CN101485695B - Guiling dispersible tablets and preparation method thereof - Google Patents
Guiling dispersible tablets and preparation method thereof Download PDFInfo
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- CN101485695B CN101485695B CN2008100430216A CN200810043021A CN101485695B CN 101485695 B CN101485695 B CN 101485695B CN 2008100430216 A CN2008100430216 A CN 2008100430216A CN 200810043021 A CN200810043021 A CN 200810043021A CN 101485695 B CN101485695 B CN 101485695B
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Abstract
The invention discloses a guiling dispersing tablet, which is mainly prepared from a supercritical extract and/or a water extract of one, two or three raw material medicines selected from tuckahoe, rhizoma atractylodis macrocephalae and angelica, or effective parts of the supercritical extract and/or the water extract and pharmaceutical excipients, wherein the pharmaceutical excipients comprise a disintegrant which is crosslinked polyvinylpyrrolidone, sodium carboxymethyl starch, microcrystalline cellulose, low-substituted hydroxyproxyl cellulose or crosslinked sodium carboxymethyl cellulose or a composition thereof, a filling agent which is microcrystalline cellulose, superfine silica gel powder, lactose, dextrin or compressible starch or a composition thereof, and a lubricating agent which is superfine silica gel powder, talcum powder or magnesium stearate or a composition thereof. The invention also discloses a method for preparing the guiling dispersing tablet. The invention adopts novel pharmaceutical excipients and novel preparation technology to ensure that the disintegration time of medicine and the dissolution time of effective constituents are greatly shortened than a common guiling tablet, and the tablet has quicker taking effect, better therapeutic effect and convenient administration, and can better meet medical demand.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation, relate in particular to a kind of Guiling dispersible tablets; In addition, the invention still further relates to the method for preparing of this Guiling dispersible tablets.
Background technology
Guiling tablets (FBD) comes from Chinese Zhang Zhongjing " Medical Treasures of the Golden Chamber " DANGGUI SHAOYAO SAN, for the modern times of traditional Chinese medical science ancient prescription in thousand are improved preparation.Plan it now and be used for blood stagnancy due to deficiency of QI type vascular dementia, it can effectively improve patient's memory and body constitution, determined curative effect the clinical trial proof.Chinese invention patent Shen Qing Publication description CN1985866A (open day: on June 27th, 2007) disclose the prescription of Guiling tablets; It is mainly by the supercritical extract and/or the water extract that are selected from a kind of, two or three crude drug in Poria, the Rhizoma Atractylodis Macrocephalae and the Radix Angelicae Sinensis, and perhaps supercritical extract and/or water extract effective site are formed.
Dispersible tablet is a kind of good novel form of developing in recent years, and the good reputation of " Peroral solid dosage form liquid " is arranged.It integrates the advantage of tablet and liquid preparation, and has overcome both deficiencies.Have following characteristics: 1) disintegration time short (requiring disintegrate in the 3min), good dispersing state; 2) the medicine stripping rapidly, absorption is fast, bioavailability is high; 3) untoward reaction is few; 4) taking convenience and instructions of taking are various, can directly swallow or in water, disperse back and fruit juice, milk and clothes, especially are fit to the patient of old, children and dysphagia.
Traditional Guiling tablets preparation is because the limitation of technology and lack many-sided quality controllable standard, severe inhibition its more be widely used and bigger market share.Its problem that mainly exists has: extraction process is coarse, and taking dose is big; Fail effectively to capture fat-soluble active ingredient in the prescription in the traditional handicraft, influenced drug effect; Preparation process falls behind, and causes human bioavailability low, and onset time is long.Guiling tablets is used for treating apoplexy, and requiring must be rapid-action, and effect so we select dispersible tablet as the research and development dosage form, is beneficial to take, and can reaches the effect of quick acting rapidly, satisfies the needs of patient's medication better.
Summary of the invention
One of technical problem that the present invention will solve provides a kind of Guiling dispersible tablets, and its onset time is faster, better efficacy, and be convenient to take, can satisfy medical demand better.
Two of the technical problem that the present invention will solve provides the method for preparing of this Guiling dispersible tablets.
For solving the problems of the technologies described above; The present invention provides a kind of Guiling dispersible tablets; This dispersible tablet is mainly by the supercritical extract and/or the water extract that are selected from a kind of, two or three crude drug in Poria, the Rhizoma Atractylodis Macrocephalae and the Radix Angelicae Sinensis; Perhaps supercritical extract and/or water extract effective site and pharmaceutic adjuvant are processed; Wherein pharmaceutic adjuvant is disintegrating agent, filler and lubricant; Described disintegrating agent is crospolyvinylpyrrolidone, carboxymethyl starch sodium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose or cross-linked carboxymethyl cellulose sodium or its compositions, and described filler is microcrystalline Cellulose, micropowder silica gel, lactose, dextrin or amylum pregelatinisatum or its compositions, and described lubricant is micropowder silica gel, Pulvis Talci or magnesium stearate or its compositions.
The preferred polyvinylpolypyrrolidone XL of described disintegrating agent, microcrystalline Cellulose and carboxymethyl starch sodium, preferred lactose of described filler and micropowder silica gel, the preferred magnesium stearate of described lubricant.
The weight portion of said crude drug is: the weight percent content that Poria 2-6 part, Rhizoma Atractylodis Macrocephalae 1-3 part, Radix Angelicae Sinensis 0.5-1.5 part, described pharmaceutic adjuvant account for Guiling tablets is polyvinylpolypyrrolidone XL 5%-20%, micropowder silica gel 0.5-2%, lactose 10%-30%, carboxymethyl starch sodium 3%-10%, microcrystalline Cellulose 10-30%.
The present invention also provides the method for preparing of this Guiling dispersible tablets, and this method comprises the following steps:
(1) mix homogeneously after the crude drug drying is ground into coarse powder, obtained supercritical extraction liquid, be concentrated into yield and be the supercritical extraction concentrated solution of 0.5-5% through carbon dioxide supercritical fluid extraction 1-5 hour, subsequent use;
(2) medicinal residues behind the above-mentioned supercritical extraction are added 6-10 times of decocting and boiled 0.5-3 hour, obtain water extract behind the water extraction, filter; Filtrating is concentrated into proportion 1.2-1.4 (60 ℃ of heat are surveyed); 60 ℃ of-70 ℃ of following vacuum dryings are crushed into the water extraction dry extract to doing, and are subsequent use;
(3) in the supercritical extraction concentrated solution that step (1) makes, add disintegrating agent, add water extraction dry extract and other adjuvant that step (2) makes again, make Guiling dispersible tablets.
Step (1) is specially: after 60 ℃ of dryings of crude drug, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was doubly measured soak with ethanol 0.5-1 hour with 0.5-2,35-45 ℃ of extraction temperature of control, system pressure 10-27Mpa, CO
2Flow 80-160 kg/h extracted 1-5 hour, collected supercritical extraction liquid, and 60 ℃ of concentrating under reduced pressure (proportion 0.85-0.9,60 ℃ of heat are surveyed) are subsequent use.
In step (2): the said water extraction dry extract that is crushed into is to pulverize 60 mesh sieves to become the water extraction dry extract.
Step (3) is specially: in the supercritical extraction concentrated solution that step (1) makes, add polyvinylpolypyrrolidone XL, stir, add micropowder silica gel, mixing again; Volatilize ethanol, cross 20 mesh sieves, add the water extraction dry extract that step (2) makes again, lactose; Carboxymethyl starch sodium, magnesium stearate, microcrystalline Cellulose, mixing; Tabletting, the bag film-coat, packing promptly gets Guiling dispersible tablets.
In step (3): the polyvinylpolypyrrolidone XL of adding is that 1-5 is than 1 with the weight ratio of supercritical extraction concentrated solution.
The consumption of Guiling dispersible tablets of the present invention and the course of treatment can be done suitably adjustment according to the light and heavy degree of dosage form, patient's age, disease; But be generally oral 3 times of every day; Each 4 (every 0.48 gram), with 1 month be a course of treatment, can use 1 course of treatment or longer time continuously.
The present invention has following beneficial effect: Guiling dispersible tablets of the present invention adopts novel adjuvant and novel preparation technique, and medicine disintegration time and the more common Guiling tablets of effective ingredient dissolution time are shortened greatly.Therefore, relatively disintegrate is faster for Guiling dispersible tablets and common Guiling tablets, absorbs better; Its clinical trial proof Guiling dispersible tablets onset time is faster; Thereby realized making the FBD composition to bring into play the target of drug effect rapidly, better efficacy, and be convenient to take; Can satisfy medical demand better, bring glad tidings to extensive patients.
The specific embodiment
Instrument that following examples and Test Example adopted and reagent: FZB-150 crushing and pelletizing machine (Pharmaceutical Equipment Factory, Wenzhou City); ZPW21A rotary tablet machine (Tianxiang Jiantai Pharmaceutical Machinery Co., Ltd., Shanghai); The multidirectional movement mixer of HAD-100 (Pharmaceutical Equipment Factory, Wenzhou City); PC160F beater grinder (Shanghai Chinese traditional medicine machine factory), ZB-1C intelligence disintegration tester (Precision Instrument Factory, Tianjin Univ.); Polyvinylpolypyrrolidone XL, polyvinylpolypyrrolidone XL
-10(ISP company), lactose (Shanghai Huamao Pharmaceutical Co), micropowder silica gel, carboxymethyl starch sodium, magnesium stearate, microcrystalline Cellulose, coating pre-mixing agent (Shanghai grand chemical industry pharmaceutical adjunct technology company limited far away)
Below through embodiment the present invention is done further elaboration:
Embodiment 1:
After Poria 833 grams, the Rhizoma Atractylodis Macrocephalae 416 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 250 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 0.5 hour, 35 ℃ of extraction temperature of control, system pressure 10Mpa, CO with 0.5 times
2Flow 80kg/h extracted 1 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 0.5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 6 times of decoctings boiled 0.5 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.2,60 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 72 grams (the polyvinylpolypyrrolidone XL of adding is 1 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 4.8 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 96 grams; Carboxymethyl starch sodium 24 grams, magnesium stearate 2 grams, microcrystalline Cellulose 96 grams, mixing; Tabletting adds coating pre-mixing agent 9 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 2
After Poria 856 grams, the Rhizoma Atractylodis Macrocephalae 428 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 215 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 0.8 hour, 40 ℃ of extraction temperature of control, system pressure 20Mpa, CO with 1 times
2Flow 120kg/h extracted 4 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 2.7%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 8 times of decoctings boiled 2 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.3,65 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 24 grams (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 2.4 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 48 grams; Carboxymethyl starch sodium 14 grams, magnesium stearate 2 grams, microcrystalline Cellulose 48 grams, mixing; Tabletting adds coating pre-mixing agent 8 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 3
After Poria 749 grams, the Rhizoma Atractylodis Macrocephalae 500 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 250 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 1 hour, 45 ℃ of extraction temperature of control, system pressure 27Mpa, CO with 2 times
2Flow 160 kg/h extracted 5 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 10 times of decoctings boiled 3 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.4,70 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL96 gram (the polyvinylpolypyrrolidone XL of adding is 5 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 9.6 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 144 grams; Carboxymethyl starch sodium 48 grams, magnesium stearate 2 grams, microcrystalline Cellulose 144 grams, mixing; Tabletting adds coating pre-mixing agent 10 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 4:
After Poria 833 grams, the Rhizoma Atractylodis Macrocephalae 416 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 250 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 0.5 hour, 35 ℃ of extraction temperature of control, system pressure 10Mpa, CO with 0.5 times
2Flow 80kg/h extracted 1 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 0.5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 6 times of decoctings boiled 0.5 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.2,60 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 72 grams (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 5 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 96 grams; Carboxymethyl starch sodium 24 grams, magnesium stearate 2 grams, microcrystalline Cellulose 96 grams, mixing; Tabletting adds coating pre-mixing agent 9 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 5
After Poria 999 grams, the Rhizoma Atractylodis Macrocephalae 250 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 250 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 0.8 hour, 40 ℃ of extraction temperature of control, system pressure 20Mpa, CO with 1 times
2Flow 120kg/h extracted 4 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 2.7%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 8 times of decoctings boiled 2 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.3,65 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL30 gram (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 7 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 50 grams; Carboxymethyl starch sodium 30 grams, magnesium stearate 2 grams, microcrystalline Cellulose 50 grams, mixing; Tabletting adds coating pre-mixing agent 8 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 6
After Poria 899 grams, the Rhizoma Atractylodis Macrocephalae 450 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 150 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 1 hour, 45 ℃ of extraction temperature of control, system pressure 27Mpa, CO with 2 times
2Flow 160kg/h extracted 5 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 10 times of decoctings boiled 3 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.4,70 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL80 gram (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 8 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 100 grams; Carboxymethyl starch sodium 40 grams, magnesium stearate 2 grams, microcrystalline Cellulose 1 00 grams, mixing; Tabletting adds coating pre-mixing agent 10 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 7:
After 60 ℃ of dryings of Poria 1499 grams, pulverized 10 mesh sieves, the extractor of packing into was measured soak with ethanol 0.5 hour, 35 ℃ of extraction temperature of control, system pressure 10Mpa, CO with 0.5 times
2Flow 80kg/h extracted 1 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 0.5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 6 times of decoctings boiled 0.5 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.2,60 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 72 grams (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 4.8 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 120 grams; Carboxymethyl starch sodium 24 grams, magnesium stearate 2 grams, microcrystalline Cellulose 96 grams, mixing; Tabletting adds coating pre-mixing agent 9 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 8
After Poria 1000 grams, the Rhizoma Atractylodis Macrocephalae 499 gram (stir-fry) 60 ℃ of dryings, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 0.8 hour, 40 ℃ of extraction temperature of control, system pressure 20Mpa, CO with 1 times
2Flow 120kg/h extracted 4 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 2.7%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 8 times of decoctings boiled 2 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.3,65 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 24 grams (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 2.5 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 96 grams; Carboxymethyl starch sodium 20 grams, magnesium stearate 2 grams, microcrystalline Cellulose 60 grams, mixing; Tabletting adds coating pre-mixing agent 8 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 9
After the Rhizoma Atractylodis Macrocephalae 1000 grams (stir-fry) and 60 ℃ of dryings of Radix Angelicae Sinensis 499 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 1 hour, 45 ℃ of extraction temperature of control, system pressure 27Mpa, CO with 2 times
2Flow 160kg/h extracted 5 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 10 times of decoctings boiled 3 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.4,70 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL70 gram (the polyvinylpolypyrrolidone XL of adding is 5 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 8 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 138 grams; Carboxymethyl starch sodium 45 grams, magnesium stearate 2 grams, microcrystalline Cellulose 80 grams, mixing; Tabletting adds coating pre-mixing agent 10 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 10:
After the Rhizoma Atractylodis Macrocephalae 1499 gram (stir-fry) 60 ℃ of dryings, pulverized 10 mesh sieves, the extractor of packing into was measured soak with ethanol 0.5 hour, 35 ℃ of extraction temperature of control, system pressure 10Mpa, CO with 0.5 times
2Flow 80kg/h extracted 1 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 0.5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 6 times of decoctings boiled 0.5 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.2,60 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL 72 grams (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 5 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 50 grams; Carboxymethyl starch sodium 48 grams, magnesium stearate 2 grams, microcrystalline Cellulose 120 grams, mixing; Tabletting adds coating pre-mixing agent 9 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 11
After 60 ℃ of dryings of Radix Angelicae Sinensis 1499 grams, pulverized 10 mesh sieves, the extractor of packing into was measured soak with ethanol 0.8 hour, 40 ℃ of extraction temperature of control, system pressure 20Mpa, CO with 1 times
2Flow 120kg/h extracted 4 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 2.7%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 8 times of decoctings boiled 2 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.3,65 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL60 gram (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 7 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 60 grams; Carboxymethyl starch sodium 35 grams, magnesium stearate 2 grams, microcrystalline Cellulose 96 grams, mixing; Tabletting adds coating pre-mixing agent 8 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Embodiment 12
After Poria 1200 grams, 60 ℃ of dryings of Radix Angelicae Sinensis 299 grams, mix homogeneously was pulverized 10 mesh sieves, and the extractor of packing into was measured soak with ethanol 1 hour, 45 ℃ of extraction temperature of control, system pressure 27Mpa, CO with 2 times
2Flow 160kg/h extracted 5 hours, collected supercritical extraction liquid, and 60 ℃ are evaporated to yield and are 5%, subsequent use; Medicinal residues behind the above-mentioned supercritical extraction are added 10 times of decoctings boiled 3 hours, obtain water extract behind the water extraction, filter, filtrating is concentrated into 1.4,70 ℃ of following vacuum dryings of proportion to doing, and pulverizing 60 mesh sieves becomes the water extraction dry extract, subsequent use; In above-mentioned supercritical extraction concentrated solution, add polyvinylpolypyrrolidone XL50 gram (the polyvinylpolypyrrolidone XL of adding is 2 to 1 with the weight ratio of supercritical extraction concentrated solution), stir, add micropowder silica gel 8 grams again, mixing; Volatilize ethanol, cross 20 mesh sieves, add above-mentioned water extraction dry extract, lactose 100 grams; Carboxymethyl starch sodium 24 grams, magnesium stearate 2 grams, microcrystalline Cellulose 70 grams, mixing; Tabletting adds coating pre-mixing agent 10 gram bag film-coats, and packing promptly gets Guiling dispersible tablets.
Below by Test Example beneficial effect of the present invention is further elaborated:
The research of Test Example 1 formulation and technology
This prescription is made up of supercritical extraction oil and the water extracted immersing paste two parts (being rich in viscosity compositions such as polysaccharide).Principal agent is a supercritical extraction oil part, and that water is put forward in the part dissolubility in cold water such as polysaccharide is also bad, processes dispersible tablet so plan it.This experiment is intended with behind the polyvinylpolypyrrolidone XL absorption supercritical extraction oil, adds appropriate amount of auxiliary materials, is pressed into dispersible tablet with the water extracted immersing paste again.
A is according to list of references, and the design preliminary experiment is following:
The adjuvant prescription is formed
| R1 | ?R2 | ?R3 | |
| Polyvinylpolypyrrolidone XL | 35％ | 24％ | 8％ |
| Lactose | 11％ | ||
| Amylum pregelatinisatum | 8％ | ||
| Micropowder silica gel | 2％ | 2％ | 2％ |
| Carboxymethyl starch sodium | 4％ | ||
| Magnesium stearate | 1％ | 1％ | 0.5％ |
| Disintegration time (min) | 20 | 25 | 20 |
| Sheet heavy (g) | 0.53 | 0.55 | 0.48 |
Experimental technique is with direct compression behind the adjuvant amount mix homogeneously of supercritical extraction oil and the water extracted immersing paste and design.The pressure of tablet machine is advisable with the minimum pressure of ability molding.According to the preliminary experiment result, find that disintegration time all is about about 20min.But the less disintegrating agent consumption that can improve of the amount of R3 adjuvant is to realize accelerating disintegrate.So with R3 is that the basis is optimized.
Different filler lactose have been compared in this experiment emphatically, micropowder silica gel, and soluble starch is to the influence of slice, thin piece mouldability, and on ability molding basis, to choose supplementary product consumption few as far as possible, and low-cost prescription carries out preferably as basis side.Experimental result shows that the water-soluble filler lactose is all better than other two to the contribution of slice, thin piece disintegration time and mouldability.Micropowder silica gel, it not only can improve powder, particulate flowability, and because of the strong polarity and the hydrophilic of its silanol base, helps moisture and infiltrate tablet, can significantly improve the dissolution rate of insoluble drug.
B optimizes technological experiment
The adjuvant prescription is formed
| R1 | R2 | R3 | |
| Polyvinylpolypyrrolidone XL | 17％ | 12％ | 15％ |
| Lactose | 3％ | 20％ | 20％ |
| Microcrystalline Cellulose | 10％ | 20％ | |
| Micropowder silica gel | 1％ | 1％ | |
| Carboxymethyl starch sodium | 10％ |
| Magnesium stearate | 0.05％ | ||
| Sheet heavy (g) | 0.58 | 0.61 | 0.74 |
| Disintegration time (min) | 15 | 9 | 5 |
The kind of disintegrating agent and consumption are most important to disintegrate, the result of extraction of dispersible tablet, are the factors that at first will consider.The general disintegrating agent swellbility that requires to select for use is greater than 5ml/g, and the most frequently used have carboxymethyl starch sodium (CMS-Na), low-substituted hydroxypropyl cellulose (L-HPC), cross-linked carboxymethyl cellulose sodium (cCMC-Na), a crospolyvinylpyrrolidone (PVPP) etc.This experiment focuses on the influence of the different disintegrating agents of comparison (polyvinylpolypyrrolidone XL, microcrystalline Cellulose and polyvinylpolypyrrolidone XL share, carboxymethyl starch sodium and polyvinylpolypyrrolidone XL share) to the disintegration time of slice, thin piece.The Yin Ben article have just been used polyvinylpolypyrrolidone XL (itself being exactly an efficient disintegrating agent) when absorbing supercritical oil, so be kind and the adjuvant interference during to the end product quality research on standard that reduces adjuvant, disintegrating agent is that the basis is studied with polyvinylpolypyrrolidone XL.Experiment shows that microcrystalline Cellulose and polyvinylpolypyrrolidone XL share the bigger disintegration time that reduces slice, thin piece when a certain amount of.
Confirming of C prescription
On the optimization experiment basis, intend and strengthen the adjuvant amount again to reduce the disintegration time of slice, thin piece.But sheet is heavy very high, is split as two so plan former slice, thin piece, improves and takes the sheet number, and it is heavy to reduce sheet.
| R1 | |
| Polyvinylpolypyrrolidone XL | 15％ |
| Lactose | 20％ |
| Microcrystalline Cellulose | 20％ |
| Micropowder silica gel | 1％ |
| Carboxymethyl starch sodium | 5％ |
| Sheet heavy (g) | 0.48 |
| Disintegration time (min) | 1 |
Other detects its dispersing uniformity, and tablet weight variation etc. are up to specification.Be the formulation and technology of last FBD dispersible tablet so confirm this prescription.
The comparison of Guiling dispersible tablets of the present invention and traditional Guiling tablets, see the following form:
| Project | Disintegration (min) | The atractylodes lactone dissolution |
| Ordinary tablet | 25 | ?60％/45min |
| Dispersible tablet | ＜3 | ?80％/5min |
Guiling dispersible tablets disintegration is in the 3min; Effective ingredient atractylodes lactone dissolution is 80% stripping in the 5min; And being scattered in does not have grittiness in the water, through clinical trial, has proved the characteristics of its quick acting; Thereby realized making the FBD composition to bring into play the target of drug effect rapidly, brought glad tidings to extensive patients.
The preparation technology of Test Example 2 Guiling dispersible tablets and the research of pharmaceutical adjunct
Be with technical will haveing breakthrough; Cost can not increase problems such as too many again; We have carried out a large amount of screenings of pharmaceutical adjunct and continuing to optimize of pelletizing press sheet technology, and it is simple finally to form production technology, use the Guiling dispersible tablets that the conventional tablet production equipment can be produced.
The absorbent of 1 supercritical extract is selected
1.1 the preparation of β-CD (beta-schardinger dextrin-) clathrate:
Less β-CD polishing the clathrate process of this supercritical extract water consumption is cured absorption.Its investigation factor is: medium adds doubly amount (water), host and guest's molecular proportion of supercritical extract and β-CD, milling time.
The arrangement preliminary experiment is following:
Use 10g supercritical extract (orthogonal experiment 8# sample), with about 50ml dissolve with ethanol, other gets 50g β-CD and is dissolved in the 150ml water, adds oil, grinds 0.5hr to pasty state, 50 ℃ of hot blast dryings in the baking oven.
Measure the extraction ratio and the inclusion rate of volatile oil in the SFE extract:
Beta-CD inclusion is used petroleum ether, and is centrifugal, and 50 ℃ of hot blast dryings get the 52.3g clathrate.
Envelop rate: 52.3/ (50+10)=87.17%
Get half beta-CD inclusion (26.61g) and survey the volatile oil extraction ratio: (being equivalent to 8# oil 5g approximately), measure by the mensuration way of a volatile oil of 2000 editions Chinese Pharmacopoeias.Get 1ml volatile oil.
Extraction ratio=1/ (0.289*5)=69.2%
Annotate: 0.289 is the volume of 8# oil 1g.
So carry out orthogonal experiment, when analysis result with regard to choice hair oil utilization rate as investigating index.
Annotate: the volatilization oil mass of detected volatilization oil mass/adding behind volatile oil utilization rate=enclose.
Experimental technique: use an amount of oil, with about 50ml dissolve with ethanol, it is soluble in water that other gets β-CD, adds oil, grinds the stipulated time to pasty state, 50 ℃ of hot blast dryings in the baking oven.By the extraction ratio of measuring volatile oil in the beta-CD inclusion by the mensuration way of a volatile oil of 2000 editions Chinese Pharmacopoeias.
Obtaining optimum process condition is: A
2B
1C
1Be that host and guest's molecular proportion is 1: 5 (oil with β-CD ratio), adding the medium amount is 5 times, and milling time is 15min.But consider that it will be very big in tablet forming technique, adding the adjuvant amount like this, take inconvenience if in tabletting, add the β-CD of 5 times of supercritical extract amounts, so his thing of alternative absorbs supercritical extract.
1.2 the absorption technique of polyvinylpolypyrrolidone XL research
1.2.1 the supercritical extract of different proportionings is mixed in mortar with polyvinylpolypyrrolidone XL, has observed the maximal absorptive capacity of flowability and polyvinylpolypyrrolidone XL.
The absorption technique result of study of table 1 polyvinylpolypyrrolidone XL
| Supercritical extract | Polyvinylpolypyrrolidone XL | Adsorbability | Mobile |
| 3 | 1 | There is part not adsorbable | Bad, it is agglomerating to be prone to bonding |
| ?2 | ?1 | Adsorbable | Bad, be prone to the bonding granulating, better mobile after the adding micropowder silica gel, be prone to mixing |
| 1 | 1 | Adsorbable | Bad, be prone to the bonding granulating |
| 1 | 2 | Adsorbable | Flowability better after placing 2hr |
| 1 | 3 | Adsorbable | Flowability better after placing 2hr |
Because of containing ethanol in the supercritical oil, when mixing with polyvinylpolypyrrolidone XL, ethanol has moistening granulation effect.But ethanol is volatile, so after placing 2hr, ethanol is volatilized, characters powder changes, flowability improve (table 1).The supercritical extract and the polyvinylpolypyrrolidone XL of the different proportionings of " 1,2,3 " expression in the table 1; Here 3 times of amount supercritical extracts have been investigated: 1 times of amount polyvinylpolypyrrolidone XL; 2 times of amount supercritical extracts: 1 times of amount polyvinylpolypyrrolidone XL; 1 times of amount supercritical extract: 1 times of amount polyvinylpolypyrrolidone XL, 1 times of amount supercritical extract: 2 times of amount polyvinylpolypyrrolidone XL, 1 times of amount supercritical extract: 3 times of these 5 kinds of different proportionings of amount polyvinylpolypyrrolidone XL.
1.2.2 supercritical extract and polyvinylpolypyrrolidone XL with different proportionings
-10The middle mixing, observe flowability and polyvinylpolypyrrolidone XL
-10Maximal absorptive capacity.
Table 2 polyvinylpolypyrrolidone XL
-10Absorption technique result of study table
| Supercritical extract | Polyvinylpolypyrrolidone XL -10 | Adsorbability | Mobile |
| 3 | 1 | There is part not adsorbable | Bad, it is agglomerating to be prone to bonding |
| 2 | 1 | Adsorbable | Bad, a large amount of granules are arranged, be difficult for mixing |
| 1 | 1 | Adsorbable | Bad, be prone to the bonding granulating |
| 1 | 2 | Adsorbable | Begin badly, place behind the 2hr better mobile |
| 1 | 3 | Adsorbable | Flowability better after placing 2hr |
Polyvinylpolypyrrolidone XL
-10Compare when mixing with polyvinylpolypyrrolidone XL, be prone to the small-particle of a large amount of adsorbed oils, be difficult for disperseing.This maybe be with polyvinylpolypyrrolidone XL
-10Particle diameter is little, and surface area is big, absorption affinity strong relevant (table 2).The supercritical extract and the polyvinylpolypyrrolidone XL of the different proportionings of " 1,2,3 " expression in the table 2
-10, investigated 3 times of amount supercritical extracts here: 1 times of amount polyvinylpolypyrrolidone XL
-10, 2 times of amount supercritical extracts: 1 times of amount polyvinylpolypyrrolidone XL
-10, 1 times of amount supercritical extract: 1 times of amount polyvinylpolypyrrolidone XL
-10, 1 times of amount supercritical extract: 2 times of amount polyvinylpolypyrrolidone XL
-10, 1 times of amount supercritical extract: 3 times of amount polyvinylpolypyrrolidone X1
-10These 5 kinds of different proportionings.
Take all factors into consideration finished product adsorbability and flowability and cost, so in this experiment, select polyvinylpolypyrrolidone XL for use: supercritical oil=2: 1, other adds an amount of micropowder silica gel influence liquidity.
Below be to adopt 3 kinds of different preparation technologies to compare, obtain the result of table 3:
Table 3
| Supercritical extract directly sprays into the extractum tabletting | Supercritical extract with β-CDBao He after tabletting | Supercritical extract is with polyvinylpolypyrrolidone XL absorption back tabletting (the present invention prepares dispersible tablet technology) |
| Technology is time-consuming | 1hr | 2 days | 3hr |
| To the supercritical extract protectiveness | Lose 50% approximately | Lose 30% approximately | Lose 10% approximately |
| The uniformity of supercritical extract in extractum | Inhomogeneous | Evenly | Evenly |
| Disintegration time | 35min | 40min | 1min |
| Use adjuvant amount (with respect to the extractum amount) | 0 times | More than 5 times | 1-2 doubly |
| Process complexity | Directly adding gets final product, and technology is simple | Need carry out technologies such as drying in addition, power consumption, complex process | Admix and shakeout placement after sieving and get final product, technology is simple |
Visible by table 3, compare with traditional handicraft, adopt preparation technology of the present invention; Simplified technological process; Technology is consuming time less, has increased the uniformity of supercritical extract in extractum, and the adjuvant amount of adding is reduced greatly; The better effects if of disintegrate (disintegrate is faster), and can avoid destroying the effective ingredient (having reduced loss of active ingredients) of Guiling dispersible tablets.
Can draw as drawing a conclusion through Test Example 1 and Test Example 2: Guiling dispersible tablets dosage form of the present invention adopts novel adjuvant and novel preparation technique; Simplified technological process; Increased the uniformity of supercritical extract in extractum; The adjuvant amount of adding is reduced greatly, medicine disintegration time and the more former tablet of effective ingredient dissolution time are shortened greatly, and can avoid destroying the effective ingredient of Guiling dispersible tablets.Therefore, relatively disintegrate is faster for Guiling dispersible tablets and former Guiling tablets agent, absorbs better, through clinical trial, has proved the characteristics of its quick acting, thereby has realized making the Guiling dispersible tablets composition to bring into play the target of drug effect rapidly.
Claims (3)
1. Guiling dispersible tablets; It is characterized in that; This dispersible tablet is by the supercritical extract and/or the water extract of Poria, the Rhizoma Atractylodis Macrocephalae and three kinds of crude drug of Radix Angelicae Sinensis; Perhaps supercritical extract and/or water extract effective site and pharmaceutic adjuvant are processed, and wherein pharmaceutic adjuvant is polyvinylpolypyrrolidone XL, microcrystalline Cellulose, carboxymethyl starch sodium, lactose, micropowder silica gel and magnesium stearate; The weight portion of said crude drug is: the weight percent content that Poria 2-6 part, Rhizoma Atractylodis Macrocephalae 1-3 part, Radix Angelicae Sinensis 0.5-1.5 part, described pharmaceutic adjuvant account for Guiling dispersible tablets is polyvinylpolypyrrolidone XL 5%-20%, micropowder silica gel 0.5-2%, lactose 10%-30%, carboxymethyl starch sodium 3%-10%, microcrystalline Cellulose 10-30%; Said Guiling dispersible tablets adopts following method to make:
(1) with after 60 ℃ of dryings of crude drug, mix homogeneously was pulverized 10 mesh sieves, and the supercritical extraction jar of packing into was doubly measured soak with ethanol 0.5-1 hour with 0.5-2,35-45 ℃ of extraction temperature of control, system pressure 10-27Mpa, CO
2Flow 80-160kg/h extracted 1-5 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to the supercritical extraction concentrated solution that yield is 0.5-5%, subsequent use;
(2) medicinal residues behind the above-mentioned supercritical extraction are added 6-10 times of decocting and boiled 0.5-3 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into proportion 1.2-1.4, and 60 ℃ of-70 ℃ of following vacuum dryings are crushed into the water extraction dry extract to doing, and are subsequent use;
(3) in the supercritical extraction concentrated solution that step (1) makes, add polyvinylpolypyrrolidone XL, stir, add micropowder silica gel, mixing again; Volatilize ethanol, cross 20 mesh sieves, add the water extraction dry extract that step (2) makes again, lactose; Carboxymethyl starch sodium, magnesium stearate, microcrystalline Cellulose, mixing; Tabletting, the bag film-coat, packing promptly gets Guiling dispersible tablets; The polyvinylpolypyrrolidone XL of said adding and the weight ratio of supercritical extraction concentrated solution are 2: 1.
2. the method for preparing of a Guiling dispersible tablets as claimed in claim 1 is characterized in that, this method comprises the following steps:
(1) with after 60 ℃ of dryings of crude drug, mix homogeneously was pulverized 10 mesh sieves, and the supercritical extraction jar of packing into was doubly measured soak with ethanol 0.5-1 hour with 0.5-2,35-45 ℃ of extraction temperature of control, system pressure 10-27Mpa, CO
2Flow 80-160kg/h extracted 1-5 hour, collected supercritical extraction liquid, and 60 ℃ are evaporated to the supercritical extraction concentrated solution that yield is 0.5-5%, subsequent use;
(2) medicinal residues behind the above-mentioned supercritical extraction are added 6-10 times of decocting and boiled 0.5-3 hour, obtain water extract behind the water extraction, filter, filtrating is concentrated into proportion 1.2-1.4, and 60 ℃ of-70 ℃ of following vacuum dryings are crushed into the water extraction dry extract to doing, and are subsequent use;
(3) in the supercritical extraction concentrated solution that step (1) makes, add polyvinylpolypyrrolidone XL, stir, add micropowder silica gel, mixing again; Volatilize ethanol, cross 20 mesh sieves, add the water extraction dry extract that step (2) makes again, lactose; Carboxymethyl starch sodium, magnesium stearate, microcrystalline Cellulose, mixing; Tabletting, the bag film-coat, packing promptly gets Guiling dispersible tablets; The polyvinylpolypyrrolidone XL of said adding and the weight ratio of supercritical extraction concentrated solution are 2: 1.
3. the method for preparing of Guiling dispersible tablets as claimed in claim 2 is characterized in that, in the step (2): the said water extraction dry extract that is crushed into is to pulverize 60 mesh sieves to become the water extraction dry extract.
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| CN1985866A (en) * | 2005-12-20 | 2007-06-27 | 上海中药制药技术有限公司 | Application of Chinese medicine composition in treating cardiac and cerebral vascular diseases |
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