CN102507381A - Colloid bismuth pectin compound and quality control method of pharmaceutical compositions thereof - Google Patents
Colloid bismuth pectin compound and quality control method of pharmaceutical compositions thereof Download PDFInfo
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Abstract
The invention relates to a colloid bismuth pectin compound and a quality control method of pharmaceutical compositions of the colloid bismuth pectin compound, and specifically provides a colloid bismuth pectin compound, new quality control indexes of pharmaceutical compositions of the colloid bismuth pectin compound and a detection method of the colloid bismuth pectin compound and the pharmaceutical compositions of the colloid bismuth. In the prior art, the quality of products having poor efficacy can not be well controlled because the efficacy-related indexes are not controlled strictly in the existing quality control methods of colloid bismuth pectin and pharmaceuticals thereof. Based on the existing quality control methods of colloid bismuth pectin and pharmaceuticals thereof, the following detection items and indexes are added: intrinsic viscosity, gel property, uniformity and galacturonic acid content. The invention can effectively ensure clinical efficacy of products, make the product quality standards more scientific, reasonable and controllable, and has great significance in quality control of the colloid bismuth pectin and the pharmaceutical preparation of colloid bismuth pectin.
Description
Technical field
The present invention relates to the quality determining method of colloidal bismmth pectin and pharmaceutical composition thereof, particularly, provide newly-increased quality control index of colloid pectin bismuth compound and pharmaceutical composition thereof and detection method thereof.Belong to drug world.
Background technology
Colloidal bismmth pectin capsule of using clinically at present and bulk drug colloidal bismmth pectin proper mass standard thereof are drafted by this research and development of products people Medicine Inst. of Datong City and the Yu Xuemin researcher of Datong Wei Min Pharmaceutical Co (former Datong District institute of materia medica pharmaceutical factory) hosting.Quality standard is Ministry of Public Health's tentative standard earlier, after transfer formal ministerial standard to, after record into 2000,2005,2010 version " Chinese pharmacopoeia.This standard was brought into use from 1993 and has been reached 18 years so far, and this standard has been brought into play certain effect in this target level of product quality of control.Along with the continuous expansion of continuous increase, output and sales volume of the manufacturer of colloidal bismmth pectin and preparation thereof and the technical progress of the drug standards and the method for inspection, there is inaccurate, defective such as science, level is low, lacuna is many, poor controllability not in this standard to control product inherent quality (index relevant with clinical efficacy) aspect.
The colloid pectin bismuth compound is to replace inorganic acid radical (nitroxylic acid root, meta-aluminic acid root), small molecular organic acid root (inferior citric acid radical) and the new bismuth salt compounds that forms with biomacromolecule pectin acid group, and its distinguishing feature and technical progress are colloid property and and the high selectivity adhesive attraction of the pathogenic bacteria helicobacter pylori (Hp) of damaged gastrointestinal mucosa and gastrointestinal disease.The power of this selective attachment effect and this compounds are proportionate to the protective effect of damaged gastrointestinal mucosa and the effect of killing Hp; Be that this selective attachment effect is strong more; To damaged gastrointestinal mucosa protective effect and strong more to the Hp killing action; Help eradicating Hp more, help the healing of gastroenteritic ulcer and the elimination of inflammation more, help reducing the recurrence rate after gastrointestinal disease is cured more.The high selectivity adhesive attraction of this compound not only depends on bismuth ion; And also be decided by the acid group that combines with it to a great extent, ratio its colloid property of decision of bismuth ion content and pectic acid radical content and with the high selectivity adhesive attraction of impaired damage gastrointestinal mucosa, Hp.Existing colloidal bismmth pectin and quality determining method in; [assay] of proper mass standard only carries out the assay of kation bismuth in the pectin bismuth molecule down, not to acid group pectin acid group carry out assay (referring to " two P852-P853 of Chinese pharmacopoeia version in 2010).
Summary of the invention
For overcoming the deficiency of existing colloidal bismmth pectin and preparation thereof (being pharmaceutical composition) quality control index and detection method; The control method that improves the quality level; For the product safety of clinical administration, effectively give security, the present invention provides the quality control index and the detection method of a kind of more efficiently colloidal bismmth pectin and preparation thereof.
Technical scheme of the present invention is following:
The invention provides the quality determining method of a kind of colloid pectin bismuth compound and pharmaceutical composition thereof, it is characterized in that comprising and measure following arbitrary or more than both: intrinsic viscosity, gelling, homogeneity or galacturonic acid content.
Wherein, The quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof; The assay method that it is characterized in that described intrinsic viscosity is: with colloidal bismmth pectin or its pharmaceutical composition porphyrize, take by weighing and place container in right amount, add water to the constant volume scale; Shake up, according to " three therapeutic methods of traditional Chinese medicine in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry is measured.
Wherein, The quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof is characterized in that the assay method of described gelling is: with colloidal bismmth pectin or its pharmaceutical composition porphyrize, take by weighing and place container in right amount; Add an amount of mixing of water; After jolting makes into rubber cement, add hydrochloric acid, form gel.
Wherein, The quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof; It is characterized in that described inhomogeneity assay method is: take by weighing screenings and screen underflow that colloidal bismmth pectin is crossed 200 mesh standard sieves, respectively according to " Chinese pharmacopoeia two colloidal bismmth pectins of version [assay] in 2010 item method is down measured bi content.
Wherein, The quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof; The assay method that it is characterized in that described galacturonic acid content is: according to " Chinese pharmacopoeia two pectin of version [assay] in 2010 item method is down measured, and measures V
1(initial titration value) and V
2(saponification titration value) with (total titer), every 1ml NaOH vs (0.1mol/L) is equivalent to the galacturonic acid of 19.414mg.
Preferably, the quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof, wherein said pharmaceutical composition is selected from capsule, tablet, granule etc.
Preferably; The quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof; The quality determining method that it is characterized in that described colloid pectin bismuth compound comprises intrinsic viscosity, gelling, homogeneity and galacturonic acid content mensuration, and:
Intrinsic viscosity [η] is for being not less than 125;
Gelling in rubber cement, add hydrochloric acid form do not flow, do not dewater, non-cracking, bubble-free gel;
Homogeneity was that the screenings of 200 mesh standard sieves and the bi content of screen underflow all should be 14-16%, and its difference must not be greater than 1.0%;
Galacturonic acid content must not be less than 60% of dry sample after the washed with isopropyl alcohol.
Preferably, the quality determining method of above-mentioned described colloid pectin bismuth compound and pharmaceutical composition thereof is characterized in that the quality determining method of described colloidal bismmth pectin capsule comprises intrinsic viscosity, gelling and galacturonic acid content mensuration, and:
Intrinsic viscosity [η] is for being not less than 125;
Gelling in rubber cement, add hydrochloric acid form do not flow, do not dewater, non-cracking, bubble-free gel;
Galacturonic acid content is the 90.0-110.0% that the galacturonic acid content of every capsules should be labelled amount.
As one of specific embodiments of the present invention, the quality determining method of described colloid pectin bismuth compound and pharmaceutical composition thereof is characterized in that:
The assay method of said intrinsic viscosity is according to " three therapeutic methods of traditional Chinese medicine in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry is measured, and is specially: precision takes by weighing through the colloidal bismmth pectin of 200 mesh sieves or colloidal bismmth pectin capsule 's content 50mg and places the 100ml volumetric flask, adds water to be settled to scale; Shake up, filter, discard filtrating just with No. 3 sintered glass funnels; Get subsequent filtrate 10ml and pack in the ball B of cleaning, dry Ubbelohde viscometer, in water bath with thermostatic control (bath temperature is 75 ± 0.05 ℃), and make the liquid level of water-bath be higher than ball C the viscosity meter vertical fixing; Place after 15 minutes, the mouth of pipe 1,3 is respectively connect an emulsion tube, clamp the sebific duct of the mouth of pipe 3; Bleed in 1 place from the mouth of pipe; Make the liquid level of need testing solution slowly be increased to the middle part of ball C, the earlier open mouth of pipe 3, the open again mouth of pipe 1; Make need testing solution whereabouts naturally in pipe, with the stopwatch accurate recording liquid level alignment m that tests oneself
1Drop to and measure line m
2The delivery time at place, replication twice, twice measured value must not differ above 0.1 second, and the mean value of getting twice is the delivery time (T) of need testing solution; The purified water that No. 3 sintered glass funnels of learning from else's experience filter, same operation, replication 2 times, twice measured value should be identical, is the delivery time (T of purified water
0); Estimated performance viscosity number ([η]):
Wherein c is for supplying the concentration of examination solution, g/ml;
The assay method of said gelling is: with colloidal bismmth pectin or colloidal bismmth pectin capsule 's content porphyrize; Take by weighing 0.75g and place the 50ml color comparison tube, add an amount of mixing of water, add water to the constant volume scale; After jolting makes into rubber cement; Add hydrochloric acid (1 → 2) 4, leave standstill after the powerful jolting, form do not flow, do not dewater, non-cracking, bubble-free gel;
Said inhomogeneity assay method is: it is an amount of to get colloidal bismmth pectin, crosses 200 mesh standard sieves, takes by weighing the screenings and the screen underflow of same amount, respectively according to " Chinese pharmacopoeia two colloidal bismmth pectins of version [assay] in 2010 item method is down measured bi content;
The assay method of said galacturonic acid content is: get colloidal bismmth pectin or colloidal bismmth pectin capsule 's content 5.0g, the accurate title, decide, and puts in the beaker; Add 5ml concentrated hydrochloric acid and 100ml60% isopropyl alcohol, stirred 10 minutes, this potpourri is through Buchner funnel (capacity 60ml) vacuum filtration of the known weight of a drying; Wherein put into the filter paper (known weight) of two-layer constant weight, wash filter residue 6 times, each 15ml with hydrochloric acid-isopropyl alcohol mixed liquor; Continue to be washed till (dripping to there not being white precipitate with 1% silver nitrate test solution) till the no chlorion of filtrating with 60% isopropyl alcohol, add isopropyl alcohol 20ml again and wash, residue was at 105 ℃ of dry 3-4 hours; Put coldly, weigh; Precision takes by weighing 1/10 weight of dry residue, puts in the 250ml conical flask, and it is wetting to add ethanol 2ml; Add decarbonation distilled water 100m, jolting adds 5 of instructions phenolphthalein solutions to all dissolvings; To blush, consuming the vs volume is V with NaOH vs (0.1mol/L) titration
1(initial titration value); Repeated hydrogenation sodium oxide molybdena vs (0.5mol/L) 20.0ml, shaken was placed 15 minutes after 5 minutes; Add hydrochloric acid vs (0.5mol/L) 20.0ml; Jolting adds 3 of instructions phenolphthalein solutions again to red color disappeared, continues shaken; With NaOH vs (0.1mol/L) titration to pink terminal point, recording volume is V
2(saponification titration value); The NaOH vs (0.1mol/L) of total every 1ml of titer (is total titer=initial titration value V
1+ saponification titration value V
2) be equivalent to the galacturonic acid of 19.414mg.
1. intrinsic viscosity
Use " three therapeutic methods of traditional Chinese medicine mensuration viscosity in the viscosimetry of Chinese pharmacopoeia version regulation in 2010, and then calculate intrinsic viscosity.
1.1 assay method
The colloidal bismmth pectin 50mg that precision takes by weighing through 200 mesh sieves places the 100ml volumetric flask, adds water and is settled to scale, shakes up; Filter with No. 3 sintered glass funnels, discard filtrating just, get subsequent filtrate 10ml and pack in the ball B of cleaning, dry Ubbelohde viscometer (see " the 3rd subtraction unit in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry); In water bath with thermostatic control (bath temperature is 75 ± 0.05 ℃), and make the liquid level of water-bath be higher than ball C the viscosity meter vertical fixing, place after 15 minutes; The mouth of pipe 1,3 is respectively connect an emulsion tube, clamp the sebific duct of the mouth of pipe 3, bleed in 1 place from the mouth of pipe; Make the liquid level of need testing solution slowly be increased to the middle part of ball C, the earlier open mouth of pipe 3, the open again mouth of pipe 1; Make need testing solution whereabouts naturally in pipe, with the stopwatch accurate recording liquid level alignment m that tests oneself
1Drop to and measure line m
2The delivery time at place, replication twice, twice measured value must not differ above 0.1 second, and the mean value of getting twice is the delivery time (T) of need testing solution.The purified water that No. 3 sintered glass funnels of learning from else's experience filter, same operation, replication 2 times, twice measured value should be identical, is the delivery time (T of purified water
0).The glutinous number of estimated performance:
C is for supplying the concentration of examination solution, g/ml.
1.2 mensuration result
Colloidal bismmth pectin sample through to different bi contents and galacturonic acid content is measured, and measures result such as following table.
| Sample number into spectrum | Bi content (%) | Galacturonic acid content (%) | C(8ml) | [η] |
| 1 | 15 | 60 | 0.1 | 147 |
| 2 | 15 | 60 | 0.1 | 151 |
| 3 | 15 | 60 | 0.1 | 154 |
| 4 | ＜14 | ＞65 | 0.1 | 121 |
| 5 | ＜14 | ＞65 | 0.1 | 118 |
| 6 | ＜14 | ＞65 | 0.1 | 120 |
| 7 | ＞16 | ＜55 | 0.1 | 109 |
| 8 | ＞16 | ＜55 | 0.1 | 104 |
| 9 | ＞16 | ＜55 | 0.1 | 97 |
Can be found out by last table: when bi content 15%, galacturonic acid content 60%, intrinsic viscosity is the highest, is 147-154; When bi content less than 14%, galacturonic acid content was greater than 65% o'clock, intrinsic viscosity is 118-121; When bi content greater than 16%, galacturonic acid content was less than 55% o'clock, intrinsic viscosity is 97-109, and is the poorest.
2. gelling
[discriminating] item is gelling down, in colloidal bismmth pectin, adds appropriate hydrochloric acid, forms the gel that does not flow and do not dewater, and confirms that through test of many times this gelling test has specificity.
2.1 assay method
With colloidal bismmth pectin or colloidal bismmth pectin capsule 's content porphyrize; Take by weighing 0.75g and place the 50ml color comparison tube, add an amount of mixing of water, add water to the constant volume scale; After jolting makes into rubber cement; Add hydrochloric acid (1 → 2) 4, leave standstill after the powerful jolting, form do not flow, do not dewater, non-cracking, bubble-free gel.
2.2 mensuration result
Respectively the colloidal bismmth pectin and the colloidal bismmth pectin capsule sample of 3 different batches are measured, measured result such as following table.
| Sample number into spectrum | Sampling amount (g) | Add acid amount (dripping) | Leave standstill the back and form gel |
| Raw material 1 | 0.7529 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
| Raw material 2 | 0.7508 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
| Raw material 3 | 0.7537 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
| Capsule 1 | 0.7598 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
| Capsule 2 | 0.7577 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
| Capsule 3 | 0.7587 | 4 | Do not flow, do not dewater, non-cracking, no bubble |
3. homogeneity
According to " Chinese pharmacopoeia two P853 colloidal bismmth pectins of version [assay] in 2010 item method is down measured.
3.1 assay method
It is an amount of to get colloidal bismmth pectin, crosses 200 mesh standard sieves, takes by weighing the screenings and the screen underflow of same amount, respectively according to " Chinese pharmacopoeia two P853 colloidal bismmth pectins of version [assay] in 2010 item method is down measured bi content.
3.2 measure result such as following table.
| Sample number into spectrum | Screenings bi content (%) | Screen underflow bi content (%) | Bi content difference (%) |
| 1 | 15.34 | 15.29 | ＜1.0 |
| 2 | 14.87 | 14.96 | ＜1.0 |
| 3 | 14.98 | 14.73 | ＜1.0 |
| 4 | 15.61 | 15.73 | ＜1.0 |
| 5 | 15.29 | 15.32 | ＜1.0 |
| 6 | 14.69 | 14.57 | ＜1.0 |
6 different batches samples, the bi content of screenings and screen underflow are all in the scope of 14.0-16.0%, and both differences are less than 1.0%.
4. galacturonic acid content is measured
Galacturonic acid is the monomer after the pectin acid group degraded, and the glycosidic bond that bronsted lowry acids and bases bronsted lowry all can will connect galacturonic acid ruptures, and makes it become the galacturonic acid monomers by the galacturonic acid condensate.According to " Chinese pharmacopoeia two P1203-P1204 pectin of version [assay] in 2010 item method is down measured.
4.1 assay method
Get colloidal bismmth pectin 5.0g, the accurate title, decide, and puts in the beaker; Add 5ml concentrated hydrochloric acid and 100ml60% isopropyl alcohol, stirred 10 minutes, this potpourri is through Buchner funnel (capacity 60ml) vacuum filtration of the known weight of a drying; Wherein put into the filter paper (known weight) of two-layer constant weight, wash filter residue 6 times, each 15ml with hydrochloric acid-isopropyl alcohol mixed liquor; (with the isopropyl alcohol of different manufacturers, the number of times of washing was different till continuation was washed till the no chlorion of filtrating with 60% isopropyl alcohol; Drip to there not being white precipitate with 1% silver nitrate test solution), add isopropyl alcohol 20ml washing again, residue is at 105 ℃ of dry 3-4 hours, puts coldly, weighs.
Precision takes by weighing 1/10 weight of dry residue, puts in the 250ml conical flask, and it is wetting to add ethanol 2ml; Add decarbonation distilled water 100m, jolting adds 5 of instructions phenolphthalein solutions to all dissolvings; To blush, consuming the vs volume is V with NaOH vs (0.1mol/L) titration
1(initial titration value).Repeated hydrogenation sodium oxide molybdena vs (0.5mol/L) 20.0ml, shaken was placed 15 minutes after 5 minutes; Add hydrochloric acid vs (0.5mol/L) 20.0ml; Jolting adds 3 of instructions phenolphthalein solutions again to red color disappeared, continues shaken; With NaOH vs (0.1mol/L) titration to pink terminal point, recording volume is V
2(saponification titration value).The NaOH vs (0.1mol/L) of total every 1ml of titer (is total titer=initial titration value V
1+ saponification titration value V
2) be equivalent to the galacturonic acid of 19.414mg.
4.1.1 specificity test
Colloidal bismmth pectin is the salt compounds that is formed by pectin (polygalacturonase) and trivalent bismuth ion; In order to investigate the specificity of content assaying method; Principle according to " chemicals Quality Control Analysis method validation technological guidance's principle () " specificity money 3 assays; Promptly can in test sample, add impurity or auxiliary material, investigate measure the result and whether disturb for the major component assay, and with the test sample comparative measurements result who does not add impurity and auxiliary material.The galacturonic acid content assay method of colloidal bismmth pectin; Used for reference the galacturonic acid content assay method of pectin; The difference of colloidal bismmth pectin and pectin is to exist in the colloidal bismmth pectin trivalent metal bismuth ion; Whether influential for the existence of investigating the trivalent bismuth ion to measuring galacturonic acid, be employed in adding trivalent metal bismuth (Bi in the colloidal bismmth pectin
2O
3) method make an experiment, if influential, the sample sizes of the different amount of the adding of then measuring trivalent metal bismuth have error; If there is not influence; Error then should be in methodological precision scope; The existence that can confirm the trivalent metal bismuth is noiseless to the content of measuring galacturonic acid in the colloidal bismmth pectin, and this method has specificity preferably to the galacturonic acid content of measuring in the colloidal bismmth pectin.
(lot number: 20080101) 5.0g, totally five parts, the content that records galacturonic acid according to method under " 4.1 " item is 2.2032g 4.1.1.1 precision takes by weighing colloidal bismmth pectin.
(lot number: 20080105) 5.0g, adds Bi respectively by totally five parts 4.1.1.2 precision takes by weighing colloidal bismmth pectin
2O
30.25g, 0.5g, 0.75g, 1.00g, 1.25g, according to " 4.1 " down method content of recording galacturonic acid be 2.2012g.Add Bi respectively
2O
30.25g, the mensuration result behind the 0.5g, 0.75g, 1.00g, 1.25g with do not add Bi
2O
3Mensuration result do not have significant difference, in the scope of precision permissible error.
4.1.1.3 the accurate Bi that is equivalent to bi content in the 5.0g colloidal bismmth pectin that takes by weighing
2O
30.85g totally five parts, the content that records galacturonic acid according to method under " 4.1 " item is 0, so Bi
2O
3Do not influence the assay result of galacturonic acid.Therefore, the 4.1.1.1-4.1.1.3 test findings shows that the trivalent metal bismuth is noiseless to the content of measuring galacturonic acid in the colloidal bismmth pectin, and this method has specificity preferably.
4.1.2 linear relationship test
Precision takes by weighing galacturonic acid (content >=97.0%) 0.25g, 0.20g, and 0.15g, 0.1g, 0.05g measures according to method under " 4.1 " item, measures result such as following table.
| Galacturonic acid (g) | 0.2501 | 0.2003 | 0.1509 | 0.1003 | 0.0509 |
| Hydrogen consuming sodium oxide molybdena (0.1mol/L) total amount (ml) | 12.59 | 10.1 | 7.5 | 5.0 | 2.6 |
Amount (g) with galacturonic acid is horizontal ordinate (X), and NaOH vs (0.1mol/L) volume (ml) is ordinate (Y), gets linear equation y=50.32X-0.0152, and (R=0.9998) linear relationship is good.
4.1.3 scope test
According to " " linear relationship of testing down can know that sample size is the good linear relation in 1～6g scope to 4.1.2.
4.1.4 accuracy (recovery) test
Precision take by weighing known content colloidal bismmth pectin (lot number: 20080101) about 2g is nine parts, according to " 4.1 " down a method measure, when operating " precision takes by weighing 1/10 weight of dry residue and puts in the 250ml conical flask "; The accurate respectively height that adds, in, the galacturonic acid of hypogravity magnitude; Continue to measure by method under " 4.1 " item then; Calculating average recovery rate is 99.02%, RSD=0.71%, n=9.The colloidal bismmth pectin recovery test is measured result such as following table.
4.1.5 precision test
4.1.5.1 replica test
Precision takes by weighing colloidal bismmth pectin, and (lot number: 20080102) 5g, totally six parts, according to method mensuration under " 4.1 " item, the mean value that records galacturonic acid is 2.117467g, RSD=0.40%.
4.1.5.2 reappearance test
Laboratory 1 4.1.5.2.1 (Datong Wei Min Pharmaceutical Co)
Instrument and reagent
Drying box: model 101-1ES (the bright Medical Instruments in Beijing factory)
Balance: model FA1604 (the auspicious Instr Ltd. in Shanghai side)
It is pure that isopropyl alcohol, ethanol, NaOH, hydrochloric acid, silver nitrate are analysis
Precision take by weighing colloidal bismmth pectin (lot number: 20080103) 5g, totally three parts, respectively according to " 4.1 " down method measure, measure result such as following table.
Laboratory 2 4.1.5.2.2 (analysis room, Medicine Inst. of Datong City)
Instrument and reagent
Drying box: model KWY-101-1 (Wuchang, Wuhan)
Balance: model 120WD (day island proper Tianjin)
Accurate claim decide colloidal bismmth pectin (lot number: 20080103) 5g, totally three parts, according to " 4.1 " down method measure mensuration result such as following table.
Mensuration result shows: this method accurately and reliably.
4.1.6 the mensuration of sample
Precision take by weighing 3 lot sample article (lot number is respectively: 20080104,20080105,20080106) each three parts, every part of about 5g.Measure by method under " 4.1 " item, measure result such as following table.
When measuring, if with the isopropyl alcohol of different manufacturers, the number of times of washing is different, but the mensuration result is unaffected; With the Buchner funnel of suitable different size, under different environment, different time, it is unaffected to record the result.
The present invention finds unexpectedly; It is on the basis of existing quality standard that colloidal bismmth pectin of the present invention and pharmaceutical composition thereof increase quality control checking project, index and detection method newly; Through having increased index and method that intrinsic viscosity, gelling, homogeneity and galacturonic acid content are measured; Can guarantee the product clinical efficacy, make target level of product quality science, reasonable, controlled more.Show through a large amount of experimental studies, bi content be 15 ± 2% with galacturonic acid (monomer of pectin) content be 60 ± 2% o'clock, the colloid property of product reaches the strongest to the selective attachment effect of damaged gastrointestinal mucosa, Hp, clinical efficacy is also best.With damaged gastrointestinal mucosa and the relevant physicochemical property of Hp high selectivity adhesive attraction; All relevant like intrinsic viscosity, gelling, content homogeneity etc. with the inherent quality of product; In quality standard, increase above-mentioned quality control index; To improving this product quality, guaranteeing clinical efficacy; Avoid the generation of toxicity, to controllable product quality property, will produce significant impact to the technical progress that improves this product and pharmaceutical industry, will produce tangible scientific-technical progress and impetus in the colloidal bismmth pectin field of quality control.
Embodiment
Following examples are in order to test and to understand technical scheme of the present invention, but do not constitute claim of the present invention not being limited.
Embodiment 1
[discriminating] item inspection of gelling down: with colloidal bismmth pectin or colloidal bismmth pectin capsule 's content porphyrize; Take by weighing 0.75g and place the 50ml color comparison tube, add an amount of mixing of water, add water to the constant volume scale; After jolting makes into rubber cement; Add hydrochloric acid (1 → 2) 4, leave standstill after the powerful jolting, form do not flow, do not dewater, non-cracking, bubble-free gel.
Embodiment 2
[inspection] item inspection of intrinsic viscosity down: colloidal bismmth pectin or colloidal bismmth pectin capsule 's content porphyrize are crossed 200 mesh sieves; Precision takes by weighing 50mg and places the 100ml volumetric flask; Add water to the constant volume scale; Shake up, according to " three therapeutic methods of traditional Chinese medicine inspection in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry, result [η] is 149.
Embodiment 3
Inhomogeneity inspection under [inspection] item: take by weighing colloidal bismmth pectin 10g, cross 200 mesh standard sieves, screenings and the screen underflow of getting equivalent respectively shines " method mensuration bi content under Chinese pharmacopoeia two P853 colloidal bismmth pectins of version [assay] in 2010 item.The result: the screenings bi content is 15.71%, and the screen underflow bi content is 15.53%, and both differences are 0.18%, conform to quality requirements.
Embodiment 4
[assay] item is the galacturonic acid Determination on content down: get colloidal bismmth pectin 5.0g, the accurate title, decide, and puts in the beaker; Add 5ml concentrated hydrochloric acid and 100ml60% isopropyl alcohol, stirred 10 minutes, this potpourri is through Buchner funnel (capacity 60ml) vacuum filtration of the known weight of a drying; Wherein put into the filter paper (known weight) of two-layer constant weight, wash filter residue 6 times, each 15ml with hydrochloric acid-isopropyl alcohol mixed liquor; Continue to be washed till (dripping to there not being white precipitate with 1% silver nitrate test solution) till the no chlorion of filtrating with 60% isopropyl alcohol, add isopropyl alcohol 20ml again and wash, residue was at 105 ℃ of dry 3-4 hours; Put coldly, weigh.
Precision takes by weighing 1/10 weight of dry residue, puts in the 250ml conical flask, and it is wetting to add ethanol 2ml; Add decarbonation distilled water 100m, jolting adds 5 of instructions phenolphthalein solutions to all dissolvings; To blush, consuming the vs volume is V with NaOH vs (0.1mol/L) titration
1(initial titration value).Repeated hydrogenation sodium oxide molybdena vs (0.5mol/L) 20.0ml, shaken was placed 15 minutes after 5 minutes; Add hydrochloric acid vs (0.5mol/L) 20.0ml; Jolting adds 3 of instructions phenolphthalein solutions again to red color disappeared, continues shaken; With NaOH vs (0.1mol/L) titration to pink terminal point, recording volume is V
2(saponification titration value).The NaOH vs (0.1mol/L) of total every 1ml of titer (is total titer=initial titration value V
1+ saponification titration value V
2) be equivalent to the galacturonic acid of 19.414mg.Galacturonic acid content is 60.57%.
Claims (9)
1. the quality determining method of colloid pectin bismuth compound and pharmaceutical composition thereof is characterized in that comprising and measures following arbitrary or more than both: intrinsic viscosity, gelling, homogeneity or galacturonic acid content.
2. the quality determining method of colloid pectin bismuth compound according to claim 1 and pharmaceutical composition thereof; The assay method that it is characterized in that described intrinsic viscosity is: with colloidal bismmth pectin or its pharmaceutical composition porphyrize; Take by weighing and place container in right amount; Add water to the constant volume scale, shake up, according to " three therapeutic methods of traditional Chinese medicine in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry is measured.
3. the quality determining method of colloid pectin bismuth compound according to claim 1 and pharmaceutical composition thereof; The assay method that it is characterized in that described gelling is: with colloidal bismmth pectin or its pharmaceutical composition porphyrize; Take by weighing and place container in right amount, add an amount of mixing of water, after jolting makes into rubber cement; Add hydrochloric acid, form gel.
4. the quality determining method of colloid pectin bismuth compound according to claim 1 and pharmaceutical composition thereof; It is characterized in that described inhomogeneity assay method is: take by weighing screenings and screen underflow that colloidal bismmth pectin is crossed 200 mesh standard sieves, respectively according to " Chinese pharmacopoeia two colloidal bismmth pectins of version [assay] in 2010 item method is down measured bi content.
5. the quality determining method of colloid pectin bismuth compound according to claim 1 and pharmaceutical composition thereof; The assay method that it is characterized in that described galacturonic acid content is: according to " Chinese pharmacopoeia two pectin of version [assay] in 2010 item method is down measured, and measures V
1(initial titration value) and V
2(saponification titration value) with (total titer), every 1ml NaOH vs (0.1mol/L) is equivalent to the galacturonic acid of 19.414mg.
6. according to the quality determining method of described colloid pectin bismuth compound of claim 1-5 and pharmaceutical composition thereof, wherein said pharmaceutical composition is selected from capsule, tablet, granule etc.
7. according to the quality determining method of described colloid pectin bismuth compound of claim 1-6 and pharmaceutical composition thereof; The quality determining method that it is characterized in that described colloid pectin bismuth compound comprises intrinsic viscosity, gelling, homogeneity and galacturonic acid content mensuration, and:
Intrinsic viscosity ([η]) is for being not less than 125;
Gelling in rubber cement, add hydrochloric acid form do not flow, do not dewater, non-cracking, bubble-free gel:
Homogeneity was that the screenings of 200 mesh standard sieves and the bi content of screen underflow all should be 14～16%, and its difference must not be greater than 1.0%;
Galacturonic acid content must not be less than 60% of dry sample after the washed with isopropyl alcohol.
8. according to the quality determining method of described colloid pectin bismuth compound of claim 1-6 and pharmaceutical composition thereof; The quality determining method that it is characterized in that described colloidal bismmth pectin capsule comprises intrinsic viscosity, gelling and galacturonic acid content mensuration, and:
Intrinsic viscosity [η] is for being not less than 125;
Gelling in rubber cement, add hydrochloric acid form do not flow, do not dewater, non-cracking, bubble-free gel;
Galacturonic acid content be the galacturonic acid content of every capsules should be labelled amount 90.0～110.0%.
9. according to the quality determining method of described colloid pectin bismuth compound of claim 1-8 and pharmaceutical composition thereof, it is characterized in that:
The assay method of said intrinsic viscosity is according to " three therapeutic methods of traditional Chinese medicine in two appendix VI of Chinese pharmacopoeia version in 2010 G viscosimetry is measured, and is specially: precision takes by weighing through the colloidal bismmth pectin of 200 mesh sieves or colloidal bismmth pectin capsule 's content 50mg and places the 100ml volumetric flask, adds water to be settled to scale; Shake up, filter, discard filtrating just with No. 3 sintered glass funnels; Get subsequent filtrate 10ml and pack in the ball B of cleaning, dry Ubbelohde viscometer, in water bath with thermostatic control (bath temperature is 75 ± 0.05 ℃), and make the liquid level of water-bath be higher than ball C the viscosity meter vertical fixing; Place after 15 minutes, the mouth of pipe 1,3 is respectively connect an emulsion tube, clamp the sebific duct of the mouth of pipe 3; Bleed in 1 place from the mouth of pipe; Make the liquid level of need testing solution slowly be increased to the middle part of ball C, the earlier open mouth of pipe 3, the open again mouth of pipe 1; Make need testing solution whereabouts naturally in pipe, with the stopwatch accurate recording liquid level alignment m that tests oneself
1Drop to and measure line m
2The delivery time at place, replication twice, twice measured value must not differ above 0.1 second, and the mean value of getting twice is the delivery time (T) of need testing solution; The purified water that No. 3 sintered glass funnels of learning from else's experience filter, same operation, replication 2 times, twice measured value should be identical, is the delivery time (T of purified water
0); Estimated performance viscosity number ([η]):
Wherein c is for supplying the concentration of examination solution, g/ml;
The assay method of said gelling is: with colloidal bismmth pectin or colloidal bismmth pectin capsule 's content porphyrize; Take by weighing 0.75g and place the 50ml color comparison tube, add an amount of mixing of water, add water to the constant volume scale; After jolting makes into rubber cement; Add hydrochloric acid (1 → 2) 4, leave standstill after the powerful jolting, form do not flow, do not dewater, non-cracking, bubble-free gel;
Said inhomogeneity assay method is: it is an amount of to get colloidal bismmth pectin, crosses 200 mesh standard sieves, takes by weighing the screenings and the screen underflow of same amount, respectively according to " Chinese pharmacopoeia two colloidal bismmth pectins of version [assay] in 2010 item method is down measured bi content;
The assay method of said galacturonic acid content is: get colloidal bismmth pectin or colloidal bismmth pectin capsule 's content 5.0g, the accurate title, decide, and puts in the beaker; Add 5ml concentrated hydrochloric acid and 100ml60% isopropyl alcohol, stirred 10 minutes, this potpourri is through Buchner funnel (capacity 60ml) vacuum filtration of the known weight of a drying; Wherein put into the filter paper (known weight) of two-layer constant weight, wash filter residue 6 times, each 15ml with hydrochloric acid-isopropyl alcohol mixed liquor; Continue to be washed till (dripping to there not being white precipitate with 1% silver nitrate test solution) till the no chlorion of filtrating with 60% isopropyl alcohol, add isopropyl alcohol 20ml again and wash, residue was at 105 ℃ of dry 3-4 hours; Put coldly, weigh; Precision takes by weighing 1/10 weight of dry residue, puts in the 250ml conical flask, and it is wetting to add ethanol 2ml; Add decarbonation distilled water 100m, jolting adds 5 of instructions phenolphthalein solutions to all dissolvings; To blush, consuming the vs volume is V with NaOH vs (0.1mol/L) titration
1(initial titration value); Repeated hydrogenation sodium oxide molybdena vs (0.5mol/L) 20.0ml, shaken was placed 15 minutes after 5 minutes; Add hydrochloric acid vs (0.5mol/L) 20.0ml; Jolting adds 3 of instructions phenolphthalein solutions again to red color disappeared, continues shaken; With NaOH vs (0.1mol/L) titration to pink terminal point, recording volume is V
2(saponification titration value); The NaOH vs (0.1mol/L) of total every 1ml of titer (is total titer=initial titration value V
1+ saponification titration value V
2) be equivalent to the galacturonic acid of 19.414mg.
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