CN101548968B - Application of chroman compound HEF-19 in preparing intestinal canal smooth muscle antispastic and antidiarrhoeal - Google Patents
Application of chroman compound HEF-19 in preparing intestinal canal smooth muscle antispastic and antidiarrhoeal Download PDFInfo
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- CN101548968B CN101548968B CN 200910011512 CN200910011512A CN101548968B CN 101548968 B CN101548968 B CN 101548968B CN 200910011512 CN200910011512 CN 200910011512 CN 200910011512 A CN200910011512 A CN 200910011512A CN 101548968 B CN101548968 B CN 101548968B
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- smooth muscle
- hef
- antispastic
- antidiarrhoeal
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Abstract
The invention relates to the field medical technology, and discloses the applications of chroman compounds HEF-19 in preparing intestinal canal smooth muscle antispastic and antidiarrhoeal. In the in vitro experiment of animals, HEF-19 can reduce tension and amplitude induced by spontaneous activities of isolated small intestine smooth muscle of a rabbit, and relax the contractions induced by acetylcholine, barium chloride, potassium chloride and histamine on isolated small intestine smooth muscle of the rabbit. Therefore, the compound can be used for preparing antispastic and antidiarrhoeal for treating intestinal canal smooth muscle spasm. The applications of the compound refer to the preparations of medicaments used for treating stomach/abdomen convulsive pain caused by various reasons,medicaments used for treating intestinal irritable syndrome, medicaments used for treating functional disturbance gastrointestinal tract caused by ulcerative colitis, and medicaments used for treatin g functional diarrhea caused by various reasons and the like.
Description
Technical field:
The present invention relates to medical technical field, is that chroman compound HEF-19 is for the preparation of the purposes of intestinal canal smooth muscle antispastic and diarrhea.
Background technology:
The chemical name of chroman compound HEF-19 is 3,4-dihydro-7-[3-(diethylamino)-propoxy] chroman hydrochloride, HEF-19 is by the chemical compound in the synthetic chroman compound series first such as the Hu Chun of organic chemistry teaching and research room of Shenyang Pharmaceutical University, and the anti-platelet aggregation activity has been carried out preliminary investigation, the result shows, this chemical compound has stronger anti-platelet aggregation active, but the report of relevant HEF-19 diastole intestinal tube smooth muscle effect that so far there are no, the applicant finds first that through many-sided experiment screening this chemical compound has intestinal tube smooth muscle spasmolysis and anti-diarrhea effect.
Chroman compound HEF-19 chemical name is 3,4-dihydro-7-[3-(diethylin) propoxyl group] the chromane hydrochlorate, its synthetic method is as follows:
Get the 1mmol7-hydroxychroman, add 1mmol 3-chloropropyl diethylamine hydrochloride, and 10mmolK
2CO
3, and behind the 0.1mmol KI, add proper amount of acetone, back flow reaction 12 hours, sucking filtration discards inorganic salt, with the solid recrystallization that obtains, obtains 3,4-dihydro-7-[3-(diethylin) propoxyl group behind the concentrated solution] chromane hydrochlorate white solid, yield 41%.MS?m/z(M)：263.38。
1HNMR(CDCl3)：δ1.44(6H，t)，1.81(2H，m)，2.04(2H，m)，2.40(4H，m)，2.55(2H，t)，2.78(2H，m)，3.94(2H，m)，4.04(2H，m)，6.23(1H，d)，6.28(1H，dd)，6.90(1H，dd)。
Summary of the invention:
Technical problem to be solved by this invention provides the purposes of chroman compound HEF-19 treatment intestinal tube smooth muscle spasm and antidiarrheal.
Studies show that: the strong contraction of intestinal tube smooth muscle causes spasm and can cause various diseases, such as stomachache, borborygmus, abdominal distention, diarrhoea, so research intestinal smooth muscle spasmolytic has very large realistic meaning, to treatment gastrointestinal convulsion angor, the functional diarrhea that the diseases such as the gastrointestinal dysfunction that irritable bowel syndrome, ulcerative colitis etc. cause and a variety of causes cause all has directive significance and reference value.
We studies show that: HEF-19 can reduce tension force and the amplitude of isolated small intestines of rabbits spontaneous activity, and diastole acetylcholine, barium chloride, potassium chloride and histamine cause the isolated small intestines of rabbits smooth muscle of contraction.Therefore, HEF-19 can be for the preparation of spasmolytic and the diarrhea for the treatment of intestinal tube smooth muscle spasm.Its minimum effective dose is 10
-6Mol/L
Description of drawings:
Fig. 1 is that HEF-19 is on the impact of isolated small intestines of rabbits smooth muscle spontaneous contractions activity
Fig. 2 is HEF-19 to causing the amount effect curve of the isolated small intestines of rabbits diastole effect that the convulsion agent shrinks
Fig. 3 is the accumulation amount effect curve (n=6) of HEF-19 diastole isolated small intestines of rabbits smooth muscle
*P＜0.05,
*P＜0.01, VS experiment contrast group
The accumulation amount effect curve (n=6) of Fig. 4 HEF-19 diastole isolated small intestines of rabbits smooth muscle
*P＜0.05,
*P＜0.01, VS experiment contrast group
The specific embodiment
Embodiment 1:
One, experiment material
Animal:
New zealand rabbit, the male and female dual-purpose, body weight 2.0～2.5kg, Shenyang Pharmaceutical University's Experimental Animal Center provides, the quality certification number: No. 033, the real moving word of the Liao Dynasty.
Hef-19: purity＞99%, Shenyang Pharmaceutical University's Lab Organic provides.
Two, experimental technique
1.HEF-19 the effect to the isolated small intestines of rabbits spontaneous activity
Behind the specimen tension stability, to bathing the HEF-19 (10 that adds respectively different final concentrations in the pipe
-6Mol/L, 10
-5Mol/L, 10
-4Mol/L) 0.1ml and aqueous solvent, the variation of observing and recording small intestinal spontaneous contractions under every kind of concentration is before the record administration, the variation of the tension force after the administration, amplitude.Tension force before the administration or amplitude be as 100%, calculates the percent of small intestinal tension force after the administration or amplitude.Experimental data represents with means standard deviation, and makes paired t-test, the significance of judgement difference.
2. the effect of shrinking causing isolated small intestines of rabbits that the convulsion agent causes
Behind the specimen tension stability, cause convulsion agent (acecoline 10 to bathing to add in the pipe
-4Mol/L, barium chloride 2mg/ml, potassium chloride 60mmol/L, histamine 10
-4Mol/L), obtain maximum collapse after, fully the flushing tissue adds with the convulsion agent that causes of concentration and again induces contrast to shrink, when with front once shrink basically identical after, totally add respectively HEF-19 (10
-6Mol/L～10
-3Mol/L), record amount effect curve.So that the maximum shrinkage amplitude of convulsion agent is 100%, draws amount effect curve, and data represent with meansigma methods ± standard error, and obtain EC
50
3.HEF-19 with ATP sensitivity K
+The relation of passage, L-type calcium channel
Add BaCl
2After (2mg/ml) contraction was stablized, accumulation added HEF-19 (10
-6Mol/L～10
-3Mol/L), obtain HEF-19 diastole BaCl
2The accumulation amount effect curve that shrinks is as blank.Flushing adds respectively glibenclamide solution (10 behind the specimen tension stability
-5Mol/L) and verapamil (10
-7Mol/L), hatched 10 minutes, again add BaCl
2Obtain HEF-19 diastole BaCl
2The accumulation amount effect curve that shrinks calculates EC
50Value is determined HEF-19 and ATP sensitivity K
+The relation of passage, L-type calcium channel.
Three, experimental result
1.HEF-19 the effect to the isolated small intestines of rabbits spontaneous activity
By table 1 and Fig. 1, HEF-19 can reduce tension force and the amplitude of isolated small intestines of rabbits spontaneous contractions as can be known.
2. the effect of shrinking causing isolated small intestines of rabbits that the convulsion agent causes
By Fig. 2 and the table 2 isolated small intestines of rabbits smooth muscle that shrinks of HEF-19 diastole acetylcholine, barium chloride, potassium chloride and histamine as can be known.
3.HEF-19 with ATP sensitivity K
+The relation of passage, L-type calcium channel
After glibenclamide and verapamil are hatched, by BaCl
2Cause contraction HEF-19 the diastole amount effect curve significant change, EC all occur
50Value changes 4.16 ± 0.22 and 3.96 ± 0.24 into by 4.36 ± 0.12 and 4.43 ± 0.19 respectively.Carry out statistics t check, there were significant differences (P＜0.05) (Fig. 3, Fig. 4).Illustrate that glibenclamide and verapamil can affect the intestinal tube diastole effect of HEF-19.The mechanism of HEF-19 diastole intestinal tube smooth muscle and open ATP sensitivity K
+Passage, blocking-up L-type calcium channel are relevant.
Table 1HEF-19 is on the impact (mean ± SDn=8, %) of Intestine in Rabbits smooth muscle spontaneous activity
*P＜0.05,
*P＜0.01 is compared with group of solvents, Student ' s t-test
Table 2.HEF-19 causes the EC of the diastole effect of intestinal smooth muscle spasm to causing the convulsion agent
50Value (* ± S.E.M)
Above experimental result explanation HEF-19 can reduce tension force and the amplitude of isolated small intestines of rabbits spontaneous activity, the isolated small intestines of rabbits that diastole acetylcholine, barium chloride, potassium chloride and histamine shrink.Therefore, HEF-19 can be for the preparation of spasmolytic and the diarrhea for the treatment of intestinal tube smooth muscle spasm.
Claims (2)
1.3,4-dihydro-7-[3-(diethylin) propoxyl group] and the application of chromane hydrochlorate in preparation treatment intestinal tube smooth muscle spasm disease and diarrhoea medicine.
2. purposes according to claim 1, it is characterized in that: described intestinal tube smooth muscle spasm disease refers to the gastrointestinal convulsion angor that a variety of causes causes, the gastrointestinal dysfunction that irritable bowel syndrome causes.
3, purposes according to claim 1 is characterized in that: described diarrhoea refers to the functional diarrhea that a variety of causes causes.
4, purposes according to claim 1 is characterized in that: its minimum effective dose is 10
-6Mol/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910011512 CN101548968B (en) | 2009-05-12 | 2009-05-12 | Application of chroman compound HEF-19 in preparing intestinal canal smooth muscle antispastic and antidiarrhoeal |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910011512 CN101548968B (en) | 2009-05-12 | 2009-05-12 | Application of chroman compound HEF-19 in preparing intestinal canal smooth muscle antispastic and antidiarrhoeal |
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|---|---|
| CN101548968A CN101548968A (en) | 2009-10-07 |
| CN101548968B true CN101548968B (en) | 2013-04-17 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268131A (en) * | 1997-08-26 | 2000-09-27 | 曾尼卡有限公司 | Process for preparing 3-isochromanome |
| CN1477105A (en) * | 2003-07-09 | 2004-02-25 | 山东大学 | Yiseman derivative and its preparation method |
| CN1944428A (en) * | 2006-10-27 | 2007-04-11 | 中国药科大学 | Chroman compound and its preparing method and use in producing medicine |
-
2009
- 2009-05-12 CN CN 200910011512 patent/CN101548968B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268131A (en) * | 1997-08-26 | 2000-09-27 | 曾尼卡有限公司 | Process for preparing 3-isochromanome |
| CN1477105A (en) * | 2003-07-09 | 2004-02-25 | 山东大学 | Yiseman derivative and its preparation method |
| CN1944428A (en) * | 2006-10-27 | 2007-04-11 | 中国药科大学 | Chroman compound and its preparing method and use in producing medicine |
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|---|---|
| CN101548968A (en) | 2009-10-07 |
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