CN104758262B - A kind of cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece and its preparation method and application equally - Google Patents
A kind of cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece and its preparation method and application equally Download PDFInfo
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Abstract
A kind of cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, and it mainly after Radix Fissistigmatis Glaucescentis extract, modifying agent, filler, disintegrant, wetting agent are mixed in proportion, is prepared after granulation, drying, whole grain, total mixed, tabletting；Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root raw material using complex enzyme water-bath；Specific preparation method includes：First glaucescent fissistigma root is pre-processed, clear cream is obtained after adding complex enzyme, enzymolysis glaucescent fissistigma root；Be dried in vacuo again, be ground into Radix Fissistigmatis Glaucescentis extract fine powder, be eventually adding modifying agent, then with mixing granulation, the tabletting in proportion of filler, disintegrant, wetting agent, produce the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divide discrete piece equally.The cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of the present invention is divided discrete piece equally and can applied in antineoplastic is prepared, have the advantages that it is rapid-action, be disintegrated that rapid, convenient to take, bioavilability is high, adverse reaction is small.
Description
Technical field
The invention belongs to traditional Chinese medicine product scope, and in particular to a kind of antitumor dispersible tablet and preparation method thereof and should
With.
Background technology
It is a kind of high-efficiency broad spectrum antineoplastic that the cancer that disappears, which divides discrete piece equally, using Chinese medicine Radix Fissistigmatis Glaucescentis extract as raw material, is added suitable
Suitable high-quality auxiliary material is prepared from, and major function is anticancer, anti-inflammatory, relievingd asthma；Available for cancer of the esophagus, stomach cancer, lung cancer, to large intestine
The Several Kinds of Malignancy such as cancer, cervical carcinoma, leukaemia, also there is certain curative effect.
The extracting method of conventional glaucescent fissistigma root preparation has decocting cooking method, water bath reflux method, alcohol extracting method, ultrasonic extraction
Deng.Such as Wang Junxiang, XIAOAIPING PIAN process study [J], Liaoning University of TCM's journal, 2013,15 (10):49-50 is with more
Sugar, the leaching content of aurantiamarin and yield of extract are the optimal extraction process by water that evaluation index determines XIAOAIPING PIAN；Application No.
201310001833.5 Chinese patent literature crushes glaucescent fissistigma root, soaks, ultrasonically treated that the flat extract of cancer that disappears is made；Shen
Number glaucescent fissistigma root please be crushed for 201210072224.4 Chinese patent literature, the flat extract of cancer that disappears is made in water-bath alcohol extracting.However,
Decocting cooking method needs to soak for a long time, typically needs 12-18h；Alcohol extracting rule uses organic solvent, easily causes solvent contamination, and production
Cost is higher；Ultrasonic extraction is not suitable for industrialization large-scale production.
In addition, the Xiaoaiping preparation against cancers listed mainly have tablet, granule, capsule etc., such as Application No.
201210072224.4 Chinese patent literature disclose a kind of Glaucescent fissistigma root granules, Application No. 201220693927.4
Chinese patent literature discloses a kind of XIAOAIPING PIAN；The Chinese patent literature of Application No. 201310735138.1 discloses one kind
Marsdenia tenacissima soft capsule and preparation method thereof；But these formulations have that dose is larger, bioavilability is not high, inherent quality is difficult to
The shortcomings of control.
The preparation method of dispersible tablet is easy, can be dissolved rapidly in water, rapid-action, bioavilability is high and energy is fine
Solution patient's dysphagia the features such as.The disintegration of dispersible tablet has direct influence, especially Chinese medicine to the quality of medicine
Dispersible tablet, therefore the suitable auxiliary material of selection improves the key that the property of raw material, the disintegrating property of raising medicine are moulding process.
Some research shows, Chinese medical extract is ground from superfine silica gel powder and is modified, and Chinese medical extract can be made to compare table while refinement
Area and voidage increase, contact angle diminish, and wetability increase, hydrophily increases therewith, reduces stickiness；Therefore, certain
The addition of auxiliary material can be reduced in degree, increases the drugloading rate of dispersible tablet, so as to reduce the dose of patient.Application No.
200510044399.4,200510032623.8 Chinese patent literature be each provided with a kind of preparation side of 'Wu-gu-teng ' stem disperser
Method, wherein superfine silica gel powder are mainly the effect of super fatting agent in prescription, and have that supplementary product consumption is big, dose big, disintegration when
Between it is long the shortcomings of.
The content of the invention
The technical problems to be solved by the invention are to overcome the shortcomings of to mention with defect that there is provided one in background above technology
Kind is rapid-action, being disintegrated rapid, convenient to take, bioavilability, high, the small cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of adverse reaction is divided equally
Discrete piece, correspondingly provides the glaucescent fissistigma root that contains that a kind of simple and efficient, time is short, cost is low, nontoxic, recovery rate is high, energy consumption is small and extracts
The cancer that disappears of thing divides the preparation method of discrete piece and its application in antineoplastic is prepared equally.
Divide equally in order to solve the above technical problems, technical scheme proposed by the present invention is a kind of cancer that disappears containing Radix Fissistigmatis Glaucescentis extract
Discrete piece, the dispersible tablet is mainly mixed by a certain percentage by Radix Fissistigmatis Glaucescentis extract, modifying agent, filler, disintegrant, wetting agent
Afterwards, prepared after granulation, drying, whole grain, total mixed, tabletting；The Radix Fissistigmatis Glaucescentis extract is extracted using complex enzyme water-bath
Obtained after glaucescent fissistigma root.
The above-mentioned Enzymatic Extraction of the present invention is on the basis of traditional solvent extraction method, to utilize enzyme reaction high specificity
Feature, cell-wall components are hydrolyzed or degraded, and are made softening of the cell wall, expansion and are collapsed, change the permeability of cell membrane, improve thin
The recovery rate of intracellular inclusion, reduces the viscosity of extract solution；And it has that simple and efficient to handle, extraction time is short, the rate of transform it is high with
And the features such as solvent-free pollution.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, preferably：The modifying agent is superfine silica gel powder, and micro mist
The consumption of silica gel is 3%~7% (being most preferably 5%) of the scattered tablet quality.It is preferred that scheme in by adding micro mist silicon
Glue to Radix Fissistigmatis Glaucescentis extract grind be modified, reduce its viscosity, can preferably overcome Radix Fissistigmatis Glaucescentis extract complicated component, viscosity compared with
Greatly, moisture is difficult to be impregnated with the defect such as scattered.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, preferably：The filler is lactose and microcrystalline cellulose
The mass ratio of the mixture of element, lactose and microcrystalline cellulose is 1: 0.8~1.0, and the consumption of filler is the dispersible tablet matter
The 60%~80% of amount；The disintegrant is the mixture of PVPP and low-substituted hydroxypropyl cellulose, and disintegrant
Consumption is the 15%~25% of the scattered tablet quality.
The wetting agent is ethanol solution.
As a total technical concept, the present invention also provides a kind of above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides scattered equally
The preparation method of piece, comprises the following steps：
(1) pretreatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, sieving (for example crosses 80 mesh
Sieve)；
(2) glaucescent fissistigma root is extracted：Glaucescent fissistigma root after above-mentioned steps (1) is added to the water, mixed liquor is obtained after stirring and (is typically stirred
The time is mixed no less than 30min), regulation pH value (being preferably 4.5~5.5) adds complex enzyme, water-bath is carried out under hydrolysis temperature
Extract, more than 90 DEG C are warming up to after the completion of extraction and inactivates complex enzyme, filter, filter residue add water refluxing extraction (preferably 110~
140min), merge extract solution, stand overnight, suction filtration, filtrate concentration obtains clear cream；
(3) post-processing：The clear cream that above-mentioned steps (2) are obtained is dried in vacuo in vacuum drying chamber, is ground into black bone
Boisiana extract fine powder；
(4) it is molded：Take the Radix Fissistigmatis Glaucescentis extract fine powder obtained by above-mentioned steps (3), add modifying agent, then with filler, collapse
Agent, wetting agent mixing granulation in proportion are solved, is dried, whole grain, dry particl alternative adds appropriate lubricant, sweetener etc.,
Well mixed, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
In above-mentioned preparation method, preferably：In the step (2), the complex enzyme includes pectase and cellulase,
And the mass ratio of pectase and cellulase is 1: 2.More preferably：In the step (2), the addition of the complex enzyme is mixed
Close the 0.25%~0.45% of feed liquid quality, and in mixed liquor glaucescent fissistigma root and water solid-liquid ratio for 1: 8~16 (more preferably 1:
12)。
In above-mentioned preparation method, preferably：In the step (2), the hydrolysis temperature is 35 DEG C~55 DEG C, during enzymolysis
Between be 80min~110min.In the step (2), the addition of the complex enzyme is the 0.37% of mixed liquor quality, described
Hydrolysis temperature is 53 DEG C, and enzymolysis time is 103min.
In above-mentioned preparation method, preferably：In the step (2), the temperature of inactivation complex enzyme is 90 DEG C~95 DEG C, is gone out
Live time is not less than 5min, and the relative density that the vacuum concentration obtains clear cream is at least 1.23.
As a total technical concept, the present invention also provide that a kind of the invention described above obtains containing Radix Fissistigmatis Glaucescentis extract
The cancer that disappears divides application of the discrete piece in antineoplastic is prepared equally.
The above-mentioned technical proposal of the present invention is based on traditional Chinese medical theory, with reference to modern high technology extraction equipment, pharmacy
Technology and chromatographic technique, with reference to glaucescent fissistigma root chemical composition and the research of pharmacological action, glaucescent fissistigma root is carried out enzyme extracting method and into
Type technique study, substantially reduces energy consumption, improves active ingredient dissolution, obtains that a kind of rapid-action, bioavilability is high, the side of taking
Just, adverse reaction is small, the determined curative effect cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally.
Compared with prior art, the advantage of the invention is that：
(1) cancer that disappears containing Radix Fissistigmatis Glaucescentis extract that the present invention is made divides discrete piece equally, and its preparation method is easy, can retain general
The curative effect and properties and characteristicses of obstruction-removing prescription type, have again it is rapid-action, be disintegrated that rapid, convenient to take, bioavilability is high, adverse reaction is small
The features such as.
(2) present invention employs multiplex-enzyme extraction glaucescent fissistigma root, its major advantage is using water as Extraction solvent, using complex enzyme
Extract, compared with conventional water extraction, alcohol extracting, ultrasonic extraction, with simplicity, quick, extraction time is short, cost is low, nontoxic, recovery rate
High the features such as；And the complex enzyme extracting method of the application present invention, total starches, the recovery rate of total saposins are substantially better than common water extraction side
Method.
(3) present invention is using inhibiting rate as the index for evaluating antitumor activity intensity, using MTT colorimetric methods to the present invention's
The extract obtained anti tumor activity in vitro extract obtained with conventional water extraction of enzyme formulation is compared, and is as a result shown,
Extraction time is not only shortened by enzyme extraction method, energy consumption is saved, cost is reduced, simplifies technique, moreover it is possible to effectively improve the system
The therapeutic effect of agent.
(4) superfine silica gel powder is added in preferred embodiments of the present invention and modification is ground to Radix Fissistigmatis Glaucescentis extract, reduce its viscosity, solution
Determined Radix Fissistigmatis Glaucescentis extract complicated component, sticky larger, moisture is difficult to be impregnated with the deficiency such as scattered, can promote collapsing for the dispersible tablet
Solution, drugloading rate can be improved to a certain extent again, reduce the dose of patient, improve curative effect.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
There is the accompanying drawing used required in technology description to be briefly described, it should be apparent that, drawings in the following description are the present invention
Some embodiments, for those of ordinary skill in the art, on the premise of not paying creative work, can also basis
These accompanying drawings obtain other accompanying drawings.
Fig. 1 is solid-liquid ratio in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 2 is enzyme ratio in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 3 is enzyme concentration in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 4 is hydrolysis temperature in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 5 is enzymolysis time in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 6 is reflux extracting time in the embodiment of the present invention 1 to total starches, the effect tendency figure of total saposins recovery rate.
Fig. 7 is enzyme addition and influence of the enzymolysis time to comprehensive grading in the embodiment of the present invention 1.
Fig. 8 is for enzymolysis time in the embodiment of the present invention 1 with hydrolysis temperature to comprehensive grading reciprocal effect.
Fig. 9 is enzyme addition and influence of the hydrolysis temperature to comprehensive grading in the embodiment of the present invention 1.
Embodiment
For the ease of understanding the present invention, more complete is made to the present invention below in conjunction with Figure of description and preferred embodiment
Face, meticulously describe, but protection scope of the present invention is not limited to embodiment in detail below.
Unless otherwise defined, the implication that all technical terms used hereinafter are generally understood that with those skilled in the art
It is identical.Technical term used herein is intended merely to describe the purpose of specific embodiment, is not intended to the limitation present invention
Protection domain.
Unless otherwise specified, various raw material, reagent, instrument and equipment used in the present invention etc. can be by city
Field is commercially available or can prepared by existing method.
Embodiment 1：
A kind of cancer that disappears of the invention containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, the dispersible tablet it is main by Radix Fissistigmatis Glaucescentis extract,
After modifying agent (modifying agent is superfine silica gel powder), filler, disintegrant, wetting agent are mixed in proportion, through granulation, drying, whole grain, mixed
Prepared after even, tabletting；Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root raw material using complex enzyme water-bath；Superfine silica gel powder
Consumption is the 5% of scattered tablet quality.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of the present embodiment divides the preparation method of discrete piece equally, specifically includes following step
Suddenly：
(1) pre-treatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, 80 mesh sieves are crossed；
(2) enzyme is extracted：Glaucescent fissistigma root after above-mentioned steps (1) is added in drinking water by certain solid-liquid ratio, stirred
30min, phosphorated acid for adjusting pH value, adds a certain amount of enzyme, and water-bath extraction is carried out under hydrolysis temperature, is warming up to after the completion of extraction
90 DEG C~95 DEG C insulation 5min, inactivate complex enzyme, and 4 layers of filtered through gauze, filter residue adds a certain amount of water refluxing extraction, filters, and closes
And extract solution twice, stand overnight, suction filtration, filtrate is concentrated into the clear cream that relative density is 1.23；
(3) post-processing：The clear cream that above-mentioned steps (2) are obtained is dried in vacuo, and is ground into Radix Fissistigmatis Glaucescentis extract fine powder；
(4) it is molded：The Radix Fissistigmatis Glaucescentis extract fine powder obtained by above-mentioned steps (3) is taken, modifying agent superfine silica gel powder, micro mist silicon is added
The consumption of glue is the 5% of scattered tablet quality, then with filler, disintegrant, wetting agent mixing granulation in proportion, dry, whole grain, mix
Close uniform, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
(1) selection of enzyme
In the preparation method of above-mentioned the present embodiment, solid-liquid ratio is first set as 1: 12, phosphorus acid for adjusting pH value is enzyme-added to 5.0
Measure as 0.2%, 60min is digested under the conditions of 50 DEG C, be separately added into pectase, cellulase and pectase and cellulase
Complex enzyme zymohydrolysis 90min, filter residue refluxing extraction 120min again, investigate different enzymes and extract to total starches and total saposins recovery rate
Influence, as a result shows, combined-enzyme method extracts total starches, the recovery rate of total saposins and is all higher than other enzyme formulations, therefore, and we select
Multiplex-enzyme extraction method.
(2) single factor experiment is designed
According to the multiplex-enzyme extraction method of above-mentioned establishment, have studied respectively solid-liquid ratio (1: 8,1: 10,1: 12,1: 14,1: 16),
The proportioning (2: 1,1: 1,1: 2,1: 3,1: 4) of pectase and cellulase, enzyme concentration (0.1%, 0.2%, 0.3%, 0.4%,
0.5%), hydrolysis temperature (30 DEG C, 40 DEG C, 50 DEG C, 60 DEG C, 70 DEG C), enzymolysis time (30min, 60min, 90min, 120min,
150min), reflux extracting time (60min, 90min, 120min, 150min, 180min) is to total starches in glaucescent fissistigma root and total soap
The influence of glycosides recovery rate.
1. influence of the solid-liquid ratio to glaucescent fissistigma root total starches and total saposins recovery rate
As Fig. 1 shows that, with the increase of extract solution consumption, the recovery rate of total starches and total saposins gradually rises, but feed liquid
Than after 1: 12 the increased amplitude of recovery rate then reduced, therefore it is optimal solid-liquid ratio that we, which select 1: 12,.
2. the influence with comparison glaucescent fissistigma root total starches with total saposins recovery rate of pectase and cellulase
As Fig. 2 shows that, with the increase of cellulase proportion, total starches, the recovery rate of total saposins gradually rise, can
Can be that the amount for improving cellulase can be more thorough because the constituent of glaucescent fissistigma root cell membrane is main based on cellulose
Ground destroy cell membrane, make active ingredient dissolution rate faster, stripping quantity it is more.When pectase and cellulase ratio are less than 1: 2
When, polysaccharide, the recovery rate increasing degree of saponin(e are obviously reduced, therefore, and selection 1: 2 is matched somebody with somebody as pectase and the optimal of cellulase
Than.
3. influence of the enzyme concentration to glaucescent fissistigma root total starches and total saposins recovery rate
Such as Fig. 3 shows that, with the increase of enzyme concentration, total starches, the recovery rate of total saposins gradually increase, but when enzyme concentration is big
When 0.3%, recovery rate increasing degree is obviously reduced, it is contemplated that Cost Problems in actual production, selects the addition of complex enzyme
Make further investigation (0.25%~0.45%) as the factor of investigation.
4. influence of the hydrolysis temperature to glaucescent fissistigma root total starches and total saposins recovery rate
As shown in figure 4, with the rise of temperature, total starches, the recovery rate of total saposins are dramatically increased, but when temperature is more than 50
DEG C when, recovery rate is decreased again, selection hydrolysis temperature (35 DEG C~55 DEG C) be explored further as investigation factor.
5. influence of the enzymolysis time to glaucescent fissistigma root total starches and total saposins recovery rate
As Fig. 5 shows that, with the extension of enzymolysis time, the recovery rate of total starches and total saposins significantly increases, but works as enzyme
When the solution time is more than 60min, the increased amplitude of recovery rate is obviously reduced, and it is 80~110min as examining that we, which select enzymolysis time,
The factor of examining is explored further.
6. influence of the reflux extracting time to glaucescent fissistigma root total starches and total saposins recovery rate
As Fig. 6 shows that, with the extension of reflux extracting time, total starches, the recovery rate of total saposins gradually increase, and work as backflow
When extraction time is more than 120min, the increased amplitude of recovery rate is obviously reduced, and gradually tends to be steady, it is contemplated that reduction energy consumption and section
About Cost Problems, therefore selection 120min is used as optimal extraction time.
In order to optimize extraction conditions, on the basis of above-mentioned single factor experiment result, software Design Expert are utilized
8.0.6, using Box-Behnken experimental designs, above-mentioned enzyme addition, enzymolysis time, hydrolysis temperature are selected as the factor of investigation,
Using total starches, total saposins recovery rate as evaluation index, preferred optimum extraction condition.Selected factor level and orthogonal experiments
Such as table 1 below, table 2.
Table 1：Enzyme puies forward technique response surface experiments factor level table
Table 2：Enzyme puies forward technique response surface design method and result
Note：Comprehensive grading=total starches recovery rate/total starches recovery rate maximum × 0.5+ total saposins recovery rate/total saposins
Recovery rate maximum × 0.5 (because this saponin(e, polysaccharide constituents are main antineoplastic component in glaucescent fissistigma root, therefore weight coefficient
It is set to 50%).
The foundation and variance analysis of comprehensive grading regression equation
Multiple regression fitting is carried out to the data of upper table 2 using Design Expert8.0.6 softwares, regression equation is solved such as
Under：
Y=93.03-6.16A+7.85B+10.33C+0.93AB+1.39AC+0.32BC-12.46A2- 7.88B2-
7.05C2(in formula：Y is comprehensive grading, and A is enzyme addition, and B is enzymolysis time, and C is hydrolysis temperature).Each factor variance of experiment
Analytical table such as table 3 below.As known from Table 3：Comprehensive grading regression model significantly (P ＜ 0.01), corrects R2=0.9458, illustrate this two
Secondary multivariate regression models is extremely notable, and this can explain the change of response well.Lose and intend item P=0.135 ＞ 0.05, show by
Lost caused by error and intend not notable, thus the models fitting degree is relatively good, test error is small.It can be seen from F values and P values
The first order and quadratic term of three factors (P values are respectively less than 0.05).
Table 3：Comprehensive grading regression model the results of analysis of variance
| Soruces of variation | Quadratic sum | The free degree | It is square | F values | P values |
| Model | 2906.77 | 9 | 322.97 | 13.57 | 0.0012 |
| A- enzyme additions | 303.32 | 1 | 303.32 | 12.75 | 0.0091 |
| B- enzymolysis times | 492.51 | 1 | 492.51 | 20.7 | 0.0026 |
| C- hydrolysis temperatures | 853.88 | 1 | 853.88 | 35.88 | 0.0005 |
| A2 | 654.16 | 1 | 654.16 | 27.49 | 0.0012 |
| B2 | 261.58 | 1 | 261.58 | 10.99 | 0.0128 |
| C2 | 209.39 | 1 | 209.39 | 8.8 | 0.0209 |
| Residual error | 166.59 | 7 | 23.8 | ||
| Lose and intend item | 119.47 | 3 | 39.82 | 3.38 | 0.135 |
| Error term | 47.12 | 4 | 11.78 | ||
| Summation | 3073.36 | 16 |
Response surface analysis and optimization：
Regression equation response surface is as shown in Fig. 7~Fig. 9, and the response of any two interaction factor all has peak, enzyme
The influence of addition and hydrolysis temperature to comprehensive grading is larger.Crow is obtained by software (Design Expert 8.0.6) analysis
The optimum extraction condition of bone rattan be enzyme concentration 0.37%, enzymolysis time 102.6min, 52.6 DEG C of hydrolysis temperature, on this condition always
Polysaccharide, the recovery rate of total saposins are respectively 1.21%, 1.16%.
Embodiment 2：The contrast of complex enzyme formulation and water extraction
A kind of cancer that disappears of the invention containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, the dispersible tablet it is main by Radix Fissistigmatis Glaucescentis extract,
After modifying agent (modifying agent is superfine silica gel powder), filler, disintegrant, wetting agent are mixed in proportion, through granulation, drying, whole grain, total
Prepared after mixed, tabletting；Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root using complex enzyme water-bath.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of the present embodiment divides the preparation method of discrete piece equally, specifically includes following step
Suddenly：
(1) pre-treatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, 80 mesh sieves are crossed；
(2) enzyme is extracted：Glaucescent fissistigma root after above-mentioned steps (1) is added in drinking water by 1: 12 liquor ratio, stirred
30min, plus watery hydrochloric acid adjust pH value to 5, add 0.37% complex enzyme (wherein the mass ratio of pectase and cellulase is 1:
2) water-bath, is carried out at 53 DEG C of hydrolysis temperature and extracts 103min, 90 DEG C~95 DEG C insulation 5min, inactivation are warming up to after the completion of extraction
Complex enzyme, 4 layers of filtered through gauze, filter residue adds the water refluxing extraction 120min of 10 times of amounts, and filtering merges extract solution twice, stood
Night, suction filtration, filter vacuum is concentrated into the clear cream that relative density is 1.23；
(3) post-processing：The clear cream that above-mentioned steps (2) are obtained is dried in vacuo, and is ground into Radix Fissistigmatis Glaucescentis extract fine powder；
(4) it is molded：The Radix Fissistigmatis Glaucescentis extract fine powder obtained by above-mentioned steps (3) is taken, modifying agent superfine silica gel powder, micro mist silicon is added
The consumption of glue is the 5% of scattered tablet quality, then with filler, disintegrant, wetting agent mixing granulation in proportion, dry, whole grain, always
Mixed, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
Control group (water extraction extraction)：Take glaucescent fissistigma root to soak 12 hours, add water to cook 3 times, 2 hours for the first time, second
1.5 hours, third time 1 hour merged extract solution, filtration, it is the clear of 1.23 (70 DEG C~80 DEG C) that filtrate, which is concentrated into relative density,
Cream, vacuum drying, is ground into fine powder, produces extract.
The present embodiment complex enzyme formulation and the result of water extraction see the table below 4, as shown in Table 4, complex enzyme formulation total starches
Average recoveries are 1.25%, and the average recoveries of total saposins are 1.15%；And the result of water extraction shows total starches, total saposins
Recovery rate be respectively 1.18%, 1.05%；Examined through t, two methods have aobvious to the recovery rate difference of total starches, total saposins
The difference (P≤0.05) of work property.Total starches recovery rate, the total saposins recovery rate of complex enzyme formulation are improved than water extraction respectively
5.93%th, 9.52%.Water extraction is extracts the most commonly used method of glaucescent fissistigma root at present, and complex enzyme formulation can not only reach higher
Recovery rate, and compared with water extraction also have the advantages that reaction is gentle, temperature is low, consume energy less, it is low for equipment requirements, may
It is because the pectin and cellulose of pectase and cellulase in a short time in fast degradation glaucescent fissistigma root cell membrane, so that broken
Its cell membrane is broken, cell membrane and membrane passage is improved, the dissolution of cell interior active ingredient is accelerated.
Table 4：Complex enzyme formulation extracts the recovery rate of glaucescent fissistigma root with water extraction
The comparison of mtt assay anti tumor activity in vitro in Different Extraction Method
MTT colorimetric methods are a kind of methods of objective, sensitive measure the sensitivity of anti cancer drugs, and the method has easy, fast
Fast the advantages of, required cell is less, has been widely used in the screening study of clinical anti-cancer medicine at present.In order to inquire into the present invention
Extraction process can effectively improve the antitumor activity of the invention preparation, we using inhibiting rate be used as evaluate antitumor activity
The index of intensity, it is extract obtained to the enzyme formulation of the invention described above with being extracted obtained by conventional water extraction using MTT colorimetric methods
The anti tumor activity in vitro of thing is compared.
Take the logarithm growth period liver cancer cells Bel-7402, intestinal cancer Lovo, esophageal cancer cell EC-9706, ovarian cancer cell
Caov-3(5×103Individual/hole) 96 orifice plates are inoculated in, in 37 DEG C, 5%CO224h is cultivated in incubator, makes cell attachment；Xiang Kongzhong
By reagent (be separately added into water extraction is extract obtained, the present embodiment complex enzyme formulation is extract obtained) is added, tested group every
Group sets 0.39 respectively, 0.65,1.00,1.80,5 different concentration of 3.00mg/ml；Every group of multiple 6 holes, continuation is cultivated respectively
24h、48h；20 μ l MTT solution (5mg/ml, i.e. 0.5%MTT) are added per hole, 37 DEG C are continued to cultivate 4h；150 μ l are added per hole
Slight oscillatory 10min, makes crystal fully dissolve on DMSO, micro oscillator, and the light absorption value in each hole is measured on ELIASA
(OD).Every group of experiment is repeated 3 times.Inhibiting rate is calculated by OD values, and using drug concentration as abscissa, OD values are ordinate, are painted
Cell growth curve processed, and try to achieve IC50(half inhibiting rate).IC50(crude drug amount)=inhibitory rate of cell growth is 50% medicine
Concentration.The anti tumor activity in vitro result of the test is as shown in table 5 below.
Table 5：Anti tumor activity in vitro result of the test
It is not difficult to find out from the experimental result in upper table 5, the external of Radix Fissistigmatis Glaucescentis extract obtained by complex enzyme formulation of the present invention resists
Tumor promotion is substantially better than water extraction.As a result show, extraction time is not only shortened by the multiplex-enzyme extraction method of the present invention, save
About energy consumption, reduces cost, simplifies technique, moreover it is possible to the effective therapeutic effect for improving said preparation.
Embodiment 3：
A kind of cancer that disappears of the invention containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, the dispersible tablet it is main by Radix Fissistigmatis Glaucescentis extract,
After modifying agent (modifying agent is superfine silica gel powder), filler, disintegrant, wetting agent are mixed in proportion, through granulation, drying, whole grain, mixed
Prepared after even, tabletting；Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root raw material using complex enzyme water-bath.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of the present embodiment divides the preparation method of discrete piece equally, specifically includes following step
Suddenly：
(1) pre-treatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, sieving；
(2) enzyme is extracted：Glaucescent fissistigma root after above-mentioned steps (1) is added in drinking water by 1: 12 liquor ratio, stirred
30min, plus watery hydrochloric acid regulation pH value be 5, add 0.37% complex enzyme (wherein the mass ratio of pectase and cellulase be 1:
2) water-bath, is carried out at 53 DEG C of hydrolysis temperature and extracts 103min, 90 DEG C~95 DEG C insulation 5min, inactivation are warming up to after the completion of extraction
Complex enzyme, 4 layers of filtered through gauze, filter residue adds the water refluxing extraction 120min of 10 times of amounts, and filtering merges extract solution twice, stood
Night, suction filtration, filter vacuum is concentrated into the clear cream that relative density is 1.23；
(3) post-processing：The clear cream that above-mentioned steps (2) are obtained is dried in vacuo, and is ground into Radix Fissistigmatis Glaucescentis extract fine powder；
(4) it is molded：The Radix Fissistigmatis Glaucescentis extract fine powder obtained by above-mentioned steps (3) is taken, modifying agent superfine silica gel powder, micro mist silicon is added
The consumption of glue is 3% (6.3g), 5% (10.5g), 7% (14.7g) 3 kinds of consumptions of scattered tablet quality (210g), and glaucescent fissistigma root is carried
Thing fine powder and superfine silica gel powder mixed grinding 10min are taken, No. 6 sieves are crossed；System is mixed in proportion with filler, disintegrant, wetting agent again
Grain, is dried, whole grain, and total mixed, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
Amount of modifier is investigated
On the premise of prescription total amount and raw material total amount are constant, prescription mixed material listed by according to the form below 6,80% ethanol system
Grain, is dried, and single-punch tablet press depresses to the tablet of 0.3g/ piece specifications, wherein 10 progress disintegration time limited inspections is taken, with SPSS
17.0 statistical softwares carry out one-way analysis of variance, the results are shown in Table 6.On the premise of prescription total amount keeps constant, equal proportion drop
The consumption of low filler and disintegrant, increases the consumption of superfine silica gel powder, can significantly reduce disintegration time (the P ＜ of dispersible tablet
0.01)；Disintegration time is most short when wherein using the consumption of superfine silica gel powder as 5%.
Table 6：The powder-modified influence (n=10) to disintegration time
Note：Compared with former technique：* P ＜ 0.01
Conclusion：From upper table 6, optimal moulding process of the invention is：Appropriate Radix Fissistigmatis Glaucescentis extract is taken, plus 5%
Superfine silica gel powder is placed in mortar body, is less than in relative humidity under 50% environmental condition, grinds 10min, is crossed No. 6 and is sieved to obtain glaucescent fissistigma root
Modifier；With 70% lactose: MCC (1: 1) for filler, 20% PVPP: L-HPC (3: 7) are disintegrant, are changed with glaucescent fissistigma root
Property thing is uniformly mixed；Using 80% ethanol as wetting agent, mixing granulation is dried, whole grain, stiffened fatty acid magnesium, appropriate sweetener,
Well mixed, tabletting produces one kind cancer that can disappear and divides discrete piece equally.
Embodiment 4
A kind of cancer that disappears of the invention containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, the dispersible tablet it is main by Radix Fissistigmatis Glaucescentis extract,
After modifying agent (modifying agent is superfine silica gel powder), filler, disintegrant, wetting agent are mixed in proportion, through granulation, drying, whole grain, mixed
Prepared after even, tabletting；Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root raw material using complex enzyme water-bath.
The above-mentioned cancer that disappears containing Radix Fissistigmatis Glaucescentis extract of the present embodiment divides the preparation method of discrete piece equally, specifically includes following step
Suddenly：
(1) pre-treatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, sieving；
(2) enzyme is extracted：Glaucescent fissistigma root after above-mentioned steps (1) is added in drinking water by 1: 12 liquor ratio, stirred
30min, the acid for adjusting pH value that phosphorates be 5, add 0.37% complex enzyme (wherein the mass ratio of pectase and cellulase be 1:
2) water-bath, is carried out at 53 DEG C of hydrolysis temperature and extracts 103min, 90 DEG C~95 DEG C insulation 5min, inactivation are warming up to after the completion of extraction
Complex enzyme, 4 layers of filtered through gauze, filter residue adds the water refluxing extraction 120min of 10 times of amounts, and filtering merges extract solution twice, stood
Night, suction filtration, filter vacuum is concentrated into the clear cream that relative density is 1.23；
(3) post-processing：The clear cream that above-mentioned steps (2) are obtained is dried in vacuo, and is ground into Radix Fissistigmatis Glaucescentis extract fine powder；
(4) it is molded：The Radix Fissistigmatis Glaucescentis extract fine powder obtained by above-mentioned steps (3) is taken, the superfine silica gel powder of modifying agent 5% is added,
By Radix Fissistigmatis Glaucescentis extract fine powder and superfine silica gel powder mixed grinding 10min, No. 6 sieves are crossed；Pressed again with filler, disintegrant, wetting agent
Ratio mixing granulation, is dried, whole grain, and total mixed, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
The cancer that disappears divides the clinical efficacy of discrete piece combination chemotherapy later period of hepatocarcinoma equally
1. clinical data
100 are inpatient, are diagnosed as middle and terminal cancer by pathologic finding and clinical examination.It is randomly divided into two
Group, wherein the cancer that disappears divides discrete piece treatment group 52 equally, male 34, women 18, average age is 54.9 years old；Chemotherapy group 48
Example, male 31, women 17, average age is 54.2 years old；Cancer type and packet are shown in Table 7：
Table 7：100 patient's packets and cancer types table
Above data is statistically analyzed, each group no significant difference, with comparativity.
2. treatment method
The advanced tumor patient 100 that observation is in hospital, control group gives chemotherapy, and test group gives the cancer that disappears and divides discrete piece equally
4~5 pieces/times, take daily 3 times, 7d is used in conjunction, was within two weeks 1 cycle, comprehensive efficacy evaluation is carried out after completing 4 cycles.
3. efficacy assessment standard
(1) use《The standard of curative effect evaluation of entity tumor》, with CR+PR, calculate efficient (OR)；With CR+PR+SD, meter
Calculate disease control rate (DCR).CR (complete incidence graph)：Cases of complete remission simultaneously continues more than 4 weeks, occurs without new focus；PR (parts
Alleviate)：Tumor regression more than 50%, and continue more than 4 weeks, occur without new focus；SD (lesion is stable)：Tumor regression 50% with
Lower or increase is not less than 25%；PD (deterioration)：New focus occurs or tumour increase more than 25%.
(2) KPS scale：By KPS standards of grading.Improving improves：>=10 points of scoring increase before relatively being treated after treatment；
It is stable：Before relatively being treated after treatment scoring change 10/it is interior；Reduction：Scoring reduces >=10 points before relatively being treated after treatment.
4. clinical efficacy result
The situation of change of entity tumor is shown in Table 8 after two groups of treatments：
Table 8：The change of entity tumor after treatment
KPS scale after two groups of treatments is shown in Table 9：
Table 9：KPS score is compared (P ＜ 0.05) before and after 100 patient's treatments
5. conclusion
Above-mentioned clinical efficacy result shows that it is efficient with control group that the cancer that disappears divides discrete piece treatment group effective percentage 50.0% equally
47.9% compares 2.5% (P ＜ 0.05).And confirm that the cancer that disappears divides discrete piece treatment group equally to patient indirectly by KPS scorings change
The recovery of functional state and immunologic function is better than chemotherapy group.The patient after chemotherapy is pointed out, in vivo growth of cancer cells
While being suppressed, normal cell also by different degrees of damage, in often occurring in therapeutic process, severe it is bad anti-
Should.And Chinese medicine antineoplastic --- the cancer that disappears divide equally discrete piece action temperature and, treat middle and advanced stage cancer, can really improve clinical symptoms,
And have effects that to significantly improve patients ' life quality.
Claims (8)
1. a kind of cancer that disappears containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, the dispersible tablet it is main by Radix Fissistigmatis Glaucescentis extract, modifying agent, fill out
Fill after agent, disintegrant, wetting agent mix in proportion, prepared after granulation, drying, whole grain, total mixed, tabletting；Its feature exists
In：The Radix Fissistigmatis Glaucescentis extract is to extract to obtain after glaucescent fissistigma root using complex enzyme water-bath；
The modifying agent is superfine silica gel powder, and the consumption of superfine silica gel powder is the 3%~7% of the scattered tablet quality；
The filler is the mixture of lactose and microcrystalline cellulose, the mass ratio of lactose and microcrystalline cellulose for 1: 0.8~
1.0, and the consumption of filler is the 60%~80% of the scattered tablet quality；
The complex enzyme includes pectase and cellulase, and the mass ratio of pectase and cellulase is 1: 2.
2. the cancer that disappears according to claim 1 containing Radix Fissistigmatis Glaucescentis extract divides discrete piece equally, it is characterised in that the disintegrant is
The mixture of PVPP and low-substituted hydroxypropyl cellulose, and disintegrant consumption for the scattered tablet quality 15%~
25%；The wetting agent is ethanol solution.
3. a kind of cancer that disappears as claimed in claim 1 or 2 containing Radix Fissistigmatis Glaucescentis extract divides the preparation method of discrete piece equally, including following
Step：
（1）The pretreatment of glaucescent fissistigma root：Raw material glaucescent fissistigma root is cleaned, cleans, dries, is crushed, sieving；
（2）Glaucescent fissistigma root is extracted：By above-mentioned steps（1）Glaucescent fissistigma root afterwards is added to the water, and mixed liquor, plus acid for adjusting pH are obtained after stirring
Value adds complex enzyme to 4.5~5.5, and water-bath extraction is carried out under hydrolysis temperature, more than 90 DEG C are warming up to after the completion of extraction and is gone out
Complex enzyme living, filtering, filter residue adds water refluxing extraction, merges extract solution, stands overnight, suction filtration, filtrate is concentrated into clear cream；
（3）Post-processing：By above-mentioned steps（2）The clear cream of acquisition is dried in vacuo, and is ground into Radix Fissistigmatis Glaucescentis extract fine powder；
（4）Shaping：Take above-mentioned steps（3）The Radix Fissistigmatis Glaucescentis extract fine powder of gained, add modifying agent, then with filler, disintegrant,
Wetting agent mixing granulation in proportion, is dried, whole grain, and total mixed, tabletting produces the cancer that disappears containing Radix Fissistigmatis Glaucescentis extract and divides discrete piece equally.
4. preparation method according to claim 3, it is characterised in that：The step（2）In, the addition of the complex enzyme
For the 0.25%~0.45% of mixed liquor quality, and the solid-liquid ratio of glaucescent fissistigma root and water is 1: 8~16 in mixed liquor.
5. the preparation method according to claim 3 or 4, it is characterised in that：The step（2）In, the hydrolysis temperature is
35 DEG C~55 DEG C, enzymolysis time is the min of 80 min~110.
6. preparation method according to claim 5, it is characterised in that：The step（2）In, the addition of the complex enzyme
Measure as the 0.37% of mixed liquor quality, the hydrolysis temperature is 53 DEG C, enzymolysis time is 103 min.
7. the preparation method according to claim 3 or 4, it is characterised in that：The step（2）In, inactivate the temperature of complex enzyme
Spend for 90 DEG C~95 DEG C, inactivation time is not less than 5 min, the relative density that the vacuum concentration obtains clear cream is at least 1.23.
What 8. a kind of as claimed in claim 1 or 2 or preparation method as any one of claim 3~7 was obtained contains
The cancer that disappears of Radix Fissistigmatis Glaucescentis extract divides application of the discrete piece in antineoplastic is prepared equally.
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| CN101322758A (en) * | 2008-08-01 | 2008-12-17 | 天津商业大学 | Method for producing spina date seed extract using complex enzyme |
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| CN101322758A (en) * | 2008-08-01 | 2008-12-17 | 天津商业大学 | Method for producing spina date seed extract using complex enzyme |
| CN103463138A (en) * | 2012-09-26 | 2013-12-25 | 成都中医药大学 | Traditional Chinese medicine dispersible tablet and preparation method thereof |
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