CN1846706A - Application ammonium glycyrrhizunate in preparing medicine for inflammatory enteropathy - Google Patents
Application ammonium glycyrrhizunate in preparing medicine for inflammatory enteropathy Download PDFInfo
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- CN1846706A CN1846706A CN 200610018369 CN200610018369A CN1846706A CN 1846706 A CN1846706 A CN 1846706A CN 200610018369 CN200610018369 CN 200610018369 CN 200610018369 A CN200610018369 A CN 200610018369A CN 1846706 A CN1846706 A CN 1846706A
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- glycyrrhizinate
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- ammonium
- inflammatory bowel
- colon
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- 208000037903 inflammatory enteropathy Diseases 0.000 title abstract description 8
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Abstract
The present invention relates to the application of ammonium glycyrrhizunate in preparing medicine for inflammatory enteropathy. Ammonium glycyrrhizunate possesses the functions of inhibiting inflammation reaction and resisting oxidation, so that the medicine of ammonium glycyrrhizunate has high curative effect on inflammatory enteropathy, high safety and other advantages.
Description
Technical field
The present invention relates to the application of ammonium glycyrrhizinate (monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammoniums) in preparation treatment inflammatory bowel medicine.
Background technology
Inflammatory bowel (Inflammatory bowel disease IBD) is a kind of doctor of puzzlement and scientist's persistent ailment for many years, mainly comprise ulcerative colitis (ulcerative colitis, UC) and clone disease (Crohn ' s disease, CD) two kinds, the former is a kind of chronic nonspecific colitis disease, ulcer even canceration take place in weight person; pathological changes is mainly involved mucous membrane of colon and tela submucosa; the clinical diarrhoea that mainly shows as; stomachache and mucopurulent bloody stool; latter's pathological changes can be involved each position of gastrointestinal tract; be a kind of chronic granulation midship inflammation, be the ladder distribution, the clinical diarrhoea that mainly shows as; stomachache; fistula and General Symptoms in various degree.In the tenth European gastroenterology's annual meeting, Europe clone disease and the chairman RodMitchell of inflammatory bowel community point out, 1,000,000 IBD patients are arranged in Europe at present, and most of regional ulcerative colitis sickness rate is stable in western countries, is up to 10 examples/100,000 populations.And the sickness rate of clone disease raise 600% in 30 years in the past, and China's sickness rate also is tangible ascendant trend, and the risk that this disease can cause the patient that colorectal cancer takes place significantly raises, the serious threat human beings'health.Although research for many years, the mankind still can't cure this disease at present fully.
Medicine at present commonly used is: (1) aminosallcylic acid class: just start from the treatment of IBD as far back as the forties, effect is preferably sulfasalazine, but can cause the acute and chronic nephrotoxicity, and side reaction is many, and the long-term prescription patient is difficult to tolerance; (2) cortical steroid: nineteen fifty-five, Truelove uses meticortelone treatment UC and obtains good effect, so far cortical steroid is still for treating the principal agent of IBD, effective especially to control of seizures, centering severe patient and active stage case as the same, but significant side effects is arranged, be difficult for life-time service, easily recurrence after the drug withdrawal; (3) immunosuppressant: the clinical practice immunosuppressant starts from 1962, become at present a kind of important method of treatment IBD, common drug comprises purine medicaments, methotrexate and cyclosporin etc., but can produce serious adverse effects such as comprising allergy and inhibition hemopoietic.As seen, develop new safety, active drug, the mankind are finally captured this pertinacious disease, have great significance.The traditional natural drug of China is gone through thousands of year clinical, provides abundant medicine source for seeking active drug, and therefore from natural, the medicine of screening treatment inflammatory bowel is not only feasiblely in the conventional medicament, and can fill up the blank of China in this field.
Characteristics such as the Radix Glycyrrhizae diammonium is mainly treated the medicine of hepatopathy at present for China, have determined curative effect, and toxic and side effects is little.But the effect of ammonium glycyrrhizinate control inflammatory bowel (IBD) does not appear in the newspapers as yet.
Summary of the invention
The present invention is directed to the problems referred to above the application of ammonium glycyrrhizinate in preparation inflammatory enteropathy medicine is provided, the medicine with the inflammatory enteropathy of ammonium glycyrrhizinate preparation has determined curative effect, characteristics such as few side effects.
Technical scheme provided by the invention is: the application of ammonium glycyrrhizinate in preparation inflammatory enteropathy medicine.
Per os of the present invention and intravenous injection give ammonium glycyrrhizinate, once a day, after 10 days, struvite mice colon organ index, colon Damage coefficient are obviously reduced, colon MPO is active obviously to raise, lipid peroxidation product MDA obviously reduces, and SOD activity and GSH content obviously raise, and shows that ammonium glycyrrhizinate can treat inflammatory bowel.
Per os of the present invention gives monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammonium 14mg/kg, and once a day, after 10 days, the colon coefficient descends 14.3%, 39.4%, 14.9% respectively; Inflammation scoring rank descends 1.5 times, 1.73 times, 1.5 times respectively; The MPO activity raises 1.25 times, 1.20 times, 0.20 times respectively.
The present invention gives diammonium glycyrhetate 14mg/kg through injection, and once a day, after 10 days, colon coefficient decline 45.7%, inflammation scoring rank descend 2.75 times, and MPO is active to raise 1.67 times.
Description of drawings
Accompanying drawing is handled 10 days protective effect figure to the damage of inflammatory bowel mice colon for ammonium glycyrrhizinate of the present invention.
The specific embodiment
The present invention is described further by following examples
Characteristics such as Chinese medicine and pharmacy often can play a significant role aspect chronic, the difficult diseases of treatment, and good effect, particularly toxic and side effects are little.The present invention selects the medicine of ammonium glycyrrhizinate as inflammatory enteropathy, by setting up the animal model of inflammatory bowel, inquires into the influence and the mechanism of drug action of ammonium glycyrrhizinate salt pair inflammatory bowel.Be intended to select a kind of inflammatory enteropathy determined curative effect, medicine that toxicity is little.
The present invention is by setting up effect and the mechanism that technology such as inflammatory bowel animal model have disclosed ammonium glycyrrhizinate salt pair inflammatory bowel.
Materials and methods
Medicine and reagent monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammoniums are provided by Shenzhen money good fortune Pharmaceutical; Beautiful Sarah's Qin's sustained-release granular formulation (Etiasa) is provided by group of Ethypharm SA; The MPO detection kit, building up bio-engineering research by Nanjing is provided.Bovine serum albumin, DTNB and GSH standard substance provide by sigma company.Reagent such as TBA, pyrogallol, acetic acid, ether are commercially available analytical reagent.
45 of the ripe male mouse of kunming of animal health, body weight 18～22g, male and female half and half are provided production licence number by Wuhan University's Experimental Animal Center: SCXK (Hubei Province) 2003-2004.Mouse feed is purchased the Experimental Animal Center in Wuhan University.
Instrument: TG328A type analysis balance, ultraviolet spectrophotometer, high speed homogenizer etc.
Experimental technique
Animal grouping and processing: kunming mice random packet: normal control group, model group, Etiasa positive drug matched group, oral group of monoammonium glycyrrhizinate, oral group of diammonium glycyrrhizinate, oral group of glycyrrhizic acid three ammoniums, diammonium glycyrrhizinate injection group.Etiasa group mice coloclysis gives Etiasa 600mg/Kg, once-a-day; Oral group of mice of ammonium glycyrrhizinate per os respectively gives monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammonium 14mg/Kg, once-a-day; The injection of diammonium glycyrrhizinate injection group mouse peritoneal gives diammonium glycyrrhizinate 14mg/Kg, once-a-day; Normal control group and model group its mouse oral give the normal saline of equivalent, once-a-day.After the administration 7 days, except that the normal control group, all the other are respectively organized the acetic acid stimulation and make colitis model, mice fasting after administration on the 6th, after administration next day, ether inhalation anesthesia injects acetic acid for the mice rectum with polyethylene tube, clear the enteral stool before the injection earlier, polyethylene tube is inserted the about 1.5cm of mice anus, inject the acetic acid of 0.1ml6%, open normal saline flushing twice with waiting behind the 1min, allow animal keep lying low, revive naturally.Normal control group rectum injects isopyknic normal saline.Each is organized mice and continues medication to the 10th day, 24h after the last administration, and the cervical vertebra dislocation is put to death, and dissects on ice, gets complete section colon, weighs, and calculates the colon organ index, carries out colitis (CMDI) scoring.Get colon and make 5% homogenate, for detecting MPO, MDA, SOD, GSH with the Tris buffer.
Detect index
Colon damage index (CMDI): get complete section colon, cut off enteric cavity along mesentery, perusal abdominal adhesions and colonic ulcer, congested situation are pressed table 1 standards of grading (CMDI) scoring.
Myeloperoxidase (MPO) (MPO) accurately takes by weighing tissue weight, and volume ratio is 1: 19 adding Tris buffering homogenate by weight, and multigelation behind the high-speed homogenization is made 5% intestinal homogenate, and the Lowry method detects protein content.Press the MPO detection kit and detect the MPO activity.
Lipid peroxidase (MDA) adopts the TBA colorimetry to detect MDA content in the intestinal homogenate.
Superoxide dismutase (SOD) adopts pyrogallol method to detect SOD vigor in the intestinal homogenate.
Glutathion (GSH) is pressed the GSH detection kit, detects the content of GSH in the intestinal homogenate.
Table 1. colon damage index (CMDI) standards of grading
| General form | Scoring |
| Abdominal adhesions: | |
| No adhesion | 0 |
| Slight adhesion | 1 |
| Severe adhesion | 2 |
| Colonic ulcer and inflammation: | |
| Non Apparent Abnormality | 0 |
| Colon hyperemia, no ulcer | 1 |
| Hyperemia, no ulcer, intestinal wall obviously thickens | 2 |
| Ulcer 1 place thickens (surface is downright bad) without hyperemia or intestinal wall | 3 |
| Intestinal wall has the petechia | 4 |
| Ulcer 1 place, the companion is congested, inflammation | 5 |
| Ulcer 2 places, the companion is congested, inflammation | 6 |
| More than ulcer 2 places | 7 |
| The place of boring a hole | 8 |
| Perforation is more than 1 place | 9 |
| Animal dead | 10 |
Two marks add up to PTS.
Experimental result
1. the protective effect of ammonium glycyrrhizinate salt pair inflammatory bowel mice colon damage
By accompanying drawing 1 as seen, but all mice colon damages that cause of significant protection acetic acid of ammonium glycyrrhizinate per os and drug administration by injection.The visible severe adhesion of model group, ulcer be more than more than 2 places, scoring rank 7.5; The visible place's ulcer of positive controls is not seen adhesion, and is slight red and swollen, 2.5 grades of scoring ranks; Oral group of monoammonium glycyrrhizinate, oral group of diammonium glycyrrhizinate, oral group of glycyrrhizic acid three ammoniums, diammonium glycyrrhizinate injection group scoring rank are respectively 3.0 grades, 2.75 grades, 3.0 grades, 2.0 grades; wherein diammonium glycyrrhizinate injection group effect is best, shows that ammonium glycyrrhizinate has significant protective effect to inflammatory bowel.The results are shown in accompanying drawing.
2. ammonium glycyrrhizinate salt pair inflammatory bowel mice colon organ coefficient, Damage coefficient, the active influence of MPO
As seen obvious the reducing inflammation property enteropathy mice colon edema of ammonium glycyrrhizinate, single ammonium group, diammonium group, three ammonium groups, diammonium injection group intestines and internal organs of the body device coefficient descend 14.3%, 39.4%, 14.9%, 45.7% respectively, compare with 16.7% of positive control drug, effect is better; Inflammation scoring rank reduces by 1.5 times, 1.73 times, 1.5 times, 2.75 times respectively, and is similar to positive control drug; Can make the MPO activity raise 1.25 times, 1.20 times, 0.20 times, 1.67 times respectively, raise than positive control drug 0.47 times to compare effect more remarkable, further shows the beneficial effect of ammonium glycyrrhizinate salt pair inflammatory bowel, the results are shown in Table 2.
Table .2 ammonium glycyrrhizinate salt pair inflammatory bowel mice colon organ coefficient, inflammation scoring, the active influence of MPO
(x±s，n＝10)
| Group | Colon coefficient (g/100g) | Inflammation scoring (rank) | MPO (U/mg.pro.) |
| The normal control group | 0.73±0.03 | 0±0 | 3.37±0.31 |
| Model group | 1.75±0.35** | 7.50±0.7** | 1.33±0.83** |
| Oral group of monoammonium glycyrrhizinate | 1.50±0.03 ▲ | 3.0±0.31 ▲▲ | 2.99±0.26 ▲▲ |
| Oral group of diammonium glycyrrhizinate | 1.06±0.31 ▲▲ | 2.75±0.18 ▲▲ | 2.93±0.26 ▲▲ |
| Oral group of glycyrrhizic acid three ammoniums | 1.49±0.08 ▲▲ | 3.0±0.21 ▲▲ | 1.59±0.94 |
| Diammonium glycyrrhizinate injection group | 0.97±0.18 ▲▲ | 2.0±0.20 ▲▲ | 3.55±0.45 ▲▲ |
| Positive controls | 1.50±0.03 ▲▲ | 2.5±0.71 ▲▲ | 1.95±0.15 ▲▲ |
Compare * * P＜0.01 with normal group; Compare a piece of writing with model group
▲P＜0.05
▲ ▲P＜0.01
3. ammonium glycyrrhizinate salt pair inflammatory bowel mice colon MDA, 6SH content and the active influence of SOD
Compare with normal group, the content of MDA significantly raises (P＜0.01) in the model group colon, and GSH content and SOD are active significantly to descend; Compare with model group, each ammonium salt of Radix Glycyrrhizae all can effectively improve These parameters, and than the positive control drug better effects if, the results are shown in Table 3.
Table 3 ammonium glycyrrhizinate salt pair inflammatory bowel mice colon MDA, GSH content and the active influence of SOD (x ± s, n=10)
| Group | MDA(nmol/mgpro.) | GSH(mg/mgpro.) | SOD(U/mgpro.) |
| The normal control group | 10.58±2.74 | 0.58±0.12 | 707±105 |
| Model group | 26.2±5.5** | 0.16±0.09** | 309±68** |
| Oral group of monoammonium glycyrrhizinate | 16.14±5.81 ▲▲ | 0.32±0.12 ▲▲ | 412±112 ▲▲ |
| Oral group of diammonium glycyrrhizinate | 8.32±5.04 ▲▲ | 0.49±0.14 ▲▲ | 505±132 ▲▲ |
| Oral group of glycyrrhizic acid three ammoniums | 16.88±5.97 ▲▲ | 0.26±0.09 ▲▲ | 368±79 ▲ |
| Diammonium glycyrrhizinate injection group | 7.85±3.55 ▲▲ | 0.27±0.13 ▲▲ | 533±101 ▲▲ |
| Positive controls | 14.29±1.77 ▲▲ | 0.37±0.03 ▲▲ | 338±15 ▲ |
Compare * * P＜0.01 with normal group; Compare with model group
▲P＜0.05,
▲ ▲P＜0.01
Experiment conclusion
Ammonium glycyrrhizinate can effectively be protected the damage of inflammatory bowel mice colon, and its mechanism may organize oxidation resistance relevant with enhancing, compares with the medicine-Etiasa of mainly treating inflammatory bowel at present, and curative effect is more remarkable.The clinical treatment that is mainly used in hepatopathy of diammonium glycyrrhizinate, long-term clinical application show that safety range is big, and toxic and side effects is little, and the systemic side effects of no hormones does not have the immunosuppressive action of immunosuppressant yet.The present invention uses dosage that ammonium glycyrrhizinate salts for treating inflammatory bowel adopts in clinical usual dose range, shows that ammonium glycyrrhizinate is not only effective in the inflammatory bowel treatment, and safety, side effect are little.
Claims (2)
1. the application of ammonium glycyrrhizinate in preparation treatment inflammatory bowel medicine.
2. application according to claim 1 is characterized in that: described ammonium glycyrrhizinate is monoammonium glycyrrhizinate, diammonium glycyrrhizinate or glycyrrhizic acid three ammoniums.
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| CNB2006100183690A CN100391466C (en) | 2006-02-17 | 2006-02-17 | Application ammonium glycyrrhizunate in preparing medicine for inflammatory enteropathy |
| US12/374,289 US20100087385A1 (en) | 2006-02-17 | 2006-08-09 | Application of glycyrrhizic acid and its breakdown product glycyrrhetinic acid for the manufacture of a medicament for the treatment of inflammatory bowel disease |
| CA002657674A CA2657674A1 (en) | 2006-02-17 | 2006-08-09 | The application of glycyrrhizic acid and its breakdown product glycyrrhetinic acid for the manufacture of a medicament for the treatment of inflammatory bowel disease |
| PCT/CN2006/002014 WO2007093090A1 (en) | 2006-02-17 | 2006-08-09 | The application of glycyrrhizic acid and its breakdown product glycyrrhetinic acid for the manufacture of a medicament for the treatment of inflammatory bowel disease |
| EP06775332A EP2067476A4 (en) | 2006-02-17 | 2006-08-09 | The application of glycyrrhizic acid and its breakdown product glycyrrhetinic acid for the manufacture of a medicament for the treatment of inflammatory bowel disease |
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| CN113197904A (en) * | 2021-03-31 | 2021-08-03 | 和田维吾尔药业股份有限公司 | Traditional Chinese medicine active ingredient composition for treating cough and preparation method thereof |
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| CN1109044C (en) * | 2000-12-21 | 2003-05-21 | 宁夏大学 | Potassium glycyrrhetate and its preparing process and use |
| CN1220496C (en) * | 2003-08-21 | 2005-09-28 | 武汉同药药业有限公司 | Bougie for treating virus hepatitis and preparing method thereof |
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| CN107308177A (en) * | 2017-07-19 | 2017-11-03 | 辽宁华润本溪三药有限公司 | A kind of pharmaceutical composition of antalgic and inflammation relieving and preparation method thereof and purposes |
| CN107308177B (en) * | 2017-07-19 | 2022-05-17 | 辽宁华润本溪三药有限公司 | Analgesic and anti-inflammatory pharmaceutical composition and preparation method and application thereof |
| CN113197904A (en) * | 2021-03-31 | 2021-08-03 | 和田维吾尔药业股份有限公司 | Traditional Chinese medicine active ingredient composition for treating cough and preparation method thereof |
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