CN1634299A - Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation - Google Patents
Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation Download PDFInfo
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Abstract
The invention relates to the application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation, the preparation employs the significant part of a single Chinese medicinal herb, thus facilitating the product stability and quality control. The release of targeting preparation on the colon can decrease the absorption on the digestive tracts.
Description
Technical field
The present invention relates to the purposes of Herba Sophorae alopecuroidis total alkali, relate in particular to the purposes of Herba Sophorae alopecuroidis total alkali in pharmaceutical field.
The invention still further relates to a kind of Herba Sophorae alopecuroidis total alkali targeting preparation for the treatment of ulcerative colitis and preparation method thereof.
Background technology
(Ulcerative Colitis UC) claims chronic non-specific ulcerative colitis again to ulcerative colitis, is that the not clear and definite as yet chronic colitis disease sexually transmitted disease (STD) of a kind of cause of disease becomes, and is the principal character of pathological changes with inflammation under large intestine (rectum and colon) mucosa and the mucosa.Primary disease is a cardinal symptom with diarrhoea, stomachache, mucus bloody purulent stool or bloody purulent stool etc. clinically, and serious part (intestinal itself) and distant place (general) complication can take place.Primary disease is outbreak repeatedly often, delay several months, and even many decades.The minority case can be the fulminant type morbidity, is in a bad way, but even threat to life.
According to western countries statistics, the annual morbidity of UC is 2～20,/10 ten thousand, and prevalence is 50～1,00/,100,000, and primary disease can betide any age, with 20-50 year for seeing more.The immunity factor plays an important role in the morbidity of ulcerative colitis.Other cause of disease also has factors such as heredity, infection, environment.Touching because of its course of disease, and ulcer is difficult to healing, and relapse rate is high and classified as one of difficult treatment by World Health Organization (WHO) in addition.In recent years because the improving constantly of living standard, the change of dietary structure, living habit, its sickness rate presents ascendant trend year by year.
The medicine of western medical treatment ulcerative colitis is at present based on aminosallcylic acid preparation, corticosteroid hormone, immunosuppressant.Wherein sulfasalazine (SASP) is to treat the most frequently used medicine of ulcerative colitis at present, be applicable to light, moderate or chronic phase patient, be generally oral, 4g/d, after oral, it does not absorb in the intestinal major part, and is metabolized to sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) by Enterobacter cloaca, and the latter can be by disturbing the synthetic therapeutical effect of bringing into play of inflammation mediator prostaglandin.This medication effect and untoward reaction are directly proportional with consumption, and in the 4g/d that takes medicine, effective percentage has 10～15% patients because of the untoward reaction drug withdrawal approximately not as good as 50%; Take medicine more than the super 4g/d, effective percentage improves, and relapse rate reduces, but untoward reaction can reach 37.5%.Therefore Western medicine have that curative effect is undesirable, shortcoming such as relapse rate height after the erious adverse reaction, drug withdrawal.
The Chinese medicine report of treatment ulcerative colitis is a lot of at present, based on for oral administration, is aided with coloclysis.Flavour of a drug for oral administration are many, and quality is wayward, and curative effect can not get guaranteeing.Coloclysis administration patient is very painful, and medical personnel's workload is big, and uses inconvenience, thereby the patient is difficult for accepting.
By the present invention can overcome that the Western medicine curative effect is undesirable, relapse rate height and the oral medicinal herb flavour of a drug are many, the shortcomings such as inconvenience used after the erious adverse reaction, drug withdrawal.
Owing to oral drugs lose the part therapeutical effect by stomach acids destroy or by the pancreatin metabolism easily, and medicine is not just influenced by these at colon.The present invention makes colon site-specific drug with Herba Sophorae alopecuroidis total bases extract, and medicine directly discharges more effective at diseased region, and can be scattered in whole colon by higher concentration, and this is very favourable to treatment of diseases.
The capsule that the present invention makes is a kind of colon targeting preparation.Coatings is by acrylic resin-S (EudragitS) and acrylic resin-L (Eudragit L), and they could dissolve in the solution of PH＞5, and preparation can pass through stomach (pH1～3) smoothly like this.Contain full-bodied hydroxypropyl emthylcellulose (HPMC) and acrylic resin-E (Eudragit E) in the medicated core.HPMC is a kind of hydrophilic expandable polymer, expands to stop drug release in small intestinal (pH6.5～7); Eudragit E could dissolve in alkaline medium, makes preparation arrive colon (pH7～8) release smoothly.
The Chinese medicine Herba Sophorae alopecuroidis (Sophora Alopecuraides L.) is cassia leguminous plant, bacillary dysentery and the enteritis of being used for the treatment of already among the people, and China's version pharmacopeia in 1977 and drug standard promulgated by the ministries or commissions of the Central Government are recorded Sophora Alopecuroides L..The Herba Sophorae alopecuroidis bitter in the mouth is cold in nature, and effects such as heat-clearing and toxic substances removing, dispeiling pathogenic wind and removing dampness, pain relieving parasite killing are arranged.Recent study shows that Herba Sophorae alopecuroidis total alkali contains multiple compositions such as matrine, oxymatrine, sophoramine, sophoridine, sophocarpine, aloperine.
Existing bibliographical information, matrine, oxymatrine, sophoramine, sophoridine, sophocarpine, aloperine all have in various degree inhibitory action to immune function of mice.Oxymatrine can suppress the short proliferation function of interleukin II to mouse boosting cell, and interleukin II activation LAK cell is had inhibitory action, also suppresses the LAK cell activity simultaneously.Oxymatrine also can suppress lipopolysaccharide-induced macrophage and discharge interleukin-1,6 and tumor necrosis factor-alpha.Oxymatrine can significantly reduce the expression of Dextran Sulfate Sodium-induced Colitis in Rats model mucosa nuclear transcription factor-kappa B activity and intercellular adhesion molecule-1.Aloperine has the effect that macrophage produces interleukin-1 that suppresses, and can directly suppress the mouse boosting cell breeder reaction, simultaneously also suppress splenocyte to the inductive T cell proliferative response of concanavalin A, Con A, also obviously reduce the ability that splenocyte produces interleukin II, suppress the inductive bone-marrow-derived lymphocyte breeder reaction of bacteria lipopolysaccharide equally.Matrine, oxymatrine, sophocarpine, sophoridine all can suppress Turnover of Mouse Peritoneal Macrophages and generate tumor necrosis factor-alpha.Herba Sophorae alopecuroidis total alkali all has antiinflammatory action to the animal inflammation that multiple proinflammatory agent brings out, wherein matrine, oxymatrine, sophocarpine and aloperine all have the significantly effect similar to hydrocortisone to various acute exudative inflammation person, but the chronic inflammatory disease that rat is brought out by cotton balls is not had obvious influence.Extract before and after the mice bilateral adrenal gland, antiinflammatory action does not have difference, illustrates that its antiinflammatory action and hypophysis-adrenal system are irrelevant, but direct antiinflammatory action.
Summary of the invention
One of purpose of the present invention is to provide the new purposes of Herba Sophorae alopecuroidis total bases extract in preparation treatment ulcerative colitis medicine.
Another object of the present invention is to provide a kind of Chinese medicine targeting preparation of more effectively treating ulcerative colitis and preparation method thereof.
Technical solution of the present invention is as follows:
1, the application of Herba Sophorae alopecuroidis total bases extract in preparation treatment ulcerative colitis medicine.
2, Herba Sophorae alopecuroidis total alkali targeting preparation, it is to be active component with the Herba Sophorae alopecuroidis total bases extract, particularly the invention reside in pectin, calcium chloride, acrylic resin-E, hydroxypropyl emthylcellulose, acrylic resin-S, acrylic resin-L, triethyl citrate, Pulvis Talci and make pharmaceutic adjuvant, and be that the proportioning of 99-1.0% is made 100% composition by to contain Herba Sophorae alopecuroidis total alkali be 1.0-99% with containing medicinal adjuvant.
In order to understand essence of the present invention better, below the zoopery and the clinical effectiveness division of the preparation method of Herba Sophorae alopecuroidis total alkali colon site-specific drug, Herba Sophorae alopecuroidis total alkali is as follows:
One, Herba Sophorae alopecuroidis total alkali colon site-specific drug:
1. the preparation method of Herba Sophorae alopecuroidis total alkali colon site-specific drug
1. take by weighing 60 ℃ of following dryings of Herba Sophorae alopecuroidis total bases extract by recipe quantity, pulverize, cross 80 mesh sieves; 2. prepare the pastille micropill: take by weighing after pharmaceutic adjuvant pectin, calcium chloride, acrylic resin-E, hydroxypropyl emthylcellulose all cross 80 mesh sieves and Herba Sophorae alopecuroidis total alkali mix homogeneously adding suitable amount of adhesive 95% ethanol mix homogeneously by recipe quantity.Then mixed material is dropped into loading hopper, extrude into cylindrical material, material is joined in the cylinder again, make the about 1.0～1.5mm pastille of diameter micropill, take out micropill, 60 ℃ dry down, sieves; 3. prepare coating solution: under continue stirring, the TEC and the adding of micronization Pulvis Talci of recipe quantity contained in the aqueous dispersion that acrylic resin-S and acrylic resin-L be made into, be made into coating solution; 4. inclusion casing: under coating parameter condition, micropill is carried out coating, the weightening finish of control coating be about 3～6%, 60 ℃ dry down; 5. adorn capsule: the screening micropill, according to pharmaceutical dosage, with the micropill suitable conventional capsule of model of packing into.
Coating parameter: coating solution flow velocity 2.5ml/min; 40 ℃ of inlet temperatures; 1.2kgf/cm is pressed in spray
2
2. dissolution in the body of Herba Sophorae alopecuroidis total alkali colon site-specific drug
Adopt the radiolabel method,, sneak in the medicine, make capsule radiosiotope Thallous chloride. (201T1) injection.The oral back of 2 routine experimenters is respectively at certain hour detection bodies internal labeling thing ruuning situation on the isotope tracker.The result: 7～8h medicine 90% is in the disintegrate of colon position.
Two, Herba Sophorae alopecuroidis total alkali animal acute toxicity experiment:
1. material
1.1 animal
Kunming mouse, body weight 18～22g, male and female half and half are purchased the Experimental Animal Center in Nanfang Medical Univ, the quality certification number: the moving probatio inspectionem pecuoarem word in Guangdong 2003A021 number.Be divided into 5 groups at random, 10 every group.
1.2 medicine
Adopt the Herba Sophorae alopecuroidis total alkali colon site-specific drug, according to preliminary experiment, maximum dose level is decided to be 390mg/kg, successively decreases with 0.8 ratio, is five dosage groups of 390,312,250,200,160 (mg/kg).
2. method
Mice fasting 6h before the administration adopts one time the gastric infusion approach, every mice dosage: 0.2ml/10g.The dissection that performs an autopsy on sb of the record various poisoning symptoms of mice and death condition after the administration, dead animal.Observed 14 days continuously.
3. result
Mouse stomach give behind the Herba Sophorae alopecuroidis total alkali a few minutes promptly occur dull, movablely reducing, stomach wall pastes down, be all of a tremble immediately, muscle spasm, orthocolosis, dead animal appears within the administration 6h mostly, the obvious pathological changes of internal organs is not seen in the dead animal postmortem.Mortality rate is tried to achieve LD with the simplification probit method
50Be 246mg/kg, its credible 225.4～266.6mg/kg that is limited to of 95%.
4. conclusion
Herba Sophorae alopecuroidis total alkali toxicity is very low, and is safe in utilization, convenient.
Three, Herba Sophorae alopecuroidis total alkali treatment rat ulcer colitis experiment
1. material
1.1 animal
Cleaning level SD male rat, body weight 180～220g.Purchase Experimental Animal Center, the quality certification number: the moving probatio inspectionem pecuoarem word in Guangdong 2003A073 number in Nanfang Medical Univ.After animal was bought back, 22 ℃ ± 1 ℃ constant temperature was raised ad lib and drinking-water.
1.2 medicine
1.2.1 medicine source
Trinitro-benzene-sulfonic acid (TNBS) is purchased the company in Sigma; Oxymatrine, pharmaceutical factory provides by the salt pond, Ningxia, lot number: 20021103; Herba Sophorae alopecuroidis total alkali, pharmaceutical factory provides by the salt pond, Ningxia, lot number: 031101; Positive control drug: mesalamine sustained release granules (5-aminosalicylic acid, 5-ASA), group of Ethypharm SA produces, lot number: 200301; SOD, MDA mensuration test kit is good for into bio-engineering research by Nanjing to be provided.
1.2.2 experimental drug agent amount
The adult calculates with the 70kg body weight, can calculate the bioequivalence of following each medicine rat according to " the dose,equivalent ratio table of body surface area conversion between humans and animals ".
Oxymatrine adult consumption every day: 300mg (with reference to the dosage of hepatitis B)
The bioequivalence of rat: 300mg * 0.018 * 5 ≈ 30mg/kg
Herba Sophorae alopecuroidis total alkali adult consumption every day: 300mg
The bioequivalence of rat: 300mg * 0.018 * 5 ≈ 30mg/kg
The large, medium and small dosage of rat experiment medication is set at 60,30 respectively, 15mg/kg
5-ASA adult consumption every day: 4g
The bioequivalence of rat: 4g * 0.018 * 5 ≈ 0.4g/kg
2. experimental technique
2.1 relatively Herba Sophorae alopecuroidis total alkali, oxymatrine are to the effect of rat ulcer colitis, method is as follows:
40 of SD rats are divided into 5 groups after 1 week that conformed at random, and 8 every group, i.e. normal group, model control group, 5-ASA group, Herba Sophorae alopecuroidis total alkali group, oxymatrine group.Insert the dark 7cm of conduit with reference to reported method such as Morris through the rat anus, 50% alcoholic solution 1ml/ of 1 property injection 5% (w/v) trinitro-benzene-sulfonic acid only.The normal group animal is irritated the equivalent normal saline.After 2 weeks, each treatment group rat coloclysis administration gavages corresponding medicinal liquid by the 2ml/200g body weight, continuous 2 weeks.Normal and model control group gives the normal saline of equivalent.
Experimental session is observed rat body weight, stool, character and the indication of occulting blood or have blood in stool, and does disease activity degree (DAI) evaluation with stool, sees Table 1.Tested the 28th day, and after the anesthesia of lumbar injection 2% pentobarbital sodium, cut rat abdomen open, observe intestinal and change substantially, take off whole section colon, longitudinal incision, follow closely on rubber slab after observing the mucosa damage, it is fixing to spend the night in 10% formalin solution, the 2nd day damaged size of measurement mucosa, get the anus 10cm intestinal segment that makes progress and make specimen, every 2cm is one section, 4 wax stones of embedding, serial section (thick 4 μ m), HE dyeing tissues observed changes, and carries out pathological score with the Cooper method of improvement, sees Table 2.
Table 1 DAI standards of grading
Score stool character is occulted blood or hemafecia
0 is normal negative
1 soft stool feminine gender
The 2 soft stools positive of occulting blood
The 3 diarrhoea positives of occulting blood
4 diarrhoea hemafecias
DAI is two score sums, and total points is 0～8 minute; Normal feces: hardness is moderate, the ball shape; Soft stool: starchiness but the anus mouth does not have the excrement mark; Diarrhoea: just thin and stick at crissum.
Table 2 pathological score standard (the Cooper method of improvement)
The sick classification extent of disease (%) that decreases of score
0 crypts harmless 0
1 crypts cryptomere expansion 1～20
2 forfeiture basilar parts, 1/3 crypts 21～40
3 forfeiture basilar parts, 2/3 crypts 41～60
The whole crypts of 4 forfeitures, epithelial layer still complete 61～80
5 whole crypts of forfeiture and epithelial layers 81～100
Pathological score is two score sums, and total points is 0～10 minute
The result: except that normal group, all the other each groups all have the minimizing of ingesting in various degree.Each treatment group weight increase value is all less than normal group.But greater than model control group.It is soft that coloclysis TNBS begins stool to occur, and stool blood, diarrhoea appear in most rats.Each group of treatment is light than the model group degree, indivedual diarrhoea, hemafecias of occurring.Normal group does not have above-mentioned ANOMALOUS VARIATIONS.
Modeling group rat colon inflammation exists under the light microscopic, shows as chronic inflammatory disease.As seen the ulcer that is healing, inflammation mainly are positioned at mucosa and Submucosa, lymphocyte and plasmocyte infiltrating, little blood vessel hyperplasia, connective tissue proliferation and fibrosis under the mucosa.Treatment respectively organizes ulcer surface and lesion degree obviously alleviates.
There were significant differences (p＜0.05) for each group of the DAI scoring of model group and pathological score and treatment, with the Herba Sophorae alopecuroidis total alkali group significant difference is arranged relatively, compare in twos through LSD, Herba Sophorae alopecuroidis total alkali group and oxymatrine group with dosage relatively have significant difference, and the former DAI scoring and pathological score value all are lower than the latter, the curative effect of Herba Sophorae alopecuroidis total alkali group is better than the oxymatrine group under the prompting Isodose condition, the results are shown in Table 3.
The scoring of each group of table 3 and pathological score (x ± s)
Group number of animals dosage DAI pathological score
(only) (mg/kg)
Normal 800
Model 8 7.48 ± 1.94 8.35 ± 1.01
5-ASA 8 400 4.88±0.98** 5.60±0.90*
Herba Sophorae alopecuroidis total alkali 8 30 4.07 ± 1.01* Δ 4.28 ± 0.92* Δ
Oxymatrine 8 30 5.43 ± 1.31* 5.62 ± 1.19*
Annotate: compare * with model, * * p＜0.05, p＜0.01
Herba Sophorae alopecuroidis total alkali and oxymatrine Δ, Δ Δ p＜0.05, p＜0.01
2.2 Herba Sophorae alopecuroidis total alkali is to the influence of superoxide dismutase (SOD), malonaldehyde (MDA) in the rat ulcer colitis:
63 of male rats, random packet, 9 every group, be respectively normal group, model control group, positive drug 5-ASA matched group, the large, medium and small dosage group of Herba Sophorae alopecuroidis total alkali, the oxymatrine group, modeling method is the same.After 3 days, each treatment group rat coloclysis every day administration gavages relative medicine by the 2ml/200g body weight, continuous two weeks.Normal and model control group gives the equivalent normal saline.Put to death all rats on the 20th day after the administration, get the above 10cm of rat anus place colonic mucosa tissue, about 2g.Add 2mlPBS, make homogenate under the water bath condition.Homogenizer 5000r/min, interval 20s, totally three times.Add 16mlPBS again, low speed centrifuge, 1500r/min.5min abandons precipitation.Get supernatant ,-80 ℃ of preservations.The SOD vigor adopts xanthine oxidase to measure.MDA content adopts the TAB colorimetric method for determining.Concrete steps reference reagent box operating instruction.
3. experimental result
Modeling group and normal group compare, active significantly reduce (p＜0.01) of the former SOD of colon.MDA content has significantly and increases (p＜0.01), and the modeling success is described.With model group relatively, rat SOD obviously raise (p＜0.05) is respectively organized in treatment.The heavy dose of group of Herba Sophorae alopecuroidis total alkali raises more remarkable (p＜0.01), and small dose group has only rising trend, not statistically significant; Treatment is respectively organized MDA content and is obviously reduced (p＜0.05), and the heavy dose of group of Herba Sophorae alopecuroidis total alkali reduces more remarkable (p＜0.01), sees Table 4.
Table 4 is respectively organized in the colon relatively (x ± s) of SOD.MDA
Group dosage SOD MDA
(mg/kg) (Nu/ml) (pmol/ml)
Normal 15.62 ± 0.60 28.54 ± 5.05
Model 8.71 ± 1.74
140.64 ± 5.24
1
Positive 800 12.97 ± 2.62
Δ33.09 ± 5.92
Δ
Herba Sophorae alopecuroidis total alkali is big by 60 14.50 ± 1.52
Δ Δ * *30.52 ± 4.68
Δ Δ *
In the Herba Sophorae alopecuroidis total alkali 30 13.22 ± 1.61
Δ* 35.45 ± 4.12
Δ
Herba Sophorae alopecuroidis total alkali is little by 15 10.22 ± and 1.78 36.41 ± 5.01
Δ
Oxymatrine 60 11.10 ± 1.50
Δ35.50 ± 4.11
Δ
Annotate: compare 1 p＜0.01 with normal group; Compare Δ, Δ Δ p＜0.05, p＜0.01 with model group.
Herba Sophorae alopecuroidis total alkali group and oxymatrine group be * relatively, * * p＜0.05, p＜0.01
Statistical method: this tests all results with mean ± standard deviations (x ± s).Adopt the SPSS10.0 statistical software, with one factor analysis of variance method (One-Way ANOVA) comparable group differences, between group in twos significance relatively adopt the LSD method.
4. conclusion:
1.TNBS/ the ethanol coloclysis can cause the rat ulcer colitis and form.This model Histological change and SOD, MDA changes of contents are to human similar, and our experimental result is consistent with bibliographical information.
2. give the Herba Sophorae alopecuroidis total alkali and the oxymatrine coloclysis of rat bioequivalence dosage, continuous 20 days, can significantly improve the pathological lesion of the inductive ulcerative colitis of TNBS, wherein the most obvious with the heavy dose of effect of Herba Sophorae alopecuroidis total alkali, and significant difference (p＜0.05) is relatively arranged with dosage Herba Sophorae alopecuroidis total alkali and oxymatrine.
3. oxygen-derived free radicals is to promote inflammation that the key factor of development takes place, what SOD can quicken that eliminate the inflammation reaction produced has the free radicals such as a large amount of superoxides ions of damage to colonic mucosa, strengthen histiocytic oxidation resistance, alleviate the colonic mucosa inflammation significantly, promote ulcer healing.When UC took place, the SOD vigor obviously descended in the colonic mucosa tissue, and MDA content obviously increases, and the high, medium and low dosage of Herba Sophorae alopecuroidis total alkali is the increased SOD vigor obviously, reduced MDA content, and had dose-effect trend.Illustrate that Herba Sophorae alopecuroidis total alkali intervened the UC pathogenic process by suppressing oxygen free radical reaction.
Four, Herba Sophorae alopecuroidis total alkali clinical trial
1. case is selected:
Continuous light, the medium-sized patients of ulcerative colitis made a definite diagnosis on inspection of collection totally 83 examples in 18 months all meet the ulcerative colitis diagnostic criteria that the whole nation, Taiyuan in 1993 chronic non-infection intestinal tract disease scientific seminar formulates.Clinical in persistence or repeatability mucus hemafecia, stomachache, with in various degree General Symptoms etc. is main, colonoscopy mucosa edema, hyperemia, ulcer, pus and blood secretions and happening part, successively divide Herba Sophorae alopecuroidis total alkali clyster group, oxymatrine clyster group, 5-ASA capsule clyster group by going to a doctor, each is organized patient and is respectively 31 examples, 27 example and 25 examples.Weekly check stool for routine from line item symptom and untoward reaction every day during the treatment, treatment before and after look blood, urine, just conventional, hepatic and renal function and intestinal mirror.Each is organized patient's ordinary circumstance and sees Table 5.
Table 5 liang group patient ordinary circumstance relatively
Group men and women's average course of disease pathological changes clinical symptoms
The age position
(year) the full tuberculosis abdominal pain potbellied blood in (moon) zone
The property intestinal time (people)
Herba Sophorae alopecuroidis 21 10 43.2 39.3 25 6 34 4.2 29
Total alkali
Oxidation bitter 12 15 42.2 37.1 24 3 25 4.0 23
Ginseng alkali
5-ASA 15 10 41.3 35.9 21 4 23 4.1 21
2. medication
Herba Sophorae alopecuroidis total alkali group 31 examples, dosage 300mg/100ml/1 time/day; Oxymatrine clyster group 27 examples, dosage 300mg/100ml/1 time/day; 5-ASA organizes 25 examples, and dosage 4g/100ml/1 time/day was for 4 weeks the course of treatment.
3. efficacy assessment standard
Produce effects (or alleviating fully): clinical symptom disappearance, the colonoscopy mucosa is normal, observes and does not have recurrence in 6 months.Effectively: clinical symptoms disappears substantially, and reaction of colonoscopy mucosa mild inflammation and part pseudopolyp form.Invalid: clinical symptoms, scope and pathologic finding do not have improvement.Because of the adverse effect drug withdrawal or disagree with check intestinal mirror person, from observe, reject in the treatment.Do not alleviate because of symptom, do not stop the person voluntarily, by invalid statistics.
4. result
4.1 curative effect:
Group produce effects enabledisable total effective rate
Herba Sophorae alopecuroidis total alkali 3 11 7 67.2%
Oxymatrine 186 60%
5-ASA 1 7 10 44.4％
4.2 untoward reaction:
Herba Sophorae alopecuroidis total alkali group, oxymatrine group are respectively finished experiment 21,15 examples, 1 routine abdominal discomfort wherein respectively occurs, and untoward reaction is respectively 4.76% (1/21), 6.67% (1/15); The 5-ASA group always has 18 examples and finishes experiment, and wherein erythra appears in 3 examples, 1 routine abdominal discomfort, and untoward reaction is 22.2% (4/18).
5. conclusion:
The total effective rate of Herba Sophorae alopecuroidis total alkali treatment patients of ulcerative colitis is respectively 67.2%.Similar to the 5-aminosalicylic acid curative effect, but adverse reaction rate (4.76%) is lower.
The present invention has following advantage:
1, the effective site of single medicinal material helps the stability and the quality control of product; 2, targeting preparation discharges at colon, reduces upper gastrointestinal absorption, directly discharges and can be scattered in whole colon by higher concentration at diseased region, and is more effective, definite to treatment of diseases; 3, targeting preparation reduces medicine to upper gastrointestinal stimulation, and untoward reaction lacks 4, easy to use, and compliance is good, and the patient easily accepts.
The specific embodiment
Embodiment 1 Herba Sophorae alopecuroidis total alkali colon site-specific drug
Herba Sophorae alopecuroidis total alkali micropill prescription:
Herba Sophorae alopecuroidis total bases extract 100g
Pectin 4g
Calcium chloride 0.4g
Eudragit?E 2g
HPMC 12g
The Herba Sophorae alopecuroidis total alkali coating fluid prescription:
Eudragit?S 15g
Eudragit?L 10g
Triethyl citrate 2g
Pulvis Talci 1g
Water 112g
The coating parameter:
Coating solution flow velocity 2.5ml/min
40 ℃ of inlet temperatures
1.2kgf/cm is pressed in spray
2
Take by weighing Herba Sophorae alopecuroidis total bases extract and various adjuvant, cross 80 mesh sieves respectively, 60 ℃ dry down, and mix homogeneously adds suitable amount of adhesive 95% ethanol, makes the about 1.0～1.5mm pastille of diameter micropill, and 60 ℃ dry down, sieves.Coating is controlled coating weightening finish 3～6%, the conventional capsule of packing under these conditions.
Embodiment 2 Herba Sophorae alopecuroidis total alkali colon site-specific drugs
Herba Sophorae alopecuroidis total alkali micropill prescription:
Herba Sophorae alopecuroidis total bases extract 100g
Pectin 4g
Calcium chloride 0.4g
Eudragit?E 2g
HPMC 12g
The Herba Sophorae alopecuroidis total alkali coating fluid prescription:
Eudragit?S 20g
Eudragit?L 5g
Triethyl citrate 2g
Pulvis Talci 1g
Water 112g
The coating parameter:
Coating solution flow velocity 2.5ml/min
40 ℃ of inlet temperatures
1.2kgf/cm is pressed in spray
2
Take by weighing Herba Sophorae alopecuroidis total bases extract and various adjuvant, cross 80 mesh sieves respectively, 60 ℃ dry down, and mix homogeneously adds suitable amount of adhesive 95% ethanol, makes the about 1.0～1.5mm pastille of diameter micropill, and 60 ℃ dry down, sieves.Coating is controlled coating weightening finish 3～6%, the conventional capsule of packing under these conditions.
Embodiment 3 Herba Sophorae alopecuroidis total alkali colon site-specific drugs
Herba Sophorae alopecuroidis total alkali micropill prescription:
Herba Sophorae alopecuroidis total bases extract 10g
Pectin 4g
Calcium chloride 0.4g
Eudragit?E 2g
HPMC 12g
The Herba Sophorae alopecuroidis total alkali coating fluid prescription:
Eudragit?S 15g
Eudragit?L 10g
Triethyl citrate 2g
Pulvis Talci 1g
Water 112g
The coating parameter:
Coating solution flow velocity 2.5ml/min
40 ℃ of inlet temperatures
1.2kgf/cm is pressed in spray
2
Take by weighing Herba Sophorae alopecuroidis total bases extract and various adjuvant, cross 80 mesh sieves respectively, 60 ℃ dry down, and mix homogeneously adds suitable amount of adhesive 95% ethanol, makes the about 1.0～1.5mm pastille of diameter micropill, and 60 ℃ dry down, sieves.Coating is controlled coating weightening finish 3～6%, the conventional capsule of packing under these conditions.
Embodiment 4 Herba Sophorae alopecuroidis total alkali colon site-specific drugs
Herba Sophorae alopecuroidis total alkali micropill prescription:
Herba Sophorae alopecuroidis total bases extract 2000g
Pectin 4g
Calcium chloride 0.4g
Eudragit?E 2g
HPMC 12g
The Herba Sophorae alopecuroidis total alkali coating fluid prescription:
Eudragit?S 15g
Eudragit?L 10g
Triethyl citrate 2g
Pulvis Talci 1g
Water 112g
The coating parameter:
Coating solution flow velocity 2.5ml/min
40 ℃ of inlet temperatures
1.2kgf/cm is pressed in spray
2
Take by weighing Herba Sophorae alopecuroidis total bases extract and various adjuvant, cross 80 mesh sieves respectively, 60 ℃ dry down, and mix homogeneously adds suitable amount of adhesive 95% ethanol, makes the about 1.0～1.5mm pastille of diameter micropill, and 60 ℃ dry down, sieves.Coating is controlled coating weightening finish 3～6%, the conventional capsule of packing under these conditions.
Embodiment 5 Herba Sophorae alopecuroidis total alkali enema
Normal saline with 1000ml dissolves the 3g Herba Sophorae alopecuroidis total bases extract, mix homogeneously, and sterilization is mixed with the enema of 300mg/100ml/ bottle, the bottling manufactured goods.
Claims (3)
1. the application of Herba Sophorae alopecuroidis total bases extract in preparation treatment ulcerative colitis medicine.
2. Herba Sophorae alopecuroidis total alkali targeting preparation as claimed in claim 1, it is to be active component with the Herba Sophorae alopecuroidis total bases extract, it is characterized in that making pharmaceutic adjuvant, and be that the proportioning of 99-1.0% is made 100% composition by to contain Herba Sophorae alopecuroidis total alkali be 1.0-99% with containing medicinal adjuvant with pectin, calcium chloride, acrylic resin-E, hydroxypropyl emthylcellulose, acrylic resin-S, acrylic resin-L, triethyl citrate, Pulvis Talci.
3. the preparation method of a Herba Sophorae alopecuroidis total alkali colon site-specific drug as claimed in claim 2 is characterized in that 1. it comprise the following steps: the Herba Sophorae alopecuroidis total bases extract drying is pulverized, and sieves; 2. prepare the pastille micropill: pectin, calcium chloride, acrylic resin-E, hydroxypropyl emthylcellulose are all sieved and the Herba Sophorae alopecuroidis total bases extract mix homogeneously after, add the binding agent mix homogeneously, make the pastille micropill, drying is sieved; 3. prepare coating solution: triethyl citrate and micronization Pulvis Talci are added in the aqueous dispersion that acrylic resin-S and acrylic resin-L be made into, be made into coating solution; 4. inclusion casing: the pastille micropill is carried out coating, drying; 5. screen micropill, the conventional capsule of packing into promptly gets the Herba Sophorae alopecuroidis total alkali colon site-specific drug.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100520290A CN100360120C (en) | 2004-11-03 | 2004-11-03 | Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100520290A CN100360120C (en) | 2004-11-03 | 2004-11-03 | Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation |
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| CN1634299A true CN1634299A (en) | 2005-07-06 |
| CN100360120C CN100360120C (en) | 2008-01-09 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100560088C (en) * | 2006-08-23 | 2009-11-18 | 兰州大学第一医院 | The purposes of Herba Sophorae alopecuroidis total alkali in the banded antiherpetic thing of preparation treatment |
| CN100586446C (en) * | 2005-10-28 | 2010-02-03 | 北京大学第三医院 | Compound herba sophorae alopecuroide active region group and its colon location preparation |
| CN1977972B (en) * | 2005-12-09 | 2010-08-25 | 四川抗菌素工业研究所有限公司 | Anti tumour drug oral colon targeting preparation and its preparing method |
| CN107233339A (en) * | 2017-06-16 | 2017-10-10 | 宁夏医科大学 | N caulophyllines are used as the sick pharmaceutical applications for the treatment of ulcerative colitis |
| CN116270549A (en) * | 2023-03-21 | 2023-06-23 | 沈阳药科大学 | Colitis-targeted matrine oxide nanoparticle, and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669950B (en) * | 2009-09-28 | 2012-02-22 | 南方医科大学 | Application of aloperin in preparation of drug for treating ulcerative colitis |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1292278A (en) * | 2000-09-08 | 2001-04-25 | 辛耀禄 | Weisushukang medicine for curing gastropathy and its preparation process |
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- 2004-11-03 CN CNB2004100520290A patent/CN100360120C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100586446C (en) * | 2005-10-28 | 2010-02-03 | 北京大学第三医院 | Compound herba sophorae alopecuroide active region group and its colon location preparation |
| CN1977972B (en) * | 2005-12-09 | 2010-08-25 | 四川抗菌素工业研究所有限公司 | Anti tumour drug oral colon targeting preparation and its preparing method |
| CN100560088C (en) * | 2006-08-23 | 2009-11-18 | 兰州大学第一医院 | The purposes of Herba Sophorae alopecuroidis total alkali in the banded antiherpetic thing of preparation treatment |
| CN107233339A (en) * | 2017-06-16 | 2017-10-10 | 宁夏医科大学 | N caulophyllines are used as the sick pharmaceutical applications for the treatment of ulcerative colitis |
| CN107233339B (en) * | 2017-06-16 | 2020-06-02 | 宁夏医科大学 | Pharmaceutical use of N-methylcytisine for treating ulcerative colitis |
| CN116270549A (en) * | 2023-03-21 | 2023-06-23 | 沈阳药科大学 | Colitis-targeted matrine oxide nanoparticle, and preparation method and application thereof |
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|---|---|
| CN100360120C (en) | 2008-01-09 |
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