CN101108173A - Application of p-hydroxybenzene ethanone and its derivant in preparation of agentia treating gallstone disease - Google Patents
Application of p-hydroxybenzene ethanone and its derivant in preparation of agentia treating gallstone disease Download PDFInfo
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Abstract
The invention discloses an application of hydroxyacetophenone and its derivatives in preparing drugs for curing cholelithiasis, which can enhance the excretion of bile and lower down the content of cholesterin and bilirubin in the bile, thus realizing the dual effects of bile expelling and lithiasis resolving. Therefore, the invention can be applied to treat lithiasis.
Description
Technical field
The present invention relates to the application of parahydroxyacet-ophenone and derivant thereof, relate in particular to the application in the medicament of preparation treatment cholelithiasis of parahydroxyacet-ophenone and derivant thereof at pharmaceutical field.
Background technology
Cholelithiasis is the commonly encountered diseases that influences human health, and most Hesperian incidences are similar, and adult's sickness rate is about 10～20%.Be about 10% in China.Female patient is about a times of male patient.The characteristics of incidence of primary disease is has age, sex, occupation, obesity and regional difference not only, also has the difference of environment, heredity etc.In acquired disposition, all can increase the sickness rate of cholelithiasis as medicine, endotoxin, infection (comprising parasitic infection), hormone, obstruction of biliary tract, liver transplantation etc.
Cholelithiasis can be divided into cholesterol calculus, bile pigment stone and mixed calculus etc. by its composition.The Main Ingredients and Appearance of cholesterol calculus is a cholesterol crystal.The Main Ingredients and Appearance of bile pigment calculus is a bile pigments calcium.Mixed calculus then is the mixing of different proportions such as bile pigments, cholesterol, calcium.Mostly western countries are cholesterol calculus, account for calculus patient's 75-80%, are one of modal gastrointestinal disease.China is in the past then based on the bile pigments calcium calculus of extrahepatic duct, and reason is to be caused by the dietary habit of China, biliary tract infection (comprising parasitic infection) etc.In recent years, China resident dietary habit changes, and animal fat increases, and sanitary condition is improved, and the average life span prolongs, and the cholesterol calculus then increases.In some flourishing cities, show that according to the analysis result to the cholelithiasis sample about 70% is cholesterol calculus in the cholelithiasis especially, 23.8% is the bile pigments calcium calculus, and other are combination calculus.
Owing to the progress of surgical operation and Minimally Invasive Surgery, many cholelithiasis patients all adopt operative treatment, have obtained good effect at present.But patient and many patients who is not suitable for performing the operation of asymptomatic cholelithiasis patient, many calculus less (1.0～1.5cm is following) silt shape calculus all need give positive cholagogic and litholytic Drug therapy.
The western medicine of cholelithiasis mainly contains two classes at present: a class is a function of gallbladder promoting, promptly promote bile secretion, increase moisture in the bile, bile is thinned out, thereby the bile amount is increased, the mobile raising brought into play the biliary tract flushing action, make like this that solid constituent can not deposit in the bile, even muddy stone can be washed gradually and reduced; It is another kind of that current to get rather noticeable in the Drug therapy at cholelithiasis be the dissolved stone medicine of chenodeoxycholic acid and ursodesoxycholic acid, thereby this class medicine or because of suppressing the synthetic of HMG-CoA reductase cholesterol reducing and secretion, and then the cholesterol level in the reduction bile, or, promote litholysis by form the liquid layer of lecithin-cholesterol in calculus surfaces.
But this class dissolved stone medicine has some often to make the patient be difficult to adhere to for a long time the side effect of taking more, particularly gastrointestinal reaction is for example suffered from diarrhoea, and taking for a long time still has abnormal liver function, the medicine that has (for example chenodeoxycholic acid) still has teratogenesis, therefore has been subjected to very big restriction.
Chinese medicine has been brought into play very outstanding effect in the treatment of cholelithiasis, based on the compound recipe of Herba Lysimachiae, obtained certain effect, but we carry out cholagogic and litholytic test with the component of Herba Lysimachiae separation and Extraction and do not obtain tangible curative effect.
Summary of the invention
Mattress Cape jasmine Huang is a jaundice eliminating medicine famous in China's Chinese medicine, has function of gallbladder promoting, reduces effects such as jaundice index, and the jaundice that causes for hepatitis has a significant effect, and wherein brings into play more important role with Herba Artemisiae Scopariae in promoting the function of the gallbladder to alleviate jaundice especially.We are by the research to Herba Artemisiae Scopariae function of gallbladder promoting effective ingredient, find that its fat-soluble ingredient function of gallbladder promoting is respond well, discover that further its effective monomer parahydroxyacet-ophenone not only has tangible function of gallbladder promoting effect, and have an effect that reduces bile cholesterol content with ursodesoxycholic acid is similar.We have studied a series of derivants of parahydroxyacet-ophenone simultaneously, all confirm certain function of gallbladder promoting or litholytic effect.
The purpose of this invention is to provide the application in the medicament of preparation treatment cholelithiasis of parahydroxyacet-ophenone and derivant thereof.
Described parahydroxyacet-ophenone derivant comprises parahydroxyacet-ophenone nicotinate, o-hydroxyacetophenone, acetanisole, m-hydroxy acetophenone, para aminoacetophenone, p-hydroxyphenyl butanone, 3,5-resacetophenone, p-nitroacetophenone and para hydroxybenzene pentanone.
Described parahydroxyacet-ophenone, m-hydroxy acetophenone and 3,5-resacetophenone also can be used for preparing function of gallbladder promoting litholytic medicament simultaneously.
Cholelithiasis of the present invention comprises cholesterol calculus disease and bile pigment calculus disease.
Parahydroxyacet-ophenone of the present invention and derivant thereof can with pharmaceutically acceptable carrier combinations, make any pharmaceutically acceptable dosage form, effective dose is 50-300mg/kg.
The structural formula of parahydroxyacet-ophenone and derivant thereof is as follows:
The acetanisole parahydroxyacet-ophenone
P-hydroxyphenyl butanone para hydroxybenzene pentanone
M-hydroxy acetophenone o-hydroxyacetophenone 3, the 5-resacetophenone
Parahydroxyacet-ophenone cigarette p-nitroacetophenone para aminoacetophenone
Acid esters
The parahydroxyacet-ophenone analog derivative can increase choleresis in the certain hour after administration, can reduce bile cholesterol and bilirubinic content again, therefore this class medicine has played the dual function of cholagogic and litholytic, and this dual function is very important for the treatment cholelithiasis.And cholelithiasis common drug ursodesoxycholic acid does not have the report that increases the bile excretion amount.Often have only one-sided effect in the medicine of cholelithiasis at present, the medicine that plays this dual function does not also occur.And para hydroxybenzene second naphthoquinone derivatives preparation method is simple, and function is certain, and is cheap, is indicating well prospect in medicine.
The specific embodiment
Experimental technique:
1. experimental animal: the SD rat, male and female half and half are about body weight 220g.Be subjected to test product: parahydroxyacet-ophenone nicotinate, o-hydroxyacetophenone, acetanisole, m-hydroxy acetophenone, para aminoacetophenone, p-hydroxyphenyl butanone, 3,5-resacetophenone, parahydroxyacet-ophenone, p-nitroacetophenone, para hydroxybenzene pentanone (ten samples).
2. route of administration: duodenal administration.
3. dosage: as shown in each example.
4. experimentation: rat abdominal cavity anesthesia (3% secobarbital, dosage 1ml/kg) after, cystic duct cannula, bile drainage, metering, and in the interval with 0-30 minute, 30-60 after preceding 30 minutes of administration, the administration minute, 60-90 minute, 90-120 minute, the bile packing of drain, the content of cholesterol detection, bilirubin and bile acid
Statistical method:
With the negative contrast of normal saline group, use parahydroxyacet-ophenone nicotinate, o-hydroxyacetophenone, acetanisole, m-hydroxy acetophenone, para aminoacetophenone, p-hydroxyphenyl butanone, 3 respectively, 5-resacetophenone, parahydroxyacet-ophenone, p-nitroacetophenone, ten groups of data of para hydroxybenzene pentanone gained and normal saline group data are done the two t of survey checks; And with behind every group of drug administration with administration before data do sided t check.
Reference examples
Negative control group: normal saline
Dosage: 0.5ml/100g;
Number of animals: 14
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 500 500 490 500 | 310 600 200 350 | 420 410 410 400 | 480 460 450 450 | 280 280 260 260 240 | 310 280 300 300 320 | 440 380 650 380 400 | 320 320 320 330 380 | 550 460 420 460 480 | 420 430 200 340 400 | 450 450 350 480 430 | 100 520 400 400 | 320 380 330 440 430 | 380 320 340 300 270 | 377 414 366 385 372 | 114 94 119 74 79 |
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 40 37.5 41.5 40.7 | 33.6 39.3 28.9 80.6 | 24.3 23.5 23.1 31.7 | 35.9 32.8 52.8 61.7 | 67.3 44.1 45 57.4 69.2 | 97.3 84.4 70.3 64.2 61.7 | 42.5 33.4 33.8 31.8 36.5 | 43.2 33.2 29.3 35.9 42 | 69.3 66.5 79.5 91.7 93 | 76.3 60.1 53.1 69.7 71.6 | 34 38.8 41.3 52.6 62.5 | 54 126.1 159.3 171.9 | 64.4 57.8 70.4 77.9 85.3 | 54.1 48.5 93 93.2 88 | 52.6 51.9 58.7 68.6 67.8 | 20.3 26.8 35.6 36.2 19.6 |
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 0.3 0.2 0.2 0.2 | 0.5 0.3 0.4 0.3 | 0.4 0.3 0.2 0.2 | 0.5 0.5 0.5 0.5 | 0 0 0 0 0 | 0.1 0 0 0 0.1 | 0.1 0.1 0.1 0.1 0.1 | 0.2 0.1 0.1 0 0 | 0 0 0 0 0 | 0.7 0.4 0.5 0.5 0.6 | 0.5 0.4 0.4 0.2 0.2 | 0.4 0.1 0.2 0.2 | 0.7 0.4 0.4 0.4 0.3 | 0.5 0.4 0.3 0.3 0.2 | 0.4 0.2 0.2 0.2 0.2 | 0.2 0.2 0.2 0.2 0.2 |
D. to the influence of bile acid content in the rat bile (X ± SD)
| Time period | Bile acid content/mmol * 10 -3 | |||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | X | SD | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 665.5 696 700.9 698.3 690.2 | 667.1 694.3 703 702.7 680.2 | 649.4 692.3 692.7 686.3 686.6 | 611.2 731.1 736.8 691.5 682.1 | 666 697.2 698.5 695.4 694 | 661.2 686 691.2 677.1 676.2 | 671.2 701 708 712.9 710.9 | 632.8 650.4 673.5 676.3 | 669.8 697.6 691 693.9 704.2 | 676.8 684 659.8 696.1 707.1 | 657.1 693 695.5 693.1 692.4 | 20.5 19.7 20.4 11.1 12.5 |
Embodiment 1
Be subjected to the reagent thing: para hydroxybenzene pentanone (Tokyo HuaCheng Industry Co., Ltd's production)
Dosage: 19.6mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 530 560 350 360 | 510 680 380 400 | 420 700 700 470 | 480 540 550 350 | 485 620 495 395 | 48.0 81.6 162.6 54.5 | * * | ** |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 40.6 32.8 29.7 29 5 | 36.3 29.2 24.1 25.1 | 28.9 15.7 23 25.9 | 18.4 34 40.8 42 | 31.1 27.9 29.4 30 6 | 9.7 8.4 8.1 7.8 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.1 0.1 0.1 0.1 | 0.3 0.1 0.1 0.1 | 0.3 0.1 0 0.1 | 0.5 0.2 0.2 0.3 | 0.3 0.1 0.1 0.2 | 0.2 0.1 0.1 0.1 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 1: the para hydroxybenzene pentanone after 30 minutes and the administration in 60-90 minute time period, significantly increases bile flow, but cholesterol and bilirubinic content is had no significant effect after administration.Confirm that the para hydroxybenzene pentanone has choleretic effect.
Embodiment 2
Be subjected to the reagent thing: p-nitroacetophenone (production of Lancaster company)
Dosage: 12.9mg/kg;
Number of animals: 14
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 820 1300 820 700 | 520 1000 850 780 | 710 1200 900 360 | 100 180 340 330 | 600 600 500 460 420 | 500 500 480 480 500 | 600 510 520 600 280 | 500 440 420 380 400 | 460 460 380 400 280 | 460 470 440 520 80 | 100 300 300 380 380 | 330 340 380 400 450 | 220 320 260 260 250 | 280 250 280 320 280 | 443 562 491 455 332 | 215 351 214 149 123 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 31.4 18 23.8 37.1 | 36.4 7.2 7.7 3.9 | 30.3 15.9 18.3 16 | 27.4 10.5 10.4 3.5 | 40.8 38.6 50.9 57.6 60.7 | 32.9 34.7 43.5 54.9 59.2 | 38.9 39.9 49.7 61.5 59 | 43 25.4 33.2 35.8 49.1 | 25.9 28 24.1 33.3 31.9 | 71.9 54.3 44.7 44.2 42.6 | 89.4 72.3 45.2 45 39.1 | 86.1 65.4 58.4 56.6 58.7 | 87.4 63.3 52.5 49.6 49.5 | 70.2 56 64.3 59.3 57.2 | 50.9 37.8 37.6 39.9 50.7 | 24.3 21.5 18 19.7 10 | * * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 0.3 0.1 0.1 0.2 | 0.4 0.1 0.1 0.2 | 0.6 0.2 0.3 0.4 | 0.3 0.2 0.2 0.2 | 0.5 0.3 0.4 0.4 0.5 | 0.5 0.4 0.4 0.4 0.3 | 0.7 0.5 0.4 0.4 0.5 | 0.6 0.4 0.5 0.5 0.4 | 0.7 0.5 0.6 0.5 0.6 | 0.1 0.1 0.1 0.1 0.1 | 0 0 0 0 0.1 | 0.1 0.1 0 0.1 0.1 | 0 0 0.1 0.1 0.1 | 0.1 0.1 0 0 0 | 0.4 0.2 0.2 0.3 0.3 | 0.3 0.2 0.2 0.2 0.2 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
D. to the influence of bile acid content in the rat bile (X ± SD)
| Time period | Bile acid content/mmol * 10 -3 | |||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 665.9 691.9 690.9 690.3 691.7 | 671.8 696 695.3 699.3 705.1 | 674 677.1 684.6 683 695.8 | 662.2 686.5 679.2 687.2 695.1 | 677.6 699.2 700.6 702.4 703.9 | 671.4 748.9 752.7 700.4 697.7 | 616.4 635.8 685.8 683.6 676.7 | 644.1 666.5 682.2 674.7 673 | 617.8 668.8 688.8 693.4 693.7 | 636.8 685.1 696 744 702.1 | 653.8 685.6 695.6 695.8 693.5 | 23.3 28.9 21.1 19.1 10.8 | * ** ** ** | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 2: after the p-nitroacetophenone administration in 60-120 minute time period, the corresponding time period with the normal saline group of content of bilirubin compares in the bile, there were significant differences, but with self not the data of administration compare, no significant difference, the reason that this difference produces may be because postoperative mouse bile reduces naturally and covers p-nitroacetophenone but due to the influence of content of bilirubin;
Compare that there were significant differences in the bile after the p-nitroacetophenone administration in 30 minutes before bile acid content and the self administration, after the administration in 30-120 minute time period, and compare the difference that highly significant is arranged before the self administration.Confirm that p-nitroacetophenone has the litholytic effect of cholesterol calculus disease.
Embodiment 3
Be subjected to the reagent thing: parahydroxyacet-ophenone (production of Lancaster company)
Dosage: 15mg/kg;
Number of animals: 13
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | ||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 520 1200 850 400 | 500 1090 840 460 | 440 610 690 400 | 620 1220 400 600 | 350 600 600 580 320 | 300 420 460 280 280 | 280 680 320 230 100 | 310 340 240 270 260 | 520 830 400 450 400 | 380 460 360 340 310 | 420 400 400 350 300 | 240 600 560 560 500 | 420 440 340 360 330 | 408 684 497 406 311 | 112 308 197 120 107 | ** | ** * |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | ||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 44.3 14.5 40.3 26.9 | 30 14.1 22.9 28.5 | 120.5 24.8 36 50.5 | 39.4 17.7 23.9 64.7 | 51.4 21.3 38.9 45.2 44.1 | 59.6 15.2 15.9 20.1 33.6 | 54.8 32.7 46 54.2 50.4 | 44.6 42.8 56.9 68.7 65.4 | 31.9 25.3 44.4 53.9 50 | 26.5 12.6 10.5 9.9 9.8 | 17 8 23.8 23.6 16.2 | 21.7 26.8 32.3 42.7 45.3 | 8.9 10 12.6 19.2 27.1 | 42.4 20.4 31.1 39.1 38 | 27.9 9.9 14.2 18.9 17.8 | * | ** * * ** |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | ||||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 1.1 0.1 0.2 0.6 | 0.2 0.1 0 0.1 | 0 0 0 0.1 | 0.6 0.1 0.1 0.3 | 0.3 0.1 0.1 0.1 0.1 | 0.1 0.1 0.1 0.1 0.1 | 0.2 0.1 0.1 0.2 0.2 | 0.1 0 0 0 0 | 0.5 0.2 0.3 0.3 0.4 | 0.4 0.3 0.3 0.3 0.4 | 0.5 0.2 0.3 0.5 0.5 | 0.3 0.2 0.2 0.2 0.2 | 0.8 0.5 0.5 0.4 0.6 | 0.4 0.2 0.2 0.2 0.3 | 0.3 0.1 0.1 0.2 0.2 | * * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
D. to the influence of bile acid content in the rat bile (X ± SD)
| Time period | Bile acid content/mmol * 10 -3 | ||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 670.7 709.1 748.8 690.5 701.2 | 659.4 702.8 699.8 702.1 677.1 | 664.9 703.8 697.7 695.7 691.7 | 681.4 703.5 706.3 703.5 697.2 | 669.4 698.9 691.3 691.5 701 | 659.8 686.9 693.6 694.1 692.5 | 701.1 715.9 710.1 696.5 700.2 | 676 685.8 684.8 695 705.1 | 678.1 765.2 768.5 766.8 717.2 | 673.4 708 711.2 704 698.1 | 12.9 23.5 28.4 24 10.9 | ** ** ** ** | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 3: after the parahydroxyacet-ophenone administration in 0-30 minute before bile flow and the self administration contrast difference of highly significant is arranged, in 30-60 minute time period, the corresponding time period with the normal saline group has been compared significant difference after the administration.Confirm that parahydroxyacet-ophenone has choleretic effect.
Compare before bile inner bag red pigment content and the self administration in 0-30 minute after the parahydroxyacet-ophenone administration that there were significant differences, the interior corresponding time period with the normal saline group of 30-120 minute time period is compared after the administration, there were significant differences, with contrast zero difference before the self administration, this possibility of result since postoperative bile mesobilirubin naturally the minimizing due to; Confirm that parahydroxyacet-ophenone has the litholytic effect to bile pigment calculus disease.
Compare before bile inner cholesterol content and the self administration in 0-60 minute after the parahydroxyacet-ophenone administration that there were significant differences, after the administration in 0-120 minute, compare difference before bile acid content and the self administration in the bile, confirm that parahydroxyacet-ophenone has the litholytic effect of good cholesterol calculus card with highly significant.
Embodiment 4
Be subjected to the reagent thing: 3,5-resacetophenone (Tokyo HuaCheng Industry Co., Ltd's production)
Dosage: 16.8mg/kg;
Number of animals: 11
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | ||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 500 390 210 380 | 300 660 320 310 | 520 700 640 450 | 260 1080 740 240 | 480 580 560 560 350 | 220 920 660 600 540 | 800 880 440 | 360 440 500 430 390 | 190 560 500 470 380 | 450 440 400 400 360 | 280 810 440 520 400 | 396 678 492 436 403 | 178 223 155 110 69 | ** | ** ** |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | ||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 116.4 71.7 51.6 78.6 | 54.7 40.5 30.2 26.9 | 20.7 22.5 48.4 53.6 | 12.8 23.4 67.7 65.7 | 29.4 29.5 30.8 32.4 28.4 | 28.6 24.8 35.6 39.1 41 | 32.5 24.7 26.3 | 33.9 28.9 40.9 42.9 41.5 | 36.5 51.7 48.9 58.4 63.7 | 46.3 20.5 25.5 26.8 31.1 | 43.4 23.2 32 26.2 29.4 | 41.4 32.9 39.8 45.1 39.2 | 27.5 15.9 13.1 18.3 13.3 | * ** | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | ||||||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 0 0.1 0.1 0.1 | 0.3 0.1 0.2 0.3 | 0.7 0 0.2 0.3 | 0.7 0.1 0.2 0.4 | 0.6 0.4 0.5 0.6 0.6 | 0.4 0.1 0.2 0.3 0.3 | 0.3 0.1 0.3 | 0.4 0.3 0.2 0.2 0.3 | 0.4 0.2 0.4 0.4 0.4 | 0.4 0.2 0.2 0.2 0.3 | 0.3 0 0.1 0.1 0.1 | 0.4 0.1 0.2 0.3 0.3 | 0.2 0.1 0.1 0.2 0.2 | ** * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
D. to the influence of bile acid content in the rat bile (X ± SD)
| Time period | Bile acid content/mmol * 10 -3 | ||||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute after the administration in 60-90 minute 90-120 minute | 670.1 685.8 666.7 674.8 679.6 | 652.6 687.7 678.8 679.9 689.1 | 646.6 683.2 677.4 | 639.4 632.8 667.5 690 697.1 | 619.2 643.7 669.8 678.4 689.9 | 678.2 709.1 717 715.1 714.5 | 676.6 754.4 756.3 715 692.5 | 654.7 685.2 690.5 692.2 693.8 | 21.7 40.5 33.8 18.4 11.7 | * ** | |
Conclusion 4:3, after the administration of 5-resacetophenone 0-30 minute, compare the difference that highly significant is arranged before bile flow and the self administration, in 30-60 minute time period, the corresponding time period with the normal saline group of bile flow is compared, and the difference of highly significant is arranged; Confirm 3, the 5-resacetophenone has choleretic effect.
3, after the administration of 5-resacetophenone 0-30 minute, the corresponding time period with the normal saline group of bile mesobilirubin content was compared, and there were significant differences; In 90-120 minute time period, the corresponding time period with the normal saline group of bile mesobilirubin content is compared, and the difference of highly significant is arranged.Confirm 3, the 5-resacetophenone has the litholytic effect of bile pigment calculus disease.
3, after the administration of 5-resacetophenone 30 minutes, compare before the cholesterol level in the bile and the self administration, the difference of highly significant is arranged, after the administration 30-60 minute, and to compare before the self administration, the cholesterol level in the bile has significant difference; After the administration 30-60 minute, and to compare before the self administration, the bile acid content in the bile has significant difference, and after the administration 90-120 minute, and to compare before the self administration, the bile acid content in the bile has the difference of highly significant.Confirm 3, the 5-resacetophenone has the litholytic effect of cholesterol calculus disease.
Embodiment 5
Be subjected to the reagent thing: p-hydroxyphenyl butanone (Tokyo HuaCheng Industry Co., Ltd's production)
Dosage: 18.0mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 120 350 400 200 | 590 500 200 | 460 720 900 590 | 520 590 830 660 | 422.5 540.0 582.5 483.3 | 208.5 155.6 337.5 247.9 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 13.7 49.6 74.3 37 | 14.6 11.1 4.8 | 37.8 12.8 8.8 18.3 | 40.9 12.9 8 17.7 | 26.8 21.6 24.0 24.3 | 14.6 18.7 33.6 11.0 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.7 0.1 0.1 0.3 | 0.6 0.3 0.3 0.4 | 0.4 0.1 0 0.1 | 0.3 0.1 0.1 0 | 0.5 0.2 0.1 0.2 | 0.2 0.1 0.1 0.2 | * * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 5: after the p-hydroxyphenyl butanone administration 0-60 minute, compare before bile cholesterol content and the self administration, there were significant differences.Confirm that p-hydroxyphenyl butanone has the litholytic effect of cholesterol calculus disease.
Embodiment 6
Be subjected to the reagent thing: para aminoacetophenone (Chemical Reagent Co., Ltd., Sinopharm Group's production)
Dosage: 15mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 750 380 360 400 | 860 360 440 480 | 330 240 240 260 | 490 390 370 380 | 607.5 342.5 352.5 380.0 | 241.4 69.5 83.0 90.9 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 33.1 6.7 5.2 7.3 | 50.4 18.8 43.8 30.2 | 24.3 13.9 6 8.3 | 29.5 24.8 19.7 18.6 | 34.3 16.1 18.7 16.1 | 11.3 7.7 18.0 10.7 | * | * * * |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.4 0.3 0.2 0.1 | 0.4 0.4 0.3 0.3 | 0.3 0.2 0.1 0.2 | 0.7 0.5 0.5 0.5 | 0.5 0.4 0.3 0.3 | 0.2 0.1 0.2 0.2 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 6: after the para aminoacetophenone administration 30 minutes, and to compare before the self administration, the content of bilirubin in the bile has the significance difference distance; After the administration 0-90 minute, the corresponding time period with the normal saline group was compared, and there were significant differences for the content of bilirubin in the bile.Confirm that para aminoacetophenone has the litholytic effect of bile pigment calculus disease.
Embodiment 7
Be subjected to the reagent thing: m-hydroxy acetophenone (Tokyo HuaCheng Industry Co., Ltd's production)
Dosage: 15mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 400 650 650 600 | 310 480 500 340 | 660 840 780 450 | 160 90 460 420 | 382.5 515.0 597.5 452.5 | 209.8 319.2 146.6 108.7 | ** | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 35.5 20.4 25 18.6 | 43.7 14.1 16.2 19 | 68.4 17.7 48.9 59.6 | 12.3 27.6 45.2 23.2 | 40.0 20.0 33.8 30.1 | 23.2 5.7 15.8 19.8 | * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.3 0.1 0 0.1 | 0.3 0.1 0 0.2 | 0.3 0.1 0.1 0.2 | 0.7 0.3 0.3 0.4 | 0.4 0.2 0.1 0.2 | 0.2 0.1 0.1 0.1 | * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 7: after the m-hydroxy acetophenone administration 30-60 minute, the corresponding time period with the normal saline group was compared, and bile flow has the difference of highly significant.Confirm that m-hydroxy acetophenone has choleretic effect.
In 30 minutes, the corresponding time period with the normal saline group is compared after the m-hydroxy acetophenone administration, and there were significant differences for the content of bilirubin in the bile, confirms that m-hydroxy acetophenone has the litholytic effect of bile pigment calculus disease.
After the m-hydroxy acetophenone administration 30-60 minute, to compare before wanting with self giving, there were significant differences for the cholesterol level in the bile, confirms that m-hydroxy acetophenone has the litholytic effect of cholesterol calculus disease.
Embodiment 8
Be subjected to the reagent thing: acetanisole (production of Fluka company)
Dosage: 16.5mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 450 460 450 460 | 210 250 280 260 | 480 530 460 440 | 410 440 300 260 | 387.5 420.0 372.5 355.0 | 121.8 119.7 95.7 110.0 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 53.3 25.4 19.4 16.5 | 20.4 14.6 16.4 20.4 | 26.6 31.5 23 27.2 | 27.7 6.1 3.5 3.5 | 32.0 19.4 15.6 16.9 | 14.6 11.3 8.5 10.0 | * * * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.2 0.1 0 0.1 | 0.3 0.1 0.1 0.1 | 0.3 0.1 0.1 0.1 | 0.3 0.2 0.1 0.2 | 0.3 0.1 0.1 0.1 | 0.0 0.1 0.1 0.1 | ** ** ** | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 8: after the acetanisole administration 0-90 minute, the corresponding time period with the normal saline group was compared, and there were significant differences for the content of bile mesobilirubin.Confirm that acetanisole has the litholytic effect of bile pigment calculus disease.
After the acetanisole administration 0-90 minute, and to compare before the self administration, the content of bile cholesterol has the gap of highly significant.Confirm that acetanisole has the litholytic effect of cholesterol calculus disease.
Embodiment 9
Be subjected to the reagent thing: o-hydroxyacetophenone (Tokyo HuaCheng Industry Co., Ltd's production)
Dosage: 15mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 420 500 480 520 | 500 400 200 340 | 660 390 400 350 | 500 300 400 380 | 520.0 397.5 370.0 397.5 | 100.7 81.8 119.4 83.4 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | ||||||
| 1 | 2 | 3 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 99.3 93.6 74.9 85.8 | 61.3 52 63.6 113.1 | 104.3 81.1 101.5 116.8 | 88.3 75.6 80.0 105.2 | 23.5 21.3 19.5 16.9 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | ||||||
| 1 | 2 | 3 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0.4 0.2 0.2 0.1 | 0.2 0 0.1 0.1 | 0.3 0.1 0.1 0.1 | 0.3 0.1 0.1 0.1 | 0.1 0.1 0.1 0.0 | * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 9: after the o-hydroxyacetophenone administration 60-90 minute, and to compare before the self administration, there were significant differences for the content of bile cholesterol.Confirm that o-hydroxyacetophenone has the litholytic effect of cholesterol calculus disease.
Embodiment 10
Be subjected to the reagent thing: parahydroxyacet-ophenone nicotinate (self-control)
The preparation feedback formula is as follows:
Dosage: 26.6mg/kg;
Number of animals: 4
A. to the influence of rat bile secretory volume (X ± SD)
| Time period | Bile flow/μ l | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 420 360 360 320 | 320 200 250 280 | 440 320 360 320 | 600 440 500 480 | 445.0 330.0 367.5 350.0 | 115.9 100.0 102.4 88.7 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
B. to the influence of rat bile mesobilirubin content (X ± SD)
| Time period | Content of bilirubin/μ mol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 113.1 83.2 85.2 97.3 | 90.8 120.2 129.5 145.3 | 117 93 90.5 88.8 | 52.1 55.9 66 74.5 | 93.3 88.1 92.8 101.5 | 29.8 26.6 26.6 30.7 | * | |
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
C. to the influence of cholesterol level in the rat bile (X ± SD)
| Time period | Cholesterol level/mmol * 10 -3 | |||||||
| 1 | 2 | 3 | 4 | X | SD | P1 | P2 | |
| After the administration administration in preceding 30 minutes after the administration in 30 minutes after the administration in 30-60 minute 60-90 minute | 0 0.1 0 0.1 | 0.4 0.1 0.1 0.1 | 0.1 0.1 0 0.1 | 0.3 0.1 0.1 0.1 | 0.2 0.1 0.1 0.1 | 0.2 0.0 0.1 0.0 | ||
P1: be t with data before the self administration and check resulting p value;
*Expression P＜0.05
P2: be t with normal saline group data and check resulting p value;
*Expression P＜0.01
Conclusion 10: in 30 minutes, the corresponding time period with the normal saline group is compared after the administration of parahydroxyacet-ophenone nicotinate, and there were significant differences for the content of bilirubin in the bile.Confirm that the parahydroxyacet-ophenone nicotinate has the litholytic effect of bile pigment calculus disease.
Embodiment 11:
According to following proportioning, with various carriers and parahydroxyacet-ophenone, adopt method preparation well known in the art to become tablet, every contains parahydroxyacet-ophenone 100mg of the present invention.
Composition 100mg tablet dosage
Parahydroxyacet-ophenone 100mg
Lactose-hydrate 125mg
Pulvis Talci 2.0mg
Magnesium stearate 2.0mg
Cross-linking sodium carboxymethyl cellulose 4.0mg.
Embodiment 12:
According to following proportioning, with various carriers and 3, the 5-resacetophenone adopts method well known in the art preparation to become tablet, every contain of the present invention 3,5-resacetophenone 100mg.
Composition 100mg tablet dosage
3,5-resacetophenone 100mg
Lactose-hydrate 125mg
Pulvis Talci 4.0mg
Magnesium stearate 2.0mg
Cross-linking sodium carboxymethyl cellulose 5.0mg.
Comparative Examples 1
Parahydroxyacet-ophenone etc. to the influence of rat bile secretory volume (
)
| Group | Number of animals (only) | Dosage (mg/kg) | The bile amount | |||
| Before the administration | Bile flow rate of change (%) after the administration | |||||
| 30min(ml) | 0～30min | 31～60min | 61～90min | |||
| Normal saline magnesium sulfate ursodesoxycholic acid parahydroxyacet-ophenone | 10 5 10 10 9 10 | 1ml/100g 100 150 50 150 300 | 0.436±0.063 0.34±0.021 0.372±0.067 0.436±0.065 0.313±0.079 0.468±0.113 | -5.22±7.11 -9.15±6.53 -22.1±18.6 11.2±5.8 81.1±69.5 * 76.5±84.7 | -4.57±6.17 -21.17±22.69 -67.3±14.0 -64.5±10.6 48.4±6.8 ** -48.3±21.3 | -7.71±3.15 -41.88±42.40 -48.9±7.26 -20.6±11.6 35.6±40.5 -40.2±29.5 |
*P＜0.05,
*Ratio before P＜0.01 and the administration
Comparative Examples 2
Parahydroxyacet-ophenone etc. to the influence of rat bile cholesterol level (
)
| Group | Number of animals (only) | Dosage (mg/kg) | Cholesterol (mmol/l) | |
| 30min before the administration | 60min after the administration | |||
| Normal saline ursodesoxycholic acid MgSO4 parahydroxyacet-ophenone | 10 10 10 10 9 10 | 1ml/100g 150 100 50 150 300 | 0.28±0.08 0.24±0.055 0.25±0.129 0.45±0.058 0.367±0.057 0.425±0.096 | 0.26±0.089 0.18±0.045 0.25±0.129 0.2±0.00 ** 0.10±0.00 ** 0.125±0.05 ** |
*Ratio before P＜0.01 and the administration
By Comparative Examples 1 and 2 as can be seen, high, medium and low three dosage of parahydroxyacet-ophenone can increase choleresis within a certain period of time, and do not increase choleresis behind the ursodesoxycholic acid, magnesium sulfate administration; And high, medium and low three dosage of parahydroxyacet-ophenone can reduce bile cholesterol and bilirubinic content again, and curative effect obviously is better than ursodesoxycholic acid.
Claims (5)
1. parahydroxyacet-ophenone and derivant thereof the application in the medicament of preparation treatment cholelithiasis.
2. application as claimed in claim 1, it is characterized in that, described derivant comprises parahydroxyacet-ophenone nicotinate, o-hydroxyacetophenone, acetanisole, m-hydroxy acetophenone, para aminoacetophenone, p-hydroxyphenyl butanone, 3,5-resacetophenone, p-nitroacetophenone and para hydroxybenzene pentanone.
3. application as claimed in claim 1 or 2 is characterized in that, parahydroxyacet-ophenone, m-hydroxy acetophenone and 3,5-resacetophenone are used to prepare function of gallbladder promoting litholytic medicament simultaneously.
4. application according to claim 1 is characterized in that, described cholelithiasis comprises cholesterol calculus disease and bile pigment calculus disease.
5. application according to claim 1 is characterized in that, parahydroxyacet-ophenone and derivant thereof and pharmaceutically acceptable carrier combinations are made any pharmaceutically acceptable dosage form.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100290175A CN101108173A (en) | 2006-07-17 | 2006-07-17 | Application of p-hydroxybenzene ethanone and its derivant in preparation of agentia treating gallstone disease |
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|---|---|---|---|
| CNA2006100290175A CN101108173A (en) | 2006-07-17 | 2006-07-17 | Application of p-hydroxybenzene ethanone and its derivant in preparation of agentia treating gallstone disease |
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| CN101108173A true CN101108173A (en) | 2008-01-23 |
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| CNA2006100290175A Pending CN101108173A (en) | 2006-07-17 | 2006-07-17 | Application of p-hydroxybenzene ethanone and its derivant in preparation of agentia treating gallstone disease |
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