CN1626076A - Andrographolide drop pills and preparation method - Google Patents
Andrographolide drop pills and preparation method Download PDFInfo
- Publication number
- CN1626076A CN1626076A CN 200310107287 CN200310107287A CN1626076A CN 1626076 A CN1626076 A CN 1626076A CN 200310107287 CN200310107287 CN 200310107287 CN 200310107287 A CN200310107287 A CN 200310107287A CN 1626076 A CN1626076 A CN 1626076A
- Authority
- CN
- China
- Prior art keywords
- andrographolide
- adjuvant
- starch
- xylitol
- lactose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 title claims abstract description 224
- 238000002360 preparation method Methods 0.000 title claims description 47
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Landscapes
- Medicinal Preparation (AREA)
Abstract
A dropping pill of andrographolide for treating inflammatory diseases is disclosed. Its advantages are high safety and lower toxic by-effect.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation, specifically the present invention relates to a kind of dripping pills of andrographolide preparation, the invention also discloses its preparation method.
Background technology
Andrographolide (Andrographolide) claims andrographolide again, for the crystallization of colourless square, rectangle or prism-shaped, is the diterpenic lactone that extracts from the Herba Andrographis medical material.Record in one one of Pharmacopoeia of People's Republic of China [version in 1997].Be widely used for the treatment of multiple infection and non-infectious inflammatory diseases clinically, especially the curative effect with intestinal and respiratory tract infection is good.
The intestinal infection aspect, andrographolide all has certain curative effect to acute chronic enteritis, bacillary dysentery, ileotyphus and intestinal infusorian, but being good to acute bacillary dysentery and acute enteritis curative effect.
Respiratory tract infection aspect, the Chinese medicine patent medicine of multiple treatment upper respiratory tract infection are principal agent with Herba Andrographis all, and clinical practice is very wide.Wherein especially preferable to viral pneumonia and upper respiratory tract infection curative effect.In addition, flu, influenza, parotitis, pharyngitis, popular asthma pneumonia, acute tonsillitis and cough etc. also there is certain curative effect.
In recent years, along with people to the going deep into of andrographolide research, the andrographolide oral formulations of having developed has: andrographolide tablet and capsule etc., but because dosage form itself, they all exist following problem:
1, solid orally ingestible (as tablet, capsule etc.) disintegration rate is slow, and the effective ingredient rate of release is low.The disintegrate of solid orally ingestible is the prerequisite of its stripping, and disintegration time is long more, and then the dissolution rate of its effective ingredient is slow more." Chinese Pharmacopoeia 2000 editions " stipulated tablet, the capsule disintegration time should be within an hour.So Chang time for the rapid release of effective ingredient beyond doubt without any helping.
2, first pass effect problem.First pass effect (First-pass Effect) claim the first pass effect again, is meant oral drugs after gastrointestinal absorption, at first arrives liver through portal vein, enters the body circulation again.By metabolism, this phenomenon becomes first pass effect to some medicine by liver the time.Oral formulations is because itself, and major part absorbs in gastrointestinal tract, is easy to generate first pass effect, and its effective ingredient is reduced.At the problem of above existence, we need a kind of quick-acting, andrographolide preparation satisfies the needs of clinical practice efficiently.
The synthetic chemical substance that modern medicine is commonly used has spreaded all over each corner of human lives, chemical synthetic drug becomes the main flow of medicine, yet, 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, the problem of utilize the high Drug therapy of pure natural degree, preventing some chemical synthetic drugs cann't be solved, 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.
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 Chinese 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 dripping pills of andrographolide preparation with the preparation of new type natural substrate adjuvant.
Another object of the present invention provides a kind of preparation method of andrographolide preparation.
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 andrographolide and adjuvant is 1: 1～10 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 andrographolide and adjuvant thereof are 1: 2.5～3.5 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 andrographolide and adjuvant thereof are the preparation of making at 1: 3, 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.
So in the preparation method of preparation, 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 liquid paraffin, methyl-silicone oil, and the condensing agent temperature is 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 heating and melting temperature is that to make temperature be that 62～66 ℃, dropper bore are that 1.2～2.5 millimeters, condensing agent are 0～8 ℃ methyl-silicone oil to 62～66 ℃, droplet.
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 can be that crude drug also can be the effective ingredient extract.
Medicine of the present invention can adopt the preparation of Chinese medicine preparation conventional method.The preparation of effective ingredient of the present invention can be adopted following method: water extraction, decoction and alcohol sedimentation technique, extraction, infusion process, percolation, reflux extraction, continuous backflow extraction method, macroreticular resin absorbing method preparation.For example, these crude drug pulverize mix homogeneously can be made powder takes after mixing it with water; Also can be with these medicines decocting together, the condensed water decocting liquid is made oral liquid then; But, preferably adopt following technology to extract, but this can not limit protection scope of the present invention to raw material in order to make each crude drug of this medicine better bring into play drug effect.
The present invention is implemented by following scheme:
Get andrographolide;
Get adjuvant, add the abundant mixing of andrographolide behind the heating and melting;
The andrographolide that mixes adjuvant is moved into the dropping-pill machine jar, splash in the cryogenic liquid paraffin, take out drop pill, wipe ball, dry;
Wherein, the related standards of the andrographolide among the step a meets the pertinent regulations under 439 pages of andrographolide items of Chinese Pharmacopoeia version in 1997.
In preparation process of the present invention, the weight ratio of andrographolide and adjuvant is 1: 2～4; The weight ratio of preferred andrographolide and adjuvant is 1: 2.5～3.5; The best andrographolide and the weight ratio of adjuvant are 1: 3.
The transconversion into heat material temperature that adds in the step (b) is 45～115 ℃; Preferably adding transconversion into heat material temperature is 60～85 ℃, and the best transconversion into heat material temperature that adds is 62～66 ℃;
Drip irrigation temperature in the step (c) is 45～95 ℃; Preferred drip irrigation temperature is 60～85 ℃, and best drip irrigation temperature is 62～66 ℃; Cryogenic liquid paraffin in the step (c), methyl-silicone oil or vegetable oil temperature are for being lower than-25～25 ℃; Preferred cryogenic liquid paraffin, methyl-silicone oil temperature are 0～18 ℃; The oil temperature of best low temperature methyl-silicone oil is 0～8 ℃.
The present invention is implemented by following concrete scheme
A kind of dripping pills of andrographolide is characterized in that adopting following steps to make:
(a) get andrographolide 150g;
(b) get xylitol and starch 450g, xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or get lactose and starch 450g, lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or get xylitol and arabic gum 450g, the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4, is heated to 62～66 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion
(c) the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0～8 ℃, take out drop pill, wipe ball, dry, make drop pill, promptly.
Multiple infection of curable substance of the present invention and non-infectious inflammatory diseases are as treatment intestinal infection, acute chronic enteritis, bacillary dysentery, ileotyphus and intestinal infusorian; Diseases such as treatment respiratory tract infection, viral pneumonia and upper respiratory tract infection, flu, influenza, parotitis, pharyngitis, popular asthma pneumonia, acute tonsillitis.
The present invention makes medicine and substrate by means such as fusions preparation, it has advantages such as surface area is big, and oral drug release rate is fast; Simultaneously it can also sublingual administration, medicine is gone into blood by sublingual vein, avoid making its effective ingredient forfeiture the present invention adopt xylitol and starch or lactose and starch or xylitol and arabic gum because of first pass effect, its natural degree height, under proper proportion, make drop pill and help the effect that andrographolide is brought into play its heat-clearing and toxic substances removing, anti-inflammation better.
Compare with traditional andrographolide sheet, dripping pills of andrographolide has following clear superiority:
1, improved dissolution rate: because andrographolide dissolubility in water is little, curative effect also is subjected to certain influence, so improve dissolution rate, is problem anxious to be solved thereby improve bioavailability.Solid dispersion method is one of method that solves insoluble drug.It is to utilize water-solubility carrier (as xylitol and starch, lactose and starch, xylitol and arabic gum etc.) to absorb with insoluble drug to make solid dispersion, make medicine be superfine colloid and ultrafine dust, even molecularity exists, simultaneously, carrier has good wettability to medicine, makes dissolution rate faster like this.The present invention is the fusion method that adopts solid dispersion method, after being about to xylitol and starch, lactose and starch, xylitol and arabic gum fusion, add the andrographolide fine powder, splash in the not miscible condensing agent by dropper, because that drop is shrunk to is spherical in capillary effect, and cooled and solidified forms drop pill, and drop pill and the former tablet of making carried out the dissolution rate in vitro contrast test, the result shows that the drop pill dissolution rate is fast than tablet.
2, the present invention has adopted " solid dispersion technology ", medicine is dispersed in has formed the molecular dispersion system in the substrate.Sublingual administration, effective ingredient can have been avoided the first pass effect that brings because of gastrointestinal absorption by sublingual vein directly into blood.
3, taking convenience: traditional andrographolide sheet taste is extremely bitter, is difficult for being accepted by the patient, and the present invention more dosage changing form is convenient to take after film coating has been covered bitterness.Because the drop pill grain is little, slick and sly, swallow conveniently, the patient that is more convenient for uses.
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, and 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 substrate 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 various infectious disease 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 that this adjuvant is made 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 dripping pills of andrographolide and the dripping pills of andrographolide made from Polyethylene Glycol substrate, drop pill soft durometer, the sticking balls of drop pill.And by following zoopery, compare with the andrographolide sheet, observe the pharmacological action of heat-clearing and toxic substances removing of the present invention, anti-inflammation.
Test example 1: the present invention with the polyethylene glycol 6000 be the sticking ball paired observation of dripping pills of andrographolide soft durometer, drop pill that adjuvant is made
Get three batches of the dripping pills of andrographolide that the different substrates adjuvant makes, 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 1.1, table 1.2.
Three batches in table 1.1 is that the dripping pills of andrographolide 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 1.2: three batches of dripping pills of andrographolide made from the new medium adjuvant (newly) with the polyethylene glycol 6000 be dripping pills of andrographolide (old) character observation made of adjuvant relatively
| 0 month | January | February | March | June | December | 18 months | ||
| Criterion | 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) do not glue (newly) slightly | Sticking (old) be sticking (newly) not |
| 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) hard (newly) | |
| 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) do not glue (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) hard (newly) | Hard slightly (old) hard (newly) | |
| 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) do not glue (newly) slightly | Sticking (old) be sticking (newly) not |
| 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) hard (newly) |
Table 1.1,1.2 result of the test show, new substrate dripping pills of andrographolide soft durometer changes and be that the dripping pills of andrographolide made of adjuvant is similar, strong slightly with the Polyethylene Glycol; Sticking ball variation, the firmness change of new substrate dripping pills of andrographolide and be that the dripping pills of andrographolide made of adjuvant is similar with the Polyethylene Glycol.The result of the test explanation, the sticking ball of the dripping pills of andrographolide 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.
Test example 2: dissolve scattered time limit, the different contrast experiment's example of the ball method of double differences
In vitro tests
The present invention be that the dripping pills of andrographolide 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 dripping pills of andrographolide of the present invention (newly) is the dripping pills of andrographolide (old) that adjuvant is made with the Polyethylene Glycol.
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 2.
Three batches of dripping pills of andrographolide made from the new medium adjuvant of table 2 (newly) with the polyethylene glycol 6000 be dripping pills of andrographolide (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) (old) | ??2′5″ ????5′9″ | ??2′5″ ????5′10″ | ??2′4″ ????5′11″ | ??2′10″ ????5′14″ | ??2′13″ ????5′18″ | ??2′12″ ????5′22″ | ??2′17″ ????5′20″ | |
| 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′5″ ????5′10″ | ??2′5″ ????5′10″ | ??2′8″ ????5′12″ | ??5′10″ ????5′15″ | ??2′12″ ????5′12″ | ??2′14″ ????5′18″ | ??2′15″ ????5′21″ | |
| 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′6″ ????5′10″ | ??2′5″ ????5′10″ | ??2′6″ ????5′12″ | ??2′8″ ????5′15″ | ??2′14″ ????5′16″ | ??2′14″ ????5′21″ | ??2′15″ ????5′20″ |
Result of the test shows, the dissolve scattered time limit of new substrate dripping pills of andrographolide is that the dripping pills of andrographolide made of adjuvant is few with the Polyethylene Glycol, and the ball method of double differences of the dripping pills of andrographolide 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 dripping pills of andrographolide 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 of the dripping pills of andrographolide that new and old substrate is made 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.
Experiment material
1, experimental drug: a kind of dripping pills of andrographolide of the present invention (hereinafter to be referred as " drop pill ") is provided by Tianjin Tasly Pharmaceutical Co., Ltd.The heavy 50mg of every ball contains lactone 12.5mg.For ease of administration, after getting drop pill before the use and adding a little distilled water heat (about 40 ℃) is melted it a little, it is standby that reuse 1% sodium carboxymethyl cellulose (CMC-Na) is made into suspension, and concentration is 14.4mg/ml; Andrographolide sheet (hereinafter to be referred as " lactone sheet ") is produced lot number: 980501 by the strong grand Pharmaceutical head office in Wuxi.Every contains lactone 50mg.For ease of administration, grind before the use, the suspension that is made into respective concentration with 1% sodium carboxymethyl cellulose (CMC-Na) is standby.Concentration: 14.4mg/ml.Irritate the long-pending 0.5ml/100g body weight that is of body of stomach.
2, laboratory animal: Wistar rat, the animal quality certification: No. 03, the real moving accurate word of Anhui doctor.Before the experiment, equal one week of breeding observing of each animal.
3, draft beer yeast: Hefei brewery provides.
4, isoproterenol hydrochloride inj: Tian Feng pharmaceutical factory, Shanghai produces, lot number 960123.
5, carrageenin: Liaoning Province's medicine provides, lot number: 950322.
Experimental technique and result
1. to the influence of rat carrageenan pedal swelling
Male Wistar rat is selected in experiment for use, and body weight 140～160g is divided into model control group (irritate stomach and give 1% CMC-Na5ml/kg) at random, and (concentration is andrographolide sheet matched group: 14.4mg/ml) with dripping pills of andrographolide group (concentration is 14.4mg/ml).Irritate the long-pending 0.5ml/100g body weight that is of body of stomach.Earlier measure right back toes place volume, and mark with volumetric method.After pressing table 1 dosed administration, in right back toes subcutaneous injection 1% carrageenin 0.1ml, and used with quadrat method in mark in 1,2,4 and 6 hour in injection back and to survey the toes volume, deduct administration front foot pawl volume and be the swelling degree, the result lists in table 1 after learning processing by statistics.
Table 1 dripping pills of andrographolide of the present invention is to the influence of rat paw edema (x ± s)
Different time pedal swelling (cm) after the moving administration
Group dosage
Thing 0.5 (h) 1 (h) 2 (h) 3 (h) 4 (h) 6 (h)
Model group 10/0.632 ± 0.164 0.910 ± 0.131 0.928 ± 0.124 0.921 ± 0.141 0.912 ± 0.123 0.908 ± 0.101
Lactone sheet group 10 72m/kg 0.539 ± 0.144 0.725
*± 0.134 0.759
*± 0.187 0.869 ± 0.173 0.889 ± 0.159 0.886 ± 0.172
Drop pill group 10 72m/kg 0.536 ± 0.145 0.706
*± 0.188 0.732
*± 0.256 0.812 ± 0.204 0.858 ± 0.257 0.846 ± 0.230
Table 1 result shows: swelling all has the obvious suppression effect to rat foot pawl for dripping pills of andrographolide of the present invention and andrographolide sheet, compares P＜0.05 with model control group.But from onset time, dripping pills of andrographolide is faster than andrographolide sheet.
2. the influence of the rat fever model that beer yeast is caused
Healthy Wistar rat, body weight 160-180g, male and female half and half, female unpregnancy are selected in experiment for use.Each rat is surveyed basal body temperature earlier before the experiment, rejects body temperature and is lower than 36.5 ℃ and be higher than 38.4 ℃ of animals.Be divided into model control group, andrographolide sheet matched group and dripping pills of andrographolide group at random.Each rat is from the draft beer yeast suspension 3ml/kg of back subcutaneous injection 10%, and every 1 hour take temperature once, when treating 1 ℃ of left and right sides of fervescence (3 hours), after different groups are administered once in the table 2, measures an anus temperature again every 30 minutes.
The situation of change of different time body temperature after the comparison administration, the result carries out the statistical procedures rank rear in table 2.
Table 2 pair draft beer yeast causes the influence (x ± s) of rat fever model
Different time after the moving normal pyrogenicity administration (minute) ℃
Group dosage
Behind the thing ℃ ℃ 30 60 90 120 150
Model group 10/37.48 38.67 39.01 ± 0.446 39.39 ± 0.314 39.12 ± 0.418 38.88 ± 0.466 38.73 ± 0.368
±????????????±
0.531??0.542
Lactone sheet 10 72m/kg 37.42 38.79 38.76 ± 0.534 38.99* ± 0.489 38.87 ± 0.276 38.54 ± 0.264 38.47 ± 0.259
±????????????±
Organize 0.603 0.614
Drop pill group 10 72m/kg 37.62 38.86 38.81 ± 0.612 38.81 ± 0.436 38.71 ± 0.411 38.53 ± 0.510 38.42 ± 0.420
±????????????±
0.565??0.611
Table 2 result shows: dripping pills of andrographolide of the present invention and andrographolide sheet all have certain refrigeration function to the rat fever model that the draft beer yeast causes, compare P＜0.05 with model control group.From onset time, dripping pills of andrographolide is faster slightly than andrographolide sheet.
Conclusion
Irritate stomach to rat and give dripping pills of andrographolide 72mg/kg, there is certain inhibition at the diagonal angle sufficient pawl swelling that causes of dish glue again
Effect is compared P＜0.05 with the model control group group.
Rat all there is certain refrigeration function because of the heating that the draft beer yeast causes.From onset time, in the Herba Andrographis
The ester drop pill is faster than andrographolide sheet.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
A. get andrographolide 150g;
B. get Sargassum alcohol 288g and dextrin 85g are mixed, be heated to 115 ℃, add the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the liquid paraffin of medicine liquid droplet to 9 ℃, take out drop pill, wipe ball, dry, make 875 bags, promptly.
Embodiment 2
A. get andrographolide 150g;
B. get xylitol 200g, hydroxypropyl emthylcellulose 100g and xanthan gum 75g and mix, fully mixing is heated to 85 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 45 ℃, in the liquid methyl silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make 875 bags, promptly.
Embodiment 3
A. get andrographolide 150g;
B. get lactose 312.5g and starch 62.5g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 60 ℃, in the methyl-silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make 875 bags, promptly.
Embodiment 4
A. get andrographolide 150g;
B. get arabitol 300g and carboxymethyl starch 75g and mix, fully mixing is heated to 70 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the liquid paraffin of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 875 bags, promptly.
Embodiment 5
A. get andrographolide 150g;
B. get xylitol 200g and methylcellulose 175g and mix, fully mixing is heated to 85 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the liquid paraffin of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make 875 bags, promptly.
Embodiment 6
A. get andrographolide 150g;
B. get sorbitol 190g and methylcellulose 185g mixture, fully mixing is heated to 65 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 60 ℃, in the methyl-silicone oil of medicine liquid droplet to 7 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 7
A. get andrographolide 150g;
B. get xylitol 346g and starch 104g and mix, fully mixing is heated to 87 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 68 ℃, in the vegetable oil of medicine liquid droplet to 4 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 8
A. get andrographolide 150g;
B. get lactose 300g and carboxymethyl cellulose 150g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 66 ℃, in the liquid paraffin of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 9
A. get andrographolide 150g;
B. get lactose 250g and arabic gum 200g and mix, fully mixing is heated to 100 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 45 ℃, in the positive silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 10
A. get andrographolide 150g;
B. get xylitol 281g and starch 169g and mix, fully mixing is heated to 62～66 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0～8 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 11
A. get andrographolide 150g;
B. get lactose 350g, carrageenan 50g and starch 50g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62 ℃, in the liquid paraffin of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 12
A. get andrographolide 150g;
B. get lactose 42g and starch 25g and mix, fully mixing is heated to 93 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 66 ℃, in the methyl-silicone oil of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make 1000 bags, promptly.
Embodiment 13
A. get andrographolide 150g;
B. get isomalt 425g and alginic acid 100g and mix, fully mixing is heated to 68 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 66 ℃, in the methyl-silicone oil of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make the 675g drop pill, promptly.
Embodiment 14
A. get andrographolide 150g;
B. get isomalt 420g and carrageenan 105g and mix, fully mixing is heated to 85 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 68 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make the 675g drop pill, promptly.
Embodiment 15
A. get andrographolide 150g;
B. get lactose 485g and arabic gum 40g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the methyl-silicone oil of medicine liquid droplet to 25 ℃, take out drop pill, wipe ball, dry, make 675g drop pill bag, promptly.
Embodiment 16
A. get andrographolide 150g;
B. get lactose 400g and dextrin 125g and mix, fully mixing is heated to 89 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 72 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make the 675g drop pill, promptly.
Embodiment 17
A. andrographolide 150g;
B. get xylitol 325g and hydroxypropyl emthylcellulose 200g and mix, fully mixing is heated to 93 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 73 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 1125 bags, promptly.
Embodiment 18
A. get andrographolide 150g;
B. get lactose 465g and alginic acid 60g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 73 ℃, in the methyl-silicone oil of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make 1125 bags, promptly.
Embodiment 19
A. get andrographolide 150g;
B. get arabitol 300g, dextrin 50g and xanthan gum 50g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 74 ℃, in the methyl-silicone oil of medicine liquid droplet to 4 ℃, take out drop pill, wipe ball, dry, make 1125 bags, promptly.
Embodiment 20
A. get andrographolide 150g;
B. get xylitol 490g and carrageenan 35g and mix, fully mixing is heated to 88 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 66 ℃, in the methyl-silicone oil of medicine liquid droplet to 4 ℃, take out drop pill, wipe ball, dry, make 1125 bags, promptly.
Embodiment 21
A. get andrographolide 150g;
B. get xylitol 150g, lactose 50g and arabic gum 100g mixture, fully mixing is heated to 85 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the methyl-silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 22
A. get andrographolide 150g;
B. get sorbitol 200g and alginic acid 100g and mix, fully mixing is heated to 87 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 67 ℃, in the liquid paraffin of medicine liquid droplet to 7 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 23
A. get andrographolide 150g;
B. get xylitol 250g, hydroxypropyl emthylcellulose 25g and starch 25g and mix, fully mixing is heated to 89 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 70 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 24
A. get andrographolide 150g;
B. get lactose 250g and Calculus Bovis from Northwest of China Millefolium 50g and mix, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 72 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 25
A. get andrographolide 150g;
B. get sorbitol 214g and polyvinylpyrrolidone 84g and mix, fully mixing is heated to 91 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 72 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 26
A. get andrographolide 150g;
B. get lactose 214g, chitin 40g and xanthan gum 46g and mix, fully mixing is heated to 91 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 72 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 27
A. get andrographolide 150g;
B. get lactose 280g and hydroxypropyl emthylcellulose 20g and mix, fully mixing is heated to 93 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 73 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 750 bags, promptly.
Embodiment 28
A. get andrographolide 150g;
B. get xylitol 500g and tragakanta 100g and mix, fully mixing is heated to 85 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 65 ℃, in the methyl-silicone oil of medicine liquid droplet to 8 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 29
A. get andrographolide 150g;
B. get sorbitol 525g and starch 75g and mix, fully mixing is heated to 87 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 67 ℃, in the methyl-silicone oil of medicine liquid droplet to 4 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 30
A. get andrographolide 150g;
B. get lactose 450g and carrageenan 150g, fully mixing is heated to 89 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 69 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 31
A. get andrographolide 150g;
B. get xylitol 350g and carboxymethyl starch 250g and mix, fully mixing is heated to 91 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 71 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 32
A. get andrographolide 150g;
B. get sorbitol 460g and methylcellulose 140g and mix, fully mixing is heated to 91 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 71 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 33
A. get andrographolide 150g;
B. get D-ribose 300g, starch 150g and arabic gum 150g and mix, fully mixing is heated to 93 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 73 ℃, in the methyl-silicone oil of medicine liquid droplet to 3 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 34
A. get andrographolide 150g;
B. get erythritol 540g and starch 60g and mix, fully mixing is heated to 95 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 80 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 35
A. get andrographolide 150g;
The mixture 600g of the amount of b. getting xylitol and starch than 1: 0.2, fully mixing is heated to 95 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 75 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 36
A. get andrographolide 150g;
B. get xylitol 461g and starch 139g, fully mixing is heated to 95 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 75 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 37
A. get andrographolide 150g;
B. get xylitol 480g and starch 120g, fully mixing is heated to 92 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 73 ℃, in the methyl-silicone oil of medicine liquid droplet to 4 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 38
A. get andrographolide 150g;
B. get lactose 461g and starch 139g, fully mixing is heated to 64 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 64 ℃, in the methyl-silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make 1250 bags, promptly.
Embodiment 39
A. get andrographolide 150g;
B. get lactose 400g and starch 100g, fully mixing is heated to 62～66 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0～8 ℃, take out drop pill, wipe ball, dry, make the 650g drop pill, promptly.
Embodiment 40
A. get andrographolide 150g;
B. get lactose 462g and starch 138g, fully mixing is heated to 62～66 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0～8 ℃, take out drop pill, wipe ball, dry, make the 650g drop pill, promptly.
Embodiment 41
A. get andrographolide 150g;
B. get xylitol 485g and arabic gum 115g, fully mixing is heated to 95 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0 ℃, take out drop pill, wipe ball, dry, make the 750g drop pill, promptly.
Embodiment 42
A. get andrographolide 150g;
B. get xylitol 500g and arabic gum 100g, fully mixing is heated to 62～68 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 63～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 6 ℃, take out drop pill, wipe ball, dry, make the 750g drop pill, promptly.
Embodiment 43
A. get andrographolide 250g;
B. get xylitol 48g and starch 120g, fully mixing is heated to 90 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion;
C. the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 70 ℃, in the methyl-silicone oil of medicine liquid droplet to 5 ℃, take out drop pill, wipe ball, dry, make the 850g drop pill, promptly.
Claims (12)
1, a kind of dripping pills of andrographolide, the weight ratio that it is characterized in that andrographolide and adjuvant is 1: 1～10 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.
2, a kind of dripping pills of andrographolide as claimed in claim 1, the weight ratio that it is characterized in that andrographolide and adjuvant is 1: 2.5～3.5 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.
3, a kind of dripping pills of andrographolide as claimed in claim 2, it is characterized in that it is by dripping pills of andrographolide, the weight ratio that it is characterized in that andrographolide and adjuvant is the preparation of making at 1: 3, 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.
4, as claim 1,2 or 3 described a kind of dripping pills of andrographolide, it is characterized in that it can also contain chemosynthesis adjuvant and animal origin adjuvant, 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.
5, a kind of dripping pills of andrographolide as claimed in claim 3 is characterized in that described adjuvant is xylitol and starch, and xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch.
6, a kind of dripping pills of andrographolide as claimed in claim 3 is characterized in that described adjuvant is lactose and starch, and lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch.
7, a kind of dripping pills of andrographolide as claimed in claim 3 is characterized in that described adjuvant is xylitol and arabic gum, and the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4.
8,, it is characterized in that this method comprises the steps: as the preparation method of claim 1,2 or 3 described a kind of dripping pills of andrographolide
(a) get andrographolide;
(b) get adjuvant, add the abundant mixing of andrographolide behind the heating and melting;
(c) andrographolide that will mix adjuvant moves into the dropping-pill machine jar, splashes in cryogenic liquid paraffin, methyl-silicone oil or the vegetable oil, takes out drop pill, wipes ball, dry, that is,
9, the preparation method of a kind of dripping pills of andrographolide as claimed in claim 8 is characterized in that the transconversion into heat material temperature that adds in the described step (b) is 45～115 ℃; Drip irrigation temperature in the step (c) is 45～95 ℃; Cryogenic liquid paraffin in the step (c), methyl-silicone oil or vegetable oil temperature are-25～25 ℃.
10, the preparation method of a kind of dripping pills of andrographolide as claimed in claim 8 is characterized in that the transconversion into heat material temperature that adds in the described step (b) is 60～85 ℃; Drip irrigation temperature in the step (c) is 60～85 ℃; Cryogenic liquid paraffin in the step (c), methyl-silicone oil temperature are 0～18 ℃.
11, the preparation method of a kind of dripping pills of andrographolide as claimed in claim 8 is characterized in that the transconversion into heat material temperature that adds in the described step (b) is 62～66 ℃; Drip irrigation temperature in the step (c) is 62～66 ℃; Low temperature methyl-silicone oil temperature in the step (c) is 0～8 ℃.
12, the preparation method of a kind of dripping pills of andrographolide as claimed in claim 8 is characterized in that adopting following steps to make:
(a) get andrographolide 150g;
(b) get xylitol and starch 450g, xylitol is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or get lactose and starch 450g, lactose is 1: 0.2～1: 0.3 with the ratio of the weight of starch; Or get xylitol and arabic gum 450g, the ratio of the weight of xylitol and arabic gum is 1: 0.2～1: 0.4, is heated to 62～66 ℃, adds the abundant mixing of above-mentioned andrographolide after the fusion
(c) the above-mentioned andrographolide that mixes adjuvant is moved into dropping-pill machine and irritate and remain on 62～66 ℃, in the methyl-silicone oil of medicine liquid droplet to 0～8 ℃, take out drop pill, wipe ball, dry, promptly.
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|---|---|---|---|
| CN 200310107287 CN1626076B (en) | 2003-12-11 | 2003-12-11 | Andrographolide drop pills and preparation method |
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|---|---|---|---|
| CN 200310107287 CN1626076B (en) | 2003-12-11 | 2003-12-11 | Andrographolide drop pills and preparation method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007098686A1 (en) * | 2006-02-28 | 2007-09-07 | Hutchison Medipharma Enterprises Limited | Andrographis extract formulations |
| CN101474218B (en) * | 2008-12-31 | 2011-04-27 | 四川禾邦阳光制药股份有限公司 | Andrographis Paniculata dropping pills and preparation method thereof |
| USRE42718E1 (en) | 2004-04-28 | 2011-09-20 | Hutchison Medipharma Enterprises Limited | Crude extracts from andrographis paniculata |
| US8557308B2 (en) | 2007-11-02 | 2013-10-15 | Nutrition Science Partners Limited | Andrographis paniculata extract |
| CN104557818A (en) * | 2014-12-16 | 2015-04-29 | 浙江维康药业有限公司 | Common andrographis herb lactone compound as well as dropping pills and soft capsules containing compound |
| CN104621714A (en) * | 2014-12-04 | 2015-05-20 | 湖北中烟工业有限责任公司 | Tobacco additive dropping pill with improved brittleness and preparation method thereof |
| CN111110640A (en) * | 2018-10-31 | 2020-05-08 | 长春海悦药业股份有限公司 | Tadalafil tablet composition and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444937A (en) * | 2003-04-21 | 2003-10-01 | 南昌弘益科技有限公司 | Drop pills of andrographolide and its preparing method |
-
2003
- 2003-12-11 CN CN 200310107287 patent/CN1626076B/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE42718E1 (en) | 2004-04-28 | 2011-09-20 | Hutchison Medipharma Enterprises Limited | Crude extracts from andrographis paniculata |
| USRE43423E1 (en) | 2004-04-28 | 2012-05-29 | Hutchison Medipharma Enterprises Limited | Crude extracts from Andrographis paniculata |
| WO2007098686A1 (en) * | 2006-02-28 | 2007-09-07 | Hutchison Medipharma Enterprises Limited | Andrographis extract formulations |
| US8557308B2 (en) | 2007-11-02 | 2013-10-15 | Nutrition Science Partners Limited | Andrographis paniculata extract |
| US8557302B2 (en) | 2007-11-02 | 2013-10-15 | Nutrition Science Partners Limited | Andrographis paniculata extract |
| CN101474218B (en) * | 2008-12-31 | 2011-04-27 | 四川禾邦阳光制药股份有限公司 | Andrographis Paniculata dropping pills and preparation method thereof |
| CN104621714A (en) * | 2014-12-04 | 2015-05-20 | 湖北中烟工业有限责任公司 | Tobacco additive dropping pill with improved brittleness and preparation method thereof |
| CN104621714B (en) * | 2014-12-04 | 2018-01-05 | 湖北中烟工业有限责任公司 | One kind improves brittle dripping pills of cigarette additive and preparation method thereof |
| CN104557818A (en) * | 2014-12-16 | 2015-04-29 | 浙江维康药业有限公司 | Common andrographis herb lactone compound as well as dropping pills and soft capsules containing compound |
| CN111110640A (en) * | 2018-10-31 | 2020-05-08 | 长春海悦药业股份有限公司 | Tadalafil tablet composition and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1626076B (en) | 2010-10-06 |
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