extract Substances 0.000 claims abstract description 4
- 235000013399 edible fruits Nutrition 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 229940087559 grape seed Drugs 0.000 claims 1
- 241000219094 Vitaceae Species 0.000 abstract description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 abstract description 2
- 235000021021 grapes Nutrition 0.000 abstract description 2
- 241000283690 Bos taurus Species 0.000 abstract 1
- 206010028289 Muscle atrophy Diseases 0.000 description 22
- 230000020763 muscle atrophy Effects 0.000 description 22
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 20
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 229920002770 condensed tannin Polymers 0.000 description 12
- 210000003141 lower extremity Anatomy 0.000 description 12
- 210000002027 skeletal muscle Anatomy 0.000 description 12
- 229930003427 Vitamin E Natural products 0.000 description 10
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 10
- 235000019165 vitamin E Nutrition 0.000 description 10
- 239000011709 vitamin E Substances 0.000 description 10
- 229940046009 vitamin E Drugs 0.000 description 10
- 206010003694 Atrophy Diseases 0.000 description 8
- 230000037444 atrophy Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 6
- 241000220225 Malus Species 0.000 description 6
- 229930003268 Vitamin C Natural products 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 235000019154 vitamin C Nutrition 0.000 description 6
- 239000011718 vitamin C Substances 0.000 description 6
- NFLLKCVHYJRNRH-UHFFFAOYSA-N 8-chloro-1,3-dimethyl-7H-purine-2,6-dione 2-(diphenylmethyl)oxy-N,N-dimethylethanamine Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Cl)=N2.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 NFLLKCVHYJRNRH-UHFFFAOYSA-N 0.000 description 5
- 235000009754 Vitis X bourquina Nutrition 0.000 description 5
- 235000012333 Vitis X labruscana Nutrition 0.000 description 5
- 240000006365 Vitis vinifera Species 0.000 description 5
- 235000014787 Vitis vinifera Nutrition 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000002994 raw material Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000021016 apples Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 235000021590 normal diet Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- OEIJRRGCTVHYTH-UHFFFAOYSA-N Favan-3-ol Chemical compound OC1CC2=CC=CC=C2OC1C1=CC=CC=C1 OEIJRRGCTVHYTH-UHFFFAOYSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 2
- 240000001417 Vigna umbellata Species 0.000 description 2
- 235000011453 Vigna umbellata Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- VEVZSMAEJFVWIL-UHFFFAOYSA-O cyanidin cation Chemical compound [O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC=C(O)C(O)=C1 VEVZSMAEJFVWIL-UHFFFAOYSA-O 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000005486 microgravity Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- XIMADJWJJOMVID-UHFFFAOYSA-N 2-phenyl-3,4-dihydro-2h-chromene-3,4-diol Chemical compound OC1C(O)C2=CC=CC=C2OC1C1=CC=CC=C1 XIMADJWJJOMVID-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical group CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- GCPYCNBGGPHOBD-UHFFFAOYSA-N Delphinidin Natural products OC1=Cc2c(O)cc(O)cc2OC1=C3C=C(O)C(=O)C(=C3)O GCPYCNBGGPHOBD-UHFFFAOYSA-N 0.000 description 1
- 235000011511 Diospyros Nutrition 0.000 description 1
- 241000723267 Diospyros Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- CITFYDYEWQIEPX-UHFFFAOYSA-N Flavanol Natural products O1C2=CC(OCC=C(C)C)=CC(O)=C2C(=O)C(O)C1C1=CC=C(O)C=C1 CITFYDYEWQIEPX-UHFFFAOYSA-N 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000218606 Pinus contorta Species 0.000 description 1
- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 description 1
- 229920000124 Prodelphinidin Polymers 0.000 description 1
- 229930182448 Prodelphinidin Natural products 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 229930014669 anthocyanidin Natural products 0.000 description 1
- 235000008758 anthocyanidins Nutrition 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 208000020538 atrophic muscular disease Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 description 1
- 235000019987 cider Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000007336 cyanidin Nutrition 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 235000007242 delphinidin Nutrition 0.000 description 1
- JKHRCGUTYDNCLE-UHFFFAOYSA-O delphinidin Chemical compound [O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC(O)=C(O)C(O)=C1 JKHRCGUTYDNCLE-UHFFFAOYSA-O 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 229930182497 flavan-3-ol Natural products 0.000 description 1
- 235000011987 flavanols Nutrition 0.000 description 1
- NWKFECICNXDNOQ-UHFFFAOYSA-N flavylium Chemical compound C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=[O+]1 NWKFECICNXDNOQ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000019990 fruit wine Nutrition 0.000 description 1
- 229940087603 grape seed extract Drugs 0.000 description 1
- 235000002532 grape seed extract Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- HKUHOPQRJKPJCJ-UHFFFAOYSA-N pelargonidin Natural products OC1=Cc2c(O)cc(O)cc2OC1c1ccc(O)cc1 HKUHOPQRJKPJCJ-UHFFFAOYSA-N 0.000 description 1
- 235000006251 pelargonidin Nutrition 0.000 description 1
- XVFMGWDSJLBXDZ-UHFFFAOYSA-O pelargonidin Chemical compound C1=CC(O)=CC=C1C(C(=C1)O)=[O+]C2=C1C(O)=CC(O)=C2 XVFMGWDSJLBXDZ-UHFFFAOYSA-O 0.000 description 1
- 235000010204 pine bark Nutrition 0.000 description 1
- 235000018192 pine bark supplement Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229920002414 procyanidin Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940106796 pycnogenol Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000000673 shore pine Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000001717 vitis vinifera seed extract Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
Landscapes
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、筋肉萎縮抑制剤に
関する。本発明は、更に具体的には、経口摂取すること
により、通常の筋肉萎縮抑制効果の知られているビタミ
ンE剤等では抑制しにくい筋肉萎縮、例えば、ギブス固
定あるいは長期臥床後に発生する(寝たきりに伴う)骨
格筋の廃用性萎縮、老化に伴う筋肉萎縮及び微小重力暴
露に伴う筋肉萎縮(宇宙空間等での筋肉萎縮)等の抑制
剤に関するものである。TECHNICAL FIELD The present invention relates to an agent for suppressing muscle atrophy. More specifically, the present invention provides a muscle atrophy that is difficult to suppress with a vitamin E agent or the like, which is known to have a normal muscle atrophy inhibitory effect, by oral ingestion, for example, occurs after fixation of casts or prolonged bed rest (bedridden The present invention relates to an agent for inhibiting disuse atrophy of skeletal muscle, accompanying aging, muscle atrophy associated with aging, and muscle atrophy associated with microgravity exposure (muscle atrophy in outer space and the like).
【0002】[0002]
【従来の技術】本出願人は、先にプロアントシアニジン
が強い抗酸化作用を有することを見い出し、プロアント
シアニジンを主成分とする抗酸化剤として特許出願した
(特公平3-7232号公報)。又プロアントシアニジンが、
ブドウ種子又は果実の搾汁粕から水や含水アルコールで
効率よく抽出できることを見い出した(特開平3-200781
号公報及び特開平11-80148号公報)。プロアントシアニ
ジンは、ポリフェノールの1種で次式2. Description of the Related Art The present applicant has previously found that proanthocyanidin has a strong antioxidant action and applied for a patent as an antioxidant containing proanthocyanidin as a main component (Japanese Patent Publication No. 3-7232). Also proanthocyanidins,
It has been found that grape seeds or fruit juice can be efficiently extracted from squeezed cake with water or hydrous alcohol (JP-A-3-200781
And JP-A-11-80148). Proanthocyanidins are a type of polyphenol and have the formula
【化1】 で表される、フラバン-3-オールまたはフラバン-3,4-ジ
オールを構成単位として、4-6位又は4-8位で縮合もしく
は重合により結合した化合物群であり、各種植物体中に
存在する縮合型タンニンである。なお上記構造式は、理
解を助けるために4-8位で縮合した場合のみを示してい
る。これらは酸処理によりシアニジン、デルフィニジ
ン、ペラルゴニジン等のアントシアニジンを生成すると
ころから、この名称が与えられているものである。Embedded image Represented by the formula: flavan-3-ol or flavan-3,4-diol as a structural unit, a group of compounds linked by condensation or polymerization at the 4-6 or 4-8 position, and is present in various plants Is a condensed tannin. Note that the above structural formula shows only a case where condensation is performed at the 4-8 position to facilitate understanding. These are given this name because they produce anthocyanidins such as cyanidin, delphinidin, pelargonidin and the like by acid treatment.
【0003】そして、上記構成単位の2量体、3量体、
4量体更に10〜30量体以上の高分子のプロシアニジ
ン、プロデルフィニジン、プロペラルゴニジン等のプロ
アントシアニジン及びそれらの立体異性体等を含むもの
である。さて骨格筋等の筋肉萎縮は、臨床的に骨折時等
のギブス固定あるいは長期臥床後等に発生してくるもの
で、その予防は、整形外科領域で解決しなければならな
い重要な課題の1つである。また、加齢に伴う骨格筋の
退行性萎縮は、だれもが避けられない問題であり、これ
が老人の骨折の原因の1つになっている。一方、微小重
力暴露に伴う筋肉萎縮(宇宙空間等での筋肉萎縮)は、
今後、人類が、宇宙空間で長期滞在ないしは生活する上
で解決しなければならない重要な課題の1つである。こ
れまでに筋肉萎縮を抑制する方法としては、充分な運動
やリハビリテーションが挙げられるが、これらだけでは
その抑制に限界がある。一方、筋肉萎縮抑制剤として
は、抗酸化剤のビタミンEあるいは鉄キレート剤である
デフェロキサミンが知られているが、それらの効果は充
分なものではなかった(医学のあゆみ、Vol.193、No.
7、2000、医歯薬出版(株)、Kondo H., Acta. Physio
l. Sscand., 142, 527-528(1991))。[0003] Then, dimers, trimers,
Tetramers and also proanthocyanidins such as procyanidins, prodelphinidins, properargonidines and the like of polymers of 10 to 30-mers or more, stereoisomers thereof and the like are included. Now, muscular atrophy such as skeletal muscle occurs clinically after a cast or a long-term bed rest at the time of a fracture, etc. Prevention is one of the important issues that must be solved in the field of orthopedic surgery. It is. In addition, degenerative atrophy of skeletal muscle accompanying aging is a problem that cannot be avoided by anyone, and this is one of the causes of fractures in elderly people. On the other hand, muscle atrophy associated with microgravity exposure (muscle atrophy in outer space, etc.)
In the future, it is one of the important issues that humanity must solve in order to stay or live in outer space for a long time. To date, methods of suppressing muscle atrophy include sufficient exercise and rehabilitation, but these alone have a limit in the suppression. On the other hand, as a muscle atrophy inhibitor, vitamin E as an antioxidant or deferoxamine as an iron chelator is known, but their effects were not sufficient (Ayumi of Medicine, Vol. 193, No.
7, 2000, Medical and Dental Publishing, Kondo H., Acta. Physio
l. Sscand., 142, 527-528 (1991)).
【0004】[0004]
【発明が解決しようとする課題】以上のような状況か
ら、本発明は、筋肉萎縮抑制の抜本的解決法のない現状
を打破し、明確な効果を示す筋肉萎縮抑制剤を広く提供
することを目的としてなされたものである。SUMMARY OF THE INVENTION Under the circumstances described above, the present invention aims to overcome the current situation where there is no drastic solution to the suppression of muscle atrophy, and to widely provide a muscle atrophy inhibitor having a clear effect. It was made for the purpose.
【0005】[0005]
【課題を解決するための手段】そこで本発明者等は、前
記目的を達成するために、鋭意検討を重ねた結果、プロ
アントシアニジンが筋肉萎縮を顕著に抑制することを見
出し、この知見に基づいて、本発明を完成するに至っ
た。すなわち第一の発明は、プロアントシアニジンを有
効成分として含有することを特徴とする筋肉萎縮抑制剤
である。第二の発明は、プロアントシアニジンが、ブド
ウ種子、果皮又は果実の搾汁液より得られる抽出物であ
る前記記載の筋肉萎縮抑制剤である。Means for Solving the Problems In order to achieve the above object, the present inventors have conducted intensive studies, and as a result, have found that proanthocyanidins significantly suppress muscle atrophy. Thus, the present invention has been completed. That is, the first invention is a muscle atrophy inhibitor comprising proanthocyanidin as an active ingredient. The second invention is the muscular atrophy inhibitor according to the above, wherein the proanthocyanidin is an extract obtained from juice of grape seeds, pericarp, or fruits.
【0006】[0006]
【発明の実施の形態】以下に、本発明を詳細に説明す
る。なお、本発明中記載の筋肉萎縮抑制剤とは、筋萎縮
を予防遅延及び/又は症状を緩和する作用を有する物質
をいう。先ず、本発明に用いられるプロアントシアニジ
ンは、ブドウ、柿、リンゴ、松、大豆、小豆等植物由来
のもの、また、ワイン、果実酒、果実ジュース等食品由
来のもの等が例として挙げられ、原料の由来あるいは原
料の利用部分、製造法、精製法については何ら制限され
ない。この中で含有量が多いことあるいは糖類等の夾雑
物の含量も少ないため、高純度のプロアントシアニジン
が抽出によって容易に得られることから、原料として
は、ブドウ種子が好適である。ブドウ種子からの抽出以
外の方法でプロアントシアニジンを得る方法としては、
小豆からの抽出〔有賀等、アグリカルチュラル・バイオ
ロジカル・ケミストリー(Agric.Biol.Chem.)第45巻、
2709-2712頁、1981年〕、松の樹皮からの抽出〔R.W.Hem
ingway等、フィトケミストリー(Phytochemistry)第22
巻、275-281頁、1983年〕、リンゴ酒からの分離〔A.G.
H.Lea等、ジャ−ナル・オブ・サイエンス・オブ・フー
ド・アグリカルチャー(J.Sci.Food Agric.)第29巻、4
71-477頁、1978年〕等が知られている。DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. In addition, the muscular atrophy inhibitor described in the present invention refers to a substance having an action of preventing or delaying muscle atrophy and / or alleviating symptoms. First, the proanthocyanidins used in the present invention include grapes, persimmons, apples, pine, soybeans, soybeans, vegetable-derived ones such as red beans, and wines, fruit wines, fruit juices, and other food-derived ones. There are no restrictions on the origin of the product or on the use of raw materials, the production method, and the purification method. Among them, grape seeds are suitable as a raw material because high content proanthocyanidins can be easily obtained by extraction because of high content or low content of impurities such as sugars. As a method of obtaining proanthocyanidins by a method other than extraction from grape seeds,
Extract from red beans [Ariga et al., Agricultural Biological Chemistry (Agric. Biol. Chem.) Vol. 45,
2709-2712, 1981), extraction from pine bark (RWHem
ingway et al., Phytochemistry No. 22
Volume, pp. 275-281, 1983), separation from apple cider (AG
H.Lea et al., Journal of Science of Food Agriculture (J.Sci. Food Agric.) Vol. 29, 4
71-477, 1978].
【0007】以上のようにして得られたプロアントシア
ニジンは、液状もしくは半固形状の形態で得られるが、
このものから抽出溶媒を減圧留去、スプレードライ、凍
結乾燥等の公知の方法によって除去すれば、そのままプ
ロアントシアニジン含有濃縮物や乾燥物として使用する
ことができる。特開平11-80148号公報の実施例に示すよ
うに、最適の原料と抽出条件を用いれば、90%以上の高
い純度を有するプロアントシアニジン組成物を、簡単に
得ることができる。プロアントシアニジンを主成分とす
る製品は市販もされており、例えば、ブドウ種子を原料
とする「KPA」、「グラヴィノ−ル」、「グラヴィノ
−ル・ス−パ−」〔キッコ−マン(株)製、りんご未熟
果を原料とする「アップルフェノン」〔ニッカウヰスキ
−(株)製〕、海岸松の樹皮を原料とする「ピクノジェ
ノ−ル」〔ホ−ファ−リサ−チ社製(スイス)〕等であ
る。経口摂取の場合、プロアントシアニジンの摂取量
は、例えば、成人で1日当たり20-1000mg、好ましくは30
-400mg程度である。ビタミン類併用時のビタミン摂取量
も、成人で1日当たり20-1000mg、好ましくは30-400mg程
度である。The proanthocyanidins obtained as described above can be obtained in liquid or semi-solid form.
If the extraction solvent is removed therefrom by a known method such as distillation under reduced pressure, spray drying, freeze drying and the like, it can be used as a proanthocyanidin-containing concentrate or dried product as it is. As shown in the examples of JP-A-11-80148, a proanthocyanidin composition having a high purity of 90% or more can be easily obtained by using optimal raw materials and extraction conditions. Products containing proanthocyanidins as a main component are also commercially available. For example, “KPA”, “Gravinol”, “Gravinol Super” using grape seeds as a raw material [Kikkoman Co., Ltd.] "Applephenone" made from unripe apples (Nikka Pesky Co., Ltd.) and "Pycnogenol" made from bark of shore pine [Hofar Research Co., Ltd. (Switzerland)]. is there. In the case of oral ingestion, the amount of proanthocyanidin may be, for example, 20-1000 mg, preferably 30
About -400mg. The amount of vitamin intake when combined with vitamins is about 20-1000 mg, preferably about 30-400 mg per day for adults.
【0008】[0008]
【発明の効果】本発明によれば、プロアントシアニジン
を摂取することにより、実験例に示すように顕著に筋肉
萎縮を抑制することができ、筋肉萎縮に悩む人々に福音
をもたらすものである。According to the present invention, by taking proanthocyanidin, muscle atrophy can be remarkably suppressed as shown in the experimental examples, and the gospel is brought to people suffering from muscle atrophy.
【0009】[0009]
【実験例】以下に、実験例を示す。[Experimental example] An experimental example is shown below.
【実験例1】グラヴィノ−ル・ス−パ−(GVS)のラッ
ト後肢筋肉萎縮抑制効果(GVSとビタミンEとの効果比較
試験結果) 近藤等の方法(Kondo H., Acta. Physiol. Sscand., 14
2, 527-528(1991))に従い、ラット後肢筋肉萎縮モデル
を作製した。すなわち、13週齢Crj:Wistarラット
(♂、6匹/群×3群、18匹)の右後肢足関節にキル
シュナー鋼線を挿入し右後肢筋肉を固定し動けなくし
た。なお、左後肢関節は固定せず自由に動く状態とし
た。当処置を行なう7日前から処置12日目までの19
日間、6匹には普通飼料のみを自由摂取させた(対照
群)。別の6匹には普通飼料に1%の割合でGVSを添加
した飼料を自由摂取させた(GVS群)。また、6匹には
普通飼料を与えながら毎日、ビタミンE(α−トコフェ
ロール) 30mg/kg体重/日×19日間腹腔内投与した
(ビタミンE群)。試験終了時に両側後肢のヒラメ筋を
サンプリングして湿重量を計測後、各群の左後肢ヒラメ
筋湿重量(非固体側)に対する右後肢ヒラメ筋湿重量
(固定側)の差から萎縮率を算出した。各群ラットの右
筋肢ヒラメ筋の平均萎縮率の結果を表1に示す。GVS群
は、対照群に比べ萎縮率の値が小さく、GVSの筋肉萎縮
抑制効果が確認された(表1)。一方、ビタミンEには
効果がなかつた(表1)。 表1 試験群 ラット後肢ヒラメ筋の平均萎縮率(%) 対照群 26.47% GVS群 13.22% ビタミンE群 36.36%[Experimental Example 1] Inhibitory effect of gravinol super (GVS) on hind limb muscle atrophy in rats (effect comparison test between GVS and vitamin E) Kondo et al.'S method (Kondo H., Acta. Physiol. Sscand. , 14
2, 527-528 (1991)), a rat hind limb muscle atrophy model was prepared. That is, a 13-week-old Crj: Wistar rat (♂, 6 rats / group × 3 groups, 18 rats) was inserted with a Kirschner steel wire in the right hind leg ankle joint to immobilize the right hind leg muscle and immobilize. The left hind limb joint was free to move without being fixed. 19 days before the treatment and 12 days after the treatment
During the day, six animals were allowed to freely take only the normal feed (control group). Another 6 animals were allowed to freely take the feed obtained by adding GVS to the normal feed at a rate of 1% (GVS group). Six animals were given an intraperitoneal injection of vitamin E (α-tocopherol) daily at 30 mg / kg body weight / day × 19 days while receiving a normal diet (vitamin E group). At the end of the test, sample the soleus muscles of both hind limbs and measure the wet weight, and calculate the atrophy rate from the difference between the wet weight of the right hind limb soleus muscle (non-solid side) and the wet weight of the right hind limb soleus muscle (non-solid side) in each group. did. Table 1 shows the results of the average atrophy rate of the soleus muscle of the right limb of each group of rats. The value of the atrophy rate was smaller in the GVS group than in the control group, and the effect of GVS on inhibiting muscle atrophy was confirmed (Table 1). On the other hand, vitamin E had no effect (Table 1). Table 1 Test group Average atrophy rate of rat soleus soleus muscle (%) Control group 26.47% GVS group 13.22% Vitamin E group 36.36%
【0010】[0010]
【実験例2】グラヴィノ−ル・ス−パ−(GVS)のラッ
ト後肢筋肉萎縮抑制効果(GVSとアップルフェノン、
ビタミンE及びビタミンCとの効果比較試験結果) 13週齢Crj:Wistarラット(♂、6匹/群×5群、30
匹)を用い上述実験例1と同様にラット後肢筋肉萎縮モ
デルを作製した。試験群は、当処置を行なう7日前から
処置12日目までの19日間、普通飼料のみを自由摂取
させた対照群、普通飼料に1%の割合でGVSを添加した
飼料を自由摂取させたGVS群、普通飼料に1%の割合で
アップルフェノン〔ニッカウヰスキー(株)製、りんご
未熟果を原料とするプロアントシアニジン、総フラバノ
ール含量:90%以上〕を添加した飼料を自由摂取させ
たアップルフェノン群、普通飼料に1%の割合で酢酸ト
コフェロールを添加した飼料を自由摂取させたビタミン
E群及び普通飼料に1%の割合でビタミンCを添加した飼
料を自由摂取させたビタミンC群である。試験終了時に
上述実験例1と同様に、各群の左後肢ヒラメ筋湿重量
(非固定側)に対する右後肢ヒラメ筋湿重量(固定側)
の差から萎縮率を算出した。 各群ラットの右後肢ヒラ
メ筋の平均萎縮率の結果を表2に示す。GVS及びビタミ
ンCに筋肉萎縮抑制効果が確認されたが、その効果は、
ビタミンCに比べGVSで強かった(表2)。一方、アップ
ルフェノン及びビタミンEには効果がなかった(表
2)。 表2 試験群 ラット後肢ヒラメ筋の平均萎縮率(%) 対照群 23.02% GVS群 19.62% アップルフェノン群 23.95% ビタミンE群 25.33% ビタミンC群 20.74%[Experimental Example 2] Effect of Gravinol Super (GVS) on hind limb muscle atrophy in rats (GVS, applephenone,
Comparative test results with vitamin E and vitamin C) 13-week-old Crj: Wistar rats (♂, 6 rats / group × 5 groups, 30 rats)
And a rat hind limb muscular atrophy model was prepared in the same manner as in Experimental Example 1 described above. The test group consisted of a control group in which the normal feed was freely ingested for 19 days from 7 days before the treatment to the 12th day of the treatment, and a GVS in which the normal diet was supplemented with a diet in which GVS was added at a ratio of 1%. Apple phenone group fed with apple phenone (produced by Nikka Whiskey Co., Ltd., proanthocyanidins made from unripe apples, total flavanol content: 90% or more) to normal feed at a rate of 1% Vitamin freely fed on diet containing 1% tocopherol acetate
Group E and a group of vitamin C in which a normal diet to which vitamin C was added at a ratio of 1% was freely ingested. At the end of the test, as in Experimental Example 1 above, the wet weight of the soleus muscle of the right hind limb (fixed side) relative to the wet weight of the soleus muscle of the left hind limb (non-fixed side) of each group.
The atrophy rate was calculated from the difference. Table 2 shows the results of the average atrophy rate of the soleus muscle of the right hind limb of each group of rats. GVS and vitamin C were confirmed to have muscle atrophy inhibitory effects, but the effects were:
GVS was stronger than Vitamin C (Table 2). On the other hand, applephenone and vitamin E had no effect (Table 2). Table 2 Test group Average atrophy rate (%) of rat soleus soleus muscle Control group 23.02% GVS group 19.62% Applephenone group 23.95% Vitamin E group 25.33% Vitamin C group 20.74%
【0011】[0011]
【実施例】以下に、実施例を示して本発明を更に具体的
に説明する。 実施例 製造例1(内服剤:錠剤) ブドウ種子抽出物〔キッコーマン(株)製、グラヴィノ−ル・ス−パ−〕100 mg 乳糖 100mg デンプン 17mg ステアリン酸マグネシウム 3mg 以上を1錠分として常法により錠剤化し、錠剤を得た。The present invention will be described more specifically below with reference to examples. Example Production Example 1 (oral medicine: tablet) Grape seed extract [Gravinol Super, manufactured by Kikkoman Corporation] 100 mg Lactose 100 mg Starch 17 mg Magnesium stearate 3 mg One tablet or more is made by a conventional method. Tablets were obtained to give tablets.
───────────────────────────────────────────────────── フロントページの続き Fターム(参考) 4C062 FF56 4C086 AA01 AA02 BA08 MA01 NA14 ZA23 ZA94 4C088 AB56 AC04 NA14 ZA23 ZA94 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C062 FF56 4C086 AA01 AA02 BA08 MA01 NA14 ZA23 ZA94 4C088 AB56 AC04 NA14 ZA23 ZA94
Claims (2)
含有することを特徴とする筋肉萎縮抑制剤。A muscular atrophy inhibitor comprising proanthocyanidin as an active ingredient.
果皮又は果実の搾汁液より得られる抽出物である請求項
1記載の筋肉萎縮抑制剤。2. The proanthocyanidin is grape seed,
The muscular atrophy inhibitor according to claim 1, which is an extract obtained from a squeezed liquid of a pericarp or a fruit.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001143602A JP2002338464A (en) | 2001-05-14 | 2001-05-14 | Muscular atrophy inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001143602A JP2002338464A (en) | 2001-05-14 | 2001-05-14 | Muscular atrophy inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002338464A true JP2002338464A (en) | 2002-11-27 |
Family
ID=18989724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001143602A Pending JP2002338464A (en) | 2001-05-14 | 2001-05-14 | Muscular atrophy inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2002338464A (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004112510A1 (en) * | 2003-06-19 | 2004-12-29 | Suntory Limited | Movement physiology improver |
| WO2005074962A1 (en) * | 2004-02-10 | 2005-08-18 | Asahi Breweries, Ltd. | Muscular tension-elevating agent |
| JP2006062976A (en) * | 2004-08-24 | 2006-03-09 | Nippon Medical School | Oral preparation for reducing muscle oxidative stress |
| WO2006057073A1 (en) * | 2004-11-29 | 2006-06-01 | Toyo Shinyaku Co., Ltd. | Athletic ability enhancing composition |
| WO2006129569A1 (en) * | 2005-05-30 | 2006-12-07 | Asahi Breweries, Ltd. | Muscle fiber type switching inhibitor |
| JP2007145809A (en) * | 2005-10-26 | 2007-06-14 | Kao Corp | Endurance improver |
| WO2008004340A1 (en) | 2006-07-05 | 2008-01-10 | Kao Corporation | Senescence inhibitor |
| EP2322158A2 (en) | 2005-10-26 | 2011-05-18 | Kao Corporation | Resveratrol and/or grape leaf extract for energy metabolism activation |
| WO2011108487A1 (en) * | 2010-03-01 | 2011-09-09 | 国立大学法人九州大学 | Muscular atrophy inhibitor |
| WO2012097061A1 (en) * | 2011-01-13 | 2012-07-19 | Abbott Laboratories | Nutritional compositions and methods for improving skeletal muscle protein metabolism |
| WO2013058194A1 (en) * | 2011-10-17 | 2013-04-25 | 花王株式会社 | Srf signal activating agent |
| JP2014012659A (en) * | 2012-06-08 | 2014-01-23 | Kao Corp | Myostatin/smad signal inhibitor |
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2001
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Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004112510A1 (en) * | 2003-06-19 | 2004-12-29 | Suntory Limited | Movement physiology improver |
| WO2005074962A1 (en) * | 2004-02-10 | 2005-08-18 | Asahi Breweries, Ltd. | Muscular tension-elevating agent |
| JP2006062976A (en) * | 2004-08-24 | 2006-03-09 | Nippon Medical School | Oral preparation for reducing muscle oxidative stress |
| WO2006057073A1 (en) * | 2004-11-29 | 2006-06-01 | Toyo Shinyaku Co., Ltd. | Athletic ability enhancing composition |
| WO2006129569A1 (en) * | 2005-05-30 | 2006-12-07 | Asahi Breweries, Ltd. | Muscle fiber type switching inhibitor |
| EP2322158A2 (en) | 2005-10-26 | 2011-05-18 | Kao Corporation | Resveratrol and/or grape leaf extract for energy metabolism activation |
| JP2007145809A (en) * | 2005-10-26 | 2007-06-14 | Kao Corp | Endurance improver |
| WO2008004340A1 (en) | 2006-07-05 | 2008-01-10 | Kao Corporation | Senescence inhibitor |
| US8962678B2 (en) | 2006-07-05 | 2015-02-24 | Kao Corporation | Senescence inhibitor |
| WO2011108487A1 (en) * | 2010-03-01 | 2011-09-09 | 国立大学法人九州大学 | Muscular atrophy inhibitor |
| WO2012097061A1 (en) * | 2011-01-13 | 2012-07-19 | Abbott Laboratories | Nutritional compositions and methods for improving skeletal muscle protein metabolism |
| WO2013058194A1 (en) * | 2011-10-17 | 2013-04-25 | 花王株式会社 | Srf signal activating agent |
| JP2014012659A (en) * | 2012-06-08 | 2014-01-23 | Kao Corp | Myostatin/smad signal inhibitor |
| WO2018105550A1 (en) | 2016-12-05 | 2018-06-14 | 大塚製薬株式会社 | Amyotrophy inhibiting composition |
| US11331366B2 (en) | 2016-12-05 | 2022-05-17 | Otsuka Pharmaceutical Co., Ltd. | Composition for suppressing muscular atrophy |
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