Background technology
Folium Ginkgo extract is the Chinese herbal and crude drugs preparations that extracts from China's Chinese herbal medicine Ginkgoaceae plant Ginkgo biloba (Ginkgo biloba L) leaf; Folium Ginkgo has important medical value; wherein mainly contain medicinal ingredients such as Folium Ginkgo total flavones class, lactone; bibliographical information Folium Ginkgo total flavones, lactone have the expansion artery blood vessel and improve and promote cardiovascular and cerebrovascular circulation and brain cell metabolism; the effect of the treatment heart, cerebrovascular disease, and aspect the protection cranial nerve effectively.The sixties in 20th century, Germany scientist found that Folium Ginkgo contains ginkgo flavonoid glycoside and bilobalide, the Shi Wabai pharmaceutical factory of Germany and French Bo Fu-beneficial Pu Shengyaochang etc. carry out a large amount of research to the chemical constituent of Folium Ginkgo and produce ladder and protect preparations such as peaceful, Tanakan and Ginaton, and the standard EGB761 of Folium Ginkgo extract is also formulated in Europe.Gingko leaf preparation and Semen Ginkgo class health food are one of plant series products the most popular on the market, the world today.With " ladder protect peaceful " and " Ginaton " is that the gingko leaf preparation of representative is gained high reputation on international medical market.Estimate according to American economist: global various gingko leaf preparations add panoramic gingkgo health care food and the cosmetics etc. that contain the Semen Ginkgo extrac composition, and present world market total sales volume is above 5,000,000,000 dollars.U.S. consumer takes the Folium Ginkgo product as the health food that prevents apoplexy and coronary heart disease.It is reported that the research worker of department of medial science of the state university of Oregon, America is found in the clinical research that reaches the time more than 3 years: the long-term oral gingko leaf preparation of over-65s old man can effectively prevent memory to degenerate and Alzheimer.Because EGB has fine reputation in American-European countries; and it is moderate; be fit to very much consumer of vast wage-earners and take, again because of EGB in the useful effect aspect the protection cranial nerve, promoted the development of gingko leaf preparation in the U.S. and other Hesperian sales volumes and research.China began to make Folium Ginkgo extractum sheet (6911) with Folium Ginkgo extractum 60~seventies of 20th century, had Folium Ginkgo tablet, capsule, oral liquid and injection to go on the market successively later on successively.Kind surplus the known Folium Ginkgo extract chemical constituent of research reaches 160 at present.Mainly contain flavonoid, terpenoid, phenols, alkaloid, polyisoamylene, quininic acid, linoleic acid, boa oxalic acid, ascorbic acid, a-olefine aldehydr, Ginnol, bilobanone etc.Be the active main body composition wherein, based on the Folium Ginkgo oral formulations,, also have injection on the market as tablet, capsule, granule and oral liquid with ginkgetin class and bilobalide.According to the particularity of the market demand and old medication, we invent and have developed the folium ginkgo dripping pill preparation.Compare with similar medicine, it is strong, rapid-action that folium ginkgo dripping pill has effect, can make things convenient for advantages such as oral application.Since in the Folium Ginkgo composition such as total flavone part have draw moist, principal agent dosage is little, Folium Ginkgo and capsular volume with the traditional method preparation are big, time disintegration is long relatively, dissolution and dissolution rate are low, supplementary product consumption is big, and old people and bed patient and dysphagia patien take inconvenience, and compliance is poor.Folium ginkgo dripping pill of the present invention is a kind of efficient, quick-acting, Chinese medicine preparation that bioavailability is high.The exploitation folium ginkgo dripping pill has practical value concerning current medical market field and old usefulness market, also embodied novelty of the present invention and practicality.
The present invention makes folium ginkgo dripping pill by using fusion method and solid-state dispersion technology, correct and overcome some defectives and the deficiency of dosage forms such as tablet, capsule, because the drop pill volume is little, easy to carry, can be oral or through the oral cavity, sublingual administration absorbs and taken place by metabolic first pass effect when reducing medicine by liver, provide great convenience to elderly patients and dysphagia patien, improved the compliance of medication.
Summary of the invention
The present invention makes folium ginkgo dripping pill by using fusion method and solid-state dispersion technology, and it is rapid that this drop pill has a disintegrate, dissolution and dissolution rate height, steady quality characteristics.Because the drop pill volume is little, easy to carry and use, can be oral or oral cavity, sublingual administration, the old people is bed patient and dysphagia patien's taking convenience especially, and compliance is good, and the bioavailability height.Relatively with tablet, capsule, folium ginkgo dripping pill agent supplementary product consumption of the present invention is few, and working condition and production equipment are simple, reduces pollutions such as dust from flying, and reduction labor intensity reduces production costs, and shows characteristics of the present invention.
By Folium Ginkgo extract is prepared into drop pill, be applied to aspect diseases such as the heart, cerebrovascular, also be characteristics of the present invention.
The existing pharmaceutic adjuvant that meets medicinal requirements of adjuvant that the present invention is selected also has the natural edible-plant adjuvant.By a large amount of Test Summaries, obtain a result, this drop pill drug component is formed and is comprised: Folium Ginkgo extract, appropriate amount of auxiliary materials, wherein adjuvant comprises fillibility dispersion adjuvant and has the plasticity adjuvant, fillibility disperses adjuvant that Macrogol 4000, polyethylene glycol 6000, polyethylene glycol 1500 are arranged, polyoxyethylene stearate (40) ester, polyoxyethylene sorbitan monoleate, xylitol, sorbitol, mannitol, lactose, insect wax, sodium stearate etc., the plasticity adjuvant has glycerin gelatine, Resina persicae, arabic gum, starch, dextrin, alginic acid, glucosamine etc.
Preferred substrate adjuvant of the present invention is Macrogol 4000 and polyethylene glycol 6000, and Macrogol 4000 is 1:0.3~0.5 with the ratio of the weight of polyethylene glycol 6000.Also have Macrogol 4000, polyethylene glycol 6000 and polyethylene glycol 1500, its weight ratio is 1:1:0.5.And the ratio of xylitol and the weight of starch is 1:0.3~1:0.5, or the ratio of sorbitol and the weight of starch is 1:0.2~1:0.5.
Folium Ginkgo extract is 1:0.5~1:20 with the ratio of the weight of adjuvant in the pharmaceutical composition of the present invention.
Preferred pharmaceutical composition Chinese medicine of the present invention is 1:1~1:12 with the ratio of adjuvant.
Best pharmaceutical composition Chinese medicine of the present invention is 1:2~1:10 with the ratio of adjuvant.
The ratio of the adjuvant of pharmaceutical composition of the present invention and amount of drug all is in pharmaceutics and the pharmacopeia allowed band, Folium Ginkgo extract is measured its main component according to the gainer under 2005 editions two items of Pharmacopoeia of People's Republic of China: Folium Ginkgo total flavones, flavone lactone equal size, feed intake by metering, Folium Ginkgo total flavones, flavone lactone content that makes every ball etc. reaches pharmacopeia regulation content and requirement, the drop pill of manufacturing of the present invention have make easy, steady quality, efficient, quick-acting, clinical administration convenient, can be oral or the advantage of oral cavity and sublingual administration.
The present invention is based on fusion method and solid-state dispersion technology, with 1 weight portion Folium Ginkgo extract and 0.5 to 5 parts by weight solvent through being dissolved into homogeneous solution, join in 1 to the 15 weight portion molten matrix by the phase process for dispersing that disperses to drip, stir, press the drop pill dropping preparation method and in coolant, drip system, be condensed into ball, wipe coolant, drying, promptly.
Specific implementation method
One, example 1
Prescription
Folium Ginkgo extract 20g
Polyethylene glycol 6000 20g
Macrogol 4000 20g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused polyethylene glycol 6000, Macrogol 4000, polyoxyethylene sorbitan monoleate composition, be stirred well under 80 ℃ evenly, with the dimethicone is coolant, makes ball for 15 ℃ following, wipes ball, drying, promptly.
Two, example 2
Prescription:
Folium Ginkgo extract 20g
Macrogol 4000 40g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused Macrogol 4000, polyoxyethylene sorbitan monoleate composition, be stirred well to evenly, with the dimethicone is coolant, makes ball for 10 ℃ following, wipes ball, drying, promptly.
Three, example 3,
Prescription:
Folium Ginkgo extract 20g
Polyethylene glycol 6000 40g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused polyethylene glycol 6000, polyoxyethylene sorbitan monoleate composition, being stirred well to evenly, is coolant with the dimethicone, makes ball for 15 ℃ following, wipe ball, drying, promptly.
Four, example 4
Macrogol 4000 30g
Polyoxyethylene stearate { 40} ester 10g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add fused Macrogol 4000, { in the substrate that the 40} ester is formed, be stirred well to evenly, be coolant with petrolatum or dimethicone to polyoxyethylene stearate, drip below 15 ℃ and make ball, wipe ball, drying, promptly.
Five, example 5,
Prescription:
Folium Ginkgo extract 20g
Polyethylene glycol 1500 40g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused polyethylene glycol 1500, polyoxyethylene sorbitan monoleate composition, be stirred well under 70 ℃ evenly, with the dimethicone is coolant, makes ball for 15 ℃ following, wipes ball, drying, promptly.
Six examples 6
Prescription:
Folium Ginkgo extract 20g
Polyethylene glycol 6000 20g
Polyethylene glycol 1500 20g
Polyoxyethylene sorbitan monoleate 0.5g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused polyethylene glycol 6000, polyethylene glycol 1500, polyoxyethylene sorbitan monoleate composition, be stirred well under 70 ℃ evenly, with the dimethicone is coolant, makes ball for 10 ℃ following, wipes ball, drying, promptly.
Seven examples 7
Prescription:
Folium Ginkgo extract 20g
Macrogol 4000 20g
Polyethylene glycol 1500 20g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused Macrogol 4000, polyethylene glycol 1500, polyoxyethylene sorbitan monoleate composition, be stirred well under 60 ℃ evenly, with the dimethicone is coolant, makes ball for 10 ℃ following, wipes ball, drying, promptly.
Eight, example 8
Prescription
Folium Ginkgo extract 20g
Polyethylene glycol 6000 20g
Macrogol 4000 10g
Polyethylene glycol 1500 10g
Polyoxyethylene sorbitan monoleate 0.6g
Ethanol 5ml
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, become Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, polyoxyethylene sorbitan monoleate composition, be stirred well under 70 ℃ evenly, with the dimethicone is coolant, makes ball for 15 ℃ following, wipes ball, drying, promptly.
Nine, example 9
Prescription
Folium Ginkgo extract 20g
Ethanol 5ml
Insect wax 20g
Sodium stearate 20g
Polyoxyethylene sorbitan monoleate 0.6g
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, add in the substrate of fused insect wax, sodium stearate, polyoxyethylene sorbitan monoleate composition, be stirred well to evenly, make ball, wipe ball with 5 ℃ following of brine ice, drying, promptly.
Ten, example 10
Prescription
Folium Ginkgo is carried thing thing 20g
Ethanol 5ml
Gelatin 30g
Glycerol 10g
Polyoxyethylene sorbitan monoleate 0.6g
Medicinal plant oil is an amount of
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, standby, gelatin, glycerol adds the water mixing, and heating in water bath stirred evenly into gelatin solution in 1 hour, is chilled to 50 ℃ and disperses ethanol liquid and vegetable oil to be mixed into Folium Ginkgo Folium Ginkgo to disperse medicinal liquid, stir, insulation to 65 ℃ adds in the gelatin and environmental sealing with the dosing pump dropping-pill machine, cools off in medicinal plant oil, dries coolant, press the soft capsule conventional drying, promptly.
11, example 11
Prescription
Folium Ginkgo extract 20g
Ethanol 5ml
Xylitol 25g
Starch 5g
Polyoxyethylene sorbitan monoleate 0.6g
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, standby, xylitol adds an amount of mixing of water, and heating in water bath 5 minutes stirs evenly into solution, be chilled to 60 ℃, add starch, polyoxyethylene sorbitan monoleate, stir, be added dropwise to Folium Ginkgo at last and disperse ethanol liquid, stir, insulation is dripped in white oil or dimethicone with dosing pump drop pill machine or water dropper to 65 ℃ and is cooled off, and dries, drying, promptly.
12, example 12
Prescription
Folium Ginkgo 20g
Ethanol 5ml
Sorbitol 30g
Starch 10g
Polyoxyethylene sorbitan monoleate 0.6g
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, standby, sorbitol adds an amount of mixing of water, and heating in water bath 5 minutes stirs evenly into solution, be chilled to 60 ℃, add starch, polyoxyethylene sorbitan monoleate, stir, be added dropwise to Folium Ginkgo at last and disperse ethanol liquid, stir, insulation is dripped in white oil or dimethicone with dosing pump drop pill machine or water dropper to 65 ℃ and is cooled off, and dries, drying, promptly.
12, example 13
Prescription
Folium Ginkgo 20g
Ethanol 5ml
Lactose 30g
Starch 10g
Polyoxyethylene sorbitan monoleate 0.6g
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, standby, lactose adds an amount of mixing of water, and heating in water bath 5 minutes stirs evenly into solution, be chilled to 60 ℃, add starch, polyoxyethylene sorbitan monoleate, stir, be added dropwise to Folium Ginkgo at last and disperse ethanol liquid, stir, insulation is dripped in white oil or dimethicone with dosing pump drop pill machine or water dropper to 65 ℃ and is cooled off, and dries, drying, promptly.
14, example 14
Prescription
Folium Ginkgo 20g
Ethanol 5ml
Xylitol 30g
Arabic gum 10g
Polyoxyethylene sorbitan monoleate 0.6g
Make 1000 balls
Method for making: Folium Ginkgo extract is dissolved in fully dissolving in the ethanol, becomes Folium Ginkgo extract and disperse ethanol liquid, standby, xylitol adds an amount of mixing of water, heats to stir evenly into solution in 5 minutes, is chilled to 60 ℃, add arabic gum, polyoxyethylene sorbitan monoleate, 65~80 ℃ of heating in water bath are to dissolving, stir, be added dropwise to Folium Ginkgo at last and disperse ethanol liquid, stir, insulation to 65 ℃ is dripped in white oil or dimethicone with dosing pump drop pill machine or water dropper and to be cooled off, dry, drying, promptly.