CN105496968A - Control method for quality and safety of colloidal bismuth pectin pharmaceutical composition - Google Patents
Control method for quality and safety of colloidal bismuth pectin pharmaceutical composition Download PDFInfo
- Publication number
- CN105496968A CN105496968A CN201610009845.6A CN201610009845A CN105496968A CN 105496968 A CN105496968 A CN 105496968A CN 201610009845 A CN201610009845 A CN 201610009845A CN 105496968 A CN105496968 A CN 105496968A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- bismuth
- colloidal bismmth
- bismmth pectin
- pectin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/245—Bismuth; Compounds thereof
-
- 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
- A61K9/141—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
- A61K9/145—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 compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
- G01N11/02—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by measuring flow of the material
- G01N11/04—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by measuring flow of the material through a restricted passage, e.g. tube, aperture
- G01N11/06—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by measuring flow of the material through a restricted passage, e.g. tube, aperture by timing the outflow of a known quantity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Plasma & Fusion (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a control method for quality and safety of a colloidal bismuth pectin pharmaceutical composition. The pharmaceutical composition is in a dry suspension dosage form and is prepared from, by weight, 130-160 parts of colloidal bismuth pectin (according to bismuth) serving as the bulk pharmaceutical chemical, 420-460 parts of mannitol serving as filler and 10-20 parts of disodium hydrogen phosphate serving as flocculant and/or corrigent. The pharmaceutical composition is characterized in that the intrinsic viscosity of the pharmaceutical composition is controlled, the pharmaceutical stability and the treatment effect of the colloidal bismuth pectin dry suspension are improved, a significant impact will be imposed on improving technical progress of the product and the pharmaceutical industry, and the pharmaceutical composition will achieve obvious technical progress and promotion effects in the quality control field of the colloidal bismuth pectin.
Description
Technical field
The application relates to a kind of preparation and method of quality control thereof of colloid pectin bismuth dry suspensoid, concrete, and the application also relates to the control method of a kind of colloidal bismmth pectin pharmaceutical composition safety.
Background technology
Colloidal bismmth pectin is the indefinite complex of composition that a kind of pectin and bismuth generate; as crude drug; belong to gastric mucosal protection medicine, it is characterized in that its molecule is the new bismuth salt compounds that the macromolecular compound that formed by the structure fragment of D-galacturonic acid methyl ester, D-galacturonic acid bismuth and D-galacturonic acid potassium and biomacromolecule acid group are formed.
Colloidal bismmth pectin can form stable colloidal dispersion in water, gel is formed in simulated gastric fluid, there is stronger colloid property, with skin surface, there is very strong affinity, promote the healing of ulcer and the disappearance of inflammation, also can irritates nucous membrane epithelial cells mucus and kill helicobacter pylori (HelicobacterPylori, HP), one deck firmly protecting film can be formed on gastric mucosa, strengthen the barrier protection effect of gastric mucosa, its distinguishing feature is the high selectivity adhesive attraction of colloid property and the pathogenic bacterium helicobacter pylori with damaged gastrointestinal mucosa and gastrointestinal disease.The power of this adhesiveness adhesive attraction; with the protective effect of damaged gastrointestinal mucosa and the proportional relation of effect killing HP; namely this selective attachment effect is stronger; to damaged gastrointestinal mucosa protective effect and stronger to helicobacter pylori killing action; more be conducive to eliminating pylorus; more be conducive to the healing of gastroenteritic ulcer and the elimination of inflammation, be more conducive to the relapse rate after reducing gastrointestinal disease healing.Compare with other colloidal state bismuth preparation, the colloid property of colloidal bismmth pectin is good, is 7.4 times of colloidal bismuth subcitrate potassium.But bismuth belongs to micro-virus kind, bismuth is distributed in health everywhere after absorbing, and maximum with kidney, liver takes second place, and the colloidal state bismuth preparation that gumminess is good, blood bismuth rises slowly in treatment, absorb few, bismuth accumulation can be reduced and affect Liver and kidney.
Secondly, bismuth belongs to micro-virus kind material.Bismuth is distributed in health everywhere after absorbing, and maximum with kidney, liver takes second place.Major part storage bismuth in vivo, in several weeks so that can be discharged by urine in the several months.
For these reasons, control each dose of bismuth because of strict, reduce bismuth accumulation and poisoning as far as possible.
Current is that " Chinese Pharmacopoeia " version second in 2010 specifies about colloidal bismmth pectin at the main reference standard of colloidal bismmth pectin crude drug, but does not specify the span of control of its intrinsic viscosity.
In addition, standard No. is that WS1-(X-104)-96Z colloidal bismmth pectin new drug standard of becoming a full member defines the drug standard of crude drug colloidal bismmth pectin, but the standard of intrinsic viscosity in colloidal bismmth pectin crude drug is specified, and for different colloidal bismmth pectin pharmaceutical compositions, its dosage form is different, the standard of its intrinsic viscosity is different, and curative effect is also different.
Application number be 201110300984.1 Chinese patent propose the quality determining method of colloidal bismmth pectin pharmaceutical composition, for the method for quality control of existing colloidal bismmth pectin and pharmaceutical preparation thereof, exist rigorous not to the index Quality Control relevant with curative effect, so that produce the problem to the poor product poor controllability of curative effect.Add intrinsic viscosity, uniformity, galacturonic acid content mensuration project and index, the clinical efficacy of effective guarantee product, but more careful research is not done to wherein each technical parameter, to such an extent as to those skilled in the art further cannot improve the curative effect of colloidal bismmth pectin.
Summary of the invention
The object of the application is to provide a kind of colloidal bismmth pectin pharmaceutical composition, and its dosage form is dry suspension.
Another object of the application is the method for quality control providing a kind of colloidal bismmth pectin pharmaceutical composition, to make up in prior art colloid pectin bismuth preparation for the blank of quality control, improve the quality of colloid pectin bismuth preparation, for product clinical application safe, effectively give security.
3rd object of the application is to provide a kind of method controlling the safety of colloidal bismmth pectin pharmaceutical composition.
For realizing the object of the application, can realize in the following manner:
Composition and the content proportioning of the application's colloid pectin bismuth dry suspensoid are as follows:
Colloidal bismmth pectin (in bismuth): 130-160 part; Filler 420-460 part; Flocculating agent 10-20 part.
The wherein optional mannitol of filler.
The optional sodium hydrogen phosphate of flocculating agent.
Also steviosin can be added, one or both in orange oil essence, as correctives in the application.
Preferably, the weight ratio of each component of the application is:
Colloidal bismmth pectin (in bismuth) 150 parts; 455 parts, mannitol; Sodium hydrogen phosphate 15 parts.
The technical scheme of the application is:
Quality control is carried out to the intrinsic viscosity of colloidal bismmth pectin pharmaceutical composition.
Wherein, the assay method of this pharmaceutical composition intrinsic viscosity measures according to the 3rd method in " Chinese Pharmacopoeia " version in 2010 two annex VI G viscosimetries.
Its assay method is, precision takes colloid pectin bismuth dry suspensoid 50mg, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale and shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer (the 3rd methods in Chinese Pharmacopoeia version in 2010 two annex VI G viscosimetries), viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η].
In formula, C is the concentration of bismuth in need testing solution, g/ml.
The Con trolling index of described pharmaceutical composition intrinsic viscosity is for being not less than 1000.
Preferably, the technical specification that the colloidal bismmth pectin pharmaceutical composition of the application's method of quality control gained has is
1) described pharmaceutical composition character should be micro-yellow powder or granule; Gas fragrance, taste is sweet;
2) described pharmaceutical composition basicity pH value should be 8.5 ~ 10.5,
3) described pharmaceutical composition less loss weight must not cross 2.0%;
4) described pharmaceutical composition sedimentation volume ratio must not lower than 0.9
5) in every 1.46g pharmaceutical composition galacturonic acid content for being not less than 0.4g;
6) the specification 150mg of described pharmaceutical composition, in bismuth;
7) 36 months effect duration of described pharmaceutical composition.
Described technical specification all measures according to related content in " Chinese Pharmacopoeia " version in 2010 second and annex thereof.
The application also controls the safety of the colloidal bismmth pectin pharmaceutical composition of above-mentioned method of quality control gained, and its method is: control the intrinsic viscosity of described pharmaceutical composition and bismuth ion uniformity of dosage units.
Wherein, in described colloidal bismmth pectin pharmaceutical composition, the control method of intrinsic viscosity measures according to the 3rd method in " Chinese Pharmacopoeia " version in 2010 two annex VI G viscosimetries;
In described pharmaceutical composition, the control method of bismuth ion uniformity of dosage units is according to Chinese Pharmacopoeia version in 2010 two annex XE uniformity of dosage units control methods, and its concrete grammar is:
(1) mensuration of bismuth ion content gets colloidal bismmth pectin pharmaceutical composition described in the application 10 bags, every bag of 1.46g, put in 500ml conical flask, add salpeter solution 10ml, in salpeter solution, the volume ratio of concentrated nitric acid and water is 1:2, heating makes dissolving, then add water 300ml and xylenol orange indicator solution 4, is titrated to yellow with Calcium Disodium Versenate volumetric solution (0.05mol/L); The Calcium Disodium Versenate volumetric solution (0.05mol/L) of every 1ml is equivalent to the bismuth (Bi) of 10.45mg,
(2) meansigma methods and the standard deviation S of 10 bags of colloidal bismmth pectin pharmaceutical composition bismuth ion content is asked in the calculating of bismuth ion uniformity of dosage units, and the absolute value A of the difference of labelled amount and average (A=|100-meansigma methods |), calculates the numerical value of A+1.8S.
Through measuring, in described colloidal bismmth pectin pharmaceutical composition, bismuth ion content should be the 90-110% of labelled amount, and the scope of uniformity of dosage units should be A+1.8S and is not more than 5.
In addition, for ensureing that described in the application, colloidal bismmth pectin pharmaceutical composition is easier to molding, described in the application, the less loss weight of colloidal bismmth pectin pharmaceutical composition also must not can be more than 3.0%; And show through zoopery, when the bismuth ion uniformity of dosage units A+1.8S of described colloidal bismmth pectin pharmaceutical composition is about 5, without any harmful effect, therefore, the bismuth ion uniformity of dosage units of described colloidal bismmth pectin pharmaceutical composition also can be controlled in A+1.8S and is not more than 5.02.
The beneficial effect of the application is:
1, the application is by controlling the intrinsic viscosity of colloidal bismmth pectin pharmaceutical composition, ensures the clinical efficacy of the application's colloid pectin bismuth preparation, makes the application's target level of product quality more scientific and reasonable controlled.
2, show through lot of experiments research; when the application's colloidal bismmth pectin pharmaceutical composition intrinsic viscosity is not less than 1000; the adhesiveness effect of described medicine is relatively strong; to the gastrointestinal mucosa protective effect of damaged with to kill the effect of Helicobacter pylori also stronger; be conducive to eliminating pylorus, healing gastroenteritic ulcer and diminish inflammation, and reducing the relapse rate after gastrointestinal disease healing.
3, the uniformity of dosage units of the bismuth ion in colloidal bismmth pectin pharmaceutical composition is measured, add the index improving the safety of colloidal bismmth pectin drug regimen, to compensate in prior art only by measure bismuth ion content judge colloidal bismmth pectin and pharmaceutical composition safety and cause may because of up to standard the do not brought potential side effect of bismuth ion content uniformity.
4,1000 are not less than by controlling intrinsic viscosity in described colloidal bismmth pectin pharmaceutical composition, the bismuth ion uniformity of dosage units A+1.8S of colloidal bismmth pectin (in bismuth) is not more than 5 or be not more than 5.02, avoid the generation of toxicity, realize quality controllable to product, further increase the safety of colloidal bismmth pectin pharmaceutical composition, will significant impact be produced to the technological progress improving this product and pharmaceutical industry, obvious scientific and technological progress and impetus will be produced in colloidal bismmth pectin field of quality control.
In sum, the application is by effectively controlling the quality index of colloidal bismmth pectin pharmaceutical composition, improve medicine stability and the therapeutic effect of colloid pectin bismuth dry suspensoid, significant impact can be produced to the technological progress improving this product and pharmaceutical industry, obvious scientific and technological progress and impetus will be produced in colloidal bismmth pectin field of quality control.
Detailed description of the invention
Embodiment
1. the preparation of colloidal bismmth pectin
(1) 166.67g purified water is joined in reaction bulb, add bismuth nitrate 29.22g; Add 40% potassium hydroxide solution of about 23.78g, regulate PH to 6-8, after making it be hydrolyzed completely (namely repetition measurement PH is constant), filter, obtain filter cake Bismuth hydrate.; Again purified water 40.56g, sorbitol 17.89g are put in beaker, again filter cake Bismuth hydrate. is added after sorbitol dissolves, stir after faling apart and add 40% potassium hydroxide solution about 50g, stir and make it fully dissolve, obtain bismuth saline solution for subsequent use;
(2) step (1) preparation bismuth saline solution is added in reaction bulb, stir, add 49ml purified water, under room temperature, add pectin soft material, finish, be warming up to about 40 DEG C stirrings, insulation reaction 0.5 hour, then add purified water 105g, temperature control 30-35 DEG C is stirred 1.5 hours; Reaction terminates, and reaction system is poured in 550ml95% ethanol, stirs 30 minutes, leaves standstill 30 minutes, and filter, appropriate 95% ethanol rinse, drains, and obtains colloidal bismmth pectin crude product wet product;
(3) colloidal bismmth pectin crude product wet product is added in 400ml95% ethanol, stir 15 minutes, leave standstill 30 minutes, filter, appropriate 95% ethanol rinse, first about the 75 DEG C vacuum dryings of filter cake 5 hours, again product is pulverized, and then carry out 95 DEG C of vacuum dryings 5 hours, packaging, obtains colloidal bismmth pectin product.
The preparation of embodiment 2. colloid pectin bismuth dry suspensoid
Prescription: colloidal bismmth pectin 1000 (in 150g bismuth)
Mannitol 455g
Sodium hydrogen phosphate 15g
Production method: 1) each supplementary material in prescription is weighed on electronic scale according to the proportioning in prescription; 2) colloidal bismmth pectin weighed up, sodium hydrogen phosphate and mannitol are dropped into successively total mixing in machine to mix, incorporation time is 30 minutes, and the speed of total mixer is 50Hz; 3) after mixing, (sampling amount is about 30g) detection is sampled to product, after qualified, be distributed into 1000 bags, vacuum seal, label, store, packaging, warehouse-in.
The preparation of embodiment 3. colloid pectin bismuth dry suspensoid
Prescription: colloidal bismmth pectin 900kg
Mannitol 409.5kg
Sodium hydrogen phosphate 13.5kg
Specification: 150mg (in bismuth)
Production method: 1) each supplementary material in prescription is weighed on electronic scale according to the proportioning in prescription; 2) colloidal bismmth pectin weighed up, sodium hydrogen phosphate and mannitol are dropped into successively total mixing in machine to mix, incorporation time is 30 minutes, and the speed of total mixer is 50Hz; 3) after mixing, (sampling amount is about 30g) detection is sampled to product, after qualified, be distributed into 900,000 bags, vacuum seal, label, store, packaging, warehouse-in.
Embodiment 4
Prescription: colloidal bismmth pectin (in bismuth) 130g
Mannitol 420g
Sodium hydrogen phosphate 10g
Production method: 1) each supplementary material in prescription is weighed on electronic scale according to the proportioning in prescription; 2) colloidal bismmth pectin weighed up, sodium hydrogen phosphate and mannitol are dropped into successively total mixing in machine to mix, incorporation time is 30 minutes, and the speed of total mixer is 50Hz; 3) after mixing, (sampling amount is about 30g) detection is sampled to product, after qualified, be distributed into 1000 bags, vacuum seal, label, store, packaging, warehouse-in.
Embodiment 5
Prescription: colloidal bismmth pectin (in bismuth) 160g
Mannitol 460g
Sodium hydrogen phosphate 20g
Production method: 1) each supplementary material in prescription is weighed on electronic scale according to the proportioning in prescription; 2) colloidal bismmth pectin weighed up, sodium hydrogen phosphate and mannitol are dropped into successively total mixing in machine to mix, incorporation time is 30 minutes, and the speed of total mixer is 50Hz; 3) after mixing, (sampling amount is about 30g) detection is sampled to product, after qualified, be distributed into 1000 bags, vacuum seal, label, store, packaging, warehouse-in.
Embodiment 6, bismuth ion Determination of Content Uniformity and control method
The mensuration of bismuth ion content gets the embodiment of the present application 2-5 gained pharmaceutical composition 10 bags, every bag of 1.46g, put in the conical flask of 500ml, add salpeter solution (1 → 2) 10ml, heating makes dissolving, add water 300ml and xylenol orange indicator solution 4 again, is titrated to solution in yellow with Calcium Disodium Versenate volumetric solution (0.05mol/L).The Calcium Disodium Versenate volumetric solution (0.05mol/L) of every 1ml is equivalent to the bismuth (Bi) of 10.45mg.
Meansigma methods and the standard deviation S of 10 bags of colloid pectin bismuth dry suspensoid bismuth ion content and the absolute value A of the difference of labelled amount and average (A=|100-meansigma methods |) are asked in the control of bismuth ion uniformity of dosage units, calculate the numerical value of A+1.8S.
The mensuration of embodiment 7. intrinsic viscosity
Precision takes prepares colloid pectin bismuth dry suspensoid 50mg according to the embodiment of the present application 2-5, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η]
In formula, C is the concentration of bismuth in need testing solution, g/ml.
The mensuration of other indexs of embodiment 8.
Described in [character] the embodiment of the present application 2-5, pharmaceutical composition is micro-yellow powder or granule; Gas fragrance, taste is sweet.
The fine powder appropriate (being about equivalent to bismuth 0.75mg) of pharmaceutical composition described in the embodiment of the present application 2-5 of [discriminating] (1), add water 10ml, stirs, use dilute sulfuric acid acidify, add 10% thiourea solution number and drip, namely generate buff.
(2) fine powder appropriate (being about equivalent to bismuth 1.5mg) of pharmaceutical composition described in the embodiment of the present application 2-5, add water 25ml, stirs, and after dilute sulfuric acid 3 ~ 5 acidifys, generate flocculent deposit, add potassium iodide test solution, namely SHENGHUANG color precipitates to brown color.
(3) fine powder appropriate (being about equivalent to bismuth 15mg) of pharmaceutical composition described in the embodiment of the present application 2-5, heating water 10ml, stirs, and lets cool, and adds ethanol 10ml, namely gelling occurs.
[inspection] basicity gets the fine powder appropriate (being about equivalent to bismuth 15mg) of pharmaceutical composition described in the embodiment of the present application 2-5, and add water 100ml, jolting, and measure (Chinese Pharmacopoeia version in 2010 two annex VI H), pH value should be 8.5 ~ 10.5 in accordance with the law.
Loss on drying gets pharmaceutical composition described in the embodiment of the present application 2-5, is dried to constant weight at 105 DEG C, and less loss weight must not cross 2.0% (Chinese Pharmacopoeia version in 2010 two annex VIII L)
The fine powder that sedimentation volume ratio gets pharmaceutical composition described in the embodiment of the present application 2-5 is about equivalent to bismuth 15mg, and add water 100ml, firmly jolting 1 minute, and leave standstill 1 hour, should conform with the regulations (Chinese Pharmacopoeia version in 2010 two annex IO), is less than 0.9.
The mensuration of other indexs of experimental example 9.
Described in [character] the embodiment of the present application 2-5, pharmaceutical composition is micro-yellow powder or granule; Gas fragrance, taste is sweet.
The fine powder appropriate (being about equivalent to bismuth 0.75mg) of pharmaceutical composition described in the embodiment of the present application 2-5 of [discriminating] (1), add water 10ml, stirs, use dilute sulfuric acid acidify, add 10% thiourea solution number and drip, namely generate buff.
(2) get the fine powder appropriate (being about equivalent to bismuth 1.5mg) of the pharmaceutical composition of application described in embodiment 2-5, add water 25ml, stirs, after dilute sulfuric acid 3 ~ 5 acidifys, generate flocculent deposit, add potassium iodide test solution, namely generate yellow to brown color and precipitate.
(3) fine powder appropriate (being about equivalent to bismuth 15mg) of pharmaceutical composition described in the embodiment of the present application 2-5, heating water 10ml, stirs, and lets cool, and adds ethanol 10ml, namely gelling occurs.
[inspection] basicity gets the fine powder appropriate (being about equivalent to bismuth 15mg) of pharmaceutical composition described in the embodiment of the present application 2-5, and add water 100ml, jolting, and measure (Chinese Pharmacopoeia version in 2010 two annex VI H), pH value should be 8.5 ~ 10.5 in accordance with the law.
Loss on drying gets pharmaceutical composition described in the embodiment of the present application 2-5, is dried to constant weight at 105 DEG C, and less loss weight must not cross 2.0% (Chinese Pharmacopoeia version in 2010 two annex VIII L)
The fine powder that sedimentation volume ratio gets pharmaceutical composition described in the embodiment of the present application 2-5 is about equivalent to bismuth 15mg, and add water 100ml, firmly jolting 1 minute, and leave standstill 1 hour, should conform with the regulations (Chinese Pharmacopoeia version in 2010 two annex IO), is less than 0.9.
Comparative example
1、
The colloidal bismmth pectin crude drug meeting standard under Chinese Pharmacopoeia version in 2010 second colloidal bismmth pectin item is prepared colloid pectin bismuth dry suspensoid according to method in the embodiment of the present application 2 or 3.
2、
To the colloidal bismmth pectin crude drug of standard described in patent CN102507381A be met, and prepare colloid pectin bismuth dry suspensoid according to method in the embodiment of the present application 2 or 3.
3、
Preparation meets Couoidal bismuth pectin capsules, granule or the tablet of standard described in patent CN102507381A.
Experimental example
1. the research of the intrinsic viscosity of colloid pectin bismuth dry suspensoid
Method: carry out research with reference to the 3rd method in Chinese Pharmacopoeia version in 2010 two annex VIG viscosimetries and measure:
1.1 Ubbelohde viscometer capillary dimensionss are on the impact of experimental result
Ubbelohde viscometer capillary tube (1) 0.57mm, (2) 0.47mm (3) 0.5-0.6mm
Accurate colloid pectin bismuth dry suspensoid 120902 crowdes of 50mg claiming to prepare according to the embodiment of the present application 2, be placed in 100ml volumetric flask, add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η]
In formula, C is the concentration of bismuth in need testing solution, g/ml
Get above-mentioned solution to measure respectively at the Ubbelohde viscometer of 0.47mm, 0.57mm, 0.5-0.6mm size capillary tube, result is as follows:
Table 1 Ubbelohde viscometer capillary dimensions selection result
Conclusion: selected capillary dimensions is different, result no significant difference, thus select sample determination around the States Pharmacopoeia specifications value 0.57mm Ubbelohde viscometer of 120 seconds ~ 180 seconds carry out the research work in later stage.
1.2 stabilities of solution are on the impact of experimental result
Get and prepare colloid pectin bismuth dry suspensoid 130902 crowdes of 125mg according to the embodiment of the present application 2, be placed in 250ml volumetric flask, add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, as need testing solution, respectively at 0 minute, 15 minutes, 30 minutes, 45 minutes, 60 minutes, operate from " getting subsequent filtrate 20ml loads clean ... " according to said method in accordance with the law.
Table 2 stability of solution investigates result
Conclusion: sample solution measured in 60 minutes, can not affect measurement result.
The temperature retention time of 1.3 solution is on the impact of experimental result:
Precision takes prepares colloid pectin bismuth dry suspensoid 120902 crowdes of 50mg according to the embodiment of the present application 2, be placed in 100ml volumetric flask, add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, get subsequent filtrate 20ml to load in the ball B of clean, dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and makes the liquid level of water-bath higher than ball C, after placing 10,15,20,30 minutes respectively, measure in accordance with the law.
Table 3 temperature retention time investigates result
Conclusion: as ambient temperature controls better, to be incubated detected solution after 10 minutes basicly stable.
Confirm by experiment, during the application's intrinsic viscosity measures, the size of Ubbelohde viscometer capillary tube, temperature retention time, the impact of standing time on the measurement result of the application's intrinsic viscosity of solution is little
The holding temperature of 1.4 solution is on the impact of experimental result
Precision takes prepares colloid pectin bismuth dry suspensoid 50mg according to the embodiment of the present application 2, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer (the 3rd methods in Chinese Pharmacopoeia version in 2010 two annex VI G viscosimetries), viscosimeter is vertically fixed in water bath with thermostatic control, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η].
Wherein, holding temperature is respectively (1) 15 ± 0.1 DEG C (2) 25 ± 0.1 DEG C (3) 50 ± 0.1 DEG C (4) 75 ± 0.1 DEG C
The measurement result of gained is in table 4.
Under table 4 different temperatures, the measurement result of intrinsic viscosity
| Temperature | 15±0.1℃ | 25±0.1℃ | 50±0.1℃ | 75±0.1℃ |
| Intrinsic viscosity | 960 | 1067 | 970 | 880 |
Conclusion: the intrinsic viscosity measured at 25 DEG C ± 0.1 DEG C is greater than 1000.
1.5 precision tests:
Get and prepare colloid pectin bismuth dry suspensoid 130902 batches according to the embodiment of the present application 2, precision takes 125mg, be placed in 250ml volumetric flask, add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, as need testing solution, measure according to method described in embodiment 7 and calculate its intrinsic viscosity.
Table 5 Precision test result
Conclusion: result shows that this method precision is better.
1.6 replica test
Get and prepare colloid pectin bismuth dry suspensoid 130902 batches according to the embodiment of the present application 2, precision takes 50mg, totally 6 parts, be placed in 100ml volumetric flask, add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, as need testing solution, according to method mensuration described in embodiment 7, also estimated performance is viscosity number.
Table 6 replica test result
Conclusion: learn from above-mentioned data, this method repeatability better.
1.7 methods are determined:
Precision takes prepares each 50mg of colloid pectin bismuth dry suspensoid according to the embodiment of the present application 2, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η].
Determine according to above-mentioned the intrinsic viscosity that rear method measures colloid pectin bismuth dry suspensoid (120902,121101,121102 batches) and corresponding raw material, result is as follows:
Table 7 sample determination result
Conclusion: the intrinsic viscosity result of three batch samples all can be greater than 1000, and testing result and raw material testing result are without significant difference.
Experimental example 2 bismuth ion is containing quantifier elimination
Record is carried out to the result recorded in embodiment 6, records the numerical value of bismuth pectin (in bismuth) content and the uniformity recorded.
Table 8 bismuth ion assay result
Conclusion: in the application's colloid pectin bismuth dry suspensoid, the content of bismuth pectin (in bismuth) is between the 90-110% of labelled amount, and show that the value of the uniformity of dosage units A+1.80S of wherein bismuth ion is for being not more than 5 or about 5 as calculated.
According to test result, by 90-110% of bismuth pectin (in bismuth) the content location labelled amount in the application's colloid pectin bismuth dry suspensoid, uniformity of dosage units is decided to be: the value of A+1.80S is not more than 5 or be not more than 5.02.
The comparison of experimental example 3. different quality control method
In conjunction with existing method of quality control, study the method for quality control in the application, its method is as follows:
The colloid pectin bismuth dry suspensoid obtained through control method described in the application and respective value in comparative example are carried out measuring and comparing, it the results are shown in Table 9.
The comparison of table 9 different quality control method
Conclusion: compared with prior art, use the colloid pectin bismuth dry suspensoid that described in the application prepared by control method, more accurately can control the content of wherein bismuth ion, and intrinsic viscosity also improves relatively, the object that the application improves pharmaceutical composition efficacy and saferry can be realized.
For the efficacy and saferry of proved application colloidal bismmth pectin pharmaceutical composition, also carry out following zoopery.
Experimental example 4 zoopery
Colloid pectin bismuth dry suspensoid described in the application is as gastrointestinal mucosa protective agent and the purposes killing helicobacter pylori, can be used for treating gastric and duodenal ulcers, chronic atrophic gastritis, chronic erosive gastritis, stomachache, abdominal distention, diarrhoea, gastrointestinal mucosal is hemorrhage, particularly helicobacter pylori dependency stomach intestine anabrosis disease or inflammation, stops the canceration of atrophic gastritis; With antibiotic, proton pump inhibitor or bisfentidine coupling, or with other bismuth salt compounds couplings, or continue to take separately after bismuth triple therapy, or 1-2 times of escalated dose of dosage routinely, for the eradication therapy of helicobacter pylori.
Utilize the quality control index of the colloidal bismmth pectin pharmaceutical composition of the application's gained, the pharmaceutical composition in the application is screened, and the inspection of pharmacodynamics is carried out to the medicine filtered out.
The therapeutic test of 4.1 pairs of rat gastric ulcers
Experimental technique: get week age consistent, the Wistar rat 50 that kind is identical with sex, be divided into 5 groups, fasting, give normal saline respectively, the colloid pectin bismuth dry suspensoid of the application's control method gained, comparative example 1, comparative example 2 and comparative example 3 control method or standard gained colloid pectin bismuth dry suspensoid or pharmaceutical composition, every rats gavaged 1ml dehydrated alcohol after 1h, after 60min, cervical dislocation is put to death, pluck full stomach and inject 1% formalin 10ml, put and fix more than 10min in the formaldehyde of same concentration and then cut off coat of the stomach along greater gastric curvature, observe gastric mucosa injury situation.
The contrast of table 10 mouse gastric ulcer curative effect
Note: * * P < 0.01, experimental group compares with matched group
Conclusion: the application's colloid pectin bismuth dry suspensoid is obvious to the effect of gastric ulcer, and suppression ratio is higher than comparative example group.
The therapeutic test of 4.2 pairs of rat antiinflammatories
Experimental technique: get the rat 50 that age in week is consistent, kind is identical with sex, be divided into 5 groups, give normal saline respectively, the application's control method gained colloidal bismmth pectin and comparative example 1, comparative example 2 and comparative example 3 control method or standard products obtained therefrom, after 1h, the Oleum Tiglii of every left in ear external 2% of animal is smeared, and is put to death by rat after 4h, cut two ears, lay round auricle with diameter 9mm card punch, torsion balance is weighed, and calculates inhibitory rate of intumesce.
The treatment situation of table 11 rat antiinflammatory
Conclusion: the antiinflammatory action of the application's gained colloidal bismmth pectin pharmaceutical composition is higher than comparative example group.
4.3 chronic gastritis experiments
Get age in week is consistent, kind is identical with sex experiment with rabbit 50, be divided into 5 groups, after artificial modeling causes chronic gastritis, give normal saline respectively, the application's control method gained colloidal bismmth pectin and comparative example 1, comparative example 2 and comparative example 3 control method or standard products obtained therefrom are treated, and observe therapeutic effect after 12 weeks.
Table 12 chronic gastritis Experiment on therapy
Note: * * P < 0.01, experimental group compares with matched group
Conclusion: the therapeutic effect of the colloid pectin bismuth dry suspensoid that control method described in the application obtains to chronic gastritis is better than the relative medicine under other standards or prescription, and experimental group compares P<0.01 with matched group, and there was a significant difference.
The eradication rate of 4.4Hp
Experimental technique: get the rat 50 that age in week is consistent, kind is identical with sex, be divided into 5 groups, artificial modeling.Give normal saline respectively, the application's control method gained colloid pectin bismuth dry suspensoid and comparative example 1-3 control method or standard gained dry suspension or pharmaceutical composition are treated, and observe therapeutic effect.
The eradication rate experiment of table 13Hp
Note: experimental group compares P<0.01 with matched group, there was a significant difference.
4.5 blood bi concns measure
The medicine of the continuous gavage therapeutic dose of rabbit 3 weeks, measures blood bi concns.Wherein institute's drug is divided into normal saline, and the application's control method gained colloid pectin bismuth dry suspensoid and comparative example 1-3 control method or standard gained dry suspension or pharmaceutical composition, it the results are shown in Table 14.
Table 14 blood bi concns is tested
Conclusion: result is known in experimental example 4.5, compared with prior art products, after the colloid pectin bismuth dry suspensoid administration of the application's control method gained, blood bi concns is low, improves safety.
Claims (9)
1. the method for quality control of a colloidal bismmth pectin pharmaceutical composition, described medicine composition dosage form is dry suspension, comprising weight portion is 130-160 part crude drug colloidal bismmth pectin (in bismuth), weight portion is the filler mannitol of 420-460 part, weight portion is flocculating agent sodium hydrogen phosphate and/or the correctives of 10-20 part, it is characterized in that, control the intrinsic viscosity of this pharmaceutical composition, make it be not less than 1000.
2. the method for quality control of colloidal bismmth pectin pharmaceutical composition according to claim 1, it is characterized in that the weight portion (in bismuth) of crude drug colloidal bismmth pectin is 150, the weight portion of mannitol is 455, and the weight portion of sodium hydrogen phosphate is 15.
3. the method for quality control of colloidal bismmth pectin pharmaceutical composition according to claim 1 and 2, it is characterized in that the assay method of the intrinsic viscosity of described pharmaceutical composition measures according to the 3rd method in " Chinese Pharmacopoeia " version in 2010 two annex VI G viscosimetries, its assay method is that precision takes each 50mg of colloid pectin bismuth dry suspensoid, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same replication 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η],
In formula, C is the concentration of bismuth in need testing solution, g/ml.
4. the control method of the colloidal bismmth pectin pharmaceutical composition safety that control method obtains as described in claim 1-3 any one, described colloidal bismmth pectin medicine composition dosage form is dry suspension, its composition comprises the colloidal bismmth pectin crude drug being calculated as 150 weight portions with bi content, 455 parts by weight of filler, 15 weight portion flocculating agent and/or correctivess; Described colloidal bismmth pectin pharmaceutical composition has index
1) described pharmaceutical composition character should be micro-yellow powder or granule; Gas fragrance, taste is sweet;
2) described pharmaceutical composition basicity pH value should be 8.5 ~ 10.5,
3) described pharmaceutical composition less loss weight must not cross 2.0%;
4) described pharmaceutical composition sedimentation volume ratio must not lower than 0.9
5) in every 1.46g pharmaceutical composition galacturonic acid content for being not less than 0.4g;
6) the specification 150mg of described pharmaceutical composition, in bismuth;
7) 36 months effect duration of described pharmaceutical composition
It is characterized in that: the uniformity of dosage units of the intrinsic viscosity in described colloidal bismmth pectin pharmaceutical composition and bismuth ion is controlled.
5. the control method of colloidal bismmth pectin pharmaceutical composition according to claim 4 safety, it is characterized in that: in described pharmaceutical composition, the uniformity of dosage units of bismuth ion is according to Chinese Pharmacopoeia version in 2010 two annex XE uniformity of dosage units methods, wherein the assay method of bismuth ion content is for getting described colloidal bismmth pectin pharmaceutical composition 10 bags, every bag of 1.46g, put in 500ml conical flask, add salpeter solution 10ml, in salpeter solution, the volume ratio of concentrated nitric acid and water is 1:2, heating makes dissolving, add water 300ml and xylenol orange indicator solution 4 again, solution is titrated in yellow with Calcium Disodium Versenate volumetric solution (0.05mol/L), the Calcium Disodium Versenate volumetric solution (0.05mol/L) of every 1ml is equivalent to the bismuth (Bi) of 10.45mg, ask colloidal bismmth pectin pharmaceutical composition bismuth ion content meansigma methods and the standard deviation S of described 10 bags, and the absolute value A of the difference of labelled amount and meansigma methods (A=|100-meansigma methods |), calculate the numerical value of A+1.8S, and control its numerical value and be not more than 5,
In described pharmaceutical composition, intrinsic viscosity measures according to the 3rd method in Chinese Pharmacopoeia version in 2010 two annex VI G viscosimetries, its method is that precision takes colloidal bismmth pectin pharmaceutical composition 50mg, be placed in 100ml volumetric flask, add water about 30ml, jolting or ultrasonicly make it dispersed, and add water and be settled to scale, shake up, filter with No. 3 sintered glass funnels, discard just filtrate, getting subsequent filtrate 20ml loads clean, in the ball B of dry Ubbelohde viscometer, viscosimeter is vertically fixed in constant temperature (25 DEG C ± 0.1 DEG C) water-bath, and make the liquid level of water-bath higher than ball C, place after 15 minutes, by the mouth of pipe 1, 3 respectively connect a latex tubing, clamp the sebific duct of the mouth of pipe 3, from the mouth of pipe 1, bleed in place, the liquid level of need testing solution is made slowly to be increased to the middle part of ball C, decontrol the mouth of pipe 3, decontrol the mouth of pipe 1 again, need testing solution is naturally fallen in pipe, with stopwatch accurate recording liquid level to measuring line m
1drop to and measure line m
2the delivery time at place, replication twice, twice measured value must not differ more than 0.1 second, and the meansigma methods of getting twice is the delivery time (T) of need testing solution, the pure water that No. 3 sintered glass funnels of learning from else's experience filter, same repetition 2 times, 2 times measured value should be identical, is the delivery time (T of pure water
0), estimated performance viscosity number [η]
In formula, C is the concentration of bismuth in need testing solution, g/ml, and its numerical value is not less than 1000.
6. according to the control method of the colloidal bismmth pectin of any one described in claim 4-5 pharmaceutical composition safety, it is characterized in that: the filler in described colloidal bismmth pectin pharmaceutical composition is mannitol, flocculating agent is sodium hydrogen phosphate and/or correctives.
7. according to the control method of the colloidal bismmth pectin of any one described in claim 4-5 pharmaceutical composition safety, it is characterized in that, in described colloidal bismmth pectin pharmaceutical composition, correctives is one or both in steviosin and orange oil essence.
8. the control method of colloidal bismmth pectin pharmaceutical composition according to claim 4 safety, is characterized in that: described pharmaceutical composition less loss weight also must not can be more than 3.0%.
9. the control method of the colloidal bismmth pectin pharmaceutical composition safety according to claim 5-8, is characterized in that: in described pharmaceutical composition, the uniformity of dosage units A+1.8S of bismuth ion also can be and is not more than 5.02.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610009845.6A CN105496968B (en) | 2015-04-07 | 2016-01-07 | A kind of quality of colloidal bismmth pectin pharmaceutical composition and the control method of safety |
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015101603744 | 2015-04-07 | ||
| CN201510160374 | 2015-04-07 | ||
| CN201510754894 | 2015-11-09 | ||
| CN2015107548948 | 2015-11-09 | ||
| CN2015109795121 | 2015-12-23 | ||
| CN201510979512 | 2015-12-23 | ||
| CN2015110204669 | 2015-12-29 | ||
| CN201511020466 | 2015-12-29 | ||
| CN201610009845.6A CN105496968B (en) | 2015-04-07 | 2016-01-07 | A kind of quality of colloidal bismmth pectin pharmaceutical composition and the control method of safety |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105496968A true CN105496968A (en) | 2016-04-20 |
| CN105496968B CN105496968B (en) | 2019-03-05 |
Family
ID=55705533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610009845.6A Active CN105496968B (en) | 2015-04-07 | 2016-01-07 | A kind of quality of colloidal bismmth pectin pharmaceutical composition and the control method of safety |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105496968B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109724897A (en) * | 2019-01-30 | 2019-05-07 | 山西振东安特生物制药有限公司 | Colloidal bismmth pectin or viscosity detection method containing colloid pectin bismuth preparation |
| CN116519543A (en) * | 2023-06-30 | 2023-08-01 | 济南辰欣医药科技有限公司 | Method for detecting characteristic viscosity number of sodium hyaluronate eye drops with average molecular weight of more than 120 ten thousand |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1919170A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Colloid pectin bismuth dry suspensoid and its preparing process |
| CN102507381A (en) * | 2011-10-09 | 2012-06-20 | 于学敏 | Colloid bismuth pectin compound and quality control method of pharmaceutical compositions thereof |
-
2016
- 2016-01-07 CN CN201610009845.6A patent/CN105496968B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1919170A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Colloid pectin bismuth dry suspensoid and its preparing process |
| CN102507381A (en) * | 2011-10-09 | 2012-06-20 | 于学敏 | Colloid bismuth pectin compound and quality control method of pharmaceutical compositions thereof |
Non-Patent Citations (2)
| Title |
|---|
| 国家药典委员会编: "《中华人民共和国药典 2010年版 二部》", 31 January 2010, 中国医药科技出版社 * |
| 王虎军主编: "《全科医师临床药物手册》", 31 January 2009, 江苏科学技术出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109724897A (en) * | 2019-01-30 | 2019-05-07 | 山西振东安特生物制药有限公司 | Colloidal bismmth pectin or viscosity detection method containing colloid pectin bismuth preparation |
| CN116519543A (en) * | 2023-06-30 | 2023-08-01 | 济南辰欣医药科技有限公司 | Method for detecting characteristic viscosity number of sodium hyaluronate eye drops with average molecular weight of more than 120 ten thousand |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105496968B (en) | 2019-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cartwright et al. | Chemical, clinical, and immunological studies on the products of human plasma fractionation. XXXIX. The anemia of infection. Studies on the iron-binding capacity of serum | |
| JP2011503073A (en) | Corticosteroid composition | |
| CN102507381B (en) | Colloid bismuth pectin compound and quality control method of pharmaceutical compositions thereof | |
| EP2922581B1 (en) | Mucoadhesive compositions comprising hyaluronic acid and chitosan for topical application | |
| EP3315946A1 (en) | Method for detecting dissolution rate of preparation containing colloidal bismuth pectin | |
| CN105496968A (en) | Control method for quality and safety of colloidal bismuth pectin pharmaceutical composition | |
| CN105125577B (en) | A kind of sugar-iron complexes of stabilization and preparation method thereof | |
| CN108938626A (en) | A kind of good and highly-safe Carbazochrome sodium sulfonate pharmaceutical composition and its preparation method and application of stability | |
| JPS6023323A (en) | Medicinal composition | |
| CN105560188A (en) | Colloidal bismuth pectin pharmaceutical composition and quality control method thereof. | |
| JP6942263B2 (en) | Method for measuring free bismuth in colloidal bismuth pectin or colloidal bismuth pectin-containing preparation | |
| Wang et al. | Pine pollen polysaccharides promote cell proliferation and accelerate wound healing by activating the JAK2-STAT3 signaling pathway | |
| CN104338122A (en) | Iron proteinsuccinylate oral solution and preparation method of iron proteinsuccinylate oral solution | |
| Ervin et al. | V1-and V2-receptor contributions to ovine fetal renal and cardiovascular responses to vasopressin | |
| CN105572126A (en) | Quality control method of colloidal bismuth pectin pharmaceutical composition | |
| CN105461823A (en) | Method for preparing colloidal bismuth pectin and method for controlling adhesiveness of medicine composition of colloidal bismuth pectin | |
| CN109724897A (en) | Colloidal bismmth pectin or viscosity detection method containing colloid pectin bismuth preparation | |
| CN103463125B (en) | Gel preparation for treating gynecological diseases and preparation method thereof | |
| CN108553413A (en) | Injection esomeprazole sodium | |
| CN103417568A (en) | Glycerin fructose sodium chloride injection and preparation method thereof | |
| CN103520238A (en) | Compound metronidazole expansion suppository and preparation process thereof | |
| Arulanandraj et al. | NANOTECHNOLOGICAL APPROACH TO ENHANCE THE STABILITY AND BIOAVAILABILITY OF THE HERBAL DRUG" MURVA" | |
| CN103877016B (en) | Pharmaceutical composition of naloxone hydrochloride injection and preparation method thereof | |
| CN103833869B (en) | A kind of banksia rose sulfated polysaccharides and its production and use | |
| CN106265664B (en) | A kind of the bioadhesive gel for nose product and preparation method of compound Rupatadine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200106 Address after: 410300 No. 6 Kangping Road, Liuyang Economic and Technological Development Zone, Changsha City, Hunan Province Patentee after: Hunan Warner great Pharmaceutical Technology Development Co., Ltd. Address before: 410329 Liuyang biological medicine Park, Changsha, Hunan Patentee before: HUNAN WARRANT PHARMACEUTICAL CO., LTD. |