CN105412010A - Matrine-containing medicinal composition and application thereof - Google Patents
Matrine-containing medicinal composition and application thereof Download PDFInfo
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Abstract
The invention provides a matrine-containing medicinal composition and application thereof, and relates to a medicinal composition. The medicinal composition is prepared by taking matrine as an active ingredient and cooperating with a carrier acceptable in pharmacy. Starch or powdered sugar or dextrin or lactose or microcrystalline cellulose or mannitol or a mixture of 2-6 of starch, powdered sugar, dextrin, lactose, microcrystalline cellulose and mannitol serves as the carrier acceptable in the pharmacy, and the mass ratio of the active ingredient matrine to the auxiliary carrier acceptable in the pharmacy is 1:(0.5-1.5). The medicinal composition is medicine used for treating diseases related to ion channels such as TMEM16A/CaCCs and is significant in effect on treating secretory diarrhea.
Description
Technical field
Technical scheme of the present invention relates to pharmaceutical composition, specifically containing pharmaceutical composition and the application thereof of matrine.
Background technology
Secretory diarrhea is a kind of common disease, its clinical manifestation be every day stool amount more than 1L (severe one reaches more than 10L); Stool is water sample, without pus and blood; Blood plasma-excrement matter infiltration is poor; The pH of feces mostly is neutral or alkaline; Fasting is suffered from diarrhoea after 48 hours still sustainable existence, and stool amount is still greater than 500ml/24h.The main reason of secretory diarrhea is caused to be abnormal medium, various abnormal medium can activate the cAMP on small intestinal and colorectal cell film, and in born of the same parents, cAMP content increases severely, and Cytoplasmic calcium content is increased, cause intestinal secretion to increase, large quantity of moisture, sodium bicarbonate, chloride and potassium ion are lost.Therefore the specific drug of exploitation treatment secretory diarrhea is significant.
Research shows, the process LAN of Ca2+-activated Cl-channels TMEM16A is the key factor (OusingsawatJ causing secretory diarrhea, MirzaM, TianY, etal.RotavirustoxinNSP4inducesdiarrheabyactivationofTMEM 16AandinhibitionofNa+absorption.PflugersArch [J] .Pfl ü gersArchiv-EuropeanJournalofPhysiology, 2011,461 (5): 579-589.).TMEM16A is distributed widely in small intestinal and the ileum of people, research shows the expression by suppressing TMEM16A, by applying specific inhibitor, TMEM16A passage is suppressed, effectively can weaken dynamics and the frequency of intestinal contraction, effectively can treat secretory diarrhea and can stop the forfeiture of chloride ion, therefore TMEM16A passage is the important drug target of for the treatment of secretory diarrhea.For traditional Chinese medical science the world of medicine of China, search and research and develop the specially good effect Chinese herbal medicine can treating secretory diarrhea and be used as to suppress the specific inhibitor of TMEM16A to be duty-bound urgent task.
Summary of the invention
Technical problem to be solved by this invention is: provide the pharmaceutical composition containing matrine and application thereof, is a kind of medicine being used for the treatment of TMEM16A/CaCCs ion channel relevant disease, Be very effective in treatment secretory diarrhea.
The present invention solves this technical problem adopted technical scheme: containing the pharmaceutical composition of matrine, being by taking matrine as active component, being aided with pharmaceutically acceptable carrier composition.
The above-mentioned pharmaceutical composition containing matrine, described pharmaceutically acceptable carrier is starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol or the wherein mixture of 2 ~ 6 kinds, and the matrine of described active component is 1: 0.5 ~ 1.5 with being aided with pharmaceutically acceptable carrier quality ratio.
The above-mentioned pharmaceutical composition containing matrine, the building form of described pharmaceutical composition is oral type administration.
The above-mentioned pharmaceutical composition containing matrine, the building form of described pharmaceutical composition is the dosage form of oral type administration is powder, granule, capsule, tablet, drop pill or oral liquid.
The above-mentioned pharmaceutical composition containing matrine, the building form of described pharmaceutical composition is parenteral type administration.
The above-mentioned pharmaceutical composition containing matrine, the building form of described pharmaceutical composition is the dosage form of parenteral type administration is injection.
The above-mentioned pharmaceutical composition containing matrine, wherein matrine is purchased from Aladdin reagent company limited, No. CAS: 519-02-8, component materials involved by other all obtains by known approach, the collocation method of the oral type administration of described pharmaceutical composition and the parenteral type administration of described pharmaceutical composition all uses pharmaceutically known acceptable form, and its compound method is that those skilled in the art can grasp.
The application of the above-mentioned pharmaceutical composition containing matrine, as TMEM16A inhibitors of ion channels, is used for the treatment of TMEM16A/CaCCs ion channel relevant disease.
The application of the above-mentioned pharmaceutical composition containing matrine, described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the secretory diarrhea disease being used for the treatment of people.
The application of the above-mentioned pharmaceutical composition containing matrine, described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the secretory diarrhea disease being used for the treatment of cattle, horse, sheep, Canis familiaris L., cat, pig or Mus.
The application of the above-mentioned pharmaceutical composition containing matrine is above-mentioned containing any one dosage form in the pharmaceutical composition of matrine as TMEM16A inhibitors of ion channels.
The application of the above-mentioned pharmaceutical composition containing matrine, involved treatment operational approach is that those skilled in the art can grasp.
The invention has the beneficial effects as follows: compared with prior art, the substantive distinguishing features that the present invention gives prominence to is as follows:
(1) the present inventor is by inquiry Chinese Traditional Medicine ancient books and records, finds that Chinese herbal medicine Radix Sophorae Flavescentis has good therapeutic effect for " damp-heat dysentery, discharging fresh blood stool ".Write in Chinese medicine works " solar corona ": " kill infantile malnutrition worm.Frying band cigarette goes out for end, under meal drink, controls hemorrhoidal hamorrhage and rushes down blood and hematodiarrhoea ", and find treating the mainly matrine wherein worked in diarrhoea by the research of a large amount of hardships.Matrine is made up through organic solvent extraction such as ethanol of the dry root of leguminous plant Radix Sophorae Flavescentis, plant, fruit, it is a kind of single component alkaloid, belong to Common Chinese Herbs, little to human body side effect, " Chinese medicine voluminous dictionary " second edition 1758 pages, " matrine function cures mainly heat clearing and damp drying, wind dispelling insecticide.Cure mainly damp-heat dysentery, discharging fresh blood stool, jaundice, dysuria, edema, leukorrhagia, pudendal pruritus, leprosy, skin pruritus, appropriate skin infection ".
(2) in recent years, the inhibitor of Ca2+-activated Cl-channels TMEM16A channel current is found in succession, such as CaCC
inh-A01, T16A
inh-A01, DIDS, NPPB etc., but the inhibitor of Ca2+-activated Cl-channels TMEM16A electric current is substantially all synthetics, exploration at present in natural product small-molecule drug is little, and these chemical synthetic drugs are comparatively large to cell damage, and the cell survival time is shorter in higher concentrations, be a very serious problem for later stage medicament research and development, therefore active development is significant to the natural product small-molecule drug that cell damage is less.
Test proves, to guinea pig ileum smooth muscle contraction, there is remarkable inhibitory action by the drug regimen containing matrine of the present invention, and proving that it reaches 90% to the outward current suppression ratio of Ca2+-activated Cl-channels TMEM16A by electro physiology experiment, half effective inhibition concentration is within 100 μMs.This effective medicine for development secretory diarrhea opens a fan gate.
Compared with prior art, marked improvement of the present invention is as follows:
(1) drug regimen containing matrine of the present invention can obviously suppress TMEM16A passage, and suppression ratio can reach 90%, and the disease treatment for secretory diarrhea aspect provides potential application prospect.
(2) drug regimen containing matrine of the present invention is higher compared with current other found inhibitor to the suppression efficiency of TMEM16A passage, and its half-inhibition concentration is within 100 μMs.
(3) matrine is a kind of natural product compound, and be the single composition alkaloid extracted from the wild Radix Sophorae Flavescentis of leguminous plant, abundance, belongs to Common Chinese Herbs, extracts simple, economical and practical.
(4) the drug regimen collocation method containing matrine of the present invention is simple, with low cost.
(5) application process of the drug regimen containing matrine of the present invention is simple, easily operates.
Accompanying drawing explanation
Below in conjunction with drawings and Examples, the present invention is further described.
Fig. 1 is in embodiment 13, the fluorescent effect comparison diagram of the Chinese hamster ovary celI of the transfection Ca2+-activated Cl-channels TMEM16A observed by laser confocal scanning microscope, wherein:
Figure 1A and Fig. 1 C is under the different visual field, does not add Ca
2+during with matrine, the Chinese hamster ovary celI fluorogram of transfection Ca2+-activated Cl-channels TMEM16A and YFP;
Figure 1B for 1A same field of view under add 600nMCa
2+after, the Chinese hamster ovary celI fluorogram of transfection Ca2+-activated Cl-channels TMEM16A and YFP;
Fig. 1 D be with 1C same field of view under add 100 μMs of matrines after the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A and YFP adding 600nMCa
2+after fluorogram;
Fig. 2 is in embodiment 14, is adding before and after matrine, the curent change typical electrical flow graph of the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A, wherein:
Fig. 2 A is that the Chinese hamster ovary celI of the transfection Ca2+-activated Cl-channels TMEM16A of non-perfusion matrine is by 600nMCa
2+the typical electrical flow graph activated;
Fig. 2 B is that the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A is by 600nMCa
2+activate, the typical electrical flow graph after re perfusion matrine;
Fig. 3 is in embodiment 14, at the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A by 600nMCa
2+after activation, the body lotion after current added containing 100 μMs of matrines is schemed over time, and is scheming over time with the body lotion flushing after current without matrine;
Fig. 4 is in embodiment 15, E
actcause guinea pig ileum contractile response to strengthen, contractile response can be suppressed to rapidly the representative experimental results figure of background level by TMEM16A inhibitors of ion channels matrine;
Figure 5 shows that matrine molecular structure.
Detailed description of the invention
The structure chart of display the present invention embodiment illustrated in fig. 5 matrine molecule used.
Embodiment 1
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with starch carrier, the mass ratio of matrine and starch carrier is 1:0.5, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 2
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with Icing Sugar carrier, the mass ratio of matrine and Icing Sugar carrier is 1:0.5, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the granule of oral type administration.
Embodiment 3
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with dextrin carrier, the mass ratio of matrine and dextrin carrier is 1:1, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the capsule of oral type administration.
Embodiment 4
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with lactose carrier, the mass ratio of matrine and lactose carrier is 1:1.5, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the tablet of oral type administration.
Embodiment 5
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with microcrystalline Cellulose carrier, the mass ratio of matrine and microcrystalline Cellulose carrier is 1:1, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the drop pill of oral type administration.
Embodiment 6
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with mannitol carrier, the mass ratio of matrine and mannitol carrier is 1:1.5, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the injection of parenteral type administration.
Embodiment 7
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, be aided with the starch sugaring powder carrier of arbitrary proportion, the starch of matrine and arbitrary proportion is 1:1 with the mass ratio of Icing Sugar, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 8
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, the dextrin being aided with arbitrary proportion adds the carrier that lactose adds microcrystalline Cellulose, it is 1:1.5 that the dextrin of matrine and arbitrary proportion adds the mass ratio that lactose adds microcrystalline Cellulose, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 9
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, the dextrin being aided with arbitrary proportion adds lactose and adds the carrier of microcrystalline Cellulose with mannitol, matrine and arbitrary proportion dextrin add lactose, and to add microcrystalline Cellulose with the mass ratio of mannitol be 1:1.5, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 10
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, the dextrin being aided with arbitrary proportion adds lactose and adds microcrystalline Cellulose with mannitol sugaring powder carrier, the dextrin of matrine and arbitrary proportion adds lactose, and to add microcrystalline Cellulose with mannitol be 1: 1 with the mass ratio of Icing Sugar, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 11
The pharmaceutical composition containing matrine of the present embodiment, take matrine as active component, the dextrin being aided with arbitrary proportion adds lactose and adds microcrystalline Cellulose and add starch carrier with mannitol with Icing Sugar, it is 1:0.5 that matrine and arbitrary proportion mush finishing lactose add the mass ratio that microcrystalline Cellulose adds starch with mannitol with Icing Sugar, its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing matrine of the present embodiment is the powder of oral type administration.
Embodiment 12
Get distilled water 500mL, add Tween-80 and make solution, then add matrine 100g, heat while stirring and make it to be dissolved into the solution containing matrine, in addition Icing Sugar 50g added the antiseptic of known standard consumption and be dissolved in distilled water 100mL, obtained Icing Sugar solution, then this Icing Sugar solution under agitation being added above-mentioned containing in the solution of matrine, adding distil water is to 1000mL, mixing, filters, is distributed into 200, sterilizing, the oral liquid of the pharmaceutical composition containing matrine of obtained the present embodiment.
In the embodiment of following the present invention containing the application of the pharmaceutical composition of matrine, the selected pharmaceutical composition containing matrine be any one in above-described embodiment 1 to embodiment 12 containing the pharmaceutical composition of matrine.
Embodiment 13
Any one in above-described embodiment 1 to embodiment 12 is contained a kind of inhibitor of pharmaceutical composition as TMEM16A ion channel of matrine, for in iodide ion yellow fluorescence protein (YFP) Fluorimetric Quenching Method, result makes transfection have the cell fluorescence of TMEM16A can not because adding Ca
2+and cancellation.
Yellow fluorescence protein (YFP) is the fluorescin that one derives from green fluorescent protein (GFP), can be excited and send yellow fluorescence under wavelength 515nm.Iodide ion can be combined with YFP and make fluorescent quenching, and two of the YFP that suddenlys change site H148Q and I152L can make YFP strengthen the sensitivity of iodide ion.CaCCs passage is not only a kind of chloride channel, and it has permeation to the most of anion comprising iodide ion.The drug screening test liposome of the present embodiment makes carrier by two sudden change YFP channel genes Chinese hamster ovary celIs of external source, makes YFP great expression in born of the same parents; Itself and passage are fully acted on drug candidate and cell incubation again; Finally observe the cancellation degree of the later YFP fluorescence of the solution added containing iodide ion.In this kind of method, make calcium ion that the medicine of YFP cancellation can not be caused can to think the inhibitor of CaCCs passage after perfusion, this result and patch clamp experiments result are confirmed mutually.
The Chinese hamster ovary celI of stable transfection YFP is cultivated in experiment the previous day in laser confocal microscope special culture dish; Within second day, by transfection YFP and the Chinese hamster ovary celI D-PBS of overnight incubation rinses 3 times, finally leave the D-PBS of 500 μ l; Add containing 150mMI
-solution 500 μ l, make I
-concentration reaches 75mM; Add 100 μMs of matrines and hatch 10min, any one storage of pharmaceutical composition containing the matrine liquid namely in embodiment 1 to embodiment 12 makes its final concentration reach 100 μMs, adds 600nMCa subsequently
2+body lotion, by laser confocal microscope real time record fluorescence intensity.
Figure 1A and 1C shows, and does not add matrine and Ca in the present embodiment
2+time cell in the representative experimental results figure of yellow fluorescent protein fluorescence intensity.This figure shows not add matrine and Ca
2+time cell in the fluorescence intensity of yellow fluorescence protein, each cell interior is strong yellow fluorescence.As the figure shows, matrine and Ca is not added
2+time YFP fluorescence intensity very high.
Figure 1B shows, and adds 600n Μ Ca in the present embodiment under 1A same field of view
2+the representative experimental results figure of yellow fluorescent protein fluorescence intensity in rear cell.This figure shows to add 600n Μ Ca
2+the fluorescence intensity of yellow fluorescence protein in rear cell, due to 600n Μ Ca
2+have activated TMEM16A ion channel, the iodide ion entered from this ion channel makes the yellow fluorescence protein generation fluorescent quenching in born of the same parents, is namely adding I
-after, the obvious cancellation of YFP fluorescence, after 5min, fluorescence almost disappears completely.
Fig. 1 D shows, and adds 100 μ Μ matrines and hatches 10 minutes, add 600n Μ Ca subsequently in the present embodiment under 1C same field of view
2+the representative experimental results figure of yellow fluorescent protein fluorescence intensity in rear cell.This figure shows to add the opening that 100 μ Μ matrines can suppress Ca2+-activated Cl-channels TMEM16A, makes 600n Μ Ca
2+tMEM16A ion channel can not be activated, even if therefore adding I
-after, YFP fluorescence is still very strong.
Embodiment 14
Any one in above-described embodiment 1 to embodiment 12 being contained the pharmaceutical composition of matrine as a kind of inhibitor of TMEM16A ion channel, having the Chinese hamster ovary celI current value of TMEM16A ion channel to suppress for making transfection:
Expression plasmid pEGFP-N1-TMEM16A is proceeded in mammalian cell CHO, after cell transfecting within 24-72h, carry out electro physiology detection.Concrete grammar is as follows:
The F12K culture fluid Secondary Culture of Chinese hamster ovary celI containing 10% hyclone, wherein adds penicillin and the 100 μ g/ml streptomycins of 100UI/ml.Transfection process Lipofectamine2000 (Invitrogen company) liposome carries out.Chinese hamster ovary celI in 37 DEG C, 5%CO
2exponential phase is cultured to for experiment in saturated humidity incubator.Electro physiology detects and carries out under the room temperature of 22 DEG C, and adopt full cell (i.e. WholeCell) logging mode (EPC-10Amplifier, HEKA company, Germany), in medicine used, liquid composition is: CsCl130mM, MgCl
26H
2o1mM, HEPES10mM, EGTA10mM and MgATP1mM, be adjusted to pH7.3 with CsOH; The outer liquid composition of medicine used is: NaCl150mM, MgCl
26H
2o1mM, CaCl
21mM, HEPES10mM, mannitol 10mM and glucose 10mM, be adjusted to pH7.4 with NaOH.The pharmaceutical composition any one in embodiment 1 to embodiment 12 being contained matrine adds in the outer liquid of medicine makes its final concentration reach 100 μMs, does negative control, and make comparisons with the electric current under 1 μM of free calcium condition with 10mMEGTA without calcium solution.By voltage depolarization activated membrane electric current, operating condition is: membrane depolarization voltage is from-100mV consecutive variations to+100mV, and ME for maintenance is 0mV.Testing result is as follows:
Fig. 2 A shows in the present embodiment and contains 600nMCa in liquid in electrode
2+time the representative experimental results figure of activated current, this figure shows, in electrode in liquid containing 600nMCa
2+time activated current, it is about 1.3nA for exemplary currents when TMEM16A ion channel is activated, steady-state current size.
Fig. 2 B shows electric current in the present embodiment and is contained 600nMCa by liquid in electrode
2+activation, subsequently with containing the body lotion perfusion of 100 μMs of matrines, and its reach stable after the typical electrical flow graph that is recorded to, its size of current can be suppressed to 120pA, therefore proves that matrine is a kind of effective Ca2+-activated Cl-channels TMEM16A inhibitor.
Fig. 3 to show in the present embodiment electric current first by 600n Μ Ca in liquid in electrode
2+activate, subsequently with the electric current variation diagram in time of the body lotion perfusion record current change continuously that contain 100 μMs of matrines, abscissa is the time, and vertical coordinate is size of current.Experimental result shows that matrine can effectively suppress TMEM16A electric current, and rinse with the body lotion without matrine subsequently, electric current can return to close to level before inhibitory effect of matrine, and therefore experimental result shows that matrine can effectively suppress TMEM16A channel current.
Embodiment 15
Any one in above-described embodiment 1 to embodiment 12 is contained a kind of inhibitor of pharmaceutical composition as TMEM16A ion channel of matrine, for suppressing TMEM16A passage, weakening guinea pig ileum and shrinking.
Get Hatley Cavia porcellus one, after killing, cut abdominal cavity open immediately, take out one section of ileum about 10cm, be placed in oxygen-saturated tyrode's solution culture dish.Along intestinal wall removing mesentery, then ileum is cut into the segment 3 ~ 8 sections that length is 1 ~ 1.5cm, draws tyrode's solution with 5ml syringe and intestinal contents is rinsed well, change with fresh tyrode's solution for subsequent use.
Get an above-mentioned intestinal tube section for subsequent use, be placed in the culture dish filling tyrode's solution, at its diagonal wall place, two ends, use suture needle threading respectively, and tie a knot.Note keeping intestinal tube unobstructed, do not make it close.Intestinal tube one end line lies on the fixation hook of bath, then puts into 37 DEG C of Magnus' baths.Again the other end of intestinal tube is bound on the cantilever beam of tonotransducer, regulates preload to 1g.After Ileum From A White stablizes 30 minutes, after recording one section of normal contraction curve, in Magnus' bath, drip medicine E successively
act, add any one in embodiment 1 to embodiment 12 subsequently containing the pharmaceutical composition of matrine, observe and record its shrinkage curve.
Fig. 4 shows E in the present embodiment
actcause guinea pig ileum contractile response to strengthen, this contractile response can be suppressed to rapidly the representative experimental results figure of background level by matrine, abscissa is the time, and vertical coordinate is Tensity size.This figure shows, in guinea pig ileum contractile response determination experiment, the contractile response caused because TMEM16A passage is activated can be suppressed to background level rapidly by matrine.Namely E is added
actwhen making final concentration in bath reach 10 μMs, TMEM16A can by E
actactivate, guinea pig ileum is produced and shrinks, add matrine subsequently and make its final concentration reach 100 μMs, suppress TMEM16A passage that the contractile response of ileum is obviously declined, this shows that matrine also has extremely significant inhibitory action to the TMEM16A passage on animal body.
Embodiment 16
Any one in above-described embodiment 1 to embodiment 12 is contained a kind of inhibitor of pharmaceutical composition as TMEM16A ion channel of matrine, be used for the treatment of the secretory diarrhea disease of people, the clinical trial of this pharmaceutical composition is as follows:
Case selection: secretory diarrhea patient 60 example, clinical manifestation with stool amount more than 1L; Stool is water sample, without pus and blood; Fasting is suffered from diarrhoea after 48 hours still sustainable existence, and it is main that stool amount is still greater than 500ml/24h, all secretory diarrhea patients without other pathological changes, without medication history, without serious systemic disease.60 routine patients be divided at random Sophorcarpidine Treating group and norfloxacin capsule treatment matched group, often organize each 30 example, treatment group male 16 example, women 14 example, age 17-68 year; Matched group male 15 example, women 15 example, age 18-69 year.The equal not statistically significant of clinical manifestation difference before the sex for the treatment of group and matched group, age, the course of disease, treatment.
Usage and dosage: advise patient to be careful in one's diet health during treatment.Sophorcarpidine Treating group adopt medicinal preparation for oral administration, every day 1 time, one time one; Norfloxacin capsule treatment group adopts norfloxacin capsule (Pharmaceutical Factory No.6, Harbin Pharmaceutical Group) oral tablet, every day 3 times, once two.
The standard of curative effect evaluation:
(1) effective: medication stool amount minimizing afterwards in 1 day, water sample stool disappears, without pus and blood.
(2) effective: medication after 3 days clinical symptoms substantially disappear, stool discharge capacity obviously reduces.
(3) invalid: still excess of defecating after more than 7 days, stool water sample, fasting is suffered from diarrhoea after 48 hours still sustainable existence.Therapeutic outcome: effective 25 examples of the matrine pharmaceutical treatment group prepared by pharmaceutical composition of the present invention, account for 83.33%; Effective 3 examples, invalid 2 examples, total effective rate is 93.33%; Effective 19 examples of norfloxacin capsule treatment group, effective 7 examples, invalid 4 examples, total effective rate is 86.67%.Sophorcarpidine Treating group total effective rate is apparently higher than norfloxacin capsule treatment group.
Claims (10)
1. containing the pharmaceutical composition of matrine, it is characterized in that: being by being active component with matrine, being aided with pharmaceutically acceptable carrier composition.
2. according to claim 1 containing the pharmaceutical composition of matrine, it is characterized in that: described pharmaceutically acceptable carrier is starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol or the wherein mixture of 2 ~ 6 kinds, and the matrine of described active component is 1: 0.5 ~ 1.5 with being aided with pharmaceutically acceptable carrier quality ratio.
3. according to claim 1 or claim 2, contain the pharmaceutical composition of matrine, it is characterized in that: the building form of described pharmaceutical composition is oral type administration.
4. according to claim 3 containing the pharmaceutical composition of matrine, it is characterized in that: the building form of described pharmaceutical composition is the dosage form of oral type administration is powder, granule, capsule, tablet, drop pill or oral liquid.
5. according to claim 1 or claim 2, contain the pharmaceutical composition of matrine, it is characterized in that: the building form of described pharmaceutical composition is parenteral type administration.
6. according to claim 5 containing the pharmaceutical composition of matrine, it is characterized in that: the building form of described pharmaceutical composition is the dosage form of parenteral type administration is injection.
7. contain the application of the pharmaceutical composition of matrine described in claim 1, it is characterized in that: as TMEM16A inhibitors of ion channels, be used for the treatment of TMEM16A/CaCCs ion channel relevant disease.
8. according to claim 7 containing the application of the pharmaceutical composition of matrine, it is characterized in that: be any one dosage form contained in the claims 1 ~ 6 in the pharmaceutical composition of matrine as TMEM16A inhibitors of ion channels.
9., according to claim 7 containing the application of pharmaceutical composition of matrine, it is characterized in that: described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the secretory diarrhea disease being used for the treatment of people.
10., according to claim 7 containing the application of pharmaceutical composition of matrine, it is characterized in that: described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the secretory diarrhea disease being used for the treatment of cattle, horse, sheep, Canis familiaris L., cat, pig or Mus.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415293A (en) * | 2002-12-04 | 2003-05-07 | 正安医药(天津)药物研究发展有限公司 | Alkaloid of matrine category utilized for mainline and its preparation method |
| CN1554339A (en) * | 2003-12-26 | 2004-12-15 | 房继忠 | Matrine enteric soluble hard capsule and its preparing method |
| CN102091049A (en) * | 2011-01-17 | 2011-06-15 | 广东东阳光药业有限公司 | Matrine dispersible tablet and preparation process thereof |
| CN102764236A (en) * | 2012-07-02 | 2012-11-07 | 兰州大学第二医院 | Matrine granules and preparation method thereof |
| CN104171326A (en) * | 2014-07-29 | 2014-12-03 | 成都巨星农牧科技有限公司 | Anti-diarrhea premix additive for pig feed |
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2016
- 2016-01-04 CN CN201610009325.5A patent/CN105412010A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415293A (en) * | 2002-12-04 | 2003-05-07 | 正安医药(天津)药物研究发展有限公司 | Alkaloid of matrine category utilized for mainline and its preparation method |
| CN1554339A (en) * | 2003-12-26 | 2004-12-15 | 房继忠 | Matrine enteric soluble hard capsule and its preparing method |
| CN102091049A (en) * | 2011-01-17 | 2011-06-15 | 广东东阳光药业有限公司 | Matrine dispersible tablet and preparation process thereof |
| CN102764236A (en) * | 2012-07-02 | 2012-11-07 | 兰州大学第二医院 | Matrine granules and preparation method thereof |
| CN104171326A (en) * | 2014-07-29 | 2014-12-03 | 成都巨星农牧科技有限公司 | Anti-diarrhea premix additive for pig feed |
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