CN1957948A - Modified montmorillonite, preparation method and application - Google Patents

Modified montmorillonite, preparation method and application Download PDF

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CN1957948A
CN1957948A CN 200610055117 CN200610055117A CN1957948A CN 1957948 A CN1957948 A CN 1957948A CN 200610055117 CN200610055117 CN 200610055117 CN 200610055117 A CN200610055117 A CN 200610055117A CN 1957948 A CN1957948 A CN 1957948A
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acid
modified montmorillonite
montmorillonitum
montmorillonite used
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吕光烈
郑海辉
胡秀荣
夏志国
陈绩馨
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Zhejiag Hailisheng Pharmaceutical Co Ltd
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Zhejiag Hailisheng Pharmaceutical Co Ltd
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Priority to PCT/CN2006/002966 priority patent/WO2007051427A1/en
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Abstract

A modified montmorillonite with exposed and increased electric charges on its end face and between layers, lower ordered structure in C axis and improved curative effect for the reversible therapy of chronic atrophic gastritis is disclosed. Its preparing process is also disclosed.

Description

Modified montmorillonite used and preparation method thereof and its application
Technical field
The present invention relates to a kind of inorganic drug, particularly relate to modified montmorillonite used, modified na-montmorillonite and preparation method thereof and its application.
Background technology
(Chronic Atrophic Gastritis CAG) is a kind of common, obstinate digestive system disease to chronic atrophic gastritis, and the sickness rate in general crowd can reach 7.5-13.8%, and China has 100,015,000 chronic atrophic gastritis patients approximately.CAG also is the gastric precancerous lesion of generally acknowledging, its carninomatosis rate is up to about 10%, and especially with the incidence rate significant correlation of intestinal-type gastric cancer, WHO classifies it as the state in early stage of gastric cancer already, and it is classified as the I level prevention of gastric cancer.
The cause of disease complexity of CAG, helicobacter pylori (H.pylori), bile, excessive drinking and NSAID (non-steroidal anti-inflammatory drug) etc. all are common paathogenic factors.China's medical science belongs to CAG categories such as " gastric abscess ", " noisy ", " feeling of fullness ", is divided into insufficiency of the spleen, wet being stranded and three types of liver energy stagnation types etc. usually, and is wherein common with spleen-deficient.But also do not have to find the effectively treatment means of blocking-up chronic atrophic gastritis at present, more do not have to find that chronic atrophic gastritis is had the treatment means of reverse effect.
Natural Montmorillonitum is the silicates mineral with dioctahedron lamellar structure and interlayer heterogeneity CHARGE DISTRIBUTION, by two one on folder structural units's layers of forming of the alumina octahedral that connects of limit altogether in the tetrahedral si-o film that connects of top altogether, and repeat to stack the crystal that forms by the construction unit layer.Aluminum to the replacement at random of aluminum, makes it have elecrtonegativity to silicon and magnesium in the structure, and is compensated by staying the commutative hydrated cation that stays in interlayer, to reach electric equilibrium.
The basic chemical composition of natural Montmorillonitum is silicate or aluminosilicate, and outward appearance is earthy, the tool soapy feeling, and has a changeable chemism, have intensive water absorption and dilatancy, expand, disperse and suspend after meeting water, and between layer and layer the trickle slit of formation; In aqueous solution, be suspended state and gelatinized, the multiple inside and outside borne pathogenic factor in the adsorbable digestive tract, and virulence factor is discharged with digestive tract self wriggling, can be used as gastral cause of disease scavenger, and do not absorbed, do not enter blood circulation, the human body avirulence by digestive tract.In addition, hydrated cation between montmorillonite layer has interchangeability, and its ion exchange is not subject to the influence of medium acid-base value, and cholic acid, the cholate of Montmorillonitum in can the sequestration digestive tract, toxin, gas and endogenous toxin etc. to virus, antibacterial and generation thereof have extremely strong fixing, inhibitory action, can make the above-mentioned former pathogenicity that loses of causing a disease; And gastrointestinal mucosal had very strong covering protection ability, have reparation, improve defense function, balance flora and the local analgesic hemostatic effect of mucosal barrier attack factor.On February 10th, 2003, " daily magazine industry news " reported that pool, Japanese Fructus Pruni woods university lecturer palace is rich in vitro tests result show: Montmorillonitum has the absorption anaphylactogen, has anti-allergic effects, and its absorbability specific activity charcoal is high 1 times.
Natural Montmorillonitum safety non-toxic, to people, animal and plant nonhazardous and corrosiveness, non-stimulated to human body skin, neural, respiratory system there is not influence, as the choice drug for the treatment of infant diarrhea with as medical carrier, and serve many purposes at pharmaceutical field, can be used for treating diseases such as hyperthyroidism, chronic renal failure, counteract oral malodour, diarrhoea and digestive tract ulcer as oral Montmorillonitum.
Montmorillonitum can form complex with multiple organic compound, and its goods show series of characteristics at aspects such as rheological characteristic, thixotropy, surface characteristic and crystal structures, had multiple industrial use.As in petroleum industry, being used as drilling mud, be used as the balling-up binding agent of molding sand and breeze in the foundary industry, textile industry is as slurry; Its mineral monomer is as the excipient of producing medicine and prescription being dispensed, as pharmaceutical necessities, carrier, slow releasing agent or controlled release agent etc., to improve stability of drug, and play the effect of slow release or controlled release drug, and the toxic and side effects of reduction medicine, reduce dosage, strengthen the pharmacologically active of medicine; Regulate medicine rate of release in vivo, reach the effect of controlled release or slow release; Minimizing is to toxic and side effects such as gastrointestinal stimulations.
Summary of the invention
The dioctahedron clay of laminar silicate mineral that natural Montmorillonitum is made up of tetrahedral si-o film and aluminum oxide octahedral sheet, aluminum and magnesium cause its charge unbalance to the replacement at random of silicon in the structure and aluminum, meet the distinctive expansion of water, absorption, charged and ion exchange property and give it.The difference that natural Montmorillonitum exists on quantity of electric charge size, CHARGE DISTRIBUTION, interlayer cation kind makes it show physico-chemical property difference great disparities such as hydration swelling in the water, dispersion, and shows different pharmacological actions.
Purpose one of the present invention provides a kind ofly has the modified montmorillonite used of therapeutical effect to the digestive tract illness, describedly modified montmorillonite usedly be meant the dioctahedron layer structure of not destroying natural Montmorillonitum and do not change its basic chemical composition, and by changing the microstructure of dioctahedron stack layer, make its stack layer attenuation, expose and increase its end face electric charge and interlayer charge, and have the lower C axle degree of order.
The C axle degree of order of the present invention is meant the crystallite dimension that the d value is calculated for 001 diffraction maximum of 12-100  in the X diffraction pattern of Montmorillonitum.
Crystallite dimension of the present invention claims relevant farmland size again, can be in order to weigh the degree of order of Montmorillonitum, and crystallite dimension is big more, and the degree of order is high more, on the contrary the degree of order is low more.
The crystal grain of common unmodified Montmorillonitum is made up of 10-15 dioctahedron stack layer, thickness is 15-23nm, and modified montmorillonite used crystal grain is made up of 2-4 dioctahedron stack layer, and thickness is 3-6nm, or form by 3-5 dioctahedron stack layer, thickness is 4-7nm; Or form by 3-4 dioctahedron stack layer, thickness is 4-6nm.As seen, of the present inventionly modified montmorillonite usedly have the stack layer thinner than natural Montmorillonitum, end face is abundanter, behind hydration swelling, can form more " carriage-type " micelle, can produce thixotropy under lower concentration.
In addition, modified montmorillonite used not only have than natural Montmorillonitum thinner pile up synusia, end face is abundanter, and its interlayer charge and end face electric charge also significantly increase, thereby, greatly strengthened the medical function of natural Montmorillonitum.The total electrical charge of described Montmorillonitum is formed by stacking by its layer charge and variable charge two parts.
Layer charge of the present invention claims " permanent charge " or " interlayer charge " again, comes from Al 3+To Si in the silicon-oxy tetrahedron 4+And Mg 2+, Fe 2+To Al in the alumina octahedral 3+The charge unbalance that causes of isomorphous substitution.
Variable charge of the present invention claims " end face electric charge " or " variable negative charge " again, comes from OH in the crystal -Group the dissociating of H+ in alkaline medium, aquation are disperseed Si-O in the tetrahedron of back, Al-O in the octahedron, and the scission of link of Al-OH chemical bond exposes, lattice surfaces A l 3+Isoionic dissociating.
The carried charge assay method of Montmorillonitum is divided into two big classes: a class is based on the crystal structure of Montmorillonitum, the structural formula of calculating from its chemical composition is to calculate its carried charge, can obtain total amount of electric charge and the electric charge distribution situation in tetrahedron and octahedral sheet, be called the structure of chemical composition computing method; Second class is based on the cation exchange capacity method serial alkylammonium exchange process different with carbon number that hydrated cation between montmorillonite layer has commutative characteristic.The cation exchange capacity method not only can exchange the interlayer hydrated cation, also can be adsorbed by electronegative end face, and the measured quantity of electric charge is interlayer negative charge and end face negative charge sum; Series straight chained alkyl ammonium method is used to measure interlayer charge amount and distribution situation thereof only to commutative hydrated cation of interlayer and number sensitivity thereof.
At present, the Chang Yong mensuration Montmorillonitum charge density and the method for CHARGE DISTRIBUTION comprise:
1. structure of chemical composition computing method: measuring with silicate complete analysis method that the back Montmorillonitum chemistry of purifying forms (mainly is SiO 2, Al 2O Si, MgO, Fe 2OSi) atomic ratio is pressed dioctahedron general structure (E0.33) { [Al again 2-x-y, Mg xFe y] (Si 4-zAl z) O 10(OH) 2.nH 2The equilibrated principle of negative charge total amount and positive charge total amount among the O (interlayer, octahedron, three positions of face body cation sum), naturalization becomes atomic number, is assigned to tetrahedral sheet and octahedral sheet, its zwitterion difference and be Montmorillonitum hemihedral crystal born of the same parents charge density value.The Ca that the electric charge of interlayer exchangeable ion is recorded by the cation exchange capacity method 2+, Mg 2+, Na +, K +Sum obtains.
2. cation exchange capacity (CEC) method: measure cation exchange total amount in the purification sample with cobaltous chloride ammonium ion exchange process, plasma is penetrated spectrographic determination Ca wherein 2+, Mg 2+, Na +, K +Component.
3. straight chained alkyl ammonium cation exchange process: the Montmorillonitum sample ore through sodium, remove organic handle back and C6-C18 straight chained alkyl ammonium and carry out exchange reaction after, with the unnecessary alkylammonium thing of 95% ethanol flush away, vacuum drying adds SiO 2Mark is that 2-30 ° of scope measured 001 diffraction locations d with X-ray diffraction method at 2 θ in doing 001, draw d 001With the graph of a relation of carbon number NC, mix number of plies relational expression at random with MCEwan and calculate monolayer to the double-deck change ratio of double-deck transition each point, draw the layer charge density distribution histogram, obtain hemihedral crystal born of the same parents layer lotus and distribute and meansigma methods.
4. end face variable charge algoscopy: based on Montmorillonitum end face electric charge variable characteristic under condition of different pH, measure the cation exchange capacity (CEC) of different pH scopes, draw the CEC-pH curve, therefrom calculate the end face quantity of electric charge with cobaltous chloride ammonium ion exchange process.
The present invention adopts straight chained alkyl ammonium cation exchange process to measure the layer charge density and the CHARGE DISTRIBUTION of Montmorillonitum, adopts the cation exchange capacity method to measure the variable charge and the layer charge of Montmorillonitum.
The layer charge of natural Montmorillonitum is generally at 0.30-0.40eq/[(Si, Al) 4O 10], variable charge 0.0072-0.058eq/[(Si, Al) 4O 10].
Further, limit the modified montmorillonite used interlayer charge of the present invention and be not less than 0.31eq/[(Si, Al) 4O 10], preferably be not less than 0.34eq/[(Si, Al) 4O 10], more preferably be not less than 0.40eq/[(Si, Al) 4O 10], most preferably be not less than 0.43eq/[(Si, Al) 4O 10].
Further, limit modified montmorillonite used variable charge of the present invention and be not less than 0.058eq/[(Si, Al) 4O 10], preferably be not less than 0.08eq/[(Si, Al) 4O 10], more preferably be not less than 0.10eq/[(Si, Al) 4O 10], most preferably be not less than 0.12eq/[(Si, Al) 4O 10].
The C axle degree of order of the present invention is the important parameter that shows the stacked configuration state of Montmorillonitum cellular construction and its dispersion, viscosity, colloidal property.C axial unordered mainly be the layer pile up cause unordered, closely related with end face electric charge (variable charge).Modified montmorillonite used C axialite particle size of the present invention is little, and the degree of order is low, and variable negative charge is big, its 001 diffraction maximum broadening disperse, and its relevant farmland is of a size of 3-4 layer or layer 2-4 or 3-5 layer; And the C axialite particle size of natural Montmorillonitum is big, degree of order height, and variable negative charge is little, and 001 diffraction maximum broadening is little, and its relevant farmland size reaches the 10-15 layer.
As far back as 1974, Toure will (Thorez) was just according to directed glycerol saturated sample, proposed to measure the peak height P of 001 diffraction maximum, peak Qiangu V, and measure the C axle degree of order with the V/P value.The V/P value is big more, and the C axle degree of order is high more, otherwise then low.
Montmorillonitum is to be to bear hexagonal crystal shape structure, sheet aluminium silicate mineral that structure is very not complete, its cellular construction layer is often randomly with 60 ° of rotations or irregular the piling up of " turbulent flow " shape, and promptly Montmorillonitum is to have that turbulence structure, crystal are thin and tiny, the mineral of structural disorder.Octahedra center heart-yang ion A l 3+By the Mg of different ions radius 2+, Fe 2+, Fe 3+The isomorphous substitution and the existence in room cause octahedra distortion, shared rib shortens and elongates, and octahedraly tilts, and forces tetrahedral sheet rotation, elongation, twisted even scission of link, has caused structural unordered.The difference of this microstructure features has caused the difference of Montmorillonitum ore deposit on absorption property, colloidal property, charge density, CHARGE DISTRIBUTION and application performance.In addition, the bottom surface portions of single Montmorillonitum stratiform crystal grain is negative electricity, and the edge can be elecrtonegativity and electropositive because of the variation of medium pH, and charging property is relevant with its colloidal property in water.The thickness of Montmorillonitum stratiform crystal grain extends the degree of order of arranging with vertical lamella C direction of principal axis pile up by its basic structural unit structure cell along lamella a, b direction of principal axis with the width size and is determined.And a, the b axle degree of order can show the degree of the crystalline distortion of Montmorillonitum, defective, fracture, and a, the b axle degree of order are low more, and its chemism is big more.Di Kuang place, Nanjing late nineteen eighties was once studied 100 diffraction (dividing by past monocline structure cell the is 020 diffraction) height (h) at peak and the ratio h/W of 2/3 peak width (W) measures the b axle degree of order, its value is big more, and the degree of order is high more, but because of interference factor is arranged, its peak type is extremely asymmetric, easily distortion.
The present invention adopts broadening peak Fourier to analyze and full figure match structure analysis method, and with crystallite dimension as the index that characterizes structurally ordered degree, study the C axle degree of order of Montmorillonitum.
In addition, the modified montmorillonite used characteristics such as low charge layer, layer charge skewness that have of the present invention, interbed mineral partial order stacked structure at random appears, claim again " superstructure (superstructure) " that the unitary diffraction maximum of periodicity that is made of 2-7 structure sheaf appears in the low angle zone that shows its X-ray diffraction spectrum.The appearance of " superstructure " is relevant with " (expanded-Collapsed-expanded) expands-cave in-expand " of structure sheaf, because having four kinds of active forces between the stack layer of Montmorillonitum: the captivation between 1. electronegative layer and its interlayer cation; 2. Van der Waals force; 3. the repulsive force between interlayer cation; 4. the repulsive force between the adjacent layer.When the interlayer negative charge density hour, the interlayer captivation plays a leading role, stay the intermediary water Heyang ion migration stay in therebetween to adjacent layer and make, and between layer and layer, carry out ionic " distribution " again, " collapse and collapse " that causes the interlayer ion migrating layer, and the cationic adjacent layer of moving into increases " expansion " that causes layer because of its cation number, thereby form " superstructure " that comparatively orderly " expanding-cave in-expand " layer constitutes, and occur the d value of diffraction maximum in the low angle zone of X-ray diffraction spectrum.Cave in layer because of no cation, and bed thickness is about 10 , and adjacent layer causes the slightly increase of interlamellar spacing because of the cationic expansion that causes layer of moving into, and the increasing degree of bed thickness is relevant with move into cationic kind and quantity.When the aquation cation was calcium, its Laminate construction thickness was about 15.3 , and when the aquation cationic layer was sodium, the thickness of its structure sheaf was about 12.5 .Therefore, can infer the number of plies of superstructure from the d value of the d value of 001 diffraction maximum and superstructure diffraction maximum.Simultaneously the superstructure middle level piles up and is unordered, the layer arrangement position therein that " cave in " also is at random, can be in any position of periodic structure, randomness stacked structure in this just cycle makes it first-order diffraction only occur in X-ray diffractogram, and secondary, three order diffractions do not occur.
Cationic type is relevant between the probability that superstructure forms and interlayer charge distribution layer.Interlayer low charge density layer is many more, distribution is irregular more even, and the probability of appearance is high more; The kind difference of interlayer cation, the complexity of its migration are also different.Though the migration of interlayer cation forms " superstructure ", total interlayer negative charge density and distribution remain unchanged, and only are that the distribution of interlayer cation changes.
Further, modified montmorillonite used modified na-montmorillonite, modification sodium ca-montmorillonite, modification hydrogen base Montmorillonitum, modification magnesio Montmorillonitum or the modified calcium-base Montmorillonitum of being selected from of the present invention is preferably modified na-montmorillonite.
" modified na-montmorillonite " of the present invention claims " the sodium type is modified montmorillonite used ", " modification sodium matter Montmorillonitum ", " sodio is modified montmorillonite used " or " sodium modification Montmorillonitum " again, is meant that modified montmorillonite used interlayer interchangeability cation is mainly the modified montmorillonite used of sodium ion.
" modification sodium ca-montmorillonite " of the present invention claims " sodium calcium type is modified montmorillonite used ", " the calcareous Montmorillonitum of modification sodium ", " the sodium calcio is modified montmorillonite used " or " the sodium calcification is modified montmorillonite used " again, is meant that modified montmorillonite used interlayer interchangeability cation is mainly the modified montmorillonite used of sodium ion and calcium ion.
" modification hydrogen base Montmorillonitum " of the present invention claims " the hydrogen base is modified montmorillonite used ", " modification hydrogen matter Montmorillonitum ", " the hydrogen fundamental mode is modified montmorillonite used " or " the hydrogen baseization is modified montmorillonite used " again, is meant that modified montmorillonite used interlayer interchangeability cation is mainly hydrionic modified montmorillonite used.
" modification magnesio Montmorillonitum " of the present invention claims " magnesio is modified montmorillonite used ", " modified magnesium Montmorillonitum ", " the magnesium type is modified montmorillonite used " or " magnesiumization is modified montmorillonite used " again, is meant that modified montmorillonite used interlayer interchangeability cation is mainly the modified montmorillonite used of magnesium ion.
" modified calcium-base Montmorillonitum " of the present invention claims " calcio is modified montmorillonite used ", " the calcium type is modified montmorillonite used ", " the calcareous Montmorillonitum of modification " or " calcification is modified montmorillonite used " again, is meant that modified montmorillonite used interlayer interchangeability cation is mainly the modified montmorillonite used of calcium ion.
Modified montmorillonite used synusia attenuation, end face electric charge (variable charge) increase, and can form the synusia end face of more positively charged behind its hydration swelling, and with electronegative synusia in the middle of interconnective carriage-type structure, improve its gel, thixotroping and hydrability.In addition, modified montmorillonite used layer charge increases (permanent charge) and increases, the synusia attenuation, and interlayer cation broadens its CHARGE DISTRIBUTION scope by hydrated ion migration between hydrogen ion or sodium hydrated ion genetic horizon.Therefore, modified montmorillonite used more natural Montmorillonitum of the present invention has better hydration swelling, can improve the delaminate separation of Montmorillonitum in water, " carriage-type " structure that increase aspect and edge constitute, the gel particles number that forms increases, and exposes more microcosmic electric charge, has better dilatancy, absorption affinity, higher cation exchange capacity, wideer CHARGE DISTRIBUTION, thereby, greatly improved the pharmacologically active of natural Montmorillonitum.
Further, slow because sodium montmorillonite is superior than the physical and chemical performance and the process technology performance of ca-montmorillonite as absorption speed, but water absorption rate and expansion multiple are big; Cation exchange capacity (CEC) is big; Good dispersion in water.In addition, sodium montmorillonite can be separated into single structure cell, its colloid index height; In addition, the thixotropy of sodium montmorillonite soliquid, viscosity, lubricity is good, pH is high, and Heat stability is good, keeps its expansion character and certain cation exchange capacity (CEC) under higher temperature, and stronger caking property and higher plasticity are arranged.As seen, sodium montmorillonite is more superior than other Montmorillonitums (as ca-montmorillonite, sodium ca-montmorillonite, hydrogen base Montmorillonitum, magnesio Montmorillonitum) at aspects such as dilatancy, absorption affinity, cation exchange capacity, CHARGE DISTRIBUTION, has better pharmacologically active.
Cation exchange capacity of the present invention (CEC) is meant the quantity of absorption exchange cation, comprises exchangeable base and exchangeable hydrogen base, and unit is mmol/100g.The size of CEC and its aquation, expansion, charging property are relevant, are the important indicators that characterizes, judges its character and purposes.
The method of measuring cation exchange capacity at present mainly contains NH4 +Exchange process (ammonium acetate elution method etc.), Mg 2+Exchange process (magnesium oxide extraction), Na +Exchange processes (sodium acetate elution method) etc. are promptly used neutral salt drip washing mineral, its whole exchangeable cation exchanges are leached out, but behaviour's part of these assay methods are loaded down with trivial details and time-consuming.
The cobaltous chloride ammonium ion exchange process that the present invention adopts the inventor to develop is measured CEC, promptly uses [Co (NH3) 6] 3+Property cation is in return measured the cation exchange capacity of clay.Because of [Co (NH3) 6] 3+Be electric charge height (3+), ionic radius big (0.2nm), absorption maximum arranged at the 474nm place, and good at pH1～14 scope internal stabilities, be ideal exchange ion; And non-clay mineral is to not influence of exchange reaction, and free metal ion is not participated in exchange reaction yet, and need not to stir and repeated exchanged when measuring.Thereby be the single-minded method of measuring CEC, have conveniently, characteristics such as sensitive, simple and direct, accuracy height.
The process that cobaltous chloride ammonium ion exchange process is measured CEC comprises: the Montmorillonitum sample is pulverized, crossed 300 mesh sieves, 60 ℃ were dried by the fire 3 hours, standby; Again with Montmorillonitum sample and a certain amount of 0.025mol/L[Co (NH 3) 6] Cl 3Solution mixes, transfer pH to 7～8, shake up, after treating ion-exchange equilibrium, survey its absorbance at the 474.0nm place, by the difference Δ A of the absorbance before and after the exchange, calculate the concentration C of ion exchange correspondence, according to the cation exchange capacity of formula CEC=300CV/W calculating clay, V is that exchanging liquid is long-pending in the formula, and W is the sample size that takes by weighing.
Further, the cation exchange capacity (CEC) that limits Montmorillonitum of the present invention is 75-140, is preferably 80-130, and more preferably 90-125 most preferably is 100-120.
Montmorillonitum abundance (purity that claims Montmorillonitum again) is to weigh the key index of bentonite quality and application performance, with its expansion, cation exchange properties, charging property, to peel off into characteristic such as nano-scale plate directly related.
The common method of measuring the Montmorillonitum abundance at present is methylene blue method (MB), alkylammonium method etc., but has shortcomings such as error is big, complex operation.
The present invention measures the method for Montmorillonitum abundance referring to document (Hu Xiurong, Lv Guanglie etc., " mineral journal ", in June, 2005,25 (2): 153-157, the quantitative approach research of Montmorillonitum abundance in the natural montmorillonite), it is very approaching and be characteristics such as linear positive correlation and measure its abundance in whole spatial scattering total amount and its abundance of falling mainly to utilize the interlayer charge density value of same place of production Montmorillonitum and cation exchange capacity value to have a specificity, unit mass Montmorillonitum.
Further, the purity that limits gained Montmorillonitum of the present invention is not less than 95%, preferably is not less than 96%, more preferably is not less than 97%, also preferably is not less than 98%, preferably is not less than 99% in addition, most preferably is not less than 99.5%.
The present invention measures the method for Montmorillonitum swelling degree, absorption affinity, heavy metal, related substance referring to document (SOP-QC-C04700, the quality standard of Montmorillonitum).
Further, the swelling degree that limits purifying montmorillonite of the present invention is not less than 4.0, preferably must not be less than 5.0, more preferably must not be less than 7.0, and also preferably must not be less than 9.0, in addition preferably must not be less than 10.0, most preferably must not be less than 12.0.
Further, the every 1g purifying montmorillonite of qualification the present invention is 0.30-0.70g to the adsorbance of sulphuric acid strychnine, is preferably 0.40-0.65g, more preferably 0.5-0.6g.
Further, the heavy metal that limits purifying montmorillonite of the present invention must not surpass 10ppm, preferably must not surpass 7ppm, and more preferably 5ppm most preferably is 3-4ppm.
Further, the related substance that limits purifying montmorillonite of the present invention must not surpass 5%, preferably must not surpass 4%, and more preferably 3%, also preferred 2%, other is preferably 1%, most preferably is 0.5%.Described " related substance " is the impurity except that Montmorillonitum.
The modified montmorillonite used medical usage of not only strengthening natural Montmorillonitum of the present invention, also special performance is to the reversal therapies effect of gastritis, especially to the reversal therapies effect of chronic atrophic gastritis, its main medical usage comprises: (1) modified montmorillonite used application in the medicine of preparation treatment digestive tract illness, described digestive tract illness comprises but only limits to digestive tract ulcer, diarrhoea, gastritis etc., preferred described gastritis is chronic gastritis, more preferably chronic atrophic gastritis most preferably is the reversal therapies effect to chronic atrophic gastritis; (2) modified montmorillonite used in preparation treatment or prevent and treat application in the hyperthyroid medicine; (3) modified montmorillonite used application in the medicine of preparation treatment chronic renal failure; (4) modified montmorillonite used application in the medicine of preparation prevention or counteract oral malodour; (5) modified montmorillonite used application in preparation pharmaceutical carrier or excipient substance, modified montmorillonite used pharmaceutical carrier or the excipient substance of can be used as, mutually compound with some antibiotic or enzyme, make the complexation medicine, as streptomycin-Montmorillonitum complex, drug component wherein has only when cation exchange reaction takes place just can discharge the performance property of medicine, strengthens Montmorillonitum to effects such as fixing, the inhibition of antibacterial, virus etc., sterilizations; (6) modified montmorillonite used application in the dermopathic medicine for external use of preparation treatment, pass through ion exchange, sterilization, bacteriostatic metal ion or antibiotics can be exchanged, are adsorbed to the interlayer of Montmorillonitum, the Montmorillonitum that contains trace sterilization metal ion or sterilization, bacteriostasis with preparation, make it possess absorption and antibacterial or sterilization dual-use function, as the dermopathic medicine for external use of treatment; (7) modified montmorillonite used application in the preparation medicament for sobering up and protecting liver.
Modified montmorillonite used to chronic atrophic gastritis treatment and the reversal therapies effect based on its following pharmacological action: modified montmorillonite used can the combination with the mucus in the digestive tract; strengthen mucous cohesiveness and viscoelasticity; synthesizing of stimulation of endogenous prostaglandin; promote mucous secretion; reduce mucous glycoprotein sulfonyl composition; increase N-acetylgalactosamine and galactose component; and complexation cholate; fixing; suppress pathogenic pathogen such as helicobacter pylori; aspect two of quality and quantities, strengthen mucous barrier action; prevent gastric acid; pepsin; cholate and nonsteroidal anti inflammatory medicine are to the erosion of gastrointestinal mucosal; help and quicken epithelial regeneration and reparation, promote the healing of impaired mucosa.The inventor is by discovering, modified montmorillonite usedly can bring into play good reverse effect in the process of development takes place in gastric mucosa atrophy, can be used for the reversal therapies of chronic atrophic gastritis.
Association has clay mineral and a spot of organic matters such as non-clay silicate minerals such as silicon dioxide, opal, Anhydrite, Gypsum Fibrosum, calcite, perlite, zeolite and kaolinite, illite, chlorite in the natural Montmorillonitum, the mineral content of its Montmorillonitum is usually at 50%-70%, and part rich ore content can reach 80%-90%.Utilize Montmorillonitum expansible characteristic in water, reach with the symbiosis nonmetallic mineral and separate, utilize the two granule size and density variation then, by eddy flow, plant equipment such as centrifugal the thick non-clay mineral of particle is separated, but granularity is tiny of tight symbiotic alpha-quartz of Montmorillonitum and the extremely tiny cristobalite that is embedded in Montmorillonitum of granularity, the hydration swelling power of Montmorillonitum still is not enough to open the high calcio soil of the two parcel situation, particularly layer charge.According to the layer charge size, add an amount of different modifier, under different pH, temperature conditions, be aided with stirring, the last dispersion by force of in the high speed centrifugation separation equipment, quickening the Montmorillonitum particle, and high density, unexpansive alpha-quartz are removed because of separation.In addition, can utilize Montmorillonitum wafer and the stability difference of cristobalite under different hydrothermal conditions, with alkaline solution with the cristobalite hydrolysis, become liquid phase, by high speed centrifugation its separation is removed.
Another object of the present invention provides a kind of method of purifying montmorillonite, comprises the steps: 1) the natural montmorillonite drying, pulverize, sieve, powder body; 2) powder body adds water, is made into the slurry of solid content 10-30%, adds the dispersant of powder body amount 0.05-1.0%, and making beating is sieved, and removes coarse sand; 3) slurry enters multistage swirler or high speed centrifugation equipment separates, and overflow slurry drops into the high speed centrifugation separation equipment after adding the suspension that water is made into solid content 1-6%, carries out high-speed separation, removes superfine α quartz; 4) overflow slurry drops into the high speed centrifugation separation equipment, and high speed centrifugation must concentrate slurry, concentrates slurry and dries after the filter press filter pressing; Or with overflow slurry or concentrated slurry spray drying, promptly.
Dispersant of the present invention is selected from sodium hexameta phosphate, sodium trimetaphosphate, heavy Polymeric sodium metaphosphate., sodium polyacrylate, ammonia, sodium hydroxide, sodium carbonate, sodium bicarbonate, waterglass, tetrasodium pyrophosphate, Ludox, sodium carboxymethyl cellulose or mixed acid, is preferably sodium hexameta phosphate, hydrochloric acid or acetic acid.
Further, described mixed acid is mixed by mineral acid and organic acid.Described mineral acid includes but are not limited to monoacid, binary acid or ternary acid; Described monoacid is selected from hydrochloric acid, nitric acid, hydrobromic acid or Fluohydric acid., and binary acid is selected from sulphuric acid, and ternary acid is selected from phosphoric acid or sulfonic acid; Preferred mineral acid is a monoacid, most preferably is hydrochloric acid, nitric acid.
Further, described organic acid includes but are not limited to carboxylic acid, hydroxy acid, keto acid, fruit acid, according to alkyl connect different, can be divided into fatty acid, aromatic acid, aminoacid, nucleic acid, saturated acid, unsaturated acids etc., can be selected from acetic acid as organic acid of the present invention, oxalic acid, citric acid, succinic acid, formic acid, propanoic acid, butanoic acid, malonic acid, succinic acid, acetone acid, glutamic acid, tartaric acid, malic acid, lactic acid, fumaric acid, the itaconic acid, ascorbic acid, Fumaric acid, α-Tong Wuersuan or carboxylic acid, preferred organic acid is an acetic acid, oxalic acid, citric acid, succinic acid, propanoic acid, butanoic acid, succinic acid or malonic acid.
Further, the consumption of preferred dispersants is the 0.10-0.80% of powder body amount, also preferred 0.15-0.70%, more preferably 0.20-0.60%, most preferably 0.25-0.5%.
Further, preferred beating time 1-3h, more preferably 1.5-2.5h most preferably is 2h.
Further, preferred 3) step or 4) solid content of described overflow slurry of step is 2-5%, is preferably 3-4%.
Further, preferred described high speed centrifugation separation equipment is a disk centrifugal separator.
For the Montmorillonitum that contains christobalite, then utilize the dissociate difference of ability of montmorillonite nano wafer and christobalite aquation in alkaline medium, the christobalite hydrolysis is become liquid phase, removed and it separates from Montmorillonitum.Therefore, the present invention also provides a kind of purification to contain the method for the Montmorillonitum of christobalite, comprises the steps: 1) the Montmorillonitum powder body is added the slip that water is made into solid content 10-30% after, the concentration of preferred slurry is 15～25%, more preferably 20%; 2) in slurry, add the 0.5-3N alkaline solution after, the concentration of preferred alkaline solution is 1-2.5N, more preferably 1.5-2N; 3) place 100-140 ℃ of hermetic container to carry out hydrothermal treatment consists in the slurry after the alkali liquor processing, filter, the deionized water wash filter cake is preferably pH7.5-8.5 to pH7-9, more preferably about pH8; 4) after filter cake added the dilution slip that water is made into solid content 1-6%, preferred solid content was 2-5%, and more preferably 3-4% drops into the high speed centrifugation separation equipment, and high speed centrifugation is removed christobalite and alpha-quartz; 5) diluted slurry drops into the high speed centrifugation separation equipment, and high speed centrifugation must concentrate slurry, concentrates slurry and dries after the filter press filter pressing; Or with diluted slurry or concentrated slurry spray drying, promptly.
Described alkaline solution is water-soluble and make by alkaline matter well known in the art, and described alkaline matter is selected from sodium carbonate, sodium fluoride, sodium sulfate, sodium hydroxide or sodium aluminate etc.
For clear statement the present invention, " dispersant " of the present invention claims " dressing agent ", " modifier " or " modification inorganic agent " again.
The present invention also provides a kind of highly purified smectite composition, it is characterized in that, the purity of described Montmorillonitum is not less than 95%, preferably be not less than 96%, more have choosing to be not less than 97%, also preferably be not less than 98%, preferably be not less than 99% in addition, most preferably be not less than 99.5%.
Further, the swelling degree that limits high-purity montmorillonite compositions of the present invention is not less than 4.0, preferably must not be less than 5.0, and more there is the choosing must not be less than 7.0, also preferably must not be less than 9.0, in addition preferably must not be less than 10.0, most preferably must not be less than 12.0.
Further, the every 1g high-purity montmorillonite of qualification the present invention compositions is 0.30-0.70g to the adsorbance of sulphuric acid strychnine, is preferably 0.40-0.65g, more preferably 0.5-0.6g.
Further, the heavy metal that limits high-purity montmorillonite compositions of the present invention must not surpass 10ppm, preferably must not surpass 7ppm, and more preferably 5ppm most preferably is 3-4ppm.
Further, the related substance that limits high-purity montmorillonite compositions of the present invention must not surpass 5%, preferably must not surpass 4%, more elect 3% as, and is also preferred 2%, and other is preferably 1%, most preferably is 0.5%.Described " related substance " is the impurity except that Montmorillonitum.
Further, high-purity montmorillonite of the present invention is selected from bentonite through the purifying montmorillonite of purification processes or modified montmorillonite used.
Further, described modified montmorillonite used modified na-montmorillonite, modification sodium ca-montmorillonite, modification hydrogen base Montmorillonitum or the modified calcium-base Montmorillonitum of being selected from is preferably modified na-montmorillonite.
Another object of the present invention provides a kind of modified montmorillonite used method for preparing, and comprises the steps: smectite content is not less than 80% bentonite, and preferred content is not less than 85%, more preferably is not less than 90%, most preferably is not less than 95%; Mixed acid with concentration 0.1-10mol/L is preferably 0.5-8mol/L, and more preferably 0.8-6mol/L most preferably is 1-5mol/L; With soil: the mass ratio of acid is 1: 1-100 mixes, and is preferably 1: 2-50, and more preferably 1: 3-25 most preferably is 1: 3-10; Heat was boiled 0.5-100 hour, was preferably 2-70 hour, and more preferably 3-40 hour, most preferably 5-20 hour; Centrifugal or remove by filter mixed acid, the washing filter cake is drying to obtain to pH 〉=4.
Further, described mixed acid is mixed by mineral acid and organic acid.Described mineral acid includes but are not limited to monoacid, binary acid or ternary acid.Described monoacid is selected from hydrochloric acid, nitric acid, hydrobromic acid or Fluohydric acid., and binary acid is selected from sulphuric acid, and ternary acid is selected from phosphoric acid or sulfonic acid; Preferred mineral acid is a monoacid, most preferably is hydrochloric acid or nitric acid.
Further, described organic acid includes but are not limited to carboxylic acid, hydroxy acid, keto acid, fruit acid, according to alkyl connect different, can be divided into fatty acid, aromatic acid, aminoacid, nucleic acid, saturated acid, unsaturated acids etc.Preferred organic acid of the present invention is selected from acetic acid, oxalic acid, citric acid, succinic acid, formic acid, propanoic acid, butanoic acid, malonic acid, succinic acid, acetone acid, glutamic acid, tartaric acid, malic acid, lactic acid, fumaric acid, itaconic acid, ascorbic acid, Fumaric acid, α-Tong Wuersuan or carboxylic acid, more preferably acetic acid, oxalic acid, citric acid, succinic acid, propanoic acid, butanoic acid, succinic acid or malonic acid.
Further, the mol ratio of described mixed acid is a mineral acid: mineral acid and/or organic acid: organic acid is 5-150: 1-200: 5-200, be preferably 10-120: 5-150: 10-150, more preferably 20-100: 10-120: 20-120 most preferably is 30-80: 20-100: 30-100; Hydrochloric acid most preferably: oxalic acid: acetic acid is the mixed acid of 30-80: 20-100: 30-100.
Except as otherwise noted, percentage ratio of the present invention all is weight percentage.
Another object of the present invention is to provide the application of disk centrifugal separator in purification high-purity montmorillonite method, described disk centrifugal separator can conveniently be removed the fine particle in the hydration swelling bentonite, as christobalite or α quartz etc., and can conveniently solve the technical barriers such as thickening difficulty of purification liquid in the wet purification Montmorillonitum method.
Disk centrifugal separator of the present invention claims " disk centrifuge ", " disk plate centrifuge ", " disk centrifuge " or " Thin-layer separation sedimentation centrifuge " again, is a kind of vertical centrifugal machine, and separating factor can reach 3000-10000.Rotary drum is contained in vertical shaft upper end, by actuating device by Motor Drive high speed rotating.One group of inverted cone dish part that is nested in mutually together is housed in the rotary drum, claims video disc again.Leave very little gap between video disc and the video disc, clearance between two dishes can be 0.5-1.5mm.Suspension (or emulsion) adds rotary drum by the feed pipe that is positioned at the rotary drum center, is distributed in and forms laminar flows between the video disc.Under centrifugal action, particles settling is to video disc inner surface and outwards slip, and clear liquid then inwardly flows along the video disc outer surface.When suspension (or emulsion) during by the gap between the video disc, solid particle (or drop) is deposited under the centrifuge effect and forms sediment (or liquid layer) on the video disc.Sediment slides and the disengaging video disc along disc surface, and accumulates in the position of rotary drum interior diameter maximum, and the liquid after the separation is discharged rotary drum from liquid outlet.Video disc has shortened the settling height of solid particle (or drop), the settling area of expansion rotary drum, improved the production capacity and the separation efficiency of seperator greatly because video disc has been installed in the rotary drum, be suitable for handling particle diameter 0.1～100mm, solid content less than 25% suspension.The solid that accumulates in the rotary drum is taken rotary drum apart by artificial removing after seperator is shut down, or discharges from rotary drum under non-stop-machine situation by slag extractor.
Also have a kind of disk centrifugal separator to be " dish formula tube centrifuge ", be characterized in that rotary drum (pipe) diameter is little, length is big, rotating speed is high, separation efficiency is very high, can handle suspension and difficult isolating emulsion that grain diameter is 0.01mm continuously.Suspension or emulsion are added by the rotary drum lower end, are rotated with angular velocity by moving the reaching rapidly with rotary drum of the longitudinal rib strip in the rotary drum.Under centrifugal action, granule or heavy-fluid layer get rid of to the drum wall and are drawn by heavy liquid exit, and light liquid then overflows from the rotary drum centre.Its centrifugalize factor can reach 65000.Industrially can be used for oil-water separation, can be used for separate microorganism and protein in the laboratory.
As seen, disk centrifuge can be finished clarification operation and lock out operation, promptly liquid-solid separation (being the separation of low concentration suspension) and liquid-liquid (or liquid-liquid-solid) separate (separation that is emulsion), its linear velocity can reach 200 meter per seconds.Characteristics such as the used disk centrifuge of the present invention has compact conformation, and floor space is little, and production capacity is big.
The present invention will remove the Montmorillonitum slip of coarse sand and other mineral, thin up becomes the slurry of solid content 1-6%, utilizing disk centrifugal separator that unexpansive α quartz is separated from the Montmorillonitum viscose glue of expansion aquation removes, and eject with high linear velocity slave unit nozzle, improving the purity of Montmorillonitum, and can conveniently solve the technical barriers such as thickening difficulty of purification liquid in the wet purification Montmorillonitum method.
Another object of the present invention is to provide the application of disk centrifugal separator in the modified montmorillonite used method of preparation, described disk centrifugal separator can conveniently solve the dehydration difficult problem of modified slurry in the preparation method.
Another object of the present invention provides a kind of pharmaceutical composition that is used for the treatment of the intestinal illness, is made up of modified montmorillonite used and pharmaceutically acceptable carrier.
Further, described digestive tract disease illness is selected from digestive tract ulcer, diarrhoea or gastritis, and preferred described gastritis is chronic gastritis, and more preferably chronic atrophic gastritis most preferably is the reversal therapies effect to chronic atrophic gastritis.
Further, modified montmorillonite used in the preferred composition: the weight ratio of adjuvant (by dry product) is 0.001-4: 1-50, is preferably 0.001-3: 1-25, more preferably 0.001-2: 1-10 most preferably is 0.001-1: 1-5.
Further, the weight percentage of Montmorillonitum is 1-100% in the compositions, is preferably 5-95%, also is preferably 10-90%, and more preferably 15-85% most preferably is 20-80%.
Compositions of the present invention can be various dosage form well known in the art, and the preparation technique that can adopt this area routine is to prepare compositions of the present invention.Be suitable for preparation of the present invention and be selected from oral formulations or external preparation, be preferably oral formulations.
Further, described oral formulations is selected from tablet, suspension, capsule, granule, pill, powder, drop pill, syrup, mixture, distillate medicinal water, effervescent, paste or medicinal tea etc.; Be preferably powder, suspension, granule, tablet, capsule or effervescent.
Further, be suitable for external preparation of the present invention and can be selected from colloid, emplastrum, plaster, cream, ointment, liniment, lotion, suppository, liniment or coagulate unguentum etc., be preferably gel.
Described pharmaceutically acceptable carrier is well known usual excipients or the adjuvant that is used to prepare above-mentioned preparation, and excipient that oral formulations or external preparation are commonly used or adjuvant include but are not limited to filler (claim not only diluent), lubricant (but also claiming fluidizer or antitack agent), dispersant, wetting agent, binding agent, regulator, solubilizing agent, antioxidant, antibacterial, emulsifying agent, correctives, odorant etc.Binding agent, for example syrup, arabic gum, gelatin, sorbitol, tragacanth, cellulose and derivant thereof, gelatine size, syrup, starch slurry or polyvinylpyrrolidone, preferred cellulose derivative is microcrystalline Cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose; Filler, for example lactose, Icing Sugar, dextrin, starch and derivant thereof, cellulose and derivant thereof, inorganic calcium salt, sorbitol or glycine, preferred inorganic calcium salt is calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate; Lubricant, for example micropowder silica gel, magnesium stearate, Pulvis Talci, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol; Disintegrating agent, for example starch and derivant thereof, polyvinylpyrrolidone or microcrystalline Cellulose, preferred starch derivatives is carboxymethyl starch sodium, Explotab, pregelatinized Starch, modified starch, hydroxypropyl starch, corn starch; Wetting agent, for example sodium lauryl sulphate, water or alcohol etc.
In addition, also active component can be mixed by its preparation requirement with pharmaceutically acceptable slow controlled release carrier, again according to the preparation method of sustained-release preparation well known in the art, as adding the blocker coating or with making micropill after the active principle microcapsulesization again, as slow-release micro-pill or controlled release micro pill; Described slow controlled release carrier includes but are not limited to oil agent, hydrophilic colloid or the coating blocker etc. of mixing, and described oil to mix agent be glyceryl monostearate, castor oil hydrogenated, Dormant oils, polysiloxanes, dimethyl siloxane; Described hydrophilic colloid is cellulose derivatives such as sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, or PVP, arabic gum, tragcanth or carbopol etc.; Described coating blocker is ethyl cellulose (EC), hydroxypropyl methylcellulose (HMPC), polyvinylpyrrolidone (PVP), cellulose acetate-phthalate (CAP), acrylic resin etc.
Another object of the present invention provides modified montmorillonite used application in the medicine of preparation treatment intestines and stomach, especially to the reversal therapies effect of gastritis, preferably to the reversal therapies effect of chronic atrophic gastritis.
The modified montmorillonite used original medical usage of natural Montmorillonitum that not only possesses reinforcement of the present invention, also special performance is to the reversal therapies effect of gastritis, especially the reversal therapies effect of chronic atrophic gastritis, its main medical usage is as follows: (1) modified montmorillonite used application in the medicine of preparation treatment digestive tract illness, described digestive tract disease comprises but only limits to acute and chronic diarrhea, reflux esophagitis, chronic gastritis, peptic ulcer, irritable bowel syndrome, inflammatory intestinal illness, gastritis etc., preferred described gastritis is chronic gastritis, more preferably chronic atrophic gastritis most preferably is the reversal therapies effect to chronic atrophic gastritis.The anti-microbial type medicine directly sterilizes though Montmorillonitum does not have, the bacteriostatic function, but can utilize the commutative characteristic of its interlayer ion, antibacterial and the absorption of its metabolism toxin are exchanged to interlayer, promote the reparation of injured intestinal mucosa, and bacterial acute and chronic diarrhea illness is had good therapeutic effect, and diarrheal therapeutic effect and its layer charge density are proportionate; In addition, Montmorillonitum has unique synusia structure, and inhomogeneous CHARGE DISTRIBUTION and slip visco-plasticity can evenly cover the digestive tract surface continuously, with static and materialization effect performance curative effect, the gastrointestinal tract illness is had good preventive and therapeutic effect; (2) modified montmorillonite used in preparation treatment or prevent and treat application in the hyperthyroid medicine; (3) modified montmorillonite used application in the medicine of preparation treatment chronic renal failure; (4) modified montmorillonite used application in the medicine of preparation prevention or counteract oral malodour; (5) modified montmorillonite used application in preparation pharmaceutical carrier or excipient substance, modified montmorillonite used pharmaceutical carrier or the excipient substance of can be used as, mutually compound with some antibiotic or enzyme, make the complexation medicine, as streptomycin-Montmorillonitum complex, drug component wherein has only when cation exchange reaction takes place just can discharge the performance property of medicine, strengthens Montmorillonitum to effects such as fixing, the inhibition of antibacterial, virus etc., sterilizations; (6) modified montmorillonite used application in the dermopathic medicine for external use of preparation treatment, pass through ion exchange, sterilization, bacteriostatic metal ion or antibiotics can be exchanged, are adsorbed to the interlayer of Montmorillonitum, the Montmorillonitum that contains trace sterilization metal ion or sterilization, bacteriostasis with preparation, make it possess absorption and antibacterial or sterilization dual-use function, as the dermopathic medicine for external use of treatment; (7) modified montmorillonite used application in the preparation medicament for sobering up and protecting liver.
Modified montmorillonite used to chronic atrophic gastritis treatment and the reversal therapies effect based on following pharmacological action: modified montmorillonite used can the combination with the mucus in the digestive tract; strengthen mucous cohesiveness and viscoelasticity; synthesizing of stimulation of endogenous prostaglandin; promote mucous secretion; reduce mucous glycoprotein sulfonyl composition; increase N-acetylgalactosamine and galactose component; and complexation cholate; fixing; suppress pathogenic pathogen such as helicobacter pylori; aspect two of quality and quantities, strengthen mucous barrier action; prevent gastric acid; pepsin; cholate and nonsteroidal anti inflammatory medicine are to the erosion of gastrointestinal mucosal; help and quicken epithelial regeneration and reparation, promote the healing of impaired mucosa.The inventor is by discovering, Montmorillonitum and modified montmorillonite used distinctive microcosmic charging property, make it can bring into play good reverse effect in the process that gastric mucosa atrophy takes place to develop, can be used for the reversal therapies of chronic atrophic gastritis, reverse effect and its microcosmic carried charge are proportionate.
Existing pharmacological research shows: natural Montmorillonitum does not have antibacterial or bactericidal action, to antibacterial mainly is adsorption, used as the medicine of treatment diarrhoea and digestive tract ulcer, the adsorbable fixation of bacteria of its " carriage-type " gel structure and its metabolism toxin are its treatment diarrheal pharmacological basis clinically.Natural Montmorillonitum also all has adsorption preferably to escherichia coli, vibrio cholera, campylobacter jejuni, golden Portugal bacterium and rotavirus and cholate; Antibacterial and its metabolism toxin had good fixation.Other has research also to show, the pathogenic charged pathogen that Montmorillonitum only adsorbs, fixed surface has an encoding proteins (CS31A) does not have fixedly scavenging action with the normal flora of CS31A to the surface, thereby avirulence.
Electronegative plate surface behind the Montmorillonitum hydration swelling is connected with the edge of positively charged, forms " compartment " the formula float of " marginal surface ", has " thixotropy " of " gel-sol-gel " sample.And " compartment " formula particle locks onto antibacterial in " compartment ", and it is removed.Of the present invention modified montmorillonite used by changing the microstructure of natural Montmorillonitum stack layer, the synusia attenuation, end face electric charge and variable charge all increase, CHARGE DISTRIBUTION broadens, and exchanges the cation of easy aquation at interlayer, and pulverizes by force to increase the edge, strengthen that its aquation is delaminated, gelling performance, increase " compartment " quantity, strengthened the removing ability of natural Montmorillonitum greatly, and greatly strengthen and expand its medical applications antibacterial and toxin.
Further, limiting the modified montmorillonite used day dosage of the present invention is 1-9g, is preferably 2-7g, and more preferably 3-6g most preferably is 4-5g.
Another object of the present invention is to provide the application of natural Montmorillonitum in the medicine of chronic atrophic gastritis, be preferably reversal therapies effect chronic atrophic gastritis.
At present, calcium-base bentonite sodium method there are usually two kinds of dry method and wet methods.Described dry method sodium method adopts sodium agent and Montmorillonitum directly to do and mixes, and handles promptly through milling.Be characterized in that technology is simple, but exist sodium inhomogeneous more, easily answer shortcomings such as calcification.
Described wet method sodium method is meant various soluble sodium saline solution and Montmorillonitum is disposed by a certain percentage that between the faintly acid, heating, stir process are promptly at alkalescence for regulator solution pH.Be characterized in that sodium is thorough, but sodium fluid dewatering difficulty.
It is modified montmorillonite used that the present invention adopts hydrogenation sodium method or direct sodium legal system to be equipped with sodio.Can adopt the method for first purification, modification, hydrogenation, sodium, or adopt the method for first modification, hydrogenation, purification, sodium, or adopt the method for first purification, modification, sodium, to prepare highly purified modified na-montmorillonite.
Another object of the present invention is to provide a kind of modified montmorillonite used method of sodio (hydrogenation sodium method) for preparing, comprise the steps: purity is not less than 95% modified calcium-base Montmorillonitum or modification magnesio Montmorillonitum, add acid solution and be made into the slip that solid content is 10-30%, stir, remove by filter acid solution, filter cake with hot wash to faintly acid, filter pressing becomes the filter cake of solid content 30-70%, adds the sodium agent suitable with cation exchange capacity, stirs sodium, make its PH be alkalescence, be drying to obtain.
Further, the purity of modified calcium-base Montmorillonitum, modification hydrogen base Montmorillonitum or modification magnesio Montmorillonitum is not less than 96%, preferably is not less than 97%, more preferably is not less than 98%, also preferably is not less than 99%, most preferably is not less than 99.5%.
Further, described acid solution is selected from mineral acid, organic acid or its mixture.Described mineral acid includes but are not limited to monoacid, binary acid or ternary acid; Described monoacid is selected from hydrochloric acid, nitric acid, hydrobromic acid or Fluohydric acid., and binary acid is selected from sulphuric acid, and ternary acid is selected from phosphoric acid or sulfonic acid; Be preferably monoacid, most preferably be hydrochloric acid, nitric acid.
Further, described organic acid includes but are not limited to carboxylic acid, hydroxy acid, keto acid, fruit acid, fatty acid, aromatic acid, aminoacid, nucleic acid, saturated acid, unsaturated acids etc., be preferably acetic acid, oxalic acid, citric acid, succinic acid, formic acid, propanoic acid, butanoic acid, malonic acid, succinic acid, acetone acid, glutamic acid, tartaric acid, malic acid, lactic acid, fumaric acid, itaconic acid, ascorbic acid, Fumaric acid, α-Tong Wuersuan or carboxylic acid, more preferably acetic acid, oxalic acid, citric acid, succinic acid, propanoic acid, butanoic acid, succinic acid or malonic acid.
Further, the concentration of acid solution is 0.1-10N, is preferably 0.2-8N, and more preferably 0.3-6N most preferably is 0.5-3N.
Further, the solid content of preferred slip is 15-25%, more preferably 20%.
Further, the solid content of preferred filter cake is 40-60%, more preferably 50%.
Further, sodium agent of the present invention claims " sodium salt modifier " again, can be with the Ca in ca-montmorillonite, magnesio Montmorillonitum or the hydrogen base Montmorillonitum 2+, Mg 2+Or H +Be exchanged into Na +, described sodium agent is this area soluble sodium salt commonly used, is selected from Na 2CO 3, NaHCO 3, NaCl, NaF, Na 3PO 4, Na 2HPO 4, sodium sulfate, NaAlO 2Or sodium hydroxide.
Another object of the present invention is to provide a kind of modified montmorillonite used method of sodio (directly sodium method) for preparing, comprise the steps: purity is not less than 95% modified calcium-base Montmorillonitum or modification magnesio Montmorillonitum or hydrogen base Montmorillonitum, add the sodium agent suitable with cation exchange capacity, be made into the slip of solid content 30-70%, stir sodium, remove by filter the solubility sodio, make it be alkalescence, be drying to obtain.
Further, the purity of modified calcium-base Montmorillonitum, modification hydrogen base Montmorillonitum or modification magnesio Montmorillonitum is not less than 96%, preferably is not less than 97%, more preferably is not less than 98%, also preferably is not less than 99%, most preferably is not less than 99.5%.
Further, described sodium agent is this area soluble sodium salt commonly used, is selected from Na 2CO 3, NaHCO 3, NaCl, NaF, Na 3PO 4, Na 2HPO 4, sodium sulfate, NaAlO 2Or sodium hydroxide.
Further, the solid content of preferred slip is 40-60%, more preferably 50%.
Montmorillonitum is carried out sodium modification can impel bentonitic imbibition, open the stack between its layer and the layer, it is dissociated into monocrystalline, the christobalite of wherein inlaying dissociating.
Montmorillonitum is based on its colloidal sol viscose properties and microcosmic charging property as the pharmacology of digestive tract medicine.Montmorillonitum after modification is handled can increase the exposure of the hiding variable center of negative charge of natural Montmorillonitum, increases the end face electric charge, the Fe in the octahedra lamella structure of stripping simultaneously 2+, Mg 2+, Fe 3+, improve its layer charge, widen the distribution of layer charge, improved the inhomogeneities of CHARGE DISTRIBUTION, improve its delaminating property of hydration swelling and charge characteristic, strengthen its pharmacologically active.
Description of drawings
The x x ray diffraction material phase analysis figure of Fig. 1 embodiment 1 gained purifying montmorillonite;
The x x ray diffraction material phase analysis figure of Fig. 2 embodiment 1 gained modified calcium-base Montmorillonitum;
The x x ray diffraction material phase analysis figure of Fig. 3 embodiment 1 gained modified na-montmorillonite;
The x x ray diffraction material phase analysis figure of Fig. 4 embodiment 2 purifying montmorillonites;
The x x ray diffraction material phase analysis figure of Fig. 5 embodiment 2 gained modified calcium-base Montmorillonitums;
The x x ray diffraction material phase analysis figure of Fig. 6 embodiment 2 gained modified na-montmorillonites;
The x x ray diffraction material phase analysis figure of Fig. 7 embodiment 3 raw ores;
The x x ray diffraction material phase analysis figure of Fig. 8 embodiment 3 purifying montmorillonites;
The x x ray diffraction material phase analysis figure of Fig. 9 embodiment 3 gained modified calcium-base Montmorillonitums;
The x x ray diffraction material phase analysis figure of Figure 10 embodiment 3 gained modified na-montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 11 embodiment 4 purifying montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 12 embodiment 4 gained modified calcium-base Montmorillonitums;
The x x ray diffraction material phase analysis figure of Figure 13 embodiment 4 gained modified na-montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 14 embodiment 5 gained purifying montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 15 embodiment 5 gained modified calcium-base Montmorillonitums;
The x x ray diffraction material phase analysis figure of Figure 16 embodiment 5 gained modified na-montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 17 embodiment 6 raw ores;
The x x ray diffraction material phase analysis figure of Figure 18 embodiment 6 purifying montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 19 embodiment 6 gained modified calcium-base Montmorillonitums;
The x x ray diffraction material phase analysis figure of Figure 20 embodiment 6 gained modified na-montmorillonites;
The x x ray diffraction material phase analysis figure of Figure 21 embodiment 6 gained modification sodium ca-montmorillonites;
Figure 22: each group of test is to the influence of rat gastric antrum mucous layer thickness level;
Figure 23: each group of test is to the influence of rat gastric antrum portion mucous layer thickness/muscular layer of mucosa thickness (L1/L2) ratio;
Figure 24: each group of test is to the influence of rat gastric antrum portion mucomembranous gland density;
Figure 25: each group of test is to the influence of rat gastric antrum portion inflammation index;
Figure 26: each group of test is to the influence of gastric mucosa of rat aminohexose level;
Figure 27: each group of test is to gastric mucosa of rat PGE 2The influence of level.
The specific embodiment
Specify the present invention below with reference to embodiment, embodiments of the invention only are used to technical scheme of the present invention is described, and non-limiting essence of the present invention.
The preparation that embodiment 1 is modified montmorillonite used
The material phase analysis of purifying montmorillonite is referring to Fig. 1.
In purifying montmorillonite, the mixed acid that adds concentration 2mol/L, the consisting of of mixed acid (hydrochloric acid: oxalic acid: the mol ratio of acetic acid is 4: 10: 6), with soil: the mass ratio of acid is to mix at 1: 3, under 100 ℃ of conditions, heat was boiled 5-6 hour, removed by filter mixed acid, filter cake with deionized water wash to pH 〉=4,100 ℃ of dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Fig. 2.
The modified calcium-base Montmorillonitum of gained is made into the slip of solid content 20% with the hydrochloric acid solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 60 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 50%, add the sodium carbonate (as the 4.5-5% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 34h 120 ℃ of dryings, is ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Fig. 3.
The preparation that embodiment 2 is modified montmorillonite used
The material phase analysis of purifying montmorillonite is referring to Fig. 4.
In purifying montmorillonite, the mixed acid that adds concentration 1mol/L, the consisting of of mixed acid (hydrochloric acid: oxalic acid: the mol ratio of acetic acid is 3: 4: 3), with soil: the mass ratio of acid is to mix at 1: 4, under 90 ℃ of conditions, heat was boiled 6-8 hour, removed by filter mixed acid, filter cake with deionized water wash to pH 〉=4,120 ℃ of dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Fig. 5.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 15% with the sulfuric acid solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 70 ℃ of hot washes to PH about about 5.5, filter pressing becomes the filter cake of solid content about 40%, add the sodium hydroxide (as the 5-5.5% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 8-9, sodium time 34h, 115 ℃ of dryings, be ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Fig. 6.
The preparation that embodiment 3 is modified montmorillonite used
The mineral composition of bentonite raw ore: referring to Fig. 8.
The raw ore drying, pulverize, cross 50 mesh sieves, the sodium hexameta phosphate that adds the water and the 0.3% original ore powder scale of construction, form the slip of solid content 20%, stir after two hours, cross three grades of hydrocyclones, the slip after the separation adds the solvent or diluent slurry of water furnishing solid content 3%, enters disk centrifugal separator and separates, the solvent or diluent slurry of separating enters another disk centrifugal separator again and concentrates, slip after the concentration obtains the filter cake of solid content 40-50% after the filter press filter pressing, filter cake is 125 ℃ of oven dry, be crushed to more than 500 orders, the mineral composition of purifying montmorillonite is referring to Fig. 8.
In purifying montmorillonite, the mixed acid (sulphuric acid: citric acid: the mol ratio of acetic acid consisted of 6: 8: 6) that adds concentration 2mol/L, with soil: the mass ratio of acid is to mix at 1: 6, and under 80 ℃ of conditions, heat was boiled 7-8 hour, remove by filter mixed acid, filter cake with deionized water wash to pH be 4.5,115 ℃ of dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Fig. 9.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 25% with the hydrochloric acid solution of 1N, stir 7h, remove by filter acid solution, filter cake with 90 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 60%, add the sodium chloride (as the 3.5-4% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 34h, 120 ℃ of dryings, be ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Figure 10.
The preparation that embodiment 4 is modified montmorillonite used
The material phase analysis of purifying montmorillonite is referring to Figure 11.
In purifying montmorillonite, the mixed acid (phosphoric acid: tartaric acid: the mol ratio of oxalic acid consisted of 10: 12: 12) that adds concentration 5mol/L, with soil: the mass ratio of acid is to mix at 1: 5, and under 70 ℃ of conditions, heat was boiled 9-10 hour, remove by filter mixed acid, filter cake with deionized water wash to pH be about 4.5,120 ℃ of dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Figure 12.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 30% with the salpeter solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 60 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 65%, add the sodium bicarbonate (as the 5-5.5% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 36h, 125 ℃ of dryings, be ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Figure 13.
The preparation that embodiment 5 is modified montmorillonite used
The material phase analysis of purifying montmorillonite is referring to Figure 14.
In purifying montmorillonite, the mixed acid (nitric acid: malic acid: the mol ratio of acetic acid consisted of 75: 120: 105) that adds concentration 3mol/L, with soil: the mass ratio of acid is to mix at 1: 3, heat was boiled 7-8 hour under 90 ℃ of conditions, removed by filter mixed acid, filter cake with deionized water wash to pH 〉=4,120 ℃ of dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Figure 15.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 10% with the hydrochloric acid solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 60 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 50%, add the sodium carbonate (as the 4-4.5% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 32h, 115 ℃ of dryings, be ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Figure 16.
The preparation that embodiment 6 is modified montmorillonite used
The mineral composition of bentonite raw ore is referring to Figure 17.
Bentonite is formed the slip that mixed acid is made into 30% solid content with 0.9N acetic acid and 0.1N hydrochloric acid, handled 2 hours at 60 ℃, remove by filter the filter cake of mix acid liquor, to pH＞5, thin up becomes the solvent or diluent slurry of 5% solid content with 60 ℃ of hot washes, slip after twice separation of disk centrifugal separator and once concentration, become the filter cake of solid content 40-50% with filter press, after 120 ℃ of oven dry, be crushed to more than 500 orders, the mineral facies of purifying montmorillonite are formed, referring to Figure 18.
In purifying montmorillonite, the mixed acid (methanesulfonic acid: oxalic acid: the mol ratio of malonic acid consisted of 40: 5: 10) that adds concentration 5mol/L, with soil: the mass ratio of acid is to mix at 1: 4, heat was boiled 5-10 hour under 60 ℃ of conditions, removed by filter mixed acid, filter cake with deionized water wash to pH 〉=4, at 120 ℃ of air dryings, be ground into the 300-500 order, promptly get the modified calcium-base Montmorillonitum, its abundance or material phase analysis are referring to Figure 19.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 20% with the hydrochloric acid solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 60 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 50%, add the sodium fluoride (as the 5-6% of modified calcium-base Montmorillonitum consumption) suitable with cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 32h, 110 ℃ of dryings, be ground into the 300-500 order, promptly get modified na-montmorillonite, its abundance or material phase analysis are referring to Figure 20.
Modified calcium-base Montmorillonitum with gained, be made into the slip of solid content 20% with the hydrochloric acid solution of 0.5N, stir 6h, remove by filter acid solution, filter cake with 70 ℃ of hot washes to PH about about 5, filter pressing becomes the filter cake of solid content about 50%, add sodium fluoride (as the 3-3.5% of modified calcium-base Montmorillonitum consumption) with half amount of cation exchange capacity, stir sodium, making its PH is 7-8, sodium time 32h, 120 ℃ of dryings, be ground into the 300-500 order, promptly get modification sodium ca-montmorillonite, its abundance or material phase analysis are referring to Figure 21.
Embodiment 7 modified montmorillonite used electric charges are measured
Available structure of chemical composition analytic process, cation exchange capacity method and linear paraffin base ammonium method are studied charge source, size, the distribution of Montmorillonitum, in the Montmorillonitum crystal structure, scission of link-Si-OH that aluminum produces in the three dimensions fracture the replacement and the crystal layer of aluminum in the aluminum oxide octahedral sheet the replacement of silicon in the tetrahedral si-o film, magnesium,-Al-OH makes its interlayer and end face present elecrtonegativity.By measuring its cation exchange capacity, to calculate its carried charge.Assay method is as follows:
1, the mensuration of interlayer charge
The Montmorillonitum sample ore carries out exchange reaction with C6-C18 straight chained alkyl ammonium chloride after handling through sodium, except that organic matter, and with the unnecessary alkylammonium chloride of 95% ethanol flush away, vacuum drying adds SiO 2Mark is that 2 °～30 ° scopes are measured 001 diffraction locations d with X-ray diffraction method at 2 θ in doing 001, draw d 001With carbon number N CGraph of a relation, mix the layer functions relational expression at random with MCEwan, calculate monolayer to the double-deck ratio that changes of double-deck transition each point, draw the layer charge density distribution histogram, obtain hemihedral crystal born of the same parents layer charge and distribute and meansigma methods.
2, variable charge density (Eq./(Al.Si) 4O 10) mensuration
Variable charge claims the end face electric charge again, and its density changes with pH value is different.With cobaltous chloride ammonium ion exchange method, in the pH4-12 scope, measure the cation exchange capacity CEC of different pH, by relation curve between CEC and pH, again in conjunction with formula LC (Eq./(Al, Si) 4O 10)=CEC * 360 * 10 -5, the unit (mmol/100g) of cation exchange capacity is converted into the (Eq./(Al.Si) of unit of layer charge 4O 10), LC presentation layer charge density in the formula, CEC represents cation exchange capacity.
The measurement result of modified montmorillonite used layer charge density, variable charge density, total charge density, swelling degree, adsorbance and the CEC for preparing according to the open method of the present invention is referring to table 1.
The measurement result of natural Montmorillonitum of table 1 and modified montmorillonite used physicochemical property parameter
Embodiment Kind Layer charge Variable charge Total charge density Swelling degree Adsorbance CEC
1 Calcio (A) 0.431 0.133 0.564 4.0 0.516 122
Sodio (G) 0.433 0.135 0.566 8.0 0.520 123
2 Calcio (B) 0.410 0.108 0.518 4.5 0.500 116
Sodio 0.415 0.110 0.520 9.0 0.504 115
3 Natural Montmorillonitum (E) 0.397 0.008 0.415 5.8 0.480 105
Sodio 0.402 0.010 0.420 11.0 0.485 107
4 Calcio (C) 0.343 0.147 0.490 7.0 0.450 98
Sodio 0.351 0.153 0.495 11.5 0.452 99
5 Calcio (D) 0.311 0.108 0.419 8.5 0.430 92
Sodio 0.320 0.118 0.425 12.5 0.429 91
6 Natural Montmorillonitum (F) 0.302 0.057 0.359 3.84 0.384 86
Sodium calcio (H) 0.304 0.062 0.364 3.90 0.388 87
The preparation of embodiment 8 powders
The modified montmorillonite used raw material pulverizing of 3000g is crossed 300 eye mesh screens, and the 750g glucose, 6g saccharin sodium, the 6g vanillin that added 100 eye mesh screens again mixed 30 minutes, and packing promptly gets modified montmorillonite used powder.
The preparation of embodiment 9 granules
The modified montmorillonite used raw material of 2000g is crossed 300 eye mesh screens, after 150g lactose, 300g starch, 5g saccharin sodium, the 3g vanillin that added 100 eye mesh screens again mixes 15 minutes, add 2%K4M hydroxypropyl emthylcellulose slurry and mixed 15 minutes, cross 20 orders and granulate; Wet granular under 65 ℃ of left and right sides conditions dry 10 hours with 20 order granulate, is packed and is promptly got modified montmorillonite used granule.
The preparation of embodiment 10 capsules
The modified montmorillonite used raw material of 2000g is crossed 300 eye mesh screens, and 300g Icing Sugar, the 100g starch that added 100 eye mesh screens again mixes and adds 10% starch slurry mixing 15 minutes after 15 minutes, crosses 20 eye mesh screens and granulates; Wet granular under 65 ℃ of left and right sides conditions dry 10 hours, with 20 eye mesh screen granulate, granule adds 1% magnesium stearate mix after, be fills up to Capsules, pack and promptly get modified montmorillonite used capsule.
The preparation of embodiment 11 suspensoids
The modified montmorillonite used raw material of 1000g is crossed 300 eye mesh screens, the 250g Icing Sugar, 100g lactose, 10g polyvinylpyrrolidine K30 (K30 is the model of molecular weight size), the 20g mannitol that added 100 eye mesh screens again, after mixing 15 minutes, add 0.5%K4M (K4M is the model of molecular weight size) hydroxypropyl emthylcellulose slurry and mixed 15 minutes, cross 18 eye mesh screens and granulate; Wet granular under 65 ℃ of left and right sides conditions dry 10 hours sprays Fructus Citri Limoniae essence, and with 20 eye mesh screen granulate, packing promptly gets modified montmorillonite used dry suspension; Or add packing again behind the water mixing, promptly get modified montmorillonite used suspension.
The preparation of embodiment 12 dispersible tablets
The modified montmorillonite used raw material of 3000g is crossed 300 eye mesh screens, the 10g Icing Sugar, 500g pregelatinized Starch, 30g polyvinylpyrrolidine K90, the 50g mannitol that added 100 eye mesh screens again, after mixing 15 minutes, add 0.2%K4M hydroxypropyl emthylcellulose slurry and mixed 15 minutes, cross 40 eye mesh screens and granulate; Wet granular under 65 ℃ of left and right sides conditions dry 12 hours with 40 eye mesh screen granulate, adds 1% magnesium stearate and 3% crospolyvinylpyrrolidone, mix homogeneously, and tabletting promptly gets modified montmorillonite used dispersible tablet.
The preparation of embodiment 13 bubble Teng sheets
The modified montmorillonite used raw material of 3000g is crossed 300 eye mesh screens, the 50g glucose, 50g anhydrous citric acid, 390g lactose, 15g polyvinylpyrrolidine K90, the 100g sodium bicarbonate that added 100 eye mesh screens again, mix 15 minutes after, tabletting, drying is 13 hours under 65 ℃ of left and right sides conditions, promptly.
The preparation of embodiment 14 pastes
The heating of 1000g vaseline is dissolved, slowly add the modified montmorillonite used and 100g starch of 200g of crossing 300 eye mesh screens more while stirring, further fully grind evenly, promptly.
The preparation of embodiment 15 gels
Get 10g polyvinylpyrrolidone, 10g hydroxypropyl emthylcellulose in the expansion of 1000g dissolved in distilled water, will spend modified montmorillonite used slowly the adding and mix homogeneously of 1000g of 300 eye mesh screens then, promptly.
Below come to verify modified montmorillonite used reversal therapies effect of the present invention by test of pesticide effectiveness example chronic atrophic gastritis.Modified montmorillonite used or sucralfate are made the suspension of 100mg/ml for examination with deionized water during test.Except as otherwise noted, the present invention tests the dosage standard of example all in the mineral crude drug.
Test example 1 Montmorillonitum is to the reversal therapies effect of chronic atrophic gastritis
Adopt healthy, sexually matured 8 age in week 120 of male SD rats, average weight 250g ± 50g adopts posture to raise in cages, 24 ± 2 ℃ of raising temperatures, humidity 55 ± 5%, per 12 hours light and shades of illumination are alternately fed with mixed fodder.
The comprehensive employing 60% ethanol, 20mmol/l sodium deoxycholate and 24 weeks of 0.1% ammonia treatment set up the CAG model according to the Si Shi modeling.Be to irritate stomach 20mmol/l sodium deoxycholate every day, wherein on every Tuesdays, five irritate stomach (on every Mondays, four took feedstuff away at late 9 o'clock, begin to irritate on an empty stomach stomach during m seq 9) on an empty stomach, dosage is as follows: rat body weight＜200g irritates stomach 1mL at every turn; Rat body weight 200～250g irritates stomach 1.5mL at every turn; Rat body weight＞250g irritates stomach 2mL at every turn.60% ethanol on every Tuesdays, five irritate on an empty stomach stomach, condition and the same sodium deoxycholate of dosage on an empty stomach; And freely drink 0.1% ammonia, and record drink amount every day.The conventional raising slaughtered in 24 weeks.
120 SD rats are divided into 12 groups, 10 every group, are set to normal group, CAG group, NS group, sucralfate group, smectite in treatment group respectively and (comprise 2 natural smectite in treatment groups, be numbered MontE and MontF group; 4 modified calcium-base smectite in treatment groups are numbered MontA to MontD and organize; 1 modified na-montmorillonite treatment group is numbered MontG; 1 modification sodium ca-montmorillonite treatment group is numbered MontH).
Normal control group (normal group), after promptly Mus CAG became mould, the conventional raising slaughtered to the 24th weekend; Placebo group (normal saline group, NS group) after promptly Mus CAG becomes mould, stops to stimulate and giving normal saline, irritates stomach every day once, slaughters to the 28th weekend; Carafate for treating group (sucralfate group) after Mus CAG becomes mould, stops stimulation and gives sucralfate suspension (100mg/mL) filling stomach, rat body weight＜200g irritates stomach 1mL//time, the rat administration 1.5ml/ of body weight 200-250g/time at every turn, the rat of rat body weight＞250g, administration 2ml//time; Smectite in treatment group, dosage regimen, stop to stimulate also and irritate the suspension (100mg/mL) that stomach gives Montmorillonitum every day after promptly Mus CAG becomes mould with the sucralfate group, and rat body weight＜200g irritates stomach 1mL//time at every turn; The rat administration 1.5ml/ of body weight 200-250g/time; The rat of rat body weight＞250g, is slaughtered to the 28th weekend by administration 2ml//time.
Can't help water after 24 hours in fasting, give 1% pentobarbital (40mg/kg) intraperitoneal anesthesia fixing after, cutting open the belly immediately exposes full stomach, takes out full stomach at distance cardia and pylorus 1.5cm place from disconnected, cuts off along greater gastric curvature, ices normal saline flushing, spreads out after filter paper blots; The 1/2 usefulness microscope slide of getting gastric antrum portion is scraped and is got gastric mucosa, liquid nitrogen freezing ,-70 ℃ of preservations.Surplus gastric mucosa specimen is liquid-solid fixed with 10% neutral formalin, and the greatly curved side slat shape in edge is drawn materials, conventional dehydration, and paraffin embedding, 5 μ m thickness serial section are copied to preventing on the microscope slide of flake processing with poly-l-lysine, carry out haematoxylin-Yihong (HE) dyeing.
The observation and the result thereof of sample histopathology index:
1) the stomach lining inflammation situation is observed: adopt semiquantitative method, under low power lens, observe whole mucosa, observe 10 visuals field respectively at gastric antrum portion stomach function regulating body for every, with reference to the gastritis diagnostic criteria in the houston, u.s.a proposition in 1994, the degree of cell infiltration is divided into 0,0.5,1.0,1.5,2.0,2.5,3.0 7 rank, write down the inflammation situation in 10 visuals field respectively in order to last method, the average inflammation index that obtains later every rat stomach body and gastric antrum portion.
2) gastric mucosa body of gland layer thickness (L1) and muscular layer of mucosa thickness (L2) and ratio (L1/L2 ratio) thereof are observed: by the mircrometer gauge of microscopically, get 5 high power fields at hole, the body of every HE stained, calculate the mean of each mucomembranous gland layer and flesh layer thickness, compare with average simultaneously and obtain L1/L2.
3) observation of gastric mucosa body of gland density: on every PE stained apart between pyloric ring, glandular stomach and glandular stomach intersection 200-1200 μ m, utilize the microscopically mircrometer gauge, measure the intrinsic body of gland number of mucosa under the certain-length, thereby obtain the intrinsic body of gland density of mucosa (unit is individual/μ m) of gastric antrum portion and body of stomach.
4) simultaneously every PE stained is noted observing the generation that has or not intestinal epithelial metaplasia, false pylorus glandular metaplasia, atypical hyperplasia, adenoma, carcinoid, adenocarcinoma.
Obtain sample biochemical indicator and assay method thereof:
1) mensuration of aminohexose: ultrasonic homogenate after adding 500ul 1 * PBS buffer in frozen gastric mucosa, 4 ℃ of centrifugal (3000r/min, 5min), get supernatant, measure the absolute concentration of aminohexose with the Neuhaus method, and according to formula, aminohexose is proofreaied and correct content (mg/g albumen)=homogenate supernatant aminohexose concentration (mg/L)/protein concentration (g/L), calculates aminohexose content.
2) the DC Protein Assay reagent that adopts Bio-Rad company to provide is measured protein.
3) prostaglandin E 2(PGE 2) mensuration: get the frozen mucosa tissue of part, add 500 μ l Krebs liquid and (add indomethacin in advance, to prevent PGE in the operating process 2Release) ,-4 ℃ centrifugal, and (2000r/min 5min) gets supernatant, presses measured by radioimmunoassay PGE 2, concentration represents with pg/ml, according to formula, and PGE 2Proofread and correct content (pg/mg albumen)=homogenate supernatant PGE 2Concentration (pg/ml)/protein concentration (mg/ml) is calculated PGE 2Content.
Result of the test adopts the variance analysis method (One-Way ANOVA) of completely random design data to analyze, and uses the SPSS11.0 statistical software and assists statistics.
The present invention adopts the CAG model of Si Shi manufactured SD rat, has observed natural Montmorillonitum, the modified montmorillonite used and sucralfate reversal therapies effect to SD rat chronic atrophic gastritis.And by observing gastric mucosa of rat morphological change and mensuration gastric mucosa of rat biochemical indicator (aminohexose, prostaglandin E under the light microscopic 2) level, the comparative study medicine is to the reversal therapies effect of rat CAG model.
Result of study shows, through a treatment in month of Montmorillonitum of the present invention, the color of the mental status of SD rat, mobility, hair and gloss all have to a certain degree improvement latter stage than modeling; The gastric tissue gross examination of skeletal muscle, visible mucosa color and luster is pink, the more mucus that is covered, mucosal surface is smooth, and pleat is walked line discipline, and common sensation has clear improvement than model control group; In the visible gastric antrum of microscopically portion mucomembranous gland marshalling, gastric pits is clear, and inflammatory cell infiltration is few, and is congested, edema is all not obvious.The measurement result of every quantitative target is as follows:
1, testing the influence of respectively organizing antrum layer thickness level can be referring to Figure 22.As seen, the gastric antrum portion mucous layer thickness of smectite in treatment group is significantly higher than carafate for treating group (P＜0.01), particularly MontG treatment group and is higher than other Montmorillonitum group treatment groups (P＜0.01) very significantly, has reached normal control group level; The other treatment group still is lower than normal control group (P＜0.01) very significantly.
2. each group of test is to gastric antrum portion mucous layer thickness/muscular layer of mucosa thickness (L1/L2) ratios affect can be referring to Figure 23.As seen, the L1/L2 ratio of CAG model control group significantly is lower than other each groups; The normal control group is significantly higher than other each groups; Property that there were significant differences between placebo group and the carafate for treating group (P＜0.05); Smectite in treatment group highly significant is higher than CAG model control group and placebo group (P＜0.01), and wherein MontG treatment group is higher than other Montmorillonitum group treatment groups (P＜0.01) very significantly.
3. (individual/mm) influence as shown in figure 24 to rat gastric antrum portion mucomembranous gland density for each group of test.As seen, CAG model control group, placebo group and carafate for treating group do not have significant difference each other, and three groups all significantly are lower than the normal control group; The smectite in treatment group is higher than CAG model control group, placebo group and carafate for treating group significantly, and the MontG group is significantly higher than other smectite in treatment groups (P＜0.05).
Each group of test to the influence of antrum inflammation index level referring to Figure 25.The result shows that aspect rat gastric antrum portion mucosal inflammation index, the smectite in treatment group significantly is lighter than CAG model control group and placebo group; MontA group significantly is lighter than carafate for treating group (P＜0.05) with the MontG group, but and does not have significant difference (P＞0.05) between the normal control group.
In addition, each group of test to the result that influences of body of stomach mucosa is: CAG control rats body of stomach is observed, the feature of the visible atrophic gastritis of mucomembranous gland, body of gland capsule sample has the expansion phenomenon, muscular layer of mucosa thickens, and between the dendritic insertion body of gland of proper mucous membrane composition, inflammation degree and gastric antrum category are seemingly.The inflammation situation of placebo group, carafate for treating group and the body of stomach of smectite in treatment group is compared with the CAG model control group, slightly take a favorable turn or take a turn for the better, all samples are not found phenomenons such as intestinal epithelial metaplasia, false pylorus glandular metaplasia, atypical hyperplasia, adenoma, carcinoid, adenocarcinoma simultaneously.
Each group of test to the influence of gastric mucosa aminohexose level referring to Figure 26.As seen, aspect gastric mucosa aminohexose content, CAG model control group, placebo group and carafate for treating group three do not have significant difference (P＞0.05) each other; The horizontal highly significant of gastric mucosa aminohexose of Montmorillonitum group rat is higher than other moduli groups (P＜0.01), and wherein the MontG group is significantly higher than other Montmorillonitum groups (P＜0.05), and highly significant is higher than Montmorillonitum F group.
6. each group of test is to gastric mucosa PGE 2The influence of level as shown in figure 27.The result shows, the gastric mucosa PGE of smectite in treatment group rat 2Level is higher than CAG model control group and carafate for treating group significantly, and MontG group highly significant is higher than Montmorillonitum F group (P＜0.01).
Conclusion: the CAG rat model is after the filling stomach treatment through a month Montmorillonitum, the atrophy of SD rat gastric antrum portion mucosa and inflammation situation all have significant improvement than CAG group and placebo group, simultaneously aspect the defence of mucosa and the synthesis capability significant recovery is being arranged all, show that promptly the CAG rat model that Montmorillonitum is set up for the Si Shi method has the reversal therapies effect, and the precognition modified na-montmorillonite can be more remarkable to the reversal therapies effect of chronic atrophic gastritis.
Than the smectite in treatment group, though the carafate for treating group has significant improvement than the CAG group on the indexs such as mucosa L1/L2 ratio, inflammation index and mucosa aminohexose content of mucous layer thickness (P＜0.01), mucosa L1/L2 ratio, inflammation index and the body of stomach of gastric antrum portion, but only on gastric antrum portion mucous layer thickness, be higher than placebo group (P＜0.01) very significantly, and the Montmorillonitum group particularly the modified na-montmorillonite group at gastric antrum portion mucous layer thickness, mucosa aminohexose content and mucosa PGE 2Etc. the aspect, all be better than the sucralfate group very significantly.As seen, sucralfate has the mucous membrane protection effect to the CAG rat model, but does not have significant reversal therapies effect; And Montmorillonitum has significant reversal therapies effect to the CAG rat model, and modified montmorillonite used particularly modified na-montmorillonite has more significant superiority to the reversal therapies effect of chronic atrophic gastritis than corresponding natural Montmorillonitum.
Montmorillonitum of the present invention is as follows to the reversal therapies mechanism of chronic atrophic gastritis:
(1) by between electric charge attract each other and with original mucous interaction, formed the gel protective layer that is covered in mucomembranous surface, promote the reparation of impaired mucosa.After Montmorillonitum was met water, by intergranular osmotic swelling and interlayer aquation, Dispersion of Particles was peeled off between the lamination, and electronegative aspect and end face interact, and crosslinked association forms the aquation gel.These aquation gels remove significant adhesiveness, can also combine with the mucus in the digestive tract, significantly strengthen mucous cohesiveness and viscoelasticity, be covered in the mucomembranous surface of damage securely, under the electrically charged constant situation of wound surface institute, the intensity of this physical action and montmorillonite gelling electronegative quantity be proportionate.And there are some researches show that Montmorillonitum reaches 93nm at the protection bed thickness that gastric mucosa surface forms, and can continue more than 6 hours.
Sucralfate is the alkaline aluminium salt of sucrose sulfuric ester, and is water-soluble hardly, but in pH＜4 o'clock, some Al 2(OH) 5 +Dissociate out from sucrose eight sulfuric acid molecules, remaining complex is electronegative, and aggregates into the gel-shaped material; attach to epithelial cell and damaged gastric mucosa surface securely; reach the protection gastric mucosa purpose, be a kind of medicine that depends on sour environment, thus can not with H 2Receptor antagonist; proton pump inhibitors etc. suppress the drug combination of gastric sour environment; and CAG patient's gastric acid secretion obviously lowers; it secretes the atrophy of acid function with the gastric gland body; increasing the weight of of intestinalization and reducing; and CAG patient's stomach inner pH value usually can not reach the onset requirement of sucralfate; sucralfate only forms a kind of muddy liquid and is covered in gastric mucosa surface at this moment; interact between shortage and impaired mucosa and original mucus; be difficult to reach the effect of protection mucosa; by contrast; the elecrtonegativity of Montmorillonitum aspect with become colloidality not to be subjected to the influence of environment pH value substantially; therefore, Montmorillonitum is more strong and lasting than sucralfate for the protective effect of CAG patient's gastric mucosa.And the powerful protective effect of montmorillonite gelling; can stop the coup injury of harmful substances such as gastric acid, pepsin, cholate and ethanol well to mucomembranous cell; for the gastric mucosal cell (especially stem cell) that is badly damaged and becomes very fragile provides the environment of stable safety, thereby created advantage for the regeneration of mucosa.
(2) absorption " being harmful to " material weakens their invasion and attack, damage gastric mucosa ability.The physical arrangement of Montmorillonitum uniqueness makes it have the not available cation exch ange adsorption ability of general gastric mucosa protectant; can be adsorbed onto the surface to some organic cation (comprising ethanol, pepsin, fibrin segment, cholate etc.) at gastric; finally secure it to interlayer; form Montmorillonitum-organic complex; to reduce of the direct injury of these deleterious aggressive materials, reached the effect of protection gastric mucosa from another aspect to gastric mucosa.This ion exchange of Montmorillonitum is subjected to the influence of its interlayer cation exchange capacity and various steric requirements, and ion exchange and average layer charge density are proportional, therefore, under the fixed prerequisite of other conditions, the ion-exchange capacity of the Montmorillonitum that average layer charge density is big is strong.
(3) interaction between microcosmic charging property and impaired mucosa improves its metabolism environment, promotes the synthetic and excretory effect of mucin.
The effects of relieving alcoholism and protecting liver that test example 2 is modified montmorillonite used
Low alcohol consumption can promote metabolism, plays the effect of relaxing muscles and tendons to promote blood circulation, can appetite stimulator, and allaying tiredness; But symptoms such as the excessive drinking meeting causes chronic alcoholism, mucosa injury, cardiac muscle is weak, blood vessel becomes fragile, the reduction of the defense function of respiratory system, renal failure, systems such as human consumption, nerve, circulation are caused serious harm, also can decrease internal organs, consumption QI and blood, cause the body physiological function disorder, the serious harm health.The present invention is by irritating after drinking, and concentration of alcohol in observation different time sections mice stomach, the intestinal contents and blood determining alcohol change studies modified montmorillonite used relieve the effect of alcohol effect and Antialcoholic liver-protecting mechanism thereof.
40 of the healthy male ICR kind Mus of body weight 25 ± 2g are divided into matched group and treatment group at random, and matched group is irritated stomach and given normal saline, and treatment group filling stomach gives of the present invention modified montmorillonite used, is divided into 4 groups with every group at random by different time again, 5 of every groups.
Water is prohibited in the mice fasting to spend the night, next day, irritate stomach by 0.10ml/25g Mus heavy prescription amount and give modified montmorillonite used suspension of the present invention and 0.9% normal saline, behind the 30min, irritate stomach by 0.15ml/25g Mus heavy prescription amount and give 56 ° of Chinese liquor, irritate after drinking, successively in 30,60,90,180min is from the about 1ml of eye socket blood sampling of each group.With gained blood sample 12000r/min centrifugalize, get serum 200 μ l afterwards in the 1.5ml centrifuge tube, add people's methanol 1 μ l, 20% chloroacetic acid solution respectively, mixing, the centrifugal 10min of 4000r/min gets supernatant, freezing preservation.
With concentration of alcohol in the gas chromatograph test sample, the results are shown in Table 2.
Ethanol content measurement result (mg/ml) in the table 2 mice blood
After drinking the time (minute) The Montmorillonitum group (X ± S) Matched group (X ± S) The P value
30 60 90 120 6.356±0.986 8.183±2.175 10.014±1.343 9.548±1.857 12.067±0.886 19.754±3.602 20.843±1.897 10.958±2.012 ＜0.001 ＜0.001 ＜0.001 ＞0.05
Result of the test shows: mouse stomach is given after drinking in the 30min-180min, Montmorillonitum different time sections ethanol is absorbed and metabolism all influential, 4 time of administration group ethanol in blood concentration all significantly is lower than matched group (P＜0.01); And the ethanol in blood measured value, the administration group descends significantly than matched group.
Modified montmorillonite used effects of relieving alcoholism and protecting liver is based on its distinctive synusia structure; inhomogeneous CHARGE DISTRIBUTION and slip visco-plasticity; can evenly cover the digestive tract surface continuously; with static and materialization effect performance curative effect; effectively suppress; delay and reduce ethanol in gastral absorption; effectively slow down and hinder ethanol and enter intravital speed and concentration; and by absorption; the metabolism and the drainage of parcel accelerating alcohol; strengthen ethanol at the gastrointestinal first pass effect; effectively reduce ethanol in vivo accumulate concentration; has good anti-intoxication and sober-up function; and can effectively protect gastrointestinal wall; reduce stimulation and the damage of ethanol, reduce the amount of bleeding of gastrointestinal wall, obviously reduce ethanol gastrointestinal to gastrointestinal wall; the harm of organs such as liver; and have good mucous membrane protection and mucosa repair, can be used as the medicine of treatment mucosa injury and Antialcoholic liver-protecting.
Test example 3 is modified montmorillonite used to hyperthyroid prevention and treatment
Prevent and treat after principle is that containing of hepatic secretion, thyroxinic bile entered in the intestinal, be absorbed into blood again, constitute enterohepatic circulation by small intestinal mucosa.When the free thyroxine in the bile in intestinal, contacted by Montmorillonitum and the absorption of trying to be the first after, to no longer be absorbed by small intestinal mucosa, and can discharge with digestive tract self wriggling, can gradually reduce the thyroxine of reuptaking into blood, to reduce the thyroxine concentration in the circulation of body inner blood, reached the purpose of prevention with the treatment hyperthyroidism.
48 of white mice, be divided into high dose group (3g/kg), middle dosage group (1.5g/kg), low dose group (0.75g/kg) and matched group, every group 12, irritate stomach and give modified montmorillonite used and respective amount normal saline of the present invention, once a day, continuous 7 days, compare with matched group, but significant prolongation hyperthyroidism white mice hypoxia endurance time, and can make the body weight of hyperthyroidism rat be tending towards normal.
48 of rat, be divided into high dose group (4g/kg), middle dosage group (2g/kg), low dose group (1g/kg) and matched group, every group 12, irritate stomach and give modified montmorillonite used and respective amount normal saline of the present invention, every day secondary, continuous 14 days, compare with matched group, but each administration group highly significant reduces TT in the hyperthyroidism rat serum 3, TT 4, FT 3And FT 4Content, in, low dose group has the effect of remarkable rising thyrotropin (TSH), high, middle dosage group also can significantly reduce hyperthyroidism rat body temperature, and can make the body weight of hyperthyroidism rat be tending towards normal.
Result of the test proves: of the present invention modified montmorillonite usedly have remarkable influence to the relevant anoxia enduring of main pharmacodynamics, thyroxin and thyrotropin (TSH), is beneficial to the control of hyperthyroidism.
Test example 4 modified montmorillonite used therapeutical effect to chronic renal failure
The treatment principle based on: the protein,split blood urea nitrogen (BUN) that the patient of chronic renal failure excreted via kidney originally, potassium ion etc. can not have been discharged by kidney, pile up the excessive toxin that becomes in vivo, and form hyperpotassemia etc.Behind the oral intestinal canal adsorbent (as modified montmorillonite used); based on Montmorillonitum the digestion mucous membrane had very strong covering protection ability; repair, improve of the defence of mucosa barrier to attack factor; in intestinal, disperse and be attached to the intestinal mucosa surface; cause the change of intestinal mucosa surface seepage pressure reduction, make the interior toxin of intestinal mucosa, potassium ion etc. be adsorbed, dialyse out, and together excrete with intestinal contents; reach the intestinal dialysis effect, and the intestinal bleeding that the acute kidney merit is declined has anastalsis.
Through clinical diagnosis, the 36 routine chronic renal merits that the cause of disease, the state of an illness is the similar substantially patient's randomized, double-blind that declines is divided into treatment and organizes 20 examples and matched group 16 examples.On the chronic renal merit declines the conventional therapy basis, comprise treatment protopathy, hemodialysis, correction water, electrolyte and the disorder of enzyme soda balance, keep nutrition of whole body etc., in the hemodialysis interval, oral Montmorillonitum of the present invention is organized in treatment, matched group Orally active charcoal, beginning in second day is to hemodialysis next time the previous day after the hemodialysis; With administration in 2-3 hour after meal, one time 3 gram of being grown up, three times on the one (8 hours 1 time), the result shows: compare with matched group, treatment group patient's plasma urea nitrogen (BUN) concentration level descends, and CO2 combining power, CO2 CP rises to some extent, shows dialysis curative effect in certain intestinal, analyze by statistics, two groups are not had significant difference.
In addition, the Calamine Lotion that is made into 2% Montmorillonitum is coated with puts the chronic renal merit skin of lower extremity that declines on the skin, its skin pruritus had tangible itching-relieving action, because of the chronic renal merit patient that declines has the accumulation of blood urea nitrogen to cause skin pruritus at its skin of lower extremity,, Montmorillonitum plays the percutaneous Dialysis and adsorbing blood urea nitrogen (BUN) by skin.In addition, Montmorillonitum is used for medical ointment, can form thin film at skin surface, to other drug is antipruritic potentiation is arranged.
Test example 5 modified montmorillonite used preventive and therapeutic effects to halitosis
Digestive tract produces zymolysis, corruption, the alteration of intestinal flora in digestive tract through oral cavity exhalation gas with foreign flavor and food, and the excessive multiplication of aerogenic bacteria lacks with mortality, each internal organs Chronic consumptions of whole body, inflammation and digestive enzyme not of the same race, metabolite is piled up relevant.The Montmorillonitum conduct is adsorbent efficiently, zymolysis, putrescible food and aerogenic bacteria surface coverage and absorption can be adsorbed the gas that produces in the digestive tract simultaneously, and by ion exchange, the character that makes the oral cavity produce gas changes, and reaches covering, filtration and deodorization.
The oral cavity does not have the exhalation foul gas, 20 of every biochemical indicator normal adults, and 10 of separating tests groups and matched group are 10 at random, and food is received and is mixed the living Bulbus Allii 15-20 gram of meal (3 lobe), at the 20th minute after the meal, the test group 3 gram Montmorillonitums of taking after mixing it with water, matched group is taken orange juice; Compare with matched group in 20 minutes in medication, simultaneously same people is subjective, and the olfactory sensation result is: the pernicious quantity of stimulus that exhalation Bulbus Allii in test group oral cavity is hidden foul smell obviously alleviates, and matched group is invalid.
Breathe out and produce 24 of the patients of foul gas by digestive tract in the oral cavity, 12 of separating tests groups and matched group are 12 at random, work the back of gargling (avoiding the assorted bacterium in oral cavity to disturb) in morning, the test group 3 gram Montmorillonitums of taking after mixing it with water, and matched group is taken orange juice; Compare with matched group in 20 minutes in medication, simultaneously same people is subjective, and the olfactory sensation result is: the pernicious quantity of stimulus of test group oral cavity exhalation foul smell obviously alleviates, and matched group is invalid.
Abundant, inexpensive, the safety non-toxic in Montmorillonitum of the present invention source, pharmacological action is strong, has very strong adsorption function, all types of virulence factors in the oral adsorbable digestive tract, strong as free thyroxine, blood urea nitrogen (BUN), potassium ion, oral cavity exhalation gas with foreign flavor and its adhesive property, be difficult for desorbing, will discharge with digestive tract self wriggling together with adsorbed, fixed virulence factor, reach covering, filtration and deodorization, be cause of disease scavenger in the digestive tract of safety.

Claims (32)

1, a kind of have the modified montmorillonite used of therapeutical effect to the digestive tract illness, it is characterized in that: do not destroy the dioctahedron layer structure of natural Montmorillonitum and do not change its basic chemical composition, and by changing the microstructure of dioctahedron stack layer, make its stack layer attenuation, expose and increase its variable charge and interlayer charge, and have the lower C axle degree of order.
2, claim 1 is described modified montmorillonite used, and the described C axle degree of order is meant the crystallite dimension that the d value is calculated for 001 diffraction maximum of 12-100  in the X diffraction pattern of Montmorillonitum.
3, according to claim 2 modified montmorillonite used, described crystallite dimension is made up of 2-4 stack layer, and thickness is 3-6nm; Or form by 3-5 stack layer, thickness is 4-7nm; Or form by 3-4 stack layer, thickness is 4-6nm.
4, according to claim 1 modified montmorillonite used, described interlayer charge is not less than 0.31eq/[(Si, Al) 4O 10], preferably be not less than 0.34eq/[(Si, Al) 4O 10], more preferably be not less than 0.40eq/[(Si, Al) 4O 10], most preferably be not less than 0.43eq/[(Si, Al) 4O 10].
5, according to claim 1 modified montmorillonite used, described variable charge is not less than 0.058eq/[(Si, Al) 4O 10], preferably be not less than 0.08eq/[(Si, Al) 4O 10], more preferably be not less than 0.10eq/[(Si, Al) 4O 10], most preferably be not less than 0.12eq/[(Si, Al) 4O 10].
6, each is described modified montmorillonite used according to claim 1-5, described modified montmorillonite used modified calcium-base Montmorillonitum, modification sodium ca-montmorillonite, modification hydrogen base Montmorillonitum, modification magnesio Montmorillonitum or the sodium montmorillonite of being selected from is preferably modified na-montmorillonite.
7, according to claim 6 modified montmorillonite used, described modified montmorillonite used cation exchange capacity is 75-140, is preferably 80-130, and more preferably 90-125 most preferably is 100-120.
8, according to claim 6 modified montmorillonite used, described modified montmorillonite used purity is not less than 95%, preferably is not less than 96%, more preferably is not less than 97%, also preferably is not less than 98%, preferably is not less than 99% in addition, most preferably is not less than 99.5%.
9, according to claim 6 modified montmorillonite used, modified montmorillonite used swelling degree is not less than 4.0, preferably must not be less than 5.0, more preferably must not be less than 7.0, and also preferably must not be less than 9.0, in addition preferably must not be less than 10.0, most preferably must not be less than 12.0.
10, according to claim 6 modified montmorillonite used, the modified montmorillonite used adsorbance to the sulphuric acid strychnine of described every 1g is 0.30-0.70g, is preferably 0.40-0.65g, more preferably 0.5-0.6g.
11, according to claim 6 modified montmorillonite used, described modified montmorillonite used heavy metal must not surpass 10ppm, preferably must not surpass 7ppm, and more preferably 5ppm most preferably is 3-4ppm.
12, according to claim 6 modified montmorillonite used, described modified montmorillonite used related substance must not surpass 5%, preferably must not surpass 4%, and more preferably 3%, also preferred 2%, other is preferably 1%, most preferably is 0.5%.
13, a kind ofly prepare modified montmorillonite used method, comprise the steps: smectite content is not less than 80% bentonite, preferred content is not less than 85%, more preferably is not less than 90%, most preferably is not less than 95%; Mixed acid with concentration 0.1-10mol/L is preferably 0.5-8mol/L, and more preferably 0.8-6mol/L most preferably is 1-5mol/L; With soil: the mass ratio of acid is 1: 1-100 mixes, and is preferably 1: 2-50, and more preferably 1: 3-25 most preferably is 1: 3-10; Heat was boiled 0.5-100 hour, was preferably 2-70 hour, and more preferably 3-40 hour, most preferably 5-20 hour; Centrifugal or remove by filter mixed acid, the washing filter cake is drying to obtain to pH 〉=4.
14, method according to claim 13, described mixed acid is mixed by mineral acid and organic acid.
15, method according to claim 13, described mineral acid is selected from monoacid, binary acid or ternary acid; Described monoacid is selected from hydrochloric acid, nitric acid, hydrobromic acid or Fluohydric acid.; Binary acid is selected from sulphuric acid; Ternary acid is selected from phosphoric acid or sulfonic acid; Preferred mineral acid is a monoacid, most preferably is hydrochloric acid or nitric acid.
15, method according to claim 13, described organic acid is selected from carboxylic acid, hydroxy acid, keto acid or fruit acid; Preferred organic acid is acetic acid, oxalic acid, citric acid, succinic acid, formic acid, propanoic acid, butanoic acid, malonic acid, succinic acid, acetone acid, glutamic acid, tartaric acid, malic acid, lactic acid, fumaric acid, itaconic acid, ascorbic acid, Fumaric acid, α-Tong Wuersuan or carboxylic acid; More preferably acetic acid, oxalic acid, citric acid, succinic acid, propanoic acid, butanoic acid, succinic acid or malonic acid.
16, method according to claim 13, the constitutive molar ratio of described mixed acid is a mineral acid: mineral acid and/or organic acid: organic acid is 5-150: 1-200: 5-200, be preferably 10-120: 5-150: 10-150, more preferably 20-100: 10-120: 20-120 most preferably is 30-80: 20-100: 30-100; Hydrochloric acid most preferably: oxalic acid: acetic acid is the mixed acid of 30-80: 20-100: 30-100.
17, a kind of pharmaceutical composition that is used for the treatment of the intestinal illness is made up of modified montmorillonite used and pharmaceutically acceptable carrier.
18, compositions according to claim 17, modified montmorillonite used in the compositions: the dry product weight ratio of pharmaceutically acceptable carrier is 0.001-4: 1-50, be preferably 0.001-3: 1-25, more preferably 0.001-2: 1-10 most preferably is 0.001-1: 1-5; Perhaps the weight percentage of Montmorillonitum is 1-100% in the compositions, is preferably 5-95%, also is preferably 10-90%, and more preferably 15-85% most preferably is 20-80%.
19, compositions according to claim 17, the dosage form of compositions is selected from oral formulations or external preparation, is preferably oral formulations.
20, compositions according to claim 19, described oral formulations is selected from tablet, suspension, capsule, granule, pill, powder, drop pill, syrup, mixture, distillate medicinal water, effervescent, paste or medicinal tea; Be preferably powder, suspension, granule, tablet, capsule or effervescent.
21, compositions according to claim 19, described external preparation are selected from gel, emplastrum, cream, ointment, liniment, lotion, suppository, liniment or coagulate unguentum, are preferably gel.
22, modified montmorillonite used application in the medicine of preparation treatment digestive tract illness.
23, application according to claim 22, described digestive tract disease are selected from acute and chronic diarrhea, reflux esophagitis, chronic gastritis, peptic ulcer, irritable bowel syndrome, inflammatory intestinal illness or gastritis; Be preferably chronic gastritis; Chronic atrophic gastritis more preferably; Most preferably be reversal therapies effect to chronic atrophic gastritis.
24, modified montmorillonite used in preparation treatment or prevent and treat application in the hyperthyroid medicine.
25, modified montmorillonite used application in the medicine of preparation treatment chronic renal failure.
26, modified montmorillonite used application in the medicine of preparation prevention or counteract oral malodour.
27, modified montmorillonite used application in preparation pharmaceutical carrier or excipient substance.
28, modified montmorillonite used application in the dermopathic medicine for external use of preparation treatment.
29, modified montmorillonite used application in the preparation medicament for sobering up and protecting liver.
30, the application of natural Montmorillonitum in the medicine of preparation chronic atrophic gastritis; Be preferably reversal therapies effect to chronic atrophic gastritis.
31, a kind of modified montmorillonite used method of sodio for preparing, comprise the steps: purity is not less than 95% modified calcium-base Montmorillonitum or modification magnesio Montmorillonitum, add acid solution and be made into the slip that solid content is 10-30%, stir, remove by filter acid solution, filter cake with hot wash to faintly acid, filter pressing becomes the filter cake of solid content 30-70%, adds the sodium agent suitable with cation exchange capacity, stirs sodium, make its PH be alkalescence, be drying to obtain.
CN 200610055117 2005-11-04 2006-02-21 Modified montmorillonite, preparation method and application Pending CN1957948A (en)

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