CN105434358A - Pharmaceutical composition containing taurine and application of pharmaceutical composition - Google Patents
Pharmaceutical composition containing taurine and application of pharmaceutical composition Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Abstract
The invention discloses a pharmaceutical composition containing taurine and application of the pharmaceutical composition, relating to the pharmaceutical composition which is prepared by taking the taurine as an active ingredient and a pharmaceutically acceptable carrier as supplementary, wherein the pharmaceutically acceptable carrier is starch, powdered sugar, dextrin, lactose, microcrystalline cellulose, mannitol or a mixture of 2 to 6 therein; the mass ratio of the taurine as the active ingredient to the pharmaceutically acceptable carrier as supplementary is 1:(0.5 to 1.5); the pharmaceutical composition containing the taurine is a drug used for treating diseases related to a TMEM16A/CaCCS ion channel, and has a significant effect on treating bronchial asthma.
Description
Technical field
Technical scheme of the present invention relates to pharmaceutical composition, specifically containing pharmaceutical composition and the application thereof of taurine.
Background technology
Bronchial asthma is the chronic airway inflammation disease participated in by various kinds of cell and cellular component, common symptoms has: with the expiratory dyspnea of wheezing sound or ictal cough, uncomfortable in chest, dry cough or cough a large amount of white foam expectorant, some teenager patients then can move time occur uncomfortable in chest, cough and dyspnea, symptoms of asthma can be shown effect in several minutes, through a few hours to a couple of days, with bronchodilators or spontaneous remission.Cause the reason of asthma to be many-sided, comprise inherited genetic factors and environmental factors, air pollution, smoking, respiratory virus infection, gestation and strenuous exercise, climate flip all can bring out asthma attack.Along with the raising of social industrialization degree, environmental pollution goes from bad to worse, and haze phenomenon is day by day serious, and this also directly results in the continuous rising of asthma prevalence.Therefore, the specific medicament that bronchial asthma is treated in positive research and development has become an extremely urgent problem.
There is bibliographical information recently, the process LAN of Ca2+-activated Cl-channels TMEM16A is the one of the main reasons causing asthma, by suppressing the expression of Ca2+-activated Cl-channels TMEM16A, effectively can treat asthma (BrettTJ.CLCA1andTMEM16A:thelinktowardsapotentialcurefora irwaydiseases [J] .ExpertReviewofRespiratoryMedicine, 2015:503-506.).TMEM16A is an important ion channel on airway smooth muscle, research shows that asthma can cause the process LAN of TMEM16A on airway smooth muscle, and the process LAN of TMEM16A can the exacerbate asthma state of an illness, therefore, by specific inhibitor, TMEM16A on airway smooth muscle is suppressed, a kind of effective means for the treatment of asthma may be become.For traditional Chinese medical science the world of medicine of China, searching and research and develop the specially good effect Chinese herbal medicine can treating bronchial asthma is duty-bound urgent task.
Summary of the invention
Technical problem to be solved by this invention is: provide the pharmaceutical composition containing taurine 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 bronchial asthma.
The present invention solves this technical problem adopted technical scheme: containing the pharmaceutical composition of taurine, being by taking taurine as active component, being aided with pharmaceutically acceptable carrier composition.
The above-mentioned pharmaceutical composition containing taurine; described pharmaceutically acceptable carrier is starch, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol or its mixture of 2 ~ 6 kinds, and the taurine of described active component is 1: 0.5 ~ 1.5 with the mass ratio being aided with pharmaceutically acceptable carrier.
The above-mentioned pharmaceutical composition containing taurine, the building form of described pharmaceutical composition is oral type administration.
The above-mentioned pharmaceutical composition containing taurine, 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 taurine, the building form of described pharmaceutical composition is parenteral type administration.
The above-mentioned pharmaceutical composition containing taurine, the building form of described pharmaceutical composition is the dosage form of parenteral type administration is injection.
The above-mentioned pharmaceutical composition containing taurine; wherein taurine is purchased from Aladdin reagent company limited; No. CAS: 107-35-7; 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 taurine, 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 taurine, described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the bronchial asthma disease being used for the treatment of people.
The application of the above-mentioned pharmaceutical composition containing taurine is above-mentioned containing any one dosage form in the pharmaceutical composition of taurine as TMEM16A inhibitors of ion channels.
The application of the above-mentioned pharmaceutical composition containing taurine, 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) there is the good recipe of much treatment asthma in Traditional Chinese Medicine, but mostly be compound medicines due to Chinese herbal medicine, be difficult to the concrete composition determining wherein to work.Inventor searches candidate's Chinese herbal medicine for the treatment of asthma according to " Chinese medicine voluminous dictionary ", find that Chinese medicine Calculus Bovis has good curative effect in treatment asthma, and the material wherein mainly worked is taurine.Taurine is isolated single component from Calculus Bovis, Chinese chemical name: 2-aminoethyl sulfonic acid, English language Chemical title: 2-Aminoethanesulfonicacid, and sterling is colourless or white oblique shape crystal, odorless.Taurine stable chemical nature is a kind of non-protein amino acid of sulfur-bearing, exists in vivo, do not participate in the biosynthesis of albumen in body with free state, little to human body side effect.
(2) nearly ten years, the inhibitor that calcium activates chlorine ion channels TMEM16A channel current was found in succession, such as CaCC
inh-A01, T16A
inh-A01, DIDS, NPPB etc., but the inhibitor of Ca2+-activated Cl-channels TMEM16A is chemosynthesis material, 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, the natural product small-molecule drug that therefore active development is less to cell damage is a far reaching research contents.
Test proves, reach 85% by of the present invention containing the pharmaceutical composition of taurine and the outward current suppression ratio of the mixing material of cell body lotion to Ca2+-activated Cl-channels TMEM16A, half effective inhibition concentration is within 100 μMs.This effective medicine for development asthma opens a fan gate.
Compared with prior art, marked improvement of the present invention is as follows:
(1) pharmaceutical composition containing taurine of the present invention can obviously suppress TMEM16A passage, and suppression ratio can reach 85%, and the disease treatment for asthma aspect provides potential application prospect.
(2) pharmaceutical composition containing taurine 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) taurine is a kind of native compound, and from the single composition of Chinese medicine Calculus Bovis, medicament sources is enriched.
(4) the pharmaceutical composition collocation method containing taurine of the present invention is simple, with low cost.
(5) application process of the pharmaceutical composition containing taurine 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 taurine, 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 1 μM of Ca
2+after, the Chinese hamster ovary celI fluorogram of transfection Ca2+-activated Cl-channels TMEM16A and YFP;
Fig. 1 D is that the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A and YFP add 100 μMs of taurines under 1C same field of view after is adding 1 μM of Ca
2+after fluorogram;
Fig. 2 is in embodiment 14, and the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A is by 1 μM of Ca
2+after activation, the curent change typical figure of perfusion taurine;
Fig. 3 is in embodiment 14, is adding before and after taurine, the curent change typical electrical flow graph of the Chinese hamster ovary celI of reflection transfection Ca2+-activated Cl-channels TMEM16A, wherein:
Fig. 3 A is that the Chinese hamster ovary celI of the transfection Ca2+-activated Cl-channels TMEM16A of non-perfusion taurine is by 1 μM of Ca
2+the typical electrical flow graph activated;
Fig. 3 B is that the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A is by 1 μM of Ca
2+activate, the typical electrical flow graph after re perfusion taurine;
Fig. 4 is in embodiment 14, at the Chinese hamster ovary celI of transfection Ca2+-activated Cl-channels TMEM16A by 1 μM of Ca
2+after activation, with the electric current variation diagram in time of the body lotion perfusion record current change continuously that contain 100 μMs of taurines, rinse after current with the body lotion not containing taurine subsequently and change typical figure in time;
Figure 5 shows that taurine molecule structure chart.
Detailed description of the invention
Embodiment 1
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with starch carrier; the mass ratio of taurine and starch carrier is 1:0.5; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the powder of oral type administration.
Embodiment 2
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with Icing Sugar carrier; the mass ratio of taurine and Icing Sugar carrier is 1:0.5; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the granule of oral type administration.
Embodiment 3
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with dextrin carrier; the mass ratio of taurine and dextrin carrier is 1:1; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the capsule of oral type administration.
Embodiment 4
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with lactose carrier; the mass ratio of taurine and lactose carrier is 1:1.5; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the tablet of oral type administration.
Embodiment 5
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with microcrystalline Cellulose carrier; the mass ratio of taurine and microcrystalline Cellulose carrier is 1:1; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the drop pill of oral type administration.
Embodiment 6
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with mannitol carrier; the mass ratio of taurine and mannitol carrier is 1:1.5; its compound method uses pharmaceutically acceptable form, and the building form of the pharmaceutical composition containing taurine of the present embodiment is the injection of parenteral type administration.
Embodiment 7
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; be aided with the starch sugaring powder carrier of arbitrary proportion; the starch of taurine 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 taurine of the present embodiment is the powder of oral type administration.
Embodiment 8
The pharmaceutical composition containing taurine of the present embodiment; take taurine 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 taurine 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 taurine of the present embodiment is the powder of oral type administration.
Embodiment 9
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; the dextrin being aided with arbitrary proportion adds lactose and adds the carrier of microcrystalline Cellulose with mannitol; taurine 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 taurine of the present embodiment is the powder of oral type administration.
Embodiment 10
The pharmaceutical composition containing taurine of the present embodiment; take taurine as active component; the dextrin being aided with arbitrary proportion adds lactose and adds microcrystalline Cellulose with mannitol sugaring powder carrier; the dextrin of taurine 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 taurine of the present embodiment is the powder of oral type administration.
Embodiment 11
The pharmaceutical composition containing taurine of the present embodiment; take taurine 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 taurine 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 taurine 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 taurine 100g; heat while stirring and make it to be dissolved into the solution containing taurine; 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 taurine; adding distil water is to 1000mL; mixing, filters, is distributed into 200; sterilizing, the oral liquid of the pharmaceutical composition containing taurine of obtained the present embodiment.
In the embodiment of following the present invention containing the application of the pharmaceutical composition of taurine, the selected pharmaceutical composition containing taurine be any one in above-described embodiment 1 to embodiment 12 containing the pharmaceutical composition of taurine.
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 taurine; 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 method of the drug screening test liposome of the present embodiment, 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 be considered to 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 the solution 500 μ l containing 150mMI-, make I-concentration reach 75mM; Add 100 μMs of taurines and hatch 10min, any one storage of pharmaceutical composition containing the taurine liquid namely in embodiment 1 to embodiment 12 makes its final concentration reach 100 μMs, adds 1 μM of Ca subsequently
2+body lotion, by laser confocal microscope real time record fluorescence intensity.
Figure 1A and Fig. 1 C shows, and does not add taurine and Ca in the present embodiment
2+time cell in the representative experimental results figure of yellow fluorescent protein fluorescence intensity.This two width figure shows not add taurine and Ca
2+time cell in the fluorescence intensity of yellow fluorescence protein, each cell interior is strong yellow fluorescence.As this two width figure shows, do not add taurine and Ca
2+time YFP fluorescence intensity very high.
Figure 1B shows, and adds 1 μ 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 1 μ Μ Ca
2+the fluorescence intensity of yellow fluorescence protein in rear cell, due to 1 μ 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.
Figure 1B shows, and adds 100 μ Μ taurines and hatches 10 minutes, add 1 μ 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 taurines can suppress Ca2+-activated Cl-channels TMEM16A, makes 1 μ 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 is contained a kind of inhibitor of pharmaceutical composition as TMEM16A ion channel of taurine, the Chinese hamster ovary celI electric current for suppressing transfection to have TMEM16A ion channel:
Proceeded to by expression plasmid pEGFP-N1-TMEM16A 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.Cell 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 (WholeCell) logging mode (EPC-10Amplifier, HEKA company, Germany), the interior liquid composition of medicine used 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 taurine joins in the outer liquid of medicine used and makes its final concentration reach 100 μMs; Do negative control with 10mMEGTA without calcium solution, and make comparisons with the electric current under 1 μM of free calcium condition.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.
Fig. 2 shows, and in the present embodiment, electric current is first by 1 μ Μ Ca in liquid in electrode
2+activate, subsequently with the also record current change continuously of the body lotion perfusion containing 100 μMs of taurines, the experimental result typical figure of electric current, abscissa is the time, and vertical coordinate is size of current; This figure shows, by 1 μ Μ Ca in liquid in electrode
2+the electric current activated; it is exemplary currents when TMEM16A ion channel is activated; steady-state current size is about 2.1nA, and its electric current effectively can be suppressed to 350pA by the body lotion containing 100 μMs of taurines, therefore proves that taurine is a kind of effective Ca2+-activated Cl-channels TMEM16A inhibitor.
Fig. 3 A shows, and contains 1 μM of Ca in the present embodiment in electrode in liquid
2+time the representative experimental results figure of activated current, this figure shows, in electrode in liquid containing 1 μM of Ca
2+time activated current, it is about 2.6nA for exemplary currents when TMEM16A ion channel is activated, steady-state current size.
Fig. 3 B shows, and in the present embodiment, electric current is contained 1 μM of Ca by liquid in electrode
2+activation, subsequently with containing the body lotion perfusion of 100 μMs of taurines, and its reach stable after the typical electrical flow graph that is recorded to, its size of current can be suppressed to 360pA, therefore proves that taurine is a kind of effective Ca2+-activated Cl-channels TMEM16A inhibitor.
Fig. 4 to show in the present embodiment electric current first by 1 μ 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 taurines, abscissa is the time, and vertical coordinate is size of current; Experimental result shows that TMEM16A electric current can effectively by Taurine inhibited, and subsequently with not rinsing containing the body lotion of taurine, electric current can return to higher level, therefore shows that taurine does not destroy the structure of passage to the suppression of TMEM16A passage.
Embodiment 15
Any one in above-described embodiment 1 to embodiment 12 is contained the pharmaceutical composition of taurine as a kind of inhibitor of TMEM16A ion channel, be used for the treatment of the asthma disease of people, the clinical trial of this pharmaceutical composition is as follows:
Case selection: asthmatic patient 56 example, clinical manifestation based on cough, uncomfortable in chest, dry cough, cough a large amount of white foam expectorant, motion time there are uncomfortable in chest and dyspnea etc., all asthmatic patients without other pathological changes, without medication history, without serious systemic disease.56 routine patients be divided at random taurine treatment group and terbutaline sulphate treatment matched group, often organize each 28 example, treatment group male 13 example, women 15 example, age 42-68 year; Matched group male 14 example, women 14 example, age 41-68 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.Taurine treatment group adopts powder, every day 3 times, once inhales 0.5mg; Terbutaline sulphate treatment group adopts terbutaline sulphate aerosol (AstraZeneca pharmaceutical Co. Ltd), every day 3 times, one time 2 spray.
The standard of curative effect evaluation:
(1) effective: the transference cures such as medication 1 day is coughed afterwards, uncomfortable in chest, dry cough, dyspnea.
(2) effective: medication after 3 days clinical symptoms greatly alleviate, the serious symptom shapes such as dyspnea disappear substantially.
(3) invalid: to take a turn for the better not yet after 7 days, the Symptoms last such as cough, uncomfortable in chest, dry cough, dyspnea occurs.
Therapeutic outcome: effective 22 examples of the taurine powder treatment group prepared by pharmaceutical composition of the present invention, account for 84.62%; Effective 4 examples, total effective rate is 92.86%; Effective 19 examples of terbutaline sulphate treatment group, effective 4 examples, invalid 5 examples, total effective rate is 82.14%.Taurine treatment group total effective rate is apparently higher than terbutaline sulphate treatment group.
In above-described embodiment, taurine is purchased from Aladdin reagent company limited; No. CAS: 107-35-7; 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.
Claims (9)
1. containing the pharmaceutical composition of taurine, it is characterized in that: being by being active component with taurine, being aided with pharmaceutically acceptable carrier composition.
2. according to claim 1 containing the pharmaceutical composition of taurine; 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 taurine of described active component is 1: 0.5 ~ 1.5 with the mass ratio being aided with pharmaceutically acceptable carrier.
3. according to claim 1 or claim 2, contain the pharmaceutical composition of taurine, 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 taurine, 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 taurine, 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 taurine, 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 taurine 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 taurine, it is characterized in that: be any one dosage form contained in the claims 1 ~ 6 in the pharmaceutical composition of taurine as TMEM16A inhibitors of ion channels.
9., according to claim 7 containing the application of pharmaceutical composition of taurine, it is characterized in that: described in be used for the treatment of TMEM16A/CaCCs ion channel relevant disease be the bronchial asthma disease being used for the treatment of people.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111557933A (en) * | 2020-05-27 | 2020-08-21 | 北京康立生医药技术开发有限公司 | Composition for promoting absorption of taurine |
| CN111821266A (en) * | 2020-07-17 | 2020-10-27 | 迪沙药业集团有限公司 | Taurine sustained-release composition and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1827093A (en) * | 2005-04-29 | 2006-09-06 | 四川三民药业有限公司 | Taurine injection and method for preparing the same |
| CN102854236A (en) * | 2012-07-16 | 2013-01-02 | 河北工业大学 | Screening method of TMEM16A calcium-activated chloride channel activator |
-
2016
- 2016-01-04 CN CN201610011173.2A patent/CN105434358A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1827093A (en) * | 2005-04-29 | 2006-09-06 | 四川三民药业有限公司 | Taurine injection and method for preparing the same |
| CN102854236A (en) * | 2012-07-16 | 2013-01-02 | 河北工业大学 | Screening method of TMEM16A calcium-activated chloride channel activator |
Non-Patent Citations (3)
| Title |
|---|
| 刘玉琪 等: "牛磺酸对哮喘豚鼠气道炎症疗效的初步观察", 《中国医科大学学报》 * |
| 周艳军: "牛磺酸片配方优选正交试验", 《现代应用药学》 * |
| 徐文忠 等: "口服牛磺酸颗粒佐治小儿支气管哮喘急性发作的临床疗效", 《实用心脑肺血管病杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111557933A (en) * | 2020-05-27 | 2020-08-21 | 北京康立生医药技术开发有限公司 | Composition for promoting absorption of taurine |
| CN111821266A (en) * | 2020-07-17 | 2020-10-27 | 迪沙药业集团有限公司 | Taurine sustained-release composition and preparation method thereof |
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Application publication date: 20160330 |