A kind of cyclovirobuxine dripping pills and preparation technology thereof
Technical field
The present invention relates to a kind of medicinal preparation, more particularly, relate to cyclovirobuxinum D (C
26H
46N
2O) and the substrate adjuvant be prepared from Traditional Chinese Medicine Dropping Pill.
Background technology
Coronary heart disease also claims ischemic heart desease, since its sickness rate height, the mortality rate height, and the healthy of the mankind in serious harm, thereby b referred to as " the first human killers ".Angina pectoris is a coronary insufficiency, and cardiac muscle is rapid, of short duration ischemia and the caused clinical syndrome of anoxia.Angina pectoris is the coronary heart disease common sympton, be more common in more than 40 years old in, the old people, the male is more than the women.Angina pectoris usually occurs in fatigue, heavy meal, catch cold and when excited, vexed pain, squeezing pain or constriction that the right occurrence scope of metosteon is not clear, and pain is shoulder, middle finger, the third finger and little finger of toe radiation to the right.At present, it is more to be used for the treatment for the treatment of coronary heart disease and angina pectoris, though Western medicine is rapid-action, curative effect is determined, but the influence of its toxic and side effects, make the patient when curing a kind of disease, the misery that faces other be arranged, appearance along with multiple difficult serious symptom miscellaneous diseases, western medical treatment presents imperfect, the human lives and the healthy reality and the up-to-date successes achieved in research have all proposed query to this situation, particularly along with the continuous appearance of chemical drugs toxic and side effects, the change of spectrum of disease and conversion of medical, make modern medicine be subjected to unprecedented challenge, and people also place hope in the application and development of traditional medicine on gradually.Advocate back to nature, pay attention to plant amedica use, hanker after traditional remedies, the trend of advocating natural drug forms, making full use of natural materials is human best selections.
At present, in the world, natural drug all has certain market, along with people increasing and the aging of population to the health requirements level of understanding, sub-health stateization, people thirst for back to nature more, utilize the high Drug therapy of pure natural degree, prevent some chemical synthetic drugs cann't be solved problem, so the background that exceeds its original traditional national culture has been expanded in the application of natural plant.From natural drug, seek the little and inexpensive medicine of side effect and become the target that countries in the world pharmaceutical manufacturer is chased.The European Community has carried out unified legislation to medical herbs, state medical herbs status such as Canada and Australia have legalized, U.S. government has also drafted the plant amedica management method, the compound recipe mix preparation that begins to accept natural drug is as curative, and these provide good international environment for Chinese medicine enters international medical market as curative.On the other hand, along with the quickening of global economic integration progress, particularly China becomes a full member of WTO, and Chinese Medicine market incorporates the breadth and depth of international medical big market and will further aggravate.Face the enormous impact of Asian countries's traditional medicine product such as the keen competition of powerful transnational medical group and Japan, Korea S, India, Thailand and European countries' plant amedica such as Germany, France, numerous products that China's Chinese medicine produces are owing to still can not meet the standard of international medical market and requirement and being kept outside of the door.And present most of Chinese medicine preparation ubiquity curative effect instability, curative effect is low, onset is slow, consumption is many shortcoming.Cyclovirobuxinum D (C
26H
46N
2O) be traditional Chinese medicinal materials assortment that records of Chinese Pharmacopoeia (version in 2000), this product promoting flow of QI and blood, removing obstruction in the collateral to relieve pain.Cyclovirobuxinum D is the effective ingredient that is divided into the raw material extraction with the xylem of Chinese little leaf boxwood.Ming Dynasty's Li Shizhen (1518-1593 A.D.) Compendium of Material Medica record has the effect of promoting flow of QI and blood, treatment of arthritis and promoting collateral and channels.Cyclovirobuxinum D is recorded in one one of pharmacopeia in 2000 as Chinese crude drug, is that unique Chinese medicine preparation Buxine Tablet of primary raw material is also recorded in one one of pharmacopeia in 2000 as Chinese patent medicine with the cyclovirobuxinum D, also has the cyclovirobuxine dripping pills agent to emerge at present, and is evident in efficacy.But expansion and human back to nature requirement along with the market global range, use the low medicine of toxic and side effects, especially pure natural medical more and more becomes people's first-selection, dropping pill formulation be a kind of have efficient, quick-acting new medicine preparations, it has overcome the shortcoming and deficiency of Chinese medicine preparation in the past, but present dropping pill formulation generally faces following problem: 1, drop pill adjuvant pure natural degree is not high: at present, drop pill substrate adjuvant mostly is synthetic, natural degree is lower, the searching of new alternative substrate adjuvant, the searching of the alternative substrate adjuvant that particularly natural degree is high and preparation technology thereof determine, it is again very difficult thing, because the required preparation condition of at present common possible natural substrates adjuvant succedaneum is very harsh, it all is to influence the key that drop pill prepares molding that adjuvant temperature and drop pill thereof drip the system condition.The too high then viscosity of adjuvant melt temperature is low, and poor plasticity is though the adjuvant melt temperature is crossed lowplastcity by force, but drop pill has shortcomings such as easily sticking ball, distortion, therefore, seek pure natural degree height, and the adjuvant that is suitable for substituting existing drop pill substrate is a very job of hardships.2, the drop pill outlet encounters problems: along with expanding economy, more and more internationalize in market, China is also just making great efforts to adapt to this trend, present Chinese medicine dripping pills preparation as health food, successful export to many countries, but also face many problems at present, because different countries is different to the approval of the selected adjuvant of Chinese medicine dropping pill formulation, especially industrial flourishing Europe, more strict to food adjuvant and medical auxiliary materials, and as the selected chemosynthesis adjuvant (as Polyethylene Glycol) of the dropping pill formulation of health food outlet not in the catalogue of some national food additive, it is very unfavorable that this moves towards the international market to the Chinese medicine dropping pill formulation, becomes the stumbling-block that Chinese medicine enters the international market, therefore, seek the new of one or more, can be particularly important, also very urgent for the substrate adjuvant that the international market is accepted.3, the shortcoming of mouthfeel and onset speed: the mouthfeel of Chinese medicine and preparation thereof is relatively poor to be the big characteristics of one, people when taking some drugs to the frightened of disagreeable taste that medicine had even be better than fear far away to disease, What is more, some patients are because can not overcome the poor taste of Chinese medicine or its preparation or abnormal smells from the patient and abandon the treatment of Chinese medicine, though can improve mouthfeel as medicine being made capsule or sugar coated tablet, reducing stimulates, but disintegration rate prolongs, be unfavorable for the rapid onset of medicine, to some disease, particularly need the disease of the rapid onset of medicine inapplicable.4, the preparation process difficulty of drop pill suitability for industrialized production: in the replacement process of dropping pill formulation adjuvant, determining of the preparation process of its suitability for industrialized production is very difficult something, as the ratio of the melt temperature of substrate adjuvant, the proportioning of dripping system temperature, adjuvant and medicine, dropper bore, condensing agent etc. all are the factors that influence drop pill, therefore, the replacement of substrate and to be suitable for suitability for industrialized production be a job consuming time, as to expend substantial contribution.
In order to change drop pill substrate adjuvant for a long time based on the situation of chemosynthesis adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and can not satisfy more and more that people require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect; Also can solve some problems that Chinese medicine preparation, particularly dropping pill formulation are run in exit procedure, strengthen the competitiveness of international market; The present invention has invented the pure Chinese medicine dripping pills preparation that a kind of toxic and side effects is low, evident in efficacy, moderate, adapt to industrialized great production by a large amount of tests and the research of preparation process.
Summary of the invention
The purpose of this invention is to provide a kind of treatment coronary heart disease, anginal medicine with the preparation of new type natural substrate adjuvant.
Another object of the present invention provides a kind of cyclovirobuxine dripping pills preparation and preparation method thereof.
The selected substrate adjuvant of the present invention is resulting by a large amount of tests, it is little to have molecular weight, soluble in water, and molten diffusing speed is faster, pure natural degree height, toxic and side effects is lower, and can reduce the medicine irritation abnormal smells from the patient, has the oral cavity of improvement acid-base value during the buccal of oral cavity, improve the characteristics of oral cavity smell, the used substrate adjuvant of the present invention is the agent of food sedan-chair flavor, takes that mouthfeel is good, the acceptant characteristics of patient, is the direction of following substrate adjuvant development.
The consumption of drug component of the present invention and the selection of adjuvant thereof also grope to sum up to draw through the inventor in a large number, each component raw material survival dose all has curative effect preferably in following ranges: the weight ratio of cyclovirobuxinum D and substrate adjuvant is 1: 30~90 preparations of making, wherein adjuvant comprises filler and plasticity substrate, said filler is selected from the natural adjuvant of following one or more plant origins: erythritol, sorbitol, fructose, D-ribonic acid-gamma lactone, arabitol, trehalose, D-ribose, low melting-point agarose, Lac, xylitol, Raffinose, glucose, malic acid, citric acid, isomalt, lactose, maltose etc., and they contain the water of crystallization chemical compound; Said plasticity substrate is selected from the natural adjuvant of following one or more plant origins: starch and derivant thereof, cellulose and derivant thereof, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Described starch and derivant thereof such as pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch, described cellulose and derivant thereof such as methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose; The consumption of preferred drug component of the present invention and the weight ratio that adjuvant is cyclovirobuxinum D and substrate adjuvant thereof are 1: 40~60 preparations of making, filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: sorbitol, xylitol, lactose, maltose, and they contain the water of crystallization chemical compound; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose; The consumption of best drug component of the present invention and the weight ratio that adjuvant is cyclovirobuxinum D and substrate adjuvant thereof are the preparation of making at 1: 51, and filler adjuvant wherein is selected from following one or more the natural adjuvant of plant origin: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum.
Can also contain chemosynthesis adjuvant and animal origin adjuvant in the above-mentioned dressing, wherein filler comprises phenylglycol, hexadecanol, octadecanol, sodium stearate, tristerin, tripalmitin, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether; Wherein plasticity substrate comprises polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, gelatin.
In screening to above adjuvant, we find: plant colloid such as carrageenan, the tragakanta, pectin, agar, arabic gum, Ficus elastica, tamarind gum, locust bean gum, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, guar gum, Konjac glucomannan, it is big that plant colloids such as POLY-karaya have viscosity, mobile poor, characteristics such as do not solidify after the condensation, and arabic gum has high dense low sticking character, can be mixed with the aqueous solution of 50% concentration and still have flowability, this is one of not available characteristics of other hydrophilic colloid, arabic gum has at high temperature, under the low concentration, can ooze, but not condensation, at low temperature, under the high concentration, be difficult for oozing, but characteristics such as energy condensation.Polysaccharide such as polysaccharide such as starch and derivant thereof (as gelling starch, carboxymethyl starch etc.), cellulose derivative (as methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose etc.), alginic acid, dextrin, cyclodextrin, lactose, in screening, find alginic acid have viscosity big, be the fruit jelly sample, dextrin has the colloid sample, characteristics such as lactose coagulability difference; And starch and derivant thereof are materials commonly used in the medical science adjuvant, thus in polysaccharide preferred starch and derivant thereof.Polyhydric alcohol such as sorbitol (88~102 ℃), xylitol (88~94.5 ℃), lactose (70~80 ℃), mannitol (166~169 ℃), maltose alcohol (135~140 ℃), isomalt polyhydric alcohol such as (98~103 ℃) screen, and find that it has following characteristics as drop pill substrate: sorbitol, lactose, isomalt are mobile poor; Mannitol, maltose alcohol fusing point are too high; The xylitol coagulability is poor slightly.After Preliminary screening, preferred xylitol, lactose, sorbitol in the selection of polyhydric alcohol, the best is an xylitol.Xylitol has following characteristics as drop pill substrate: in the time of 91 ℃, molten condition has appearred in xylitol, but not fusion fully, cooling rapidly, it separates out crystallization very soon, xylitol mixes the back good fluidity with extractum at certain proportion, can drip and can condensation, but be condensed into Powdered thing, loosely organized, the toughness extreme difference, that pinches is promptly broken.Organic acid and salt, alkali such as citric acid (100 ℃), sorbic acid (133 ℃), succinic acid (181~189 ℃), sodium acetate organic acid such as (58 ℃) and salt, alkali, its as drop pill substrate have fusing point too high, with Chinese medical concrete can't mixing etc. shortcoming.
Because of above single adjuvant existing shortcoming in as the drop pill preparation process, particularly we by above-mentioned Preliminary screening after, determine two kinds of adjuvants are used and screen: mainly be that above various adjuvants are carried out combined sorting, final determine following several: the plant colloid cooperates with the plant colloid, the cooperating of polyhydric alcohol and polyhydric alcohol, polyhydric alcohol and plant colloidally cooperate, the cooperating of the cooperating of xylitol and arabic gum, lactose and arabic gum, based on the composite auxiliary material of xylitol.Find preferred the cooperation to be xylitol, lactose and the compound use of other adjuvant, this kind combination has following characteristics: make up with mannitol: can drip not condensation; Make up with sorbic acid: both do not dissolve each other; Make up with lactose: can drip the energy condensation, but frangible; Make up with pomelo-pectin, tragakanta, sodium alginate: viscosity is big, can't drip; Make up with arabic gum: can drip, coagulability is poor slightly; Make up with dextrin: can drip, coagulability is poor slightly; Make up with starch: can drip, coagulability is also better.Determine that at last best of breed is that xylitol cooperates with arabic gum with starch, xylitol with starch, lactose.
At xylitol and starch, lactose and starch, in the research of xylitol and arabic gum combination, xylitol and starch Application of composite being prepared some required in the process of drop pill factors investigated, mainly is to the xylitol type, condensed fluid, condensate temperature influences the drop pill mouldability, xylitol and starch proportion influence mouldability, temperature is to the influence of drop pill mouldability, the extractum amount influences the drop pill mouldability, mixing time influences the drop pill mouldability, the dropper bore is to the influence of drop pill particle diameter, the formulation optimization of drop pill, the Preliminary Determination of drop pill, dissolve scattered time limit is investigated.Find that the solid xylitol has three types of powder, granular and crystallinity, and the easiest fusion of powder xylitol, again can fine dissolving be dispersed in the mixed liquor that starch, extractum forms, good fluidity, drippage is easy, and granular and crystalline xyhose alcohol is difficult for fusion, solubility property is also slightly poor, the mix flow that they and starch, extractum form is relatively poor, viscosity is very big, almost cannot drip, and therefore drips first-selected powder xylitol in the system process at drop pill.
At ratio of adjuvant molding is found in the sex research, in the combination of xylitol and starch, lactose and starch, xylitol and arabic gum, low melting point substrate adjuvant is 1: 0~1: 1.5 with the ratio of the weight of plasticity substrate adjuvant, be preferably 1: 0.1~1: 0.9, the best is 1: 0.1~1: 0.5.Low melting point substrate adjuvant of being formed within this scope and plasticity substrate adjuvant, the drug matrices fused solution all can ooze, and can condensation.Specific to each combination, xylitol is preferably 1: 0.2 with the ratio of the weight of starch~1: 0.3, and lactose is preferably 1: 0.2 with the ratio of the weight of starch~1: 0.3, and the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2~and 1: 0.4.Find that in the research of temperature temperature is big especially to the influence of drop pill mouldability to the influence of drop pill mouldability, when temperature is too low, owing to the too big effect that oozes that influences drop pill of viscosity of substrate, when temperature is too high, not condensation of drop pill.Find that mixing time can have influence on the mouldability of drop pill in mixing time in to the sex research of drop pill molding, mixing time is too short, and mobile poor, influence oozes, and mixing time is oversize, influences the condensation of drop pill.Dripping under the system temperature, mixing time in 1~120 minute all can, suitable mixing time was at 10~30 minutes.Consider that mixing time can not be too short in the suitability for industrialized production, adopt the method that low temperature stirs for a long time, high temperature drips system.Find that in the research of dropper bore to the influence of drop pill particle diameter the dropper bore influences the size of drop pill and the flowability of fusion substrate, the system effect is dripped in influence.Drop pill diminishes and diminishes along with bore, but after 1.4 millimeters, along with the bore change of size that diminishes is not obvious, but the matrix flow reduction, system is dripped in influence.
In the preparation method of medicine of the present invention, these two kinds of methods of fusion method and solvent-fusion method all can be used as the method for making drop pill, but the preferred molten method.
With the uniformity of dosage units is index, can find out that the uniformity of dosage units of fusion method and solvent-fusion method is all up to specification (A+1.80S≤15.0), sees Table 6.But solvent-fusion method operation is more numerous and diverse, and whether ethanol is got rid of totally in bad definite fused solution, the difficult operation of big commercial production, and cost is also bigger; From appearance luster, the drop pill color that fusion method is made is off-white color, and size is even, smooth surface, solid colour; The drop pill color that solvent-fusion method is made is faint yellow, size evenly, solid colour, but there is plaque on its surface, rough, this be because ethanol is got rid of not exclusively and heat time heating time long due to.Therefore, preferred molten method.
The drop pill uniformity of dosage units of table 1, different melting methods
Melting method | Direct mixed melting | Solvent-fusion |
Appearance luster | Off-white color | Faint yellow |
X | 97.4 | 97.2 |
S | 5.67 | 5.24 |
A | 2.60 | 2.80 |
A+1.08S | 12.81 | 12.23 |
In the process of making cyclovirobuxinum D-adjuvant fused solution, because the stirring that need not stop, so that make fused solution become a homogeneous system, so in fused solution, contain air in certain amount.But in making the process of drop pill, must exclude air, otherwise can influence the roundness of drop pill.Therefore, after fused solution makes, must insulation place a period of time, the air in the fused solution is got rid of totally fully.Fused solution has a little hangover when water dropper drips, and when moving, fused solution then may bring the sub-fraction air into again in air, if the condensed fluid upper temp is too low, then hangover has little time withdrawal, air has little time to discharge fused solution and promptly solidifies, influences shaped degree of drop pill and surface flatness.Condensed fluid lower floor temperature is too high, and the fused solution condensation is incomplete, and drop pill can also influence the drop pill roundness in condensate line bottom adhesion.Certain at principal agent cyclovirobuxinum D and substrate adjuvant ratio, under the certain situation of fused solution temperature, the major influence factors of drop pill weight and the different size of the ball method of double differences has the water dropper bore, drips speed, drips distance.The present invention uses orthogonal tests to investigate to water dropper bore, the factors such as speed, a distance of dripping.In the preparation method of medicine of the present invention, medicine mixes mixing time with the substrate adjuvant be 10~30 minutes; The mixed heating and melting temperature of medicine and substrate adjuvant is 45~115 ℃, dripping the system temperature is 45~95 ℃, and liquid coolant is liquid paraffin, methyl-silicone oil or vegetable oil (Oleum Glycines, Semen Ricini wet goods), and the temperature of liquid coolant is-20~25 ℃, dropper mouth internal diameter is 1.0~4.0 millimeters; Preferred heating and melting temperature is 60~85 ℃, and dripping a system temperature is 60~85 ℃, and condensing agent is that liquid paraffin, methyl-silicone oil condensing agent temperature are 0~18 ℃, and the dropper bore is 1.1~3.5 millimeters, and the difference of dropper mouth external diameter and internal diameter is less for well; Best for the heating and melting temperature is 64 ℃, drip that to make temperature be that 64 ℃, dropper bore are that 1.2~2.5 millimeters, condensing agent are 0 ℃ methyl-silicone oil; Preferred top condensed fluid height is 10~35cm, and bottom condensed fluid height is 20~40cm, drips apart from being 2~10cm, and dripping speed is 20~40 droplets/minute; Best top condensed fluid height is 20cm, and bottom condensed fluid height is 30cm, drips apart from being 5cm, and dripping speed is 30 droplets/minute.
The substrate adjuvant of the best of the present invention is xylitol and starch, and xylitol is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2~1: 0.4.
Xylitol is a kind of natural plant sweetening agent, approve through World Health Organization (WHO), xylitol is a kind of safest sweeting agent, countries in the world are extensive use of in fields such as food and oral-cavity articles, xylitol enters the help that need not insulin in the cell, when sugar utilizes obstacle, can not cause blood sugar increasing yet, can improve diabetics symptom, have the ketoplastic effect of powerful inhibition, can promote the generation of liver glycogen, directly infiltrate the Developmental and Metabolic Disorder that tissue is participated in metabolism, can be corrected protein, fat and steroid; Xylose is the internal metabolism intermediate product, and body has higher toleration to it.Clinical practice proves: the highest oral dosis tolerata can reach 220g every day, and intravenous drip every day can reach 100g.The oral 25700mg/Kg of median lethal dose(LD 50) (LD50) mice, quiet notes 6400mg/Kg, the quiet notes of rat 6200mg/Kg.
Medicine mesostroma adjuvant of the present invention and amount of drug are than being the scope that allows on the galenic pharmacy, and medicine described here is meant Buxine or the medicine of same therapeutical effect is arranged with it.
Medicine of the present invention can adopt the preparation conventional method to be prepared into any conventional formulation.As make tablet, granule, pill etc., but in order to make this medicine better bring into play drug effect, preferred the present invention adopts and is prepared as follows the method preparation, but this can not limit protection scope of the present invention.
The preparation method of medicine of the present invention is as follows:
Take by weighing adjuvant by formula ratio, heat fused, the cyclovirobuxinum D of adding formula ratio, fully stir and make its complete fusion, be uniformly dispersed, make fused solution, perhaps take by weighing cyclovirobuxinum D by formula ratio, add an amount of dehydrated alcohol, after the slight fever dissolving, add in the adjuvant fused solution of formula ratio, mix, volatilize ethanol, after being uniformly dispersed, make fused solution; Fused solution is put in the surge drum of drop pill machine, insulation splashes in the condensed fluid, collects drop pill, and drop is clean, drying.
The preparation method of medicine of the present invention is as follows:
(a): the weight ratio of getting cyclovirobuxinum D and substrate adjuvant is 1: 30~90 standby;
(b): in appropriate amount of auxiliary materials, add cyclovirobuxinum D, fully mix, mixture is at 45~115 ℃ of heating and meltings, stir, mixing time is 1~120 minute, insulation, at 45~95 ℃ of temperature following system, dropper bore is 1.0~4.0 millimeters, splash in-20~25 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, make drop pill, promptly.
Preferred preparation method of the present invention is as follows:
(a): the weight ratio of getting cyclovirobuxinum D and substrate adjuvant is 1: 40~60 standby;
(b): in appropriate amount of auxiliary materials, add and go up cyclovirobuxinum D, fully mix, mixture stirs at 60~85 ℃ of heating and meltings, mixing time is 10~30 minutes, insulation is 1.1~3.5 millimeters at 60~85 ℃ of temperature following system, dropper bore, splashes in 0~18 ℃ the liquid paraffin, methyl-silicone oil, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried is made drop pill, promptly.
The preparation method of best medicine of the present invention is as follows:
(a): the weight ratio of getting cyclovirobuxinum D and substrate adjuvant be 1: 51 standby;
(b): in appropriate amount of auxiliary materials, add above-mentioned cyclovirobuxinum D, fully mix, mixture stirs at 64 ℃ of heating and meltings, mixing time is 10~30 minutes, insulation is 1.2~2.5 millimeters at 64 ℃ of temperature following system, dropper bore, splashes in 0 ℃ the methyl-silicone oil, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried is made drop pill, promptly.
Best low melting point substrate adjuvant is xylitol and starch, and xylitol is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2~1: 0.4.
Claim the substrate adjuvant by formula ratio, heat fused, the cyclovirobuxinum D of adding formula ratio, fully stir and make its complete fusion, be uniformly dispersed, perhaps take by weighing cyclovirobuxinum D by recipe quantity, add an amount of dehydrated alcohol, after the slight fever dissolving, add in the substrate adjuvant fused solution of formula ratio, mix, volatilize ethanol, after being uniformly dispersed, put in the surge drum of drop pill machine the insulation certain hour, size according to external diameter in the surge drum water dropper bore, adjust and drip distance, at the uniform velocity splash in the condensed fluid, collect drop pill with the suitable speed of dripping, drop is clean, wipe the paraffin on drop pill surface away, place natural drying, promptly.
In preparing, top condensed fluid height is 10~35cm, and bottom condensed fluid height is 20~40cm, drips apart from being 2~10cm, and dripping speed is 20~40 droplets/minute; Being preferably top condensed fluid height is 20cm, and bottom condensed fluid height is 30cm, drips apart from being 5cm, and dripping speed is 30 droplets/minute.
Best preparation method of the present invention:
The ratio of getting 25.5g, weight is the mixture of 1: 0.2~1: 0.3 xylitol and starch; Or the ratio of weight is 1: 0.2~1: 0.3 the lactose and the mixture of starch; Or the ratio of weight is 1: 0.2~1: 0.4 the xylitol and the mixture of arabic gum, at 64 ℃ of heating and meltings, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, system is dripped in 64 ℃ of insulations, and dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0 ℃ of methyl-silicone oil, collects drop pill, and drop is clean, wipe the paraffin on drop pill surface away, place natural drying, make 1000, promptly.
The quality standard of raw material cyclovirobuxinum D meets regulation under cyclovirobuxinum D item of Chinese Pharmacopoeia version in 2000 in the prescription of medicine of the present invention.
More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.
The medicine of other any dosage form; as adopt selected adjuvant of the present invention; only medicine is wherein replaced in the invention process; change other any medicine or effective ingredient into or be Chinese medicine extract, middle pharmaceutically active ingredient, Chinese crude drug; gene formulations etc.; but selected excipient substance is an adjuvant of the present invention, and then this medicine is all in protection scope of the present invention.
Medicine of the present invention can be determined usage and dosage according to patient's situation in use, but every day 1-3 time, and every day, each crude drug consumption was as the criterion with the state-promulgated pharmacopoeia dosage, was no more than the pharmacopeia ormal weight.
The drop pill that the present invention is prepared, conventional drop pill advantage is simple as preparing except having, steady quality, can make liquid medicine solidification, convenient drug administration, efficient, quick-acting, its biggest advantage is:
1, the selected adjuvant pure natural of the present invention degree height: the substrate adjuvant that employed substrate adjuvant derives from natural plants or originates based on natural plants among the present invention, selected substrate adjuvant is xylitol and starch or lactose and starch or xylitol and arabic gum, this substrate adjuvant has pure natural degree height, toxic and side effects is low, mouthfeel is good, dissolve scattered time limit is short, rapid-action, it is a kind of new medium adjuvant, can be used for substituting present chemosynthesis adjuvant, the drop pill made from this kind adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and more and more can not satisfy people and require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect.
2, some problems in the outlet of solution Chinese medicine: medicine of the present invention also can solve Chinese medicine preparation, some problems of in exit procedure, being run into of dropping pill formulation particularly, solve because different countries, especially the European countries of industry prosperity are to the difference identification of the selected adjuvant of Chinese medicine dropping pill formulation, overcome as the selected adjuvant Polyethylene Glycol of the dropping pill formulation of the health food outlet defective in some national food additive catalogue not, improve the Chinese medicine dripping pills preparation and move towards the international market, strengthen the competitiveness of international market.
3, solve the relatively poor problem of drop pill taste and further improve drug effect speed (dissolve scattered time limit): the medicinal dropping ball made from this kind substrate adjuvant of the present invention, can improve Chinese medicine preparation, the particularly present not good shortcoming of dropping pill formulation taste, improve mouthfeel, more easy for patients to accept, and the drop pill that adopts the selected adjuvant of medicine of the present invention to make has shorter dissolve scattered time limit, making drug effect faster, is the medicine that coronary heart disease, angina pectoris, myocardial ischemia are treated in a kind of onset faster.
4, higher safety and solve some problems in the drop pill storage process: the selected substrate of the present invention is not only additive, nutrient commonly used in the food industry, and can do medicinal, but do not see that it uses as the drug matrices adjuvant, therefore, with regard to substrate, be perfectly safe, have no side effect, a large amount of evidences, the drop pill made from this adjuvant can reduce effective ingredient separating out in storage process, the sticking ball of drop pill, easy shortcomings such as moisture absorption deliquescing, but the big production of suitability for industrialized.
In order to understand the present invention better, below with test explanation advantages of the present invention such as the dissolve scattered time limit of new substrate cyclovirobuxine dripping pills and the cyclovirobuxine dripping pills made for the substrate adjuvant with the Polyethylene Glycol, drop pill soft durometer, the sticking balls of drop pill.Test example 1: dissolve scattered time limit, weight differential contrast experiment's example
In vitro tests
The present invention be that the cyclovirobuxine dripping pills that adjuvant is made compares with the Polyethylene Glycol, by measuring dissolve scattered time limit, investigate its good releasing effect; By measuring indexs such as the ball method of double differences is different, whether ripe, whether be fit to suitability for industrialized production if investigating its preparation technology.
1. test medication: the new substrate cyclovirobuxine dripping pills of the present invention (newly) is provided by the Jinshili Medicine Research ﹠. Development Co., Ltd., Tianjin; With the Polyethylene Glycol is the cyclovirobuxine dripping pills (old) that adjuvant is made, and drips system referring to document.
2. method and result:
Dissolve scattered time limit: by " method is measured under this item of Chinese pharmacopoeia; The ball method of double differences is different: by " method is measured under this item of Chinese pharmacopoeia.Result of the test sees Table 1.
Three batches of cyclovirobuxine dripping pills made from the new medium adjuvant of table 1 (newly) with the polyethylene glycol 6000 be cyclovirobuxine dripping pills (old) dissolve scattered time limit made of adjuvant, weight differential relatively
| 0 month | January | February | March | June | December | 18 months |
1 batch | Criterion | The result |
Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
Dissolve scattered time limit (newly) (30 minutes) | ??2′22″ ????4′19″ | ??2′23″ ????4′20″ | ??2′24″ ????4′21″ | ??2′19″ ????4′24″ | ??2′26″ ????4′28″ | ??2′28″ ????4′28″ | ??2′27″ ????4′30″ |
2 batches | Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
Dissolve scattered time limit (newly) (30 minutes) (old) | ??2′20″ ????4′20″ | ??2′23″ ????4′26″ | ??2′23″ ????4′25″ | ??2′25″ ????4′29″ | ??2′25″ ????4′22″ | ??2′29″ ????4′28″ | ??2′22″ ????4′25″ |
3 batches | Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
Dissolve scattered time limit (newly) (30 minutes) (old) | ??2′21″ ????4′29″ | ??2′22″ ????4′23″ | ??2′23″ ????4′26″ | ??2′27″ ????4′20″ | ??2′23″ ????4′26″ | ??2′29″ ????4′21″ | ??2′23″ ????4′26″ |
Test data shows, the dissolve scattered time limit of new substrate cyclovirobuxine dripping pills is lacking of the cyclovirobuxine dripping pills made of adjuvant with the Polyethylene Glycol, and the ball method of double differences of the cyclovirobuxine dripping pills that new and old substrate is made is different all to be controlled in the pharmacopeia prescribed limit.Result of the test explanation, the molten diffusing speed of the cyclovirobuxine dripping pills made from novel adjuvant is faster, is more conducive to medicine and plays a role in the shortest time; The ball method of double differences is different all to be controlled in the pharmacopeia prescribed limit, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, but suitability for industrialized production.
Test example 2: the present invention with the polyethylene glycol 6000 be the sticking ball comparative observation of cyclovirobuxine dripping pills soft durometer, drop pill that adjuvant is made
The present invention be that the cyclovirobuxine dripping pills that adjuvant is made compares with the Polyethylene Glycol, by measuring indexs such as above-mentioned, investigate its effect.
1. test medication: the new substrate cyclovirobuxine dripping pills of the present invention (newly) is provided by the Jinshili Medicine Research ﹠. Development Co., Ltd., Tianjin; With the Polyethylene Glycol is the cyclovirobuxine dripping pills (old) that adjuvant is made, and is provided by the Jinshili Medicine Research ﹠. Development Co., Ltd., Tianjin.
2. method and result:
Get three batches of new, old substrate cyclovirobuxine dripping pills, be loaded in the porcelain vase respectively, and use the bottle stopper good seal.Putting it into the bottom has in the exsiccator of saturated Nacl (humidity 75%) solution, exsiccator is put into 40 ℃ of drying baker of constant temperature again, and timing sampling is observed situations such as drop pill soft durometer, the sticking ball of drop pill, the results are shown in Table 2.1, table 2.2.
Three batches in table 2.1 is that the cyclovirobuxine dripping pills reserved sample observing that adjuvant is made compares with the polyethylene glycol 6000
| 0 month | January | February | March | June | December | 18 months |
1 batch | Criterion | The result |
Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Harder | Harder |
2 batches | Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Harder | Harder |
3 batches | Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Harder | Harder |
Table 2.2: three batches of cyclovirobuxine dripping pills made from the new medium adjuvant (newly) with the polyethylene glycol 6000 be cyclovirobuxine dripping pills (old) character observation made of adjuvant relatively
| 0 month | January | February | March | June | December | 18 months |
| Judge mark | The result |
1 batch | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly | Sticking (old) be sticking (newly) slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard (old) hard (newly) | Hard slightly (old) be hard (newly) slightly | Hard slightly (old) be hard (newly) slightly |
2 batches | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard (old) hard (newly) | Hard slightly (old) hard (newly) | Hard slightly (old) be hard (newly) slightly |
3 batches | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly | Sticking (old) be sticking (newly) slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard slightly (old) hard (newly) | Hard slightly (old) be hard (newly) slightly |
Result of the test shows, new substrate cyclovirobuxine dripping pills soft durometer changes and be that the cyclovirobuxine dripping pills made of adjuvant is similar, strong slightly with the Polyethylene Glycol; The sticking ball variation of new substrate cyclovirobuxine dripping pills, firmness change and be that the cyclovirobuxine dripping pills made of adjuvant is similar with the Polyethylene Glycol.Presentation of results, the sticking ball of the cyclovirobuxine dripping pills that new and old substrate adjuvant is made changes, firmness change is similar, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, but suitability for industrialized production.
The specific embodiment
Below in conjunction with embodiment the present invention is done step explanation, following each embodiment only is used to the present invention is described and is not limitation of the present invention.
Embodiment one
Get the 21.25g xylitol and mix, add cyclovirobuxinum D 0.5g, fully mix with 4.25g starch, mixture is at 64 ℃ of heating and meltings, stir, mixing time is 10~30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splash in 0 ℃ the methyl-silicone oil, make 1000, to the greatest extent and wipe liquid coolant the drop pill drop that forms, back packing to be dried, promptly.
Embodiment two
(a): get cyclovirobuxinum D 0.5g, lactose 19.6g, starch 5.9g is standby;
(b): in lactose and the mixed compound of starch, add above-mentioned cyclovirobuxinum D, fully mix, mixture is at 64 ℃ of heating and meltings, stir, mixing time is 10~30 minutes, puts in the surge drum of drop pill machine insulation, in following system of 64 ℃ of temperature, surge drum water dropper gauge inner-diameter is 1.2 millimeters, and external diameter is 4.0 millimeters, and adjusting a distance is 8cm, the speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0 ℃ the methyl-silicone oil, make 1000, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, make drop pill, promptly.
Embodiment three
Get the mixture of xylitol 18.2g and arabic gum 7.3g, add cyclovirobuxinum D 0.5g, mixture is at 60~85 ℃ of heating and meltings,, to put in the surge drum of drop pill machine, system is dripped in 60~66 ℃ of insulations, surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 25cm is 20 ± 2 ℃, and the temperature of bottom 35cm is 2 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 10cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment four
(a): it is standby to get cyclovirobuxinum D 0.5g, xylitol 21.3, starch 4.2, tragakanta 1.5g, tween 80 1.0g;
(b): it is evenly mixed to get xylitol, starch, tragakanta and tween 80, adds above-mentioned cyclovirobuxinum D, fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, in 64 ℃ of temperature following system, water dropper gauge inner-diameter is 2.0 millimeters, and external diameter is 4.0 millimeters, splashes in 0 ℃ the methyl-silicone oil, make 1000, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.
Embodiment five
(a): get cyclovirobuxinum D 0.5g, lactose 18.5g, chitin 2.0g is standby;
(b): in lactose and chitin, add above-mentioned cyclovirobuxinum D, fully mix, mixture stirs at 64 ℃ of heating and meltings, mixing time is 10~30 minutes, insulation is 1.2~2.5 millimeters at 64 ℃ of temperature following system, dropper bore, splashes in 0 ℃ the methyl-silicone oil, make 1000, liquid coolant is use up and wiped to the drop pill drop that forms, back packing to be dried, promptly.
Embodiment six
Get sorbitol 25.5, Furcellaran 5.5g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 95 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 2.0 millimeters, and external diameter is 4.5 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 10cm is 10 ± 2 ℃, and the temperature of bottom 40cm is-5 ± 1 ℃) in the liquid Paraffin condensed fluid with 45 droplets/minute the speed of dripping apart from being 15cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment seven
Get lactose 10.3g, carboxymethyl starch 3.1g, Lac 1.5g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 105 ℃ are incubated 40 minutes, and surge drum water dropper gauge inner-diameter is 2.5 millimeters, and external diameter is 4.5 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 40cm is 45 ± 2 ℃, and the temperature of bottom 35cm is 5 ± 1 ℃) in the liquid Paraffin condensed fluid with 40 droplets/minute the speed of dripping apart from being 10cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment eight
Get isomalt 5.0g, xylitol 40.g, methylcellulose 2.5g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 85 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.0 millimeters, and external diameter is 2.6 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 45cm is 25 ± 2 ℃, and the temperature of bottom 40cm is-8 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 3cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment nine
Get cyclovirobuxinum D 0.5g, add the 15ml dehydrated alcohol, after the slight fever dissolving, add in 20.2g lactose, the 5.5g erythritol fused solution, mix, volatilize ethanol, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment ten
Get cyclovirobuxinum D 0.5g, add the 15ml dehydrated alcohol, after the slight fever dissolving, add in 35.0g Raffinose, the arabic gum 1.5g fused solution, mix, volatilize ethanol, put in the surge drum of drop pill machine, 72 ℃ are incubated 40 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 7cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 11
Get tripalmitin 5.5g,, xylitol 20.5g heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 95 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 12
Get xylitol 20.4g, starch 6.1g and mix, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 75 ℃ are incubated 40 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 8cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 13
Get the mixture of xylitol 17.5g, starch 3.5g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 110 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 2.0 millimeters, and external diameter is 4.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 45 ± 2 ℃, and the temperature of bottom 35cm is 3 ± 1 ℃) in the liquid Paraffin condensed fluid with 20 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 14
Get xylitol 28g, starch 7g and mix, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 80 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 40 ± 2 ℃, and the temperature of bottom 35cm is 1 ± 1 ℃) in the liquid Paraffin condensed fluid with 35 droplets/minute the speed of dripping apart from being 10cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 15
Get the mixture of xylitol 38.6g and starch 3.9g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 95 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 2.0 millimeters, and external diameter is 4.5 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 15cm is 10 ± 2 ℃, and the temperature of bottom 30cm is-3 ± 1 ℃) in the liquid Paraffin condensed fluid with 40 droplets/minute the speed of dripping apart from being 15cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 16
Get the mixture of xylitol 9.4g and starch 5.6g, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 85 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.0 millimeters, and external diameter is 2.6 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 25 ± 2 ℃, and the temperature of bottom 35cm is-8 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 3cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 17
Get cyclovirobuxinum D 0.5g, add the 15ml dehydrated alcohol, after the slight fever dissolving, add the mixture of xylitol 17g and starch 8.5g, mix, volatilize ethanol, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 18
Get the mixture of 12.25g lactose and 12.25g starch, mix the post-heating fusing, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 99 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 19
Get the mixture of 28.5g lactose and 6g sesbania gum, mix the post-heating fusing, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 80 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 40 ± 2 ℃, and the temperature of bottom 35cm is 1 ± 1 ℃) in the liquid Paraffin condensed fluid with 35 droplets/minute the speed of dripping apart from being 10cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 20
Get the mixture of lactose 20.3g, Ficus elastica 3.5g, tragakanta 2.4g, mix the post-heating fusing, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 85 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.0 millimeters, and external diameter is 2.6 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 30cm is 25 ± 2 ℃, and the temperature of bottom 35cm is-8 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 2cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 21
Get the mixture of 15.7g lactose and 7.05 Furcellaran, mix the post-heating fusing, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the liquid Paraffin condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 22
Get the mixture of 4g xylitol and 1g chitin, mix the post-heating fusing, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 80 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 40 ± 2 ℃, and the temperature of bottom 40cm is 1 ± 1 ℃) in the liquid Paraffin condensed fluid with 35 droplets/minute the speed of dripping apart from being 10cm, collect drop pill, drop is clean, puts the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 23
Get the mixture of 4.5g xylitol and 0.5g starch, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the methyl-silicone oil condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the methyl-silicone oil on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 24
Get the mixture of 18g lactose and 8.5g xanthan gum, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 95 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.3 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 25cm is 20 ± 2 ℃, and the temperature of bottom 35cm is 0 ± 1 ℃) in the methyl-silicone oil condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the methyl-silicone oil on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 25
Get the mixture of 21.5g xylitol and 8.5g arabic gum, heat fused adds cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 80 ℃ are incubated 20 minutes, and surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 40 ± 2 ℃, and the temperature of bottom 60 is 1 ± 1 ℃) in the methyl-silicone oil condensed fluid with 30 minutes the speed of dripping apart from being 10, collect drop pill, drop is clean, puts the methyl-silicone oil on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 26
Get cyclovirobuxinum D 0.5g, add the 15ml dehydrated alcohol, after the slight fever dissolving, the ratio that adds 25.5g, weight is in the mixture fused solution of 1: 0.2~1: 0.4 xylitol and arabic gum, mixes, and volatilizes ethanol, put in the surge drum of drop pill machine, 90 ℃ are incubated 40 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the methyl-silicone oil condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the methyl-silicone oil on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 27
The ratio of getting 25.5g, weight is 1: 0.2~1: 0.4 the xylitol and the mixture of arabic gum, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the kerosene condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the kerosene on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 28
The ratio of getting 26.5g, weight is 1: 0.2~1: 0.4 the xylitol and the mixture of arabic gum, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 95 ℃ are incubated 30 minutes, surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the kerosene condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the kerosene on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 29
The ratio of getting 30.0g, weight is 1: 0.2~1: 0.4 the xylitol and the mixture of arabic gum, heat fused, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 80 ℃ are incubated 20 minutes, surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 35cm is 40 ± 2 ℃, and the temperature of bottom 35cm is 1 ± 1 ℃) in the kerosene condensed fluid with 35 minutes the speed of dripping apart from being 10, collect drop pill, drop is clean, puts the kerosene on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 30
Get cyclovirobuxinum D 0.5g, add the 15ml dehydrated alcohol, after the slight fever dissolving, the ratio that adds 25.5g, weight is in the mixture fused solution of 1: 0.2~1: 0.4 xylitol and arabic gum, mixes, and volatilizes ethanol, put in the surge drum of drop pill machine, 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.7 millimeters, and external diameter is 3.3 millimeters.Adjust and drip, at the uniform velocity splash into (temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃) in the vegetable oil condensed fluid with 30 droplets/minute the speed of dripping apart from being 5cm, collect drop pill, drop is clean, puts the kerosene on drop pill surface on the skin, place natural drying, make 1000, promptly.
The embodiment hentriaconta-
Get pectin 26.5g, heat fused adds cyclovirobuxinum D 0.5g, fully stirs and makes its complete fusion, is uniformly dispersed, and puts in the surge drum of drop pill machine, and 90 ℃ are incubated 30 minutes, and surge drum water dropper gauge inner-diameter is 1.5 millimeters, and external diameter is 3.0 millimeters.Adjusting a distance is 6cm, the speed of dripping with 30 minutes splash at the uniform velocity that (temperature of condensed fluid top 30cm is 30 ± 2 ℃ in liquid Paraffin and methyl-silicone oil (1: 1) the condensation by mixing liquid, the temperature of bottom 35cm is 1 ± 1 ℃), collect drop pill, drop is clean, puts the kerosene on drop pill surface on the skin, places natural drying, make 1000, promptly.
Embodiment 32
Get xylitol and starch mixture 25.5g, 60~85 ℃ of heating and meltings add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 60~85 ℃ of insulation systems of dripping, dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0~18 ℃ of liquid Paraffin condensed fluid, collects drop pill, and drop is clean, put the paraffin on drop pill surface on the skin, place natural drying, make 1000, promptly.
Embodiment 33
Get lactose 20.4g, starch 4.1g, the two is fully mixed, and mixture is at 64 ℃ of heating and meltings, add cyclovirobuxinum D 0.5g, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, system is dripped in 64 ℃ of insulations, and dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less at the uniform velocity to splash in 0 ℃ of methyl-silicone oil condensed fluid with 40 droplets/minute the speed of dripping for well, collects drop pill, drop is clean, place natural drying, make 1000 drop pill, promptly.
Embodiment 34
Get the mixture of xylitol 20g and starch 5.5g,, add cyclovirobuxinum D 0.5g at 60~70 ℃ of heating and meltings, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 62~66 ℃ of insulation systems of dripping, dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0~8 ℃ of methyl-silicone oil, collects drop pill, and drop is clean, wipe the paraffin on drop pill surface away, place natural drying, make 1000, promptly.
Embodiment 35
Get the mixture of lactose 21.2g and starch 4.25g,, add cyclovirobuxinum D 0.5g at 64~68 ℃ of heating and meltings, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 63~66 ℃ of insulation systems of dripping, dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 40 droplets/minute at the uniform velocity splashes in 0 ℃ of methyl-silicone oil, collects drop pill, and drop is clean, wipe the paraffin on drop pill surface away, place natural drying, make 1000, promptly.
Embodiment 36
Get the mixture of lactose 12.5g and starch 4.5g,, add cyclovirobuxinum D 1.0g at 64~68 ℃ of heating and meltings, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 63~66 ℃ of insulation systems of dripping, dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 40 droplets/minute at the uniform velocity splashes in 0~8 ℃ of methyl-silicone oil, collects drop pill, and drop is clean, wipe the paraffin on drop pill surface away, place natural drying, make 1000, promptly.
Embodiment 37
Get the mixture of xylitol 19.8g and starch 5.9g,, add cyclovirobuxinum D 0.3g at 64~68 ℃ of heating and meltings, fully stir and make its complete fusion, be uniformly dispersed, put in the surge drum of drop pill machine, 63~66 ℃ of insulation systems of dripping, dropper mouth internal diameter is 1.2~2.5 millimeters, the difference of dropper mouth external diameter and internal diameter is less for well, the speed of dripping with 40 droplets/minute at the uniform velocity splashes in 0 ℃ of methyl-silicone oil, collects drop pill, and drop is clean, wipe the paraffin on drop pill surface away, place natural drying, make 1000, promptly.