JPH0319209B2 - - Google Patents
Info
- Publication number
- JPH0319209B2 JPH0319209B2 JP14132483A JP14132483A JPH0319209B2 JP H0319209 B2 JPH0319209 B2 JP H0319209B2 JP 14132483 A JP14132483 A JP 14132483A JP 14132483 A JP14132483 A JP 14132483A JP H0319209 B2 JPH0319209 B2 JP H0319209B2
- Authority
- JP
- Japan
- Prior art keywords
- type
- hydroxyvitamin
- dystrophy
- present
- vitamin
- 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.)
- Expired
Links
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 claims description 8
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical group C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 201000006938 muscular dystrophy Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000007901 soft capsule Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- -1 For example Chemical compound 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229930003316 Vitamin D Natural products 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 235000019166 vitamin D Nutrition 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- BJYLYJCXYAMOFT-RRXOBRNQSA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r)-5-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCC(O)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C BJYLYJCXYAMOFT-RRXOBRNQSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010061728 Bone lesion Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000013038 Hypocalcemia Diseases 0.000 description 1
- 208000000038 Hypoparathyroidism Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000007623 Lordosis Diseases 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 206010061533 Myotonia Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- WFZKUWGUJVKMHC-UKBUZQLGSA-N calcitetrol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CC[C@@H](O)C(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C WFZKUWGUJVKMHC-UKBUZQLGSA-N 0.000 description 1
- 239000011612 calcitriol Substances 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000705 hypocalcaemia Effects 0.000 description 1
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 1
- 208000021005 inheritance pattern Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 206010039722 scoliosis Diseases 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- BJYLYJCXYAMOFT-RSFVBTMBSA-N tacalcitol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@@H](O)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C BJYLYJCXYAMOFT-RSFVBTMBSA-N 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 208000032349 type 2B vitamin D-dependent rickets Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、1α−ヒドロキシビタミンD3類を含
有する抗筋ジストロフイー症剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antimuscular dystrophy agent containing 1α-hydroxyvitamin D 3 .
近年、デルカ（De Luca）等及びコデイツク
（Kodiek）等の一連の研究の結果、ビタミンD3
の生体内活性物質が1α，25−ジヒドロキシビタ
ミンD3（以下1α，25−（OH）2−D3と略称する）で
あり、また1α位の水酸基の存在がその生物活性
の発現には必須であることが明らかにされた。以
後この活性型の1α，25−（OH）2−D3の類似体、
例えば1α−ヒドロキシビタミンD3（以下1α−
（OH）−D3と略称する）、1α，24−ジヒドロキシ
ビタミンD3（以下1α，24−（OH）2−D3と略称す
る）など多くの1α−ヒドロキシビタミンD3類が
合成され、1α，25−（OH）2−D3とともにそのビ
タミンＤ様生物活性が注目されており、1α−
（OH）−D3は慢性腎不全、副甲状腺機能低下症、
ビタミンＤ抵抗性クル病・骨軟下症におけるビタ
ミンＤ代謝異常を伴う諸症状（低カルシウム血
症、テタニー、骨痛、骨病変等）の改善に適応さ
れている。 In recent years, as a result of a series of studies by De Luca et al. and Kodiek et al., vitamin D3
The active substance in the body is 1α,25-dihydroxyvitamin D 3 (hereinafter abbreviated as 1α,25-(OH) 2 -D 3 ), and the presence of a hydroxyl group at the 1α position is essential for the expression of its biological activity. It was revealed that. Hereafter analogs of this active form of 1α,25-(OH) 2 -D 3 ,
For example, 1α-hydroxyvitamin D 3 (hereinafter 1α-
(OH)-D 3 ), 1α,24-dihydroxyvitamin D 3 (hereinafter abbreviated as 1α,24-(OH) 2 -D 3 ), and many other 1α-hydroxyvitamin D 3 types have been synthesized. Along with 1α,25−(OH) 2 −D 3 , its vitamin D-like biological activity has attracted attention, and 1α−
(OH)-D 3 is chronic renal failure, hypoparathyroidism,
It is indicated for improving various symptoms associated with vitamin D metabolic abnormalities (hypocalcemia, tetany, bone pain, bone lesions, etc.) in vitamin D-resistant rickets and osteomalacia.
本発明者等は、その後鋭意研究を続けた結果、
1α−ヒドロキシビタミンD3類に筋ジストロフイ
ー症に対する有効性を見出し、本発明を完成し
た。 As a result of continued intensive research, the inventors found that
The present invention was completed based on the discovery that 1α-hydroxyvitamin D type 3 is effective against muscular dystrophy.
即ち本発明は、1α−ヒドロキシビタミンD3類
の抗筋ジストロフイー症剤に関する。 That is, the present invention relates to an antimuscular dystrophy agent of the 1α-hydroxyvitamin D 3 class.
筋ジストロフイー症は骨格筋の進行性変性を特
徴とするミオパチーの一群で、遺伝的因子に依つ
て発症する。1868年にDuchenneによつて仮性肥
大型筋ジストロフイー症の小児例が詳細に記述さ
れて以来、種々の臨床亜型が相次いで報告され、
この疾患がかなり多様性に富んだ症候群であるこ
とがわかつてきた。そこで従来主として臨床的な
立場からの分類、すなわち発病年齢、罹患筋の分
布、性差、遺伝型式、経過の緩急などに基づいた
分類等が行なわれてきたが、世界神経学連合の分
類（1968年）によれば、遺伝性疾患として(1)
Duchenne（仮性肥大）型、(2)顔面肩甲上腕型、(3)
肢帯型、(4)遠位型、(5)眼筋型、(6)眼咽頭型に大別
することができる。また、Walton and Gardner
−Medwin（1969）はDuchenne型、肢帯型を遺伝
様式で分け、前者の呼称をＸ染色体型に限定して
使用すべきだとしており、さらに筋緊張症を(1)先
天型、(2)寒冷増悪型、(3)萎縮性筋緊張型に分けて
分類に含めている。 Muscular dystrophies are a group of myopathies characterized by progressive degeneration of skeletal muscles, and their onset depends on genetic factors. Since Duchenne described a pediatric case of pseudohypertrophic muscular dystrophy in detail in 1868, various clinical subtypes have been successively reported.
It has become clear that this disease is a highly diverse syndrome. Conventionally, classifications have been made mainly from a clinical standpoint, that is, based on age of onset, distribution of affected muscles, gender differences, genetic type, and gradualness of course. ), as a genetic disease (1)
Duchenne (pseudohypertrophic) type, (2) facioscapulohumeral type, (3)
It can be broadly classified into limb-girdle type, (4) distal type, (5) ocular muscle type, and (6) oculopharyngeal type. Also, Walton and Gardner
-Medwin (1969) divided Duchenne type and limb-girdle type based on inheritance pattern, and stated that the former should be used only for the X-chromosome type, and further classified myotonia as (1) congenital type, (2) It is classified into cold-exacerbated type and (3) atrophic muscle tone type.
代表的な例としてDuchenne型の特徴をあげて
みると次の如くである。すなわち、Turner症候
群が女性にごく稀に発症する以外は、男性のみに
発症する（伴性劣性遺伝）。２〜５歳の間に発病
する。初め腰帯筋の筋力低下が起り、次いで肩帯
筋が左右対称性におかされる。仮性肥大が主とし
て下腿筋に必ず発現する。常に症状が進行増悪
し、発病後10年以内に歩行不能となる。心筋障害
がしばしばみられる。腰部前彎および脊椎側彎が
進行性に現れる。多くは20歳前後に栄養失調、呼
吸器感染症、心不全などによつて死亡する。 As a typical example, the characteristics of the Duchenne type are as follows. That is, except for Turner syndrome, which occurs very rarely in women, it occurs only in men (sex-linked recessive inheritance). Onset occurs between the ages of 2 and 5. Initially, the lumbar girdle muscles become weaker, and then the shoulder girdle muscles become symmetrical. Pseudohypertrophy always occurs mainly in the crural muscles. Symptoms always progress and worsen, and patients become unable to walk within 10 years after onset of the disease. Myocardial damage is often seen. Lumbar lordosis and scoliosis develop progressively. Most die around the age of 20 from malnutrition, respiratory infections, heart failure, etc.
筋ジストロフイー症は所謂難病であり、完全に
治癒せしめる療法や薬剤は未だ見出されていな
い。しかしその治療とともに薬剤により延命を計
ることができるならば、それは重大な進歩である
と伝える。 Muscular dystrophy is a so-called incurable disease, and no therapy or drug that can completely cure it has yet been found. However, if it is possible to prolong life through treatment and drugs, that would be a significant advance.
本発明において用いられる1α−ヒドロキシビ
タミンD3類とは
1α−（OH）−D3，1α，25−（OH）2−D3，1α，
24S−（OH）2−D3，1α，24R−（OH）2−D3，
1α，24S，25−（OH）3−D3，1α，24R，25−
（OH）3−D3，1α，25S，26−（OH）3−D3，1α，
25K，26−（OH）3−D3，1α，25−（OH）2−23
−OXO−D3，1α，25−（OH）2−24−OXO−
D3，1α，25S，26−（OH）3−23−OXO−D3，
1α，25R，26−（OH）3−23−OXO−D3，1α，
25S−（OH）2−D3−26，23S−lactone，
1α，25R−（OH）2−D3−26，23S−lactone，
1α−（OH）−24，25，26，27−tetraucr−23−
COOH−D3
等が含まれる。 The 1α-hydroxyvitamin D 3 used in the present invention is 1α-(OH)-D 3 , 1α, 25-(OH) 2 -D 3 , 1α,
24S−(OH) 2 −D 3 , 1α, 24R−(OH) 2 −D 3 ,
1α, 24S, 25− (OH) 3 −D 3 , 1α, 24R, 25−
(OH) 3 −D 3 , 1α, 25S, 26−(OH) 3 −D 3 , 1α,
25K, 26−(OH) 3 −D 3 , 1α, 25−(OH) 2 −23
−OXO−D 3 ,1α,25−(OH) 2 −24−OXO−
D 3 , 1α, 25S, 26−(OH) 3 −23−OXO−D 3 ,
1α, 25R, 26−(OH) 3 −23−OXO−D 3 , 1α,
25S−(OH) 2 −D 3 −26, 23S−lactone, 1α, 25R−(OH) 2 −D 3 −26, 23S−lactone, 1α−(OH)−24, 25, 26, 27−tetraucr− 23−
Includes COOH-D 3 , etc.
これらの本物質は例えばU.S.Patent 3697559，
特開昭51−76252，特開昭51−76254，U.S.
Patent 3741996，特開昭55−22655，特開昭55−
22656，特開昭56−61351，Arch，Biochem.
Biophys.，204，387（1981），H.F.De Luca，ビ
タミンＤ−［その新しい流れ］，講談社，サイエン
テイフイク（1982）などに開示されている。 These substances are, for example, US Patent 3697559,
JP 51-76252, JP 51-76254, US
Patent 3741996, Japanese Patent Publication No. 55-22655, Japanese Patent Application Publication No. 1987-22655
22656, JP-A-56-61351, Arch, Biochem.
Biophys., 204 , 387 (1981), HFDe Luca, Vitamin D - [The New Trend], Kodansha, Scientific (1982), etc.
本発明のおいては光学異性体のいずれを用いて
もよく、又、二種以上を混合して用いてもよい。 In the present invention, any of the optical isomers may be used, or two or more types may be mixed and used.
本発明の抗筋ジストロフイー症剤は活性成分と
して上記本物質を含有して、下記に示す種々の製
剤形態にて用いられる。本発明の抗筋ジストロフ
イー症剤は、経口的、非経口的に投与される。 The anti-muscular dystrophy agent of the present invention contains the above substance as an active ingredient and is used in various formulations shown below. The antimuscular dystrophy agent of the present invention is administered orally or parenterally.
投与形態としては例えば、圧縮錠剤、被覆錠
剤、硬又は軟弾性ゼラチンカプセル、エチルアル
コール溶液、油性または水性溶液または懸濁液な
どが用いられる。 Examples of dosage forms that can be used include compressed tablets, coated tablets, hard or soft elastic gelatin capsules, ethyl alcohol solutions, oily or aqueous solutions or suspensions.
油性溶液の溶媒としては、植物油例えばヤシ
油、トウモロコシ油、棉実油、ココナツツ油、落
花生油、魚肝油、油状エステル例えばポリソルベ
ート80などを使用することができる。 As solvents for oily solutions, vegetable oils such as coconut oil, corn oil, cottonseed oil, coconut oil, peanut oil, fish liver oil, oily esters such as polysorbate 80, etc. can be used.
直腸内投与の場合には坐剤ベース例えばカカオ
脂またはそのトリグリセライドなどを含む薬用組
成物とすることができる。 For rectal administration, the pharmaceutical composition may include a suppository base, such as cocoa butter or its triglycerides.
本物質は単位投与形態の中、２×10-5乃至１×
10％、好ましくは２×10-4乃至１％を含有する。 The substance may be present in unit dosage forms ranging from 2×10 -5 to 1×
10%, preferably 2×10 −4 to 1%.
又、投与量は0.1乃至104μｇ／日／人、好まし
くは0.5乃至103μｇ／日／人とすることができる。
そして、上記量的関係が保持されるように、１日
１〜３回の投与回数となるように調製される。 Further, the dosage can be 0.1 to 10 4 μg/day/person, preferably 0.5 to 10 3 μg/day/person.
Then, in order to maintain the above-mentioned quantitative relationship, the dosage is adjusted to be administered 1 to 3 times a day.
以下、実施例により本発明を詳述する。 Hereinafter, the present invention will be explained in detail with reference to Examples.
実施例 １
筋ジストロフイー症のモデル動物である
C57BL／6J dy／dy系雄マウス（以下、本動物と
いう）を４週齢で日本クレアより購入し、５週齢
より0.001％のイソプロパノール（以下、IPAと
略す）水溶液に溶かした0.02μｇ／Kg／日に相当
する、1α−（OH）−D3，1α，25−（OH）2−D3及
び1α，24R−（OH）2−D3のそれぞれの溶液を飲
料水として本動物に投与した。Example 1 Model animal for muscular dystrophy
C57BL/6J dy/dy male mice (hereinafter referred to as the animals) were purchased from CLEA Japan at the age of 4 weeks, and from the age of 5 weeks, 0.02 μg/Kg dissolved in a 0.001% isopropanol (hereinafter abbreviated as IPA) aqueous solution was used. Each solution of 1α-(OH)-D 3 , 1α,25-(OH) 2 -D 3 and 1α,24R-(OH) 2 -D 3 was administered to the animal as drinking water, equivalent to /day. did.
また対照群には0.001％IPA水溶液を、無処置
群には水道水を、それぞれ飲料水として自由摂取
させた。 In addition, the control group was allowed to drink 0.001% IPA aqueous solution, and the untreated group was allowed to drink tap water ad libitum.
投与開始後150日目、即ち本動物の平均寿命と
言われる４〜５ケ月目（医歯薬出版刊、「疾患モ
デル動物ハンドブツク」421頁）に相当する時期
における各群の生存率を求めた。 The survival rate of each group was determined on the 150th day after the start of administration, which corresponds to 4 to 5 months, which is said to be the average lifespan of the animals (Ishiyaku Publishing, "Disease Model Animal Handbook" p. 421). .
無処置群、対照群の生存率はいずれも16.7％で
あつたのに対し、1α−（OH）−D3，1α，25−
（OH）2−D3及び1α，24R−（OH）2−D3投与群の
生存率は、それぞれ60％，62％，55％であつた。 The survival rate of both the untreated group and the control group was 16.7%, whereas the survival rate of 1α-(OH)-D 3 , 1α, 25-
The survival rates of the (OH) 2 -D 3 and 1α,24R-(OH) 2 -D 3 administration groups were 60%, 62%, and 55%, respectively.
尚、1α−（OH）−D3，1α，25−（OH）2−D3及
び1α，24R−（OH）2−D3の経口投与による急性
毒性値（LD50）はそれぞれ680，2500＜，2000μ
ｇ／Kgであつた。 The acute toxicity values (LD 50 ) of 1α-(OH)-D 3 , 1α,25-(OH) 2 -D 3 and 1α,24R-(OH) 2 -D 3 by oral administration are 680 and 2500, respectively. ＜，2000μ
g/Kg.
以上の結果から、1α−ヒドロキシビタミンD3
類が抗筋ジストロフイー症剤として有効であるこ
とが示された。 From the above results, 1α-hydroxyvitamin D 3
It has been shown that these drugs are effective as antimuscular dystrophy agents.
実施例 ２
1α−（OH）−D3をパナセート800（日本油脂製、
中鎖脂肪酸のトリグリセライド）に10μｇ／mlの
濃度に溶解し、１カプセル中に1α−（OH）−D3を
1μｇ含有するように下記剤皮成分を加温溶解し、
軟カプセル製造機を用いて常法により軟カプセル
剤を作成した。Example 2 1α-(OH)-D 3 was added to Panacet 800 (NOF Co., Ltd.,
One capsule contains 1α-(OH) -D3 dissolved in medium-chain fatty acid triglyceride) at a concentration of 10 μg/ml.
The following skin components were dissolved by heating to contain 1μg,
Soft capsules were prepared by a conventional method using a soft capsule making machine.
剤皮処方例
ゼラチン 10 重量部
グリセリン ２ 重量部
防腐剤（エチルパラベン） 0.05重量部
チタンホワイト 0.2 重量部
水 0.2 重量部
（最終形態に於ける重量部）
実施例 ３
実施例２の1α−（OH）−D3に代えて1α，25−
（OH）2−D3を用い、以下同様にして1α，25−
（OH）2−D3を１カプセル当り1μｇを含有する軟
カプセル剤を得た。 Shell formulation example Gelatin 10 parts by weight Glycerin 2 parts by weight Preservative (ethylparaben) 0.05 parts by weight Titanium White 0.2 parts by weight Water 0.2 parts by weight (parts by weight in final form) Example 3 1α-(OH of Example 2) )−D 1α, 25− instead of 3
Using (OH) 2 −D 3 , 1α, 25−
Soft capsules containing 1 μg of (OH) 2 -D 3 per capsule were obtained.
実施例 ４
実施例２の1α−（OH）−D3に代えて1α，24R−
（OH）2−D3を用い、以下同様にして1α，24R−
（OH）2−D3を１カプセル当り1μｇを含有する軟
カプセル剤を得た。Example 4 1α,24R- in place of 1α-(OH)-D 3 in Example 2
Using (OH) 2 −D 3 , 1α, 24R−
Soft capsules containing 1 μg of (OH) 2 -D 3 per capsule were obtained.
Claims (1)
とを特徴とする抗筋ジストロフイー症剤。1. An antimuscular dystrophy agent characterized by containing 1α-hydroxyvitamin D 3 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14132483A JPS6045517A (en) | 1983-08-02 | 1983-08-02 | Antimyodystrophia agent containing 1alpha-hydroxyvitamin d3 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14132483A JPS6045517A (en) | 1983-08-02 | 1983-08-02 | Antimyodystrophia agent containing 1alpha-hydroxyvitamin d3 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6045517A JPS6045517A (en) | 1985-03-12 |
| JPH0319209B2 true JPH0319209B2 (en) | 1991-03-14 |
Family
ID=15289273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14132483A Granted JPS6045517A (en) | 1983-08-02 | 1983-08-02 | Antimyodystrophia agent containing 1alpha-hydroxyvitamin d3 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6045517A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08198756A (en) * | 1995-01-23 | 1996-08-06 | Minsei Kagaku Kyokai | Agent for inhibiting progress of muscular dystrophy |
| CN103142476B (en) * | 2013-03-21 | 2014-11-12 | 青岛正大海尔制药有限公司 | Calcitriol suspension and preparation method thereof |
| CN103142471B (en) * | 2013-03-21 | 2014-08-20 | 青岛正大海尔制药有限公司 | Calcitriol solution and preparation method thereof |
| IT202100007655A1 (en) * | 2021-03-29 | 2022-09-29 | Abiogen Pharma Spa | USE OF COLECALCIFEROL AS AN ADJUVANT IN THE TREATMENT OF MUSCULAR DYSTROPHIES |
-
1983
- 1983-08-02 JP JP14132483A patent/JPS6045517A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6045517A (en) | 1985-03-12 |
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