CN103720770A - Glossy privet fruit-astragalus membranaceus effervescent preparation and preparation method thereof - Google Patents
Glossy privet fruit-astragalus membranaceus effervescent preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a glossy privet fruit-astragalus membranaceus effervescent preparation and a preparation method thereof. The glossy privet fruit-astragalus membranaceus effervescent preparation is prepared from 25-40 parts of glossy privet fruit, 50-80 parts of astragalus membranaceus and a proper amount of accessories, wherein the accessories include 15-25 parts of acid agent, 20-35 parts of alkaline agent, 10-20 parts of filler and 1-10 parts of a lubricant. The effervescent preparation disclosed by the invention can solve problems of an existing glossy privet fruit-astragalus membranaceus which is simple in dosage form and inconvenient to take, and optimizes a preparation process; the produced preparation is completely dissolved, rapid to become effective and better in curative effect.
Description
Technical field
The present invention relates to a kind of loyal stilbene effervescent formulation and preparation method thereof, belong to Chinese drug preparation technique field.
Background technology
Loyal stilbene preparation is mainly comprised of the Radix Astragali, Fructus Ligustri Lucidi, Radix Astragali life invigorating QI to consolidate the body surface resistance, diuresis toxin expelling, and Fructus Ligustri Lucidi nourishing the liver and kidney, item black hair.The like product of domestic production is at present mainly ZHENQI FUZHENG KELI, and dosage form is comparatively single, and said preparation has raising body's immunity; Hemocytes increasing, protection bone marrow, adrenal cortex and liver function; Promote interferon to produce; Coordinate tumor patient Radiotherapy chemotherapy, alleviate the toxic and side effects during patient's Radiotherapy chemotherapy, promote the effect of the recovery of normal function.While taking ZHENQI FUZHENG KELI, it fully need to be dissolved and stir with hot water, take inconvenience.
And effervescent granule is to take the novel immediate-release granules agent that effervescent is disintegrating agent, compare with plain particles agent, during dissolving without stirring, use warm water or cold water can make at short notice clear and bright Liquid drug preparation, shortened dissolution time, easy to use, good absorbing, onset is rapid, bioavailability is high, and good palatability.
Therefore, the present invention will study loyal stilbene effervescent formulation.
Summary of the invention
The object of the invention is to, a kind of loyal stilbene effervescent formulation and preparation method thereof is provided, can solve existing loyal stilbene preparation formulation single, take inconvenient problem, and optimized preparation technology, gained preparation leaches complete, rapid-action, better efficacy.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
A loyal stilbene effervescent formulation, calculates by weight, and it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, adds appropriate amount of auxiliary materials to make; Described adjuvant comprises 1～10 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricant.
Aforesaid loyal stilbene effervescent formulation, calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, adds following adjuvant: 1～5 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricant, adopt dry granulation technique to make.
Preferred weight proportion following (calculating by weight): crude drug: 70 parts of the Radixs Astragali, 35 parts of Fructus Ligustri Lucidi; Adjuvant: 20 parts of acidizers, 30 parts of alkaline agents, 15 parts of filleies, 3 parts of lubricants.
Aforesaid loyal stilbene effervescent formulation, calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, adds following adjuvant: 2～10 parts of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricants, adopt wet granulation technology to make.
Preferred weight proportion following (calculating by weight): crude drug: 66 parts of the Radixs Astragali, 33 parts of Fructus Ligustri Lucidi; Adjuvant: 20 parts of acidizers, 30 parts of alkaline agents, 15 parts of filleies, 5 parts of lubricants.
Aforesaid loyal stilbene effervescent formulation, calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, add following adjuvant: 1～5 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies, 1～5 part of lubricant and binding agent, adopt non-water granulating process to make.
Preferred weight proportion following (calculating by weight): crude drug: 66 parts of the Radixs Astragali, 33 parts of Fructus Ligustri Lucidi; Adjuvant: 20 parts of acidizers, 30 parts of alkaline agents, 15 parts of filleies, 3 parts of lubricants, 2 parts of binding agents.
In aforesaid loyal stilbene effervescent formulation, described acidizer is tartaric acid or citric acid; Described alkaline agent is sodium bicarbonate or sodium carbonate; Described filler is that mannitol and/or lactose (can reduce hygroscopicity with lactose; If irradiate with infrared lamp at feeding port place during tabletting, control the temperature of granule, can increase the lubricity of granule, reduce hygroscopicity and the sticking phenomenon of effervescent tablet); Lubricant is micropowder silica gel and/or PEG6000.Wherein, micropowder silica gel can absorb the moisture up to 39%, and keep that milli is noncohesive simultaneously can flow regime, add in granule and can stop caking, also can play the effect of fluidizer, disintegrating agent.
In aforesaid loyal stilbene effervescent formulation, described binding agent is PVP K30 ethanol solution.
Aforesaid loyal stilbene effervescent formulation can adopt following preparation method preparation:
1, dry granulation, comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) by filtrate, at 75～80 ℃, vacuum, be under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) add acidizer, alkaline agent and the lubricant after sieving, mix homogeneously, drops into dry granulating machine and makes 40～60 order granules, granulate, and subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
2, wet granulation, comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) by filtrate, at 75～80 ℃, vacuum, be under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) alkaline agent after vacuum drying is ground into fine powder, the lubricant parcel with melting, is ground into fine powder, standby; Lubricant is selected PEG6000 herein, with Polyethylene Glycol, by microcapsule packaging method, alkaline agent is wrapped up, and avoids directly contacting with acidizer, has increased stability, the sticking problem while also having solved tabletting simultaneously;
(5) acidizer after vacuum drying is ground into fine powder,, medicated powder and the rest lubricant of step (3) gained are mixed homogeneously, makes 40～60 order granules with the lubricant wrappage fine powder of step (4) gained, granulate, subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
3, non-water is granulated, and comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) filtrate is under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05 at 75～80 ℃, vacuum;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) acidizer that is ground into fine powder is joined in medicated powder, mix homogeneously, sieves, and with PVP K30 ethanol solution, makes binding agent, granulate, and granulate;
(5) add alkaline agent, lubricant to mix, make 40～60 order granules, granulate, subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
In the preparation method of aforesaid loyal stilbene effervescent formulation, by filtrate, at 75～80 ℃, vacuum, be under 0.07～0.09Mpa condition, to carry out concentrating under reduced pressure, can reach and not destroy the effective ingredient in medicinal liquid as far as possible, drying efficiency is high, the dry cream of gained is crisp, easily scrape, and quality is good, of light color, equipment needed thereby input and drying cost are low simultaneously, all have better advantage on drying time and drying effect.
In the preparation method of aforesaid loyal stilbene effervescent formulation, described granulation, granulate, tabletting, packaging step all control environment relative humidity below 30%.
For guaranteeing the drug effect of preparation of the present invention, applicant has carried out a series of experimental study and screening to the kind of adjuvant and consumption, and its drug effect has been carried out to contrast experiment's research.
One, adjuvant screening
When adjuvant screens, mainly conventional acidizer, alkaline agent, filler to be screened, the effect of each adjuvant refers to table 1.
Table 1 adjuvant title and effect thereof
1, the screening of acidizer and alkaline agent
In order to increase the stability of effervescent formulation, applicant strictly screens acidizer and alkaline agent in prescription, particularly acidizer is screened; And its stability is investigated, guarantee that the effervescent formulation making, in storage and use procedure, when ensureing the effervescent effect and melting that effervescent formulation is good, can not produce the unfavorable conditions such as swollen bag, air-blowing.
In the selection of effervescent, sodium bicarbonate and sodium carbonate amount are few, gas production is large, and the present invention adopts sodium bicarbonate or sodium carbonate as alkaline agent, the screening of filling a prescription.Alternative acidizer has fumaric acid, malic acid, tartaric acid, citric acid, adipic acid, adds acidizer and the alkaline agent of same amount, carries out many experiments, and experimental result is in Table 2.
The selection result of table 2 acidizer and alkaline agent
As seen from the above table, by the investigation to factors such as granulation, effervescent and dissolubilities, select citric acid and tartaric acid as acidizer, with alkaline agent (sodium bicarbonate and sodium carbonate) jointly as effervescent.
In addition, citric acid or tartaric acid, meeting after water reacts and produce great amount of carbon dioxide with sodium bicarbonate or sodium carbonate, are acid because carbon dioxide is water-soluble, can benumb taste bud, in prescription, can double as correctives, play the effect that improves mouthfeel.Applicant has carried out mouthfeel test to 150 people, thinks and 146 people that have that the mouthfeel of loyal stilbene preparation has clear improvement accounts for 97.3% of total number of persons.
Take citric acid, sodium bicarbonate is below example, and the consumption of acidizer and alkaline agent is carried out to screening experiment, the results are shown in Table 3.
The consumption the selection result of table 3 acidizer and alkaline agent
| Tested number | Citric acid (g) | Sodium bicarbonate (g) | pH |
| 1 | 1 | 0.62 | 4.49 |
| 2 | 1 | 0.85 | 5.02 |
| 3 | 1 | 1.30 | 5.98 |
| 4 | 1 | 1.50 | 6.51 |
| 5 | 1 | 1.71 | 6.72 |
| 6 | 1 | 1.94 | 7.16 |
As seen from the above table, the pH of No. 4 and No. 5 effervescent formulations changes little, and while adopting No. 4 ratios, acid-base reaction is substantially complete, and alkali consumption is less, and mouthfeel might as well.Therefore selecting the weight ratio of citric acid and sodium bicarbonate is 1:1.5.
2, the screening of filler kind and consumption
(1) screening of filler kind
The filler that now adds same amount, screens filler by investigating hygroscopicity and hardness, the results are shown in Table 4.
The selection result of table 4 filler kind
| Filler | Hygroscopicity | Hardness |
| Mannitol | A little less than | Moderate |
| Sucrose | By force | Moderate |
| Lactose | A little less than | Moderate |
| Glucose | By force | Softer |
| Lactose+mannitol | A little less than | Moderate |
| Icing Sugar | By force | Greatly |
| Dextrin | By force | Greatly |
| Starch | A little less than | Greatly |
As can be seen from the above table, select mannitol, lactose or both mixture better as filler effect.
(2) screening of filler loading
Get 5 parts of not commensurability filleies, crude drug (25～40 parts of Fructus Ligustri Lucidi, 50～80 parts of the Radixs Astragali) and the amount of other adjuvants are consistent, granulate, dry.According to its hygroscopicity, hardness and mobility overall merit, screening filler optimum amount, the results are shown in Table 5.
The selection result of table 5 filler loading
| Filler loading | Hygroscopicity | Hardness | Mobility |
| 5 parts | Slower | Firmly | Good |
| 10 parts | Slowly | Moderate | Good |
| 15 parts | Slowly | Good | Good |
| 20 parts | Slowly | Good | Slightly poor |
| 25 parts | Slowly | Softer | Poor |
As can be seen from the above table, the amount of filler in prescription, account for 10 parts～20 parts all can, especially take 15 parts as best.
3, the screening of lubricant kind and consumption
Because the lubricant that 3 kinds of method of granulating described in the present invention are used is different, be therefore lubricated respectively the screening experiment of agent kind and consumption.
(1) dry granulation and non-water are granulated
1. the screening of lubricant kind
By above-mentioned selected formula preparation granule, add respectively the lubricant of variety classes or consumption, tabletting, and sticking situation, clarity, unilateral bright and clean situation, hardness and foaming intensity while investigating tabletting, the results are shown in Table 6.
The selection result of lubricant kind in table 6 dry granulation and the granulation of non-water
| Lubricant kind | Sticking situation | Clarity | Unilateral bright and clean situation | Hardness | Foaming intensity |
| Magnesium stearate | Sticking not | Poor | Smooth | Softer | Slightly poor |
| Micropowder silica gel | Sticking not | Good | Smooth | Good | Stronger |
| Stepanol MG | Sticking | Poor | Rough | Good | By force |
As seen from the above table, add not only sticking not of micropowder silica gel, clarity, unilateral fineness etc. are all good than other lubricants, therefore select micropowder silica gel as dry granulation of the present invention the lubricant with the granulation of non-water.
2. the screening of lubricant quantity
By above-mentioned selected prescription (wherein crude drug is 25～40 parts of Fructus Ligustri Lucidi, 50～80 parts of the Radixs Astragali), prepare granule, the micropowder silica gel that adds respectively Different Weight part, tabletting, and angle of repose, hardness, disintegration, pH value and the gas release of sticking situation, unilateral bright and clean situation, granule while investigating tabletting, the results are shown in Table 7.
The selection result of lubricant quantity in table 7 dry granulation and the granulation of non-water
Result shows, the micropowder silica gel adding in prescription, account for 1 part～5 parts all can, sticking not only, institute's tabletting smooth in appearance and disintegration, gas release are all better, the 3 parts of micropowder silica gels of especially take are best as lubricant.
(2) screening of lubricant kind and consumption in wet granulation
By above-mentioned selected prescription (wherein crude drug is 25～40 parts of Fructus Ligustri Lucidi, 50～80 parts of the Radixs Astragali), prepare granule, add respectively the lubricant of variety classes and weight portion to mix after abundant mixing, tabletting, and sticking situation, unilateral bright and clean situation, hardness, disintegration, gas release, pH value and clarity while investigating tabletting, the results are shown in Table 8.
The selection result of lubricant kind and consumption in table 8 wet granulation
Result shows, adds 2 parts of PEG6000 and 3 parts of micropowder silica gels to make lubricant, not only not sticking, institute's tabletting smooth in appearance, and disintegration, gas release are all better.
4, the screening of binding agent kind and consumption
(1) screening of binding agent kind
By above-mentioned selected formula preparation granule, add respectively different types of binding agent to mix after abundant mixing, tabletting, and investigate outward appearance, hardness, friability and disintegration, the results are shown in Table 9.
The selection result of table 9 binding agent kind
As can be seen from the above table: consider the factors such as outward appearance, hardness, friability and disintegration, PVP K30 dehydrated alcohol is optimum selection as binding agent.
(2) screening of binder dosage
During granulation, the consumption of PVP K30 dehydrated alcohol directly affects size, degree of tightness and the fine granularity of granule, thereby tabletting is produced to certain impact.Get 5 parts of not commensurability PVP K30 ethanol solutions, crude drug (25～40 parts of Fructus Ligustri Lucidi, 50～80 parts of the Radixs Astragali) and the amount of other adjuvants are consistent, granulate, dry.This experiment is screened by different PVP K30 dehydrated alcohol consumptions, and take granule qualification rate and tabletting situation is index, and preferably best PVP K30 dehydrated alcohol consumption, the results are shown in Table 10.
The selection result of table 10 binder dosage
The result of the test of upper table shows: during granulation, the consumption of PVP K30 dehydrated alcohol accounts for 1 part～5 parts even particle size of making in prescription, and the tablet requirement up to specification of extrusion selects 40 eye mesh screens to granulate, and the granular size making is moderate, and granule qualification rate is high.When PVP K30 dehydrated alcohol is 2 parts, granulation qualification rate tends to balance simultaneously, from economic aspect, considers, we select 2 parts for binding agent optimum amount.
5, melting contrast
Method: get loyal stilbene effervescent formulation and each 10g of existing ZHENQI FUZHENG KELI, add warm water 200mL, do not stir, observed at 1 minute, 5 minutes, 10 minutes, 30 minutes respectively, the results are shown in Table 11.
The contrast of the loyal stilbene effervescent formulation of table 11 and existing ZHENQI FUZHENG KELI melting
The melting of the loyal stilbene effervescent formulation of preparing according to the present invention as seen from the above table, is better than existing common ZHENQI FUZHENG KELI.
Two, pharmacodynamic experiment research
1, experiment material
1.1 Experimental agents: commercially available ZHENQI FUZHENG KELI; The loyal stilbene effervescent formulation of preparing according to the present invention; Facing the used time, all with the distilled water of 2% Tween 80, to be made into respective concentration standby.
1.2 laboratory animals: Kunming mouse, ♀ ♂ half and half, body weight 20 ± 0.7g, is provided by Guiyang Medical College Experimental Animal Center; Laboratory illumination is sufficient, and ventilation is good, 18～22 ℃ of room temperatures, humidity 50%～70%, routinely regularly sterilization; Freely drink water, diet, mice rearging cage sub-cage rearing, observes and adapts to 5 days before zoopery, checks after qualified and starts to enter formal experiment.
1.3 animal groupings: get 60 of mices, by body weight sex, be divided at random 6 groups, Normal group and model control group, positive administration group gavage ZHENQI FUZHENG KELI 4.27g crude drug/kg, the loyal stilbene effervescent formulation of loyal stilbene effervescent formulation high dose group gavage 8.55g crude drug/kg, the loyal stilbene effervescent formulation of dosage group gavage 4.27g crude drug/kg in loyal stilbene effervescent formulation, the loyal stilbene effervescent formulation of loyal stilbene effervescent formulation low dose group gavage 2.18g crude drug/kg.
1.4 instrument and equipments: VIS-7220 type spectrophotometer, OLYMPUS CHK2-H-GS type microscope, centrifuge, water-bath, constant incubator, refrigerator, 96 hole Microhemagglutination plates, cell counting count board, enumerator, claims liquid device.
2, experimental technique
2.1 impacts on serum hemolysin
Normal group and model control group such as all give at the distilled water gavage of holding 2% Tween 80, and each organizes successive administration 10 days.Administration rises except Normal group on the 8th day, and other each groups are all at subcutaneous injection cyclophosphamide 40mgkg
-1d
-1, every day 1 time, totally 3 times.Administration the 4th day, each only organizes mouse peritoneal injection 5%CRBC suspension 0.2mL/, carries out immunity.After last administration 24 hours, each Mus femoral artery was got blood in centrifuge tube, placed 1 hour under room temperature, and the centrifugal 10min of 2000rpm, gets 100 times of normal saline dilutions for serum.Get dilute serum 1mL, mix with 5% chicken red blood cell (CRBC) suspension 0.5mL, 100% complement 0.5mL, in 37 ℃ of calorstats, be incubated 30min, after in 0 ℃ of refrigerator cessation reaction.Centrifugal, get supernatant in spectrophotometer 540nm place colorimetric, separately establish the not blank of increase serum, get its supernatant withered as blank, using optical density (OD) value as the index of judging that serum hemolysin is tired, mean ± standard deviation for data acquisition
represent, between group, relatively adopt t check.Experimental result is in Table 12.
The affect comparison of each group of table 12 on serum hemolysin
Note: with model control group comparison:
*p<0.05,
*p<0.01.
Experimental result shows, loyal stilbene effervescent formulation is to the caused by cyclophosphamide immunologic hypofunction mice serum hemolysin obvious potentiation of having tired, 8.55g crude drug/kg, two dosage groups of 4.27g crude drug/kg and model control group comparing difference all have statistical significance, 2.18g crude drug/kg dosage group and model control group relatively have enhancing trend, but difference not statistically significant.Difference not statistically significant between loyal stilbene effervescent formulation 4.27g crude drug/kg and ZHENQI FUZHENG KELI 4.27g crude drug/kg.
2.2 impacts on serum agglutinin
Normal group and model control group such as all give at the distilled water gavage of holding 2% Tween 80, and each organizes successive administration 10 days.Administration rises except Normal group on the 8th day, and other each groups are all at subcutaneous injection cyclophosphamide 40mgkg
-1d
-1, every day 1 time, totally 3 times.Administration the 4th day, each only organizes mouse peritoneal injection 5%CRBC suspension 0.2mL/, carries out immunity.After last administration 24 hours, each Mus femoral artery was got blood in centrifuge tube, places 1 hour under room temperature, and the centrifugal 10min of 2000rpm, gets 56 ℃ of water-bath deactivation 30min of serum, with normal saline, is two-fold dilution.The dilution serum of difference is added respectively in Microhemagglutination brassboard, every hole 50 μ L, then add CRBC suspension 0.5 μ L, and mix, add a cover and be placed in incubator 3 hours.So that the numeric representation serum agglutinin antibody titer of the serum maximum dilution multiple of coagulation appears in blood cell, carry out statistical procedures, mean ± standard deviation for data acquisition
represent, and t check between organizing.Experimental result is in Table 13.
The affect comparison of each group of table 13 on serum agglutinin
Note: with model control group comparison:
*p<0.05,
*p<0.01.
Experimental result shows, loyal stilbene effervescent formulation has obvious potentiation to caused by cyclophosphamide immunologic hypofunction mice serum agglutinin antibody titer.
2.3 cause the impact of the murine interleukin that hemopoietic function is low to cyclophosphamide
Normal group and model control group such as all give at the distilled water gavage of holding 2% Tween 80, and each organizes and is administered once every day, successive administration 15 days.Except Normal group, other each groups are in administration the 6th day and the 7th day intraperitoneal injection of cyclophosphamide 100mgkg
-1; The 8th day and the 9th day be intraperitoneal injection of cyclophosphamide 100mgkg again
-1.After last administration 1 hour, each organizes the mouse orbit 20 μ L that take a blood sample, and adds in 0.38mL leukocyte diluent, in blood countng chamber, calculates leukocyte.Experimental result is in Table 14.
The affect comparison of each group of table 14 on the minimizing of caused by cyclophosphamide murine interleukin
Note: with model control group comparison:
*p<0.05,
*p<0.01.
Experimental result shows, loyal stilbene effervescent formulation has obvious castering action to the low mice peripheral leukocytes of caused by cyclophosphamide hemopoietic function.
In sum, loyal stilbene effervescent formulation prepared by the present invention has obvious regulating action to immune function of mice, and the mice serum hemolysin of caused by cyclophosphamide immunologic hypofunction and serum agglutinin antibody titer are all had to remarkable potentiation; Caused by cyclophosphamide mice peripheral leukocytes is declined and also has obvious castering action, and its action effect is better than existing ZHENQI FUZHENG KELI.
Compared with prior art, the present invention has the following advantages:
1, can reduce supplementary product consumption, easy-formation, is difficult for moisture absorption, and effervescent speed is fast, and effervescent is effective, and melting is good, after effervescent medicinal liquid clarity good, without breeze foreign body etc.
2, loyal stilbene effervescent formulation of the present invention is very stable, can at room temperature preserve for a long time.Because production technology of the present invention is simple, material, production cost are all lower, so the requirement that production environment is controlled humidity also reduces greatly.Product can keep steady quality in a long time, and the phenomenons such as aerogenesis, packing tympanites, disintegrate, deliquescence can not occur, and the stable of product active ingredient also played to good facilitation, and can access significant prolongation the storage period of product.
3, use advanced effervescent formulation technology, enriched the dosage form of loyal stilbene preparation, product of the present invention dissolves rapidly, absorbs soon, and bioavailability is high, has Comprehensive Treatment effect, adds warm water or cold water, without stirring, is solubilized, facilitates patients.
The specific embodiment
The embodiment of the present invention 1: a kind of loyal stilbene effervescent granule, it is made by Fructus Ligustri Lucidi 35g, Radix Astragali 70g, citric acid 20g, sodium bicarbonate 30g, mannitol 15g and micropowder silica gel 3g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 78 ℃, vacuum, be under 0.08Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Mannitol is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 165 ℃ of inlet temperature, 80 ℃ of leaving air temps, obtain medicated powder, standby; Add citric acid, sodium bicarbonate and micropowder silica gel after sieving, mix homogeneously, drops into dry granulating machine and makes 40～60 order granules, granulate, and subpackage, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 2: a kind of loyal stilbene effervescent tablet, it is made by Fructus Ligustri Lucidi 25g, Radix Astragali 50g, tartaric acid 15g, sodium carbonate 20g, lactose 10g and micropowder silica gel 1g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 75 ℃, vacuum, be under 0.07Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Lactose is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160 ℃ of inlet temperature, 75 ℃ of leaving air temps, obtain medicated powder, standby; Add tartaric acid, sodium carbonate and micropowder silica gel after sieving, mix homogeneously, drops into dry granulating machine and makes 40～50 order granules, granulate, and by gained granule tabletting, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 3: a kind of loyal stilbene effervescent granule, it is made by Fructus Ligustri Lucidi 40g, Radix Astragali 80g, tartaric acid 25g, sodium bicarbonate 35g, mannitol 10g, lactose 10g and micropowder silica gel 5g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 80 ℃, vacuum, be under 0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Mannitol, lactose are dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 170 ℃ of inlet temperature, 90 ℃ of leaving air temps, obtain medicated powder, standby; Add tartaric acid, sodium bicarbonate and micropowder silica gel after sieving, mix homogeneously, drops into dry granulating machine and makes 50～60 order granules, granulate, and subpackage, then packing, obtains.
The embodiment of the present invention 4: a kind of loyal stilbene effervescent tablet, it is made by Fructus Ligustri Lucidi 33g, Radix Astragali 66g, tartaric acid 20g, sodium bicarbonate 30g, mannitol 15g, micropowder silica gel 3g and PEG60002g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 78 ℃, vacuum, be under 0.08Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Mannitol is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 165 ℃ of inlet temperature, 80 ℃ of leaving air temps, obtain medicated powder, standby; Sodium bicarbonate after vacuum drying is ground into fine powder, and the PEG6000 parcel with melting, is ground into fine powder, standby; Tartaric acid after vacuum drying is ground into fine powder, mixs homogeneously with PEG6000 wrappage fine powder, medicated powder and micropowder silica gel, make 40～60 order granules, granulate, by gained granule tabletting, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 5: a kind of loyal stilbene effervescent granule, it is made by Fructus Ligustri Lucidi 25g, Radix Astragali 50g, citric acid 15g, sodium carbonate 20g, lactose 10g, micropowder silica gel 1.2g and PEG60000.8g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 75 ℃, vacuum, be under 0.07Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Lactose is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160 ℃ of inlet temperature, 75 ℃ of leaving air temps, obtain medicated powder, standby; Sodium carbonate after vacuum drying is ground into fine powder, and the PEG6000 parcel with melting, is ground into fine powder, standby; Citric acid after vacuum drying is ground into fine powder, mixs homogeneously with PEG6000 wrappage fine powder, medicated powder and micropowder silica gel, make 40～50 order granules, granulate, subpackage, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 6: a kind of loyal stilbene effervescent tablet, it is made by Fructus Ligustri Lucidi 40g, Radix Astragali 80g, citric acid 25g, sodium bicarbonate 35g, mannitol 12g, lactose 8g, micropowder silica gel 6g and PEG60004g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; By filtrate, at 80 ℃, vacuum, be under 0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05; Mannitol, lactose are dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 170 ℃ of inlet temperature, 90 ℃ of leaving air temps, obtain medicated powder, standby; Sodium bicarbonate after vacuum drying is ground into fine powder, and the PEG6000 parcel with melting, is ground into fine powder, standby; Citric acid after vacuum drying is ground into fine powder, mixs homogeneously with PEG6000 wrappage fine powder, medicated powder and micropowder silica gel, make 50～60 order granules, granulate, by gained granule tabletting, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 7: a kind of loyal stilbene effervescent granule, it is made by Fructus Ligustri Lucidi 33g, Radix Astragali 66g, citric acid 20g, sodium bicarbonate 30g, lactose 15g, micropowder silica gel 3g and PVP K30 ethanol solution 2g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; Filtrate is under 0.08Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05 at 77 ℃, vacuum; Lactose is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 165 ℃ of inlet temperature, 80 ℃ of leaving air temps, obtain medicated powder, standby; The citric acid that is ground into fine powder is joined in medicated powder, and mix homogeneously, sieves, and with PVP K30 ethanol solution, makes binding agent, granulate, and granulate; Add sodium bicarbonate, micropowder silica gel to mix, make 40～60 order granules, granulate, subpackage, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 8: a kind of loyal stilbene effervescent tablet, it is made by Fructus Ligustri Lucidi 25g, Radix Astragali 50g, citric acid 15g, sodium carbonate 20g, mannitol 10g, micropowder silica gel 1g and PVP K30 ethanol solution 1g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; Filtrate is under 0.07Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05 at 75 ℃, vacuum; Mannitol is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160 ℃ of inlet temperature, 75 ℃ of leaving air temps, obtain medicated powder, standby; The citric acid that is ground into fine powder is joined in medicated powder, and mix homogeneously, sieves, and with PVP K30 ethanol solution, makes binding agent, granulate, and granulate; Add sodium carbonate, micropowder silica gel to mix, make 40～50 order granules, granulate, by gained granule tabletting, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
The embodiment of the present invention 9: a kind of loyal stilbene effervescent granule, it is made by Fructus Ligustri Lucidi 40g, Radix Astragali 80g, tartaric acid 25g, sodium carbonate 35g, mannitol 8g, lactose 12g, micropowder silica gel 5g and PVP K30 ethanol solution 5g.The Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate; Filtrate is under 0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05 at 80 ℃, vacuum; Mannitol, lactose are dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 170 ℃ of inlet temperature, 90 ℃ of leaving air temps, obtain medicated powder, standby; The tartaric acid that is ground into fine powder is joined in medicated powder, and mix homogeneously, sieves, and with PVP K30 ethanol solution, makes binding agent, granulate, and granulate; Add sodium carbonate, micropowder silica gel to mix, make 50～60 order granules, granulate, subpackage, then packing, obtains.After dissolving by cold water or warm water, take, each serving consumption, by primary crude drug, count 12.5g, every day 2 times.
Granulation in above-described embodiment, granulate, tabletting, packaging step preferably all control environment relative humidity below 30%.
Claims (10)
1. a loyal stilbene effervescent formulation, is characterized in that: calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, adds appropriate amount of auxiliary materials to make; Described adjuvant comprises 1～10 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricant.
2. loyal stilbene effervescent formulation according to claim 1, it is characterized in that, calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, add following adjuvant: 1～5 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricant, adopt dry granulation technique to make.
3. loyal stilbene effervescent formulation according to claim 1, it is characterized in that: calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, add following adjuvant: 2～10 parts of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies and lubricants, adopt wet granulation technology to make.
4. loyal stilbene effervescent formulation according to claim 1, it is characterized in that: calculate by weight, it is that to take 50～80 parts of 25～40 parts of Fructus Ligustri Lucidi and the Radixs Astragali be crude drug, add following adjuvant: 1～5 part of 15～25 parts of acidizers, 20～35 parts of alkaline agents, 10～20 parts of filleies, 1～5 part of lubricant and binding agent, adopt non-water granulating process to make.
5. according to the loyal stilbene effervescent formulation described in claim 2,3 or 4, it is characterized in that: described acidizer is tartaric acid or citric acid; Described alkaline agent is sodium bicarbonate or sodium carbonate; Described filler is mannitol and/or lactose; Lubricant is micropowder silica gel and/or PEG6000.
6. loyal stilbene effervescent formulation according to claim 4, is characterized in that: described binding agent is PVP K30 ethanol solution.
7. the preparation method of loyal stilbene effervescent formulation as claimed in claim 2, is characterized in that, comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) by filtrate, at 75～80 ℃, vacuum, be under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) add acidizer, alkaline agent and the lubricant after sieving, mix homogeneously, drops into dry granulating machine and makes 40～60 order granules, granulate, and subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
8. the preparation method of loyal stilbene effervescent formulation as claimed in claim 3, is characterized in that, comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) by filtrate, at 75～80 ℃, vacuum, be under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) alkaline agent after vacuum drying is ground into fine powder, the lubricant parcel with melting, is ground into fine powder, standby;
(5) acidizer after vacuum drying is ground into fine powder,, medicated powder and the rest lubricant of step (3) gained are mixed homogeneously, makes 40～60 order granules with the lubricant wrappage fine powder of step (4) gained, granulate, subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
9. the preparation method of loyal stilbene effervescent formulation as claimed in claim 4, is characterized in that, comprises the following steps:
(1) Radix Astragali, Fructus Ligustri Lucidi are decocted with water three times, add for the first time 8 times of amounts of water, decoct 2.5 hours, add for the second time, for the third time 6 times of amounts of water, decoct 1.5 hours, filter merging filtrate;
(2) filtrate is under 0.07～0.09Mpa condition, to be evaporated to the clear paste that 60 ℃ of relative densities are 1.05 at 75～80 ℃, vacuum;
(3) filler is dropped into fluidized bed granulation chamber, then clear paste is sprayed into vaporific, control 160～170 ℃ of inlet temperature, 75～90 ℃ of leaving air temps, obtain medicated powder, standby;
(4) acidizer that is ground into fine powder is joined in medicated powder, mix homogeneously, sieves, and with PVP K30 ethanol solution, makes binding agent, granulate, and granulate;
(5) add alkaline agent, lubricant to mix, make 40～60 order granules, granulate, subpackage, then packing, obtains effervescent granule; By gained granule tabletting, then packing, obtains effervescent tablet.
10. according to the preparation method of the loyal stilbene effervescent formulation described in claim 7 or 8 or 9, it is characterized in that: described granulation, granulate, tabletting, packaging step all control environment relative humidity below 30%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104161261A (en) * | 2014-07-23 | 2014-11-26 | 北京中泰天和科技有限公司 | Composition for strengthening immunity function of organism and preparation method thereof |
| CN104173407A (en) * | 2014-09-12 | 2014-12-03 | 皖南医学院 | Burdock oligosaccharide effervescent tablet and preparation method thereof |
| CN104840972A (en) * | 2015-05-14 | 2015-08-19 | 宁波御坊堂生物科技有限公司 | Tablet preparation method capable of overcoming hang punching of tablet press |
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| CN1723986A (en) * | 2005-06-10 | 2006-01-25 | 湖南麓山天然植物制药有限公司 | Effervescent tablets contg. Astragalus root and fructus ligustric lucidi for strengthening the body resistance, and its prepn. art |
| CN103039956A (en) * | 2012-12-28 | 2013-04-17 | 四川同道堂药业集团股份有限公司 | White fungus effervescent tablet and preparation method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1723986A (en) * | 2005-06-10 | 2006-01-25 | 湖南麓山天然植物制药有限公司 | Effervescent tablets contg. Astragalus root and fructus ligustric lucidi for strengthening the body resistance, and its prepn. art |
| CN103039956A (en) * | 2012-12-28 | 2013-04-17 | 四川同道堂药业集团股份有限公司 | White fungus effervescent tablet and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104161261A (en) * | 2014-07-23 | 2014-11-26 | 北京中泰天和科技有限公司 | Composition for strengthening immunity function of organism and preparation method thereof |
| CN104173407A (en) * | 2014-09-12 | 2014-12-03 | 皖南医学院 | Burdock oligosaccharide effervescent tablet and preparation method thereof |
| CN104173407B (en) * | 2014-09-12 | 2017-07-18 | 皖南医学院 | A kind of burdock oligosaccharide effervescent tablet and preparation method thereof |
| CN104840972A (en) * | 2015-05-14 | 2015-08-19 | 宁波御坊堂生物科技有限公司 | Tablet preparation method capable of overcoming hang punching of tablet press |
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