CN102204892A - Gingko flavanone aglycone dropping pills and preparation method thereof - Google Patents
Gingko flavanone aglycone dropping pills and preparation method thereof Download PDFInfo
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- CN102204892A CN102204892A CN 201110116535 CN201110116535A CN102204892A CN 102204892 A CN102204892 A CN 102204892A CN 201110116535 CN201110116535 CN 201110116535 CN 201110116535 A CN201110116535 A CN 201110116535A CN 102204892 A CN102204892 A CN 102204892A
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Abstract
The invention discloses a gingko flavanone aglycone dropping pills and a preparation method thereof. The dropping pills are prepared from gingko flavanone aglycone, a matrix and an antioxidant, wherein the matrix is polyethylene glycol 4000 to polyethylene glycol 10000; the antioxidant is vitamin C; the mass ratio of the gingko flavanone aglycone to the matrix is 1:(10-1):80; and the antioxidant accounts for 1 to 3 percent of all the materials. The preparation method comprises the following steps of: (1) uniformly mixing the gingko flavanone aglycone and the matrix in proportion, adding the vitamin C into the mixture, uniformly mixing, stirring and heating the mixture in a heating container until the mixture is melted, and preserving the heat; (2) adjusting the dropping disc temperature of a pill dropping machine to be between 65 and 85 DEG C and the temperature gradient of condensate to be between 30 and 10 DEG C to be between 4 and -4 DEG C; (3) dropping the melted material into the condensate through a dropping head on a dropping disc; and (4) taking out concentrated and formed dropping pills from the outlet of the pill dropping machine, removing the condensate, and drying the dropping pills to obtain the gingko flavanone aglycone dropping pills. The dropping pills have quick effect and high bioavailability and medicament stability and are suitable for industrial production.
Description
Technical field
The present invention is relevant with the medicinal preparation that contains from plant, and is particularly relevant with ginkgetin, furthermore, relates to the preparation of ginkgo flavone aglycone.
Background technology
Flavone compound in Semen Ginkgo (the Ginkgo biloba L.) leaf has only after the glucosidase of intestinal microbial population decomposes usually there not to be active glucosides combining form to exist, and forms just biologically active of ginkgo flavone aglycone; The glucosides type gingkgo flavonoids that is decomposed by intestinal microbial population is not difficult for being absorbed, and directly goes into intestinal from bile secretion and excretes.Many ginkgo flavone aglycones that studies show that have multiple biological activity, except that effect such as antibiotic, antiinflammatory, mutation, blood pressure lowering, heat-clearing and toxic substances removing, calmness, diuresis, in antioxidation, anticancer, anti-cancer, suppress aspect such as lipase remarkable result is also arranged.The preparation that contains ginkgetin at present has Folium Ginkgo etc., but the active component oral absorption in these preparations is poor, and bioavailability is low.Water insoluble and the aqueous medium of ginkgo flavone aglycone is so it is low because of its slightly solubility drug loading to make injection; And make oral formulations because of its slightly solubility, and medicine external speed in water is slower, and bioavailability is low.
The patent of Southern Yangtze University application No. 200510095762.5 " a kind of preparation method of flavone aglycone micro capsule " is to be core with isoflavone genin or ginkgo flavone aglycone, be mixed as the wall material with maltodextrin etc. respectively with gelatin, lactalbumin or soybean protein isolate, and with 95% ethanol or dehydrated alcohol lytic agent as core, the flavone aglycone of making is a capsule, but the adjuvant that this technology adopts is complicated, production cost is higher, and has problems such as organic solvent residual.And drop pill is a kind of bioavailability height, release fast, quick produce effects, medicament contg height, accurate measurement, taking convenience, cheap preparation.In the Chinese patent database, relevant drop pill is many, for example No. 02117473.3 " dropping pill of pueraria flavone and method for making ", No. 200410081605.4 " drop pills of hippophase rhamnoides and preparation method thereof ", No. 200610093611.0 " a kind of drop pills of seabuckthorn fruit flavone and preparation method thereof ".Still there is not at present the patent application of ginkgo flavone aglycone drop pill.
Summary of the invention
The objective of the invention is to remedy the deficiencies in the prior art, a kind of bioavailability height, fast release, produce effects, ginkgo flavone aglycone drop pill that toxic and side effects is little fast are provided.
Another purpose of the present invention provides the preparation method of ginkgo flavone aglycone drop pill, for the reasonable utilization of ginkgo flavone aglycone provides an industrial approach.
The inventor is at absorption characteristic in the medical value of ginkgetin and the body thereof, adopt prior art from the Folium Ginkgo medical material, to extract ginkgo flavone aglycone, this effective site is hydrolyzed, make glycoside material wherein slough glycosyl, generation has more bioactive aglycon, as the effective ingredient of ginkgo flavone aglycone drop pill.
The ginkgo flavone aglycone drop pill that the inventor provides is made jointly with ginkgo flavone aglycone and substrate and antioxidant, and described substrate is Macrogol 4000～cetomacrogol 1000 0, and described antioxidant is vitamin C; The mass ratio of ginkgo flavone aglycone and substrate is 1: 10～1: 80, and the mass fraction of antioxidant is 1%～3% of whole materials.
In the above-mentioned substrate, described matrix optimization Macrogol 4000.
The preferred mass ratio of above-mentioned ginkgo flavone aglycone and described substrate is 1: 40.
The preparation method of the ginkgo flavone aglycone drop pill that the inventor provides comprises:
The first step with ginkgo flavone aglycone and the substrate mass ratio mix homogeneously according to 1: 10～1: 80, adds the vitamin C mix homogeneously of whole materials 1%～3% again, places and is heated to fusion in the heating container while stirring, insulation;
Second step, adjust the temperature control system of drop pill machine, make the dish temperature of dripping of drop pill machine remain on 65 ℃～85 ℃, and to make the thermograde of condensed fluid be 30 ℃～10 ℃ → 4 ℃～-4 ℃;
In the 3rd step, the temperature of dripping dish and condensed fluid for the treatment of the drop pill machine was in for second step respectively during desired state of temperature, and the fused materials of the first step is splashed in the condensed fluid by a water dropper that drips on coiling;
In the 4th step, the drop pill that will be shunk molding by the outlet of drop pill machine takes out, and removes the condensed fluid on surface, is drying to obtain.
In the above-mentioned first step, the fused temperature that is heated to of described heating container is 65 ℃～90 ℃.
In above-mentioned second step, the preferred temperature of described dropping-pill machine dish is 80 ℃, error＜2%.
In above-mentioned the 3rd step, described water dropper diameter is 1.0～4.0mm; Described condensed fluid is any one in liquid paraffin, methyl-silicone oil, the vegetable oil.
In above-mentioned the 4th step, described drying mode is that room temperature is air-dry.
In order to realize said method, the inventor has done a series of tests, to determine process conditions, mainly contains:
Experiment 1 is selected to carry out the experiment of prescription without substrate
Experimental design: carry out the influence of prescription to product in order to observe ginkgo flavone aglycone and different substrates, respectively with Macrogol 4000,6000,10000 is substrate, mixed with 1: 30 is even respectively with ginkgo flavone aglycone and last 3 kinds of substrate, other is according to the step of preparation method, the material that each configuration set is good is heated to fusion respectively, utilize the drop pill machine, regulating its temperature control system and make and satisfy preparation method second requirement in step, is condensed fluid with the methyl-silicone oil, is prepared according to above-mentioned technical process, obtain the prescription experiment of 3 ginkgo flavone aglycones and different substrates, and obtain 3 groups of different experimental results and see Table 1:
Table 1 ginkgo flavone aglycone and the mutually blended experiment of different substrates
Result by table 1 can see: can find out from embodiment gained result, when selecting above 3 kinds of different substrates, all be not very big to every index influence.
Test the test of 2 ginkgo flavone aglycones and the different proportionings of substrate
Experimental design: carry out the influence of prescription with substrate with different ratios to product in order to observe ginkgo flavone aglycone, respectively with 1: 10/1: 30/1: 80 ratio, ginkgo flavone aglycone and substrate are carried out mix homogeneously, substrate is selected Macrogol 4000 for use, other is according to the step of preparation method, the material that each configuration set is good is heated to fusion respectively, utilize the drop pill machine, regulate its temperature control system and make the requirement of satisfying preparation method, with the methyl-silicone oil is condensed fluid, be prepared according to described technology, obtain the prescription experiment of 3 ginkgo flavone aglycones and the different proportionings of substrate, and obtain 3 groups of different experimental results and see Table 2:
The experiment of table 2 ginkgo flavone aglycone and the different proportionings of substrate
By table 2 as seen: when the mixed proportion of crude drug and substrate reached 1: 30, every index is corresponding to enter a preferable scope, and 1: though 80 index is also preferable, because therefore low administration specification that do not meet of drug loading does not select this ratio combination.
Test the experiment of selecting different water dropper temperature in 3 preparation process
Experimental design: select of the influence of different water dropper temperature in the preparation process for observing, utilize the drop pill machine, and adjust the temperature control system of drop pill machine to product, make its dish temperature remain on 80 ℃, 85 ℃, 90 ℃, temperature error＜2%, and make condensate temperature meet the method second step requirement; Substrate is selected Macrogol 4000 for use, ginkgo flavone aglycone and substrate is even with 1: 30 mixed, the material that configures is heated to fusion, with the methyl-silicone oil is condensed fluid, be prepared according to described method, 3 differences are dripped the experiment of coiling temperature and are obtained 3 groups of different experimental results, see attached list 3:
Table 3 is selected different experiments of dripping the dish temperature
| Drip the dish temperature | Effective ingredient (mass fraction)/% | Rounding rate/% | Dissolve scattered time limit/minute | The ball method of double differences is different/% | Hardness |
| 80℃ | 101.2 | 85 | ＜30 | ＞10 | +++ |
| 85℃ | 95.8 | 96 | ＜30 | ＜10 | +++ |
| 90℃ | 100.3 | 91 | ＜30 | ＜10 | +++ |
By table 3 as seen: when selecting different dripping to coil temperature, rounding rate, the different index of the ball method of double differences are influenced to some extent, and dissolve scattered time limit and hardness are not had obvious influence.
Test the experiment of selecting different condensed fluid in 4 preparation process
Experimental design: select of the influence of different condensed fluid in the preparation process to product for observing, respectively with liquid paraffin, methyl-silicone oil, vegetable oil as condensed fluid, other are all according to the condition and the step of preparation method, substrate is selected Macrogol 4000 for use, ginkgo flavone aglycone and substrate is even with 1: 30 mixed, the material that configures is heated to fusion, utilize the drop pill machine, regulate its temperature control system and satisfy the method requirement in described second step, be prepared according to described method, the experiment of 3 different condensed fluid obtains 3 groups of different experimental results and sees attached list 4 again:
Table 4 is selected the experiment of different condensed fluid
| Condensed fluid | Effective ingredient (mass fraction)/% | Rounding rate/% | Dissolve scattered time limit/minute | The ball method of double differences is different/% | Hardness |
| Liquid paraffin | 95.7 | 93 | ＜30 | ＜10 | +++ |
| Methyl-silicone oil | 98.4 | 96 | ＜30 | ＜10 | +++ |
| Vegetable oil | 105.2 | 90 | ＜30 | ＜10 | +++ |
By table 4 as seen: when selecting different condensed fluid, every index is not all had obvious influence.
Test the experiment of selecting different condensate temperatures in 5 preparation process
Experimental design: select of the influence of different condensate temperatures in the preparation process to product for observing, utilize the drop pill machine, and the refrigeration control system of adjustment drop pill, make the thermograde of condensing agent in the condensation column remain on 10 ℃ → 0 ℃ respectively, 20 ℃ →-2 ℃, 30 ℃ →-4 ℃, temperature error＜5%, substrate is selected Macrogol 4000 for use, other are all according to described method, ginkgo flavone aglycone and substrate is even with 1: 30 mixed, the material that configures is heated to fusion, with the methyl-silicone oil condensed fluid, utilize the drop pill machine, regulate its temperature control system and make the requirement of satisfying described second step of method, be prepared according to described method, the experiment of 3 different condensate temperatures obtains 3 groups of different experimental results and sees attached list 5:
Table 5 is selected the experiment of different condensate temperatures
By table 5 as seen: when selecting different condensate temperatures, little to every index influence.
Inventor's explanation: the hardness method for expressing in the above-mentioned table is that drop pill is placed on the glass plate, press...withes one's finger it, observes its metamorphosis."+" expression flicking promptly is out of shape, " ++ " expression distortion of firmly pressing, and " +++" expression is indeformable by it.
The present invention has been prepared into dropping pill formulation with ginkgo flavone aglycone first, compares with other dosage forms, and drug effect is fast, bioavailability is high, and medication is convenient, consumption is accurate; The medicine stability height, not facile hydrolysis, oxidation is not subject to the influence of crystal formation, and drug quality is guaranteed; Drop pill both can be swallowed, but also sublingual administration, also can be through the nasal feeding administration; After adding the antioxidant vitamin C, guarantee that the significant change of its related substances can not take place medicine in effective storage life.The drop pill cost is low, is suitable for suitability for industrialized production.
The specific embodiment
Following example can further specify the present invention:
Substrate is taken Macrogol 4000, and the mass ratio of ginkgo flavone aglycone and substrate is 1: 30.With ginkgo flavone aglycone and Macrogol 4000 mix homogeneously, add the vitamin C mix homogeneously of whole materials 1%～3% again, place to be heated to 80 ℃ in the heating container while stirring fusion, insulation;
The DWJDW-III type drop pill machine that adopts the rich gloomy pharmaceutical machine company limited in Yantai, Shandong to produce, and the temperature control system of adjustment drop pill machine, make the dish temperature of dripping of drop pill machine remain on 85 ℃, error＜2%, and to make the thermograde of condensed fluid be 30 ℃～10 ℃ → 4 ℃～-4 ℃;
The temperature for the treatment of dropping-pill machine dish and condensed fluid was in for second step respectively during desired state of temperature, will be fused material (the water dropper diameter is 1.0～4.0mm), splashes into methyl-silicone oil (condensed fluid of this example is selected the basic silicone oil of first for use) with suitable speed by dripping on the dish water dropper;
The drop pill that will be shunk molding by the outlet of drop pill machine takes out, and removes the condensed fluid on surface, the air-dry ginkgo flavone aglycone drop pill that is drying to obtain of room temperature.
Claims (7)
1. ginkgo flavone aglycone drop pill is characterized in that to be it make jointly with ginkgo flavone aglycone and substrate and antioxidant, and described substrate is Macrogol 4000～cetomacrogol 1000 0, and described antioxidant is vitamin C; The mass ratio of ginkgo flavone aglycone and substrate is 1: 10～1: 80, and the mass fraction of antioxidant is 1%～3% of whole materials.
2. according to the described ginkgetin aglycone dropping pill of claim 1, it is characterized in that it makes jointly with ginkgo flavone aglycone and substrate and antioxidant, described substrate is Macrogol 4000, described antioxidant is vitamin C; The mass ratio of ginkgo flavone aglycone and substrate is 1: 40, and the mass fraction of antioxidant is 1%～3% of whole materials.
3. the method for preparing the described ginkgetin drop pill of claim 1, its feature comprises:
The first step with ginkgo flavone aglycone and the substrate mass ratio mix homogeneously according to 1: 10～1: 80, adds the vitamin C mix homogeneously of whole materials 1%～3% again, places and is heated to fusion in the heating container while stirring, insulation;
Second step, adjust the temperature control system of drop pill machine, make the dish temperature of dripping of drop pill machine remain on 65 ℃～85 ℃, and to make the thermograde of condensed fluid be 30 ℃～10 ℃ → 4 ℃～-4 ℃;
In the 3rd step, the temperature of dripping dish and condensed fluid for the treatment of the drop pill machine was in for second step respectively during desired state of temperature, and the fused materials of the first step is splashed in the condensed fluid by a water dropper that drips on coiling;
In the 4th step, the drop pill that will be shunk molding by the outlet of drop pill machine takes out, and removes the condensed fluid on surface, is drying to obtain.
4. according to the described preparation method of claim 3, it is characterized in that in the described first step that the fused temperature that is heated to of described heating container is 65 ℃～90 ℃ ℃.
5. according to the described preparation method of claim 3, it is characterized in that the temperature of described dropping-pill machine dish is 80 ℃, error＜2% in second step.
6. according to the described preparation method of claim 3, it is characterized in that described water dropper diameter is 1.0～4.0mm in the 3rd step; Described condensed fluid is a kind of in liquid paraffin, methyl-silicone oil, the vegetable oil.
7. according to the described preparation method of claim 3, it is characterized in that described drying mode is that room temperature is air-dry in the 4th step.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274322A (en) * | 2013-07-11 | 2015-01-14 | 天士力制药集团股份有限公司 | Method for preparing drop pill by high-speed vibration in dropping way |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1876028A (en) * | 2005-05-12 | 2006-12-13 | 贵阳云岩西创药物科技开发有限公司 | Pharmaceutical preparation for treating coronary heart disease, its preparation process and quality control method |
| CN1921771A (en) * | 2004-02-18 | 2007-02-28 | 百太国际技术创新社 | Composition for preventing a cold |
| CN101780030A (en) * | 2010-03-09 | 2010-07-21 | 贵州大学 | Ginkgo flavone aglycone solid dispersion and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1921771A (en) * | 2004-02-18 | 2007-02-28 | 百太国际技术创新社 | Composition for preventing a cold |
| CN1876028A (en) * | 2005-05-12 | 2006-12-13 | 贵阳云岩西创药物科技开发有限公司 | Pharmaceutical preparation for treating coronary heart disease, its preparation process and quality control method |
| CN101780030A (en) * | 2010-03-09 | 2010-07-21 | 贵州大学 | Ginkgo flavone aglycone solid dispersion and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274322A (en) * | 2013-07-11 | 2015-01-14 | 天士力制药集团股份有限公司 | Method for preparing drop pill by high-speed vibration in dropping way |
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Application publication date: 20111005 |