CN104739812A - Pharmaceutical composition containing resveratrol and application of pharmaceutical composition - Google Patents
Pharmaceutical composition containing resveratrol and application of pharmaceutical composition Download PDFInfo
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Abstract
The invention discloses a pharmaceutical composition containing resveratrol and an application of the pharmaceutical composition, and relates to a pharmaceutical preparation of the pharmaceutical composition containing resveratrol. The pharmaceutical composition takes resveratrol as an active ingredient, and is supplemented with a pharmaceutically acceptable carrier which is starch, sugar, dextrin, lactose, microcrystalline cellulose, mannitol or a mixture of 2-6 of the starch, sugar, dextrin, lactose, microcrystalline cellulose and mannitol, wherein a weight ratio of the resveratrol to the carrier is 1 to (0.4-1.6). The pharmaceutical composition which is taken as an activator of a TMEM16A ion channel is used as a drug for treating TMEM16A/CaCCS ion channel-associated diseases, for example gastrointestinal motility disorder, so that the defect that the existing drug for treating the gastrointestinal motility disorder has side reaction to different extents, and is limited in clinical application.
Description
Technical field
Technical scheme of the present invention relates to the pharmaceutical preparation of the pharmaceutical composition containing resveratrol, specifically containing pharmaceutical composition and the application thereof of resveratrol.
Background technology
Resveratrol (trans-3,4 ', 5-trihydroxystilbene, Resveratrol) is a kind of natural stilbene compound, natural Polyphenols, antioxidant and phytoalexin, its molecular formula: C
14h
12o
3, molecular weight is 228, No. CAS: 501-36-0.Be mainly derived from: the natural plants such as Fructus Vitis viniferae and Semen arachidis hypogaeae.Resveratrol is considered to (.Metabolism and bioavailability of trans-resveratrol [J] the .Molecular Nutrition & Food Research such as WENZEL E that plays an important role in " French contradiction ", 2005,49:472 – 481).
In prior art, resveratrol is the chemopreventive agent reducing platelet aggregation, keep unblocked blood flowing and reduction blood viscosity, prevention and therapy atherosclerosis and cardiovascular and cerebrovascular disease.It is except cardiovascular protective effect, resveratrol also because of its have antiinflammatory, antitumor, estrogen-like effects, reproducibility (
antioxidant activity of food constituents:an overview [J] .Arch Toxicol, 2012,86:345 – 391) and extend unicellular lower eukaryote body life time and improve the effect of the aspects such as mammals health and be subject to extensive concern.
Gastrointestinal motility disorders (Disorders of gastrointestinal motility, DGIM) common disease is belonged to, its form of expression is various, existing gastrointestinal function weakens, gastrointestinal function is hyperfunction, also gastrointestinal dysfunction is had, the major measure of current these diseases for the treatment of regulates digestive tract power, short digestive tract power reinforcing medicine is main treatment means, but all there is side reaction in various degree in these medicines, clinical practice is restricted (Mc Callum R W.Motility agenis and the gastrointestinai tract.Am J Med Sci, 1996, 312 (1): 19-25).Gastrointestinal motility disorder causes due to neural or muscle changes, comprises functional intestinal disease and gastrointestinal motility disorder, is mainly common in gastroesophageal reflux disease, functional dyspepsia, irritable bowel syndrome and chronic constipation etc.Along with the development of society, gastrointestinal motility disorder disease prevalence rises year by year and affects the quality of life of people, and this type of disease also becomes the focus of research both at home and abroad.The adjustment of gastrointestinal motility is mainly by the impact of two aspect factors: namely Nervous system is unified humoral factor.Recent research shows, TMEM16A ion channel can regulate the humoral selection of gastrointestinal, thus motion (the .Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles.The Journal of Physiology.2009 such as Hwang SJ of regulation and control gastrointestinal, 587.20:4887 – 4904), TMEM16A gene expression is in small intestinal Interstitial cell, and it can control the contraction rhythm and pace of moving things of smooth muscle.
But do not find so far not retrieve about the pharmaceutical composition containing resveratrol is used for the treatment of TMEM16A/CaCCs ion channel relevant disease as the report of the medicine of gastrointestinal motility disorder aspect and pertinent literature yet.
Summary of the invention
Technical problem to be solved by this invention is: provide the pharmaceutical composition containing resveratrol and application thereof, should containing the pharmaceutical composition of resveratrol using resveratrol as a kind of activator of TMEM16A ion channel, be used for the treatment of TMEM16A/CaCCs ion channel relevant disease as the medicine of gastrointestinal motility disorder aspect, overcome existing medicine in treatment gastrointestinal motility disorders, all there is the defect that side reaction in various degree and clinical practice be restricted.
The present invention solves this technical problem adopted technical scheme: containing the pharmaceutical composition of resveratrol, take resveratrol as active component, is aided with pharmaceutically acceptable carrier.
The above-mentioned pharmaceutical composition containing resveratrol, described pharmaceutically acceptable carrier is starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol or its mixture of 2 ~ 6 kinds, and the resveratrol of described active component is 1: 0.4 ~ 1.6 with the weight ratio of the consumption being aided with pharmaceutically acceptable carrier.
The above-mentioned pharmaceutical composition containing resveratrol, described pharmaceutical composition is oral type administration.
The above-mentioned pharmaceutical composition containing resveratrol, the dosage form of the oral type administration of described pharmaceutical composition is powder, granule, capsule, tablet, drop pill or oral liquid.
The above-mentioned pharmaceutical composition containing resveratrol, described pharmaceutical composition is parenteral type administration.
The above-mentioned pharmaceutical composition containing resveratrol, the parenteral type administration of described pharmaceutical composition is injection.
The above-mentioned pharmaceutical composition containing resveratrol, involved component materials 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 outfit method is that those skilled in the art can grasp.
The application of the above-mentioned pharmaceutical composition containing resveratrol, as a kind of activator of TMEM16A ion channel, is used for the treatment of TMEM16A/CaCCs ion channel relevant disease.
The application of the above-mentioned pharmaceutical composition containing resveratrol, described a kind of activator as TMEM16A ion channel is above-mentioned containing any one in the pharmaceutical composition of resveratrol.
The application of the above-mentioned pharmaceutical composition containing resveratrol, described TMEM16A/CaCCs ion channel relevant disease refers to the gastrointestinal motility disorder disease of people.
The above-mentioned pharmaceutical composition containing resveratrol also can be applicable to treat the gastrointestinal motility disorder disease of cattle, horse, sheep, Canis familiaris L., cat, pig or Mus.
The application of the above-mentioned pharmaceutical composition containing resveratrol, involved treatment operational approach is that those skilled in the art can grasp.
The invention has the beneficial effects as follows: the substantive distinguishing features that the present invention gives prominence to is:
For stomach and intestine dynamics disorders, TMEM16A activator can be used for treatment digestive tract power deficiency (as constipation) (Namkung W, Yao Z, Finkbeiner WE, Verkman AS.Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction.FASEB J.2011.25:4048-4062).By the further investigation for resveratrol, inventor finds the TMEM16A passage that resveratrol passes through to act on gastrointestinal epithelial cell and plays a role, and resveratrol by activating TMEM16A passage, and then affects contraction frequency and the tension force of gastrointestinal smooth muscle.
Marked improvement of the present invention is:
(1) resveratrol is used for the control of digestive tract power disease particularly gastrointestinal motility disorder by activating TMEM16A passage, have brand-new mechanism of action, having a good application prospect, it will have potential clinical value in gastrointestinal motility disorder disease.
(2) resveratrol one is a kind of natural stilbene compound, is mainly derived from: the plant of the natural fecund such as Fructus Vitis viniferae and Semen arachidis hypogaeae, abundance.
(3) the pharmaceutical composition collocation method containing resveratrol of the present invention is simple, with low cost.
(4) application process of the pharmaceutical composition containing resveratrol 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 the experimental result of HEK293 cell curent change situation under the effect of variable concentrations free calcium ions and resveratrol of transfection TMEM16A passage under inside-out pattern, wherein:
Fig. 1 a is the representative experimental results figure of the blank group activated current of the HEK293 cell of not transfection TMEM16A ion channel.
Fig. 1 b be in embodiment 13 in body lotion containing the representative experimental results figure of the activated current under concentration 30 μMs of resveratrol conditions.
Fig. 1 c be in embodiment 13 in body lotion containing the representative experimental results figure of the activated current under concentration 100 μMs of resveratrol conditions.
Fig. 1 d be in embodiment 13 100 μMs of tannin in body lotion containing the inhibiting representative experimental results figure of activated current under concentration 100 μMs of resveratrol conditions.
Fig. 1 e is the representative experimental results figure of activated current when containing 1 μM of free calcium ions in embodiment 13 in body lotion.
Fig. 2 a is that in embodiment 14, resveratrol causes guinea pig ileum contractile response to strengthen, and contractile response can be suppressed to rapidly the representative experimental results of background level by TMEM16A inhibitors of ion channels CaCCinh-A01.
Fig. 2 b shows resveratrol can enlarge markedly gastrointestinal tract contraction tension force block diagram in embodiment 14.
Fig. 3 is the representative experimental results that under the same visual field, resveratrol affects the fluorescence intensity of yellow fluorescence protein as TMEM16A ion channel activator, wherein:
Fig. 3 a is the representative experimental results figure of yellow fluorescent protein fluorescence intensity in cell when not adding resveratrol in embodiment 15.
Fig. 3 b is the representative experimental results adding yellow fluorescent protein fluorescence intensity in cell after resveratrol in embodiment 15.
Fig. 4 is under the same visual field under the effect of TMEM16A inhibitors of ion channels tannin, the representative experimental results that resveratrol affects the fluorescence intensity of yellow fluorescence protein, wherein:
Fig. 4 a is the representative experimental results figure of yellow fluorescent protein fluorescence intensity in cell when not adding resveratrol in embodiment 15.
Fig. 4 b is the representative experimental results adding yellow fluorescent protein fluorescence intensity in cell after resveratrol in embodiment 15.
Detailed description of the invention
Fig. 1 a illustrated embodiment shows, the blank group activated current of the HEK293 cell of not transfection TMEM16A ion channel is background current, and steady-state current is less than 6pA.
Fig. 1 b illustrated embodiment shows, in embodiment 13, containing activated current during 30 μMs of resveratrols in body lotion, it is about 50pA for exemplary currents when TMEM16A ion channel is activated, steady-state current size, and display is than the obviously increase of blank group.
Fig. 1 c illustrated embodiment shows, in embodiment 13, containing the activated current under concentration 100 μMs of resveratrol conditions in body lotion, steady-state current size is about 100pA.
Fig. 1 d illustrated embodiment shows, 100 μMs of tannin are to the inhibitory action containing the activated current under concentration 100 μMs of resveratrol conditions in body lotion, because tannin is the inhibitor of calcium-activated potassium current, so Fig. 1 d electric current shown in the embodiment shown in Fig. 1 b and Fig. 1 c is the electric current that TMEM16A ion channel mediates, TMEM16A ion channel can be activated by resveratrol.
Fig. 1 e illustrated embodiment shows, in embodiment 13, containing the activated current under concentration 1 μM of calcium ion condition in body lotion, steady-state current size is about 50pA, and display obviously increases than blank group.
Fig. 2 a illustrated embodiment shows, in embodiment 14, in guinea pig ileum contractile response determination experiment, resveratrol can cause guinea pig ileum contractile response to strengthen, and contractile response can be suppressed to background level rapidly by TMEM16A inhibitors of ion channels CaCCinh-A01.
Fig. 2 b illustrated embodiment shows, in embodiment 14, in guinea pig ileum contractile response determination experiment, resveratrol significantly can increase and promote gastrointestinal tract contraction power.The independent experiment number of times of the present embodiment is 6 times.In figure, * * represents compared with matched group, and resveratrol processed group exists pole significant difference (P<0.01).
Fig. 3 a illustrated embodiment shows, in embodiment 15, the fluorescence intensity of yellow fluorescence protein in cell when not adding resveratrol, each cell interior is strong yellow fluorescence.
Fig. 3 b illustrated embodiment shows, in embodiment 15, the fluorescence intensity of yellow fluorescence protein in cell when adding resveratrol, because resveratrol 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.
Fig. 4 a illustrated embodiment shows, and in embodiment 15, under the condition adding TMEM16A inhibitor tannin, non-resveratrol adds the fluorescence intensity of yellow fluorescence protein in fashionable cell, and each cell interior is strong yellow fluorescence.
Fig. 4 b illustrated embodiment shows, in embodiment 15, under the condition adding TMEM16A inhibitor tannin, and the fluorescence intensity of yellow fluorescence protein in cell when adding resveratrol, because tannin inhibits TMEM16A ion channel, iodide ion is not caused to enter in born of the same parents, thus the not cancellation of the yellow fluorescence of cell.
Embodiment 1
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with starch carrier, the weight ratio of the consumption of resveratrol and starch carrier is 1:0.4, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 2
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with Icing Sugar carrier, the weight ratio of the consumption of resveratrol and Icing Sugar carrier is 1:0.4, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the granule of oral type administration.
Embodiment 3
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with dextrin carrier, the weight ratio of the consumption of resveratrol and dextrin carrier is 1:1, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the capsule of oral type administration.
Embodiment 4
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with lactose carrier, the weight ratio of the consumption of resveratrol and lactose carrier is 1:1.6, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the tablet of oral type administration.
Embodiment 5
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with microcrystalline Cellulose carrier, the weight ratio of the consumption of resveratrol and microcrystalline Cellulose carrier is 1:1, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the drop pill of oral type administration.
Embodiment 6
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with mannitol carrier, the weight ratio of the consumption of resveratrol and mannitol carrier is 1:0.7, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the injection of parenteral type administration.
Embodiment 7
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, be aided with the starch sugaring powder carrier of arbitrary proportion, the starch of resveratrol and arbitrary proportion is 1:1 with the weight ratio of the consumption of Icing Sugar, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 8
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, the dextrin being aided with arbitrary proportion adds the carrier that lactose adds microcrystalline Cellulose, it is 1:1.6 that the dextrin of resveratrol and arbitrary proportion adds the weight ratio that lactose adds the consumption of microcrystalline Cellulose, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 9
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, the dextrin being aided with arbitrary proportion adds lactose and adds the carrier of microcrystalline Cellulose with mannitol, resveratrol and arbitrary proportion dextrin add lactose, and to add microcrystalline Cellulose with the weight ratio of the consumption of mannitol be 1:1.6, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 10
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol as active component, the dextrin being aided with arbitrary proportion adds lactose and adds microcrystalline Cellulose with mannitol sugaring powder carrier, the dextrin of resveratrol and arbitrary proportion adds lactose, and to add microcrystalline Cellulose with mannitol be 1: 1 with the weight ratio of the consumption of Icing Sugar, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 11
The pharmaceutical composition containing resveratrol of the present embodiment, take resveratrol 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 1:0.4 that resveratrol and arbitrary proportion mush finishing lactose add microcrystalline Cellulose adds the consumption of starch with Icing Sugar weight ratio with mannitol, its outfit method uses pharmaceutically acceptable form, and the pharmaceutical composition containing resveratrol of the present embodiment is the powder of oral type administration.
Embodiment 12
Get distilled water 500mL, add Tween-80 and make solution, add resveratrol 100g again, heat while stirring and make it to be dissolved into the solution containing resveratrol, in addition sucrose 50g added the antiseptic of known standard consumption and be dissolved in distilled water 100mL, obtained sucrose solution, again this sucrose solution is under agitation added above-mentioned containing in the solution of resveratrol, adding distil water is to 1000mL, mixing, filters, is distributed into 200, sterilizing, the oral liquid of the pharmaceutical composition containing resveratrol of obtained the present embodiment.
In the embodiment of following the present invention containing the application of the pharmaceutical composition of resveratrol, the selected pharmaceutical composition containing resveratrol be any one in above-described embodiment 1 to embodiment 12 containing the pharmaceutical composition of resveratrol.
Embodiment 13
Any one pharmaceutical composition containing resveratrol in above-described embodiment 1 to embodiment 12, as a kind of activator of TMEM16A ion channel, has the HEK293 cell currents value of TMEM16A ion channel to strengthen for making transfection:
Expression plasmid pEGFP-N1-TMEM16A is proceeded in mammalian cell HEK293.After cell transfecting within 24-72h, patch clamp technique is utilized to carry out electro physiology detection.Concrete grammar is as follows:
DMEM (high sugar) the culture fluid Secondary Culture of HEK293 cell containing 10% hyclone, namely adds penicillin and the 100 μ g/mL streptomycins of 100UI/mL.Transfection process Invitrogen Products Lipofectamine 2000 liposome carries out.Cell in 37 DEG C, the CO of 5%
2exponential phase is cultured to for experiment in saturated humidity incubator.Electro physiology detects and at room temperature carries out, adopt inside-out (Inside-Out) logging mode (EPC-10Amplifier, HEKA company, Germany), outside interior liquid and basis, the composition of liquid is (unit: mM): CsCl 140, MgCl
26H
2o, HEPES 10, EGTA 5, is adjusted to pH7.3 with CsOH.The concentration adding resveratrol in the outer liquid of medicine is set to 30 μMs and 100 μMs respectively, whether express with 100nM free calcium ions test TMEM16A passage, negative control is done without calcium solution with 10mM EGTA, the mixed solution finally adding 100 μMs of tannin suppresses calcium channel, and makes comparisons with the electric current under 1 μM of free calcium condition.By voltage depolarization activated membrane electric current, process conditions are: membrane depolarization voltage is from-80mV to+80mV, and step is 20mV, and ME for maintenance is 0mV.
Result is as shown in Fig. 1 a ~ Fig. 1 c, and activated current increases along with the concentration increase of resveratrol in body lotion.The resveratrol of high concentration (100 μMs) is suitable with high concentration free calcium ions (1 μM) to the activation degree of TMEM16A passage, making veratryl alcohol clear has the HEK293 cell of TMEM16A plasmid to have obvious activation to transfection, is the activator of TMEM16A modality specificity.
Embodiment 14
Any one pharmaceutical composition containing resveratrol in above-described embodiment 1 to embodiment 12, as a kind of activator of TMEM16A ion channel, for activating TMEM16A passage, causes guinea pig ileum to shrink.
Resveratrol can activate TMEM16A passage, impels guinea pig ileum to shrink:
Get Hatley Cavia porcellus one, after killing, cut abdominal cavity open immediately, take out one section of ileum and be about 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 bath fixation hook, 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 10 ~ 30 minutes, after recording one section of normal contraction curve, in Magnus' bath, drip medicine successively, observe and record its shrinkage curve.
As shown in Figure 3 a, add the resveratrol 0.2mL of 100uM, after tens of second, resveratrol enters cell-stimulating TMEM16A passage and impels the contraction of ileum significantly to increase; To change dressings after 3 minutes liquid, add the CaCCinh-A01 solution 0.2mL of 30uM, suppress TMEM16A passage that the contractile response of ileum is obviously declined, this shows that resveratrol also has very significant activation to the TMEM16A passage on animal body.
Embodiment 15
Any one pharmaceutical composition containing resveratrol in above-described embodiment 1 to embodiment 12 as a kind of activator of TMEM16A ion channel, the cell fluorescence generation cancellation for making transfection have TMEM16A in iodide ion yellow fluorescence protein (YFP) Fluorimetric Quenching Method:
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 site H148Q and I 152L that suddenlys change 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.This drug screening test by the YFP channel genes HEK293 cell of external source, makes YFP great expression in born of the same parents by the method for liposome; 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, method can make the medicine of the obvious cancellation of YFP can be considered to the activator of CaCCs passage, and prove that the pharmaceutical composition containing resveratrol of the present embodiment is the activator of CaCCs passage thus, this result and patch clamp experiments result are confirmed mutually.
Resveratrol can make transfection have the cell fluorescence generation cancellation of TMEM16A in iodide ion YFP Fluorimetric Quenching Method:
The HEK293 cell of stable transfection YFP is cultivated in experiment the previous day in the burnt special ware of copolymerization; Within second day, by transfection YFP and the HEK293 cell D-PBS of overnight incubation rinses 3 times, finally leave 500 μ L D-PBS; Add the solution 500 μ L of 150mM I-, make I-concentration reach 75mM, hatch 10min, record fluorescence intensity is Baseline fluorescence intensity; By laser confocal microscope real time record fluorescence intensity, now add and make its final concentration reach 300 μMs containing 100mM resveratrol storage liquid 15 μ L, the change of record YFP fluorescence intensity.
As shown in fig. 4 a, the fluorescence intensity first adding YFP during I-is very high; After adding resveratrol, as shown in Figure 4 b, the obvious cancellation of YFP fluorescence, after 2min, fluorescence almost disappears completely; Only add in another group and do not add in the matched group of resveratrol containing the solution of iodide ion, the fluorescence intensity of YFP does not change all the time, makes the activator that veratryl alcohol is TMEM16A passage clear.
First I is added
-solution, then add tannin (TMEM16A specific inhibitor) and hatch 10 to 20min, then add resveratrol, in this process, the fluorescence intensity of YFP is always without significant change, make clear veratryl alcohol be activate be TMEM16A passage.
To sum up embodiment proves, resveratrol can the TMEM16A passage of effective active cell, is that the pharmaceutical composition of active component can treat gastrointestinal motility disorder disease with resveratrol.
Embodiment 16
Any one pharmaceutical composition containing resveratrol in above-described embodiment 1 to embodiment 12 is as a kind of activator of TMEM16A ion channel, and be used for the treatment of the gastrointestinal motility disorder disease of people, the clinical trial of this pharmaceutical composition is as follows:
Case selection: gastrointestinal motility disorder patient 78 example, clinical manifestation based on inappetence, stomachache, abdominal distention, feel sick, early full, vomiting, diarrhoea and difficult defecation etc., all patients become, without medication history, without serious systemic disease without other digestive tract makings sexually transmitted disease (STD)s except gastrointestinal motility disorder.78 routine patients be divided at random resveratrol treatment group and motilium treatment matched group, often organize each 39 example, treatment group male 18 example, women 21 example, age 16-65 year; Matched group male 19 example, women 20 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.Resveratrol treatment group adopt medicinal preparation for oral administration, every day 1 time, one time one; Motilium treatment group adopt motilium (Xian-Janssen Pharmaceutical Ltd.) oral tablet, every day 3 times, one time one.
The standard of curative effect evaluation:
(1) effective: medication is vomitted for 2 days afterwards, symptom of diarrhea goes down, and without nausea, appetite strengthens.
(2) effective: medication after 5 days clinical symptoms substantially disappear, appetite is strengthened.
(3) invalid: still had stomachache, abdominal distention more than 10 days, feel sick, early full, vomiting, the symptom such as diarrhoea and difficult defecation.
Therapeutic outcome: effective 33 examples of the resveratrol pharmaceutical treatment group prepared by pharmaceutical composition of the present invention, account for 84.62%; Effective 6 examples, total effective rate is 100%; Effective 29 examples of motilium treatment group, effective 4 examples, invalid 6 examples, total effective rate is 84.61%.Resveratrol treatment group total effective rate is apparently higher than motilium treatment group.
Claims (9)
1. containing the pharmaceutical composition of resveratrol, it is characterized in that: be active component with resveratrol, be aided with pharmaceutically acceptable carrier.
2. according to claim 1 containing the pharmaceutical composition of resveratrol, it is characterized in that: described pharmaceutically acceptable carrier is starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol or its mixture of 2 ~ 6 kinds, the resveratrol of described active component is 1: 0.4 ~ 1.6 with the weight ratio of the consumption being aided with pharmaceutically acceptable carrier.
3. according to claim 1 or claim 2, contain the pharmaceutical composition of resveratrol, it is characterized in that: described pharmaceutical composition is oral type administration.
4., according to claim 3 containing the pharmaceutical composition of resveratrol, it is characterized in that: the dosage form of the oral type administration of described pharmaceutical composition is powder, granule, capsule, tablet, drop pill or oral liquid.
5. according to claim 1 or claim 2, contain the pharmaceutical composition of resveratrol, it is characterized in that: described pharmaceutical composition is parenteral type administration.
6., according to claim 5 containing the pharmaceutical composition of resveratrol, it is characterized in that: the parenteral type administration of described pharmaceutical composition is injection.
7. the application of the above-mentioned pharmaceutical composition containing resveratrol, is characterized in that: as a kind of activator of TMEM16A ion channel, is used for the treatment of TMEM16A/CaCCs ion channel relevant disease.
8., according to claim 7 containing the application of pharmaceutical composition of resveratrol, it is characterized in that: described a kind of activator as TMEM16A ion channel be any one described in claim 1 ~ claim 6 containing the pharmaceutical composition of resveratrol.
9., according to claim 7 containing the application of the pharmaceutical composition of resveratrol, it is characterized in that: described TMEM16A/CaCCs ion channel relevant disease refers to the gastrointestinal motility disorder disease of people.
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| CN106389395A (en) * | 2016-10-21 | 2017-02-15 | 温州市人民医院 | Use of resveratrol in preparation of drug for treating irritable bowel syndrome (IBS) |
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| CN103845311A (en) * | 2012-11-28 | 2014-06-11 | 青岛恒润源通果蔬专业合作社 | New medical use of resveratrol |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106389395A (en) * | 2016-10-21 | 2017-02-15 | 温州市人民医院 | Use of resveratrol in preparation of drug for treating irritable bowel syndrome (IBS) |
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