CN102085252A - Pharmaceutical composition for treating ulcerative colitis and colon-targeted micro-pill preparation thereof - Google Patents
Pharmaceutical composition for treating ulcerative colitis and colon-targeted micro-pill preparation thereof Download PDFInfo
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Abstract
The invention provides a pharmaceutical composition for treating ulcerative colitis and a micro-pill preparation with colon-targeted properties thereof, relating to the technical field of medicines. The pharmaceutical composition takes bighead atractylodes rhizome as a monarch medicine, coptis as a ministerial medicine and radix sileris as an adjuvant medicine, and is prepared from the following components in concrete parts by weight: 30-60 parts of bighead atractylodes rhizome, 30-45 parts of coptis and 30-60 parts of radix sileris. The extracts of the bighead atractylodes rhizome, coptis and radix sileris are respectively prepared into stomach-soluble micro-pills and intestine-soluble micro-pills, and then, the stomach-soluble micro-pills and the intestine-soluble micro-pills are proportionally mixed to prepare an oral colon-targeted administration system of micro-pills prepared from bighead atractylodes rhizome and coptis, thereby realizing the purpose of colon-targeted administration and better exerting the effect of the composition. The pharmaceutical composition provided by the invention and the oral colon-targeted administration system of micro-pills prepared from bighead atractylodes rhizome and coptis have the dual-treatment characteristics of treating both principal and secondary aspects of diseases and simultaneously considering overall and local aspects, and are safe and convenient in oral administration and low is cost. The animal experiment shows that the pharmaceutical composition and the oral colon-targeted administration system have an obvious treatment effect on ulcerative colitis (the treatment effect is close to or even superior to the treatment effect of a positive control medicine salicylazosulfapyridine (SASP)), and have small side effects, thus the pharmaceutical composition and the oral colon-targeted administration system can be used for preparing medicines for treating ulcerative colitis.
Description
Technical field
The present invention relates to medical technical field, is a kind of pellet preparations for the treatment of the Chinese medicine composition of ulcerative colitis and having segmented intestine targeted characteristic.
Background technology
(Ulcerative Colitis UC) claims chronic non-specific ulcerative colitis again to ulcerative colitis, is a kind of common autoimmune disease.Diarrhoea, mucopurulent bloody stool, stomachache or tenesmus with outbreak repeatedly are main clinic symptoms, its course of disease delay is difficult, reach the several months to many decades, 80% patient can show effect repeatedly, the state of an illness constantly increases the weight of, patient's canceration rate of 30 years courses of disease can be up to 40%, so be defined as one of 14 kinds of refractory diseases by The World Health Organization (WHO).Ulcerative colitis can be sent out in any age, but with 20～40 years old for seeing more, the sickness rate of China is about 5-40/10 ten thousand.Nervous and Mental Factors, overtired, improper diet, infection are the main outbreak inducements of ulcerative colitis.Along with the change of the increasing the weight of of the quickening of modern society's rhythm of life, survival pressure, dietary structure, this sick incidence rate is the trend that rises year by year.According to statistics, the sickness rate of nearly 10 years China's ulcerative colitiss has become one of common clinical and frequently-occurring disease than having increased by 10 times the fifties in last century.
At present, the common drug of treatment ulcerative colitis has: adrenocortical hormones, as dexamethasone; The aminosallcylic acid class is as sulfasalazine, 5-aminosalicylic acid; Immunosuppressant, as ciclosporin, or the like.Though said medicine has certain therapeutic effect, drug target is single, can only relief of symptoms, so only be suitable for the short-term medication; If long term administration also can cause multiple side effect such as serious gastrointestinal reaction, hemopoietic function of bone marrow inhibition, allergy.
For the treatment of ulcerative colitis, all there is certain deficiency in traditional oral and rectally.After conventional tablet, capsule were oral, medicine was promptly absorbed by whole body before arriving colon or degrades; Behind external therapy of Chinese herb such as suppository, the enema preparation rectally, medicine only is confined to rectum and descending colon, can't arrive main ulcer focal zone such as transverse colon, ascending colon, has influenced the performance of curative effect of medication.The oral colon-target drug-supplying system is by appropriate formulations technology, make and avoid after the medicine oral administration discharging, discharge behind the ileocecum and a kind of novel targeted drug-supplying system of performance part or whole body therapeutic effect but be transported at stomach, duodenum, jejunum and ileum front end.Its technology of preparing has multiple, comprises pH dependence, enzyme dependence and time, pressure control etc.Wherein, pH dependent form colon targeting drug administration system has clearer and more definite release mechanism and preparation method, stability of formulation and favorable reproducibility, and medicine does not discharge under one's belt, and only the location is released to distal small intestine and colon.Its principle is: the gastrointestinal tract pH value increases progressively (stomach 0.9～1.5, small intestinal 6.5～7, colon 6.8～7.5) gradually, and the strange Eudragit L/S of macromolecular material acrylic resin You Te respectively only＞pH 6.0 and＞dissolve in pH 7.0 environment, therefore, can be by mixing and regulate both consumptions, obtain the only dissolved material of ability under the colon pH value, be used for drug coating.Using maximum enteric coated preparation at present is coated micropill and coated tablet.Compare with coated tablet, micropill is dispersed into up to a hundred units with the medicine of a dosage, and the breakage of single micropill coating membrane only makes small amount of drug dash forward and releases, and can not cause whole pellet release irregular; Micropill is not subject to the gastric emptying rate influence, can be uniformly distributed in intestinal; The micropill good fluidity is suitable for the industrialization packing, so coated micropill has curative effect and technology repeatability preferably, the segmented intestine targeted location that more can guarantee the ulcerative colitis medicine than coated tablet.(see for details: [1] Zheng Jiaju, Shi Xiaohua, Guo Zhirong. the epidemiological study method and the progress of inflammatory bowel. CHINESE JOURNAL OF INTERNAL MEDICINE, 2009,48 (6): 522-523; [2] Yang L, Chu JS, Fix JA.Colon-specific drug delivery:new approachesand in vitro/in vivo evaluation.Int J Pharm, 2002,235 (1-2): 1[3] Ulrich K, Matthias S.Topicaldelivery of therapeutic agents in the treatment of inflammatory bowel disease.Adv Drug DeliverRev, 2005,57 (2): 267; [4] Sheng Yanmei, Xie Xingliang, Yang Ming studies medical Leader, 2008,27 (3): 258-261 etc. the Chinese medicine new compound peaceful prescription of intestinal of healing; [5] Yang Ming, Feng Yi, Xu Desheng, etc. the one Chinese medicine modernization of technical Lines for Advanced TCM Drug Release System World Science technology, 2006,8 (5): 10-15).
Chinese medicine is unique advantage aspect the chronic gastroenteropathy that comprehensively causes of treatment multi-pathogenesis, can realize antiinflammatory, analgesia by the multipath effect, and the great attention to whole balance.Therefore, searching and development of new medicament for resisting ulcerative colitis have good development potentiality and important scientific value from Chinese medicine.
Summary of the invention
The invention provides a kind of pellet preparations for the treatment of the Chinese medicine composition of ulcerative colitis and having segmented intestine targeted characteristic.
The present invention has invigorating the spleen and benefiting QI, dehumidifying anti-diarrhea effect according to the Chinese crude drug Rhizoma Atractylodis Macrocephalae; Rhizoma Coptidis has heat clearing and damp drying, thick intestinal ends sharp effect; The Radix Saposhnikoviae nature and flavor are hot fragrant, the hot stagnation of liver-QI of loosing, and the perfume (or spice) stomach of being amusing, it has the effect of dampness removing and diarrhea-relieving; With the Rhizoma Atractylodis Macrocephalae is monarch, and Rhizoma Coptidis is a minister, and Radix Saposhnikoviae is assistant, forms pharmaceutical composition, and their weight proportion is:
30～60 parts of the Rhizoma Atractylodis Macrocephalaes;
30～45 parts of Rhizoma Coptidis;
30～60 parts of Radix Saposhnikoviaes.
Above-mentioned composition is decocted into oral liquid routinely to get final product.
Further, their extracts are separately made respectively to be mixed in proportion behind gastric solubleness micropill and the enteric coated micropill make Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill oral colon-target drug-supplying system, then can realize the purpose of conlon targeting target administration, can bring into play the effect of this pharmaceutical composition better.The weight proportion of each extract is in the Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill:
24～36 parts of Rhizoma Atractylodis Macrocephalae extract Rhizoma Atractylodis Macrocephalae volatile oils
3～9 parts of Rhizoma Coptidis extract berberine
9～27 parts of Radix Saposhnikoviae extracts.
Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis microsphere and its preparation of the present invention is as follows:
1. preparation Rhizoma Atractylodis Macrocephalae volatile oil
Adopt the volatile oil composition in supercritical CO 2 abstraction technique (SFE-CO2) the extraction medical material, that is: with Rhizoma Atractylodis Macrocephalae pulverizing medicinal materials to coarse powder, drop in the supercritical extraction reactor, extraction temperature is 50 ℃, extracting pressure is 35MPa, and the CO2 flow is 3Lh-1, and the extraction time is 3h, collect extraction product, get Rhizoma Atractylodis Macrocephalae volatile oil;
2. preparation Radix Saposhnikoviae extract
Adopt ultrasonic extraction to prepare Radix Saposhnikoviae extract, that is:
The Radix Saposhnikoviae medical material is crushed to coarse powder, puts in the ultrasonic extraction device, add the ethanol water of 6 times of weight 75%, supersound extraction 2 times, each 30min, the extracting solution filtration merges, and decompression recycling ethanol also to doing, gets Radix Saposhnikoviae extract;
3. the effective ingredient of Rhizoma Coptidis is alkaloids substances such as berberine, adopts commercially available berberine to get final product;
4. prepare Rhizoma Atractylodis Macrocephalae volatile oil cyclodextrin clathrate and gastric solubleness micropill
1) preparation clathrate
The 10g Rhizoma Atractylodis Macrocephalae volatile oil is made into 50% Rhizoma Atractylodis Macrocephalae volatile oil solution with dehydrated alcohol, get beta-schardinger dextrin-30g, after adding 4 times of weight distilled water and grinding well, slowly add 50% Rhizoma Atractylodis Macrocephalae volatile oil solution of above-mentioned preparation, be ground to into pasty state, sucking filtration gets clathrate, under 30～60 ℃ clathrate is washed 3 times with petroleum ether, each 100mL, 40 ℃ of vacuum drying 5h must do clathrate, and are standby.
2) preparation gastric solubleness micropill
With the strange Eudragit RS100 of You Te is coating material, adopts low temperature to extrude round as a ball granulator and prepares Rhizoma Atractylodis Macrocephalae volatile oil beta-CD inclusion micropill, i.e. gastric solubleness micropill;
5. prepare Rhizoma Coptidis, Radix Saposhnikoviae extract enteric coated micropill
1) preparation medicine carrying micropill
With the Nonpareil grain is celphere, and HPMC-E15 is a binding agent, the berberine 2g and the Radix Saposhnikoviae extract 6g that learn from else's experience and pulverized 100 mesh sieves, and spray suspension method medicine-feeding at the bottom of the fluid bed, 60 ℃ of dry 6h promptly get the medicine carrying micropill;
2) preparation enteric coated micropill
Get 20g medicine carrying micropill and place fluid bed,, make weightening finish 2% (w/w) with HPMC solution coating; Then with pH sensitive material Eudragit L30D-55: Eudragit S100=2: 1 mixes, enteric-coating layer; Wrap one deck clothing film as the contagion gown layer by weightening finish 2% (w/w) with HPMC more at last; 60 ℃ of heat treatment 2h make enteric coated-pellet;
6. prepare Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill
Divide the capsule of packing into by proportioning after with the gastric solubleness micropill of above-mentioned preparation and enteric coated micropill mixing, be Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations of the present invention.
Confirm that through zoopery pharmaceutical composition of the present invention or Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations all have notable therapeutic effect to the chronic ulcerative colitis rat model.
Pharmaceutical composition of the present invention or Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations preparation method are simple, with low cost, can be used for preparing the medicine for the treatment of ulcerative colitis.
Advantage of the present invention is as follows:
1. pharmaceutical composition of the present invention can invigorating the spleen and benefiting QI, improves gastrointestinal function and promotes absorption of nutrient ingredients, effectively adjusts whole immunologic function; Again can be antibiotic, antiinflammatory, hemostasis, to the damage of anti-ulcerative colitis local inflammation, can play the dual characteristic that treating both the principal and secondary aspects of a disease, whole part are taken into account, for light moderate colitis based on watery stool, effective relief of symptoms, the body constitution that can regulate the patient again has good effect.
2. Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations of the present invention has embodied the technical characterictic of " two steps discharged ", be oral after, stomach inner pH value is lower, the at first disintegrate under the stomach sour environment of Rhizoma Atractylodis Macrocephalae gastric solubleness micropill, and effective ingredient such as atractylodes lactone play the effect of setting upright spleen invigorating, QI invigorating antidiarrheal at gastric; The enteric coated micropill of Rhizoma Coptidis, Radix Saposhnikoviae extract then entering the higher colon position release of pH value, has played the effect of segmented intestine targeted directional drug release, effects such as at this, the local performance of compositions such as berberine and Radix Saposhnikoviae chromone is antibiotic, antiinflammatory, hemostasis." two steps discharged " embodied Chinese medicine ulcerative colitis treating both the principal and secondary aspects of a disease, the whole and local treatment theory that combines.
3. pharmaceutical composition of the present invention or Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations oral administration, not only convenient but also safety has been avoided multiple side effect such as drug-induced serious gastrointestinal reaction such as hormones, aminosallcylic acid class or immunosuppressant, hemopoietic function of bone marrow inhibition, allergy.
The specific embodiment
Now in conjunction with the embodiments the present invention is described in detail.
Embodiment 1 preparation pharmaceutical composition of the present invention
1) by weight getting respectively: 30 parts of the Rhizoma Atractylodis Macrocephalaes, 30 parts of Rhizoma Coptidis, 30 parts of Radix Saposhnikoviaes decoct into the oral administration solution packing routinely and get final product.
2) by weight getting respectively: 45 parts of the Rhizoma Atractylodis Macrocephalaes, 40 parts of Rhizoma Coptidis, 45 parts of Radix Saposhnikoviaes decoct into the oral administration solution packing routinely and get final product.
3) by weight getting respectively: 55 parts of the Rhizoma Atractylodis Macrocephalaes, 40 parts of Rhizoma Coptidis, 60 parts of Radix Saposhnikoviaes decoct into the oral administration solution packing routinely and get final product.
A kind of Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations of embodiment 2 preparations
1. preparation Rhizoma Atractylodis Macrocephalae volatile oil
Get Rhizoma Atractylodis Macrocephalae medical material 600g, be crushed to coarse powder, drop in the supercritical extraction reactor, extraction temperature is 50 ℃, and extracting pressure is 35MPa, CO
2Flow is 3Lh
-1, the extraction time is 3h, collects extraction product, gets Rhizoma Atractylodis Macrocephalae volatile oil 29.7g;
2. preparation Radix Saposhnikoviae extract
Get Radix Saposhnikoviae medical material 600g, be crushed to coarse powder, put in the ultrasonic extraction device, add 75% ethanol water of 6 times of weight, supersound extraction 2 times, each 30min, the extracting solution filtration merges, and decompression recycling ethanol also to doing, gets Radix Saposhnikoviae extract 17.4g;
3. prepare the Rhizoma Atractylodis Macrocephalae volatile oil cyclodextrin clathrate
Get beta-schardinger dextrin-90g, after adding 4 times of weight distilled water and grinding well, slowly add 29.6g Rhizoma Atractylodis Macrocephalae volatile oil (be made in advance with dehydrated alcohol 50% solution), be ground to into pasty state, sucking filtration, get clathrate, about 50 ℃, clathrate is washed 3 times each 300mL, 40 ℃ of vacuum drying 5h with petroleum ether, must do clathrate, standby;
4. prepare the gastric solubleness micropill
With the strange Eudragit RS100 of You Te (German goldschmidt chemical corporation) is coating material, and high speed homogenize 20min adopts low temperature to extrude round as a ball granulator routinely and prepares Rhizoma Atractylodis Macrocephalae volatile oil beta-CD inclusion micropill, and this is a Rhizoma Atractylodis Macrocephalae volatile oil gastric solubleness micropill;
5. prepare Rhizoma Coptidis, Radix Saposhnikoviae extract medicine carrying micropill
With the Nonpareil grain is celphere (German Romo Co.,Ltd), HPMC-E15 (U.S. international special product company) is a binding agent, get berberine (Changzhou Yabang Pharmaceutical Co., Ltd) and 17.4g Radix Saposhnikoviae extract that 5.8g crosses 100 mesh sieves after crushed, in berberine: the ratio of Radix Saposhnikoviae extract=1: 3, spray suspension method medicine-feeding at the bottom of the fluid bed, 60 ℃ of dry 6h promptly get the medicine carrying micropill;
6. prepare Rhizoma Coptidis, Radix Saposhnikoviae extract enteric coated micropill
Get 60g medicine carrying micropill and place fluid bed,, make weightening finish 2% (w/w) with HPMC (U.S. international special product company) solution coating; Then with pH sensitive material Eudragit L30D-55: Eudragit S100=2: 1 (German goldschmidt chemical corporation) mixed enteric-coating layer; Wrap one deck clothing film as the contagion gown layer by weightening finish 2% (w/w) with HPMC more at last, 60 ℃ of heat treatment 2h make enteric coated-pellet;
7. prepare Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill
In the gastric solubleness micropill: the ratio of enteric coated micropill=1: 1 is divided the capsule of packing into after with the gastric solubleness micropill of above-mentioned preparation and enteric coated micropill mixing, is Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations of the present invention.
The weight proportion of each composition of this Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations is:
Rhizoma Atractylodis Macrocephalae extract: 29.7 parts,
Berberine: 5.8 parts,
Radix Saposhnikoviae extract: 17.4 parts.
A kind of Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations of embodiment 3 preparations
The weight proportion of each composition of this Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis pellet preparations is:
Rhizoma Atractylodis Macrocephalae extract: 36 parts,
Berberine: 7 parts,
Radix Saposhnikoviae extract: 21 parts.
Preparation method is with embodiment 2.
Evaluating drug effect:
Select for use the ulcerative colitis rat model to carry out the evaluating drug effect of medicine of the present invention.
1. laboratory animal
Healthy male SD rat, the cleaning level, body weight 180g～200g purchases the Shanghai Experimental Animal Center in the Chinese Academy of Sciences, the animal quality certification number: [SYXK (Shanghai) 2002-0026], ad lib and drinking-water.
2. reagent
Pharmaceutical composition of the present invention (being called for short BHF) is by (1) preparation of embodiment 1;
TNBS purchases the company in Sigma, is 5% (w/v) aqueous solution, lot number (71K5009);
Sulfasalazine (SASP) is produced for Shanghai Sunve Pharmaceutical Co., Ltd., lot number (200904C28), scrape off the outer coating of SASP tablet gently with blade after, pulverized 80 mesh sieves, take by weighing a certain amount of powder, adding distilled water, to be made into the SASP suspension of 0.1g/ml standby.
3. instrument and equipment
UV-2100 type ultraviolet-uisible spectrophotometer (day island proper Tianjin company); TGL-16G high speed tabletop refrigerated centrifuge (Anting Scientific Instrument Factory, Shanghai); Rotary Evaporators (Shensheng Science ﹠ Tech. Co., Ltd., Shanghai); W201B type thermostat water bath (Shensheng Science ﹠ Tech. Co., Ltd., Shanghai); XW-80A vortex mixer (the special Analytical Instrument Co., Ltd of Shanghai fine jade).
4. the foundation of animal grouping and ulcerative colitis rat model
Get 60 of male SD rats, be divided into 6 groups at random, every group 10, be the normal control group, model control group, the high, medium and low dosage group of BHF extracting solution, dosage is followed successively by by body weight: high dose group 15g/kg (expression per kilogram of body weight 15g mixing crude drug amount, down together), middle dosage group 10g/kg, low dose group 5g/kg; The positive contrast medicine of SASP, positive controls SASP dosage is 0.3g/kg, after water 24h is can't help in fasting, except that the normal control group, all the other respectively organize the rat modeling, the sodium pentobarbital of lumbar injection 2%, after making the slight anesthesia of rat, the latex tubing per anum of diameter 2mm is inserted in the rat body approximately 8cm place gently, TNBS is dissolved in 50% ethanol water with the modeling agent, with TNBS solution with in the disposable enteric cavity that is injected into rat of syringe, TNBS dosage is mentioned the afterbody of rat for by body weight 125mg/kg, is inverted 30 seconds, prevent modeling agent seepage, make the modeling agent fully infiltrate through the enteric cavity of rat.
5. medication and evaluation index
Beginning administration in 6 hours after the modeling, once a day, successive administration 7 days.High, medium and low dosage group of BHF and positive controls difference gastric infusion 2ml every day; Normal control group and model control group rat are irritated the normal saline of stomach with volume every day.Observe BHF respectively to ulcerative colitis rat model body weight change, the influence of suffering from diarrhoea, having blood in stool.
Each organized the rat administration after 7 days, injected excessive pentobarbital sodium and caused death, and cut rat abdomen open, observed intestinal and changed substantially.To take out apart from the long latter end colon of anus 10cm, along the mesentery longitudinal incision, with the ice normal saline flushing, with claiming quality behind the filter paper suck dry moisture.Mucosa towards last expansion, is observed mucosa injury and marked according to the standards of grading of Wallace and Keenan1990: 0 minute, NIP and ulcer; 1 minute, contrafluxion but do not have ulcer; 2 minutes, ulcer but do not have hyperemia; 3 minutes, a place's ulcer and an inflammation; 4 minutes, above ulcer in two places or two places and inflammation; 5 minutes, ulcer extended beyond 2cm.
Get the anus 8cm intestinal segment that makes progress and roll, place 10% neutral formalin liquid fixing, use paraffin embedding, the thick holostrome section of row 4 μ m, H-E dyeing is observed colon's pathology variation in microscopically.
6. experimental result
(1) the BHF extracting solution is to the influence of ulcerative colitis rat model body weight change
Rats in normal control group was owing to fasting 1 day, and body weight returns to initial body constitution amount gradually after alleviating slightly, and increases to 115% of former body weight gradually.The body weight of model control group rat descends rapidly after modeling, dropped to 86% of former body weight at the 2nd day, be lower than normal rats body weight (P＜0.05) at 1～7 day endosome representation work, it is very fast that middle and high dosage group of BHF and positive controls rat body weight recover, returned to original weight gradually in 5～6 days, and the body weight of rat is significantly higher than rat model (P＜0.05) in 1～7 day.
(2) BHF is to the ulcerative colitis rat model diarrhoea and the influence of having blood in stool
Each is organized rat and diarrhoea took place in 1,3,5,7 day sees Table 1 with the rat number of having blood in stool.Diarrhoea does not take place and has blood in stool in rats in normal control group, and it is matt in a jumble that the rat after the TNBS modeling shows as hair color, and the look asthenia is dispirited, has all occurred diarrhoea in various degree at the 1st day and has had blood in stool.But with increasing of administration natural law, the symptom of the middle and high dosage group of BHF of the present invention significantly is lighter than model control group, and particularly arrive administration the 7th day, middle and high dosage group of BHF and positive controls were similar.Illustrate that BHF has therapeutical effect to the diarrhoea of rat model with having blood in stool.
The influence (n=10) that table 1BHF extracting solution is suffered from diarrhoea and had blood in stool the ulcerative colitis rat model
(3) the BHF extracting solution is to the influence of ulcerative colitis rat model colon damage scoring
Rat is dissected the back observe colon outward appearance and mucous membrane surface discovery, the colon of model group rat is most to have slight adhesion with adjacent internal organs, the colon congestion and edema, at the anus mouth 8cm place that makes progress bigger ulcer sexually transmitted disease (STD) kitchen range is arranged, the affected area colon wall thickens, the curing ulcer erosion necrosis takes place in the intestinal mucosa surface, compares with normal rats, and colon obviously shortens.Middle and high dosage of BHF extracting solution and SPSA administration group can be improved inflammatory symptoms such as colon congestion and edema, reduce the ulcer area, alleviate colon weight, reduce rat model colon damage scoring (P＜0.05).The influence that damage is marked to ulcerative colitis rat model colon of table 2BHF extracting solution (
N=10)
* compare with model control group P＜0.05; Compare with model control group * P＜0.01
(4) the BHF extracting solution is to ulcerative colitis rat model colon pathological effect
Pathological examination shows, normal rat colon clear in structure, and mucosa is complete, and enteraden is abundant in the lamina propria, arranges closely; Rat colon histology after the TNBS modeling shows the mucosa necrosis and comes off, ulcer, and mucosa and Submucosa have a large amount of neutrophilic granulocytes, lymphocytic infiltration, and remaining body of gland goblet cell disappears, fibrohistiocytic's hypertrophy, interstitial edema is obvious.Middle and high dosage of BHF extracting solution and the active proliferation of SASP group rat colon mucosa, surface mucous is recovered substantially, ulcer healing, mucosa and Submucosa neutrophilic granulocyte obviously reduce, but a matter still has Mild edema and a small amount of lymphocytic infiltration.The histology shows proof BHF extracting solution, and damage has the improvement effect to ulcerative colitis rat model intestinal mucosa, and has the removing neutrophilic granulocyte, the effect that reduces inflammation.
The pharmacodynamic study content of Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill is identical with BHF extracting solution pharmacodynamic study content, result of study shows, Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill colon targeting drug administration system has better pharmacodynamic action, and it is stronger to the partial action effect of ulcerative colitis rat model colon, pathology result of its colon and the scoring that colon is damaged all are better than BHF extracting solution group, therapeutic effect near in addition be better than positive control drug SASP, and treating both the principal and secondary aspects of a disease, pay attention to whole machine balancing, side effect is little, therefore can be used for preparing the medicine for the treatment of ulcerative colitis.
Claims (2)
1. a pharmaceutical composition that is used for the treatment of ulcerative colitis is characterized in that with the Rhizoma Atractylodis Macrocephalae being monarch, and Rhizoma Coptidis is a minister, and Radix Saposhnikoviae is formed for assistant, and weight proportion is: 30～60 parts of the Rhizoma Atractylodis Macrocephalaes; 30～45 parts of Rhizoma Coptidis; 30～60 parts of Radix Saposhnikoviaes.
2. segmented intestine targeted Rhizoma Atractylodis Macrocephalae Rhizoma Coptidis micropill that is used for the treatment of ulcerative colitis of forming by the extract of described each component of pharmaceutical composition of claim 1, it is characterized in that proportioning is: 24～36 parts of Rhizoma Atractylodis Macrocephalae extract Rhizoma Atractylodis Macrocephalae volatile oils, 3～9 parts of Rhizoma Coptidis extract berberine, 9～27 parts of Radix Saposhnikoviae extracts, preparation method is: Rhizoma Atractylodis Macrocephalae volatile oil is made the gastric solubleness micropill, berberine and Radix Saposhnikoviae extract are made enteric coated micropill, be distributed into capsule by proportioning after with gastric solubleness micropill and enteric coated micropill mixing again and get final product.
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| CN102512377A (en) * | 2011-12-22 | 2012-06-27 | 杭州高成生物营养技术有限公司 | Tasteless quick-releasing berberine hydrochloride pellet |
| CN103393602A (en) * | 2013-07-19 | 2013-11-20 | 东北制药（沈阳）科技发展有限公司 | Berberine ultrafine-particle intestinal adhesion-type sustained-release pellet and preparation method thereof |
| CN105963583A (en) * | 2016-07-11 | 2016-09-28 | 甘肃鑫晟源生物科技开发有限责任公司 | Radix et rhizoma rhei colon-targeting capsules for treating colonitis |
| CN107281160A (en) * | 2017-07-28 | 2017-10-24 | 昆明邦宇制药有限公司 | A kind of berberine enteric-coated micro-pill and preparation method thereof, application |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101601743A (en) * | 2008-06-10 | 2009-12-16 | 中山大学 | A kind of pharmaceutical composition for the treatment of ulcerative colitis and preparation method thereof |
-
2011
- 2011-01-21 CN CN2011100235713A patent/CN102085252B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101601743A (en) * | 2008-06-10 | 2009-12-16 | 中山大学 | A kind of pharmaceutical composition for the treatment of ulcerative colitis and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《中医药导报》 20050531 汪良会 白连汤内服加苦黄汤灌肠治疗慢性溃疡性结肠炎44例临床观察 第25-26页 1-2 第11卷, 第5期 2 * |
| 《辽宁中医药大学学报》 20100630 穆丽萍等 溃疡性结肠炎的中药治疗研究进展 第276-278页 1-2 第12卷, 第6期 2 * |
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| CN103393602A (en) * | 2013-07-19 | 2013-11-20 | 东北制药（沈阳）科技发展有限公司 | Berberine ultrafine-particle intestinal adhesion-type sustained-release pellet and preparation method thereof |
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| CN108888670A (en) * | 2018-09-10 | 2018-11-27 | 复旦大学附属肿瘤医院 | A kind of segmented intestine targeted capsule that treating ulcerative colitis and its preparation process |
| CN108888670B (en) * | 2018-09-10 | 2022-03-04 | 复旦大学附属肿瘤医院 | Colon targeting capsule for treating ulcerative colitis and preparation process thereof |
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