CN103655479A - Andrographolide composition wettable solid dispersing powder and preparation method thereof - Google Patents
Andrographolide composition wettable solid dispersing powder and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of pharmaceutic preparations, and discloses andrographolide composition wettable solid dispersing powder and a preparation method thereof. The andrographolide composition wettable solid dispersing powder comprises the following original auxiliary materials in parts by weight: 1-20 parts of andrographolide, 2-39 parts of hydroxyethyl-beta-cyclodextrin, 1-10 parts of a suspending agent, 12-20 parts of sodium dihydrogen phosphate, 11.8-27.4 parts of glucosum anhydricum and 0.0002-0.004 parts of an antioxidant acceptable on pharmacy. The andrographolide composition wettable solid dispersing powder has the advantages that the dispersibility of the andrographolide in the water is improved obviously, multiple andrographolide preparations can be prepared, and the promotion and application of the andrographolide in poultry and livestock breeding as well as pet feeding is facilitated.
Description
Technical field
The invention belongs to technical field of medicine, particularly a kind of andrographolide compositions wettability solid divides loose powder and preparation method thereof.
Background technology
Andrographolide, claim again andrographolide, from acanthaceous plant Herba Andrographis, to extract the diterpene ginkgolide obtaining, it is one of main effective ingredient of Chinese medicine Herba Andrographis, its taste is extremely bitter, and people are referred to as " king in hardship " conventionally, are soluble in ethanol, acetone, pyridine, be slightly soluble in water and chloroform, be dissolved in hardly ether.Andrographolide, molecular formula is C
20h
30o
5, molecular weight 350.44, has structure shown in formula I:
Research finds that andrographolide has the multiple pharmacologically actives such as antibacterial, antiviral, antipyretic, antiinflammatory, immunomodulating, anticancer, antiplatelet aggregation, the growth of inhibition acute promyelocytic leukemia cell, treatment cardiovascular and cerebrovascular disease and hepatic cholagogic.Clinically, andrographolide is used to prevent and treat leptospirosis, meningitis, pneumonia, bacillary dysentery and upper respiratory tract infection etc., especially to bacillary, has special efficacy with viral upper respiratory tract infection and dysentery, is described as natural antibiotics medicine.On veterinary clinic, Herba Andrographis is often used in the respiratory tract disease of poultry and domestic animal and the control of viral disease, for example, and infectious laryngotracheitis of chicken, the white scour of chicken, typhoid fever and cholera etc.; Pig Hakuri, hyopneumoniae, baby pig edema, bacterial enteritis etc.; And cattle and sheep ruminant because the glandular stomach that mixed infection causes is slow, grainsick and expansion, flatulence, ruminate unable etc.Studies confirm that, these application of Herba Andrographis are mainly the wherein effects of andrographolide, so andrographolide has very high value for animals.But due to andrographolide poorly water-soluble, water-soluble and other aqueous mediums hardly, thereby limited its application.Although there is in the market andrographolide tablet, dispersible tablet, drop pill, capsule and soft capsule dosage form, these dosage form administrations are inconvenient, and be not suitable for for animals, so not yet there is at present andrographolide veterinary formulations.
In order to allow andrographolide better applied aspect poultry, livestock-raising and raising pets, develop a kind of good water solubility, be applicable to varying number fauna, andrographolide novel form easy to use is very necessary.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of andrographolide compositions wettability solid minute loose powder and preparation method thereof.This andrographolide compositions wettability solid minute loose powder has significantly improved the dispersibility of andrographolide in water, can be for the preparation of multiple andrographolide preparation.
In order to realize goal of the invention of the present invention, the present invention adopts following technical scheme:
The invention provides a kind of andrographolide compositions wettability solid minute loose powder, the supplementary material that it comprises following weight portion:
Andrographolide compositions wettability solid minute loose powder provided by the invention refers to the wettable powder that applying solid dispersion technology prepares, this andrographolide compositions wettability solid minute loose powder had both had the characteristic of part solid dispersion, had again the characteristic of wettable powder.By the supplementary product kind to wherein, supplementary product consumption, screen and obtained suitable formula, significantly improved the dispersibility of andrographolide in water, experimental result shows that this andrographolide compositions wettability solid minute loose powder can make multiple andrographolide preparation, easy to use, applicable for animals, be more conducive to the promotion and application of andrographolide in poultry, livestock-raising and raising pets.
Preferably, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In some embodiments of the invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In other embodiment of the present invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In other embodiment of the present invention, the supplementary material in andrographolide compositions wettability solid minute loose powder provided by the invention also comprises a kind of or both the above mixture in pharmaceutically acceptable sweeting agent, pharmaceutically acceptable bitterness screening agent, pharmaceutically acceptable bitter inhibitor.
Andrographolide taste is extremely bitter, palatability is poor, so a kind of or both the above mixture that add therein in pharmaceutically acceptable sweeting agent, pharmaceutically acceptable bitterness screening agent, pharmaceutically acceptable bitter inhibitor can be sheltered its bitterness, improve its palatability, avoid the reload stress of the sharp-nosed animals such as pig when administration.Experimental result shows, andrographolide compositions wettability solid minute loose powder provided by the invention does not produce the stress that reloads in drinking-water administration process, does not affect the feed intake of disease pig.
In some embodiments of the invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In other embodiment of the present invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In other embodiment of the present invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
In other embodiment of the present invention, the supplementary material that andrographolide compositions wettability solid minute loose powder provided by the invention comprises following weight portion:
Preferably, the suspending agent in andrographolide compositions wettability solid minute loose powder provided by the invention is a kind of or both the above mixture in sodium carboxymethyl cellulose, carboxymethyl starch sodium, gelatin, sodium alginate, tragakanta, arabic gum, xanthan gum, carbomer or glucosan.
In some embodiments of the invention, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable suspending agent is sodium carboxymethyl cellulose.
Preferably, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable antioxidant is Butylated hydroxyanisole, 2, a kind of or both the above mixture in 6-di-tert-butyl-4-methy phenol, vitamin E or propyl gallate.
In some embodiments of the invention, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable antioxidant is Butylated hydroxyanisole, 2,6-di-tert-butyl-4-methy phenol or propyl gallate.
Preferably, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable sweeting agent is a kind of or both the above mixture in aspartame, acesulfame potassium, glucide, saccharin sodium, sucralose or neotame.
In some embodiments of the invention, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable sweeting agent is aspartame.
Preferably, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable bitterness screening agent is a kind of or both the above mixture in tannic acid, tartaric acid, citric acid or lactic acid.
In some embodiments of the invention, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable bitterness screening agent is tannic acid.
Preferably, on andrographolide compositions wettability solid minute loose powder Chinese materia medica provided by the invention, acceptable bitter inhibitor is a kind of or both the above mixture in styrene acid derivative bitter inhibitor, phosphatidic acid or AMP and analog bitter inhibitor thereof.
Styrene acid derivative bitter inhibitor in the present invention comprises a kind of or both the above mixture in styrene acid, coumaric acid, caffeic acid, ferulic acid or sinapic acid.
AMP in the present invention and analog bitter inhibitor thereof comprise a kind of or both the above mixture in AMP, 5 '-monophosphate thymidine, 5 '-adenosine diphosphate (ADP), 3 '-AMP, ATP or inosinic acid.
In some embodiments of the invention, the pharmaceutically acceptable bitter inhibitor in andrographolide compositions wettability solid minute loose powder provided by the invention is phosphatidic acid.
The present invention also provides a kind of preparation method of andrographolide compositions wettability solid minute loose powder, comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 1～20 weight portion, the hydroxyethyl-β-cyclodextrin of 2～39 weight portions and 0.0002～0.004 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 11.8～27.4 weight portions, the sodium dihydrogen phosphate of 12～20 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 1～10 weight portion under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
Preferably, preparation method step 1 first provided by the invention also comprises: in organic solvent, add the pharmaceutically acceptable bitterness screening agent of 0.1～10 weight portion and the pharmaceutically acceptable bitter inhibitor of 0.1～10 weight portion before mixing.
Preferably, preparation method step 2 second provided by the invention also comprises: the pharmaceutically acceptable sweeting agent that adds 0.1～1 weight portion before mixing.
Preferably, the organic solvent in preparation method provided by the invention is ethanol.
In some embodiments of the invention, preparation method provided by the invention comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 9～13 weight portions, the hydroxyethyl-β-cyclodextrin of 36～39 weight portions and 0.0018～0.0026 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 11.8～14.1 weight portions, the sodium dihydrogen phosphate of 14～16 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 6.5～9 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 9 weight portions, the hydroxyethyl-β-cyclodextrin of 36 weight portions and 0.0018 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 11.8 weight portions, the sodium dihydrogen phosphate of 16 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 9 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 13 weight portions, the hydroxyethyl-β-cyclodextrin of 39 weight portions and 0.0026 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 14.1 weight portions, the sodium dihydrogen phosphate of 14 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 6.5 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get the andrographolide of 1～20 weight portion, first mixing in organic solvent of the pharmaceutically acceptable antioxidant of the hydroxyethyl-β-cyclodextrin of 2～39 weight portions, the pharmaceutically acceptable bitterness screening agent of 0.1～10 weight portion, the pharmaceutically acceptable bitter inhibitor of 0.1～10 weight portion and 0.0002～0.004 weight portion obtains the first product;
Step 2: get step 1 gained the first product, add the pharmaceutically acceptable sweeting agent of 0.1～1 weight portion, the anhydrous glucose of 11.8～27.4 weight portions, the sodium dihydrogen phosphate of 12～20 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 1～10 weight portion under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get the andrographolide of 9～13 weight portions, first mixing in organic solvent of the pharmaceutically acceptable antioxidant of the hydroxyethyl-β-cyclodextrin of 36～39 weight portions, the pharmaceutically acceptable bitterness screening agent of 6.5～9 weight portion, the pharmaceutically acceptable bitter inhibitor of 6.5～9 weight portion and 0.0018～0.0026 weight portion obtains the first product;
Step 2: get step 1 gained the first product, add the pharmaceutically acceptable sweeting agent of 0.2～0.4 weight portion, the anhydrous glucose of 11.8～14.1 weight portions, the sodium dihydrogen phosphate of 14～16 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 6.5～9 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get the andrographolide of 9 weight portions, first mixing in organic solvent of the pharmaceutically acceptable antioxidant of the hydroxyethyl-β-cyclodextrin of 36 weight portions, the pharmaceutically acceptable bitterness screening agent of 9 weight portion, the pharmaceutically acceptable bitter inhibitor of 9 weight portion and 0.0018 weight portion obtains the first product;
Step 2: get step 1 gained the first product, add the pharmaceutically acceptable sweeting agent of 0.2 weight portion, the anhydrous glucose of 11.8 weight portions, the sodium dihydrogen phosphate of 16 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 9 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: get the andrographolide of 13 weight portions, first mixing in organic solvent of the pharmaceutically acceptable antioxidant of the hydroxyethyl-β-cyclodextrin of 39 weight portions, the pharmaceutically acceptable bitterness screening agent of 6.5 weight portion, the pharmaceutically acceptable bitter inhibitor of 6.5 weight portion and 0.0026 weight portion obtains the first product;
Step 2: get step 1 gained the first product, add the pharmaceutically acceptable sweeting agent of 0.4 weight portion, the anhydrous glucose of 14.1 weight portions, the sodium dihydrogen phosphate of 14 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 6.5 weight portions under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
The present invention also provides a kind of andrographolide compositions wettability solid minute loose powder, and its preparation method comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 1～20 weight portion, the hydroxyethyl-β-cyclodextrin of 2～39 weight portions and 0.0002～0.004 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 11.8～27.4 weight portions, the sodium dihydrogen phosphate of 12～20 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 1～10 weight portion under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
The present invention also provides a kind of andrographolide preparation, and it comprises andrographolide compositions wettability solid minute loose powder provided by the invention, the supplementary material that this andrographolide compositions wettability solid minute loose powder comprises following weight portion:
The preparation method of this andrographolide compositions wettability solid minute loose powder comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 1～20 weight portion, the hydroxyethyl-β-cyclodextrin of 2～39 weight portions and 0.0002～0.004 weight portion, obtain the first product;
Step 2: get step 1 gained the first product, add the anhydrous glucose of 11.8～27.4 weight portions, the sodium dihydrogen phosphate of 12～20 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get step 2 gained the second product, after dry 1h～6h, add the suspending agent of 1～10 weight portion under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
Preferably, andrographolide preparation provided by the invention is injection or suspensoid.
In other embodiment of the present invention, andrographolide injection provided by the invention comprises liquid infusion agent and injectable powder.
In other embodiment of the present invention, andrographolide injection provided by the invention is made by andrographolide compositions wettability solid minute loose powder provided by the invention and water.
Because andrographolide compositions wettability solid minute loose powder provided by the invention has good dispersibility in water, can be evenly distributed in water for a long time, so it can make injectable powder, according to quantity, carry out subpackage, in use, add water suspensoid, injection; Also can be directly and water be mixed and made into liquid infusion agent for injection.Experimental result has also confirmed that andrographolide compositions wettability solid minute loose powder provided by the invention can make injection, for drug administration by injection.
In other embodiment of the present invention, andrographolide compositions wettability solid provided by the invention divides the loose powder can be directly as dry suspension, in use, add water suspension, for the administration of drinking water.Experimental result confirms, an andrographolide compositions wettability solid minute loose powder provided by the invention add water suspension for the administration of drinking water, easy to use, and do not produce the stress that reloads.
The invention provides a kind of andrographolide compositions wettability solid minute loose powder and preparation method thereof.The supplementary material that this andrographolide compositions wettability solid minute loose powder comprises following weight portion: the andrographolide of 1～20 part, the hydroxyethyl-β-cyclodextrin of 2～39 parts, the suspending agent of 1～10 part, the sodium dihydrogen phosphate of 12～20 parts, the anhydrous glucose of 11.8～27.4 parts and the pharmaceutically acceptable antioxidant of 0.0002～0.004 part.Experimental result shows, this andrographolide compositions wettability solid minute loose powder has significantly improved the dispersibility of andrographolide in water, can make multiple andrographolide preparation, more be conducive to the promotion and application of andrographolide in poultry, livestock-raising and raising pets.
The specific embodiment
The invention discloses a kind of andrographolide compositions wettability solid minute loose powder and preparation method thereof.Those skilled in the art can be with reference to this paper content, obtain this andrographolide compositions wettability solid minute loose powder, realize its application, special needs to be pointed out is, all similar replacements and change apparent to those skilled in the artly, they are all deemed to be included in the present invention.Preparation method of the present invention and application are described by preferred embodiment, related personnel obviously can change this paper preparation method and application or suitably change and combination within not departing from content of the present invention, spirit and scope, realizes and apply the technology of the present invention.
In a kind of andrographolide compositions wettability solid minute loose powder provided by the invention and preparation method thereof, reagent used and raw material all can be buied by market.
In order to make those skilled in the art can understand better technical scheme of the present invention, below in conjunction with embodiment, further set forth the present invention:
Embodiment 1 andrographolide compositions wettability solid divides the formula screening of loose powder
Supplementary product kind, consumption and auxiliary material combination etc. are the key factors that affects the quality of the pharmaceutical preparations, and can these factors be directly connected to the quality that obtain pharmaceutical preparation and the quality of the pharmaceutical preparations that obtains.For the present invention's " andrographolide compositions wettability solid minute loose powder ", topmost investigation index is dispersion and sedimentation velocity.The andrographolide compositions wettability solid minute loose powder of be uniformly dispersed in order to prepare, sedimentation velocity is slow, the present invention screens its pharmaceutical formulation.
Formula:
7 different andrographolide compositions wettability solids of experimental design divide loose powder formula, and each formula forms in Table 1.
Table 1 andrographolide compositions of the present invention wettability solid divides the formula of loose powder
Preparation method:
According to the formula of table 1, get andrographolide, hydroxyethyl-β-cyclodextrin, tannic acid, phosphate ester, Butylated hydroxyanisole mixes in ethanol, after dissolving, add sodium dihydrogen phosphate, aspartame and anhydrous glucose, after mix homogeneously, aeration-drying 3h under 50 ℃ of conditions, then add sodium carboxymethyl cellulose, after mix homogeneously, 1000 orders are pulverized, and obtain.
The quality evaluation of the andrographolide compositions wettability solid minute loose powder that different formulations makes:
Adopt dispersion, settling volume than and palatability evaluate the quality of the andrographolide compositions wettability solid minute loose powder that the present invention makes, concrete grammar is as follows:
Dispersion is evaluated: get according to table 1 formula 1～formula 7 each 1g of andrographolide compositions wettability solid minute loose powder that make, drop in 1000mL water, observe or stir and observe its deployment conditions.Disperse slower and inhomogeneous being chosen as " poor "; Disperse slower, in dispersive process, have caking or granule, agitation as appropriate can be uniformly dispersed, and is chosen as " qualified "; Disperse soon, gentle agitation can be uniformly dispersed, and is chosen as " good "; Disperse soon, need not stir and can be uniformly dispersed, be chosen as " excellent ".The results are shown in Table 3.
Settling volume is than evaluating: by the settling volume that " takes solution, suspensoid for oral administration orally, takes Emulsion orally " in < < People's Republic of China (PRC) veterinary drug allusion quotation (version in 2010) > > appendix, than inspection technique requirement, to carrying out settling volume ratio by formula 1～formula 7 andrographolide compositions wettability solid minute loose powder that make, measure.Sample thief 0.25g puts in 50mL tool plug graduated cylinder, adds water to 50mL, fills in closely, and firmly jolting 1min, writes down suspended matter and start height H
0, within standing 3 hours, write down the final height H of suspended matter, be calculated as follows: settling volume ratio=H/H
0, settling volume ratio should be not less than 0.90.The results are shown in Table 3.
Palatability quality evaluation: will convert drinking water by 0.625% concentration (being 6.25mg/mL) respectively by the andrographolide compositions wettability solid minute loose powder of 1～formula, 7 preparations of filling a prescription in table 1, for healthy swinery, drink, observe and record swinery and drink situation, choose palatability grade, evaluation criterion is in Table 2.The results are shown in Table 3.
Table 2 Palatability evaluation criteria of quality evaluation
| opinion rating | evaluation criterion |
| excellent | when the drinking-water of dosing is provided, swinery is induced by abnormal smells from the patient, initiatively fights for and drinks. |
| good | when the drinking-water of dosing is provided, swinery is drunk by daily drinking habit. |
| poor | when the drinking-water of dosing is provided, swinery refusal is drunk or the amount of drinking decline relatively usually. |
Table 3 andrographolide compositions of the present invention wettability solid divides the quality evaluation result of loose powder
Listed three indexs of his-and-hers watches 3 are carried out comprehensive analysis and can be obtained: formula 1～formula is 6 all qualified, wherein again filling a prescription 4, formula 5 optimums.
Embodiment 2 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 0.4kg, hydroxyethyl-β-cyclodextrin 3.9kg, add dehydrated alcohol 200mL, Butylated hydroxyanisole 40mg, be stirred to dissolve, add anhydrous glucose 2.7kg, sodium dihydrogen phosphate 2kg, after mix homogeneously, 50 ℃ of aeration-drying 6h, add sodium carboxymethyl cellulose 1kg, mix, 4000 orders are pulverized, and obtain.
Embodiment 3 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 4.0kg, hydroxyethyl-β-cyclodextrin 4.0kg, tannic acid 2kg, phosphatidic acid 2kg, add dehydrated alcohol 4000mL, propyl gallate 800mg, be stirred to dissolve, add aspartame 0.2kg, anhydrous glucose 5kg, sodium dihydrogen phosphate 2.4kg, mix homogeneously, 50 ℃ of aeration-drying 5h, add sodium carboxymethyl cellulose 0.4kg, mix, 1000 orders are pulverized, and obtain.
Embodiment 4 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 20kg, hydroxyethyl-β-cyclodextrin 39kg, add dehydrated alcohol 10L, vitamin E2 000mg, propyl gallate 2000mg, be stirred to dissolve, add anhydrous glucose 11.8kg, sodium dihydrogen phosphate 12kg, after mix homogeneously, 65 ℃ of aeration-drying 1h, add sodium carboxymethyl cellulose 1kg, mix, 80 orders are pulverized, and obtain.
Embodiment 5 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 1kg, hydroxyethyl-β-cyclodextrin 2kg, vitamin E2 00mg, add dehydrated alcohol 4L, be stirred to dissolving, add anhydrous glucose 27.4kg, sodium dihydrogen phosphate 20kg, after mix homogeneously, 35 ℃ of aeration-drying 6h, add sodium carboxymethyl cellulose 0.5kg, carboxymethyl starch sodium 0.5kg, mix, 1000 orders are pulverized, and obtain.
Embodiment 6 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 9kg, hydroxyethyl-β-cyclodextrin 36kg, vitamin E 900mg, Butylated hydroxyanisole 450mg, 2,6-di-tert-butyl-4-methy phenol 450mg, add dehydrated alcohol 20L, be stirred to dissolving, add anhydrous glucose 11.8kg, sodium dihydrogen phosphate 16kg, mix homogeneously, 50 ℃ of aeration-drying 6h, add gelatin 4.5kg, sodium alginate 4.5kg, mix, 1000 orders are pulverized, and obtain.
Embodiment 7 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 13kg, hydroxyethyl-β-cyclodextrin 39kg, add dehydrated alcohol 10L, Butylated hydroxyanisole 2000mg, 2,6-di-tert-butyl-4-methy phenol 600mg, be stirred to dissolving, add anhydrous glucose 14.1kg, sodium dihydrogen phosphate 14kg, after mix homogeneously, 50 ℃ of aeration-drying 6h, add arabic gum 1kg, tragakanta 5.5kg, mix, 100 orders are pulverized, and obtain.
Embodiment 8 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 10kg, hydroxyethyl-β-cyclodextrin 37kg, add dehydrated alcohol 15L, Butylated hydroxyanisole 1000mg, 2,6-di-tert-butyl-4-methy phenol 1000mg, be stirred to dissolving, add anhydrous glucose 13kg, sodium dihydrogen phosphate 15kg, after mix homogeneously, 40 ℃ of aeration-drying 6h, add xanthan gum 4kg, carbomer 4kg, mix, 800 orders are pulverized, and obtain.
Embodiment 9 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 1kg, hydroxyethyl-β-cyclodextrin 2kg, tannic acid 0.1kg, phosphatidic acid 0.05kg, AMP 0.05kg, add dehydrated alcohol 4L, 2,6-di-tert-butyl-4-methy phenol 200mg, is stirred to dissolve, and adds aspartame 0.05kg, acesulfame potassium 0.05kg, anhydrous glucose 27.4kg, sodium dihydrogen phosphate 20kg, mix homogeneously, 50 ℃ of aeration-drying 4h, add sodium carboxymethyl cellulose 5kg, glucosan 2.5kg, carboxymethyl starch sodium 2.5kg, mix, 2000 pulverize, and obtain.
Embodiment 10 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 11kg, hydroxyethyl-β-cyclodextrin 39kg, tannic acid 5kg, tartaric acid 5kg, phosphatidic acid 10kg, add dehydrated alcohol 20L, Butylated hydroxyanisole 200mg, vitamin E2 000mg, be stirred to dissolving, add glucide 7kg, anhydrous glucose 11.8kg, sodium dihydrogen phosphate 15kg, after mix homogeneously, 50 ℃ of aeration-drying 4h, add sodium carboxymethyl cellulose 1kg, mix, 2000 pulverize, and obtain.
Embodiment 11 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 9kg, hydroxyethyl-β-cyclodextrin 36kg, tannic acid 9kg, caffeic acid 4.5kg, phosphatidic acid 4.5kg, add dehydrated alcohol 30L, 2,6-di-tert-butyl-4-methy phenol 1800mg, be stirred to dissolving, add saccharin sodium 0.2kg, anhydrous glucose 11.8kg, sodium dihydrogen phosphate 16kg, after mix homogeneously, 50 ℃ of aeration-drying 4h, add sodium carboxymethyl cellulose 3kg, xanthan gum 3kg, carbomer 3kg, mix, 800 pulverize, and obtain.
Embodiment 12 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 13kg, hydroxyethyl-β-cyclodextrin 39kg, tannic acid 6.5kg, caffeic acid 4.5kg, ferulic acid 2kg, add dehydrated alcohol 30L, 2,6-di-tert-butyl-4-methy phenol 1000mg, vitamin e1 600mg, be stirred to dissolving, adds sucralose 0.4kg, anhydrous glucose 14.1kg, sodium dihydrogen phosphate 14kg, mix homogeneously, 40 ℃ of aeration-drying 6h, add sodium carboxymethyl cellulose 6.5kg, mix, 3000 pulverize, and obtain.
Embodiment 13 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 12kg, hydroxyethyl-β-cyclodextrin 28kg, add dehydrated alcohol 30L, 2,6-di-tert-butyl-4-methy phenol 1500mg, Butylated hydroxyanisole 1500mg, be stirred to dissolving, adds sucralose 0.15kg, neotame 0.15kg, anhydrous glucose 14kg, sodium dihydrogen phosphate 18kg, after mix homogeneously, 65 ℃ of aeration-drying 1h, add sodium carboxymethyl cellulose 7kg, mix, 4000 pulverize, and obtain.
Embodiment 14 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 5kg, hydroxyethyl-β-cyclodextrin 25kg, tannic acid 5.5kg, lactic acid 2.5kg, add dehydrated alcohol 30L, 2,6-di-tert-butyl-4-methy phenol 2000mg, is stirred to dissolving, adds anhydrous glucose 23kg, sodium dihydrogen phosphate 17kg, after mix homogeneously, 60 ℃ of aeration-drying 3h, add sodium carboxymethyl cellulose 9kg, mix, 3000 pulverize, and obtain.
Embodiment 15 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 15kg, hydroxyethyl-β-cyclodextrin 15kg, caffeic acid 4kg, inosinic acid 2kg, phosphatidic acid 2kg, add dehydrated alcohol 40L, 2,6-di-tert-butyl-4-methy phenol 2000mg, vitamin e1 000mg, Butylated hydroxyanisole 1000mg, be stirred to dissolving, add anhydrous glucose 19kg, sodium dihydrogen phosphate 13kg, after mix homogeneously, 50 ℃ of aeration-drying 5h, add sodium carboxymethyl cellulose 10kg, mix, 4000 pulverize, and obtain.
Embodiment 16 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 10kg, hydroxyethyl-β-cyclodextrin 10kg, caffeic acid 4kg, 3 '-AMP 2kg, phosphatidic acid 2kg, add dehydrated alcohol 30L, 2,6-di-tert-butyl-4-methy phenol 2500mg, is stirred to dissolving, adds sucralose 0.25kg, aspartame 0.25kg, anhydrous glucose 20kg, sodium dihydrogen phosphate 19kg, after mix homogeneously, 50 ℃ of aeration-drying 6h, add sodium carboxymethyl cellulose 1kg, mix, 1000 pulverize, and obtain.
Embodiment 17 andrographolide compositions wettability solids divide the preparation of loose powder
Get andrographolide 20kg, hydroxyethyl-β-cyclodextrin 5kg, tannic acid 8kg, caffeic acid 4kg, ferulic acid 4kg, add dehydrated alcohol 40L, 2,6-di-tert-butyl-4-methy phenol 1000mg, is stirred to dissolving, adds anhydrous glucose 15kg, sodium dihydrogen phosphate 20kg, mix homogeneously, 35 ℃ of aeration-drying 2h, add sodium carboxymethyl cellulose 5kg, mix, 1000 pulverize, and obtain.
The oral andrographolide compositions of embodiment 18 wettability solid divides the clinical tests of loose powder to hyopneumoniae
Get the andrographolide compositions wettability solid minute loose powder that embodiment 3 makes, investigate its treatment curative effect to hyopneumoniae, commercially available tilmicosin pre-mixing agent is as positive control.By percentage to the quality, in commercially available tilmicosin pre-mixing agent, the content of tilmicosin is 20%.
Case: hyopneumoniae case 48 examples of Chengdu suburbs and counties under the jurisdiction of a large city first pig farm natural occurrence, sick pig body weight is suitable, and ill situation is similar.Clinical main manifestations is: heating, lack of appetite, cough, diminished breath sound; Nasal cavity stream mucus, expired gas has corrupt abnormal smells from the patient.
Method: at random above-mentioned 48 sick pigs are divided into 3 groups, 16 every group, are labeled as respectively positive controls, experimental group and negative control group.Positive controls provides commercially available tilmicosin pre-mixing agent, the administration of spice mode, and by percentage to the quality, in feedstuff, the content of tilmicosin is 0.01%, by the daily method for breeding feedstuff of throwing something and feeding, is used in conjunction 7 days; The andrographolide compositions wettability solid minute loose powder that experimental group provides the embodiment of the present invention 3 to make, drinking-water administration, by percentage to the quality, in water, the content of andrographolide is 0.005%, by daily method for breeding, supplies water, and is used in conjunction 7 days; Negative control group is raised according to daily feeding manner, not administration.Three groups of sick pig feeding methods are identical, the sick pig clinical manifestation of daily check, recording exceptional response situation.
Efficacy determination method: medication is after 7 days, transference cure, it is normal that spiritual appetite is recovered, and is judged to recovery from illness; After medication 7 days, symptom alleviates, and spiritual appetite takes a turn for the better, and is judged to effectively; After medication 7 days, symptom is not improved, and it is invalid to be judged to.
After medication 7 days, add up respectively the ill situation of the sick pig of positive controls, experimental group and negative control group, the therapeutic effect of the sick pig of different groups is in Table 4.
The treatment clinical tests result of the sick pig of the different groups of table 4
Known from table 4 data, the andrographolide compositions wettability solid minute loose powder that embodiment 3 makes is better than tilmicosin pre-mixing agent to the therapeutic effect of hyopneumoniae.Experiment is discovery also, and the feed intake of the sick pig of experimental group is not affected, and does not occur the stress that reloads; And positive controls is because having added the medicine stress that occurs reloading in feedstuff, during administration, in positive controls, the feed intake of sick pig all decreases, and feed intake declines 5%～30%, compares with other groups, has significant difference.So the andrographolide compositions wettability solid minute loose powder that embodiment 3 makes can adopt drinking-water administration, convenient drug administration, and improved the palatability of andrographolide, and do not affect the feed intake of disease pig, be more conducive to popularization and the use of andrographolide.
Adopt identical experimental technique, the treatment curative effect of the andrographolide compositions wettability solid minute loose powder that investigation embodiment 2, embodiment 4 to embodiment 17 make to hyopneumoniae, has obtained similar experimental result.So, the andrographolide compositions wettability solid minute loose powder that embodiment 2, embodiment 4 to embodiment 17 make can adopt drinking-water drug treatment hyopneumoniae, convenient drug administration, and improved the palatability of andrographolide, be more conducive to popularization and the use of andrographolide.
The clinical tests of embodiment 19 andrographolide injections to piglet pujos blancos disease
Get andrographolide compositions wettability solid minute loose powder 100g and the 100mL water for injection that embodiment 2 makes and be mixed and made into andrographolide injection, in quality percent by volume, wherein the content of andrographolide is 2%.Investigate the treatment curative effect of gained andrographolide injection to piglet pujos blancos disease, commercially available CHUANXINLIAN ZHUSHEYE is as positive control.The every 1mL of commercially available CHUANXINLIAN ZHUSHEYE is equivalent to crude drug in whole 1g.
Case: piglet pujos blancos case 35 examples of pig farm, Pixian County natural occurrence, sick pig sizableness, ill situation is similar.Clinical main manifestations is: sick pork chop white, canescence or the stench loose stool of yellow-white; Through laboratory diagnosis, it is coli-infection.
Method: at random above-mentioned 35 sick pigs are divided into three groups, are divided into positive controls, experimental group and negative control group, 12 sick pigs of positive controls wherein, 12 sick pigs of experimental group, 11 sick pigs of negative control group.Positive controls provides commercially available Chuanxinlian injection, by the every 1kg body weight of 0.2mL/kg.bw(administration 0.2mL, i.e. and every 1kg body weight administration 0.2g) dosage intramuscular injection, every day 1 time, be used in conjunction 3 days; The above-mentioned andrographolide injection that experimental group provides the andrographolide compositions wettability solid minute loose powder that made by embodiment 2 to prepare, according to the every 1kg body weight of 0.3mg/kg.bw(administration 0.3mg) dosage intramuscular injection, every day 1 time, be used in conjunction 3 days; Negative control group is raised by daily feeding manner, not administration.
Efficacy determination method: medication is after 3 days, and it is normal that spiritual appetite is recovered, and clinical symptom disappearance, is judged to recovery from illness; After medication 3 days, spiritual appetite takes a turn for the better, and clinical symptom relief is judged to effectively; After medication 3 days, symptom is not improved, and it is invalid to be judged to.
After medication 3 days, the ill situation of difference statistical experiment group, positive controls and the sick pig of negative control group, the therapeutic effect of the sick pigs of different groups is in Table 5.
The clinical tests result of table 5 injection andrographolide to piglet pujos blancos
From table 5, data are known, the andrographolide injection that the andrographolide compositions wettability solid minute loose powder being made by embodiment 2 and water for injection are made is better than positive controls to the treatment curative effect of piglet pujos blancos, and because andrographolide injection provided by the invention is usingd water as solvent, thus while using to the essentially no stimulation of sick pig.So the andrographolide compositions wettability solid minute loose powder that embodiment 2 makes can be made injection, gained injection is usingd water as solvent, and side effect is little, is more conducive to popularization and the use of andrographolide.
Adopt identical experimental technique, the clinical tests of the injection that the andrographolide compositions wettability solid minute loose powder that investigation embodiment 3 to embodiment 17 makes is made to piglet pujos blancos disease, has all obtained similar experimental result.So the andrographolide compositions wettability solid minute loose powder that embodiment 3 to embodiment 17 makes can be made injection, gained injection is usingd water as solvent, and side effect is little, is more conducive to popularization and the use of andrographolide.
Below be only the preferred embodiment of the present invention, it should be pointed out that above-mentioned preferred implementation should not be considered as limitation of the present invention, protection scope of the present invention should be as the criterion with claim limited range.For those skilled in the art, without departing from the spirit and scope of the present invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (9)
1. andrographolide compositions wettability solid divides a loose powder, it is characterized in that the supplementary material that it comprises following weight portion:
2. andrographolide compositions wettability solid according to claim 1 divides loose powder, it is characterized in that the supplementary material that it comprises following weight portion:
3. andrographolide compositions wettability solid according to claim 1 divides loose powder, it is characterized in that the supplementary material that it comprises following weight portion:
4. andrographolide compositions wettability solid according to claim 1 divides loose powder, it is characterized in that, described supplementary material also comprises a kind of or both the above mixture in pharmaceutically acceptable sweeting agent, pharmaceutically acceptable bitterness screening agent, pharmaceutically acceptable bitter inhibitor.
5. andrographolide compositions wettability solid divides a preparation method for loose powder, it is characterized in that, comprises the following steps:
Step 1: get pharmaceutically acceptable antioxidant first mixing in organic solvent of the andrographolide of 1～20 weight portion, the hydroxyethyl-β-cyclodextrin of 2～39 weight portions and 0.0002～0.004 weight portion, obtain the first product;
Step 2: get described the first product, add the anhydrous glucose of 11.8～27.4 weight portions, the sodium dihydrogen phosphate of 12～20 weight portions after dissolving, second mixes, and obtains the second product;
Step 3: get described the second product, after dry 1h～6h, add the suspending agent of 1～10 weight portion under 35 ℃～65 ℃ conditions, the 3rd mixes, and 80 order～4000 orders are pulverized, and obtain.
6. preparation method according to claim 5, is characterized in that, described in step 1 first mix before, also comprise:
In described organic solvent, add the pharmaceutically acceptable bitterness screening agent of 0.1～10 weight portion and the pharmaceutically acceptable bitter inhibitor of 0.1～10 weight portion.
7. preparation method according to claim 5, is characterized in that, described in step 2 second mix before, also comprise:
The pharmaceutically acceptable sweeting agent that adds 0.1～1 weight portion.
8. the andrographolide compositions wettability solid minute loose powder that the preparation method as described in any one in claim 5 to 7 makes.
9. an andrographolide preparation, is characterized in that, it comprises andrographolide compositions wettability solid minute loose powder as described in any one in claim 1 to 4 or 8.
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| CN101433522A (en) * | 2008-12-19 | 2009-05-20 | 天津大学 | Method for preparing andrographolide solid dispersion |
| CN101485646A (en) * | 2009-02-12 | 2009-07-22 | 吉林大学 | Andrographolide catablasm and preparation method thereof |
| CN102614129A (en) * | 2012-04-16 | 2012-08-01 | 武汉回盛生物科技有限公司 | Enrofloxacin dry suspension |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101433522A (en) * | 2008-12-19 | 2009-05-20 | 天津大学 | Method for preparing andrographolide solid dispersion |
| CN101485646A (en) * | 2009-02-12 | 2009-07-22 | 吉林大学 | Andrographolide catablasm and preparation method thereof |
| CN102614129A (en) * | 2012-04-16 | 2012-08-01 | 武汉回盛生物科技有限公司 | Enrofloxacin dry suspension |
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