CN107028961A - A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds and preparation method thereof - Google Patents
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds and preparation method thereof Download PDFInfo
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- CN107028961A CN107028961A CN201710201588.0A CN201710201588A CN107028961A CN 107028961 A CN107028961 A CN 107028961A CN 201710201588 A CN201710201588 A CN 201710201588A CN 107028961 A CN107028961 A CN 107028961A
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- mangiferin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
Abstract
The present invention relates to a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds and preparation method thereof.Pharmaceutical preparation of the present invention containing mangiferin compounds, it is characterised in that be made up of mangiferin compounds, ginsenoside and auxiliary material, pH value is 7.0~8.2, and its preparation process includes：First, the ethanol solution of mangiferin compounds is slowly dropped into the ginsenoside aqueous solution, forms micellar solution, be then freeze-dried or be spray-dried, obtain the drug powder containing mangiferin compounds and ginsenoside；Further, the drug powder is prepared into effervescent tablet pharmaceutical preparation.Mangiferin compounds and the nano-micelle of ginsenoside formation can strengthen the solubility of mangiferin compounds, and ginsenoside can strengthen the drug effect of mangiferin compounds, with good bioavilability.Pharmaceutical preparation of the present invention containing mangiferin compounds, can be changed into uniform, stable solution rapidly after the stirring that adds water, facilitate patients.
Description
Technical field
The present invention relates to the effervescent tablet pharmaceutical preparation of a kind of mangiferin containing mangiferin compounds and preparation method thereof, belong to
Pharmaceutical technology field.
Background technology
Mangiferin, also known as mangiferin, mangiferin, mainly from Anacardiaceae plant mango leaf, almond leaf, fruit,
Bark, gentianaceae plant Northeastern Radix Gentianae, Bupleurum scorzonerifoliumWild, the liliaceous plant wind-weed, Plants of Polypodiaceae balt pyrrosia herb, Thymelaeceae tree
The natural polyphenol class chemical combination that extracting and developing and purifying are obtained in the aerial part of wood, the plant such as hypericum perforatum, the root of syringa reticulata var mandshurica
Thing, is the double benzene pyrrones compounds of carbon glycosides, category of tetrahydroxy pyrrone.Mangiferin can be used for treatment chronic bronchitis to have preferable treatment
Effect, is the principle active component that Swertia mussotii treats hepatitis, is antiviral active component in Asphodeloides Bge Rhizome.According to the literature, awns
There is fruit glycosides obvious central nervous system stimulant to act on, and mangiferin intraperitoneal injection can make animal subject action tremor occur, erect
Hair, it is mandatory beat up with autonomic activities increase etc. symptom.Mangiferin has external anti-I type herpes simplex virus（HSV-I）Effect,
Its antivirus action is attributed to it and suppresses the ability that intracellular virus are replicated.The pharmacological action of mangiferin is clear and definite；Plant origin is wide
It is general, respiratory disease is clinically mainly used at present.In addition, mangiferin has anticancer, antiviral and anti-diabetic etc.
Activity, is increasingly paid close attention to by people, it is believed that with going deep into for research, and mangiferin will possess before exploitation well
Scape.Mangiferin water-soluble extreme difference, makes it be restricted greatly in clinical practice.And go the mangiferin aglycon of glycogen to improve its water
Dissolubility, but water-soluble or relatively low.Conventional oral solid formulation, mangiferin compounds can not be well with molecule
Stastus format is disperseed, and dissolubility is poor, bioavilability is low.
The content of the invention
It is an object of the invention to provide a kind of water-soluble is good, the high medicine containing mangiferin compounds of bioavilability
Thing preparation and preparation method thereof.
To realize the purpose of the present invention, the present invention is adopted the following technical scheme that：
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds, it is by mangiferin compounds, ginsenoside and auxiliary material
The effervescent tablet being made, pH value is 7.0~8.2.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, described mangiferin compounds are
Any one of mangiferin or mangiferin aglycon.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, described ginsenoside is ginseng soap
Any one of glycosides Ro, Rb1, Rc or more than one.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, described auxiliary material includes acid
Matter, alkaline matter, polyethylene glycol, polyvinylpyrrolidone, flavouring and pH adjusting agent.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, the acidic materials are selected from lemon
Acid, tartaric acid, fumaric acid, adipic acid, malic acid, fumarase, cinnamic acid, bayer acid, forulic acid, water-soluble amino acids,
One or two or more kinds in azelaic acid, decanedioic acid, laurate, capric acid, silicic acid, Taurine.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, the alkaline matter is selected from carbonic acid
One or two or more kinds in potassium, saleratus, sodium carbonate, sodium acid carbonate, calcium carbonate, calcium bicarbonate.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, described pH adjusting agent is citric acid
One or more in sodium, sodium tartrate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium lactate, sodium acetate.
A kind of preparation method of the effervescent tablet pharmaceutical preparation containing mangiferin compounds, comprises the following steps：
（1）The ethanol solution of mangiferin compounds is added dropwise in the aqueous solution containing ginsenoside, 10 ~ 90 are quickly stirred
Min, forms micellar solution, is then freeze-dried or is spray-dried, obtains the powder containing mangiferin compounds and ginsenoside
Last agent A；Mixing speed is 100 ~ 3000 r/min, preferably 600 r/min；
（2）The step of taking 2 parts of identical weights（1）Gained powder agent A, a copy of it adds acidic materials and mixed, and is placed in high-efficiency wet
In method mixer-granulator, acid grain is made for 10% polyvinylpyrrolidone ethanol solution in spray mass concentration, and another adds alkali
Property material mix, be placed in another efficient wet mixer-granulator, spray mass concentration for 10% polyvinylpyrrolidone ethanol it is molten
Alkaline grain is made in liquid；
（3）By step（2）The acid grain of gained and alkaline grain are dried respectively in the ebullated bed that EAT is 40 ~ 80 °C,
Then they are uniformly mixed, add appropriate polyethylene glycol, flavouring and pH adjusting agent, stir and evenly mix, through tabletting, gone out
Bacterium produces effervescent tablet pharmaceutical preparation；Preferably 60 °C of drying temperature.
The molecular weight of polyethylene glycol as described above is 2000 ~ 10000 dalton, preferably 6000 dalton.
A kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds as described above, with for antitumor, antigout,
Hypoglycemic purposes.
Mangiferin or mangiferin aglycon are formed micellar solution, then freeze-dried or spraying by the present invention with ginsenoside
Dry, be further prepared into effervesce tablet preparation.
The present invention forms micella, and more than 95% micella particle diameter is below 1 micron；The effervescent tablet of preparation has good water solubility,
The characteristics of bioavilability is high.
Brief description of the drawings
Transmission electron microscope photos of the Fig. 1 for the mangiferin of the present invention and the micella of ginsenoside Rb1's formation after freeze-dried；
Transmission electron microscope photos of the Fig. 2 for the mangiferin aglycon of the present invention and the micella of ginsenoside Ro's formation after freeze-dried.
Embodiment
For a further understanding of the present invention, with reference to embodiment, the present invention is described in detail.It is understood that
These descriptions are simply to further illustrate the features and advantages of the present invention, rather than limiting to the claimed invention.
Embodiment 1
The effervescent tablet preparation technology containing mangiferin of the present invention is as follows：
（1）It is that 100 L concentration are 1.5 mg/ that the ethanol solution that 10 L concentration are 1 mg/ml mangiferins is slowly dropped into concentration
In ml ginsenoside Rb1's solution, 60 min are stirred, mixing speed is 500 r/min, obtains the micella containing mangiferin molten
Liquid；
（2）The above-mentioned micellar solution spray drying containing mangiferin is obtained into the powder containing mangiferin；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin of gained, a copy of it adds 12.1 grams of tartaric acid
Mix, be placed in efficient wet mixer-granulator, acid is made in the polyvinylpyrrolidone ethanol solution that spray mass concentration is 10%
Property grain；Another adds 21.9 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 20 minutes in 60 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, add 1.5 grams of Macrogol 6000s, 1.3 grams L- Ah
Sugared, the appropriate 0.89 gram of mango essence of uncle and 0.1 gram of sodium dihydrogen phosphate are drawn, is stirred and evenly mixed, whole grain, the moisture of dry particl are sieved with 1 mm
Control is below 3%；
（6）Mangiferin content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
Embodiment 2
The effervescent tablet preparation technology containing mangiferin of the present invention is as follows：
（1）It is that 120 L concentration are 1.3 that the ethanol solution that 10 L concentration are 1.2 mg/ml mangiferins is slowly dropped into concentration
In mg/ml ginsenoside Ro's solution, 40 min are stirred, mixing speed is 400 r/min, obtains the micella containing mangiferin molten
Liquid；
（2）The above-mentioned micellar solution spray drying containing mangiferin is obtained into the powder containing mangiferin；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin of gained, a copy of it adds 12.8 grams of tartaric acid
Mix, be placed in efficient wet mixer-granulator, acid is made in the polyvinylpyrrolidone ethanol solution that spray mass concentration is 10%
Property grain；Another adds 22.7 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 15 minutes in 62 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, 1.2 grams of Macrogol 6000s, 1.09 grams of L- are added
Arabinose, appropriate 0.85 gram of mango essence and 0.3 gram of sodium dihydrogen phosphate, are stirred and evenly mixed, and whole grain, the water of dry particl are sieved with 1 mm
Sub-control system is below 3%；
（6）Mangiferin content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
Embodiment 3
The effervescent tablet preparation technology containing mangiferin of the present invention is as follows：
（1）It is that 150 L concentration are 1.0 that the ethanol solution that 10 L concentration are 1.5 mg/ml mangiferins is slowly dropped into concentration
In mg/ml Ginsenoside Rc's solution, 50 min are stirred, mixing speed is 600 r/min, obtains the micella containing mangiferin molten
Liquid；
（2）The above-mentioned micellar solution spray drying containing mangiferin is obtained into the powder containing mangiferin；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin of gained, a copy of it adds 16.5 grams of citric acid
Mix, be placed in efficient wet mixer-granulator, acid is made in the polyvinylpyrrolidone ethanol solution that spray mass concentration is 10%
Property grain；Another adds 25.3 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 15 minutes in 58 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, add 1.1 grams of Macrogol 6000s, 1.2 grams L- Ah
Uncle's sugar, 0.6 gram of mango essence and 0.25 gram of sodium dihydrogen phosphate are drawn, is stirred and evenly mixed, whole grain, the moisture control of dry particl are sieved with 1 mm
Below 3%；
（6）Mangiferin content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
Embodiment 4
The effervescent tablet preparation technology containing mangiferin aglycon of the present invention is as follows：
（1）It is that 160 L concentration are that the ethanol solution that 10 L concentration are 1.1 mg/ml mangiferin aglycons is slowly dropped into concentration
In 1.0 mg/ml ginsenoside Rb1's solution, 60 min are stirred, mixing speed is 550 r/min, is obtained containing mangiferin glycosides
The micellar solution of member；
（2）The above-mentioned micellar solution spray drying containing mangiferin aglycon is obtained into the powder containing mangiferin aglycon；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin aglycon of gained, a copy of it adds citric acid 13
Gram mix, be placed in efficient wet mixer-granulator, spray mass concentration be 10% polyvinylpyrrolidone ethanol solution, be made
Acid grain；Another adds 21 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 20 minutes in 60 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, 0.96 gram of Macrogol 6000,1.5 grams of L- are added
Arabinose, appropriate 0.8 gram of mango essence and 0.3 gram of sodium dihydrogen phosphate, are stirred and evenly mixed, and whole grain, the water of dry particl are sieved with 1 mm
Sub-control system is below 3%；
（6）Mangiferin Aglycones content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
Embodiment 5
The effervescent tablet preparation technology containing mangiferin aglycon of the present invention is as follows：
（1）It is that 110 L concentration are that the ethanol solution that 10 L concentration are 1.25 mg/ml mangiferin aglycons is slowly dropped into concentration
1.1 in mg/ml Ginsenoside Rc's solution, stirring 45 min, mixing speed is 520 r/min, is obtained containing mangiferin aglycon
Micellar solution；
（2）The above-mentioned micellar solution spray drying containing mangiferin aglycon is obtained into the powder containing mangiferin aglycon；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin aglycon of gained, a copy of it adds citric acid 15
Gram mix, be placed in efficient wet mixer-granulator, spray mass concentration be 10% polyvinylpyrrolidone ethanol solution, be made
Acid grain；Another adds 22.5 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 20 minutes in 60 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, 1.52 grams of Macrogol 6000s, 2.5 grams of L- are added
Arabinose, 0.5 gram of mango essence and 0.1 gram of sodium dihydrogen phosphate, are stirred and evenly mixed, and whole grain, the moisture control of dry particl are sieved with 1 mm
System is below 3%；
（6）Mangiferin Aglycones content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
Embodiment 6
The effervescent tablet preparation technology containing mangiferin aglycon of the present invention is as follows：
（1）It is that 200 L concentration are that the ethanol solution that 12 L concentration are 0.8 mg/ml mangiferin aglycons is slowly dropped into concentration
In 0.9 mg/ml ginsenoside Ro's solution, 55 min are stirred, mixing speed is 430 r/min, is obtained containing mangiferin aglycon
Micellar solution；
（2）The above-mentioned micellar solution spray drying containing mangiferin aglycon is obtained into the powder containing mangiferin aglycon；
（3）The step of taking 2 parts of identical weights（2）The powder containing mangiferin aglycon of gained, a copy of it adds citric acid 14
Gram mix, be placed in efficient wet mixer-granulator, spray mass concentration be 10% polyvinylpyrrolidone ethanol solution, be made
Acid grain；Another adds 21.3 grams of mixings of sodium acid carbonate, is placed in another efficient wet mixer-granulator, and spray mass concentration is
Alkaline grain is made in 10% polyvinylpyrrolidone ethanol solution；
（4）Respectively by step（3）The acid grain of gained and alkaline grain are dried 20 minutes in 60 °C of ebullated bed；
（5）Dried acid grain and alkaline grain are uniformly mixed, 1.01 grams of Macrogol 6000s, 2.1 grams of L- are added
Arabinose, appropriate 0.3 gram of mango essence and 0.12 gram of sodium dihydrogen phosphate, are stirred and evenly mixed, and whole grain, the water of dry particl are sieved with 1 mm
Sub-control system is below 3%；
（6）Mangiferin Aglycones content in dry particl is determined, according to measurement result, tabletting, packaging produces effervescent tablet.
The obtained mangiferin aglycon effervescent tablet of detection, disintegration ﹤ 3 minutes, friability 0.65%, gas release ﹥ 15ml, pH value
7.63, mangiferin Aglycones content 12.2%.
Embodiment 7：Bioavailability study
1st, trial drug：
Mangiferin raw material (content 98.7%), mangiferin aglycon raw material (99.3%), mangiferin effervescent tablet (prepared by embodiment 2), awns
Fruit glycosides aglycon effervescent tablet (prepared by embodiment 5).Mangiferin reference substance (Nat'l Pharmaceutical ＆ Biological Products Control Institute)；Mangiferin aglycon
Reference substance (offer of Chengdu Puffy moral Bioisystech Co., Ltd)；Aurantiin reference substance (the limited public affairs of Chengdu Puffy moral biotechnology
Department provides)；
2nd, experimental animal：SD rats, male and female half and half, body weight is between 160 to 200 g；
3rd, plasma sample mangiferin and mangiferin aglycon method for measurement of concentration：
3.1 reagent：Methanol (Merck), chromatographically pure；Acetic acid (DIMA companies), chromatographically pure；Water, ultra-pure water, self-control；Sulfatase,
Beta-glucuronic acid glycosidase (Sigma companies)；
3.2 administration：4 groups of animal point, every group 6, gastric infusion, mangiferin raw material (26.5 mg/kg), mangiferin aglycon raw material
(16.5 mg/kg), mangiferin effervescent tablet (equivalent to the mg/kg of mangiferin 26.5), mangiferin aglycon effervescent tablet is (equivalent to mango
The mg/kg of glycosides aglycon 16.5)；
3.3 sample collection：Respectively at before administration（Blank control）And medication after 0.5,1,1.5,2,2.5,3,4,5,6,7,8,
10th, 12,24 h adopt the mL of venous blood 0.5 by eye socket, put anticoagulant heparin, and 3500 r/min centrifuge 10 min, separated plasma double
Saved backup in -80 °C of refrigerators；
3.4 plasma sample mangiferins and mangiferin aglycon LC-MS/MS assay methods：
Chromatographic condition：Chromatographic column, Agilent C18 posts（2.7 μm of packing material size, 150 mm of post specification × 3.0mm）；Flowing
Phase, acetic acid aqueous solution=50/50 of methanol/0.15%；Flow velocity, 0.25 ml/min, column temperature：35 °C；Sample size, 10 μ L；
Mass Spectrometry Conditions：ESI ion guns；Capillary, -3kV；Gas Temp, 350 °C；Gas Flow, 12 mL/min；
Nebulizer, 30 psi；Positive ion mode detects that scan mode is multiple-reaction monitoring (MRM), is distinguished for quantitative ion
For mangiferin m/z, parent ion 421, daughter ion 301, fragmentation voltage 120V, collision energy 17V；Mangiferin aglycon m/z, parent ion
259, daughter ion 215, fragmentation voltage 130V, collision energy 22V；Internal standard aurantiin m/z, parent ion 579, daughter ion 271, fragmentation
Voltage 180V, collision energy 31V；Sweep time is 0.61s；
3.5 plasma sample processing methods：
Precision measures the μ L of blood plasma 100 and is placed in blank centrifuge tube, adds sulfatase (2 KU/mL) and β-glucuronic acid glucosides
Enzyme (90 KU/mL) each 10 μ L, vortex 30s, is incubated 60 min in 37 °C of water-baths；The blood sample being incubated is taken, aurantiin is added
Inner mark solution (1 μ g/mL) 10 μ L, vortex 40s, adds the 1 mol/L μ L of hydrochloric acid 10 acidifying blood samples, be vortexed 40 s, in whole
Then sample sequentially adds 1 mL 0.5% acetic acid aqueous solution and 1 in the solid phase pillar through 1 mL methanol, 1mL water disposal activatings
ML 5% methanol aqueous solution elution, is drained, and adds the elution of 1 mL methanol, is collected meoh eluate nitrogen in 50 °C of water-baths and is blown
It is dry, take 200 μ L mobile phases to redissolve, be vortexed 4 min, 10000 r/min centrifuge 10 min, take the μ L sample introductions of supernatant 10 to analyze.
It the results are shown in Table 1 and table 2.
Table 1：Pharmacokinetic parameter (the n of mangiferin and mangiferin in mangiferin effervescent tablet rat plasma of the present invention
=6)
| Pharmacokinetic parameter | Mangiferin | Mangiferin effervescent tablet of the present invention |
| Cmax（μg/L） | 146 | 2509 |
| T1/2（h） | 1.83 | 2.32 |
| AUC（μg·h/L） | 2516 | 69769 |
Table 2：The pharmacokinetics of mangiferin aglycon and mangiferin in mangiferin aglycon effervescent tablet rat plasma of the present invention is joined
Number (n=6)
| Pharmacokinetic parameter | Mangiferin aglycon | Mangiferin aglycon effervescent tablet of the present invention |
| Cmax（μg/L） | 4987 | 12329 |
| T1/2（h） | 4.76 | 5.73 |
| AUC（μg·h/L） | 211082 | 529322 |
AUC data results by table 1,2 are visible, and mangiferin oral administration biaavailability is very low, mangiferin effervescent tablet of the present invention
Oral administration biaavailability improves about 28 times compared with mangiferin；And mangiferin aglycon oral administration biaavailability is quite a lot of compared with mangiferin, awns
Fruit glycosides aglycon effervescent tablet oral administration biaavailability improves about 2.5 times compared with mangiferin aglycon.Show mangiferin bubble of the present invention
Rise piece and mangiferin aglycon effervescent tablet dissolubility is good, with high bioavilability.
Embodiment 8：Anti-trioxypurine drug effect compares
1st, test material：
For reagent product：Mangiferin raw material (content 98.7%), mangiferin aglycon raw material (99.3%), mangiferin effervescent tablet (embodiment 1
Prepare), mangiferin aglycon effervescent tablet (prepared by embodiment 4).Mangiferin reference substance (Nat'l Pharmaceutical ＆ Biological Products Control Institute)；Awns
Fruit glycosides aglycon reference substance (offer of Chengdu Puffy moral Bioisystech Co., Ltd).Testing uric acid kit is by abundant biological section of upper Hisense
Skill Co., Ltd provides；
2nd, experimental animal：Healthy mice, male, body weight 18-22 g, by Peking University, Experimental Animal Center is provided；
3rd, test method and result：
The g of male mice body weight 18~22, is randomly divided into 7 groups, every group 10, is respectively：Mangiferin, mangiferin aglycon, mangiferin
Effervescent tablet, mangiferin aglycon effervescent tablet group, Normal group, high lithemia model control group, Allopurinol positive controls.Fill respectively
Stomach gives isometric solvent (0.5% CMC-Na), the mg/kg of mangiferin 5.8, mangiferin effervescent tablet (equivalent to mangiferin 5.8
Mg/kg), the mg/kg of mangiferin aglycon 3.8, mangiferin aglycon effervescent tablet (equivalent to mangiferin aglycon 3.8mg/kg), and not fast
The mg/kg of alcohol 1, by 10 ml/kg daily administrations 2 times, continuous 5 times.The mg/ of uricase inhibitor Oteracil Potassium 350 is injected intraperitoneally
Kg, suppresses uricase activity, causes hyperuricemia mouse, Normal group then injects isometric 0.5% CMC-Na solution, notes
Penetrate and eye blood sampling is pulled out after the test compound that rear 1 h gavages give final dose, 1 h, 3000 r/min centrifuge 10 min, take blood
Clearly, serum uric acid level is determined using phosphotungstic acid method, the results are shown in Table 3.
Table 3：Effervescent tablet containing mangiferin compounds is to Oteracil Potassium induced Acute hyperuricemia mouse blood uric acid
Influence
| Group | Dosage（mg/kg） | Uric acid level（μmol/L） |
| Normal control | 0.5% CMC-Na | 142.3 ± 23.2 |
| Model comparison | 0.5% CMC-Na | 256.2 ± 59.7 |
| Mangiferin | 5.8 | 193.7 ± 78.4 |
| Mangiferin effervescent tablet | 5.8 | 156.5 ± 38.6 |
| Mangiferin aglycon | 3.8 | 219.3 ± 35.7 |
| Mangiferin aglycon effervescent tablet | 3.8 | 179.2 ± 41.1 |
| Allopurinol | 1 | 147.1 ± 37.9 |
After the result of table 3, model control group animal intraperitoneal injection uricase inhibitor Oteracil Potassium, serum uric acid level shows
Write and be higher than Normal group, the statistically significant (P of difference<0.01), hints model is tested successfully.After gastric infusion 5 times, mango
Glycosides effervescent tablet group, mangiferin aglycon effervescent tablet group can significantly reduce the serum uric acid level of hyperuricemia mouse.And mangiferin
Group and mangiferin aglycon group display that anti-trioxypurine is acted on, but anti-trioxypurine degree is notable not as corresponding effervesce tablet preparation effect.
Show that mangiferin effervescent tablet of the present invention and mangiferin aglycon effervescent tablet bioavilability are high, anti-trioxypurine effect is obvious.
The explanation of above example is only intended to help the product and method and its core concept that understand the present invention；It should refer to
Go out, for those skilled in the art, under the premise without departing from the principles of the invention, can also be to the present invention
Some improvement and modification are carried out, these are improved and modification is also fallen into the protection domain of the claims in the present invention.
The foregoing description of the disclosed embodiments, enables professional and technical personnel in the field to realize or using the present invention.
A variety of modifications to these embodiments will be apparent for those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, it is of the invention
The embodiments shown herein is not intended to be limited to, and is to fit to and principles disclosed herein and features of novelty phase one
The most wide scope caused.
Claims (8)
1. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds, it is characterised in that it is by mangiferin compounds, people
The effervescent tablet that ginseng saponin(e and auxiliary material are made, pH value is 7.0~8.2.
2. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1, it is characterised in that described
Mangiferin compounds be any one of mangiferin or mangiferin aglycon.
3. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1, it is characterised in that described
Ginsenoside be any one of ginsenoside Ro, Rb1, Rc or more than one.
4. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1, it is characterised in that described
Auxiliary material include acidic materials, alkaline matter, polyethylene glycol, polyvinylpyrrolidone, flavouring and pH adjusting agent.
5. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1 and 4, it is characterised in that
The acidic materials be selected from citric acid, tartaric acid, fumaric acid, adipic acid, malic acid, fumarase, cinnamic acid, bayer acid,
One or two or more kinds in forulic acid, water-soluble amino acids, azelaic acid, decanedioic acid, laurate, capric acid, silicic acid, Taurine.
6. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1 and 4, it is characterised in that
The one kind or two kinds of the alkaline matter in potassium carbonate, saleratus, sodium carbonate, sodium acid carbonate, calcium carbonate, calcium bicarbonate
More than.
7. a kind of effervescent tablet pharmaceutical preparation containing mangiferin compounds according to claim 1 and 4, it is characterised in that
Described pH adjusting agent is one kind in sodium citrate, sodium tartrate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium lactate, sodium acetate
Or more than one.
8. a kind of preparation method of the effervescent tablet pharmaceutical preparation containing mangiferin compounds, comprises the following steps：
Step（1）, the ethanol solution of mangiferin compounds is added dropwise in the aqueous solution containing ginsenoside, 10 are quickly stirred
~ 90 min, form micellar solution, are then spray-dried, obtain the powder agent A containing mangiferin compounds and ginsenoside；
Step（2）, the step of taking 2 parts of identical weights（1）Gained powder agent A, a copy of it adds acidic materials and mixed, and is placed in height
Imitate in wet mixing pelletizer, acid grain is made for 10% polyvinylpyrrolidone ethanol solution in spray mass concentration, and another adds
Enter alkaline matter mixing, be placed in another efficient wet mixer-granulator, the polyvinylpyrrolidone second that spray mass concentration is 10%
Alkaline grain is made in alcoholic solution；
Step（3）, by step（2）The acid grain of gained and alkaline grain are respectively in EAT in 40 ~ 80 °C of ebullated bed
Dry, then they are uniformly mixed, appropriate polyethylene glycol, flavouring and pH adjusting agent is added, stir and evenly mix, with sieve
Whole grain, through tabletting, sterilizing, thus obtaining the product effervescent tablet pharmaceutical preparation.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104000797A (en) * | 2014-06-17 | 2014-08-27 | 昆明制药集团股份有限公司 | Pharmaceutic preparation including mangiferin glycoside and preparation method thereof |
| CN105475800A (en) * | 2015-11-24 | 2016-04-13 | 广西壮族自治区农业科学院农产品加工研究所 | Mango effervescent tablet and preparation method thereof |
| CN105640968A (en) * | 2016-01-14 | 2016-06-08 | 孙妙囡 | Ginseng saponin combination and application thereof |
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2017
- 2017-03-30 CN CN201710201588.0A patent/CN107028961A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104000797A (en) * | 2014-06-17 | 2014-08-27 | 昆明制药集团股份有限公司 | Pharmaceutic preparation including mangiferin glycoside and preparation method thereof |
| CN105475800A (en) * | 2015-11-24 | 2016-04-13 | 广西壮族自治区农业科学院农产品加工研究所 | Mango effervescent tablet and preparation method thereof |
| CN105640968A (en) * | 2016-01-14 | 2016-06-08 | 孙妙囡 | Ginseng saponin combination and application thereof |
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Application publication date: 20170811 |