CN104739990A - Compound combined medicine for treating ulcerative colitis and preparation method and application thereof - Google Patents
Compound combined medicine for treating ulcerative colitis and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a compound combined medicine for treating ulcerative colitis. The compound combined medicine is prepared from the following components in parts by weight: 2-9 parts of coptis chinensis, 6-15 parts of scutellaria baicalensis, 10-30 parts of patrinia, 6-20 parts of fried angelica sinensis, 5-20 parts of parched white peony roots, 5-15 parts of raw garden burnets, 5-20 parts of lithospermum, 5-15 parts of madders, 6-15 parts of radix angelicae, 3-12 parts of simmered elecampane and 2-6 parts of raw liquorice. The invention further discloses a preparation method and application of the ompound combined medicine. The invention provides an effective therapeutic medicine for treating the refractory diseases ulcerative colitis and is economical and practical and broad in clinical application prospect. The compound combined medicine is simple in preparation method, simple, fast, efficient and easy to operate, and prepared granules are convenient to carry and take.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of compound composite medicament for the treatment of ulcerative colitis and preparation method thereof and application
Background technology
Ulcerative colitis (UC) is a kind of chronic nonspecific inflammation of mainly involving rectum, colonic mucosa, belongs to inflammatory bowel category.Its course of disease feature is chronic, delay, recurrent exerbation, also has and the probability of canceration occurs.Because of its etiology unknown, be difficult to cure, easily recur, be classified as difficult diseases by World Health Organization (WHO).
Current UC western medical treatment medicine has: 1. aminosalicyclic acid supplement, be a current line medication, but sulfasalazine toxic and side effects is obvious, mesalazine, Olsalazine, balsalazide price are high, have nephrotoxicity side effect, limit clinical long-term taking, the curative effect of Control in recurring is still undesirable.2. glucocorticoid: mainly contain succinic acid hydrocortisone, prednisolone, methyl meticortelone etc., easily produce drug dependence, side effect is obvious, is difficult to prolonged application.3. immunosuppressant: mainly contain ciclosporin, azathioprine, Ismipur, has obvious toxic and side effects, and only for above-mentioned case of failing to respond to any medical treatment, curative effect can not be affirmed.4. biological preparation: be most important therapeutic advance, mainly contains anti-tumor necrosis factor (TNF-α) preparation infliximab, anti-cellular adhesion molecule preparation, natural anti-inflammatory preparation and other preparations.Infliximab needs to be proved to the curative effect of ulcerative colitis and most suitable using method, and not in Asia clinical practice, all the other are still in the preclinical study stage.
This disease was given priority in active stage and catabasis pathogenesis,, there is retention of damp-heat in the interior intestinal internal organs primary disease active stage more, qi depression to blood stasis, the pathological change that the rotten blood of meat loses, when based on bowel relieving removing dampness, mainly with Radix Paeoniae Decoction or Radix Pulsatillae Decoction plus-minus, the product of the bitter colds such as conventional Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, the Radix Pulsatillae, Cortex Fraxini, it should be noted that not only hindering taste by bitter cold was good for fortune, and had the fraud of cool latent heat poison and injuring YIN due to production of dryness.Ulcerative colitis active stage is main mainly with damp and hot, stagnant heat simultaneously, should focus on the treatment of bowel relieving removing dampness, cooling blood for hemostasis, lacks the compound medicine of optimal drug proportioning at present clinically, still can not promote the use.
Summary of the invention
Technical problem to be solved by this invention is to provide that a kind of curative effect is high, the compound composite medicament of the treatment ulcerative colitis of few side effects.
The technical problem that the present invention also will solve is to provide the preparation method of above-mentioned compound composite medicament.
The technical problem that the present invention finally will solve is to provide the application of above-mentioned compound composite medicament.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A kind of compound composite medicament for the treatment of ulcerative colitis, it comprises the component of following parts by weight:: Rhizoma Coptidis 2 ~ 9 parts, Radix Scutellariae 6 ~ 15 parts, Herba Patriniae 10 ~ 30 parts, Radix Angelicae Sinensis (parched) 6 ~ 20 parts, Radix Paeoniae Alba (parched) 5 ~ 20 parts, Radix Sangusorbae 5 ~ 15 parts, Radix Arnebiae (Radix Lithospermi) 5 ~ 20 parts, 5 ~ 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 6 ~ 15 parts, Radix Aucklandiae (roasted) 3 ~ 12 parts, Radix Glycyrrhizae 2 ~ 6 parts.
Above-mentioned compound composite medicament, preferably includes the component of following parts by weight: Rhizoma Coptidis 6 parts, Radix Scutellariae 10 parts, Herba Patriniae 15 parts, Radix Angelicae Sinensis (parched) 10 parts, Radix Paeoniae Alba (parched) 15 parts, Radix Sangusorbae 10 parts, Radix Arnebiae (Radix Lithospermi) 15 parts, 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 10 parts, Radix Aucklandiae (roasted) 6 parts, Radix Glycyrrhizae 6 parts.
Wherein, described medicine comprises medicine Chinese medicine compound being combined the various dosage forms made with pharmaceutically acceptable carrier, and described dosage form is tablet, capsule, granule, injection or oral liquid.
The preparation method of the compound composite medicament of above-mentioned treatment ulcerative colitis, by the Rhizoma Coptidis of formula ratio, Radix Scutellariae, Herba Patriniae, Radix Angelicae Sinensis (parched), Radix Paeoniae Alba (parched), Radix Sangusorbae, Radix Arnebiae (Radix Lithospermi), Radix Rubiae, the Radix Angelicae Dahuricae, Radix Aucklandiae (roasted) and Radix Glycyrrhizae mixing, after soaking, decoct 1 ~ 4 time, each 1 ~ 3h, merge decoction liquor filtration and obtain filtrate, after concentrating under reduced pressure, be extract.
Wherein, the weight of water is 5 ~ 20 times of Traditional Chinese drug mixture weight.
Wherein, soak time is 30 ~ 60 minutes.
The compound composite medicament for the treatment of ulcerative colitis of the present invention comprises medicine Chinese medicine compound being combined the various dosage forms made with pharmaceutically acceptable carrier, and described dosage form is tablet, capsule, granule, injection or oral liquid, preferred particulates agent.
The compound composite medicament for the treatment of ulcerative colitis of the present invention is when making tablet, and the extract of Chinese medicine compound raw material and carrier lactose or corn starch, granulate, dry, add magnesium stearate lubricant when needing, mix homogeneously, then tablet made by tabletting.
The compound composite medicament for the treatment of ulcerative colitis of the present invention, when making capsule, is mixed homogeneously the extract of Chinese medicine compound raw material with carrier lactose or corn starch, granulate, then encapsulatedly makes capsule.
The compound composite medicament for the treatment of ulcerative colitis of the present invention is when making granule, precipitation is removed in centrifugal for the extract of Chinese medicine compound raw material or filtration, continue to be evaporated to relative density 1.20 ~ 1.35 (60 DEG C) again and obtain clear paste, take dextrin, put in fluid bed, get above-mentioned clear paste and be diluted with water to the thick paste that relative density is 1.15 ~ 1.18 (20 DEG C), when temperature of charge rises to 50 DEG C, start spraying, dry, sieve, obtain granule.Wherein, the inlet temperature of fluid bed is 60 ~ 95 DEG C, and sample introduction speed is below 0.8kg/min, atomizing pressure is 0.1 ~ 0.5MPa, intake is 800 ~ 1200m
3/ hr.Wherein, baking temperature is 50 ~ 80 DEG C, and drying time is 1 ~ 2 hour.
The application of above-mentioned compound composite medicament in preparation treatment ulcerative colitis medicine.Traditional Chinese compound medicine of the present invention, through clinical verification for many years, has bowel relieving removing dampness, regulating qi and activating blood, holds back effect of infections granulation promoting.Cure mainly ulcerative colitis patients with active, show as the damp-heat brewing internally patient such as diarrhoea, bloody purulent stool or hemafecia, stomachache, tenesmus, red tongue with yellowish and greasy fur, slippery and rapid pulse.
Beneficial effect: the present invention provides effective medicine for this refractory disease of clinical treatment ulcerative colitis, and economical and practical, and potential applicability in clinical practice is wide; Its preparation method, simple and quick, efficient, be easy to operation, prepare granule and be easy to carry, conveniently take.Compound composite medicament of the present invention has following advantage:
1, the understanding to ulcerative colitis pathogenesis has been deepened: damp and hotly accumulate intestinal, qi depression to blood stasis, blood loses meat corruption and become infections to be active stage basic pathogenesis.Damp and hot stagnant in large intestine, stifling intestinal, fights mutually with QI and blood and ties, qi stagnation hemagglutination, and make intestinal conduct mistake department, fat network is injured, thus produces a series of diseases of UC, and then impairing the spleen and stomach of a specified duration, causes weakness of the spleen and stomach, and damp and hot difficulty is gone; Or patient is congenital insufficiency of the spleen, or because of diet, overstrain, prolonged illness equivalent damage taste, temper is impaired, transporting mistake department, and water is wet to stop gathering, poly-heat-dissipating of a specified duration, diarrhea inducing dysentery between damp and hot multiple abscess intestinal.Damp and hotly damp and hotly delaying the major pathogenetic factor that large intestine is it through primary disease all the time as seen, is also the direct factor of its morbidity.
2, reasonable recipe, the lower profit of primary disease stomachache, stool often has blood, and color be just scarlet, be gradually dark red, and position is also more fixing bitterly, therefore disease and in blood, heat in blood, blood stasis are two large pathological factors.Must join in method for the treatment of with the square medicine of removing heat from blood, clots absorbing, should prosecute to the end.Emphasize the importance controlling ulcerative colitis from damp and hot-heat in blood-blood stasis opinion.Be instruct with above-mentioned theory, in conjunction with clinical practice, repeated screening, residence Liu Wansu " Radix Paeoniae Decoction " and Zhang Zhongjing " Radix Pulsatillae Decoction ", in one, constitute and embody bowel relieving removing dampness, the compound medicine of regulating qi and activating blood method for the treatment of.Rhizoma Coptidis, Radix Scutellariae bowel relieving removing dampness, eliminating pathogenic heat from blood to cure dysentery; The Radix Paeoniae Alba easing the affected liver reason spleen, QI and blood regulating, and antidiarrheal dysentery stomachache; Radix Angelicae Sinensis (parched) is relatively invigorated blood circulation; The stagnant gas of the capable large intestine of the Radix Aucklandiae; Radix Sanguisorbae cooling blood for hemostasis, removing toxic substances sore, compatibility Herba Patriniae heat-clearing and toxic substances removing, eliminating carbuncle evacuation of pus; Radix Arnebiae (Radix Lithospermi) clearing away heat and cooling blood, promoting blood circulation and detoxication; Radix Rubiae enters blood system, cooling blood for hemostasis; The evacuation of pus of Radix Angelicae Dahuricae detumescence support skin ulcer; Radix Glycyrrhizae coordinating the actions of various ingredients in a prescription, raw by the effect still having heat-clearing and toxic substances removing.Full side embodies damp and hot-heat in blood-blood stasis at the developing importance of pathogenesis of ulcerative colitis, and collection removing damp-heat, eliminating pathogenic heat from blood to cure dysentery, regulating QI and blood are integrated.Just answering the pathogenesis that UC active stage damp-heat accumulation, qi depression to blood stasis, intestinal network are impaired.
3, research method is advanced: this compound recipe of clinical research confirmation can not only the clinical symptoms of reduction of patient, and has good intestinal mirror and pathology curative effect.In experimentation, its mechanism is immunity moderation, antiinflammatory, reparation colonic mucosa barrier, promotes the reparation of Traumatic Colon.
4, preparation process is reasonable: this preparation technology is simple and quick, efficient, be easy to operation, the granule prepared has reduction medication volume, increase medicine stability, be convenient to storage transport, carry, the advantage such as to take, both maintain decoction drug effect and played feature rapidly, overcome again the large perishable mould shortcoming lost of decoction medication volume.
Accompanying drawing explanation
Fig. 1 is after this Drug therapy, and each group rat colon tissue mucosa repairs situation.
Blank group Colonic Mucosa organizational structure is complete, has no mucosal erosion ulcer.
The visible mucosa of model group rats, the extensive ulcer of Submucosa, the inflammatory cell infiltrations such as a large amount of neutrophilic granulocyte, lymphocyte, body of gland destroys, structure disturbance, and goblet cell reduces, and crypt abscess is formed.
The each dosage group in bowel relieving removing dampness side and SASP group comparatively model group are clearly better, and main manifestations is moderate chronic inflammation, and part mucosa and Submucosa still have a small amount of cell infiltration, and downright bad mucosal epithelium is repaired substantially, and ulcer heals substantially, and crypt abscess disappears.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But those skilled in the art will readily understand, the content described by embodiment only for illustration of the present invention, and should can not limit the present invention described in detail in claims yet.
Embodiment 1:
Treat a compound composite medicament for ulcerative colitis, comprise the component of following parts by weight: Rhizoma Coptidis 6 parts, Radix Scutellariae 10 parts, Herba Patriniae 15 parts, Radix Angelicae Sinensis (parched) 10 parts, Radix Paeoniae Alba (parched) 15 parts, Radix Sangusorbae 10 parts, Radix Arnebiae (Radix Lithospermi) 15 parts, 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 10 parts, Radix Aucklandiae (roasted) 6 parts, Radix Glycyrrhizae 6 parts.
Preparation method: by the Rhizoma Coptidis of formula ratio, Radix Scutellariae, Herba Patriniae, Radix Angelicae Sinensis (parched), Radix Paeoniae Alba (parched), Radix Sangusorbae, Radix Arnebiae (Radix Lithospermi), Radix Rubiae, the Radix Angelicae Dahuricae, Radix Aucklandiae (roasted) and Radix Glycyrrhizae mixing, add the water soaking of 10 times of weight after 60 minutes, decoct 1h, filter, then add the water of 10 times amount, decoct 1 hour, filter, merge filtrate again, being evaporated to relative density is 1.2 (60 DEG C), filter, filtrate is for subsequent use.Take dextrin appropriate, put in fluid bed, arranging inlet temperature is 85 DEG C, get above-mentioned clear paste to add purified water and be diluted to the thick paste that relative density is 1.15 ~ 1.18 (20 DEG C), when temperature of charge rises to 50 DEG C, start feed liquor, and regulate sample introduction speed (0 ~ 0.5kg/min), atomizing pressure (0.1 ~ 0.2MPa), intake (800 ~ 1000M3/hr) in time according to the situation of material in fluid bed, spraying terminates, continue dry (60 DEG C) 1 hour, sieve, subpackage, obtains granule.
Embodiment 2:
Treat a compound composite medicament for ulcerative colitis, comprise the component of following parts by weight: Rhizoma Coptidis 2 parts, Radix Scutellariae 6 parts, Herba Patriniae 10 parts, Radix Angelicae Sinensis (parched) 6 parts, Radix Paeoniae Alba (parched) 5 parts, Radix Sangusorbae 5 parts, Radix Arnebiae (Radix Lithospermi) 5 parts, 5 parts, Radix Rubiae, the Radix Angelicae Dahuricae 6 parts, Radix Aucklandiae (roasted) 3 parts, Radix Glycyrrhizae 2 parts.
Preparation method: by the Rhizoma Coptidis of formula ratio, Radix Scutellariae, Herba Patriniae, Radix Angelicae Sinensis (parched), Radix Paeoniae Alba (parched), Radix Sangusorbae, Radix Arnebiae (Radix Lithospermi), Radix Rubiae, the Radix Angelicae Dahuricae, Radix Aucklandiae (roasted) and Radix Glycyrrhizae mixing, add the water soaking of 20 times of weight after 30 minutes, decoct 3h, filter, filtrate reduced in volume to relative density is 1.2 (60 DEG C), filters, and filtrate is concentrated, dry, pulverizing, with carrier lactose or corn starch, granulate, dry, add magnesium stearate lubricant when needing, mix homogeneously, then tablet made by tabletting.
Embodiment 3:
Treat a compound composite medicament for ulcerative colitis, comprise the component of following parts by weight: Rhizoma Coptidis 9 parts, Radix Scutellariae 15 parts, Herba Patriniae 30 parts, Radix Angelicae Sinensis (parched) 20 parts, Radix Paeoniae Alba (parched) 20 parts, Radix Sangusorbae 15 parts, Radix Arnebiae (Radix Lithospermi) 20 parts, 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 15 parts, Radix Aucklandiae (roasted) 12 parts, Radix Glycyrrhizae 4 parts.
Preparation method: by the Rhizoma Coptidis of formula ratio, Radix Scutellariae, Herba Patriniae, Radix Angelicae Sinensis (parched), Radix Paeoniae Alba (parched), Radix Sangusorbae, Radix Arnebiae (Radix Lithospermi), Radix Rubiae, the Radix Angelicae Dahuricae, Radix Aucklandiae (roasted) and Radix Glycyrrhizae mixing, add the water soaking of 5 times of weight after 40 minutes, decoct 4 times, each 2h, filter, merge filtrate again, being evaporated to relative density is 1.2 (60 DEG C), filters, filtrate is concentrated, dry, pulverizing, mix homogeneously with carrier lactose or corn starch, granulate, then encapsulatedly makes capsule.
Embodiment 4:
1, clinical research:
1) with the comparative study of mesalazine slow releasing tablet: treatment group patient gives that Chinese medicine bowel relieving removing dampness side (embodiment 1) is oral, and it is oral that matched group gives Mesalazine table 4g/d, 12 weeks courses for the treatment of.Relatively two groups of patients symptomatic's integrations, intestinal mirror and pathology curative effect, remission rates, and monitor drug safety.
Result: at the end for the treatment of, the improvement for the treatment of group to bloody purulent stool, symptom total mark is better than matched group (P < 0.05).Two groups of patient's diarrhoea, stomachache, abdominal distention, burning sensation of the anus, tenesmus, intestinal mirror and pathological manifestations are all improved, but no difference of science of statistics between two groups.Mucosa healing rate (43.3%vs50.0%), remission rate (30.0%vs36.7%) all no difference of science of statistics between two groups.Conclusion: bowel relieving eliminating dampness method treatment UC active stage damp-heat brewing internally is effective and safety, and is better than mesalazine to the improvement of bloody purulent stool, general symptom.
2, study mechanism
1) experiment material
1.1 laboratory animals: healthy male SD rat, body weight (220 ± 30) g, is provided by Jiangsu TCM Hospital's pharmacological evaluation room Experimental Animal Center, conventional raising.
1.2 Experimental agents: test group: bowel relieving removing dampness side (embodiment 1); Matched group: sulfasalazine (sulfasalazine) is purchased from extra large three-dimensional pharmaceutical Co. Ltd.
2) method
2.1 animal models and grouping: 60 Balb/c mices are divided into 6 groups at random: dosage group, bowel relieving removing dampness side low dose group, SASP group, model control group, blank group in bowel relieving removing dampness side high dose group, bowel relieving removing dampness side, often organize 10.Modeling method: after fasting 24h, 10% chloral hydrate intraperitoneal injection of anesthesia; Gastric perfusion needle is inserted mice anus gently, and pushes TNBS solution (100mg/kgTNBS+ equal-volume 50% ethanol), clutch anus, after carrying tail handstand 3min, naturally revive, conventional raising.
2.2 medicine preparation and interventions: bowel relieving removing dampness side low dose group: 16.9gkg-1; Dosage group: 33.8gkg in bowel relieving removing dampness side
-1; Bowel relieving removing dampness side high dose group: 67.6gkg
-1; It is 0.1g/ml solution that sulfasalazine group is made into mass concentration by 1.0g/kg distilled water.After modeling 24h, each group starts administration (2ml/100g).Model group and Normal group give equal-volume normal saline, every day 1 time, continuous 10 days.
2.3 sample receptions: fasting 24h after last administration, put to death mice, get its colon (about 5cm), cut off, rinse well with cold saline along the mesentery longitudinal axis.Part colon gives that 10% formaldehyde is fixed, paraffin embedding, and 4 μm of serial section, dye for HE.
3) statistical procedures
Application SPSS 19.0 statistical software, data represent with x scholar s.Compare with variance analysis between many groups of measurement data, do not meet the employing rank test of homogeneity of variance and normal distribution, P < 0.05 has statistical significance for difference.
4) observation item
4.1 ordinary circumstance
After modeling success, observe the changes such as the rat mental status, chroma of hair, feed inflow, weight, stool situation every day.Percentage ratio is increased to rat weight and carries out statistical analysis.
4.2 weights increase percentage ratio=(the tenth day rat weight-first day rat weight)/first day rat weight * 100%
4.3 colon general forms:
Perusal rat colon general form, record it and whether have the situations such as hyperemia, edema, erosion, ulcer, and according to list of references [Strober W, Fuss I J, Blumberg RS.The immunology of mucosal models ofinflammation.Annu Rev Immunol, 2002; 20:495-549.] mark.
1. not damaged, 0 point;
2. mucosa hyperemia, edema, there is not ulcer, 1 point;
3. mucosa hyperemia, edema, slight rotten to the corn, without ulcer, 2 points;
4. mucosa hyperemia, edema, moderate be rotten to the corn, have single ulcer, 3 points;
5. mucosa hyperemia, edema, highly rotten to the corn, have multiple ulcer, 4 points;
6. the ulcer that mucosa hyperemia, edema, moderate be rotten to the corn, have >1cm, 5 points
4.4 colon's pathological examination:
Light Microscopic observation colonic mucosal tissue HE stained, the standard with reference to Dieleman LA etc. carries out carrying out histological score to the ulcer degree of depth, scope, degree of inflammation.
Table 1 colon histological scores standard
5) statistical procedures:
Application SPSS 19.0 statistical analysis software, if measurement data meets homogeneity of variance and normal distribution t checks, does not meet homogeneity of variance or normal distribution rank test, enumeration data X 2 test or rank test.Have statistical significance using P<0.05 as checked difference, P<0.01 has remarkable statistical significance as checked difference.
6) result
6.1 ordinary circumstances: compared with normal group, after modeling success all there is lethargy, asthenia in various degree in rat, drowsiness, hair is matt in a jumble, feed inflow is few, and stool also changes to some extent.Normal group stool is how partially dry, granulates.Model group loose stool is heavier, and become to stick with paste sample, foul smell, has two within the 6th, eight days, to occur naked eyes hemafecia in modeling.The each dosage group in bowel relieving removing dampness side loose stool sometimes, the soft shaping of many matter of defecating, does not observe obvious hemafecia.
6.2 weights increase percentage ratio
Table 2 respectively group weight increases situation (X ± s)
Note: compare with model group,
*p < 0.01,
*p < 0.05
Normal group, compared with model group, has remarkable statistical significance (P < 0.01).The each dosage group in bowel relieving removing dampness side increases compared with model group with SASP group weight, has statistical significance (P < 0.05).Compare with SASP group, no significant difference (P > 0.05).(see table 2)
6.3 colon general forms:
Normal rats colon mucosa is smooth, pleat clean mark, has no mucosa congestion and edema, and without ulcer, without adhesion between intestinal tissue, intestinal wall does not thicken.The visible extensively congestion and edema of model group rats colon, companion is rotten to the corn, the visible ulcer of naked eyes, and pleat disappears, and intestinal wall thickens, and even forms megacolon, intestinal adhesions, enteric cavity pneumatosis, organizes quality crisp, tractive easy fracture.Rat colon pathological changes after pharmaceutical intervention obviously alleviates, pleat compared with normal, and local mucosa congestion and edema, accidental several pieces of festers, intestinal is without adhesion, and enteric cavity is without obvious pneumatosis.
Table 3 Ge Zu colon general form scoring (X ± s)
Note: compare with model group,
*p < 0.01,
*p < 0.05
Normal group, compared with model group, has remarkable statistical significance (P < 0.01).The each dosage group in bowel relieving removing dampness side, SASP group, compared with model group, have remarkable statistical significance (P < 0.01).Compare between bowel relieving removing dampness side each dosage group group, no significant difference, compares with SASP group, no significant difference (P > 0.05).(see table 3)
6.4 colon's pathological examinations:
Light microscopic undertissue of normal rats colon form is normal, and gut wall structure is clear, and body of gland is even, has no congested, rotten to the corn, ulcer, and visible a small amount of lymph follicle is formed.Model group rats colon ulcer, a large amount of acute inflammatory cells infiltrates, and goblet cell reduces, Glandular Dilatation, forms crypt abscess.Pharmaceutical intervention group pathological changes obviously alleviates, and part mucosa and Submucosa are shown in a small amount of inflammatory cell infiltration, ulcer healing, occasionally has Glandular Dilatation, sees crypt abscess individually, and granulation tissue is formed, and goblet cell increases.
Table 4 Ge Zu colon pathological score (X ± s)
Note: compare with model group,
*p < 0.01,
*p < 0.05
Normal group, compared with model group, has remarkable statistical significance (P < 0.01).The each dosage group in bowel relieving removing dampness side, SASP group, compared with model group, have remarkable statistical significance (P < 0.01).Compare between bowel relieving removing dampness side each dosage group group, middle and high dosage group is better than low dose group, no significant difference, compares with SASP group, no significant difference (P > 0.05) (see table 4, seeing Fig. 1).
Embodiment 5: antiinflammatory and analgesic pharmacodynamic experiment are studied.
1) medicine and reagent
Chinese medicine compound bowel relieving removing dampness side (embodiment 1); Gastrophageal reflux disease; Dexamethasone acetate tablets; Aspirin effervescent tablets; Tramadol hydrochloride; Dimethylbenzene; Sodium chloride injection; Glacial acetic acid; AZO-blue, Solution on Chemical Reagents in Shanghai company.
2) laboratory animal and key instrument
ICR mice is supplied by Shao Yan (Suzhou) new drug research centered finite company.The quality certification: SCXK (Soviet Union)-2013-0003.Before and after administration, laboratory animal sub-cage rearing, feeds full-valence pellet feed, freely drinks water, room temperature 22 ± 2 DEG C.TGL-16G centrifuge (Anting Scientific Instrument Factory, Shanghai), balance (Sartorius B71250, Sai Duolisi scientific instrument company limited), microplate reader (Spectra Max 190, MD company of the U.S.).
3) experimental technique
3.1 bowel relieving removing dampness sides are on the impact of mice ear
Get ICR male mice 40, body weight 18-22g, be divided into 5 groups at random, often organize 8: (1) matched group, gives isopyknic distilled water; (2) positive group: dexamethasone acetate tablets 1mg/kg; (3) bowel relieving removing dampness side low dose group: 16.9gkg-1; (4) dosage group: 33.8gkg in bowel relieving removing dampness side
-1; (5) bowel relieving removing dampness side high dose group: 67.6gkg
-1.According to the continuous gavage of the dosage of 0.2mL/10g 7 days, positive group started continuous gavage 3 days at the 5th day.In administration last day after 1 hour at mice left auricle two sides uniform application dimethylbenzene (0.03mL/ only), auris dextra is not painted with normal ear, after 30 minutes, mice is taken off cervical vertebra to put to death, left and right two ears under auricle edge scissor, be that the card punch of 7mm takes off round auricle in left and right sides ear same area with diameter, use scales/electronic balance weighing immediately, calculate auricle swelling degree, and calculate ear swelling suppression ratio.Computing formula: swelling=left auricle weight-auris dextra sheet weight; Ear swelling suppression ratio %=(the average swelling of matched group-average swelling of administration group) average swelling × 100% of/matched group.
3.2 bowel relieving removing dampness sides are on the impact of mouse peritoneal capillary permeability
Get ICR mice 40, male and female half and half, body weight 18-22g, be divided into 5 groups at random, often organize 8: (1) Normal group, gives isopyknic distilled water; (2) positive group: aspirin effervescent tablets 0.25gkg
-1; (3) bowel relieving removing dampness side low dose group: 16.9gkg
-1; (4) dosage group: 33.8gkg in bowel relieving removing dampness side
-1; (5) bowel relieving removing dampness side high dose group: 67.6gkg
-1.According to the continuous gavage of the dosage of 0.2mL/10g 7 days, positive group started continuous gavage 3 days at the 5th day.Administration last day is after 1 hour, and 5 groups of mices are by tail vein injection 0.5% azovan blue 0.1mL10g
-1, lumbar injection 0.7% glacial acetic acid 0.2mL immediately, after 20 minutes, de-cervical vertebra puts to death mice, cut off abdominal cavity, divide with 5mL normal saline and wash abdominal cavity, sucking-off cleaning mixture, centrifugal 10 minutes of 3000r/min for several times, get supernatant, add in 96 orifice plates, microplate reader compares absorbance in 590nm wavelength place.
The impact that 3.3 bowel relieving removing dampness sides react mouse writhing
Get ICR mice 40, male and female half and half, body weight 18-22g, be divided into 5 groups at random, often organize 8: (1) Normal group, gives isopyknic distilled water; (2) positive group: aspirin effervescent tablets 0.25gkg
-1; (3) bowel relieving removing dampness side low dose group: 16.9gkg
-1; (4) dosage group: 33.8gkg in bowel relieving removing dampness side
-1; (5) bowel relieving removing dampness side high dose group: 67.6gkg
-1.According to the continuous gavage of the dosage of 0.2mL/10g 7 days, positive group started continuous gavage 3 days at the 5th day.Administration last day is after 1 hour, every lumbar injection 0.6% glacial acetic acid 0.2mL, observes each group of writhing response in 20 minutes (abdominal part indent, stretch hind leg, buttocks raises) number of times.
The impact that 3.4 bowel relieving removing dampness sides react mouse hot-plate
Constant water bath box is heated to (55.0 ± 0.5) DEG C, puts into wherein by 500ml beaker, makes beaker bottom contact the water surface and fixes.Get mice 1 at every turn, put into beaker, with stopwatch record mice from dropping into beaker to occurring that the time of licking metapedes is as its pain threshold, the pain threshold of every mice is first measured before administration, survey 2 times altogether, reject happiness leaper, each measuring interval at least 5 minutes, selects the mice of average pain threshold 10 ~ 30s for formal experiment.Qualified 40 Female ICR mice are divided into 5 groups at random, often organize 8, be respectively (1) matched group, give isopyknic distilled water; (2) positive group: tramadol hydrochloride 66.7mg/kg; (3) bowel relieving removing dampness side low dose group: 16.9gkg-1; (4) dosage group: 33.8gkg-1 in bowel relieving removing dampness side; (5) bowel relieving removing dampness side high dose group: 67.6gkg-1.According to the continuous gavage of the dosage of 0.2mL/10g 7 days, positive group started continuous gavage 3 days at the 5th day.Measure the pain threshold of 0,30,45,60,90 minute each mice after last administration respectively.Respectively organize the difference of different time pain threshold after mice medication.
3.5 statistical analysis
SPSS13.0 statistical software carries out data analysis, and data acquisition is used
represent, compare employing one factor analysis of variance between group, P<0.05 is that difference has statistical significance.
4) experimental result
4.1 bowel relieving removing dampness sides are on the impact of mice ear
Experimental result display (table 5): the middle and high dosage group in bowel relieving removing dampness side compares with matched group, significantly can improve the inflammatory reaction (P<0.01) of mice caused by dimethylbenzene xylene ear swelling.
Table 5 bowel relieving removing dampness side xylol causes the impact of mice ear
Note: compare with matched group: * P<0.05, * * P<0.01
4.2 bowel relieving removing dampness sides are on the impact of mouse peritoneal capillary permeability
Experimental result display (table 6): in bowel relieving removing dampness side, dosage group compares with matched group, obviously can reduce mouse peritoneal capillary permeability (P<0.05); Bowel relieving removing dampness side high dose group compares with matched group, significantly can reduce mouse peritoneal capillary permeability (P<0.01).
Table 6 bowel relieving removing dampness side is on the impact of mice capillary permeability
Note: compare with matched group: * P<0.05, * * P<0.01
The impact that 4.3 bowel relieving removing dampness sides react mouse writhing
Experimental result display (table 7): bowel relieving removing dampness side low dose group compares with matched group, obviously can reduce acetic acid and cause mouse writhing reaction times (P<0.05); The middle and high dosage group in bowel relieving removing dampness side compares with matched group, significantly can reduce acetic acid and cause mouse writhing reaction times (P<0.01).
Table 7 bowel relieving removing dampness side Dichlorodiphenyl Acetate causes the impact of mouse writhing reaction
Note: compare with matched group: * P<0.05, * * P<0.01
The impact that 4.4 bowel relieving removing dampness sides react mouse hot-plate
Experimental result display (table 8): bowel relieving removing dampness side low dose group compares with matched group, significantly extended the action time (P<0.05) of mouse hot-plate reaction at 30 minutes; In bowel relieving removing dampness side, dosage group compares with matched group, significantly extends the action time (P<0.05) of mouse hot-plate reaction at 45 minutes; Bowel relieving removing dampness side high dose group compares with matched group, significantly can extend the action time (P<0.01, P<0.05) of mouse hot-plate reaction at 30 minutes, 60 minutes.
The impact that table 8 bowel relieving removing dampness side reacts different time points mouse hot-plate
Note: compare with matched group: * P<0.05, * * P<0.01
Treatment of ulcerative colitis is with giving consideration to both the incidental and fundamental, and strengthening vital QI to eliminate pathogenic factors is basic principle, notes distinguishing specimen emergency, cold and heat and asthenia and sthenia, and at gas at blood, balance treats.Active stage, mostly is damp-heat accumulation, qi depression to blood stasis, and intestinal network is impaired, controls with heat clearing and damp drying, and regulating QI and blood are main.The lower profit of primary disease stomachache, stool often has blood, and color be just scarlet, be gradually dark red, and position is also more fixing bitterly, therefore disease and in blood, heat in blood, blood stasis are two large pathological factors.Must join in method for the treatment of with the square medicine of removing heat from blood, clots absorbing, should prosecute to the end.
Clinical effectiveness shows, bowel relieving removing dampness side treatment active ulcerative colitis has curative effect advantage, experimental studies results shows, after adopting the treatment of bowel relieving removing dampness side, the increase of rat weight is better than model group, colon general form and histopathology are obviously better than model group, and colonic mucosa can be repaired thus treatment ulcerative colitis by prompting bowel relieving removing dampness side.Pharmacodynamic study show to improve mice caused by dimethylbenzene xylene ear swelling inflammatory reaction, reduce mouse peritoneal capillary permeability, reduce the action time that acetic acid causes mouse writhing reaction times and extend mouse hot-plate reaction, there is good antiinflammatory, analgesic activity.
Claims (10)
1. treat a compound composite medicament for ulcerative colitis, it is characterized in that, it comprises the component of following parts by weight: Rhizoma Coptidis 2 ~ 9 parts, Radix Scutellariae 6 ~ 15 parts, Herba Patriniae 10 ~ 30 parts, Radix Angelicae Sinensis (parched) 6 ~ 20 parts, Radix Paeoniae Alba (parched) 5 ~ 20 parts, Radix Sangusorbae 5 ~ 15 parts, Radix Arnebiae (Radix Lithospermi) 5 ~ 20 parts, 5 ~ 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 6 ~ 15 parts, Radix Aucklandiae (roasted) 3 ~ 12 parts, Radix Glycyrrhizae 2 ~ 6 parts.
2. the compound composite medicament for the treatment of ulcerative colitis according to claim 1, is characterized in that, it comprises the component of following parts by weight: Rhizoma Coptidis 6 parts, Radix Scutellariae 10 parts, Herba Patriniae 15 parts, Radix Angelicae Sinensis (parched) 10 parts, Radix Paeoniae Alba (parched) 15 parts, Radix Sangusorbae 10 parts, Radix Arnebiae (Radix Lithospermi) 15 parts, 15 parts, Radix Rubiae, the Radix Angelicae Dahuricae 10 parts, Radix Aucklandiae (roasted) 6 parts, Radix Glycyrrhizae 6 parts.
3. the compound composite medicament for the treatment of ulcerative colitis according to claim 1 and 2, it is characterized in that, described medicine comprises medicine Chinese medicine compound being combined the various dosage forms made with pharmaceutically acceptable carrier, and described dosage form is tablet, capsule, granule, injection or oral liquid.
4. the preparation method of the compound composite medicament for the treatment of ulcerative colitis according to claim 1, it is characterized in that, by the Rhizoma Coptidis of formula ratio, Radix Scutellariae, Herba Patriniae, Radix Angelicae Sinensis (parched), Radix Paeoniae Alba (parched), Radix Sangusorbae, Radix Arnebiae (Radix Lithospermi), Radix Rubiae, the Radix Angelicae Dahuricae, Radix Aucklandiae (roasted) and Radix Glycyrrhizae mixing, after soaking, decoct 1 ~ 4 time, each 1 ~ 3h, merges decoction liquor filtration and obtains filtrate, be extract after concentrating under reduced pressure.
5. preparation method according to claim 4, is characterized in that, the weight of water is 5 ~ 20 times of Traditional Chinese drug mixture weight.
6. preparation method according to claim 4, is characterized in that, soak time is 30 ~ 60 minutes.
7. preparation method according to claim 4, it is characterized in that, extract is centrifugal or filter and remove precipitation, then continue to be evaporated to relative density 1.20 ~ 1.35 (60 DEG C) clear paste, take dextrin, put in fluid bed, get above-mentioned clear paste and be diluted with water to the thick paste that relative density is 1.15 ~ 1.18 (20 DEG C), when temperature of charge rises to 50 DEG C, start spraying, drying, sieves, and obtains granule.
8. preparation method according to claim 7, is characterized in that, the inlet temperature of fluid bed is 60 ~ 95 DEG C, and sample introduction speed is below 0.8kg/min, atomizing pressure is 0.1 ~ 0.5MPa, intake is 800 ~ 1200m
3/ hr.
9. preparation method according to claim 7, is characterized in that, baking temperature is 50 ~ 80 DEG C, and drying time is 1 ~ 2 hour.
10. the application of compound composite medicament according to claim 1 in preparation treatment ulcerative colitis medicine.
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| CN108904746A (en) * | 2018-10-12 | 2018-11-30 | 刘启泉 | A kind of Chinese medicine composition and its preparation method and application for treating ulcerative colitis |
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| CN111053741B (en) * | 2019-12-31 | 2021-09-28 | 江苏省中医院 | Oral multi-sensitive micelle prodrug based on beta-sitosterol and 5-ASA for treating inflammatory bowel disease |
| CN111467409A (en) * | 2020-04-23 | 2020-07-31 | 蓝明见 | Traditional Chinese medicine preparation for treating proctitis and preparation method thereof |
| CN111686202A (en) * | 2020-06-16 | 2020-09-22 | 张家港市中医医院 | Compound traditional Chinese medicine composition for inhibiting inflammatory progression of active ulcerative colitis and preparation method and application thereof |
| CN112826858A (en) * | 2021-04-08 | 2021-05-25 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | Traditional Chinese medicine composition for treating ulcerative colitis and traditional Chinese medicine preparation and application thereof |
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