CN107118285A - High-purity colloidal bismuth pectin compound and structural formula, molecular formula, the confirmation of molecular weight - Google Patents
High-purity colloidal bismuth pectin compound and structural formula, molecular formula, the confirmation of molecular weight Download PDFInfo
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Abstract
The invention discloses the preparation method of high-purity colloidal bismuth pectin compound and chemical structural formula, molecular formula, the determination of molecular weight and application technology.The preparation method (patent) for the colloidal bismmth pectin that the compound is open before being different from, implement, former patent technique is due to producing the raw material and preparation method in the intermediate liquid pectin and bismuth salt solution of colloidal bismmth pectin, cause to contain a large amount of organic impurities (sorbierite, pectin etc.) and inorganic impurity (nitrate and hydroxide bismuth) in product, product purity is low (being only 80%), and quality standard level is low, weak curative effect.The invention provides the preparation method of several preparation high-purity (98%) colloidal bismuth pectin compounds, wherein method for optimizing five；And structural formula, molecular formula and the molecular weight of the compound are determined by spectroscopic assay and parsing.The new medicinal preparation prepared with the high-purity compound has obvious clinical advantage.
Description
Technical field
The invention belongs to pharmaceutical field (including bulk drug and pharmaceutical preparation).
Background technology
Gastrointestinal disease is clinically common disease, frequently-occurring disease, and incidence is up to 40%, and such disease easily recurs, acute attack
Gastrorrhagia is easily caused, atrophic gastritis has cAMP content, be to threaten human life and health a very big class disease.
Especially because Australian Scientists Barry Marshall, guest sieve Warren find that helicobacter pylori (Hp) is
After the pathogenic bacteria of gastrointestinal disease, because Hp has the toxic side effect for causing mucosal atrophy, bismuth to the resistance and proton pump of Multiple Classes of Antibiotics
Salt compounds turn into the treatment safe and effective medicine of gastrointestinal disease.
Bismuth salt compounds and bismuth preparation both have mucosa, the characteristic with anti-Hp, and no Hp is to antibiotic
Resistance problems.It is bismuth subcarbonate and bismuth subnitrate to be applied to clinical bismuth salt compounds earliest, because its molecular weight is big, bismuth
Content is high, more molten than great, extremely difficult, and the adhesion with mucous membrane is poor, and the protective effect to mucous membrane is weaker.In addition, above-mentioned bismuth salt class
Compound has the tendency of to cause alkalosis, and long-term taking is also easy to produce constipation, therefore clinically using seldom.1980s is Dutch
The little particle that granularity superfine (between nanometer and micron) is made using modern micropowder technology for company is readily taken the opportunity to, with certain glue
Bulk properties, enhances the adhesion with mucomembranous epithelial cell, while compound preparation is made with colloidality material, trade name is readily taken the opportunity to
Stomach (Roten).The German big pharmaceutical factory research and development in center have listed meta-aluminic acid bismuth and its compound preparation bisuc stomach tablet (Bisnc).Nitrate anion with
Aluminate is inorganic acid radical, and the salt with the formation of trivalent metal bismuth ion is difficulty soluble salt, and compound system only is made with colloidality material
Agent, could produce adhesion and protective effect to mucomembranous epithelial cell.The patented technology of Dutch Gast-Brocadis companies research and development
(CBS) the imitated DELE CHONGJI of domestic beautiful pearl preparation, is water-soluble bismuth salt, and the protective effect to gastrointestinal mucosa is preferable, but dissociation
Degree is high, is absorbed into blood circulation, causes the possibility of bismuthosis.
1992, it was basis in foregoing bismuth salt compounds and its preparation that Medicine Inst. of Datong City researcher Yu Xue is quick
On, according to chemical constitution and Relation between Biological Activity theory, synthesize colloidal bismmth pectin (CBP) and its preparation Couoidal bismuth pectin capsules
(colloidal bismuth petin), the compound replaces what is formed after inorganic acid radical and small molecular organic acid root to constitute by large biological molecule acid group
Indefinite compound (complex compound), but because the product purity is low, impurity is more, containing a large amount of organic impurities (sorbierite, not into salt
Pectin etc.) spectroscopic assays result can not provide accurate molecular formula, molecular weight and structural formula, only provide what is contained in molecule
Hydroxide galacturonic acid bismuth and structure fragment of the galacturonic acid methyl esters by α-Isosorbide-5-Nitrae-glycosidic bond formation.
Retrieved through domestic and foreign literature and have no document and the patent about compound and pharmaceutical preparation, belong to the country be it is pioneering,
And by Patent Office of the People's Republic of China's Grant Patent Right for Invention, the patent No.：ZL92114663.9, patentee is Medicine Inst. of Datong City,
Patented invention is artificial quick etc. in learning.
The preparation method of colloidal bismmth pectin that ZL92114663.9 is disclosed is：Jelly powder add water the pectin rubber cement to be formed with by
Bismuth nitrate adds after the metabismuthic acid potassium solution reaction that sorbierite, potassium hydroxide be made, with ethanol precipitation, separate, dry, crush,
Colloidal bismmth pectin crude product, through being refined into finished product.Colloidal bismmth pectin chemical purity prepared by the method is relatively low (＜ 80%), containing big
Measure organic and inorganic impurity.
On December 29th, 2009, State Intellectual Property Office has accepted " a kind of colloidal bismuth pectin compound and its drug regimen
The patent of thing and preparation method and application ", because compound and structural formula and the patent 92114663.9 of the patent protection belong to
Different compounds, thus State Intellectual Property Office is in Grant Patent Right for Invention on June 12nd, 2013, Patent No.：
201110230600.3, patentee and patented invention are artificial quick in learning.
The content of the invention
Present invention aims at there is provided high-purity colloidal bismuth pectin compound be first alkali formula bismuth potassium pectic acid (English name
For：Basic potassium bismuth of pectic acid) chemical structural formula, molecular formula, molecular weight；Secondly provide
Its physicochemical property and it is several can prepare and produce high-purity, chemical constitution it is clear and definite, of fine quality, inexpensive, with obvious clinic
The new production technology of the high-purity colloidal bismmth pectin bulk drug of advantage and bioadhesive drug formulations.
Spectroscopic assay and parsing
Structural formula：
Molecular formula：133(C6H9O8Bi).277(C6H7O6K).371(C7H10O6)
Molecular weight：(average) 180362
Spectrum analysis
From13The different equivalent carbon atom of three kinds of chemical environments, their chemical shift are can be seen that on C nmr spectrums
Respectively 45,75 and 180, peak height or peak area ratio between them are 2: 1: 3, with pectin molecule (polygalacturonase)
Monomer galacturonic acid hemiacetal structure (pyranoid ring) in carbon atom chemical environment it is identical.There is a carbon original in pyranoid ring
Son is carboxyl carbon atom (- COO-) or its methyl esters, due to the pi-conjugated effect High-Field displacement 160-185 of p-, measured value is 180, two
Carbon atom is connected with the hetero atom (oxygen) in pyranoid ring, is moved to low field, chemical shift is 45, and the other three carbon atom is respectively with two
Individual carbon atom, hydrogen atom, a hydroxyl are connected, and chemical shift is 75.The skeleton of galacturonic acid can be drawn from above
For1 carbon atom is carboxyl carbon atom, and 2 and 6 carbon atoms are directly connected with hetero atom (oxygen)
Carbon atom, 3,4 and 5 carbon atoms are to be connected with two adjacent carbon atoms, a hydrogen atom and a hydroxyl
Carbon atom.Peak is consistent (before changing) with control at sample (after change) peak.
Infrared spectrum (KBr tablettings) is in 3600cm-1And 3000cm-1There is maximum absorption band at place, clearly provides the compound point
There is provided the information that there is carboxylate in molecule at peak containing carboxyl and hydroxyl association in son.In 1600cm-1Place have it is very strong not
The anionic carboxyl peak of symmetrical carboxylate, in 1400cm-1To 1340cm-1There is symmetrical carboxylate anion peak at place, it may be determined that should
There is the structure of carboxylate and carboxylate in compound molecule：
Ultraviolet spectra (aqueous solution) has an acromion at 220nm, corresponding to the n- π transition of carboxylate, is also provided that this
There is above-mentioned carboxylic acid bismuth salt and the structure of sylvite in compound molecule.
The significant high-quality several peaks in high-quality area of mass-spectrogram are 653 and 688, are corresponded respectively to [M+3H]+[M+
K]+；In mean quality number area, mass number corresponds respectively to [M-CO for 315 and 3532Bi-CO2K+H]+[M-CO2Bi-CO3K+H
+K]+；Represent the structure containing carboxylate in the fragment after cracking.In low quality number area, mass number is corresponded to respectively for 207 and 245
In [315-6H2O]+[353-6H2O]+.Hydroxy compounds cracks that dehydration number is consistent with hydroxyl value in mass spectrogram, and collection of illustrative plates is shown
Containing 6 hydroxyls in fragment 315 and 353, prompting and the hydroxyl value (containing the hydroxyl on carboxyl) one in galacturonic acid molecules
Cause, there is galacturonic acid or aldehydic acid ester in molecular structureStructure.
Structural identification
The main method of structural identification research：Ir spectrophotometry (IR), uv-spectrophotometric (UV), nuclear magnetic resoance spectrum
(NNR), mass spectrum (MS), herein basis again with high performance liquid chromatography detect the retention time of pectin, the retention time of sorbierite,
Atomic absorption spectroscopy determination Bi and K content are to testify, it is determined that its chemical constitution.
Analysis result：Through to high-purity colloidal bismuth pectin compound carry out infrared, ultraviolet, nuclear-magnetism, mass spectrum, elementary analysis,
Atomic absorption and transmitting and viscosimetric analysis, as a result show：Bismuth ion content 15% in high-purity colloidal bismmth pectin molecule ±
1.0%, potassium content 6.28% ± 0.5%., galacturonic acid content >=74%, methoxyl content >=8% in dry fruit glue
(esterification degree 57%).Viscosimetry determines molecular weight between 120000-135000, and mean molecule quantity is 129651.
Calculated according to above method：Esterification galacturonic acid residues total molecular weight is mean molecule quantity X esterification degrees
=73901 (129651 × 0.57), 73901 divided by esterification galacturonic acid residues molecular weight (190) n, n=371.It is average
Molecular weight, which subtracts esterification galacturonic acid residues total molecular weight, must dissociate the sour residue total molecular weight 55750 of galactonic acid
(129651-13901), P, P=410 are obtained with itself divided by its residue molecular weight (176).Pectin molecule is two kinds of structure fragments (half
Lactose aldehyde and galacturonic methyl esters) the chain large biological molecule that is connected to by α-Isosorbide-5-Nitrae-glycosidic bond.Due to liquid pectin preparation side
Method is identical, and pectin structure and technological parameter prepared by two methods is also identical.Assay result C through colloidal bismuth pectin Bi and K again,
(Bi is that 15%, K is 6%) row linear equation in two unknowns group, i.e. 410=h+m
Solving equations obtain h=133, m=277.
Determined with reference to above-mentioned Spectrum Analysis, Bi elements and K element, pH value, pectin Ban Ru Tang Chuo acid contents, methoxyl content
As a result two class residue quantity and in molecular weight, pectin, carries out comprehensive analysis, and the chemical constitution of colloidal bismmth pectin can be expressed as follows：
P=h+m h=133 m=277 n=371
Molecular formula：135(C6H9O6Bi).277(C6H7O6K).371(C7H10O6)371
Molecular weight：52110+59555+70490=182155
One of new production technology of high-purity colloidal bismmth pectin bulk drug of the present invention.Will be using citrus leather jelly powder as starting
Raw material, heated water (more than 80 DEG C) is stirred afterwards makes dispersed formation pectin glue (being suspension), room temperature is cooled to, with nitre
Sour bismuth adds sorbierite, the metabismuthic acid potassium solution reaction of potassium hydroxide formation.With gained crude product after alcohol precipitation, then ethanol solution is used
Refine repeatedly, the impurity such as a large amount of sorbierites in product is removed to greatest extent, product purity (98%) is improved.
Patented method two of the present invention：Jelly powder prepared by orange peel, is scattered in hot water (more than 80 DEG C), forms pectin
Glue (slurry), with a kind of bismuth compound be not added with sorbierite or less plus sorbierite the bismuth solution reaction, the wine that prepare it is heavy, it is refined after glue
Body colloidal bismuth pectin product.This method, which can be greatly lowered in the content of sorbierite, the target level of product quality of the technique productions, to be increased
Sorbierite limitation inspection project, sorbierite limitation can be set to ＜ 1.0%.
Patented method three of the present invention.Glue preparation method is prepared with method two, will formed with method one, metabismuthic acid potassium solution
Colloidal bismmth pectin glue it is heavy without wine, use instead spray drying process directly by colloidal bismmth pectin liquid it is dry crude product, it is molten through ethanol
Liquid impurity is refining to obtain finished product, and its sorbierite limitation still can ＜ 1.0%.The colloidal bismmth pectin bulk drug of current pharmacy corporation production
Between (preparation method is patent of invention ZL 1146663.9 technique), sorbierite ＞ 15%-20%, category colloidal bismmth pectin and mountain
The mixture goods high-purity colloidal bismmth pectin of pears alcohol.
Patented method four of the present invention, to prepare the raw citrus peels (tangerine peel, lemon peel, orange peel, shaddock ped) of jelly powder
For initiation material, after the impurity such as decolouring, deodorization, deionization, pectin is extracted with diluted acid, dilute glue is made, is concentrated under reduced pressure, added
Metabismuthic acid potassium solution prepared by method one, uses ethanol precipitation, dehydration, dry, crushing, sieving are refining to obtain product after being sufficiently stirred for.
Product purity is higher than method one, and the jelly powder of method one is not completely soluble in water, and the intermediate of formation is suspension, molten with bismuth salt
The reaction of liquid is still to have to contain a small amount of pectin as impurity in the unreacted pectin in part, product in heterogeneous reaction, particle, this
Method is the pectin solution that is extracted by tangerine peel, and bismuth salt solution reaction, is to be practically free of impurity fruit in homogeneous reaction, reaction product
Glue.
Patented method five of the present invention, pectin glue preparation method is prepared with method two, three with method four, bismuth salt solution.Will
Add a small amount of sorbierite or be not added with after the pectin solution reaction that the metabismuthic acid potassium solution of sorbierite preparation extracts concentration with method four,
Spray drying, obtains product, product sorbierite ＜ 1.0% after refining, the handicraft product quality standard can increase sorbierite limitation
Check, ＜ 1.0% can be set to.Nitrate anion limitation is reduced to 0.1% by 0.3%.
The comparison and optimization of method.Method through one-method of method five is compared, screens, optimized is in method five
Most preferably, it the advantage is that：(1) bulk drug cost is low, yield is high, unit consumption is low, impurity is few, purity is high.Orange peel is agricultural byproducts
And tinned fruit processing waste residue, aboundresources；Current domestic price is 2000-3000 members/T, as the raw material for extracting pectin,
Orange peel unit consumption is 2.5T/T, the ten thousand/T of cost 0.4 ten thousand -0.5.The unit consumption that liquid pectin produces colloidal bismuth pectin is prepared by raw material of jelly powder
For 0.6T/T, country's pectin price is ten thousand yuan of 8-9 per ton at present, and pectin cost is 5.36 ten thousand yuan -6.03 ten thousand yuan per ton.(2) side
Metabismuthic acid potassium solution preparation process in method one, need to use large-scale purification water, and repeatedly top is washed, to remove NO3-, bismuth yield is low, unit consumption is high,
(increasing to 0.46T/T by theoretical unit consumption 0.37T/T) loss is more, and has pollution (discharge heavy metal ion) to environment.And nitric acid
Bismuth is expensive, and bismuth nitrate existing market price is ten thousand yuan/T of 7-8, and bismuth salt, which is lost, causes cost to increase by 0.63 ten thousand yuan/T.Using
Bismuth salt solution bismuth ion prepared by method three, four, five is almost without loss, and bismuth yield >=99%, unit consumption is 0.38 ten thousand yuan/T, cost
Reduce by 0.61 ten thousand yuan/T.Heavy metal bismuth ion is free of in the almost nil discharge of the bismuth ion of method five, industrial wastewater.(3) method two,
3rd, in four, five bismuth salt solution process for preparation, sorbierite consumption can be greatly lowered, and You Yiwu is optimal.
Production cost is contrasted, and is produced colloidal bismmth pectin with water-soluble chemical conversion pectin rubber cement with jelly powder and is prepared the original of jelly powder
Expect that orange peel particle is made pectin rubber cement and reacted with bismuth salt, production colloidal bismmth pectin raw material consumption and Cost comparisons' such as following table (work
Industry scale).
Quality standard inspection project of the present invention adds the limitation inspection of chloride, chlorination on the basis of standards of pharmacopoeia
The limitation of thing can be set to 0.5%.Increase the limitation inspection of sorbierite, limit the quantity as ＜ 1.0%.Reduce nitrate limitation (by
0.1%) 0.3% be down to.
Five colloidal bismmth pectins produced are bulk drug to pharmaceutical preparation in the process of the present invention, add compound bio adhesion material
(auxiliary material), which can be used for preparing, is being damaged the biologic adhesion preparation of gastrointestinal mucosa target administration and anelasticity medicine, such as capsule,
The various preparations such as tablet, granule, dry suspensoid agent, dry gels, liquid oral medicine, powder, dripping pill.Curative effect and toxic side effect
It is identical with the high-purity colloidal bismmth pectin that method one is produced.
Brief description of the drawings
Fig. 1 be change initiation material (liquid pectin) source before nuclear magnetic resonance map (13C is composed).
Fig. 2 be change initiation material (liquid pectin) source before nuclear magnetic resonance map (1H is composed).
Fig. 3 be change initiation material (liquid pectin) source after nuclear magnetic resonance map (13C is composed).
Fig. 4 be change initiation material (liquid pectin) source after nuclear magnetic resonance map (1H is composed).
Fig. 5 is colloidal bismmth pectin (1#) infrared spectrogram behind change initiation material (liquid pectin) source.
Fig. 6 is colloidal bismmth pectin (2#) infrared spectrogram before change initiation material (liquid pectin) source.
Fig. 7 is colloidal bismmth pectin ultraviolet spectrogram behind change initiation material (liquid pectin) source.
Fig. 8 is colloidal bismmth pectin ultraviolet spectrogram before change initiation material (liquid pectin) source.
Fig. 9 is colloidal bismmth pectin (sample) mass spectrogram behind change initiation material (liquid pectin) source.
Figure 10 is colloidal bismmth pectin (reference substance) mass spectrogram before change initiation material (liquid pectin) source.
Figure 11 is sorbierite standard items high-efficient liquid phase chromatogram, and wherein ordinate is peak height (nRIU), and abscissa is reservation
Time (min).
Figure 12 is colloidal bismuth pectin impurity sorbierite high-efficient liquid phase chromatogram, and wherein ordinate is peak height (nRIU), and abscissa is
Retention time (min).
Figure 13 is that initiation material (liquid pectin) high-efficient liquid phase chromatogram wherein ordinate is peak height (nRIU), and abscissa is stream
Go out the time (min).
Figure 14 is colloidal bismuth pectin high-efficient liquid phase chromatogram, and wherein ordinate is peak height (nRIU), and abscissa is the delivery time
(min)。
Embodiment
The embodiment to the present invention is described in detail below.It should be appreciated that described herein specific
Embodiment is merely to illustrate and explain the present invention, and is not intended to limit the invention.
Embodiment 1
The dry orange peel particles (particle diameter 2.5mm-3.5mm) of 165kg, plus 1200L purified waters is taken to heat (50-90 DEG C) immersion
30-60 minutes, centrifuge and remove decolouring water, add water washing 3-4 times.It is molten that wet peel residue through decolouring is added to dilute HCl/water
In liquid (pH2-2.5), at a temperature of 70-90 DEG C, 90-120 minutes are incubated, glue is centrifuged out.Glue through high speed solid-liquid from
Centrifugal separator remove it is a small amount of hang thing and solid impurity admittedly, obtain refined glue, being concentrated under reduced pressure, (vacuum -0.7MPa, temperature of charge is
60 DEG C or so), glue volume is reduced to 1/3rd-a quarter of dilute glue, obtain the dense rubber cement of pectin.By 11.11kg hydrogen-oxygens
Change bismuth to be added in 100kg purified waters, heating stirring makes to be separated into colloidal solution, adds potassium hydroxide (50%) aqueous solution
25kg, is sufficiently stirred for, and makes to be completely dissolved as bismuth salt solution.The bismuth salt solution of amount of calculation (10kg) is added to pectin under agitation
In rubber cement, it is sufficiently stirred for making reaction completely (color is white by xanthochromia), obtains colloidal bismmth pectin liquid.By colloidal bismmth pectin liquid Mono pump
Spray drying tower is continuously injected into, regulation inlet temperature is 170-190 DEG C, and outlet temperature is 70-90 DEG C, continuous spray drying is obtained
Colloidal bismmth pectin crude product, through refined, centrifugation, dry, crushing, sieving, obtains finished product colloidal bismmth pectin.Bi content 14-
16%, NO3 -＜ 0.1%, Cl-＜ 0.5%, SO4 2-＜ 0.08%, Pb ＜ 0.002%, As ＜ 0.0002%, settle molten product and compare ＞
98%.Gelation is tested：Take 0.7g jelly powders to add 50mL purified waters, add a small amount of acid (HCl or HNO3) shaking i.e. formation is not
Flow, be not dehydrated, the gel without tomography, without steam bubble.Moisture content 5.5-6.5%, sorbierite ＜ 1.0%, starch ＜ 0.1%.Dry tangerine
Skin unit consumption 2.5kg/kg, 6.25 yuan/kg of unit cost (2.5 yuan/kg of unit price)；Bismuth salt unit consumption 0.46kg/kg, unit cost is
36.8 yuan/kg, primary raw material unit cost 43.05kg/kg (80 yuan/kg of unit price)；49.3 yuan of main raw material(s) unit cost/
kg.Sampling carries out spectrum and chromatography, and analysis result is shown in accompanying drawing 3,4,5,7,9,11,12,13,14, and analysis result is shown in right
Claim.
Comparative example 1
Jelly powder 6kg is slowly stirred down by former technique (patent ZL92114663.9) to be added in 150L hot water, is fully stirred
Mixing makes dispersed into suspension, is cooled to less than 30 DEG C, adds bismuth nitrate, sorbierite, the method for the aqueous solution of potassium hydroxide
The bismuth salt solution 12L (bi content 0.1275kg/ml) of preparation is sufficiently stirred for, and it is 10.5-11.0 to make pH (deficiency need to add KOH).
Isometric ethanol is added, is precipitated, centrifugation, filtering, dry, crushing, sieving, refined, packaging, pectin unit consumption 0.67kg/kg, unit
60 yuan/kg of cost (90 yuan/kg of unit price), bismuth salt unit consumption 0.46kg/kg, unit cost are 36.8 yuan/kg (80 yuan/kg of unit price),
Ethanol unit consumption 4kg/kg, 32 yuan/kg of unit cost (8 yuan/kg of unit price), three primary raw material unit costs, 128.8 yuan/kg is main
Feed material cost is higher by 79.5 yuan/kg compared with embodiment.Product quality embodiment and comparative example meet Chinese Pharmacopoeia two
2000 editions, 2005 editions, 2010 editions, 2015 editions requirements.The indices of colloidal bismmth pectin, the internal control quality that pharmacopeia is not included in refers to
Mark, such as Cl-Embodiment is identical with comparative example ,≤0.5%, sorbierite embodiment≤1.0%, comparative example sorbierite ＞
18%.Dry total impurities embodiment is 1.66%, purity 98.4%；Comparative example total impurities ＞ 19.6%, purity ＜
80.4%.Sampling carries out spectrum and chromatography, as a result sees accompanying drawing 1,2,6,8,10.
Embodiment 2
The preparation of high-purity colloidal bismmth pectin bioadhesion time lag piece
(1) preparation of bioadhesive composite auxiliary material：High-purity colloidal bismmth pectin 333.33g is taken, cross-linked carboxymethyl is separately taken
Sodium cellulosate 18.52g, PVPP 18.52g, microcrystalline cellulose 35g, adding water dissolves it, and spray drying is made compound auxiliary
Material.
(2) prepared by label：High purity pectin bismuth meal is well mixed with composite auxiliary material, direct dry method (DC) tabletting, with this
As core material, disintegration time limited is determined in 0.1mol/L hydrochloric acid solution, be should be less than 10 minutes.
(3) it is coated：Ethanol (70%) mixed solution containing HPMC3% and containing PEG6000 2% is prepared, separation layer is carried out
It is coated.95% ethanol solution containing EudragitE 100 10%, PVP6%, PEG6000 2% is prepared, is wrapped as time lag layer
Clothing liquid carries out time lag layer and is coated.Pharmaceutical preparation fater disintegration in gastric juice releases the drug, and gastrointestinal mucosa epithelium is adhered to for a long time thin
Born of the same parents (reaching 6-8h) protection is damaged gastrointestinal mucosa, is conducive to the treatment of eliminating pylorus correlation gastrointestinal disease.
Comparative example 2：
The preparation of Couoidal bismuth pectin capsules, weighs colloidal bismmth pectin 333.33g, and (shallow lake is first made in the dried starch for adding equivalent
Powder particles are crushed, sieved again), to increase the proportion of starch, it is sufficiently mixed uniform, capsule loader dress capsule.Disintegration time≤30
Point, it is 2-3h in the Slack time of intestines and stomach
In Figure 11, the retention time and peak area at each peak see the table below：
In Figure 12, the retention time and peak area at each peak see the table below：
In Figure 13, the retention time and peak area at each peak see the table below：
In Figure 14, the retention time and peak area at each peak see the table below：
Claims (9)
- High-purity colloidal bismmth pectin 1. (alkali formula bismuth potassium pectic acid) compound, is pectic acid (the how poly- D (+) of part esterification half Lactobionic acid) with trivalent metal bismuth ion, the basic salt of potassium ion formation, through its raw material pectin and colloidal bismuth pectin are carried out it is infrared, Ultraviolet, mass spectrum,13C is composed and efficient liquid phase chromatographic analysis, elementary analysis, determines that its chemical structural formula is as follows：Molecular formula：133(C6H9O8Bi).277(C6H7O6K).371(C7H10O6)Molecular weight：(average) 180362.
- 2. highly pure bases formula bismuth potassium pectic acid compound according to claim 1, it is characterised in that the highly pure bases formula The physicochemical constant of bismuth potassium pectic acid compound：Character is Yellow amorphous powder, is insoluble in water, aqueous colloidal dispersion is formed in water System, addition is precipitated with the miscible organic solvent of water；Colloidal solution acid adding formation gel, plus alkali redissolve again；Insoluble in first The organic solvents such as alcohol, ethanol, acetone, ether；214-217 DEG C of decomposition point, bi content average out to 15.06%, potassium ion average out to 6.28%, pH8.5-10.5, NO3 -＜ 0.1%, Cl-＜ ＜ 0.5%, moisture content 5.5-7.5%, sorbierite ＜ 1.0%.
- 3. a kind of method of the highly pure bases formula bismuth potassium pectic acid compound prepared described in claim 1,2, it is characterised in that can The jelly powder prepared with orange peel, which is dissolved in water, prepares liquid pectin, and the liquid pectin of preparation can also be directly extracted using orange peel to rise Beginning raw material (1), to prepare and produce.
- 4. preparation method according to claim 3, it is characterised in that with compound (such as bismuth nitrate, hydroxide of bismuth metal Bismuth etc.) prepare initiation material (2) metabismuthic acid potassium solution new method and new technology, the consumption of sorbierite is greatly reduced, makes It is greatly lowered as the sorbierite limitation of impurity in product, makes former technique (patent ZL92114664.7) colloidal bismmth pectin sorb Alcohol content is reduced to ＜ 1.0% by ＞ 20%, while nitrate is reduced to 0.1% by 0.3%.
- 5. the preparation method according to claim 3 or 4, it is characterised in that manufacture colloid pectin described in claim 1 and 2 , can or spray drying process production height heavy with wine after two kinds of initiation materials (glue and metabismuthic acid potassium solution) reaction of bismuth raw material medicine Purity colloidal bismmth pectin bulk drug.
- 6. the preparation method according to claim 3-5, its production technology and technique are public compared with Patent No. ZL92114663.9 The colloidal bismmth pectin product purity for the preparation method production opened is significantly improved, and production cost is greatly lowered.
- 7. it is the new technology of preferred preparation method in compound described in claim 1 or 2 and claim 3~6, new technology, new Equipment production colloidal bismmth pectin bulk drug can be used for manufacture various new pharmaceutical preparations, with ZL92114663.9 and The product that technology disclosed in ZL20111020600.3 patents is produced, which is compared, has obvious clinical advantage.
- 8. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is included described in claim 1 or 2 with high-purity glue The new modern medicines preparation that body colloidal bismuth pectin is bulk drug and bioadhesive material is auxiliary material preparation.
- 9. pharmaceutical composition according to claim 8, it is characterised in that when described pharmaceutical composition includes colloidal bismmth pectin The new pharmaceutical preparations such as stagnant type capsule, colloidal bismmth pectin bioadhesion dry gels, the segmented intestine targeted spacer of colloidal bismmth pectin, but It is not limited to above-mentioned preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111217937A (en) * | 2020-03-25 | 2020-06-02 | 山西振东安特生物制药有限公司 | Method for preparing colloidal bismuth pectin |
| CN111965266A (en) * | 2020-04-17 | 2020-11-20 | 山西振东安特生物制药有限公司 | Method for detecting sorbitol residual quantity in colloidal bismuth pectin or colloidal bismuth pectin-containing preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765937A (en) * | 2005-12-02 | 2006-05-03 | 凌沛学 | Bismuth potassium hyalurate and its preparation method and uses |
| CN1919170A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Colloid pectin bismuth dry suspensoid and its preparing process |
| CN102391389A (en) * | 2011-08-12 | 2012-03-28 | 于学敏 | Colloidal bismuth pectin compound and medicinal composition thereof, and preparation methods and application thereof |
| CN103360513A (en) * | 2013-07-31 | 2013-10-23 | 三门峡富元果胶工业有限公司 | Production method for colloidal pectin bismuth |
-
2016
- 2016-08-31 CN CN201610770012.1A patent/CN107118285A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765937A (en) * | 2005-12-02 | 2006-05-03 | 凌沛学 | Bismuth potassium hyalurate and its preparation method and uses |
| CN1919170A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Colloid pectin bismuth dry suspensoid and its preparing process |
| CN102391389A (en) * | 2011-08-12 | 2012-03-28 | 于学敏 | Colloidal bismuth pectin compound and medicinal composition thereof, and preparation methods and application thereof |
| CN103360513A (en) * | 2013-07-31 | 2013-10-23 | 三门峡富元果胶工业有限公司 | Production method for colloidal pectin bismuth |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111217937A (en) * | 2020-03-25 | 2020-06-02 | 山西振东安特生物制药有限公司 | Method for preparing colloidal bismuth pectin |
| CN111965266A (en) * | 2020-04-17 | 2020-11-20 | 山西振东安特生物制药有限公司 | Method for detecting sorbitol residual quantity in colloidal bismuth pectin or colloidal bismuth pectin-containing preparation |
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