CN103655479B - A kind of andrographolide composition wettability solid dispersal powder and preparation method thereof - Google Patents
A kind of andrographolide composition wettability solid dispersal powder and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to technical field of medicine, disclose a kind of andrographolide composition wettability solid dispersal powder and preparation method thereof.This andrographolide composition wettability solid dispersal powder comprises the supplementary material of following weight portion: the pharmaceutically acceptable antioxidant of 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 0.0002 ~ 0.004 part.This andrographolide composition wettability solid dispersal powder significantly improves 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.
Description
Technical field
The invention belongs to technical field of medicine, particularly a kind of andrographolide composition wettability solid dispersal powder and preparation method thereof.
Background technology
Andrographolide, also known as andrographolide, from acanthaceous plant Herba Andrographis, extract the diterpene ginkgolide obtained, it is one of principle active component of Chinese medicine Herba Andrographis, its taste is extremely bitter, and people are referred to as usually " king in hardship ", are soluble in ethanol, acetone, pyridine, be slightly soluble in water and chloroform, be dissolved in ether hardly.Andrographolide, molecular formula is C
20h
30o
5, molecular weight 350.44, has structure shown in formula I:
Research finds that andrographolide has antibacterial, antiviral, antipyretic, antiinflammatory, immunomodulating, anticancer, antiplatelet aggregation, suppression acute promyelocytic leukemia cell growth, multiple pharmacologically active such as treatment cardiovascular and cerebrovascular disease and hepatic cholagogic etc.Clinically, andrographolide is used to prevent and treat leptospirosis, meningitis, pneumonia, bacillary dysentery and upper respiratory tract infection etc., especially has special efficacy to bacillary 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, such as, 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 the glandular stomach that cattle and sheep ruminant causes because of mixed infection is slow, grainsick and expansion, flatulence, ruminate unable etc.Research confirms, the effect of these application of Herba Andrographis mainly wherein andrographolide, so andrographolide has very high veterinary importance.But due to andrographolide poorly water-soluble, water-soluble and other aqueous mediums hardly, thus limit its application.Although there is andrographolide tablet, dispersible tablet, drop pill, capsule and soft capsule dosage form in the market, these dosage administration are inconvenient, and are not suitable for for animals, so not yet have andrographolide veterinary formulations at present.
In order to allow andrographolide better be applied in poultry, livestock-raising and raising pets, developing a kind of good water solubility, being 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 composition wettability solid dispersal powder and preparation method thereof.This andrographolide composition wettability solid dispersal powder significantly improves the dispersibility of andrographolide in water, may be used for preparing 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 composition wettability solid dispersal powder, it comprises the supplementary material of following weight portion:
Andrographolide composition wettability solid dispersal powder provided by the invention refers to the wettable powder that applying solid dispersion technology prepares, this andrographolide composition wettability solid dispersal powder had both had the characteristic of fraction solids dispersant, had again the characteristic of wettable powder.By screening obtain suitable formula to supplementary product kind wherein, supplementary product consumption, significantly improve the dispersibility of andrographolide in water, experimental result shows this andrographolide composition wettability solid dispersal powder can make multiple andrographolide preparation, easy to use, be applicable to for animals, be more conducive to the promotion and application of andrographolide in poultry, livestock-raising and raising pets.
Preferably, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In some embodiments of the invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In other embodiment of the present invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In other embodiment of the present invention, the supplementary material in andrographolide composition wettability solid dispersal 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 added wherein in pharmaceutically acceptable sweeting agent, pharmaceutically acceptable bitterness screening agent, pharmaceutically acceptable bitter inhibitor can shelter its bitterness, improve its palatability, avoid the reload stress of the sharp-nosed animals such as pig when administration.Experimental result shows, andrographolide composition wettability solid dispersal powder provided by the invention does not have generation to reload stress in drinking water administration process, does not affect the feed intake of disease pig.
In some embodiments of the invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In other embodiment of the present invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In other embodiment of the present invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
In other embodiment of the present invention, andrographolide composition wettability solid dispersal powder provided by the invention comprises the supplementary material of following weight portion:
Preferably, the suspending agent in andrographolide composition wettability solid dispersal 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 composition wettability solid dispersal powder Chinese materia medica provided by the invention, acceptable suspending agent is sodium carboxymethyl cellulose.
Preferably, on andrographolide composition wettability solid dispersal powder Chinese materia medica provided by the invention, acceptable antioxidant is a kind of or both the above mixture in Butylated hydroxyanisole, 2,6-di-tert-butyl-4-methy phenols, vitamin E or propyl gallate.
In some embodiments of the invention, on andrographolide composition wettability solid dispersal powder Chinese materia medica provided by the invention, acceptable antioxidant is Butylated hydroxyanisole, 2,6-di-tert-butyl-4-methy phenols or propyl gallate.
Preferably, on andrographolide composition wettability solid dispersal 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 composition wettability solid dispersal powder Chinese materia medica provided by the invention, acceptable sweeting agent is aspartame.
Preferably, on andrographolide composition wettability solid dispersal 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 composition wettability solid dispersal powder Chinese materia medica provided by the invention, acceptable bitterness screening agent is tannic acid.
Preferably, on andrographolide composition wettability solid dispersal 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 composition wettability solid dispersal powder provided by the invention is phosphatidic acid.
Present invention also offers a kind of preparation method of andrographolide composition wettability solid dispersal powder, comprise the following steps:
Step 1: get the andrographolide of 1 ~ 20 weight portion, the hydroxyethyl-β-cyclodextrin of 2 ~ 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0002 ~ 0.004 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 ~ 27.4 weight portions, 12 ~ 20 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 1 ~ 10 weight portion, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
Preferably, preparation method step 1 first provided by the invention also comprises: 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 in organic solvent before mixing.
Preferably, preparation method step 2 second provided by the invention also comprises: the pharmaceutically acceptable sweeting agent adding 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 the andrographolide of 9 ~ 13 weight portions, the hydroxyethyl-β-cyclodextrin of 36 ~ 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0018 ~ 0.0026 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 ~ 14.1 weight portions, 14 ~ 16 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 6.5 ~ 9 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
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, the hydroxyethyl-β-cyclodextrin of 36 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0018 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 weight portions, 16 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 9 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
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, the hydroxyethyl-β-cyclodextrin of 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0026 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 14.1 weight portions, 14 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 6.5 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: pharmaceutically acceptable antioxidant first mixing in organic solvent of getting the andrographolide of 1 ~ 20 weight portion, the hydroxyethyl-β-cyclodextrin of 2 ~ 39 weight portions, 0.1 ~ 10 weight portion pharmaceutically acceptable bitterness screening agent, 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 first product, adds 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, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 1 ~ 10 weight portion, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: pharmaceutically acceptable antioxidant first mixing in organic solvent of getting the andrographolide of 9 ~ 13 weight portions, the hydroxyethyl-β-cyclodextrin of 36 ~ 39 weight portions, 6.5 ~ 9 weight portion pharmaceutically acceptable bitterness screening agent, 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 first product, adds 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, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 6.5 ~ 9 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: pharmaceutically acceptable antioxidant first mixing in organic solvent of getting the andrographolide of 9 weight portions, the hydroxyethyl-β-cyclodextrin of 36 weight portions, 9 weight portion pharmaceutically acceptable bitterness screening agent, the pharmaceutically acceptable bitter inhibitor of 9 weight portion and 0.0018 weight portion, obtains the first product;
Step 2: get step 1 gained first product, adds 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, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 9 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: pharmaceutically acceptable antioxidant first mixing in organic solvent of getting the andrographolide of 13 weight portions, the hydroxyethyl-β-cyclodextrin of 39 weight portions, 6.5 weight portion pharmaceutically acceptable bitterness screening agent, 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 first product, adds 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, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 6.5 weight portions, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
Present invention also offers a kind of andrographolide composition wettability solid dispersal powder, its preparation method comprises the following steps:
Step 1: get the andrographolide of 1 ~ 20 weight portion, the hydroxyethyl-β-cyclodextrin of 2 ~ 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0002 ~ 0.004 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 ~ 27.4 weight portions, 12 ~ 20 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 1 ~ 10 weight portion, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
Present invention also offers a kind of andrographolide preparation, it comprises andrographolide composition wettability solid dispersal powder provided by the invention, and this andrographolide composition wettability solid dispersal powder comprises the supplementary material of following weight portion:
The preparation method of this andrographolide composition wettability solid dispersal powder comprises the following steps:
Step 1: get the andrographolide of 1 ~ 20 weight portion, the hydroxyethyl-β-cyclodextrin of 2 ~ 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0002 ~ 0.004 weight portion, obtain the first product;
Step 2: get step 1 gained first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 ~ 27.4 weight portions, 12 ~ 20 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get step 2 gained second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 1 ~ 10 weight portion, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
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 up of andrographolide composition wettability solid dispersal powder provided by the invention and water.
Because andrographolide composition wettability solid dispersal 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, subpackage is carried out according to quantity, in use, add water suspensoid, injection; Also can directly and water be mixed and made into liquid infusion agent for injecting.Experimental result also demonstrate that andrographolide composition wettability solid dispersal powder provided by the invention can make injection, for drug administration by injection.
In other embodiment of the present invention, andrographolide composition wettability solid dispersal powder provided by the invention can directly as dry suspension, in use, add water suspension, for drinking water administration.Experimental result confirms, andrographolide composition wettability solid dispersal powder provided by the invention add water suspension for drinking water administration, easy to use, and do not have generation to reload stress.
The invention provides a kind of andrographolide composition wettability solid dispersal powder and preparation method thereof.This andrographolide composition wettability solid dispersal powder comprises the supplementary material of following weight portion: the pharmaceutically acceptable antioxidant of 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 0.0002 ~ 0.004 part.Experimental result shows, this andrographolide composition wettability solid dispersal powder significantly improves the dispersibility of andrographolide in water, multiple andrographolide preparation can be made, be more conducive to the promotion and application of andrographolide in poultry, livestock-raising and raising pets.
Detailed description of the invention
The invention discloses a kind of andrographolide composition wettability solid dispersal powder and preparation method thereof.Those skilled in the art can with reference to present disclosure, obtain this andrographolide composition wettability solid dispersal powder, realize its application, special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, 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 not depart from content of the present invention, spirit and scope this paper preparation method and application are changed or suitably change with combination, realize and apply the technology of the present invention.
Reagent used in a kind of andrographolide composition wettability solid dispersal powder provided by the invention and preparation method thereof and raw material all can be buied by market.
In order to enable those skilled in the art understand technical scheme of the present invention better, below in conjunction with embodiment, set forth the present invention further:
The recipe determination of embodiment 1 andrographolide composition wettability solid dispersal powder
Supplementary product kind, consumption and auxiliary material combination etc. are the key factors affecting the quality of the pharmaceutical preparations, these factors be directly connected to can obtain pharmaceutical preparation and obtain the quality of the quality of the pharmaceutical preparations.For the present invention's " andrographolide composition wettability solid dispersal powder ", topmost inspection target is dispersion and sedimentation velocity.Be uniformly dispersed to prepare, andrographolide composition wettability solid dispersal powder that sedimentation velocity is slow, the present invention screens its pharmaceutical formulation.
Formula:
The andrographolide composition wettability solid dispersal powder formula that experimental design 7 is different, each formula composition is in table 1.
The formula of table 1 andrographolide composition wettability of the present invention solid dispersal powder
Preparation method:
According to the formula of table 1, get andrographolide, hydroxyethyl-β-cyclodextrin, tannic acid, phosphate ester, Butylated hydroxyanisole mix in ethanol, sodium dihydrogen phosphate, aspartame and anhydrous glucose is added after dissolving, after mix homogeneously, aeration-drying 3h under 50 DEG C of conditions, then add sodium carboxymethyl cellulose, after mix homogeneously, 1000 orders are pulverized, and to obtain final product.
The quality evaluation of the andrographolide composition wettability solid dispersal powder that different formulations obtains:
Adopt dispersion, sedimentation volume ratio and palatability to evaluate the quality of the andrographolide composition wettability solid dispersal powder that the present invention obtains, concrete grammar is as follows:
Dispersion is evaluated: get according to the obtained each 1g of andrographolide composition wettability solid dispersal powder of table 1 formula 1 ~ formula 7, drop in 1000mL water, observe or stir and observe its deployment conditions.Disperse slower and to be unevenly chosen as " poor "; Dispersion is comparatively slow, and have caking or granule in dispersive process, agitation as appropriate can be uniformly dispersed, and is chosen as " qualified "; Dispersion is fast, and gentle agitation can be uniformly dispersed, and is chosen as " good "; Dispersion is fast, need not stir and can be uniformly dispersed, be chosen as " excellent ".The results are shown in Table 3.
Sedimentation volume ratio is evaluated: by " solution for oral administration, suspensoid for oral administration, Emulsion for oral administration " sedimentation volume ratio inspection technique requirement in " People's Republic of China's veterinary drug allusion quotation (version in 2010) " annex, carry out sedimentation volume ratio mensuration to the andrographolide composition wettability solid dispersal powder obtained by formula 1 ~ formula 7.Sample thief 0.25g puts in 50mL tool plug graduated cylinder, adds water to 50mL, fills in close, and firmly jolting 1min, writes down suspended matter and start height H
0, leave standstill and within 3 hours, write down the final height H of suspended matter, be calculated as follows: sedimentation volume ratio=H/H
0, sedimentation volume ratio should be not less than 0.90.The results are shown in Table 3.
Palatability quality evaluation: the andrographolide composition wettability solid dispersal powder prepared by formula 1 ~ formula 7 in table 1 is converted drinking water by the concentration (i.e. 6.25mg/mL) of 0.625% respectively, drink for healthy swinery, 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 providing the drinking-water of dosing, swinery is induced by abnormal smells from the patient, initiatively fights for and drinks. |
| good | when providing the drinking-water of dosing, swinery is drunk by daily drinking habit. |
| difference | when providing the drinking-water of dosing, swinery refusal is drunk or the amount of drinking declines relatively usually. |
The quality evaluation result of table 3 andrographolide composition wettability of the present invention solid dispersal powder
Listed three indexs of his-and-hers watches 3 are carried out comprehensive analysis and can be obtained: formula 1 ~ formula 6 is all qualified, wherein again with formula 4, formula 5 optimum.
The preparation of embodiment 2 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add sodium carboxymethyl cellulose 1kg, mixing, 4000 orders are pulverized, and to obtain final product.
The preparation of embodiment 3 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 5h, add sodium carboxymethyl cellulose 0.4kg, mixing, 1000 orders are pulverized, and to obtain final product.
The preparation of embodiment 4 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 1h, add sodium carboxymethyl cellulose 1kg, mixing, 80 orders are pulverized, and to obtain final product.
The preparation of embodiment 5 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add sodium carboxymethyl cellulose 0.5kg, carboxymethyl starch sodium 0.5kg, mixing, 1000 orders are pulverized, and to obtain final product.
The preparation of embodiment 6 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add gelatin 4.5kg, sodium alginate 4.5kg, mixing, 1000 orders are pulverized, and to obtain final product.
The preparation of embodiment 7 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add arabic gum 1kg, tragakanta 5.5kg, mixing, 100 orders are pulverized, and to obtain final product.
The preparation of embodiment 8 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add xanthan gum 4kg, carbomer 4kg, mixing, 800 orders are pulverized, and to obtain final product.
The preparation of embodiment 9 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 4h, add sodium carboxymethyl cellulose 5kg, glucosan 2.5kg, carboxymethyl starch sodium 2.5kg, mixing, 2000 pulverize, and to obtain final product.
The preparation of embodiment 10 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 4h, add sodium carboxymethyl cellulose 1kg, mixing, 2000 pulverize, and to obtain final product.
The preparation of embodiment 11 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 4h, add sodium carboxymethyl cellulose 3kg, xanthan gum 3kg, carbomer 3kg, mixing, 800 pulverize, and to obtain final product.
The preparation of embodiment 12 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add sodium carboxymethyl cellulose 6.5kg, mixing, 3000 pulverize, and to obtain final product.
The preparation of embodiment 13 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 1h, add sodium carboxymethyl cellulose 7kg, mixing, 4000 pulverize, and to obtain final product.
The preparation of embodiment 14 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 3h, add sodium carboxymethyl cellulose 9kg, mixing, 3000 pulverize, and to obtain final product.
The preparation of embodiment 15 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 5h, add sodium carboxymethyl cellulose 10kg, mixing, 4000 pulverize, and to obtain final product.
The preparation of embodiment 16 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 6h, add sodium carboxymethyl cellulose 1kg, mixing, 1000 pulverize, and to obtain final product.
The preparation of embodiment 17 andrographolide composition wettability solid dispersal 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 DEG C of aeration-drying 2h, add sodium carboxymethyl cellulose 5kg, mixing, 1000 pulverize, and to obtain final product.
Embodiment 18 oral andrographolide composition wettability solid dispersal powder is to the clinical tests of hyopneumoniae
The andrographolide composition wettability solid dispersal powder that Example 3 is obtained, 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 example of Chengdu suburbs and counties under the jurisdiction of a large city first pig farm natural occurrence, sick pig body weight is suitable, and disease condition 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, often organizes 16, is labeled as positive controls, experimental group and negative control group respectively.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%, to throw something and feed feedstuff, be used in conjunction 7 days by daily method for breeding; The andrographolide composition wettability solid dispersal powder that experimental group provides the embodiment of the present invention 3 obtained, drinking water administration, by percentage to the quality, in water, the content of andrographolide is 0.005%, supplies water by daily method for breeding, 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, spiritual appetite recovers normal, is judged to recovery from illness; Medication is after 7 days, and symptom alleviates, and spiritual appetite takes a turn for the better, and is judged to effectively; Medication is after 7 days, and symptom is not improved, and it is invalid to be judged to.
Medication, after 7 days, adds up the disease condition of the sick pig of positive controls, experimental group and negative control group respectively, and the therapeutic effect of the sick pig of different group is in table 4.
The treatment clinical tests result of the sick pig of the different group of table 4
Known from table 4 data, the therapeutic effect of andrographolide composition wettability solid dispersal powder to hyopneumoniae that embodiment 3 obtains is better than tilmicosin pre-mixing agent.Experiment also finds, the feed intake of the sick pig of experimental group is not affected, and does not occur the stress that reloads; And stress appears reloading in positive controls because with the addition of medicine in feedstuff, during administration, in positive controls, the feed intake of sick pig all decreases, and feed intake declines 5% ~ 30%, compared with other groups, has significant difference.So the andrographolide composition wettability solid dispersal powder that embodiment 3 obtains can adopt drinking water administration, convenient drug administration, and improves the palatability of andrographolide, does not affect the feed intake of disease pig, is more conducive to popularization and the use of andrographolide.
Adopt identical experimental technique, the andrographolide composition wettability solid dispersal powder that investigation embodiment 2, embodiment 4 to embodiment 17 obtain, to the treatment curative effect of hyopneumoniae, obtains similar experimental result.So, the andrographolide composition wettability solid dispersal powder that embodiment 2, embodiment 4 to embodiment 17 obtain can adopt drinking water administration to treat hyopneumoniae, convenient drug administration, and the palatability improving andrographolide, be more conducive to popularization and the use of andrographolide.
Embodiment 19 andrographolide injection is to the clinical tests of piglet pujos blancos disease
The andrographolide composition wettability solid dispersal powder 100g that Example 2 is obtained and 100mL water for injection are mixed and made into andrographolide injection, and with quality volume percentage, wherein the content of andrographolide is 2%.Investigate gained andrographolide injection to the treatment curative effect of 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 example of pig farm, Pixian County natural occurrence, sick pig sizableness, disease condition is similar.Clinical main manifestations is: sick pork chop white, canescence or yellow-white are smelt as of rotten fish loose stool; Be coli-infection through laboratory diagnosis.
Method: at random above-mentioned 35 sick pigs are divided into three groups, are divided into positive controls, experimental group and negative control group, wherein positive controls 12 sick pigs, experimental group 12 sick pigs, negative control group 11 sick pigs.Positive controls provides commercially available Chuanxinlian injection, by 0.2mL/kg.bw(every 1kg body weight 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 composition wettability solid dispersal powder obtained by embodiment 2 to prepare, according to 0.3mg/kg.bw(every 1kg body weight 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 spiritual appetite recovers normal, and clinical symptom disappearance, is judged to recovery from illness; Medication is after 3 days, and spiritual appetite takes a turn for the better, clinical symptom relief, is judged to effectively; Medication is after 3 days, and symptom is not improved, and it is invalid to be judged to.
Medication is after 3 days, and the disease condition of the sick pig of statistical experiment group, positive controls and negative control group respectively, the therapeutic effect of the sick pig of different group is in table 5.
The clinical tests result of andrographolide to piglet pujos blancos injected by table 5
From table 5, data are known, the treatment curative effect of andrographolide injection to piglet pujos blancos that the andrographolide composition wettability solid dispersal powder obtained by embodiment 2 and water for injection are made is better than positive controls, and because andrographolide injection provided by the invention is using water as solvent, therefore to the essentially no stimulation of sick pig when using.So the andrographolide composition wettability solid dispersal powder that embodiment 2 obtains can make injection, gained injection is using water as solvent, and side effect is little, is more conducive to popularization and the use of andrographolide.
Adopt identical experimental technique, the injection that the andrographolide composition wettability solid dispersal powder that investigation embodiment 3 to embodiment 17 obtains is made, to the clinical tests of piglet pujos blancos disease, all obtains similar experimental result.So the andrographolide composition wettability solid dispersal powder that embodiment 3 to embodiment 17 obtains can make injection, and gained injection is using 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. an andrographolide composition wettability solid dispersal powder, is characterized in that, it comprises the supplementary material of following weight portion:
2. andrographolide composition wettability solid dispersal powder according to claim 1, it is characterized in that, it comprises the supplementary material of following weight portion:
3. andrographolide composition wettability solid dispersal powder according to claim 1, it is characterized in that, it comprises the supplementary material of following weight portion:
4. andrographolide composition wettability solid dispersal powder according to claim 1, 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. a preparation method for andrographolide composition wettability solid dispersal powder, is characterized in that, comprise the following steps:
Step 1: get the andrographolide of 1 ~ 20 weight portion, the hydroxyethyl-β-cyclodextrin of 2 ~ 39 weight portions and pharmaceutically acceptable antioxidant first mixing in organic solvent of 0.0002 ~ 0.004 weight portion, obtain the first product;
Step 2: get described first product, adds the sodium dihydrogen phosphate of the anhydrous glucose of 11.8 ~ 27.4 weight portions, 12 ~ 20 weight portions after dissolving, the second mixing, obtains the second product;
Step 3: get described second product, under 35 DEG C ~ 65 DEG C conditions after dry 1h ~ 6h, adds the suspending agent of 1 ~ 10 weight portion, the 3rd mixing, and 80 order ~ 4000 orders are pulverized, and to obtain final product.
6. preparation method according to claim 5, is characterized in that, before the first mixing described in step 1, also comprises:
The pharmaceutically acceptable bitterness screening agent of 0.1 ~ 10 weight portion and the pharmaceutically acceptable bitter inhibitor of 0.1 ~ 10 weight portion is added in described organic solvent.
7. preparation method according to claim 5, is characterized in that, before the second mixing described in step 2, also comprises:
Add the pharmaceutically acceptable sweeting agent of 0.1 ~ 1 weight portion.
8. the andrographolide composition wettability solid dispersal powder obtained as the preparation method in claim 5 to 7 as described in any one.
9. an andrographolide preparation, is characterized in that, it comprises as andrographolide composition wettability solid dispersal powder as described in any one in Claims 1-4 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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| 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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