JPH0374330A - Remedy of demyelinating disease - Google Patents
Remedy of demyelinating diseaseInfo
- Publication number
- JPH0374330A JPH0374330A JP1206679A JP20667989A JPH0374330A JP H0374330 A JPH0374330 A JP H0374330A JP 1206679 A JP1206679 A JP 1206679A JP 20667989 A JP20667989 A JP 20667989A JP H0374330 A JPH0374330 A JP H0374330A
- Authority
- JP
- Japan
- Prior art keywords
- remedy
- sah
- adverse effect
- active ingredient
- compound
- 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
- 208000016192 Demyelinating disease Diseases 0.000 title claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- ZJUKTBDSGOFHSH-WFMPWKQPSA-N S-Adenosylhomocysteine Chemical compound O[C@@H]1[C@H](O)[C@@H](CSCC[C@H](N)C(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZJUKTBDSGOFHSH-WFMPWKQPSA-N 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 9
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 230000000694 effects Effects 0.000 abstract description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000007924 injection Substances 0.000 abstract description 4
- 238000002347 injection Methods 0.000 abstract description 4
- 229930105110 Cyclosporin A Natural products 0.000 abstract description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 abstract description 3
- 108010036949 Cyclosporine Proteins 0.000 abstract description 3
- 230000037396 body weight Effects 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 201000002364 leukopenia Diseases 0.000 abstract description 3
- 231100001022 leukopenia Toxicity 0.000 abstract description 3
- 238000006462 rearrangement reaction Methods 0.000 abstract description 2
- 230000002411 adverse Effects 0.000 abstract 3
- 206010062016 Immunosuppression Diseases 0.000 abstract 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract 1
- 208000019423 liver disease Diseases 0.000 abstract 1
- 239000000829 suppository Substances 0.000 abstract 1
- 208000033068 episodic angioedema with eosinophilia Diseases 0.000 description 9
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 208000003926 Myelitis Diseases 0.000 description 5
- 206010033799 Paralysis Diseases 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 229960003444 immunosuppressant agent Drugs 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 2
- MEFKEPWMEQBLKI-AIRLBKTGSA-O S-adenosyl-L-methionine Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H]([NH3+])C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-O 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 208000010726 hind limb paralysis Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ZTVZLYBCZNMWCF-WDSKDSINSA-N L,L-homocystine zwitterion Chemical group OC(=O)[C@@H](N)CCSSCC[C@H](N)C(O)=O ZTVZLYBCZNMWCF-WDSKDSINSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 108010038083 amyloid fibril protein AS-SAM Proteins 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000027905 limb weakness Diseases 0.000 description 1
- 231100000861 limb weakness Toxicity 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- -1 salt compounds Chemical group 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000005758 transcription activity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、Ｓ−アデノシル−Ｌ−ホモシステイン（以下
ＳＡＨと略記する）若しくはその塩を有効成分とする新
規な脱髄疾患治療剤に関する。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel therapeutic agent for demyelinating diseases containing S-adenosyl-L-homocysteine (hereinafter abbreviated as SAH) or a salt thereof as an active ingredient.
（従来の技術）
脱（Ｆ！ （ｄｅｍｙｅｌｉｎａｔｉｏｎ）疾患は、中
枢神経系の白質血管の周囲炎あるいは神経を包む髄鞘が
一次性に崩壊することに起因する疾患群で、多発性硬化
症や視神経を髄炎、急性汎発性脳を髄炎、感染後脳を髄
炎などの疾患が含まれる。これらの疾患では、神経系の
崩壊によって筋肉麻痺や感覚異常が発生し、ついには死
に至ることが多い。現在のところ治療方法も確立されて
おらず難病の一つである。また、この神経系の崩壊には
非化膿性の炎症が原因であるとも言われている。(Prior art) F! (demyelination) diseases are a group of diseases caused by peritis of white matter blood vessels in the central nervous system or primary breakdown of myelin sheaths surrounding nerves, including multiple sclerosis and optic nerve disease. This includes diseases such as myelitis, acute generalized myelitis of the brain, and myelitis of the brain after infection.In these diseases, the breakdown of the nervous system causes muscle paralysis and paresthesia, and can eventually lead to death. Currently, there is no established treatment method and it is an incurable disease. It is also said that non-suppurative inflammation is the cause of this nervous system breakdown.
これらの脱髄性疾患の中でも特に多発性硬化症（ｍｕｌ
ｔｉｐｌｅ ５ｃｌｅｒｏｓｉｓ）は多発性病巣の発生
と増悪、寛解を繰り返す特徴があり、増悪と寛解を繰り
返しながら病状が進行し、また発症数も他の脱髄性疾患
に比較して多く、治療方法の早急な開発が望まれている
。Among these demyelinating diseases, multiple sclerosis (mulple sclerosis) is particularly
5 clerosis) is characterized by repeated occurrence of multiple lesions, exacerbations, and remissions, and the disease progresses through repeated exacerbations and remissions, and the number of cases is higher than other demyelinating diseases, so it is urgent to find a treatment method. Further development is desired.
多発性硬化症は動物における実験的アレルギー性脳を髄
炎（Ｅｘｐｅｒｉｍｅｎｔａｌ Ａｌｌｅｒｇｉｃ Ｅ
ｎｃｅｐｈａｌ。Multiple sclerosis causes experimental allergic brain myelitis in animals.
ncephal.
ｍｙｅｌｉｔｉｓ、以下ＥＡＥという）がヒトの疾患モ
デルになるといわれている。特に、脱髄病変については
病理学的にも同一であるといわれている（昭和５９年２
月２５日 ソフトサイエンス社発行、京極方久編「難治
疾患のモデルと動物実験」第２７５頁〜２９７頁参照）
。myelitis (hereinafter referred to as EAE) is said to serve as a human disease model. In particular, demyelinating lesions are said to be pathologically the same (February 1982).
(See "Models and Animal Experiments for Intractable Diseases," edited by Kyogoku Katsuhisa, pp. 275-297, published by Soft Science Co., Ltd., March 25th)
.
（発明が解決しようとする課題）
このような動物モデルを使用した実験の結果、サイクロ
スポリンＡのような免疫抑制剤が多発性硬化症の治療効
果を示すことが明らかとなり、脱髄性疾患の治療に光明
を与えることとなった。しかし、この種の免疫抑制剤は
肝障害、白血球減少等の強い副作用を示し、副作用の少
ない脱髄性疾患の治療剤の開発が強く望まれている。(Problems to be Solved by the Invention) As a result of experiments using such animal models, it has become clear that immunosuppressants such as cyclosporin A have a therapeutic effect on multiple sclerosis, and it has been shown that immunosuppressants such as cyclosporin A are effective in treating multiple sclerosis. This has shed light on the treatment of However, this type of immunosuppressants exhibit strong side effects such as liver damage and leukopenia, and there is a strong desire to develop therapeutic agents for demyelinating diseases with fewer side effects.
本発明者らは、多発性硬化症などの脱髄疾患の治療方法
をＥＡＥモデルを使用して研究を行った結果、既知化合
物であるＳ Ａ Ｔ（がＥＡＥの進行を抑制する効果を
見出し、本発明を完成するに至った。The present inventors conducted research on treatment methods for demyelinating diseases such as multiple sclerosis using an EAE model, and as a result, discovered that a known compound, SAT, has the effect of suppressing the progression of EAE. The present invention has now been completed.
本発明で使用するＳＡＨはメチオニンの代謝の過程で生
威し生体内に広く分布しており、その安全性も広く知ら
れている。SAH used in the present invention is produced in the process of methionine metabolism and is widely distributed in living organisms, and its safety is also widely known.
本発明においては、副作用の少ないＳＡＨ若しくはその
塩を有効成分とする新規な脱髄性疾患の治療剤を提供す
ることを目的とする。An object of the present invention is to provide a novel therapeutic agent for demyelinating diseases containing SAH or its salt as an active ingredient with few side effects.
（課題を解決するための手段）
本発明は、ＳＡＨ若しくは製薬上使用し得るその塩類を
有効成分として含有することを特徴とする脱髄疾患治療
剤である。(Means for Solving the Problems) The present invention is a therapeutic agent for demyelinating diseases characterized by containing SAH or a pharmaceutically usable salt thereof as an active ingredient.
本発明に於いて使用するＳＡＨは下記構造式を有する化
合物である。The SAH used in the present invention is a compound having the following structural formula.
ＳＡＨは生体内に広く分布し、生体内メチル基転位反応
後の産物として生成する。すなわち、メチル基転位反応
は、Ｓ−アデノシル−Ｌ−メチオニン（以下ＳＡＭと略
記する）をメチル基供与体とし、核酸や蛋白質をメチル
基受容体として、種々のメチル基転位酵素によって触媒
される。反応後、ＳＡＭはメチル基を失ってＳＡＨにな
る。このメチル基転位反応は、遺伝子の転写活性の調節
、細胞分化など重要な働きを担っていることが知られて
いる （Ｎ、Ｍ、Ｋｒｅｄｉｃｈ他Ｃｅ１ｌ １２巻９
３１〜９３８．１９７７年）。このようにＳＡＨは生体
組織内の反応に大きく関係しているが、医薬品としての
用途は明らかにされていない。特開昭５４−１４５２２
２号公報には、Ｓ Ａ Ｈが鎮静剤、抗痙型剤、睡眠誘
発剤として有用であることが開示されている。また、上
述したタレディソヒらはＳＡＨがＴリンパ腫細胞に障害
を与えることを開示している。しかし、本発明で開示さ
れる脱髄疾患に有効であるという報告は文献には未だ記
載されていない。SAH is widely distributed in living organisms and is produced as a product after an in vivo methyl group rearrangement reaction. That is, the methyl group transfer reaction is catalyzed by various methyl group transfer enzymes using S-adenosyl-L-methionine (hereinafter abbreviated as SAM) as a methyl group donor and nucleic acids or proteins as methyl group acceptors. After the reaction, SAM loses its methyl group and becomes SAH. This methyl group translocation reaction is known to play important roles such as regulating gene transcription activity and cell differentiation (N, M, Kredich et al., Ce11, Vol. 12, 9).
31-938.1977). As described above, SAH is greatly involved in reactions within living tissues, but its use as a pharmaceutical has not been clarified. Japanese Patent Publication No. 54-14522
Publication No. 2 discloses that S A H is useful as a sedative, an anticonvulsant, and a sleep-inducing agent. Taredisohi et al., mentioned above, have also disclosed that SAH damages T lymphoma cells. However, there have been no reports in the literature that it is effective against the demyelinating disease disclosed in the present invention.
ＳＡＨは上述したように、生体内成分として各組織に広
く分布しており、その安全性は良く知られている。例え
ば、前掲の特開昭５４−１４５２２２号公報にはＳ Ａ
Ｈを２００匹の二十日ネズ砒に１回当りＩｇ／ｋｇ（
経口または経腹腔投与）、有効投与回数１．０００なる
条件での投与は毒性の徴候を何ら示さなかったと記載さ
れている。ＳＡＨはその構造内にアミノ基、カルボキシ
ル基、塩基性の窒素原子を有しており、これらに結合し
た塩類化合物も本発明に含まれる。特に製薬上で使用さ
れるような非毒性の酸付加塩類である塩酸塩、硫酸塩、
リン酸塩、クエン酸塩、マレイン酸塩、コハク酸塩ある
いはホモシスチン残基のカルボキシル基のナトリウム塩
、アンモニウム塩などが例示できる。As mentioned above, SAH is widely distributed in various tissues as an in vivo component, and its safety is well known. For example, in the above-mentioned Japanese Patent Application Laid-Open No. 54-145222, S.A.
Ig/kg (
It is stated that no signs of toxicity were shown when the drug was administered (orally or intraperitoneally) and the number of effective doses was 1,000. SAH has an amino group, a carboxyl group, and a basic nitrogen atom in its structure, and salt compounds bonded to these are also included in the present invention. Non-toxic acid addition salts, particularly those used in pharmaceuticals, such as hydrochlorides, sulfates,
Examples include phosphates, citrates, maleates, succinates, and sodium salts and ammonium salts of the carboxyl group of homocystine residues.
ＳＡＨ若しくはその塩は、単独あるいは従来公知の製剤
成分と混合して、散剤、錠剤、カプセル剤として使用し
てもよい。さらに溶解補助剤等を加えて溶解ないし懸濁
し、必要に応じて凍結乾燥を行って注射剤として使用す
ることができる。SAH or its salt may be used alone or in combination with conventionally known formulation components in the form of powders, tablets, and capsules. Furthermore, it can be dissolved or suspended by adding a solubilizing agent and the like, and if necessary, freeze-dried and used as an injection.
脱髄疾患に対して投与するときは、注射、または経口、
あるいは原剤として投与することができ、１日体重当り
で０．１〜５０■／ ｋｇを投与すると効果を示す。When administered for demyelinating diseases, it can be administered by injection or orally,
Alternatively, it can be administered as a raw material, and it is effective when administered at a dose of 0.1 to 50 kg per body weight per day.
（実施例） 以下、実施例に基づき、さらに本発明を具体的に示す。(Example) Hereinafter, the present invention will be explained in more detail based on Examples.
実施例ｌ
５ＡＨ１１１の １゛告 （１）
ＳＡＨ１ｇを乳糖１００ｇと混合し、打錠器で打錠し錠
剤とした。この錠剤は１錠中に５ＡＨＩＯ■を含有し、
経口剤として使用される。Example 1 1. Notice of 5AH111 (1) 1 g of SAH was mixed with 100 g of lactose and compressed into tablets using a tablet press. This tablet contains 5AHIO■ in one tablet,
Used as an oral agent.
実施例２
ＳＡＨ１１１の １１゛告 （２）
ＳＡＨｌｏｇを乳１ｉ１ｊ！の生理食塩水に溶解し、０
．２２μｍのごリポアフィルターで無菌濾過した。この
液を５ ｍＲのバイアル瓶に２ ｍｌずつ分注し、凍結
乾燥後、直ちに密栓し、注射用粉末製剤を作製した。木
製剤は’ｌ ｍＲの注射用藤留水を加え溶解して使用す
る。Example 2 SAH111's 11゛Notification (2) SAHlog is milk 1i1j! Dissolved in physiological saline of 0
．． It was sterile filtered using a 22 μm lipopore filter. This solution was dispensed in 2 ml portions into 5 mR vials, freeze-dried, and immediately sealed tightly to prepare a powder preparation for injection. The wooden preparation is used by adding 1 mR of Fujidome water for injection and dissolving it.
実施例３
ＳＡＨｌ の１１゛告（３）
Ｓ Ａ Ｈクエン酸塩２５ｇ、乳ｌｆｆ１７５Ｅを混合
、粉砕、造粒後、ゼラチンカプセルにｌＱＯｍｇずつ充
填し、カプセル剤１ 、０００カプセルを製造した。Example 3 (3) 25 g of SAH citrate and milk lff175E were mixed, crushed and granulated, and then filled into gelatin capsules in an amount of 1QOmg to produce 1,000 capsules.
実施例４
ＳＡＨによるＥＡＥラソトの治療
脱髄疾患の１種、多発性硬化症モデルであるＥＡＥラソ
トの治療効果を示す。Example 4 Treatment of EAE Lasotho with SAH The therapeutic effect of EAE Lasotho, which is a multiple sclerosis model, which is a type of demyelinating disease, will be shown.
Ｌｅｗｉｓラソト（メス６退会）を１群５匹とし、ＥＡ
Ｅ誘発の抗原として同系ラットの脳ホモシュネートをフ
ロイント完全アジュバント（デイフコ製）と同量混合し
たものを脳ホモシュネート８０■換算となるようにウソ
１−の後肢足跡に免疫した。Lewis Lasoto (6 females withdrawn) was set as 5 animals per group, and EA
As an antigen for E induction, brain homogenate from a syngeneic rat was mixed with Freund's complete adjuvant (manufactured by Difco) in the same amount, and the hind leg footprints of bullfinch 1- were immunized in an amount equivalent to 80 ml of brain homogenate.
免疫当日より１８日間、表１に示すように対照群に食塩
水を、実験群にＳＡＨを、それぞれ腹腔内に投与し、毎
日体重測定とＥＡＥ症状観察を行った。ＥＡＥの症状と
しては６段階評価をした。即ち、０：異常なし、１：尾
麻痺、２：尾麻痺を伴う後肢衰弱、３：尾麻痺を伴う後
肢麻痺、４：後肢麻痺を伴う前肢衰弱、５：四肢麻痺ま
たは前瀕死、６：死亡 として各症状の累積症状度によ
り効果を判定した。For 18 days from the day of immunization, as shown in Table 1, saline was administered intraperitoneally to the control group and SAH to the experimental group, and body weight was measured and EAE symptoms observed every day. EAE symptoms were evaluated on a 6-level scale. That is, 0: No abnormality, 1: Tail paralysis, 2: Hind limb weakness accompanied by tail paralysis, 3: Hind limb paralysis accompanied by tail paralysis, 4: Forelimb weakness accompanied by hind limb paralysis, 5: Quadrilateral paralysis or front moribund, 6: Death. The effectiveness was determined based on the cumulative severity of each symptom.
ＳＡＨの投与は、実施例２で得られた製剤を動物に８■
／ ｋｇの量で投与した。結果は表１に示した。For administration of SAH, the preparation obtained in Example 2 was administered to animals for 8 days.
/kg. The results are shown in Table 1.
表Ｉ ＳＡＨのＥＡＥラソトに対する治療効果ＳＡＨ
８５１５９，０７２（４２）
ＳＡＨ投与群では対照群とほぼ同様、平均で９日目に発
症した。しかしう・７１・の症状は軽く、最大症状は３
であった。一方対照群では、５匹中、４匹が実験期間中
に死亡した。Table I Therapeutic effect of SAH on EAE Lasotho SAH
85159,072 (42) In the SAH-administered group, symptoms occurred on the 9th day on average, almost the same as in the control group. However, the symptoms of 71. are mild, and the maximum symptoms are 3.
Met. On the other hand, in the control group, 4 out of 5 animals died during the experimental period.
以上の結果から、ＳＡＨは明らかにＥＡＥに有効である
ことが確認された。From the above results, it was confirmed that SAH is clearly effective against EAE.
（発明の効果）
本発明の脱髄疾患治療剤によれば副作用の少ないＳＡＨ
若しくはその塩を有効成分とするので、従来の肝障害や
白血球減少等の強い副作用を示す免疫抑制剤とは異なり
、毒性のない新規な脱髄疾患治療剤の提供が可能となる
。(Effect of the invention) According to the therapeutic agent for demyelinating disease of the present invention, SAH with fewer side effects
or a salt thereof as an active ingredient, it is possible to provide a novel non-toxic therapeutic agent for demyelinating diseases, unlike conventional immunosuppressants that exhibit strong side effects such as liver damage and leukopenia.
Claims (1)
薬上使用し得るその塩類を有効成分として含有すること
を特徴とする脱髄疾患治療剤。(1) A therapeutic agent for demyelinating disease characterized by containing S-adenosyl-L-homocysteine or a pharmaceutically usable salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1206679A JPH0374330A (en) | 1989-08-11 | 1989-08-11 | Remedy of demyelinating disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1206679A JPH0374330A (en) | 1989-08-11 | 1989-08-11 | Remedy of demyelinating disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0374330A true JPH0374330A (en) | 1991-03-28 |
Family
ID=16527318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1206679A Pending JPH0374330A (en) | 1989-08-11 | 1989-08-11 | Remedy of demyelinating disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0374330A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008515994A (en) * | 2004-10-13 | 2008-05-15 | ジェネラル アトミクス | Reversible inhibitor of S-adenosyl-L-homocysteine hydrolase and use thereof |
| CN102363229A (en) * | 2011-11-15 | 2012-02-29 | 大连理工大学 | Process for machining multi-tooth gear blank by utilizing graduated disk with small number of slots |
| JP2021046375A (en) * | 2019-09-19 | 2021-03-25 | ポッカサッポロフード＆ビバレッジ株式会社 | β3 ADRENERGIC RECEPTOR AGONIST |
-
1989
- 1989-08-11 JP JP1206679A patent/JPH0374330A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008515994A (en) * | 2004-10-13 | 2008-05-15 | ジェネラル アトミクス | Reversible inhibitor of S-adenosyl-L-homocysteine hydrolase and use thereof |
| JP2012197314A (en) * | 2004-10-13 | 2012-10-18 | General Atomics | Composition for reversibly inhibiting s-adenosyl-l-homocysteine hydrolase and its use |
| CN102363229A (en) * | 2011-11-15 | 2012-02-29 | 大连理工大学 | Process for machining multi-tooth gear blank by utilizing graduated disk with small number of slots |
| JP2021046375A (en) * | 2019-09-19 | 2021-03-25 | ポッカサッポロフード＆ビバレッジ株式会社 | β3 ADRENERGIC RECEPTOR AGONIST |
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