JP2003081843A - Agent for critical prevention and treatment of type ii diabetic nephropathy containing organogermanium compound as active ingredient - Google Patents
Agent for critical prevention and treatment of type ii diabetic nephropathy containing organogermanium compound as active ingredientInfo
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- JP2003081843A JP2003081843A JP2001273043A JP2001273043A JP2003081843A JP 2003081843 A JP2003081843 A JP 2003081843A JP 2001273043 A JP2001273043 A JP 2001273043A JP 2001273043 A JP2001273043 A JP 2001273043A JP 2003081843 A JP2003081843 A JP 2003081843A
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、有機ゲルマニウム
化合物、好ましくは3ーオキシゲルミルプロピオン酸を
有効成分とするII型糖尿病性腎症の発症予防又は治療剤
に係る。TECHNICAL FIELD The present invention relates to an agent for preventing or treating the onset of type II diabetic nephropathy, which comprises an organic germanium compound, preferably 3-oxygermylpropionic acid, as an active ingredient.
【０００２】[0002]
【従来技術】有機ゲルマニウム化合物、殊に3−オキシ
ゲルミルプロピオン酸は、複雑な重合性を有する化合物
として知られており、特公昭５７−５３８００号には、
各種構造体の存在の可能性が記載されている。本発明者
等は、さらに複数の構造体の存在を発見し、高活性構造
体を特定するに至った（特開平７−２３８０２２号）。
また、この化合物は、抗ウイルス作用（特公昭５７−５
３８００号）を初めとして、多様な薬理活性を有するこ
とから、多くの用途に関する研究がなされている。本発
明者等は、本化合物について、インターフェロン産生増
強作用（特開平２−１３４８１８号）、インターフェロ
ン効果増強作用（特開平７−２３８０２２号）、MCP-1
拮抗作用（特開２０００−１３６１３９号）等を発見
し、本化合物がウイルス性肝炎、慢性関節リウマチ、膵
炎、疼痛肺肉芽腫症、肺線維症、腎炎、Ｉ型糖尿病性組
織炎症、アトピー性皮膚炎及び喘息の予防又は治療剤と
して有用であることを開示してきた。しかし、II型糖尿
病性腎症に対する作用については明らかにされていなか
った。2. Description of the Related Art Organic germanium compounds, especially 3-oxygermylpropionic acid, are known as compounds having complicated polymerizability, and Japanese Patent Publication No. 57-53800 discloses that:
The possible presence of various structures is described. The present inventors have further discovered the existence of a plurality of structures and have identified a highly active structure (JP-A-7-238022).
In addition, this compound has an antiviral effect (Japanese Patent Publication No. 57-5).
3800) and various pharmacological activities, and therefore, many studies have been conducted on its use. The inventors of the present invention have found that the compound enhances interferon production (JP-A-2-134818), enhances interferon effect (JP-A-7-238022), and MCP-1.
An antagonistic action (Japanese Patent Laid-Open No. 2000-136139) was discovered, and the compound was viral hepatitis, rheumatoid arthritis, pancreatitis, pulmonary granulomatosis pain, pulmonary fibrosis, nephritis, type I diabetic tissue inflammation, atopic skin. It has been disclosed that it is useful as a prophylactic or therapeutic agent for inflammation and asthma. However, its effect on type II diabetic nephropathy has not been clarified.
【０００３】II型糖尿病は、食事療法、運動療法等と共
に、血糖降下剤、糖吸収阻害剤等の薬物治療により血糖
をコントロールして、その進展を遅延させることを目的
とする対症療法が主な治療法となっているが、現在、糖
尿病を完全に治癒させることは不可能である。そのた
め、II型糖尿病患者の一部は、やがて、糖尿病性腎症、
糖尿病性神経症、糖尿病性網膜症などの合併症を併発す
る。II型糖尿病性腎症の発症機序については、高血糖自
身や血糖由来の後期糖化反応産物（AGE）による直接的
な腎細胞障害、腎糸球体のメサンギウム細胞増殖等によ
る機能異常等が報告されているが、その遺伝学的背景と
ともに、現在でも完全には解明されてはいない。[0003] Type II diabetes is mainly symptomatic therapy aimed at controlling and delaying the progress of blood glucose by drug treatment such as hypoglycemic agents and glucose absorption inhibitors as well as diet therapy and exercise therapy. Although a cure, it is currently not possible to completely cure diabetes. Therefore, some type II diabetic patients eventually diabetic nephropathy,
Complications such as diabetic neuropathy and diabetic retinopathy occur together. Regarding the pathogenic mechanism of type II diabetic nephropathy, direct renal cell damage due to hyperglycemia itself or the late glycation reaction product (AGE) derived from blood glucose, functional abnormality due to proliferation of mesangial cells in renal glomeruli, etc. have been reported. However, its genetic background and its background have not yet been fully elucidated.
【０００４】現在、II型糖尿病性腎症の治療に使用され
ている、又は開発中の薬物としては、糖尿病治療剤とし
て(i)血糖低下を目的とする血糖降下剤及び糖吸収阻害
剤、(ii)インシュリン抵抗性改善剤、また、腎症の進展
抑制剤として(iii)AGE産生阻害剤、(iv)ACE(angiotensi
n converting enzyme)阻害剤等が挙げられる。しかし、
血糖降下剤、糖吸収阻害剤等の血糖コントロールによ
り、腎症発症のリスクを軽減できるが腎症の進展は防止
できず、インシュリン抵抗性改善剤の使用については、
治療効果とともに死亡例を含む無視できない重篤な副作
用が報告されている（Ann.Int.Med. 129:1080, 199
8）。また、AGE産生阻害剤及びACE阻害剤は、基礎研究
は進められているが、実用化までにはさらに時間が必要
である。そのため、腎症の進展阻止効果を有する新たな
薬剤の開発が切に望まれている。Drugs currently used or under development for the treatment of type II diabetic nephropathy include as therapeutic agents for diabetes (i) hypoglycemic agents and glucose absorption inhibitors for the purpose of lowering blood glucose, ( ii) Insulin sensitizer, and (iii) AGE production inhibitor, (iv) ACE (angiotensi)
n converting enzyme) inhibitors and the like. But,
By controlling blood glucose with hypoglycemic agents, glucose absorption inhibitors, etc., the risk of developing nephropathy can be reduced, but the progression of nephropathy cannot be prevented.
Serious side effects including deaths have been reported along with therapeutic effects (Ann.Int.Med. 129: 1080, 199).
8). Further, although basic research is underway for AGE production inhibitors and ACE inhibitors, it will take more time before they are put into practical use. Therefore, the development of a new drug having an effect of inhibiting the progression of nephropathy is eagerly desired.
【０００５】[0005]
【発明が解決しようとする課題】本発明は、II型糖尿病
性腎症の発症予防または治療剤を提供することを課題と
する。The object of the present invention is to provide a preventive or therapeutic agent for the onset of type II diabetic nephropathy.
【０００６】[0006]
【課題を解決するための手段】本発明者等は、有機ゲル
マニウム化合物、中でも、3−オキシゲルミルプロピオ
ン酸について、II型糖尿病性腎症の実験動物モデルであ
るC57BL/KSJ-db/dbマウスの自然発症糖尿病性腎症に対
する薬効薬理試験を行い、II型糖尿病性腎症の発症に対
する予防又は治療剤としての可能性について検討した。
その結果、当該化合物が、II型糖尿病性腎症の発症及び
進展を顕著に抑制することを見出し、本発明を完成する
に至った。[Means for Solving the Problems] The present inventors have found that organogermanium compounds, especially 3-oxygermylpropionic acid, are C57BL / KSJ-db / db mice, which are experimental animal models of type II diabetic nephropathy. A pharmacological and pharmacological study was conducted on spontaneous diabetic nephropathy to examine its potential as a preventive or therapeutic agent for the onset of type II diabetic nephropathy.
As a result, they have found that the compound markedly suppresses the onset and progress of type II diabetic nephropathy, and completed the present invention.
【０００７】[0007]
【発明の実施の形態】本発明に使用される有機ゲルマニ
ウム化合物は、以下式BEST MODE FOR CARRYING OUT THE INVENTION The organic germanium compound used in the present invention has the following formula:
【化３】
（式中、ｎは２以上の数、Aは低級アルキル基）で表さ
れる化合物で、好ましくは、Aは炭素数１から３の低級
アルキル基である。また、更に好ましくは、AがCH２CH
２である3−オキシゲルミルプロピオン酸である。[Chemical 3] (In the formula, n is a number of 2 or more and A is a lower alkyl group), and preferably A is a lower alkyl group having 1 to 3 carbon atoms. Further, more preferably, A is CH 2 CH
2- oxygermylpropionic acid which is 2.
【０００８】3−オキシゲルミルプロピオン酸は、以下
式3-Oxygermylpropionic acid has the formula:
【化４】
［式中、Rは−CH２CH２COOH、mはプロパゲルマニウムプ
ロピルエステルの重量平均分子量から換算した重量平均
重合度で、１３７±８４（平均値±標準誤差3σ）を示
す。最小構成単位：(O１／２)３GeCH２CH２COOH 実験
式：C６H１０Ge２O ７］にて示される８員性構造体であ
ると考えられ、表１及び表２に記載の物理化学的性質を
有する。尚、表中本化合物を「ＳＫー８１８」として記
載する。表１は光散乱法による分子量測定結果を、表２
は粉末X線解析により求めた格子定数を示す。[Chemical 4]
[Wherein R is -CHTwoCHTwoCOOH, m is a propa germanium pump
Weight average calculated from the weight average molecular weight of ropyl ester
Degree of polymerization shows 137 ± 84 (average value ± standard error 3σ)
You Minimum unit: (O1/2)ThreeGeCHTwoCHTwoCOOH experiment
Formula: C6H10GeTwoO 7] The 8-membered structure shown by
And the physicochemical properties listed in Table 1 and Table 2
Have. In the table, this compound is referred to as "SK-818".
List. Table 1 shows the results of molecular weight measurement by the light scattering method.
Indicates the lattice constant obtained by powder X-ray analysis.
【０００９】[0009]
【表１】 [Table 1]
【００１０】[0010]
【表２】 [Table 2]
【００１１】本発明に係る3-オキシゲルミルプロピオン
酸は、II型糖尿病性腎症の発症予防または治療剤として
提供されるものである。本化合物を実際にヒトに投与す
る場合は、本化合物を0.005重量%〜5重量%に対して作用
活性化安定化担体を0.005重量%〜50重量%を含有するよ
うに調製された組成物として使用されることが好まし
い。作用活性化安定化担体としては、乳糖、ショ糖、デ
キストラン類等の糖類、ヒドロキシプロピルセルロース
等のセルロース系高分子性物質、アルブミン等の天然性
高分子物質が使用される。本発明に係る3-オキシゲルミ
ルプロピオン酸は、通常は経口製剤として用いられる
が、座剤、鼻腔製剤、注射製剤等としても利用すること
ができる。本発明薬剤をヒトに投与する場合の投与量
は、剤型・患者の年齢等に依存するが、一日あたり1mg
〜1500mgの範囲内であり、体重50ｋgの成人に対する経
口投与では、一日あたり60mg〜120mgが好ましい。The 3-oxygermylpropionic acid according to the present invention is provided as a preventive or therapeutic agent for the onset of type II diabetic nephropathy. When the present compound is actually administered to humans, the compound is prepared as a composition prepared so as to contain 0.005% to 50% by weight of the action activation stabilizing carrier with respect to 0.005% to 5% by weight of the present compound. It is preferably used. As the action activation stabilizing carrier, saccharides such as lactose, sucrose and dextran, cellulosic polymeric substances such as hydroxypropylcellulose, and natural polymeric substances such as albumin are used. The 3-oxygermylpropionic acid according to the present invention is usually used as an oral preparation, but can also be used as a suppository, a nasal preparation, an injection preparation and the like. The dose of the drug of the present invention when administered to humans depends on the dosage form, patient age, etc., but is 1 mg per day.
It is within the range of ˜1500 mg, and is preferably 60 mg to 120 mg per day for oral administration to an adult weighing 50 kg.
【００１２】[0012]
【実施例】以下には本発明化合物の製造例、薬効薬理試
験例、製剤例を挙げ、本発明を更に詳細に説明する。EXAMPLES The present invention will be described in more detail below with reference to production examples of the compounds of the present invention, pharmacological test examples, and formulation examples.
【００１３】製造例
２５２ｇ(1モル）の３−トリクロロゲルミルプロピオン
酸をエチルアルコール２リットル中に溶解させ、この溶
液温度を20℃に保ちつつ、水1．5リットルを数時間をか
けて添加する。一昼夜放置した後、吸引ろ過により結晶
を濾取し、アセトンにて洗浄し減圧乾燥する事により、
収率90%で3-オキシゲルミルプロピオン酸重合体を得
た。得られた本発明化合物は、光散乱法により分子量を
測定し、粉末Ｘ線解析法により格子定数を測定した。結
果は前記表１及び表２に示す通りであった。[0013]Production example
252 g (1 mol) of 3-trichlorogermylpropion
Dissolve the acid in 2 liters of ethyl alcohol,
Keep the liquid temperature at 20 ° C and add 1.5 liters of water for several hours.
Add. After leaving it overnight, crystallize by suction filtration
Was collected by filtration, washed with acetone and dried under reduced pressure,
3-Oxygermylpropionic acid polymer was obtained with a yield of 90%.
It was The molecular weight of the obtained compound of the present invention was determined by a light scattering method.
The measurement was performed and the lattice constant was measured by the powder X-ray analysis method. Conclusion
The fruits were as shown in Tables 1 and 2 above.
【００１４】組成物製造例
ヒドロキシプロピルセルロース１重量に対して、本発明
化合物２重量をエタノールを浸潤剤として練合し、50℃
以下の温度で乾燥後、粉末または粒状の組成物を得た。[0014]Composition production example
The present invention is based on 1 weight of hydroxypropyl cellulose.
Knead 2 parts of compound with ethanol as a wetting agent,
A powdery or granular composition was obtained after drying at the following temperatures.
【００１５】カプセル剤製造例 以下の処方で常法によりカプセル剤を調製した。 ３−オキシゲルミルプロピオン酸重合体 １０．０ 乳糖 １６５．５ ヒドロキシプロピルセルロース ２．７ ステアリン酸マグネシウム １．８ 合計重量 １８０．０ｍｇ[0015]Capsule manufacturing example Capsules were prepared by the usual method with the following formulation. 3-Oxygermylpropionic acid polymer 10.0 Lactose 165.5 Hydroxypropyl cellulose 2.7 Magnesium stearate 1.8 Total weight 180.0mg
【００１６】錠剤製造例 以下の処方により圧縮錠剤を調製した。 ３−オキシゲルミルプロピオン酸重合体 １０．０ 乳糖 １５９．２ CMC-Na ８．０ 軽質無水ケイ酸 ２．０ ステアリン酸マグネシウム １．８ 合計重量 １８０．０ｍｇ[0016]Tablet production example A compressed tablet was prepared according to the following formulation. 3-Oxygermylpropionic acid polymer 10.0 Lactose 159.2 CMC-Na 8.0 Light anhydrous silicic acid 2.0 Magnesium stearate 1.8 Total weight 180.0mg
【００１７】以下に本発明化合物である3-オキシゲルミ
ルプロピオン酸の薬理試験例を示す。尚、本発明化合物
の3-オキシゲルミルプロピオン酸は「SK-818」と示す。薬理試験例
C57BL/KSJ-db/dbマウスの糖尿病性腎症に対するSK-818
の効果
（１）実験方法
C57BL/KSJ-db/db雄性マウスを8週齢で購入し、約1週間
の馴化飼育の後に採尿して、血糖値、尿中糖濃度、尿中
アルブミン濃度により群間に差がないように群分けし
た。SK-818は、粉末マウス飼料CRF-1に混合して投与し
た。投与量は、あらかじめ測定しておいた摂餌量から１
日あたり1mg/kg及び5mg/kgと換算された。投与開始後16
週目に採尿、解剖し、採血及び腎摘出を行った。尿中ア
ルブミン値をELISA法（Bethyl Laboratories Inc）で、
血糖値、血中遊離脂肪酸濃度を市販の測定試薬(和光純
薬、協和メディックス)を用いてオートアナライザー
（日立）で測定した。腎臓の組織学的検査は、画像解析
ソフトIPAP-WIN（住化テクノサービス）でPAS染色陽性
領域面積を測定することにより、実施した。The 3-oxygermi which is the compound of the present invention is as follows.
An example of a pharmacological test of lupropionic acid is shown. The compound of the present invention
3-oxygermylpropionic acid of is shown as "SK-818".Pharmacological test example
SK-818 for diabetic nephropathy in C57BL / KSJ-db / db mice
Effect of
(1) Experimental method
Purchase C57BL / KSJ-db / db male mice at 8 weeks of age, and
Blood samples, urine sugar levels,
Group into groups so that there is no difference between albumin concentrations.
It was SK-818 was administered by mixing with powdered mouse feed CRF-1.
It was The dose is 1 based on the food intake measured in advance.
Converted to 1 mg / kg and 5 mg / kg per day. 16 after the start of administration
At the week, urine was collected, dissected, and blood was collected and nephrectomy was performed. In urine
Lubumin value is measured by ELISA method (Bethyl Laboratories Inc)
Commercially available reagents for measuring blood sugar level and free fatty acid concentration in blood (Wako Pure
Drug, Kyowa Medix)
(Hitachi). Histological examination of the kidney, image analysis
PAS staining positive with soft IPAP-WIN (Sumika Techno Service)
It was carried out by measuring the area of the area.
【００１８】（２）結果及び考察
下記の表３〜６に結果を示した。SK-818投与開始後16週
目における薬物無処置コントロール群の尿中アルブミン
値は、正常対照のC57BL/KSJ-db/+mマウスやC57BL/6マウ
スに比較して60倍以上になった。SK-818は5mg/kgで尿中
アルブミン濃度を有意に低下させ、腎症の発症及び進展
を顕著に抑制した。また、薬物無処置コントロール群の
血中遊離脂肪酸濃度は、正常対照のC57BL/KSJ-db/+mマ
ウスやC57BL/6マウスに比較して40％増加した。SK-818
は1mg/kg及び5mg/kgで血中遊離脂肪酸濃度を有意に低下
させ、5mg/kgでは86％抑制した。更に、腎臓の組織学的
検査では、薬物無処置コントロール群の periodic acid
Schiff （PAS）染色陽性領域面積は、正常対照のC57BL/
KSJ-db/+mマウスやC57BL/6マウスに比較して2.8倍に増
加した。SK-818は1mg/kg及び5mg/kgでPAS染色陽性領域
面積を有意に低下させ、腎糸球体の機能異常を著明に防
止した。一方、薬物無処置コントロール群の血糖値は、
正常マウスに比較して4倍以上になったが、SK-818は1mg
/kg及び5mg/kgで血糖値には全く作用せず、血糖降下剤
のような糖尿病に対する直接作用はなかった。(2) Results and Discussion The results are shown in Tables 3 to 6 below. At 16 weeks after the start of SK-818 administration, the urinary albumin level in the drug-free control group was 60 times or more that of the normal control C57BL / KSJ-db / + m mouse and C57BL / 6 mouse. SK-818 significantly reduced urinary albumin concentration at 5 mg / kg and significantly suppressed the onset and progression of nephropathy. The blood free fatty acid concentration in the drug-free control group was increased by 40% as compared with the normal control C57BL / KSJ-db / + m mouse and C57BL / 6 mouse. SK-818
Significantly reduced blood free fatty acid concentration at 1 mg / kg and 5 mg / kg, and suppressed 86% at 5 mg / kg. Furthermore, a histological examination of the kidney revealed that periodic acid in the drug-free control group was
Schiff (PAS) staining positive area is C57BL /
It increased 2.8 times compared to KSJ-db / + m and C57BL / 6 mice. SK-818 significantly reduced the area of PAS-staining positive region at 1 mg / kg and 5 mg / kg, and significantly prevented renal glomerular dysfunction. On the other hand, the blood glucose level of the drug-free control group is
4 times more than normal mice, but SK-818 is 1 mg
/ kg and 5 mg / kg had no effect on blood glucose level, and had no direct effect on diabetes like hypoglycemic agents.
【００１９】[0019]
【表３】 [Table 3]
【００２０】[0020]
【表４】 [Table 4]
【００２１】[0021]
【表５】 [Table 5]
【００２２】[0022]
【表６】 [Table 6]
【００２３】[0023]
【発明の効果】上記の薬理試験例に示された結果は、II
型糖尿病性腎症の動物モデルであるC57BL/KSJ-db/dbマ
ウスの糖尿病性腎症において、3-オキシゲルミルプロピ
オン酸が有意な予防又は治療効果を有することを示して
いる。これは、本化合物がII型糖尿病性腎症の発症・進
展に効果を発現することを示している。すなわち、本発
明は、有機ゲルマニウム化合物好ましくは3ーオキシゲ
ルミルプロピオン酸が、II型糖尿病性腎症の予防又は治
療剤となることを示している。The results shown in the above pharmacological test examples are II
It is shown that 3-oxygermylpropionic acid has a significant preventive or therapeutic effect in diabetic nephropathy of C57BL / KSJ-db / db mice, which is an animal model of type 2 diabetic nephropathy. This indicates that this compound exerts an effect on the onset / progress of type II diabetic nephropathy. That is, the present invention shows that an organogermanium compound, preferably 3-oxygermylpropionic acid, serves as a preventive or therapeutic agent for type II diabetic nephropathy.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 粟谷 寿一 名古屋市東区東外堀町35番地 株式会社三 和化学研究所内 Ｆターム(参考） 4C086 AA01 AA02 DA33 MA01 NA14 ZA81 ZC35 ─────────────────────────────────────────────────── ─── Continued front page (72) Inventor Juichi Awaya 35 Higashi-gaboricho, Higashi-ku, Nagoya-shi San Co., Ltd. Inside the Waseda Institute F-term (reference) 4C086 AA01 AA02 DA33 MA01 NA14 ZA81 ZC35
Claims (4)
れる有機ゲルマニウム化合物を有効成分とするII型糖尿
病性腎症の発症予防又は治療剤。1. The following formula: (In the formula, n is a number of 2 or more and A is a lower alkyl group) An agent for preventing or treating the onset of type II diabetic nephropathy, which comprises an organic germanium compound represented by the following formula.
ある、請求項１に記載のII型糖尿病性腎症の発症予防又
は治療剤。2. The preventive or therapeutic agent for the onset of type II diabetic nephropathy according to claim 1, wherein A is a lower alkyl group having 1 to 3 carbon atoms.
ルミルプロピオン酸である、請求項１に記載のII型糖尿
病性腎症の発症予防又は治療剤。3. The agent for preventing or treating the onset of type II diabetic nephropathy according to claim 1, wherein the organogermanium compound is 3-oxygermylpropionic acid.
下式 【化２】 ［式中、Rは−CH２CH２COOH、mはプロパゲルマニウムプ
ロピルエステルの重量平均分子量から換算した重量平均
重合度で、１３７±８４（平均値±標準誤差3σ）を示
す。最小構成単位：(O１／２)３GeCH２CH２COOH 実験
式：C６H１０Ge２O ７］にて示される８員性構造体であ
ることを特徴とする、請求項３に記載のII型糖尿病性腎
症の発症予防又は治療剤。4. 3-Oxygermylpropionic acid is
The following formula [Chemical 2] [Wherein R is -CHTwoCHTwoCOOH, m is a propa germanium pump
Weight average calculated from the weight average molecular weight of ropyl ester
Degree of polymerization shows 137 ± 84 (average value ± standard error 3σ)
You Minimum unit: (O1/2)ThreeGeCHTwoCHTwoCOOH experiment
Formula: C6H10GeTwoO 7] The 8-membered structure shown by
Type II diabetic kidney according to claim 3, characterized in that
A preventive or therapeutic agent for the onset of illness.
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| JP2001273043A JP2003081843A (en) | 2001-09-10 | 2001-09-10 | Agent for critical prevention and treatment of type ii diabetic nephropathy containing organogermanium compound as active ingredient |
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|---|---|---|---|
| JP2001273043A JP2003081843A (en) | 2001-09-10 | 2001-09-10 | Agent for critical prevention and treatment of type ii diabetic nephropathy containing organogermanium compound as active ingredient |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011093308A1 (en) | 2010-01-28 | 2011-08-04 | 株式会社 三和化学研究所 | Prophylactic or therapeutic agent for crohn's disease comprising organic acid polymer as active ingredient |
| JP2012127879A (en) * | 2010-12-16 | 2012-07-05 | Kanazawa Univ | Method for determining progress of nephropathy, and fibrillation inhibitor |
| WO2015020040A1 (en) | 2013-08-06 | 2015-02-12 | 国立大学法人九州大学 | Medicine for preventing or suppressing survival of cancer cells and having organic acid polymer as active ingredient |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0466529A (en) * | 1990-07-02 | 1992-03-02 | Sanwa Kagaku Kenkyusho Co Ltd | Cytopathogenic inhibitor and organotoxic reliever |
| JPH0859485A (en) * | 1994-08-26 | 1996-03-05 | Sanwa Kagaku Kenkyusho Co Ltd | Maillard reaction inhibitor consisting mainly of 3-oxygermylpropionic acid compound |
| JPH09238688A (en) * | 1996-03-11 | 1997-09-16 | Takeda Chem Ind Ltd | Production of human mcp-1 receptor protein and its use |
| JPH11263764A (en) * | 1997-12-19 | 1999-09-28 | Takeda Chem Ind Ltd | Anilide derivative and its production and use |
| JP2000136139A (en) * | 1998-10-30 | 2000-05-16 | Sanwa Kagaku Kenkyusho Co Ltd | Mcp-1 receptor antagonist containing organic germanium compound and preventive or treating agent for onset of inflammatory disease or organopathy relating to mcp-1 |
| JP2000229856A (en) * | 1999-02-08 | 2000-08-22 | Sanwa Kagaku Kenkyusho Co Ltd | Prophylactic or therapeutic agent for onset of arteriosclerotic disease containing organogermanium compound as active ingredient |
-
2001
- 2001-09-10 JP JP2001273043A patent/JP2003081843A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0466529A (en) * | 1990-07-02 | 1992-03-02 | Sanwa Kagaku Kenkyusho Co Ltd | Cytopathogenic inhibitor and organotoxic reliever |
| JPH0859485A (en) * | 1994-08-26 | 1996-03-05 | Sanwa Kagaku Kenkyusho Co Ltd | Maillard reaction inhibitor consisting mainly of 3-oxygermylpropionic acid compound |
| JPH09238688A (en) * | 1996-03-11 | 1997-09-16 | Takeda Chem Ind Ltd | Production of human mcp-1 receptor protein and its use |
| JPH11263764A (en) * | 1997-12-19 | 1999-09-28 | Takeda Chem Ind Ltd | Anilide derivative and its production and use |
| JP2000136139A (en) * | 1998-10-30 | 2000-05-16 | Sanwa Kagaku Kenkyusho Co Ltd | Mcp-1 receptor antagonist containing organic germanium compound and preventive or treating agent for onset of inflammatory disease or organopathy relating to mcp-1 |
| JP2000229856A (en) * | 1999-02-08 | 2000-08-22 | Sanwa Kagaku Kenkyusho Co Ltd | Prophylactic or therapeutic agent for onset of arteriosclerotic disease containing organogermanium compound as active ingredient |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011093308A1 (en) | 2010-01-28 | 2011-08-04 | 株式会社 三和化学研究所 | Prophylactic or therapeutic agent for crohn's disease comprising organic acid polymer as active ingredient |
| JP2012127879A (en) * | 2010-12-16 | 2012-07-05 | Kanazawa Univ | Method for determining progress of nephropathy, and fibrillation inhibitor |
| WO2015020040A1 (en) | 2013-08-06 | 2015-02-12 | 国立大学法人九州大学 | Medicine for preventing or suppressing survival of cancer cells and having organic acid polymer as active ingredient |
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