JPS6251951B2 - - Google Patents
Info
- Publication number
- JPS6251951B2 JPS6251951B2 JP55136784A JP13678480A JPS6251951B2 JP S6251951 B2 JPS6251951 B2 JP S6251951B2 JP 55136784 A JP55136784 A JP 55136784A JP 13678480 A JP13678480 A JP 13678480A JP S6251951 B2 JPS6251951 B2 JP S6251951B2
- Authority
- JP
- Japan
- Prior art keywords
- propionylcarnosine
- aluminum
- aluminum salt
- ulcer
- present
- 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
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 10
- -1 aluminum alkoxide Chemical class 0.000 claims description 6
- 229910052782 aluminium Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 208000025865 Ulcer Diseases 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000008469 Peptic Ulcer Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 208000011906 peptic ulcer disease Diseases 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000001187 pylorus Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 1
- 108010087806 Carnosine Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- JPUHCPXFQIXLMW-UHFFFAOYSA-N aluminium triethoxide Chemical compound CCO[Al](OCC)OCC JPUHCPXFQIXLMW-UHFFFAOYSA-N 0.000 description 1
- VAYMRGDBPHCZCI-NUBCRITNSA-N aluminum;(2r)-2-acetamido-5-amino-5-oxopentanoic acid Chemical compound [Al+3].CC(=O)N[C@@H](C(O)=O)CCC(N)=O VAYMRGDBPHCZCI-NUBCRITNSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 1
- 229940044199 carnosine Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000002656 inhibitory effect on ulcer Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は次式（）
で表わされる新規なＮ―プロピオニルカルノシン
アルミニウム塩及びその製造法に関する。
近年、消化性潰瘍患者は増加する傾向にあり、
その治療剤の開発のために種々の研究が行なわれ
ている。
そこで本発明者らは多くの化合物を合成し、そ
の薬理効果を検計したところ、上記式（）で表
わされるＮ―プロピオニルカルノシンアルミニウ
ム塩が極めて優れた消化性潰瘍治療効果を有する
ことを見出し、本発明を完成した。
従つて、本発明の目的は新規なＮ―プロピオニ
ルカルノシンアルミニウム塩を提供せんとするに
ある。
本発明の他の目的は、Ｎ―プロピオニルカルノ
シンアルミニウム塩を製造するための新規な方法
を提供せんとするにある。
本発明のＮ―プロピオニルカルノシンアルミニ
ウム塩は例えばＮ―プロピオニルカルノシンにア
ルミニウムアルコキシドを反応せしめることによ
り製造される。
Ｎ―プロピオニルカルノシンとしてはＤ―体、
Ｌ―体、DL―体が使用される。
また、アルミニウムアルコキシドとしては、ア
ルミニウムメトキシド、アルミニウムエトキシ
ド、アルミニウムイソプロポキシド、アルミニウ
ムｔ―プトキシド、アルミニウムシクロヘキシル
オキシド等が使用される。このアルミニウムアル
コキシドが水酸化アルミニウム又はその重合体等
の不純物含んでいる場合には蒸留、溶媒抽出等に
よつて不純物を除去したものを使用するのが好ま
しい。
反応は適当な溶媒中、室温ないし80℃の温度で
行うのが好ましい。
溶媒としては、水又はメタノール、エタノー
ル、イソプロパノール、プタノール等の有機溶媒
あるいはこれらの混和物が使用される。反応後、
反応液から溶媒及び副生するアルコール類を除去
すれば、目的（）が単離される。
次に、本発明のＮ―プロピオニルカルノシンア
ルミニウム塩について、その消化性潰瘍治療効果
を試験した結果を示す。尚、比較対照化合物とし
て従来抗潰瘍作用を有することが知られているＮ
―アセチル―Ｌ―グルタミンアルミニウム塩、蔗
糖硫酸エステルアルミニウム塩を用いた。
実験 １
幽門結紮潰瘍に対する作用：
体重210〜230ｇのドンリユウ系雄ラツトを１群
10匹とした。Shayら（Gastroenterology，５，
43〜61，1945）の方法に従い48時間絶食し、エー
テル麻酔下に幽門部を結紮する。14時間絶食、絶
水下に放置し、胃をとり出し、胃液を採取後、前
胃部に発生する潰瘍の面積（mm2）を解剖顕微鏡下
（10倍）にて計測し潰瘍指数として表わした。薬
物は幽門結紮直後に経口的に投与した。
結果を表１に示す。
The present invention is based on the following formula () This invention relates to a novel N-propionylcarnosine aluminum salt represented by the following formula and a method for producing the same. In recent years, the number of peptic ulcer patients has been increasing.
Various studies are being conducted to develop therapeutic agents for this. Therefore, the present inventors synthesized many compounds and examined their pharmacological effects, and found that N-propionylcarnosine aluminum salt represented by the above formula () has an extremely excellent peptic ulcer treatment effect, The invention has been completed. Therefore, an object of the present invention is to provide a novel N-propionylcarnosine aluminum salt. Another object of the present invention is to provide a new method for producing N-propionylcarnosine aluminum salt. The N-propionylcarnosine aluminum salt of the present invention is produced, for example, by reacting N-propionylcarnosine with an aluminum alkoxide. N-propionylcarnosine is D-form,
L-body and DL-body are used. Further, as the aluminum alkoxide, aluminum methoxide, aluminum ethoxide, aluminum isopropoxide, aluminum t-poxide, aluminum cyclohexyl oxide, etc. are used. When this aluminum alkoxide contains impurities such as aluminum hydroxide or its polymer, it is preferable to use one from which the impurities have been removed by distillation, solvent extraction, or the like. The reaction is preferably carried out in a suitable solvent at a temperature of room temperature to 80°C. As the solvent, water or an organic solvent such as methanol, ethanol, isopropanol, butanol, or a mixture thereof is used. After the reaction,
By removing the solvent and by-product alcohols from the reaction solution, the object () can be isolated. Next, the results of testing the peptic ulcer therapeutic effect of the N-propionylcarnosine aluminum salt of the present invention will be shown. In addition, as a comparative compound, N
-Acetyl-L-glutamine aluminum salt and sucrose sulfate ester aluminum salt were used. Experiment 1 Effect on pylorus ligation ulcer: 1 group of male rats weighing 210-230 g
The number was 10. Shay et al. (Gastroenterology, 5,
43-61, 1945), the patient is fasted for 48 hours, and the pylorus is ligated under ether anesthesia. The animals were left without food or water for 14 hours, the stomach was removed, and gastric juice was collected. The area (mm 2 ) of ulcers occurring in the forestomach was measured under a dissecting microscope (10x magnification) and expressed as an ulcer index. Ta. Drugs were administered orally immediately after pyloric ligation. The results are shown in Table 1.
【表】
以上の実結果から明らかな如く、本発明のＮ―
プロピオニルカルノシンアルミニウム塩は、潰瘍
モデルに対し優れた抑制効果を示す。すなわち、
幽門結紮潰瘍試験において、Ｎ―プロピオニルカ
ルノシンアルミニウム塩はラツトに1000mg／Kgを
経口投与した場合、潰瘍に対して有意な抑制効果
を示し、既存の抗潰瘍剤と比較しても優れた効果
を示す。
次に実施例によつて本発明をさらに具体的に説
明する。
実施例 １
アルミニウムイソプロポキシド0.76ｇを含むイ
ソプロピルアルコール15mlに60℃でＮ―プロピオ
ニル―Ｌカルノシン1.75ｇを加え、１時間撹拌し
溶解させる。次に水10mlを加え30分間撹拌した
後、減圧下、イソプロピルアルコールを留去し、
残留した水を加え、均一の溶液とし、凍結乾燥す
ることによりＮ―プロピオニル―Ｌ―カルノシン
アルミニウム塩1.9ｇ（定量的）を得た。
融点：220゜（分解）
〔α〕２５ Ｄ：＋14.1゜（Ｃ＝１％，水）
IR νＫＢｒ ｎａｘcm-1：3400（OH），1640（Ｃ＝Ｏ
），
1540，1400
NMR（D2O）δ：1.02（3H，ｔ，ＣＨ 3CH2
―）、2.10（2H，ｑ，CH3CＨ ２―）、2.42
（2H，ｔ，COCＨ 2CH2NH―）、3.13
（2H，ｍ，[Table] As is clear from the above actual results, the N-
Propionylcarnosine aluminum salt shows excellent suppressive effects on ulcer models. That is,
In the pyloric ligation ulcer test, N-propionylcarnosine aluminum salt showed a significant inhibitory effect on ulcers when administered orally to rats at 1000 mg/Kg, and it also showed superior effects compared to existing anti-ulcer drugs. . Next, the present invention will be explained in more detail with reference to Examples. Example 1 1.75 g of N-propionyl-L carnosine is added to 15 ml of isopropyl alcohol containing 0.76 g of aluminum isopropoxide at 60°C, and the mixture is stirred for 1 hour to dissolve. Next, after adding 10 ml of water and stirring for 30 minutes, the isopropyl alcohol was distilled off under reduced pressure.
The remaining water was added to make a homogeneous solution, which was freeze-dried to obtain 1.9 g (quantitative) of N-propionyl-L-carnosine aluminum salt. Melting point: 220° (decomposition) [α] 25 D : +14.1° (C=1%, water) IR ν KBr nax cm -1 : 3400 (OH), 1640 (C=O
),
1540, 1400 NMR (D 2 O) δ: 1.02 (3H, t, CH 3 CH 2
--), 2.10 (2H, q, CH 3 C H 2 --), 2.42
(2H, t, COC H 2 CH 2 NH-), 3.13
(2H, m,
【式】）、3.32
（2H，ｔ，COCH2CＨ 2NH―）、4.44
（1H，ｍ，[Formula]), 3.32 (2H, t, COCH 2 C H 2 NH-), 4.44
(1H, m,
【式】）、7.08，
8.27（1H×２，ｓ×２，イミタゾール環プロト
ン）
元素分析
（C12H17N4O4）5A13（OH）4として
計算値（％）
Ｃ：46.32，Ｈ：5.78，Ｎ：18.01
分析値（％）
Ｃ：46.25，Ｈ：5.72，Ｎ：17.94
[Formula]), 7.08, 8.27 (1H x 2, s x 2, imitazole ring proton) Elemental analysis (C 12 H 17 N 4 O 4 ) 5 A 13 (OH) Calculated value as 4 (%)
C: 46.32, H: 5.78, N: 18.01 Analysis value (%)
C: 46.25, H: 5.72, N: 17.94
Claims (1)
ニウム塩。 ２ Ｎ―プロピオニルカルノシンにアルミニウム
アルコキシドを反応せしめることを特徴とする次
の式 で表わされるＮ―プロピオニルカルノシンアルミ
ニウム塩の製造法。[Claims] 1. N-propionylcarnosine aluminum salt represented by: 2 The following formula characterized by reacting aluminum alkoxide with N-propionylcarnosine A method for producing N-propionylcarnosine aluminum salt represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55136784A JPS5762266A (en) | 1980-10-02 | 1980-10-02 | N-propionylcarnosine aluminum salt and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55136784A JPS5762266A (en) | 1980-10-02 | 1980-10-02 | N-propionylcarnosine aluminum salt and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5762266A JPS5762266A (en) | 1982-04-15 |
| JPS6251951B2 true JPS6251951B2 (en) | 1987-11-02 |
Family
ID=15183432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55136784A Granted JPS5762266A (en) | 1980-10-02 | 1980-10-02 | N-propionylcarnosine aluminum salt and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5762266A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4882324A (en) * | 1986-11-21 | 1989-11-21 | Wright Arthur P G | Essentially pure acid hydroxyl ligand aluminum complexes and their preparation |
-
1980
- 1980-10-02 JP JP55136784A patent/JPS5762266A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5762266A (en) | 1982-04-15 |
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