Summary of the invention
The object of the present invention is to provide a kind of preparation method that strengthens the tea volatile oil period of the day from 11 a.m. to 1 p.m-Benexate Hydrochloride dosage form of the tea volatile oil stability period of the day from 11 a.m. to 1 p.m.
To achieve these goals, technical scheme of the present invention is: the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride dosage form preparation method, it is characterized in that: comprise the steps:
1). the period of the day from 11 a.m. to 1 p.m, tea extracted volatile oil: choose Rhizoma Atractylodis 25-45 part, Radix Bupleuri 25-45 part, Rhizoma Et Radix Notopterygii 25-45 part, Radix Saposhnikoviae 25-45 part, Radix Angelicae Dahuricae 25-45 part, Rhizoma Chuanxiong 25-45 part, Herba Pogostemonis 25-45 part, Radix Peucedani 25-45 part, Fructus Forsythiae 25-45 part, Pericarpium Citri Reticulatae 25-45 part, Fructus Crataegi 25-45 part, Fructus Aurantii Immaturus 25-45 part, Fructus Hordei Germinatus 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata 25-45 part, Folium Perillae 25-65 part, Cortex Magnoliae Officinalis 25-65 part, black tea 700-1300 part by weight, distillating extracting oil, the aqueous solution behind the distillating extracting oil device are in addition collected standby;
2). the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride preparation: (1). choose raw material: be by weight: the period of the day from 11 a.m. to 1 p.m 1 part of tea volatile oil, beta-schardinger dextrin-3-12 part, water 20-140 part, choose raw material; (2). beta-schardinger dextrin-is mixed with water, be heated to 50-70 ℃ of dissolving, be chilled to room temperature and make the beta-schardinger dextrin-aqueous solution; (3). with adding the tea volatile oil period of the day from 11 a.m. to 1 p.m in the above-mentioned beta-schardinger dextrin-aqueous solution, stir with agitator or tissue mashing machine, mixing time is 5-100 minute, and cold preservation is centrifugal, dry at normal temperatures 1-3 hour, promptly gets tea volatile oil-Benexate Hydrochloride period of the day from 11 a.m. to 1 p.m;
3). the preparation of dosage form: get Fructus Hordei Germinatus, Radix Glycyrrhizae, Radix Platycodonis, Massa Medicata Fermentata, black tea, Fructus Crataegi Six-element, be by weight: Fructus Hordei Germinatus 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata 25-45 part, black tea 700-1300 part, Fructus Crataegi 25-45 part, water be the period of the day from 11 a.m. to 1 p.m tea crude drug 19 flavor gross weights 6-10 doubly, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is left standstill; The aqueous solution of getting behind supernatant and the period of the day from 11 a.m. to 1 p.m tea distillating extracting oil merges, and concentrates, and is concentrated into the tea crude drug 19 highly seasoned amounts period of the day from 11 a.m. to 1 p.m: concentrated solution weight=1: 1-2, add ethanol equivalent and make precipitation, get supernatant concentration and become thick paste, add starch, thick paste and starch are 1 by weight: 0.2-2, make particulate matter, drying is put cold, add and to make whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, mixing, the capsulae vacuus of packing into promptly gets capsule; Or adopting tabletting behind the mixing, coating promptly gets tablet.
By Fig. 1-3 as can be known, to beta-schardinger dextrin-and the period of the day from 11 a.m. to 1 p.m tea volatile oil mixture, beta-schardinger dextrin-and the period of the day from 11 a.m. to 1 p.m tea volatile oil clathrate test respectively, the result shows, the period of the day from 11 a.m. to 1 p.m tea volatile oil-beta-schardinger dextrin-mixture and the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride the X-diffraction pattern have than big-difference, mixture is the stack at volatile oil and beta-schardinger dextrin-diffractive features peak, and clathrate shows brand-new collection of illustrative plates.
Stability experiment shows, the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride stability better, prediction effect duration can reach 2 years, meets the regulation that medicine is deposited.
The present invention can prevent the tea volatile oils period of the day from 11 a.m. to 1 p.m by beta-cyclodextrin inclusion compound tea period of the day from 11 a.m. to 1 p.m volatile oil, strengthens the stability of the tea volatile oil period of the day from 11 a.m. to 1 p.m, increases its water solublity, improves its bioavailability, provides reliable assurance for further developing the serial oral formulations of the tea period of the day from 11 a.m. to 1 p.m.
The specific embodiment
One, tea extraction period of the day from 11 a.m. to 1 p.m volatile oil is prior art: choose Rhizoma Atractylodis 25-45 part by weight, Radix Bupleuri 25-45 part, Rhizoma Et Radix Notopterygii 25-45 part, Radix Saposhnikoviae 25-45 part, Radix Angelicae Dahuricae 25-45 part, Rhizoma Chuanxiong 25-45 part, Herba Pogostemonis 25-45 part, Radix Peucedani 25-45 part, Fructus Forsythiae 25-45 part, Pericarpium Citri Reticulatae 25-45 part, Fructus Crataegi 25-45 part, Fructus Aurantii Immaturus 25-45 part, Fructus Hordei Germinatus (stir-fry) 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata (stir-fry) 25-45 part, Folium Perillae 25-65 part, Cortex Magnoliae Officinalis 25-65 part, black tea 700-1300 part, distillating extracting oil, the aqueous solution behind the distillating extracting oil device are in addition collected standby;
The period of the day from 11 a.m. to 1 p.m, tea optimal period weight portion proportioning was:
30 parts of Rhizoma Atractylodis, 30 parts of Radix Bupleuri, 30 parts of Rhizoma Et Radix Notopterygiis, 30 parts of Radix Saposhnikoviaes, 30 parts of the Radixs Angelicae Dahuricae,
30 parts of Rhizoma Chuanxiongs, 30 parts of Herba Pogostemoniss, 30 parts of Radix Peucedanis, 30 parts of Fructus Forsythiaes, 30 parts of Pericarpium Citri Reticulataes,
30 parts of Fructus Crataegis, 30 parts of Fructus Aurantii Immaturuss, 45 parts in Fructus Hordei Germinatus (stir-fry), 30 parts in Radix Glycyrrhizae, 45 parts of Radix Platycodoniss,
30 parts of Massa Medicata Fermentatas (stir-fry), 45 parts of Folium Perillaes, 45 parts of Cortex Magnoliae Officinalis, black tea 960.
Two, the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride, it by the period of the day from 11 a.m. to 1 p.m tea volatile oil, beta-schardinger dextrin-and water form, the parts by weight of each component are: the period of the day from 11 a.m. to 1 p.m 1 part of tea volatile oil, beta-schardinger dextrin-3-12 part, water 20-140 part.
The period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride preparation technology, comprise the steps: 1). choose raw material: be by weight: the period of the day from 11 a.m. to 1 p.m 1 part of tea volatile oil, beta-schardinger dextrin-3-12 part, water 20-140 part, choose raw material; 2). beta-schardinger dextrin-is mixed with water, be heated to 50-70 ℃ of dissolving, be chilled to room temperature and make the beta-schardinger dextrin-aqueous solution; 3). with adding the tea volatile oil period of the day from 11 a.m. to 1 p.m in the above-mentioned beta-schardinger dextrin-aqueous solution, stir with agitator or tissue mashing machine, mixing time is 5-100 minute, and cold preservation is centrifugal, dry at normal temperatures 1-3 hour, promptly gets tea volatile oil-Benexate Hydrochloride period of the day from 11 a.m. to 1 p.m.
Three, the period of the day from 11 a.m. to 1 p.m, tea volatile oil-Benexate Hydrochloride was prepared into various dosage forms:
1). the preparation of granule:
Get Fructus Hordei Germinatus (stir-fry), Radix Glycyrrhizae, Radix Platycodonis, Massa Medicata Fermentata (stir-fry), black tea, Fructus Crataegi Six-element, be by weight: Fructus Hordei Germinatus (stir-fry) 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata (stir-fry) 25-45 part, black tea 700-1300 part, Fructus Crataegi 25-45 part, water be the period of the day from 11 a.m. to 1 p.m tea crude drug 19 flavor gross weights 6-10 doubly, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is left standstill; The aqueous solution of getting behind supernatant and the period of the day from 11 a.m. to 1 p.m tea distillating extracting oil merges, concentrate and (to be concentrated into the tea crude drug 19 highly seasoned amounts period of the day from 11 a.m. to 1 p.m: concentrated solution weight=1: 1-2), add ethanol equivalent and make precipitation, get supernatant concentration and become thick paste, add cane sugar powder, thick paste and cane sugar powder are 1 by weight: 1-6, make particulate matter, drying, put cold, add and to make whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, mixing promptly gets granule.
2) preparation of tablet
Get Fructus Hordei Germinatus (stir-fry), Radix Glycyrrhizae, Radix Platycodonis, Massa Medicata Fermentata (stir-fry), black tea, Fructus Crataegi Six-element, be by weight: Fructus Hordei Germinatus (stir-fry) 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata (stir-fry) 25-45 part, black tea 700-1300 part, Fructus Crataegi 25-45 part, water be the period of the day from 11 a.m. to 1 p.m tea crude drug 19 flavor gross weights 6-10 doubly, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is left standstill; The aqueous solution of getting behind supernatant and the period of the day from 11 a.m. to 1 p.m tea distillating extracting oil merges, and concentrates (to be concentrated into the tea crude drug 19 highly seasoned amounts period of the day from 11 a.m. to 1 p.m: concentrated solution weight=1: 1-2), add ethanol equivalent and make precipitation, get supernatant concentration and become thick paste, add starch, thick paste and starch are 1 by weight: 0.2-2, make particulate matter, dry, put coldly, add and to make whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, tabletting, coating promptly gets tablet.
3) preparation of capsule
Get Fructus Hordei Germinatus (stir-fry), Radix Glycyrrhizae, Radix Platycodonis, Massa Medicata Fermentata (stir-fry), black tea, Fructus Crataegi Six-element, be by weight: Fructus Hordei Germinatus (stir-fry) 25-65 part, Radix Glycyrrhizae 25-45 part, Radix Platycodonis 25-45 part, Massa Medicata Fermentata (stir-fry) 25-45 part, black tea 700-1300 part, Fructus Crataegi 25-45 part, water be the period of the day from 11 a.m. to 1 p.m tea crude drug 19 flavor gross weights 6-10 doubly, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is left standstill; The aqueous solution of getting behind supernatant and the period of the day from 11 a.m. to 1 p.m tea distillating extracting oil merges, and concentrates (to be concentrated into the tea crude drug 19 highly seasoned amounts period of the day from 11 a.m. to 1 p.m: concentrated solution weight=1: 1-2), add ethanol equivalent and make precipitation, get supernatant concentration and become thick paste, add starch, thick paste and starch are 1 by weight: 0.2-2, make particulate matter, dry, put coldly, add and to make whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, mixing, the capsulae vacuus of packing into promptly gets capsule.
Four, example:
1 experiment material
Beta-schardinger dextrin-: purity is more than 95%; The period of the day from 11 a.m. to 1 p.m tea volatile oil; Agitator; DS-1 high-speed tissue mashing machine; Volatile oil determination apparatud; The illumination experiment instrument; D/MAX-III type X-ray diffractometer (Japan) etc.
2 methods and result
2.1 the period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride preparation technology
Adopt saturated water solution method, take by weighing β-CD, add water with the 28ml/g ratio, heating for dissolving is chilled to room temperature.Add the tea volatile oil period of the day from 11 a.m. to 1 p.m, stir, take out and put into refrigerator and cooled but 1 hour with agitator or tissue mashing machine.Centrifugal, dry 2 hours at normal temperatures, promptly get tea volatile oil-beta-CD inclusion period of the day from 11 a.m. to 1 p.m, by table 1 as seen, the proper extension mixing time can increase the yield of clathrate.
The preparation technology of table 1 tea period of the day from 11 a.m. to 1 p.m volatile oil clathrate compound
Example | β-CD (g) | Water | The tea volatile oil period of the day from 11 a.m. to 1 p.m (mL) | Mixing time (min) | Clathrate output (g) | Clathrate yield (g) | Oil content (%) | Oil utilization rate (%) |
1 2 3 4 5 6 | 4.0 4.0 4.0 4.0 4.0 4.0 | 112 112 112 112 112 112 | 1 1 1 1 2 2 | Stirring 30 stirs 30 and stirs 60 and stir 60 groups 5 groups 5 | 4.0 3.9 4.2 4.4 8.8 8.8 | 80.7 78.7 84.7 88.8 88.8 88.8 | 9.41 9.23 9.29 11.49 9.84 9.47 | 39.4 37.7 40.8 52.9 45.3 41.6 |
2.2 the period of the day from 11 a.m. to 1 p.m tea volatile oil-beta-CD inclusion stability
2.2.1 illumination experiment
With the period of the day from 11 a.m. to 1 p.m tea volatile oil-beta-CD inclusion place lighting box (30001X) to place 10d, respectively at 0,3,5,10d sampling and measure the tea volatile oil content period of the day from 11 a.m. to 1 p.m (seeing Table 2) with volatile oil determination apparatud.The result shows that the clathrate capsule is stable to light.
Table 2 tea period of the day from 11 a.m. to 1 p.m volatile oil clathrate compound illumination experimental result
Time (d) | Outward appearance | The period of the day from 11 a.m. to 1 p.m tea volatile oil abnormal smells from the patient | Clathrate oil content (%) | Catabolite | Concentration (%) |
0 3 5 10 | The little Huang of the little Huang of the little Huang of little Huang | Little have little have little have littlely have | 10.66 10.47 10.32 10.24 | Do not have | 100.00 98.22 96.81 96.06 |
2.2.2 high temperature experiment
The results are shown in Table 3.As seen from table, temperature is high more, and cosmetic variation is big more.This illustrates that each sample is inner in high temperature experiment complicated variation has taken place, but is not simple zero level or first order reaction, therefore, should method routinely ask and calculates effect duration.
Table 3 tea period of the day from 11 a.m. to 1 p.m volatile oil clathrate compound high temperature experimental result
Time (d) | Outward appearance | The period of the day from 11 a.m. to 1 p.m tea volatile oil abnormal smells from the patient | Clathrate oil content (%) | Catabolite | Concentration (%) |
0 40℃ 3 40℃ 5 60℃ 10 | White white white white | Little have little have little have littlely have | 10.66 10.62 10.54 10.43 | Do not have | 100.00 99.62 98.87 97.84 |
60℃ 3 60℃ 5 60℃ 10 80℃ 3 80℃ 5 80℃ 10 | The white little Huang of light yellow complexion of white is deep yellow | Little have little have little have little have little have littlely have | 10.15 10.06 9.25 10.03 9.40 10.28 | Do not have | 95.22 94.37 86.77 94.09 88.18 96.44 |
2.2.3 accelerated tests
The results are shown in Table 4.The result shows, the clathrate capsule is at 40 ℃, deposit 3 months under relative humidity 75% condition after, its relative amount is still more than 90%.Press the U.S. FDA standard, the clathrate effect duration with above-mentioned experimental result is more than 2 years.(FDA regulation: solid drugs is under 37 ℃~40 ℃, relative humidity 75% or higher situation, and still in prescribed limit, then effect duration can be decided to be more than 2 years its effective ingredient).
The accelerated tests result of table 4 tea period of the day from 11 a.m. to 1 p.m volatile oil clathrate compound
Time (d) | Outward appearance | The period of the day from 11 a.m. to 1 p.m tea volatile oil abnormal smells from the patient | Clathrate oil content (%) | Catabolite | Concentration (%) |
1 2 3 | The little Huang of the little Huang of little Huang | Little have little have littlely have | 10.24 9.84 10.07 | Do not have | 96.06 92.31 94.47 |
2.3 the period of the day from 11 a.m. to 1 p.m tea volatile oil-beta-CD inclusion the X-diffraction analysis
2.3.1 test condition
Scan mode: qualitative, step-scan;
Voltage/current: 35kV/30mA;
Scanning speed: 10 °/min, step-length: 0.02 ° (2 θ);
Preset time: 0.2s; Target: Cu target;
Sweep limits: (2 θ) 5-60 °.
2.3.1 sample determination
Get each test sample powder, place x-ray diffractometer to measure, obtain X-ray diffracting spectrum, see Fig. 1-3.
3 results
3.1 as can be known by Fig. 1-3, beta-schardinger dextrin-, both mixture, both clathrate are tested respectively, the result shows, the period of the day from 11 a.m. to 1 p.m tea volatile oil beta-cyclodextrin mixture and the period of the day from 11 a.m. to 1 p.m tea volatile oil beta cyclodextrin inclusion complex the X-diffraction pattern have than big-difference, mixture is the stack at volatile oil and beta-schardinger dextrin-diffractive features peak, and clathrate shows brand-new collection of illustrative plates, thereby judges the enclose success.
3.2 stability experiment shows, the period of the day from 11 a.m. to 1 p.m tea volatile oil beta cyclodextrin inclusion complex stability better, prediction effect duration can reach 2 years, meets the regulation that medicine is deposited.
3.3 cyclodextrin inclusion technique is meant that a kind of molecule is embedded in by bag in the opening structure of another kind of molecule, forms the technology of clathrate.This clathrate is to be formed by host molecule and two kinds of component adductions of enclosed molecule, and host molecule has bigger opening structure, in being enough to enclosed molecule is contained in.Clathrate behind the enclose can improve significantly by many physicochemical properties such as the dissolubility of enclose medicine, stability.This experiment can prevent the tea volatile oils period of the day from 11 a.m. to 1 p.m by beta-cyclodextrin inclusion compound tea period of the day from 11 a.m. to 1 p.m volatile oil, strengthens the stability of the tea volatile oil period of the day from 11 a.m. to 1 p.m, increases its water solublity, improves its bioavailability, provides reliable assurance for further developing the serial oral formulations of the tea period of the day from 11 a.m. to 1 p.m.
Embodiment 7:
The period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride, it by the period of the day from 11 a.m. to 1 p.m tea volatile oil, beta-schardinger dextrin-and water form, the parts by weight of each component are: the period of the day from 11 a.m. to 1 p.m 1 part of tea volatile oil, 3 parts of beta-schardinger dextrin-s, 20 parts in water.
Above-mentioned period of the day from 11 a.m. to 1 p.m tea volatile oil-Benexate Hydrochloride preparation technology, comprise the steps: 1). choose raw material: be by weight: the period of the day from 11 a.m. to 1 p.m, 1 part of tea volatile oil, β-ring were stuck with paste 20 parts of 3 parts, water, chose raw material; 2). beta-schardinger dextrin-is mixed with water, be heated to 50 ℃ of dissolvings, be chilled to room temperature and make the beta-schardinger dextrin-aqueous solution; 3). with adding the tea volatile oil period of the day from 11 a.m. to 1 p.m in the above-mentioned beta-schardinger dextrin-aqueous solution, stir with agitator, mixing time is 5 minutes, and cold preservation is centrifugal, dry 1 hour at normal temperatures, promptly gets tea volatile oil-Benexate Hydrochloride period of the day from 11 a.m. to 1 p.m.
Above-mentioned period of the day from 11 a.m. to 1 p.m, tea volatile oil-Benexate Hydrochloride was prepared into various dosage forms (granule, tablet, capsule):
Get Fructus Hordei Germinatus (stir-fry), Radix Glycyrrhizae, Radix Platycodonis, Massa Medicata Fermentata (stir-fry), black tea, Fructus Crataegi Six-element, be by weight: 25 parts in Fructus Hordei Germinatus (stir-fry), 25 parts in Radix Glycyrrhizae, 25 parts of Radix Platycodoniss, 25 parts of Massa Medicata Fermentatas (stir-fry), 700 parts of black tea, 25 parts of Fructus Crataegis, water are 6 times of crude drug 19 flavor gross weights, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is left standstill; The aqueous solution of getting behind supernatant and the period of the day from 11 a.m. to 1 p.m tea distillating extracting oil merges, concentrate and (to be concentrated into crude drug 19 highly seasoned amounts: concentrated solution weight=1: 1-2), add ethanol equivalent and make precipitation, get supernatant concentration and become thick paste, add cane sugar powder, thick paste and cane sugar powder are 1 by weight: 1-6, make particulate matter, drying is put cold, add and to make whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, promptly get granule.If get supernatant concentration and become thick paste, add starch, thick paste and starch are 1 by weight: 0.2-2, make particulate matter, drying is put coldly, and adding makes whole period of the day from 11 a.m. to 1 p.m of tea volatile oil-Benexate Hydrochloride, mixing, the capsulae vacuus of packing into promptly gets capsule; Continue tabletting if adopt behind the mixing, coating promptly gets tablet.