CN101406683A - Chinese medicine compound and preparation method thereof - Google Patents
Chinese medicine compound and preparation method thereof Download PDFInfo
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- CN101406683A CN101406683A CNA2007101639370A CN200710163937A CN101406683A CN 101406683 A CN101406683 A CN 101406683A CN A2007101639370 A CNA2007101639370 A CN A2007101639370A CN 200710163937 A CN200710163937 A CN 200710163937A CN 101406683 A CN101406683 A CN 101406683A
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Abstract
The invention belongs to the technical field of traditional Chinese medicine and discloses a traditional Chinese medicine composition and a preparation method thereof. The prescription of the traditional Chinese medicine composition is as follows: 5 to 8 weight portions of rhizoma atractylodis, 5 to 8 weight portions of Magnolia officinalis, 5 to 8 weight portions of peony, 5 to 8 weight portions of dried orange peel, 5 to 8 weight portions of umbellate pore furgus, 5 to 8 weight portions of Alisma orientale, 5 to 8 weight portions of Atractylis ovata, 5 to 8 weight portions of Tuckahoe, 4 to 6 weight portions of Chinese cinnamon, 1 to 3 weight portions of date, 1 to 3 weight portions of ginger, and 1 to 3 weight portions of liquorice. The preparation method comprises the following steps: the medicinal materials are added with water for boiling for 2 to 4 times, 0.5 to 3 hours each time; decoctions are mixed, filtered and then condensed to obtain a liquid extract; and a pharmaceutical preparation is prepared by adding auxiliary materials and then pelletizing by a fluidized bed. To better embody the soul of traditional Chinese medicine, the method proposes that the traditional Chinese medicine composition is prepared by extracting medicines by water and combining modern concentration and pelleting processes according to the guiding theory of observing the traditional Chinese medicine, and summarizes technological parameters and applicable auxiliary materials of the preparation which are optimally matched with the traditional Chinese medicine composition. The preparation method furthest reserves the experience accumulation of the traditional Chinese medicine, and can also adapt to the fast-paced modern preparation form in modern society.
Description
[technical field]
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of Chinese medicine composition and preparation method thereof.
[background technology]
In recent decades, the production of Chinese herbal medicine has realized mechanization and semi-mechanization to a certain degree.Chinese medicine often is considered to that active constituent content is low, impurity is many, quality is unstable, so medication is based upon on the empirical basis more, can not integrate with modern medicine.For addressing this problem, Chinese medicine must be walked the road of extraction and purification.The extraction of Chinese medicine comprises many unit operationss such as leaching, clarification, filtration and evaporation.
As most important active component in the Radix Glycyrrhizae, glycyrrhizin has functions such as detoxifcation, dental caries, anti-inflammatory.Glycyrrhizin does not have haemolysis, thereby stops hemolysin close to erythrocyte because it can absorb hemolysin by erythrocyte surface, can be used for treating chronic hepatitis B.
Peoniflorin have resist myocardial ischemia, the anticoagulant effect; Spasmolysis; Analgesia, sedation; Antiinflammatory, antiulcer action; Hepatoprotective effect; Regulate immunity; Resisting oxygen lack etc.The peoniflorin clinical practice is used for the treatment of coronary heart disease; Be used for Senile disease, can make ancillary drug in aspect, the especially treatments of senile chronic respiratory tract disease such as health invigorating and immunologic function, antiinflammatory cough-relieving, eliminating phlegm and relieving asthma.
[summary of the invention]
The preparation method that the purpose of this invention is to provide a kind of new Chinese medicine composition.Basis of the present invention prescription derives from Chinese medicine composition.
Chinese medicine composition of the present invention, its prescription consists of: Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, each 5-8 weight portion of Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi) 4-6 weight portion, Fructus Jujubae, Rhizoma Zingiberis Recens, each 1-3 weight portion of Radix Glycyrrhizae.
Wherein the prescription of You Huaing is: Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, each 6 weight portion of Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi) 5 weight portions, Fructus Jujubae, Rhizoma Zingiberis Recens, each 2 weight portion of Radix Glycyrrhizae.
Preparation method of the present invention is: above-mentioned Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi), Fructus Jujubae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae are decocted with water 2-4 time, each 0.5-3 hour, merge decocting liquid, filter the back concentrate fluid extract, add behind the adjuvant with behind the fluidized bed granulation useful in preparing drug formulations.
The proportion of above-mentioned fluid extract is 1.10-1.35, preferred 1.12-1.30.
Above-mentioned decocting liquid can carry out centrifugation earlier, gets clarifying decocting liquid, and centrifugal rotation speed is 1500-20000 rev/min, and preferred 1500-10000 rev/min, more preferably 2000-8000 rev/min, most preferably 3000-5000 rev/min.
Above-mentioned decocting liquid can adopt the method for membrane filtration to filter.
Above-mentioned membrane filtration comprises one of filter method of employing ultrafiltration and nanofiltration or ultrafiltration and nanofiltration is used in combination.
Above-mentioned ultrafilter membrane is selected from cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile-cellulose diacetate blend film, the dynamic ultrafilter membrane that forms, one of and the Modified Membrane of above-mentioned film, its molecular retention amount is below the 6000-10000.
The filter membrane aperture of above-mentioned ultrafiltration is: the 0.22-0.45 micron.
The membrane ultrafiltration device that above-mentioned ultrafiltration is adopted can be commercial doughnut or plate ultrafilter membrane separator.
Above-mentioned NF membrane molecular retention amount is 500-2000, preferred 500-1000, more preferably 700-1000.
The process of above-mentioned membrane filtration preferably with the process ultrafiltration earlier of decocting liquid, is carried out nanofiltration again.
Above-mentioned adjuvant is selected from microcrystalline Cellulose, powdery cellulose, mannitol, starch, lactose, gelatin, methylcellulose, dextrin, pregelatinized Starch, micropowder silica gel, hydroxypropyl methylcellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, Polyethylene Glycol, xylitol, lactose, glucose, glycine, mannitol, tartaric acid, silicon dioxide, one or more in calcium stearate and the magnesium stearate.
The said medicine preparation comprises granule, tablet, capsule, powder, drop pill.
The at present used extracting technique of Chinese medicine compound recipes that adopt certain density ethanol extraction Chinese medicine more, help reclaiming solvent like this and reduce impurity, but the method that adopts alcohol extraction has deviated from the experience accumulation of the treatment disease of Chinese medicine since 3000, has ignored for the purpose that can arrive " quality controllable " comparatively simply under the guiding theory of " modernization of Chinese medicine " " effectiveness " even " safety ".
In sum, the hysteresis of Chinese medicine extraction separating technology development becomes the bottleneck of traditional Chinese medicine development and existence, must be optimized, reform and strengthen original technology.The reinforcement technique of chemical separating and mass transfer will provide strong assurance for this reason, and realization Chinese medicine subject intersects with Chemical Engineering, will help realizing the modernization of Chinese medicine production equipment.With the Chinese medicine extraction separation process that induces one of notion, the theory of Chemical Engineering.Utilize available research achievements,,, technological process, production equipment, operating condition are done modernization overlay and careful groping, provided feasible scheme from basic influence factor's research staff in conjunction with the concrete condition that Chinese medicine is produced.
In order to return the marrow of traditional medicine treatment disease, the present invention proposes the guiding theory according to " abiding by Gu " with Chinese medicine composition classics side, use the water extraction medicine, concentrated, granulating process in conjunction with modern have summed up the preparation process parameter and the suitable adjuvant that mate the most with Chinese medicine composition.Kept the experience accumulation of traditional medicine to greatest extent, and it is allegro as dosage forms such as tablet, capsule, granule, powder, drop pills to adapt to modern society.
Guaranteed the stable content of peoniflorin and glycyrrhizin among the present invention, for the standardization production of preparation is laid a good foundation.By realization of the present invention, can be under the prerequisite that the effective ingredient in the Chinese medicine composition is extracted to greatest extent, reducing in the extract macromolecular substances such as impurity such as tannin, polyphenol, resin, protein, phlegmatic temperament and solid particle effectively removes, keep the active ingredient in the Chinese medicine preparation of the present invention, for the preparation of oral drug preparation is provided convenience.
[specific embodiment]
Following embodiment further describes the present invention, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.Following examples Chinese crude drug unit of feeding intake is gram.
| Embodiment | Rhizoma Atractylodis | Cortex Magnoliae Officinalis | Radix Paeoniae | Pericarpium Citri Reticulatae | Polyporus | Rhizoma Alismatis | The Rhizoma Atractylodis Macrocephalae | Poria | Cortex cinnamomi japonici (Ramulus Cinnamomi) | Fructus Jujubae | Rhizoma Zingiberis Recens | Radix Glycyrrhizae |
| Embodiment 1 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 2 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 3 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 40 | 40 | 40 | 10 |
| Embodiment 4 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 60 | 60 | 60 | 30 |
| Embodiment 5 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 60 | 60 | 60 | 30 |
| Embodiment 6 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 7 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 8 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 40 | 40 | 40 | 10 |
| Embodiment 9 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 60 | 60 | 60 | 30 |
| Embodiment 10 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 60 | 60 | 60 | 30 |
| Embodiment 11 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 12 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 60 | 50 | 50 | 50 | 20 |
| Embodiment 13 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 40 | 40 | 40 | 10 |
| Embodiment 14 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 60 | 60 | 60 | 30 |
| Embodiment 15 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 60 | 60 | 60 | 30 |
Embodiment 1
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 2 hours, amount of water was 12 times of medical material, merge the water extract, filter decompression and solvent recovery, get fluid extract (proportion is 1.13-1.18), add adjuvant boiling granulating in fluid bed, promptly get granular preparation of the present invention.
Embodiment 2
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 2 hours, amount of water was 8 times of medical material, merge the water extract, filter, decompression and solvent recovery gets fluid extract (proportion is 1.12-1.21), add adjuvant boiling granulating in fluid bed, encapsulated, promptly obtain capsule preparations of the present invention.
Embodiment 3
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 2 hours, amount of water was 10 times of medical material, merged the water extract, filter, decompression and solvent recovery gets fluid extract (proportion is 1.10-1.19), adds adjuvant boiling granulating in fluid bed, add the adjuvant tabletting, promptly obtain tablet of the present invention.
Embodiment 4
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 3 hours, amount of water was 10 times of medical material, merge the water extract, filter, decompression and solvent recovery gets fluid extract (proportion is 1.20-1.26), add adjuvant boiling granulating in fluid bed, add vegetable oil substrate, pill promptly obtains drop pill of the present invention.
Embodiment 5
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 2.5 hours, amount of water was 10 times of medical material, merge the water extract, filter, decompression and solvent recovery gets fluid extract (proportion is 1.19-1.25), add adjuvant boiling granulating in fluid bed, add 800 gram vegetable oil, mix homogeneously promptly obtains soft capsule of the present invention with being pressed into soft capsule after the colloid mill grinding.
Embodiment 6
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 1.5 hours, amount of water was 10 times of medical material, merge the water extract, filter, decompression and solvent recovery gets fluid extract (proportion is 1.20-1.24), add adjuvant boiling granulating in fluid bed, pulverize, promptly obtain powder of the present invention.
Embodiment 7
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 2 hours, amount of water was 6 times of medical material, merged the water extract, filtered, and filtrate is 8000 three cellulose acetate membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 500 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.85 times of former ultrafiltrate, get fluid extract (proportion is 1.18-1.25), add adjuvant boiling granulating in fluid bed, promptly get granular preparation of the present invention.
Embodiment 8
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 2 hours, amount of water was 8 times of medical material, merged the water extract, filtered, and filtrate is 6000 cyanoethyl cellulose membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 500 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.8 times of former ultrafiltrate, get fluid extract (proportion is 1.25-1.34), add adjuvant boiling granulating in fluid bed, encapsulated, promptly obtain capsule preparations of the present invention.
Embodiment 9
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 2 hours, amount of water was 6 times of medical material, merged the water extract, filtered, and filtrate is 10000 polysulfone membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 500 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.75 times of former ultrafiltrate, get fluid extract (proportion is 1.28-1.35), add adjuvant boiling granulating in fluid bed, add the adjuvant tabletting, promptly obtain tablet of the present invention.
Embodiment 10
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 3 hours, amount of water was 10 times of medical material, merged the water extract, filtered, and filtrate is 6000 SPSF membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 1000 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.7 times of former ultrafiltrate, get fluid extract (proportion is 1.26-1.30), add adjuvant boiling granulating in fluid bed, add vegetable oil substrate, pill promptly obtains drop pill of the present invention.
Embodiment 11
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times with water extraction, each 2.5 hours, amount of water was 10 times of medical material, merged the water extract, filtered, and filtrate is 8000 poly (ether sulfone) film ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 2000 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.75 times of former ultrafiltrate, get fluid extract (proportion is 1.21-1.32), add adjuvant boiling granulating in fluid bed, add 200 gram vegetable oil, mix homogeneously promptly obtains soft capsule of the present invention with being pressed into soft capsule after the colloid mill grinding.
Embodiment 12
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times with water extraction, each 1.5 hours, amount of water was 10 times of medical material, merged the water extract, filtered, and filtrate is 6000 sulfonated polyether sulfone membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.It is to handle in 500 the rolling nanofiltration device that ultrafiltration gained filtrate is selected molecular cut off for use through system, wherein the nanofiltration amount of water can be controlled in about 0.65 times of former ultrafiltrate, get fluid extract (proportion is 1.28-1.34), add adjuvant boiling granulating in fluid bed, pulverize, promptly obtain powder of the present invention.
Embodiment 13
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times each 2 hours with water extraction, amount of water is 8 times of medical material, merges the water extract, centrifugal (rotating speed is 2000 rev/mins), filter, filtrate is 6000 three cellulose acetate membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.Ultrafiltration gained filtrate decompression reclaims solvent, gets fluid extract (proportion is 1.12-1.25), adds adjuvant boiling granulating in fluid bed, promptly gets granular preparation of the present invention.
Embodiment 14
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 3 times each 2 hours with water extraction, amount of water is 8 times of medical material, merges the water extract, centrifugal (rotating speed is 2500 rev/mins), filter, filtrate is 8000 cyanoethyl cellulose membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.Ultrafiltration gained filtrate decompression reclaims solvent, gets fluid extract (proportion is 1.17-1.24), adds adjuvant boiling granulating in fluid bed, and is encapsulated, promptly obtains capsule preparations of the present invention.
Embodiment 15
Take by weighing the pulverizing medicinal materials of recipe quantity, decoct 2 times each 2 hours with water extraction, amount of water is 8 times of medical material, merges the water extract, centrifugal (rotating speed is 5000 rev/mins), filter, filtrate is 6000 polysulfone membrane ultrafiltration with molecular cut off, filter type employing cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1 MPa, and low 0.5 kPa of the liquid outlet pressure ratio inlet pressure of ultrafiltration progressively boosts during ultrafiltration.In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1 MPa.Ultrafiltration gained filtrate decompression reclaims solvent, gets fluid extract (proportion is 1.18-1.30), adds adjuvant boiling granulating in fluid bed, adds the adjuvant tabletting, promptly obtains tablet of the present invention.
Determining of the amount of experimental example 1-dry extract of the present invention
Embodiment 1-15 fluid extract with among the present invention does not add adjuvant, and directly lyophilization obtains dry extract, data such as following table 1:
The data of the amount of table 1 dry extract of the present invention
By realization of the present invention, can be under the prerequisite that the effective ingredient in the Chinese medicine composition of the present invention is extracted to greatest extent, reducing in the extract macromolecular substances such as impurity such as tannin, polyphenol, resin, protein, phlegmatic temperament and solid particle effectively removes, the active ingredient that keeps medicine is for the preparation of oral drug preparation is provided convenience.
Experimental example 2-carries out the liquid phase analysis research of Chinese medicine composition with high performance liquid chromatograph
One, materials and methods
(1), experimental drug
Standard substance peoniflorin that this research is used and glycyrrhizin are available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
(2), instrument and equipment and experiment condition
1. instrument and equipment
Liquid phase pump: Applied Biosystems (ABI) 400 * 2
Injection valve: Rheodyne Type 7125 (10 μ L loop)
The automatic gradient controller of mobile phase controller: ABI
Detector: ABI 1000s photodiode array detector
2. analysis condition
Pre-column: μ-Bondapak TMC18 (Millipore, Milford, MA, USA)
Chromatographic column: Cosmosil 5C18-MS, 5 μ m, 25cm * 4.6mm (Nacalai Tesque, Kyoto, Japan)
Mobile phase: (A) 0-50 mM/rise KH2PO4 is adjusted to pH 2.5-6.5 with 5%H3PO4
(B)H2O/CH3CN：30/70-10/90(V/V)
Flow velocity: 1.0 ml/min
Detect wavelength: 230nm
Gradient elution program: as table 1
(3), experimental technique
1. the discussion of the mobile phase of different salt densities
With optimal chromatographic column, in mobile phase (A), use respectively 0,10,20,30,40 and 50 mMs/liter potassium dihydrogen phosphate, analyze with the gradient elution program of table 1, each group repeats biphasic injection.
Table 1 is analyzed the gradient elution program of Chinese medicine composition
2. the discussion of the mobile phase of different pH-values
With the biphosphate potassium concn of optimization, in mobile phase (A), add not commensurability 5% phosphoric acid or ammonia, the buffer solution of preparation different pH values, pH value is respectively 2.5,3.5,4.5,5.5 and 6.5, and each organizes repetitive operation twice.
3. the discussion of the mobile phase of different acetonitrile ratios
Because the adding of salt, mobile phase (B) must contain an amount of water, separates out to prevent salt, and obtains more smooth baseline, therefore prepares the mobile phase of different water/acetonitrile ratio, is respectively 30/70,25/75,20/80,15/85 and 10/90.Select the buffer solution condition of above-mentioned optimization to analyze, twice of every group of repetitive operation.
4. prepare standard solution and production standard curve
(1) gets 10.0 milligrams BPB (n-butyl p-hydroxy benzoate) and be dissolved in 10 milliliters 70% methanol aqueous solution, as internal standard product (IS) solution.Take by weighing 10.0 milligrams peoniflorin and glycyrrhizin respectively, be made into 20 milliliters of standard substance mother solutions with 70% methanol aqueous solution.Every kind of standard substance mother solution got 5,2,1,0.5,0.1 and 0.05 milliliters again and placed measuring bottle then, adds 1 milliliter of internal standard product solution separately, is made into 10 milliliters of standard solutions with 70% methanol aqueous solution at last.With above-mentioned optimization condition, each concentration repeats double injection, injects 10 microlitres at every turn, gets its meansigma methods production standard curve.
(2) precision takes by weighing the Chinese medicine composition powder of 1.0 grams, with 20 milliliters of 70% methanol aqueous solutions as extractant, ultrasound concussion 30 minutes, centrifugal filtration, triplicate, combining extraction liquid is concentrated into 10 milliliters.Get in 5 milliliters of concentrated solution to 10 milliliter measuring bottles, add 1 milliliter of internal standard product solution, be diluted to 10 milliliters with 70% methanol aqueous solution.Use 0.45 μ m filter to filter,, repeat double injection, inject 10 microlitres at every turn, average as analysis result as quantitative inspection liquid.
(4), the suitability of analysis condition assessment
1. repeatability
Get 2.0 milliliters of standard substance mother solutions to measuring bottle, add 1.0 milliliters of internal standard product solution, be diluted to 10.0 milliliters, as inspection liquid with 70% methanol aqueous solution.Repeat six injections on the same day, do not amount on the same day and repeat six injections, inject 10 microlitres at every turn.
2. the response rate
Precision takes by weighing 1.0 gram Chinese medicine composition powder, with 20 milliliters of 70% methanol aqueous solutions, and as extractant, ultrasound concussion 30 minutes, centrifugal filtration, triplicate, combining extraction liquid is concentrated into 10 milliliters.Get 5.0 milliliters of concentrated solution to 10 milliliter measuring bottles, add 1.0 milliliters of standard substance mother solutions, add 1.0 milliliters of internal standard product solution again, be diluted to 10.0 milliliters with 70% methanol aqueous solution, after 0.45 μ m filter filters as quantitative inspection liquid.Repeat double injection, inject 10 microlitres at every turn, get the average result of double injection.
3. detectability
Dilution standard product solution progressively injects chromatographic column and detects, up to S/N than (signal to noise ratio) less than 3, calculate injection rate and concentration thereof.
4. the quantitative analysis of preparation composition
Precision takes by weighing 2.5 gram Chinese medicinal composition granules (embodiment 13), with 20 milliliters of 70% methanol aqueous solutions as extractant, ultrasound concussion 30 minutes, centrifugal filtration, triplicate, combining extraction liquid is concentrated into 10 milliliters.Get in 5 milliliters of concentrated solution to 10 milliliter measuring bottles, add 1 milliliter of internal standard product solution, be diluted to 10 milliliters, filter through 0.45 μ m filter, as quantitative inspection liquid with 70% methanol aqueous solution.Repeat double injection, inject 10 microlitres at every turn, get its meansigma methods.
Two, result and discussion
(1) discussion of analysis condition
For inquiring into the influence of phosphate, in mobile phase (A), add the phosphate of variable concentrations to resolution.Because higher salt density can reduce chromatographic column life-span and the loss that increases pump, so select the concentration of 30mM phosphate as mobile phase (A).
Next the pH value with solution is adjusted to 2.5,3.5,4.5,5.5 and 6.5 respectively.When pH value is 2.5 to 4.5, holdup time of index components be there is no evident difference.PH value is 2.5 o'clock, and chemical compound 4 and 5 number of theoretical plate (are respectively 2.5 * 10 than pH 3.5 and pH 4.5 height
4With 2.82 * 10
4).When pH is higher than 5.5, the phenomenon that baseline can drift about.So select with 30 mMs/rise KH
2PO
4Aqueous solution is with 5%H
3PO
4Adjust the composition of pH value to 2.5 as mobile phase (A).
Owing to contain salt in the mobile phase (A), when with the mobile phase that is entirely organic solvent (B) when mixing, be easy to separate out salt.And consider when two mobile phases are mixed, to have variation of temperature, may cause the shakiness of baseline, should comprise an amount of water, can keep smooth baseline to prevent that salt from separating out also so main body is the mobile phase (B) of organic solvent.This experiment is set at 30/70,25/75,20/80,15/85 and 10/90 respectively with the volume ratio of water/acetonitrile, inquires into the influence of the ratio of mobile phase (B) to the holdup time.When the ratio of acetonitrile was lower than 80%, the liquid phase time surpassed 90 minutes, and the acetonitrile ratio is higher, and the holdup time of each composition is shorter.When the ratio of acetonitrile 85% when above, good resolution is all arranged, but when ratio is too high, is easier to cause salt to separate out.So select water: the volume ratio of acetonitrile is 15: 85 compositions as mobile phase (B).
The suitability assessment of analysis condition
1. the making of standard curve
With the relation of ratio (y) Yu the constituent concentration (x, mcg/ml) of range upon range of mountains area and internal standard product area, mapping can obtain standard curve (seeing Table 2).Except chemical compound 4, the correlation coefficient of all the other chemical compounds is all greater than 0.999, and being presented at this scope of experiment has extraordinary linear relationship, more increases the credibility to this quantitative method.Chemical compound 4 may be because mobile phase (A) and graded (B) are bigger in this time, causes baseline displacement a little, and only pipe is like this, and its correlation coefficient is still near 0.999.
The standard curve of table 2 index components
2. repeatability
With the optimization analysis condition each chemical compound is carried out quantitatively, for inquiring into the repeatability of this experiment, on the same day in duplicate injection six times, not on the same day also duplicate injection amount to six times, calculate the relative standard deviation (RSD) of each composition respectively with range upon range of mountains area and holdup time.The result is as shown in table 3, and the relative standard deviation of range upon range of mountains area ratio on the same day is between 0.76-2.26%, and the relative standard deviation of holdup time is between 0.45-1.33%; The relative standard deviation of range upon range of mountains area ratio on the same day is not between 0.84-2.94%, and the relative standard deviation of holdup time is between 0.53-1.88%.Haply, not experimental result on the same day with do not have great difference on the same day, repeatability that this expression is analyzed is better.
The repeatability assessment of table 3 analysis condition
Experimental example 3-preparation index substance of the present invention assay
With embodiment 1-15 fluid extract, do not add adjuvant, directly lyophilization obtains dry extract according to above test condition detection level, and gained peoniflorin and glycyrrhizin content are as follows:
The effective ingredient peoniflorin is investigated in table 1 sample
The effective ingredient glycyrrhizin is investigated in table 2 sample
Conclusion: guaranteed the stable content of peoniflorin and glycyrrhizin among the present invention, for the standardization production of preparation is laid a good foundation.By realization of the present invention, can be under the prerequisite that the effective ingredient in the Chinese medicine composition is extracted to greatest extent, reducing in the extract macromolecular substances such as impurity such as tannin, polyphenol, resin, protein, phlegmatic temperament and solid particle effectively removes, keep the active ingredient in the Chinese medicine preparation of the present invention, for the preparation of oral drug preparation is provided convenience.
Claims (7)
1. Chinese medicine composition, its prescription consists of: it is characterized in that its prescription consists of: Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, each 5-8 weight portion of Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi) 4-6 weight portion, Fructus Jujubae, Rhizoma Zingiberis Recens, each 1-3 weight portion of Radix Glycyrrhizae.
2. Chinese medicine composition according to claim 1 is characterized in that its prescription consists of: Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, each 6 weight portion of Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi) 5 weight portions, Fructus Jujubae, Rhizoma Zingiberis Recens, each 2 weight portion of Radix Glycyrrhizae.
3. the preparation method of claim 1 or 2 arbitrary described Chinese medicine compositions, it is characterized in that Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Radix Paeoniae, Pericarpium Citri Reticulatae, Polyporus, Rhizoma Alismatis, the Rhizoma Atractylodis Macrocephalae, Poria, Cortex cinnamomi japonici (Ramulus Cinnamomi), Fructus Jujubae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae are decocted with water 2-4 time, each 0.5-3 hour, merge decocting liquid, filter the back concentrate fluid extract, add behind the adjuvant with behind the fluidized bed granulation useful in preparing drug formulations.
4. preparation method according to claim 3, the proportion that it is characterized in that described fluid extract is 1.12-1.30.
5. according to the arbitrary described preparation method of claim 3-4, it is characterized in that described decocting liquid can carry out centrifugation earlier, get clarifying decocting liquid, centrifugal rotation speed is 1500-20000 rev/min.
6. preparation method according to claim 5 is characterized in that described decocting liquid can adopt the method for membrane filtration to filter.
7. preparation method according to claim 6 is characterized in that described membrane filtration comprises ultrafiltration and nanofiltration.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180094234A1 (en) * | 2011-11-02 | 2018-04-05 | Texas Tech University System | Media Compositions for Promoting Bacterial and Fungal Growth |
| US11753617B2 (en) | 2011-11-02 | 2023-09-12 | Texas Tech University System | Media compositions for promoting bacterial and fungal growth |
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2007
- 2007-10-12 CN CNA2007101639370A patent/CN101406683A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180094234A1 (en) * | 2011-11-02 | 2018-04-05 | Texas Tech University System | Media Compositions for Promoting Bacterial and Fungal Growth |
| US10696942B2 (en) | 2011-11-02 | 2020-06-30 | Texas Tech University System | Media compositions for promoting bacterial and fungal growth |
| US11753617B2 (en) | 2011-11-02 | 2023-09-12 | Texas Tech University System | Media compositions for promoting bacterial and fungal growth |
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