CN105194691A - Neck rehabilitation particle simulation agent and preparation method of neck rehabilitation particle simulation agent - Google Patents
Neck rehabilitation particle simulation agent and preparation method of neck rehabilitation particle simulation agent Download PDFInfo
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Abstract
The invention provides a neck rehabilitation particle simulation agent, which is prepared from the following ingredients in percentage by mass: 58.00 to 60.00 percent of dextrin, 27.60 to 30.00 percent of spray drying lactose, 5.00 to 5.20 percent of beta-cyclodextrin, 0.70 to 0.73 percent of caramel color (through being metered by solid matters), 0.001 to 0.002 percent of sodium copper chlorophyllin, 0.040 to 0.050 percent of lemon yellow, 3.36 to 4.43 percent of broadleaf holly leaf extracts (through being metered by solid matters), 0.50 to 1.00 percent of 6-percent starch slurry (through being metered by starch quantity) 0.500 to 1.000 percent of light-weight magnesium stearate and 0.010 to 0.020 percent of volatile oil, wherein the mass percentage of all ingredients is 100 percent. The invention also provides a preparation method of the neck rehabilitation particle simulation agent. Through experiments, the simulation agent has higher consistency with neck rehabilitation particles, and can be used as the neck rehabilitation particle simulation agent.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of JINGFUKANG KELI simulant.
Background technology
In " new Chinese medicine clinical research rule " (exposure draft/2012 year November) that state food pharmaceuticals administration general bureau (CFDA) issues, require that placebo makes and should meet following requirement:
placebo would not produce harm to health when being used for clinical trial, can not produce obvious adverse reaction (except the slight untoward reaction produced by the pharmaceutic adjuvant identical with trial drug).2. clinical trial placebo all should be similar to trial drug/or positive drug in the features such as color, abnormal smells from the patient, taste, shape, texture, or make clinical trial participant be difficult to judge trial drug/or positive drug and placebo.Rational method need be adopted to judge its similarity and the suitability and evaluate (the sensory evaluation method that food or cosmetics etc. can be used for reference), and correlational study data is provided.3. placebo without obvious therapeutic action, should can not disturb the observation to trial drug effectiveness to trial drug indication used.4. placebo supplementary material used should meet the prescription of corresponding route of administration, and the supplementary material used of the placebo as oral test medicine should meet the relevant statutory standards such as medicine or food.5. kind and the consumption of placebo prescription supplementary material should be specified; The least possiblely should add the material that may produce interference to trial drug safety and efficacy.Placebo adjuvant should be identical with trial drug as far as possible.6. should set up the quality standard of placebo, ensure the safe, stable, homogeneous of placebo.7. the specification, outward appearance, packaging, label, mark etc. of placebo should be consistent with trial drug.Existing placebo renames as simulant.
Chinese medicinal granule simulant then requires to carry out overall organoleptic's characteristic evaluation with tested material, and its quantum evaluation has: (1) exterior and interior packing test item: 1. inner packaging material: quality, color, shape, size; 2. housing material: quality, color, shape, size; 3. other extra objects (as seal inspection etc.): mark, color, shape, size.(2) label/description test item (then not assessing without description): 1. word: content, font, size, color, form; 2. icon: shape, color, size, position; 3. material: quality, shape, color, size; 4. label application position.(3) organoleptic attribute evaluation item: the 1. form of solid state, color, texture, taste, abnormal smells from the patient assessment (range estimation, mouth are tasted and smell taste), and be described in detail.2. (test medicine and simulant add certain volume hot water and dissolve the liquid of granule under the impulsive motion state that adds water respectively, stir 5 minutes) color, texture (whether solution transparent), taste, abnormal smells from the patient assessment (range estimation, mouth taste and smell taste), and to be described in detail.3. getting above-mentioned solution puts to room temperature, measures the pH value of solution.(4) assessment result is inserted overall organoleptic's characteristic evaluation table of tested material " simulant with ", " placebo impulsive motion state organoleptic attribute is simulated and compared log ", and carry out mathematics statistics to it, no difference of science of statistics can think that this simulant is successfully prepared.
Summary of the invention
For ensureing the safe, stable and homogeneous of Chinese medicine simulant, the applicant is on the basis of JINGFUKANG KELI simulant Study on Preparation and evaluation, in conjunction with by the actual organoleptic feature of simulation test medicine JINGFUKANG KELI and quality standard, provide a kind of JINGFUKANG Chinese medicinal granule simulant.
The invention provides a kind of JINGFUKANG KELI simulant, described simulant is prepared from by each component of following mass percent: dextrin 58.00-60.00%, spray-dried lactose 27.60-30.00%, beta-schardinger dextrin-5.00-5.20%, burnt sugar coloring 0.70-0.73%(is with solids basis), sodium copper chlorophllin 0.001-0.002%, lemon yellow 0.040-0.050%, Folum Ilicis extract 3.36-4.43%(is with solids basis), 6% starch slurry 0.50-1.00%(is with starch gauge used), lightweight magnesium stearate 0.500-1.000%, volatile oil 0.010-0.020%, the mass percent sum of each component is 100%.
Preferably, described simulant is prepared from by each component of following mass percent: dextrin 59.60%, spray-dried lactose 28.60%, beta-schardinger dextrin-5.20%, burnt sugar coloring 0.73%(are with solids basis), sodium copper chlorophllin 0.001%, lemon yellow 0.050%, Folum Ilicis extract 4.43%(be with solids basis), 6% starch slurry 0.50%(is with starch gauge used), lightweight magnesium stearate 0.874%, volatile oil 0.015%.
Preferably, the preparation method of described Folum Ilicis extract is: get Folium Ilicis and decoct with water, concentrate filtrate to relative density 1.10-1.30(50 DEG C), solid content is 44-46%, to obtain final product.
Preferably, the preparation method of described volatile oil is: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder, wait mass ratio to mix, and after adding water retting, vapor distillation extracts, and obtains volatile oil.
Second object of the present invention is to provide the preparation method of JINGFUKANG KELI simulant, and step is as follows:
(1) prepare volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder and mix, after adding water retting, vapor distillation extracts, and obtains volatile oil;
(2) Folum Ilicis extract is prepared: get Folium Ilicis and decoct with water, concentrate filtrate to relative density 1.10-1.30(50 DEG C), now solid content is 44-46%, obtains Folum Ilicis extract;
(3) prepare starch slurry: get starch, first add a small amount of water dissolution, then add boiling water punching, be stirred to bright, make the mass percentage of starch be 6%;
(4) prepare hybrid pigment aqueous solution: sodium copper chlorophllin and the lemon yellow 60 of getting formula ratio, be added in the water of 50 DEG C ~ 60 DEG C, stirring and dissolving, prepare the hybrid pigment aqueous solution that mass percentage is 5-15%;
(5) prepare burnt sugar coloring hot water diluent: the hot water adding 70 ~ 80 DEG C in burnt sugar coloring, being diluted to mass percent is 70-80% solution, to obtain final product;
(6) elementary mixing liquid is prepared: get the dextrin of formula ratio, lactose and beta-schardinger dextrin-, after mix homogeneously, then carry out secondary mixing, add burnt sugar coloring hot water diluent prepared by step (5) and Folum Ilicis extract prepared by step (2), mix homogeneously, obtains elementary mixing liquid;
(7) in the elementary mixing liquid obtained in step (6), add the hybrid pigment aqueous solution that step (4) obtains, appropriate mass percentage be 55% ethanol and the starch slurry that obtains of step (3), prepare soft material after mixing, obtain dried particles through post processing;
(8) spray into 2% volatile oil alcoholic solution mixing in the dried particles prepared in step (7), add the lightweight magnesium stearate of formula ratio after airtight placement again, mixing, makes granule, to obtain final product.
Preferably, Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, Myrrha described in step (1) such as are at the mass ratio mixing.
When mixing Deng mass ratio, the abnormal smells from the patient of the volatile oil obtained and the abnormal smells from the patient of JINGFUKANG KELI the most close.
Preferably, decocting with water described in step (2) is decoct with water 3 times, and decocting time is respectively 1 hour, 1 hour and 45 minutes, and add water 8 times amount at every turn.
Now, the taste of the Folum Ilicis extract obtained and the taste of JINGFUKANG KELI the most close.
Preferably, described in step (8), the preparation method of 2% volatile oil alcoholic solution is: the volatile oil of 0.2 volume is added 95% ethanol to 10 volume, stir evenly, to obtain final product.
Through test, simulant of the present invention and JINGFUKANG KELI have higher concordance, can use as JINGFUKANG KELI simulant.
Accompanying drawing explanation
Accompanying drawing is used to provide a further understanding of the present invention, and forms a part for description, together with embodiments of the present invention for explaining the present invention, is not construed as limiting the invention.In the accompanying drawings:
Fig. 1 is that JINGFUKANG KELI simulant of the present invention compares with the outward appearance of JINGFUKANG KELI;
Fig. 2 is that JINGFUKANG KELI simulant HPLC differentiates collection of illustrative plates;
To be JINGFUKANG KELI simulant solution compare with the outward appearance of JINGFUKANG KELI and organoleptic attribute Fig. 3; Wherein 1-JINGFUKANG KELI simulant (20131104); 2-JINGFUKANG KELI (390375); 3-JINGFUKANG KELI simulant (20131105); 4-JINGFUKANG KELI (390290); 5-JINGFUKANG KELI simulant (20131106); 6-JINGFUKANG KELI (390300).
Detailed description of the invention
Following embodiment is convenient to understand the present invention better, but does not limit the present invention.Experimental technique in following embodiment, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions, is commercially available.
embodiment 1
The applicant prepare the principle of JINGFUKANG KELI simulant and step as follows:
(1) JINGFUKANG KELI prescription composition and JINGFUKANG KELI simulant compound basis
JINGFUKANG KELI is recorded in Chinese Pharmacopoeia version in 2010 the 1138th page ~ 1139 pages.There is promoting blood circulation to remove obstruction in the collateral, loose wind pain-relieving functions.For the cervical spondylosis caused by rheumatism stasis blocking, disease sees dizziness, neck stiffness, aching pain in should and back, disease of hand.
JINGFUKANG KELI prescription is made up of 21 tastes such as Rhizoma Et Radix Notopterygii, Rhizoma Chuanxiong, Radix Puerariae, Radix Gentianae Macrophyllae, Radix Clematidis, Rhizoma Atractylodis, Radix Salviae Miltiorrhizae, the Radix Paeoniae Alba, Pheretima (processed with wine), Flos Carthami, Olibanum (system), the Radix Astragali, Radix Codonopsis, Radix Rehmanniae, Concha Haliotidis, Ophicalcitum, Cortex Phellodendri, Semen Vaccariae, Semen Persicae, Myrrha (processed), Eupolyphaga Seu Steleophagas (processed with wine).
More than [method for making], 20 simply, and Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, Myrrha extract volatile oil, volatile oil beta-schardinger dextrin-inclusion, for subsequent use after inclusion complex drying; Medicinal residues and decoct with water secondary, each 2 hours, collecting decoction with ten Six-elements such as Radix Puerariae, filter, filtrate reduced in volume concentrates, spraying dry.Add volatile oil beta-cyclodextrin (inclusion complex and appropriate lactose), lightweight magnesium stearate, mix homogeneously, makes granule, to obtain final product.
By to by the analysis of aids drug " JINGFUKANG KELI " prescription and method for making, specify that the adjuvant used in the preparation of these product has three kinds, is lactose (Lactose), beta-schardinger dextrin-(Betacyclodextrin respectively; β-CD) and lightweight magnesium stearate (MagnesiumStearate).According to the principle of " placebo adjuvant should be identical with trial drug as far as possible ", containing lactose, beta-schardinger dextrin-and lightweight magnesium stearate in prescription of the present invention.
By to JINGFUKANG KELI physical aspect, color, taste, abnormal smells from the patient, the simulation of solid and solution texture, simulant with studied by aids drug organoleptic feature similarity evaluation, and test agent (20131104 in JINGFUKANG KELI simulant three batches, 20131105, 20131106) preparation and the evaluation test of analog approximation degree, determine JINGFUKANG KELI simulant prescription composition: the present invention is by 5 kinds of pharmaceutic adjuvants and 3 kinds of food additive and Folum Ilicis extract (bitters) and formed by aids drug volatile oil on a small quantity, the supplementary material kind used, purposes and quality accounting are in table 1.
table1
jINGFUKANG KELI simulant prescription analysis table
6% starch slurry is pressed solid content and is calculated, the starch-containing 6g of 100ml.
Burnt sugar coloring is pressed solid content and is calculated, and is about 40% containing solid content.
Folum Ilicis extract is pressed solid content and is calculated, and is about 45% containing solid content.
Being prepared as follows of volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes (JINGFUKANG KELI volatile oil is drawn flavour of a drug); make coarse powder; equal proportion mixes; add water 8 times amount; flood 1 hour; vapor distillation extracts volatile oil (yield about 0.3%) in 6 hours, is separated volatile oil, and another device shading low temperature seal is preserved (this volatile oil is yellow lightweight volatile oil).
Because test medicine " JINGFUKANG KELI " is oral administration route, so the supplementary material that " JINGFUKANG KELI simulant " uses is have imperial pharmaceutic adjuvant and food additive etc.Its bitterness adopts medicine to eat general Folum Ilicis extract simulation, and special odor uses " JINGFUKANG KELI " to form flavour of a drug Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum and the simulation of Myrrha Mixed chaotic sequences." JINGFUKANG KELI simulant " component standard resource is in table 2, and use standard is in table 3.
table2
jINGFUKANG KELI simulant component standard resource
table3
jINGFUKANG KELI simulant component uses standard
The burnt sugar coloring used in this product, sodium copper chlorophllin and lemon yellow are food additive (coloring agent).Be mainly used in the simulation of solution colour after simulant solid and impulsive motion.Its beverage class using standard to specify for GB2760-2011 " national food safety standard food additive uses standard " (except 14.01 packaging drinking water classes) maximum use standard.GB2760-2011 specifies simultaneously: solid beverage increases use amount by extension rate.JINGFUKANG KELI simulant usage and dosage is identical with by aids drug JINGFUKANG KELI, i.e. every 5g(1 bag) orally use with after 150 ~ 200ml hot water impulsive motion, its extension rate is minimum is 30 times.Calculate with this: the maximum use amount of sodium copper chlorophllin is 15g/kg(0.01g/kg), the maximum use amount of lemon yellow is 3g/kg(0.5g/kg).
With this criterion, in this product, the consumption of food additive all meets GB2760-2011 food additive use standard regulation.
Folum Ilicis extract system extracts obtained fluid extract (every 1ml is equivalent to 1g Folium Ilicis) by Folium Ilicis through decocting, and relative density is 1.10(50 DEG C), solid content is about 45%; Every 1g Folum Ilicis extract is equivalent to 0.91g Folium Ilicis.By JINGFUKANG KELI simulant usage and consumption: one time 1 ~ 2 bag (5 ~ 10g), 2 times on the one.Daily Folium Ilicis total amount is 1.82g to the maximum.The consumption that Guangdong Province's Chinese crude drug standard (first) specifies under version " Folium Ilicis " item for 2004 is: " 6 ~ 9g, boiled water is taken after being infused in hot water or decoction or is decocted in water for oral dose ", and its consumption in simulant is significantly less than standardized amount.
(2) simulant safety and the analysis to clinical trial interference
Regulation in " new Chinese medicine clinical research rule ": harm would not be produced to health when placebo is used for clinical trial, can not obvious adverse reaction be produced; Placebo without obvious therapeutic action, should can not disturb the observation to trial drug effectiveness to trial drug indication used.
In the JINGFUKANG KELI simulant of the application, not containing material trial drug safety and efficacy being produced to interference, its prescription is primarily of the composition such as pharmaceutic adjuvant and food additive of almost parmacodynamics-less activity, the supplementary material used all meets the Chinese Pharmacopoeia relevant statutory standards such as version or food additive in 2010, harm can not be produced to health, can not obvious adverse reaction be produced.
1. dextrin (Dextrin)
Molecular formula: (C
6h
10o
5)
nh
2o, CAS number: 9004-53-9; For by the pharmaceutic adjuvant used in aids drug " JINGFUKANG KELI ", this product press filler use in the simulant of the application.
2. lactose (Lactose)
Molecular formula: (C
12h
22o
11) H
2o; Molecular weight: 360.31; CAS numbers: 5989-81-1; In this application, spray-dried lactose (alpha-lactose is used; Lactose monohydrate; Containing 10% noncrystalline lactose of having an appointment), this specification lactose is relatively applicable to granule and uses, and powder is circular, and mobility is strong, and its granularity is between 100-200 order.Lactose monohydrate about contains the water of crystallization of the adsorbed water 5.0% of 0.1%, and can lose 75% water of crystallization when 103 ~ 105 DEG C, lose 100% water of crystallization when 120 DEG C, 80 DEG C of dryings can only remove adsorbed water.
Lactose is by the pharmaceutic adjuvant used in aids drug " JINGFUKANG KELI ", presses filler and use in the simulant of the application.
3. beta-schardinger dextrin-(Betacyclodextrin)
Molecular formula: (C
6h
10o
5)
7; Molecular weight: 1134.99; CAS numbers: 7585-39-9; This product is by the pharmaceutic adjuvant used in aids drug " JINGFUKANG KELI ", and this product is pressed filler and used in simulant.
4. hard magnesium (MagnesiumStearate)
Molecular formula: Mg [CH
3(CH
2)
16cOO]
2; CAS numbers: 557-04-0; This product is pressed lubricant and is used % in the simulant of the application.
5. starch (Starch)
Molecular formula: (C
6h
10o
5)
n; CAS numbers: 9005-25-8.
Owing to not being rendered as clear solution by aids drug " JINGFUKANG KELI " after hot water impulsive motion, its aqueous solution has nontransparent texture feature (little cloudy).And the raw and auxiliary material used in simulant (except starch) is all water-soluble under the condition of (5g → 150ml) hot water (70 ~ 80 DEG C) impulsive motion, and then form clear solution.For making the solution texture after simulant hot water impulsive motion closer to JINGFUKANG KELI, appropriate amount of starch is added when prepared by simulant, partial starch (in starch, amylopectin accounts for 80% ~ 90%) is utilized to be insoluble to hot water but the characteristic of colloid solution can be pasted into, the little cloudy texture of simulation test medicine aqueous solution.Starch is made 6% starch slurry and can be used as adhesive use.In addition, add a small amount of starch and also can solve because dextrin consumption is excessive, viscosity increase is unfavorable for the problem of wet granulation.
6. burnt sugar coloring (caramelcolour)
Chinese: burnt sugar coloring (caramel); English name: caramelcolourclassIV-ammoniasulphiteprocess; CNS numbers: 08.109.
Because most of Chinese medicine test medicine all presents darker color, so it is very important to mix corresponding color to placebo.JINGFUKANG KELI outward appearance is that yellowish-brown is to tan granule, add water after dissolving and present yellowish-brown to sepia, because natural Chinese medicine more or less presents caramel composition, and burnt sugar coloring is soluble in water, Diluted Alcohol, transparent brown of 0.1% aqueous solution, can keep under daylight stablizing for 6 hours, therefore can use as traditional Chinese medicine placebo coloring agent, while coloring solid powder or granule, also play the effect of certain adhesive, and can use by normal demand.Burnt sugar coloring safety does not have problems.In addition burnt sugar coloring has happy bitterness, also adapts with the micro-bitter characteristic of JINGFUKANG KELI.
This product uses according to toner in the simulant of the application.
7. pigment
Except burnt sugar coloring, containing two kinds of pigments (food additive) in the simulant of the application, be respectively sodium copper chlorophllin and lemon yellow.Be mainly used in become more meticulous adjustment and the simulation of JINGFUKANG KELI simulant solution colour after hot water impulsive motion.
(1) sodium copper chlorophllin (SodiumCopperChlorophyllin)
CNS numbers: 08.009;
INS numbers: 141ii;
CAS numbers: 65963-40-8;
Molecular formula and molecular weight: C
34h
38o
6n
4cuNa; 744.11
This product uses according to the toner simulation of solution colour (after the impulsive motion) in the simulant of the application.
(2) lemon yellow (Tartrazine)
Model: lemon yellow 60(content 60%)
Chemical name: 1-(4 '-sulfonic group phenyl)-3-carboxyl-4-(4 '-sulphenyl azo group)-5-pyrazolone trisodium salt.
Molecular formula and molecular weight: C
16h
9n
4na
3o
9s
2; 534.36;
CNS numbers: 08.005;
INS numbers: 102;
CAS numbers: 3844-45-9;
This product uses according to the toner simulation of solution colour (after the impulsive motion) in the simulant of the application.
8. bitters (Bitter)
In the present invention, bitters is the aqueous extract of Folium Ilicis.Folium Ilicis is containing amaroid, and aqueous extract taste is extremely bitter, slightly sugariness, close with test medicine bitterness, and this product safety does not have problems.Though Folium Ilicis has certain effect, but with test medicine clinical efficacy without direct correlation, and in simulant consumption less (1.62g/ day), be equivalent to 18.0% ~ 27.0% of Folium Ilicis standardized amount, still do not reach pharmacological action dosage or act on more weak, therefore can not have influence on the judgement to test medicine clinical efficacy.
This product is pressed the bitters simulation of solution taste (after solid and the impulsive motion) and is used in simulant.
9. volatile oil (Volatileoil)
Owing to being contained volatile oil by aids drug JINGFUKANG KELI, cause and make it have special abnormal smells from the patient (after comprising hot water impulsive motion), and this kind of abnormal smells from the patient cannot be simulated out with essence or spice, therefore extract with a small amount of test medicine crude drug the volatile oil obtained is sprayed in simulant granule, to simulate the special odor of JINGFUKANG KELI after ethanol dilution.
The preparation method of volatile oil is: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes (JINGFUKANG KELI volatile oil is drawn flavour of a drug); make coarse powder; equal proportion mixes; add water 8 times amount; flood 1 hour; vapor distillation extracts volatile oil (yield about 0.3%) in 6 hours, is separated volatile oil, and another device shading low temperature seal is preserved.
In JINGFUKANG KELI simulant, volatile oil content is 0.15ml/kg, maximum day taking dose be 3 μ l, because volatile oil consumption is little, do not reach pharmacology response concentration or effect more weak, therefore can not have influence on the judgement to test medicine clinical efficacy.In addition, the method is adopted can also to cover the burnt odor taste of burnt sugar coloring.This product is pressed the aromatic simulation of solution special odor (after solid and the impulsive motion) and is used in simulant.
In sum, the raw and auxiliary material that JINGFUKANG KELI simulant of the present invention uses is without incompatibility, and safety is good.For harm can not be produced to health during clinical trial, obvious adverse reaction can not be produced; To trial drug indication without obvious therapeutic action, the observation to trial drug effectiveness can not be disturbed.
embodiment 2
The formula of a kind of JINGFUKANG KELI simulant of the present invention is by mass percentage:
Dextrin 59.60%, spray-dried lactose 28.60%, beta-schardinger dextrin-5.20%, burnt sugar coloring 0.73%(are with solids basis), sodium copper chlorophllin 0.001%, lemon yellow 0.050%, Folum Ilicis extract 4.43%(be with solids basis), 6% starch slurry 0.50%(is with starch gauge used), lightweight magnesium stearate 0.874%, volatile oil 0.015%.
The preparation method of a kind of JINGFUKANG KELI simulant of the present invention comprises the following steps:
(1) preparation of volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder, wait mass ratio to mix, add water 8 times amount, floods 1 hour, and vapor distillation extracts volatile oil (yield about 0.3%) in 6 hours, be separated volatile oil, another device shading low temperature seal is preserved.
(2) the concrete preparation method of Folum Ilicis extract: get Folium Ilicis, decoct with water 3 times, decocting time is respectively 1 hour, 1 hour and 45 minutes, add water 8 times amount at every turn, collecting decoction, filters, be evaporated to relative density 1.17(50 DEG C), its solid content about 45%, to obtain final product.Conversion ratio: every 1g Folum Ilicis extract is equivalent to 0.91g Folium Ilicis.
(3) the concrete preparation method of starch slurry: get starch, first add a small amount of water dissolution, then add boiling water punching, being stirred to the bright mass percentage of starch that makes is 6%.
(4) get sodium copper chlorophllin and the lemon yellow 60 of formula ratio, be added in the water of 50 DEG C ~ 60 DEG C, stirring and dissolving, prepare the hybrid pigment aqueous solution that mass percentage is 10%.
(5) dextrin of formula ratio, lactose and beta-schardinger dextrin-is got, after mix homogeneously, carry out secondary mixing (each 20-30min of rotating) again, can mixing of materials be made like this evenly), slowly at the uniform velocity add Folum Ilicis extract prepared by burnt sugar coloring hot water diluent and step (2), mix homogeneously, obtains elementary mixing liquid; Described burnt sugar coloring hot water diluent method for making is heating water 70 ~ 80 DEG C, and being diluted to mass percent is 75%(w/w) solution, cool, for subsequent use.Face used time preparation.Burnt sugar coloring diluent relative density is about 1.055(20 DEG C).Because commodity burnt sugar coloring is pitchy thick liquid, solid content about 40%, if directly add in mixed powder, then not easily disperses, and causes granule color flower.For head it off, need to burnt sugar coloring thin up.
(6) in the elementary mixing liquid obtained in step (5), add the hybrid pigment aqueous solution that step (4) obtains, appropriate mass percentage be 55% ethanol (in pharmaceutics, ethanol is wetting agent, need to determine addition according to granulation, ethanol is volatile, and the amount of time on ethanol of granulation has impact) and the starch slurry that obtains of step (3), prepare soft material after mixing, granulate with 14 mesh sieves, in 55 DEG C ~ 60 DEG C dryings, 10 ~ 60 mesh sieve granulate, prepare dried particles; First should blow 30 ~ 45min with cold wind during particle drying, prevent soluble pigment in particle drying procedures from moving to particle surface, form mottle.When preparing soft material, ethanol should spray evenly, granulates fast, prevents because ethanol volatilization causes granule color and luster uneven and produce stiff granule.
(7) evenly spray into 2% volatile oil alcoholic solution mixing in the dried particles obtained in step (6), airtight placement 8 hours, then the lightweight magnesium stearate adding formula ratio, mixing, makes granule, can obtain the simulant of Chinese medicinal granule pharmaceutical composition.The compound method of 2% volatile oil alcoholic solution is: 0.2ml volatile oil adds 95% ethanol to 10ml, stirs evenly, to obtain final product.
The dry powder raw material that in simulant of the present invention, quality accounting is larger is dextrin, lactose and beta-schardinger dextrin-, wherein dextrin loss on drying < 10%, lactose < 1.0%(80 DEG C; Adsorbed water), beta-schardinger dextrin-< 14%; Its maximum basic water content about 6.97%.
In burnt sugar coloring water diluent water content conversion be about 1.72%, convert water content 4.88% in Folium Ilicis, convert in the hybrid pigment aqueous solution of 10% water content be 0.19%, 6% starch slurry conversion water content be 10.0%, amount to water content be 16.79%.Add the maximum basic water content total of above-mentioned dry powder and be about 23.76%.Consider the character of institute's spent material, this water content just leaves leeway to adding of 55% ethanol when soft material processed, and it is excessively wet, excessively loose, excessively glutinous to be unlikely to soft material, cannot granulate.
embodiment 3
The formula of a kind of JINGFUKANG KELI simulant of the present invention is by mass percentage:
Dextrin 58.43%, spray-dried lactose 30.00%, beta-schardinger dextrin-5.20%, burnt sugar coloring 0.73%(are with solids basis), sodium copper chlorophllin 0.002%, lemon yellow 0.050%, Folum Ilicis extract 4.00%(be with solids basis), 6% starch slurry 1.00%(is with starch gauge used), lightweight magnesium stearate 0.568%, volatile oil 0.020%.
The preparation method of a kind of JINGFUKANG KELI simulant of the present invention comprises the following steps:
(1) preparation of volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder, wait mass ratio to mix, add water 8 times amount, floods 1 hour, and vapor distillation extracts volatile oil (yield about 0.3%) in 6 hours, be separated volatile oil, another device shading low temperature seal is preserved.
(2) the concrete preparation method of Folum Ilicis extract: get Folium Ilicis, decoct with water 3 times, decocting time is respectively 1 hour, 1 hour and 45 minutes, add water 8 times amount at every turn, collecting decoction, filters, be evaporated to relative density 1.1(50 DEG C), its solid content about 44%, to obtain final product.Conversion ratio: every 1g Folum Ilicis extract is equivalent to 0.91g Folium Ilicis.
(3) the concrete preparation method of starch slurry: get starch, first add a small amount of water dissolution, then add boiling water punching, being stirred to the bright mass percentage of starch that makes is 6%.
(4) get sodium copper chlorophllin and the lemon yellow 60 of formula ratio, be added in the water of 50 DEG C ~ 60 DEG C, stirring and dissolving, prepare the hybrid pigment aqueous solution that mass percentage is 5%.
(5) dextrin of formula ratio, lactose and beta-schardinger dextrin-is got, after mix homogeneously, carry out secondary mixing (each 20-30min of rotating) again, can mixing of materials be made like this evenly), slowly at the uniform velocity add Folum Ilicis extract prepared by burnt sugar coloring hot water diluent and step (2), mix homogeneously, obtains elementary mixing liquid; Described burnt sugar coloring hot water diluent method for making is heating water 70 ~ 80 DEG C, and being diluted to mass percent is 70%(w/w) solution, cool, for subsequent use.Face used time preparation.Burnt sugar coloring diluent relative density is about 1.055(20 DEG C).Because commodity burnt sugar coloring is pitchy thick liquid, solid content about 40%, if directly add in mixed powder, then not easily disperses, and causes granule color flower.For head it off, need to burnt sugar coloring thin up.
(6) in the elementary mixing liquid obtained in step (5), add the hybrid pigment aqueous solution that step (4) obtains, appropriate mass percentage be 55% ethanol (in pharmaceutics, ethanol is wetting agent, need to determine addition according to granulation, ethanol is volatile, and the amount of time on ethanol of granulation has impact) and the starch slurry that obtains of step (3), prepare soft material after mixing, granulate with 14 mesh sieves, in 55 DEG C ~ 60 DEG C dryings, 10 ~ 60 mesh sieve granulate, prepare dried particles; First should blow 30 ~ 45min with cold wind during particle drying, prevent soluble pigment in particle drying procedures from moving to particle surface, form mottle.When preparing soft material, ethanol should spray evenly, granulates fast, prevents because ethanol volatilization causes granule color and luster uneven and produce stiff granule.
(7) evenly spray into 2% volatile oil alcoholic solution mixing in the dried particles obtained in step (6), airtight placement 8 hours, then the lightweight magnesium stearate adding formula ratio, mixing, makes granule, can obtain the simulant of Chinese medicinal granule pharmaceutical composition.The compound method of 2% volatile oil alcoholic solution is: 0.2ml volatile oil adds 95% ethanol to 10ml, stirs evenly, to obtain final product.
embodiment 4
The formula of a kind of JINGFUKANG KELI simulant of the present invention is by mass percentage:
Dextrin 59.90%, spray-dried lactose 29.00%, beta-schardinger dextrin-5.00%, burnt sugar coloring 0.70%(are with solids basis), sodium copper chlorophllin 0.001%, lemon yellow 0.041%, Folum Ilicis extract 3.36%(be with solids basis), 6% starch slurry 1.00%(is with starch gauge used), lightweight magnesium stearate 0.988%, volatile oil 0.010%.
The preparation method of a kind of JINGFUKANG KELI simulant of the present invention comprises the following steps:
(1) preparation of volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder, wait mass ratio to mix, add water 8 times amount, floods 1 hour, and vapor distillation extracts volatile oil (yield about 0.3%) in 6 hours, be separated volatile oil, another device shading low temperature seal is preserved.
(2) the concrete preparation method of Folum Ilicis extract: get Folium Ilicis, decoct with water 3 times, decocting time is respectively 1 hour, 1 hour and 45 minutes, add water 8 times amount at every turn, collecting decoction, filters, be evaporated to relative density 1.3(50 DEG C), its solid content about 46%, to obtain final product.Conversion ratio: every 1g Folum Ilicis extract is equivalent to 0.91g Folium Ilicis.
(3) the concrete preparation method of starch slurry: get starch, first add a small amount of water dissolution, then add boiling water punching, being stirred to the bright mass percentage of starch that makes is 6%.
(4) get sodium copper chlorophllin and the lemon yellow 60 of formula ratio, be added in the water of 50 DEG C ~ 60 DEG C, stirring and dissolving, prepare the hybrid pigment aqueous solution that mass percentage is 15%.
(5) dextrin of formula ratio, lactose and beta-schardinger dextrin-is got, after mix homogeneously, carry out secondary mixing (each 20-30min of rotating) again, can mixing of materials be made like this evenly), slowly at the uniform velocity add Folum Ilicis extract prepared by burnt sugar coloring hot water diluent and step (2), mix homogeneously, obtains elementary mixing liquid; Described burnt sugar coloring hot water diluent method for making is heating water 70 ~ 80 DEG C, and being diluted to mass percent is 80%(w/w) solution, cool, for subsequent use.Face used time preparation.Burnt sugar coloring diluent relative density is about 1.055(20 DEG C).Because commodity burnt sugar coloring is pitchy thick liquid, solid content about 40%, if directly add in mixed powder, then not easily disperses, and causes granule color flower.For head it off, need to burnt sugar coloring thin up.
(6) in the elementary mixing liquid obtained in step (5), add the hybrid pigment aqueous solution that step (4) obtains, appropriate mass percentage be 55% ethanol (in pharmaceutics, ethanol is wetting agent, need to determine addition according to granulation, ethanol is volatile, and the amount of time on ethanol of granulation has impact) and the starch slurry that obtains of step (3), prepare soft material after mixing, granulate with 14 mesh sieves, in 55 DEG C ~ 60 DEG C dryings, 10 ~ 60 mesh sieve granulate, prepare dried particles; First should blow 30 ~ 45min with cold wind during particle drying, prevent soluble pigment in particle drying procedures from moving to particle surface, form mottle.When preparing soft material, ethanol should spray evenly, granulates fast, prevents because ethanol volatilization causes granule color and luster uneven and produce stiff granule.
(7) evenly spray into 2% volatile oil alcoholic solution mixing in the dried particles obtained in step (6), airtight placement 8 hours, then the lightweight magnesium stearate adding formula ratio, mixing, makes granule, can obtain the simulant of Chinese medicinal granule pharmaceutical composition.The compound method of 2% volatile oil alcoholic solution is: 0.2ml volatile oil adds 95% ethanol to 10ml, stirs evenly, to obtain final product.
embodiment 5
The performance of JINGFUKANG KELI simulant of the present invention is tested, specific as follows:
Prepare test agent in three batches (20131104,20131105,20131106) according to the method in embodiment 2, and its performance is tested.
(1) character:
The character specified under Chinese Pharmacopoeia version in 2010 " JINGFUKANG " item is: " this product is that yellowish-brown is to tan granule; Mildly bitter flavor ".The outward appearance of simulant and organoleptic attribute also should with basically identical by aids drug.Therefore, the character of JINGFUKANG KELI simulant order for: " this product is yellowish-brown to tan granule; Mildly bitter flavor.Outward appearance and organoleptic attribute should be similar to JINGFUKANG KELI.”
In this product three batches, test agent (20131104,20131105,20131106) is through inspecting compare with JINGFUKANG KELI three batches of commercial samples (390375,390290,390300), is yellowish-brown to tan granule; Mildly bitter flavor.The outward appearance of simulant and organoleptic attribute to by aids drug JINGFUKANG KELI similar (specifically see Fig. 1).
(2) differentiate:
As requested, simulant the least possiblely should add or not containing the material likely trial drug safety and efficacy being produced to interference, without obvious therapeutic action, should can not disturb the observation to trial drug effectiveness to trial drug indication used.Simulant should carry out the detection of chemical composition, and selected index components can accurately differentiate simulant manufactured goods, and can accurate response its not containing the chemical active ingredient identical with test medicine or component.
Be labeled chemical composition with puerarin under Chinese Pharmacopoeia version in 2010 " JINGFUKANG " assay item.And not containing flavour of a drug such as Radix Puerariaes in simulant, therefore content assaying method under selection " JINGFUKANG " item, detect whether containing Radix Puerariae or other Related Components in simulant, and with puerarin reference substance (purchased from National Institute for Food and Drugs Control, lot number: 110752-200912; Specification: 20mg/ props up.) and JINGFUKANG KELI as positive control, to distinguish simulant and JINGFUKANG KELI.
Discrimination method is as follows: get simulant of the present invention appropriate, porphyrize, accurately weighed 0.5g, put in tool plug conical flask, precision adds methanol 25ml, close plug, weighed weight, supersound process (power 160W, frequency 59KHz) 30 minutes, let cool, more weighed weight, the weight of less loss is supplied with methanol, shake up, get supernatant, filter, get filtrate, as simulant need testing solution.Get JINGFUKANG KELI appropriate, porphyrize, accurately weighed 0.5g, is made in the same way of JINGFUKANG KELI need testing solution.Separately get puerarin reference substance appropriate, accurately weighed, add methanol and make the solution of every 1ml containing 50 μ g, solution in contrast.Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 annex VD), take octadecylsilane chemically bonded silica as filler, with methanol-water-phosphoric acid (25:75:0.2) for mobile phase, determined wavelength is 250nm.The each 5 μ l of the above-mentioned three kinds of solution of accurate absorption respectively, injection liquid chromatography.In the chromatograph of record, the retention time of JINGFUKANG KELI main peak should be consistent with the retention time of reference substance main peak; In simulant chromatograph there is not corresponding chromatographic peak in retention time place corresponding to reference substance main peak.
As shown in Figure 2, in this product three batches, test agent (20131104,20131105,20131106) does not all detect puerarin.In the chromatograph of record, the retention time of JINGFUKANG KELI main peak is consistent with the retention time of reference substance main peak; In simulant chromatograph there is not corresponding chromatographic peak in retention time place corresponding to reference substance main peak.Illustrate under above-mentioned chromatographic condition, not to be correlated with flavour of a drug containing Radix Puerariae or by aids drug in simulant, can accurately distinguish simulant and by aids drug.
(3) check
Owing to being granule by aids drug JINGFUKANG KELI, therefore every regulation that JINGFUKANG KELI simulant inspection item is relevant under should meeting granule item (Chinese Pharmacopoeia version in 2010 annex I C).
moisturespecify under rules of preparations granule (Chinese Pharmacopoeia version in 2010 annex I C) item that moisture " measures according to aquametry (Chinese Pharmacopoeia version in 2010 annex Ⅸ H), must not cross 6.0% ".Lump within the shelf-life for preventing simulant, the problem such as deliquescence, regulation this product moisture must not cross 6.0%.
On inspection, the equal conformance with standard regulation of test agent (20131104,20131105,20131106) moisture in this product three batches.
granularityunder rules of preparations granule (Chinese Pharmacopoeia version in 2010 annex I C) item, designated size " measures according to granulometry (Chinese Pharmacopoeia version in 2010 annex Ⅺ B second method); not by No. 1 sieve and the summation of sieving by No. 5, must not cross 15.0% ".
On inspection, the equal conformance with standard regulation of test agent (20131104,20131105,20131106) granularity in this product three batches.
meltingunder rules of preparations granule (Chinese Pharmacopoeia version in 2010 annex I C) item, regulation granule should carry out melting inspection: " get test sample 1 bag; heating water 200ml, stir 5 minutes, observe immediately; should all to dissolve or in suspendible shape, mix suspension grain should be able to suspendible even." " granule checks as stated above, all must not have breeze etc.”
On inspection, the equal conformance with standard regulation of test agent (20131104,20131105,20131106) melting in this product three batches.
microbial limitunder rules of preparations granule (Chinese Pharmacopoeia version in 2010 annex I C) item, regulation granule should carry out limit test of microbe: " check according to microbial limit test (Chinese Pharmacopoeia version in 2010 annex Ⅹ III C), should conform with the regulations ".
This product not containing the oral Preparation inspection of the former powder of medical material, should meet following provisions: bacterial population with reference to microbial limit test (Chinese Pharmacopoeia version in 2010 annex Ⅹ III C): every 1g must not cross 1000cfu; Yeast and mold number: every 1g must not cross 100cfu; Escherichia coli: every 1g must not detect.
On inspection, the equal conformance with standard regulation of test agent (20131104,20131105,20131106) microbial limit in this product three batches.Concrete parameters is see table 4.
In table 4 JINGFUKANG KELI simulant, test agent checks data
heavy metalcheck according to heavy metal inspection technique (Chinese Pharmacopoeia version in 2010 annex Ⅸ E second method).This is the inspection of simulant general safety.
The main component material of simulant of the present invention is dextrin, lactose and beta-schardinger dextrin-, and Chinese Pharmacopoeia version in 2010 two regulation dextrin heavy metals must not cross 20/1000000ths, and beta-schardinger dextrin-must not cross 10/1000000ths, and lactose must not cross 5/1000000ths.Burnt sugar coloring standard regulation heavy metal (in Pb) must not cross 25mg/kg(25/1000000ths); Pigment total amount accounts for 0.019% of simulant, and volatile oil is 0.15%, and consumption is lower, can ignore; In Folium Ilicis medical material standard, heavy metal item is not specified.
Check according to heavy metal inspection technique (Chinese Pharmacopoeia version in 2010 annex Ⅸ E second method), in this product three batches, test agent (20131104,20131105,20131106) heavy metal is not all more than 10/1000000ths.
arsenic saltcheck according to arsenic salt inspection technique (Chinese Pharmacopoeia version in 2010 annex Ⅸ F first method).This is the inspection of simulant general safety.
The main component material of simulant of the present invention is dextrin, lactose and beta-schardinger dextrin-, and Chinese Pharmacopoeia version in 2010 two middle dextrin, lactose and beta-schardinger dextrin-arsenic salt limit all do not specify; Burnt sugar coloring standard regulation arsenic (in As) must not cross 1.0mg/kg(1,000,000/); Pigment total amount accounts for 0.019% of simulant, and volatile oil is 0.15%, and consumption is lower, can ignore; In Folium Ilicis medical material standard, arsenic salt is not specified.
Check according to arsenic salt inspection technique (Chinese Pharmacopoeia version in 2010 annex Ⅸ F first method), in this product three batches, test agent (20131104,20131105,20131106) arsenic salt is not all more than 2/1000000ths.
solution appearance and organoleptic attributebecause simulant need to be taken after mixing it with water use with hot water, the color of simulant aqueous solution must be similar to by aids drug JINGFUKANG KELI aqueous solution, otherwise have the probability of unblinding.
Its outward appearance and organoleptic attribute comprise solution colour, texture, taste, abnormal smells from the patient etc.
For making simulant compare under the same conditions with by aids drug, with reference to melting inspection method under rules of preparations granule (Chinese Pharmacopoeia version in 2010 annex I C) item, determine that hot water volume is 150ml.
In simulant of the present invention three batches, test agent (20131104,20131105,20131106) is through inspecting compare with JINGFUKANG KELI three batches of commercial samples (390375,390290,390300), is yellowish-brown to brown liquid; The outward appearances such as simulant solution texture, taste, abnormal smells from the patient and organoleptic attribute to by aids drug JINGFUKANG KELI similar (outward appearance contrasts specifically see Fig. 3).
stabilitysimulant removing inner packing of the present invention is placed 10 days at 60 DEG C of temperature or (4500lx ± 500lx) places 10 days under strong illumination condition, undertaken detecting (appearance character and organoleptic attribute, solution appearance and organoleptic attribute, moisture, melting) by stability high spot reviews project, the data of result and 0 day compare, indices changes without significance, points out simulant of the present invention to stablize high temperature or strong illumination.
Simulant removing inner packing of the present invention is in high humidity environment (relative humidity 92.5% ± 5%; 25 DEG C) place 10 days, carry out detecting (appearance character and organoleptic attribute, solution appearance and organoleptic attribute, moisture) by stability high spot reviews project, the data of result and 0 day compare, and moisture significantly raises, granule generation caking phenomenon, color burn.Point out simulant of the present invention easily moisture absorption under high humidity conditions.Illustrate that simulant of the present invention (25 DEG C, RH92.5%) under high humidity places 10 days instability.
Simulant of the present invention adopts composite film packaging (Biaxially oriented polypropylene/aluminising biaxial stretching polyester/polyvinyl medicine composite packing film), in high humidity environment (relative humidity 92.5% ± 5%; 25 DEG C) place 10 days under condition, except moisture slightly raises (non-overrun regulation), all the other indexs change without significance.Sealing and the moisture-resisting excellent effect of simulant packaging material of the present invention are described, sample moisture-proof stability in a short time under conditions of high humidity can be protected.
According to test agent (20131104,20131105,20131106) 24 months long term test study on the stability interpretation of result in simulant of the present invention three batches, it is 24 months that the shelf-life of simulant of the present invention fixes tentatively.
(3) fidelity evaluation
1. the blind of JINGFUKANG KELI and JINGFUKANG KELI simulant judges
For the emulator of checking JINGFUKANG KELI simulant, prevent unblinding in clinical research process and cause test failure, again need evaluate (blind) clinical research JINGFUKANG KELI simulant, independent the making simulant sample and test medicine of evaluation and test person is allowed to compare and to judge, assessment simulant emulator.
Assessment sample:
1. clinical research JINGFUKANG KELI simulant integral packaging 2 large (1 batch);
2. clinical research JINGFUKANG KELI integral packaging 2 large (1 batch).
Evaluation and test person is made up of (having neither part nor lot in simulant to study and preparation person) 10 people, man, each 5 people of female, and the age is between 18 ~ 55 years old; Everyone is independent (often organizes 4 increment product to evaluation and test thing; 2 parts is test medicine, and 2 parts is simulant, random number; Blind result is established in explanation) carry out identification.Requiring that evaluation and test person is from solution characteristics aspect after sample particle surface character, particle characteristic and impulsive motion, is that to make subjective be non-judgement for test medicine or simulant to evaluation and test sample.Being prepared as of solution: get above-mentioned sample and tear aluminium plastic packaging bag, by clean for granule tasteless transparent vessel, heating water 150ml, stirs 5 minutes, observe and decide immediately respectively.Result is as shown in table 5.
The blind of table 5 test medicine and simulant judges statistical table
Adopt test of goodness of fit (Goodness-ofFitTest) statistical analysis, judge that all judges are judged as whether being set up by aids drug or the consistent hypothesis of simulant ratio.Set up if suppose, then reflecting judge has and is used as simulant by the tendency of aids drug.Otherwise simulant is with by aids drug, there were significant differences.
Result display X
2=0.922, P=0.631>0.0005, not statistically significant, judges that all judges are judged as that test medicine or the consistent hypothesis of simulant ratio set up.
2. the comparison of formulation consistency
Evaluation and test person is made up of (identical with trial drug exterior and interior packing tag compliance evaluation and test person with simulant) 10 people, man, female half and half, and the age is between 18 ~ 55 years old; After everyone independent content (granule) outward appearance to test medicine JINGFUKANG KELI and JINGFUKANG KELI simulant and content (granule) organoleptic feature and the impulsive motion that adds water, (utilizing vision, sense of touch, taste and smell to mark) is evaluated and tested and marked to the concordance of organoleptic feature, require that evaluation and test person gets test medicine or each 1 bag of simulant, tear aluminium plastic packaging bag, to clean tasteless and in the transparent vessel of same size, heating water 150ml respectively, stir 5 minutes, observe immediately, evaluate and test its outward appearance and organoleptic feature concordance.
scoring design: completely the same scoring=3; Basically identical scoring=2; Obvious difference scoring=1; Complete inconsistent scoring=0.
result judges: projects evaluation and test average score is greater than 2 for basically identical, and projects evaluation and test average score is less than 2 for obvious difference.If occur in each subitem, more than 1 and 1 average score is less than 2, be then considered as obvious difference.
Result judges that the scoring of each project is all greater than 2, for basically identical.Specifically see table 6.
Table 6 JINGFUKANG simulant and JINGFUKANG KELI formulation consistency grade form
。
Last it is noted that the foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although with reference to previous embodiment to invention has been detailed description, for a person skilled in the art, it still can be modified to the technical scheme described in foregoing embodiments, or carries out equivalent replacement to wherein portion of techniques feature.Within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (8)
1. a JINGFUKANG KELI simulant, it is characterized in that: described simulant is prepared from by each component of following mass percent: dextrin 58.00-60.00%, spray-dried lactose 27.60-30.00%, beta-schardinger dextrin-5.00-5.20%, burnt sugar coloring 0.70-0.73%(is with solids basis), sodium copper chlorophllin 0.001-0.002%, lemon yellow 0.040-0.050%, Folum Ilicis extract 3.36-4.43%(is with solids basis), 6% starch slurry 0.50-1.00%(is with starch gauge used), lightweight magnesium stearate 0.500-1.000%, volatile oil 0.010-0.020%, the mass percent sum of each component is 100%.
2. a kind of JINGFUKANG KELI simulant according to claim 1, is characterized in that: described simulant is prepared from by each component of following mass percent: dextrin 59.60%, spray-dried lactose 28.60%, beta-schardinger dextrin-5.20%, burnt sugar coloring 0.73%(are with solids basis), sodium copper chlorophllin 0.001%, lemon yellow 0.050%, Folum Ilicis extract 4.43%(be with solids basis), 6% starch slurry 0.50%(is with starch gauge used), lightweight magnesium stearate 0.874%, volatile oil 0.015%.
3. a kind of JINGFUKANG KELI simulant according to claim 1 and 2, it is characterized in that: the preparation method of described Folum Ilicis extract is: get Folium Ilicis and decoct with water, concentrate filtrate to relative density 1.10-1.30(50 DEG C), solid content is 44-46%, to obtain final product.
4. a kind of JINGFUKANG KELI simulant according to claim 1 and 2, is characterized in that: the preparation method of described volatile oil is: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder, mix Deng mass ratio, after adding water retting, vapor distillation extracts, and obtains volatile oil.
5. the preparation method of the arbitrary described JINGFUKANG KELI simulant of claim 1-4, is characterized in that: step is as follows:
(1) prepare volatile oil: get Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, the Myrrha five tastes, make coarse powder and mix, after adding water retting, vapor distillation extracts, and obtains volatile oil;
(2) Folum Ilicis extract is prepared: get Folium Ilicis and decoct with water, concentrate filtrate to relative density 1.10-1.30(50 DEG C), now solid content is 44-46%, obtains Folum Ilicis extract;
(3) prepare starch slurry: get starch, first add a small amount of water dissolution, then add boiling water punching, be stirred to bright, make the mass percentage of starch be 6%;
(4) prepare hybrid pigment aqueous solution: sodium copper chlorophllin and the lemon yellow 60 of getting formula ratio, be added in the water of 50 DEG C ~ 60 DEG C, stirring and dissolving, prepare the hybrid pigment aqueous solution that mass percentage is 5-15%;
(5) prepare burnt sugar coloring hot water diluent: the hot water adding 70 ~ 80 DEG C in burnt sugar coloring, being diluted to mass percent is 70-80% solution, to obtain final product;
(6) elementary mixing liquid is prepared: get the dextrin of formula ratio, lactose and beta-schardinger dextrin-, after mix homogeneously, then carry out secondary mixing, add burnt sugar coloring hot water diluent prepared by step (5) and Folum Ilicis extract prepared by step (2), mix homogeneously, obtains elementary mixing liquid;
(7) in the elementary mixing liquid obtained in step (6), add the hybrid pigment aqueous solution that step (4) obtains, appropriate mass percentage be 55% ethanol and the starch slurry that obtains of step (3), prepare soft material after mixing, obtain dried particles through post processing;
(8) spray into 2% volatile oil alcoholic solution mixing in the dried particles prepared in step (7), add the lightweight magnesium stearate of formula ratio after airtight placement again, mixing, makes granule, to obtain final product.
6. method according to claim 5, is characterized in that: Rhizoma Chuanxiong, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Olibanum, Myrrha described in step (1) such as are at the mass ratio mixing.
7. method according to claim 5, is characterized in that: decocting with water described in step (2) is decoct with water 3 times, and decocting time is respectively 1 hour, 1 hour and 45 minutes, and add water 8 times amount at every turn.
8. method according to claim 5, is characterized in that: described in step (8), the preparation method of 2% volatile oil alcoholic solution is: the volatile oil of 0.2 volume is added 95% ethanol to 10 volume, stir evenly, to obtain final product.
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| 罗丹: "中药颗粒剂的安慰剂评价及制备工艺研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
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