JP3459013B2 - An agent for treating arthritis containing uridine as an active ingredient - Google Patents
An agent for treating arthritis containing uridine as an active ingredientInfo
- Publication number
- JP3459013B2 JP3459013B2 JP52525594A JP52525594A JP3459013B2 JP 3459013 B2 JP3459013 B2 JP 3459013B2 JP 52525594 A JP52525594 A JP 52525594A JP 52525594 A JP52525594 A JP 52525594A JP 3459013 B2 JP3459013 B2 JP 3459013B2
- Authority
- JP
- Japan
- Prior art keywords
- uridine
- active ingredient
- agent
- treating arthritis
- containing uridine
- 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 - Fee Related
Links
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 title claims description 50
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 title claims description 24
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 title claims description 24
- 229940045145 uridine Drugs 0.000 title claims description 24
- 239000004480 active ingredient Substances 0.000 title description 3
- 206010003246 arthritis Diseases 0.000 title description 3
- 239000003814 drug Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 206010063409 Acarodermatitis Diseases 0.000 claims 1
- 241000447727 Scabies Species 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 208000005687 scabies Diseases 0.000 claims 1
- 230000008961 swelling Effects 0.000 description 6
- 208000010412 Glaucoma Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000011694 lewis rat Methods 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 102000000503 Collagen Type II Human genes 0.000 description 3
- 108010041390 Collagen Type II Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 229940027941 immunoglobulin g Drugs 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
- 239000000203 mixture Substances 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- 208000019932 Aciduria Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 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
- 241000699670 Mus sp. Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 241001125046 Sardina pilchardus Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000022159 cartilage development Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002905 effect on arthritis Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 210000003035 hyaline cartilage Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002956 necrotizing effect Effects 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 230000006824 pyrimidine synthesis Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (AREA)
Description
【発明の詳細な説明】
技術分野
本發明はウリジンを有效成分とする關節炎治療劑に關
し,更に詳しくは,ヌクレオシドであるウリジンの新規
な藥效である關節炎治療效果としての用途及びこれを含
有する藥劑に關するものである.
背景技術
ウリジンはRNAを構成するのに必要な4個のリボヌク
レオシド中の一つとして自然界で廣範圍に分布されてい
る物質として,その分子量は244.20であり,分子式はC9
H12N2O6で10あり,その構造式は次の通りだ.
今まで知られたいるウリジンの藥理作用はウリジンが投
與されると體内でウリジンキナゼ酵素の觸媒作用によっ
てウリジン5'−ホスヌァートへ直ちに轉換されるので,
酵素の缺乏またはピリミジンヌクレオチジト缺乏と核酸
合成の缺乏に有用してオルチク酸尿症(HEREDITARY OR
OTIC ACIDURIA)を輕減させる藥劑として使われた報告
(MATINDALE,1989,1627)があり,實際,大韓民國内に
ても複合製劑の成分としているいるの藥效のため使用さ
れたことがありますが,ウリジン自體が關節炎に效果を
有することと報告されることはない.本發明者は生藥と
して使用されている成分を研究する中,單一成分として
分離精製された各種物質の藥效スクリニングした結果,
該植物より分離された成分中の一が優れた關節炎治療效
果を有することが發見して,物質に對する分子構造を糾
明した結果,ウリジンであることを確認して本發明を完
成した.
ウリジンが今まで醫藥品に使用された場合は他の藥效
物質とともに複合製劑として血管性腦疾患,肝腸保護,
末梢神腦症,組經織低酸素症等に使われることが知られ
ているが,その關節炎治療效果は知られていない.
發明の開示
本發明の目的は,式
で表されるウリジンを有效成分とする關節炎改善劑を提
供するものである.
圖面の簡單な説明
圖1は對照群と,ウリジンを投與した群の關節炎發生
部位の浮腫が拔けるの腦時推移を表わされるグラフであ
る.
發明を實施するための最良の形態
本發明はウリジンを有效成分とする關節炎改善劑を提
供することでウリジン0.6−60mg/kgを投與する場合,關
節炎に對する優れた效果を表わされる.それの有效成分
を腦口投與するにあっては錠劑,藥劑,カプセル劑等の
投與製劑とすることができ,これらは通常用いられる方
法に從い製造することができる.これらの製劑を製造す
るために乳糖,とうもろこし澱粉,ステアリン酸マグネ
シウム等の賦形劑を添加することができる.
本發明者は實驗によってウリジンが軟骨形成を促進
し,骨吸收(BONE RESORPTION)を抑制させて關節で組
織の炎症を低下させ,再生を促進する作用が有ることを
確認した.
即ち,ウリジンの關節炎の治療效果を確認するために
リューマチ性關節炎の動物實驗のモデルであるコラーゲ
ン誘發−關節炎實驗(COLLAGEN−INDUCED ARTHRITIS)
を施行して對照群に比べて關節炎部位の浮腫が拔ける速
度が早い,犠牲される前までの最終浮腫の拔ける程度も
有意の差を表わされる效果が有るのでウリジンがコラー
ゲン關節炎が生ずる組織の炎症を低減させ,再生を促進
することを確認した.また,コラーゲン關節炎は自己免
疫疾患の範疇として,ウリジンがほかの自己免疫疾患の
治療にも效果が有ることと考える.ウリジンに對する毒
性實驗の結果,元氣なラット及びマウスにウリジン0.0
1,0.1,10,100mg/Kgずつ投與し,1週日以上觀察した所,
とんなの異状も發見かることができなが」ったことを確
認した.
實施例
以下,實施例により本發明をさらに具體的に説明する
が,本發明はこれらにより限定されるものではない.
實施例1.コラーゲン關節炎に對する藥效實驗
(1)コラーゲン關節炎の誘導と觀察
天然牛型IIコラーゲン(Native bovine type II coll
agen)を2mg/mlなるように溶解した後,未完成のプロイ
ント(Freund)坐藥とを1:1で混合してエマルジョンを
調製した.このエマルジョンをルイスラットの尾根で1m
lずつ皮下注射した.8日後,同一な方法だエマルジョン
を調製した後,1mlずつ腹腔内注射した.以後,關節炎が
發生したラット對照群と,ウリジンを投與した群(ウリ
ジン群1は10μgずつ一日あたり2回,ウリジン群2は
1mgずつ一日あたり2回)にてわけて觀察し,適當な間
隔で關節炎が發生した足の厚さと廣さを測定した.ま
た,コラーゲンタイプIIに對する抗體力價の腦時變化を
觀察するために一定間隔で尾の靜脈で血清を準備した.
(2)コラーゲンタイプIIに對する抗體力價の腦時變化
の觀察
タナテクイムロン4プレート(Danatech Immulon 4 p
late)に各ウェル(well)當50μlのコラーゲンタイプ
II溶液(10μg/ml)を添加し,一夜,コティングした
後,また一夜3%BSA−PBS(bovine serum albumin−ph
osphate buffered saline)溶液でブロキングした.こ
のプレートをまずPBSで4回洗滌し,上記のルイスラッ
トより得た血清を添加した後,一夜,反應させた.その
後PBSで4回洗滌し,過酸化酵素を標識したヤギのアン
ティ−ラットイムノグロブリンG(IgG)抗體を添加し
た.一夜後,PBSで4回洗滌しO−フェニレンジアミンを
基質として發色させた後,ETAプレート判讀器(ETA plat
e reader)にて405nmで吸光度を測定した.
(3)3H−チミジン吸收分析
2つの群のラットを犠牲させて得た脾臓でメッシュを
利用して脾臓細胞を得た.各各のウェルに0.5%の同一
群の血清を含むDulbecco修正イグルス培地に浮遊させた
2.5x106程度の脾臓細胞を入れて,コラーゲンタイプII
を0μg/ml,0.01μg/ml,0.1μg/ml,1μg/ml,10μg/mlな
るようにいれた.CO2インキュベータの中で56時間放置し
た後,0.5μCiの3H−チミジンを添加した.16時間後,自
動收穫器にて收穫し,シンチレーション計数管(scinti
llation counter)にて放射能を測定した.
(4)病理組織學的檢査
3H−チミジン吸收分析のためにルイスラットを犠牲す
る時,關節炎が發生した後足をホルマリンで固定し,無
機物を除去してスライドを製作して病理組織學的所見を
觀察した.
本實驗に對する結果は關節炎が發生した後,一日2回
ずつウリジンを投與したルイスラット群と蒸溜水たけを
投與した群とのあいたには圖1で表わされるように關節
炎が發生した足の浮腫(edema)が拔ける程度と速度で
有意の差が有することを認められる.しかし表1と表2
で示めしたように2つの群のあいたに抗體力價の變化や
脾臓細胞の3H−チミジン吸收の差はほどんとなかった.
病理組織學的の所見で,ウリジンを投與したルイスラッ
トは蒸溜水を投與したラットの場合とは違く硝子軟骨
(hyaline cartilage)がたくさん殘ていり,纎維軟骨
の形成ももっと活溌することとした示めた.また,炎症
の所見は2つの群で,すべての部位によって程度の差を
示めしたいるが,骨吸收の所見は蒸溜水を投與した群の
たけで示めることを確認される.
實施例2.藥劑學的錠劑の製造
(1)通常の方法に從ってウリジンの藥效にさしつかえ
ない賦形劑を下記の組成に依って添加し,混合して錠劑
を製造した.
(2)通常の方法に從って下記の組成に依って錠劑を製
造した.
Description: TECHNICAL FIELD The present invention relates to a therapeutic agent for the treatment of common sores that contains uridine as an active ingredient. More specifically, the use of uridine, which is a nucleoside, is a novel therapeutic effect for the treatment of common sores and its effects. It is the one that is contained in the garbage. Background Art Uridine is one of the four ribonucleosides necessary for constructing RNA and is distributed in nature in a wide range. Its molecular weight is 244.20 and its molecular formula is C 9
H 12 N 2 O 6 is 10, and its structural formula is as follows. The known pharmacological action of uridine is that when uridine is thrown, it is immediately converted into uridine 5'-phosphate by the catalytic action of uridine quinase enzyme in the body.
Useful for enzyme deficiency or pyrimidine nucleotidite deficiency and nucleic acid synthesis deficiency.
There is a report (MATINDALE, 1989,1627) that was used as a pottery to reduce OTIC ACIDURIA), and it was used as a component of a composite sardine even in the Republic of Korea. Uridine itself is not reported to have any effect on sores. While studying the components used as raw herbs, the present researcher screened various substances that were separated and purified as a single ingredient,
It was found that one of the components isolated from the plant had an excellent therapeutic effect on scabitis, the molecular structure of the substance was revealed, and as a result, it was confirmed that it was uridine and the present study was completed. . When uridine has been used in medical supplies, it is used as a compound iron with other drugs to treat vascular disease, hepatointestinal protection,
It is known to be used for peripheral dementia, brachyplasty hypoxia, etc., but its curative effect on arthritis is not known. Disclosure disclosure The purpose of this disclosure is to formula The present invention provides a swelling-improving syrup containing uridine as an effective ingredient. A simple explanation of the face. Rake 1 is a graph showing the time course of edema at the swelling site of the swelling of the swelling of the urateru group and the group receiving uridine. This is the best mode for the treatment of glaucoma. This glaucoma has an excellent effect of treating glaucoma when uridine of 0.6-60 mg / kg is provided by providing an improving ingredient of glaucoma containing uridine. . In the case of poaching the active ingredient thereof, it can be made into a pot-making product such as tablets, porridges, capsules, etc., which can be manufactured according to a commonly used method. In order to produce these shavings, lactose, corn starch, and shaping syrups such as magnesium stearate can be added. The present authors have confirmed that uridine promotes cartilage formation and suppresses bone resorption (BONE RESORPTION), and reduces inflammation of the tissues in the spinal joint, and promotes regeneration by the bone marrow. That is, in order to confirm the therapeutic effect of uridine on scabitis, COLLAGEN-INDUCED ARTHRITIS, which is a model of animal disease of rheumatoid arthritis.
The edema of the swelling part of the arthralitis is faster than that of the sera group, and the extent of the final edema before the sacrifice is significantly different. It was confirmed that the resulting tissue inflammation was reduced and regeneration was promoted. In addition, we believe that uridine is effective in the treatment of other autoimmune diseases, as collagen scabitis is a category of autoimmune diseases. As a result of the toxicity of uridine, uridine was 0.0% in the original rats and mice.
1,0.1,10,100mg / Kg each, and observed for more than 1 week,
I couldn't detect any abnormalities. " Examples Hereafter, the present invention will be explained more concretely by the following examples, but the present invention is not limited thereto. Example 1. Collagen scabitis and its effects (1) Induction and observation of collagen scabitis. Native bovine type II coll (Native bovine type II coll)
agen) was dissolved to 2 mg / ml and mixed with unfinished Proint (Freund) zabuta 1: 1 to prepare an emulsion. 1m of this emulsion on a Lewis rat ridge
8 days later, an emulsion was prepared by the same method, and then 1 ml was intraperitoneally injected. After that, a group of rats with scabitis and a group with uridine (Uridine group 1 10 μg twice a day, Uridine group 2
1 mg each twice a day), and the thickness and height of the foot on which the arthritis was caused were measured at appropriate intervals. Serum was prepared at regular intervals in the veins of the tail to observe the anti-hypertensive changes in collagen type II. (2) Observation of the anti-hypertensive effect of collagen type II on the swelling time Tanatech Immulon 4 p
late) 50μl of each well type collagen type
After adding II solution (10 μg / ml) and coating overnight, 3% BSA-PBS (bovine serum albumin-ph) was added overnight.
Blocking was performed with an osphate buffered saline) solution. The plate was first washed with PBS four times, and the serum obtained from the Lewis rat was added to the plate, which was then reacted overnight. Then, the cells were washed 4 times with PBS, and anti-rat immunoglobulin G (IgG) anti-rat of goat labeled with peroxidase was added. After overnight, washing with PBS four times, and using O-phenylenediamine as a substrate, and then bleaching, ETA plate reading device (ETA plat
The absorbance was measured at 405 nm with an e reader). (3) 3 H-thymidine absorption analysis Spleen cells were obtained by using a mesh with the spleen obtained by sacrificing two groups of rats. Suspended in Dulbecco's modified Igls medium containing 0.5% of the same serum in each well
Put about 2.5x10 6 spleen cells, collagen type II
Was added to 0 μg / ml, 0.01 μg / ml, 0.1 μg / ml, 1 μg / ml, 10 μg / ml. After standing in a CO 2 incubator for 56 hours, 0.5 μCi of 3 H-thymidine was added. .16 hours later, harvested with an automatic harvester, scintillation counter (scinti
Radioactivity was measured using an llation counter). (4) Histopathological Examination When Lewis rats were sacrificed for 3 H-thymidine uptake analysis, the hindpaw, which suffered from osteoarthritis, were fixed with formalin, and inorganic substances were removed to prepare slides for histopathology. I observed the findings. The result of this study was that after the necrotizing outbreak, Lewis rats fed twice daily with uridine and the group fed with distilled water were treated with glaucoma as indicated by 圖 1. It is recognized that there is a significant difference in the degree and speed at which the edema of the foot in which the swelling occurs occurs. But Tables 1 and 2
As shown in Fig. 4, there was little difference between the two groups in the change in anti-tumor activity and in the 3 H-thymidine absorption of spleen cells.
From histopathological findings, Lewis rats fed with uridine had more hyaline cartilage than the rats fed with distilled water, and the formation of fibrous cartilage was more active. I showed you that. In addition, the findings of inflammation were shown to be different to all extent in the two groups, but the findings of bone resorption were confirmed to be shown only in the group to which distilled water was poured. Example 2 Production of Chinese medicine tablets (1) According to the usual method, a tablet which could not be effective against the effect of uridine was added according to the following composition and mixed to produce tablets. (2) Tablets were produced according to the following composition according to a conventional method.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平4−243830(JP,A) 特開 平2−25425(JP,A) 特開 昭60−136515(JP,A) 特開 昭62−145019(JP,A) FOX, R. I., et a l., TREATMENT OF R HEUMATOID ARTHRITI S(RA) WITH THE PYR IMIDINE SYNTHESIS INHIBITOR TRIACETY L−6−AZAURIDINE, Ar thritis Rheum., 1992, 35(Suppl. 9), p. S203 (58)調査した分野(Int.Cl.7,DB名) A61K 31/70 - 31/713 A61P 1/00 - 43/00 C07H 19/00 - 19/067 CA(STN) REGISTRY(STN) WPI(DIALOG)─────────────────────────────────────────────────── --- Continuation of the front page (56) References JP-A-4-243830 (JP, A) JP-A-2-25425 (JP, A) JP-A 60-136515 (JP, A) JP-A 62- 145019 (JP, A) FOX, R.A. I. , Et al. , TREATMENT OF R HEUMATOID ARTHRITIS (RA) WITH THE PYR IMIDINE SYNTHESIS INHIBITOR TRIACETY L-6-AZAURIDINE, Ar thresholds Rheum. , 1992, 35 (Suppl. 9), p. S203 (58) Fields investigated (Int.Cl. 7 , DB name) A61K 31/70-31/713 A61P 1/00-43/00 C07H 19/00-19/067 CA (STN) REGISTRY (STN) WPI (DIALOG)
Claims (2)
請求項1記載の關節炎治療劑.2. The treatment powder for scabitis according to claim 1, wherein the said syrup is a tablet.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR1993/000043 WO1994026280A1 (en) | 1993-05-19 | 1993-05-19 | Remedy for arthritis containing uridine as active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO1994026280A1 JPWO1994026280A1 (en) | 1995-08-03 |
| JP3459013B2 true JP3459013B2 (en) | 2003-10-20 |
Family
ID=19349351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52525594A Expired - Fee Related JP3459013B2 (en) | 1993-05-19 | 1993-05-19 | An agent for treating arthritis containing uridine as an active ingredient |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP3459013B2 (en) |
| WO (1) | WO1994026280A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE521031C2 (en) | 1999-05-05 | 2003-09-23 | Srinivas Uppugunduri | New specific inhibitors of acute and chronic inflammation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60136515A (en) * | 1983-12-23 | 1985-07-20 | Yasuo Komoda | Hypnotic agent |
| JPS62145019A (en) * | 1985-12-19 | 1987-06-29 | Senjiyu Seiyaku Kk | Anti-inflammatory agent |
| IT1219667B (en) * | 1988-06-21 | 1990-05-24 | Polifarma Spa | USE OF URIDINE IN THE PHARMACOLOGICAL TREATMENT OF DISORDERS DUE TO ALTERATED DOPAMINERGIC BALANCE |
| IT1241984B (en) * | 1990-06-13 | 1994-02-02 | Polifarma Spa | USE OF URIDINE IN THE PHARMACOLOGICAL TREATMENT OF PERIPHERAL COMPLICATIONS OF DIABETES |
-
1993
- 1993-05-19 JP JP52525594A patent/JP3459013B2/en not_active Expired - Fee Related
- 1993-05-19 WO PCT/KR1993/000043 patent/WO1994026280A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| FOX, R. I., et al., TREATMENT OF RHEUMATOID ARTHRITIS(RA) WITH THE PYRIMIDINE SYNTHESIS INHIBITOR TRIACETYL−6−AZAURIDINE, Arthritis Rheum., 1992, 35(Suppl. 9), p. S203 |
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| Publication number | Publication date |
|---|---|
| WO1994026280A1 (en) | 1994-11-24 |
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