CN104719910B - EGCG solid dispersion compositions with heat endurance and its preparation method and application - Google Patents

EGCG solid dispersion compositions with heat endurance and its preparation method and application Download PDF

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CN104719910B
CN104719910B CN201510183570.3A CN201510183570A CN104719910B CN 104719910 B CN104719910 B CN 104719910B CN 201510183570 A CN201510183570 A CN 201510183570A CN 104719910 B CN104719910 B CN 104719910B
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egcg
preparation
glycitols material
starch
glycitols
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CN104719910A (en
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张耿元
王保红
唐湘成
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Nanjing Runtong Changda Pharmaceutical Technology Co.,Ltd.
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FUZHOU QIANZHENG PHARMACEUTICAL Co Ltd
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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    • A61K9/2022—Organic macromolecular compounds
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    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract

The present invention provides EGCG and glycitols material solid dispersion composition, and the glycitols material includes following one or more compositions：Fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, Oligomeric manna sugar, solid polyethylene glycol, dextrin, cyclodextrin, hydroxypropyl beta cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, neotame, stevioside, and glycitols material is with EGCG using weight ratio as (12~80):1 ratio combination, the present invention also provides the preparation method of the solid dispersions and the application in the preparation compositions of different dosage forms are prepared；Solid dispersion composition of the present invention effectively increases EGCG stability.

Description

EGCG solid dispersion compositions with heat endurance and its preparation method and application
Technical field
The present invention relates to a kind of healthy product composition, and its preparation method and application, specifically EGCG solid dispersions Composition, with and its preparation method and application.Healthy product composition of the present invention, including but not limited to medicine, nutrition Healthy product, medical food, special diet, health food or functional food, ordinary food etc..
Background technology
EGCG, i.e. Epigallo-catechin gallate (EGCG), structural formula are as follows,
,
EGCG is a kind of native compound that extracting and developing is obtained from green tea, is most efficient activity list in Tea Polyphenols Body composition, with good security and extensive physiological activity, research shows, EGCG has antitumor, antiviral, anti- Bacterium, immune regulation, Green Tea Extract infringement, anti-oxidant, anti-oxidation stress, antithrombus formation, anti arteriosclerosis, protection nerveous system System, antiangiogenic, protection cardiovascular and cerebrovascular and antiinflammatory action, it is particularly significant for health.
However, disadvantageously, EGCG less stable is vulnerable to the influence of the factors such as temperature, water, pH, especially in liquid Deposited 7 days in body environment, its hydrolysis/degradation rate reaches more than 17%, even if in the solid state, although stability is relative to be carried Height, but more sensitive for temperature, can progressively degrade under thermal environment, have a strong impact on product quality and EGCG preparations/product Exploitation, serious harmful effect is brought for preparation, storage, circulation of product etc..
Inventor has found that EGCG under solid state, is derived from solid for hot unstability again after further research Itself contain a small amount of water or the water being free in air absorption in body powder on EGCG molecules, under thermal environment, accelerate EGCG hydrolysis process, therefore, suppresses EGCG hydrolysis under solid state (such as particle, powder), is to protect its steady Qualitatively important means.
The content of the invention
Inventor surprisingly has found, due to containing more hydroxyl in EGCG molecular structures, as EGCG and glycitols material During mixing, the molecule formation hydrogen bond that EGCG molecules can be with glycitols material, with intermolecular Van der Waals force, improves EGCG's Heat endurance；
Nonetheless, EGCG and glycitols material mixed system can improve EGCG degree of heat stability, sometimes Preparation or product are relatively inaccessible in long-term storage and ensures the requirement of product quality, thus inventor pass through it is further creative Research is found, when EGCG and glycitols material reach the ratio necessarily matched and forms mixed system, especially glycitols material It is more than 12 with EGCG weight proportion:When 1, EGCG molecules by substantial amounts of glycitols material " flooding " or can be surrounded, sugar alcohol Class material meeting peptizaiton is dredged the energy effect of heat from EGCG molecules in the thermal energy on EGCG molecules and come, so that Improve the stability for further increasing EGCG to heat.Acted on by above-mentioned both sides, EGCG heat can be improved well Stability.
Research and practice based on more than, the invention provides the technology contents of following aspect:
First aspect, solid dispersions there is provided EGCG and glycitols material, and preparation method thereof, composition application and Prepare；
Second aspect, there is provided a kind of EGCG and the solid dispersions of glycitols material and other pharmaceutical carriers, and it Preparation method, application.
EGCG of the present invention " solid dispersions " refer to EGCG high uniformities being scattered in solid carrier (dispersion material Material), such as a kind of decentralized system existed in solid form formed in glycitols material, or further made by decentralized system Into the decentralized system of solid pharmaceutical preparation, the latter such as granule, pulvis；The purpose is to EGCG is fully contacted with glycitols material, is mixed Close and scattered.
In a first aspect, it is an object of the invention to provide a kind of EGCG and the solid dispersion composition of glycitols material, institute Stating glycitols material includes following one or more compositions：It is fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet Reveal alcohol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, Oligomeric manna sugar, the poly- second two of solid Alcohol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, Polyethylene glycol-2000）, dextrin, ring paste Essence, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, shallow lake Pulverized sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, neotame, stevioside, And glycitols material is with EGCG using weight ratio as (12~80):1 ratio combination；
It is preferred that glycitols material and EGCG are using weight ratio as (15~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~65):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (35~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (40~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (50~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (55~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (60~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~40):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~35):1 ratio combination；
Specifically, for example preferred glycitols material and EGCG are using weight ratio as 12:1、13:1、14:1、15:1、16:1、17: 1、18:1、19:1、20:1、21:1、22:1、23:1、24:1、25:1、26:1、27:1、28:1、29:1、30:1、31:1、32:1、 33:1、34:1、35:1、36:1、37:1、38:1、39:1、40:1、41:1、42:1、43:1、44:1、45:1、46:1、47:1、 48:1、49:1、50:1、51:1、52:1、53:1、54:1、55:1、56:1、57:1、58:1、59:1、60:1、61:1、62:1、 63:1、64:1、65:1、66:1、67:1、68:1、69:1、70:1、71:1、72:1、73:1、74:1、75:1、76:1、77:1、 78:1、79:1 or 80:1 equal proportion is combined.
Present invention also offers EGCG and the solid dispersions of glycitols material three kinds of preparation methods：
The dry pigmentations of method one, this method includes:EGCG and glycitols material are taken respectively, 80 mesh sieves are crushed respectively, preferably 100 mesh sieves are crossed, it is well mixed according to equal increments, or dry granulation, drying, whole grain, optionally can further it crush, and obtain Solid dispersions, wherein the glycitols material includes following one or more compositions：It is fructose, xylitol, FOS, oligomeric It is xylose, polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, oligomeric sweet Dew sugar, solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, polyethylene glycol - 2000 etc.）, it is dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pre- Gelling starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, wood Sugar, neotame, stevioside；
The wet granulation process of method two, this method includes:EGCG is dissolved in ethanol or ethanol-water solution, the solution is equal It is even to be sprayed on glycitols material, wet granulation is carried out, softwood processed, granulation, drying, whole grain optionally can further be crushed, produced To solid dispersions, wherein the glycitols material includes following one or more compositions：Fructose, xylitol, oligomeric fruit Sugar, xylo-oligosaccharide, polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomaltoketose Alcohol, Oligomeric manna sugar, solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, poly- Ethylene glycol -2000 etc.）, dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, hydroxypropyl it is fine Tie up element, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, An Sai Honey, stachyose, neotame, stevioside；
The solvent methods of method three, this method includes:EGCG and glycitols material are taken, solvent is added, stirring makes EGCG and sugar alcohol Class material is dissolved or dispersed in solvent, removes solvent after being well mixed from the mixture, and dry, crush and obtain solid Dispersion, wherein the glycitols material includes following one or more compositions：It is fructose, xylitol, FOS, oligomeric It is xylose, polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, oligomeric sweet Dew sugar, solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, polyethylene glycol - 2000 etc.）, it is dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pre- Gelling starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, wood Sugar, neotame, stevioside；The solvent is selected from ethanol, water (such as distilled water or purified water) or ethanol water.In above-mentioned system In standby, the method for removing solvent and drying can take Rotary Evaporators to be evaporated off, remove under reduced pressure, be dried under reduced pressure, be dried in vacuo, freeze One or more in drying, spray drying, fluidized bed drying, heating, drying.
The above-mentioned preparation method of the present invention can be dispersed by EGCG and the glycitols material, resulting solid point Granular media, is the solid powder or particle of high degree of dispersion, and EGCG is highly dispersed in glycitols material, in the blending of glycitols material In the state of scattered, the molecule formation hydrogen bond that GCG molecules can be with glycitols material, with intermolecular Van der Waals force, is improved EGCG heat endurance, in addition, glycitols material and EGCG weight proportion are more than 12:When 1, EGCG molecules can be by substantial amounts of sugar Alcohols material " flooding " is surrounded, and glycitols material meeting peptizaiton is in the thermal energy on EGCG molecules, the energy of heat Effect is dredged from EGCG molecules comes, so as to improve the stability for further increasing EGCG to heat.
The present invention is provided can be administered consolidating for EGCG of the present invention and glycitols material by any appropriate approach Body dispersion, but generally pass through oral route.In order to carry out this kind of application, the solid dispersions of EGCG and glycitols material can be with By adding, suitable pharmaceutical carrier is prepared as acceptable any pharmaceutical dosage form in pharmacy, but, said composition it is definite Form naturally depends on form of medication.
Further, it is present invention also offers above-mentioned EGCG and the solid dispersions of glycitols material purposes, i.e., above-mentioned Application of the solid dispersions of EGCG and glycitols material in the preparation compositions of different dosage forms are prepared.
Second aspect, there is provided the solid point of the solid dispersions and other pharmaceutical carriers of a kind of EGCG and glycitols material Dispersion composition, and its preparation method；The pharmaceutical dosage form of the composition is any medicine of acceptable in pharmacy Formulation；Wherein described glycitols material includes following one or more compositions：Fructose, xylitol, FOS, xylo-oligosaccharide, Polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, Oligomeric manna sugar, Solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, Polyethylene glycol-2000）、 Dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinated form sediment Powder, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, neotame, Stevioside, and glycitols material and EGCG are using weight ratio as (12~80):1 ratio combination；
It is preferred that glycitols material and EGCG are using weight ratio as (15~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~65):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (35~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (40~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (50~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (55~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (60~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~40):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~35):1 ratio combination,
Specifically, for example preferred glycitols material and EGCG are using weight ratio as 12:1、13:1、14:1、15:1、16:1、17: 1、18:1、19:1、20:1、21:1、22:1、23:1、24:1、25:1、26:1、27:1、28:1、29:1、30:1、31:1、32:1、 33:1、34:1、35:1、36:1、37:1、38:1、39:1、40:1、41:1、42:1、43:1、44:1、45:1、46:1、47:1、 48:1、49:1、50:1、51:1、52:1、53:1、54:1、55:1、56:1、57:1、58:1、59:1、60:1、61:1、62:1、 63:1、64:1、65:1、66:1、67:1、68:1、69:1、70:1、71:1、72:1、73:1、74:1、75:1、76:1、77:1、 78:1、79:1 or 80:1 equal proportion is combined；And it is further, using corresponding pharmaceutical carrier or auxiliary material, using different systems Standby technique may be manufactured without same compound medicinal formulation.It should be appreciated that compound preparation refers to consolidating EGCG and glycitols material Single preparation is made as medicament active composition for body dispersion, can be acceptable any medicine agent in pharmacy (including dispersible tablet, enteric coatel tablets, chewable tablets, oral cavity collapse for type, preferably oral formulations, such as granule, pulvis, dry suspensoid agent, tablet Solve piece, effervescent tablet, etc.), hard capsule (including capsulae enterosolubilis), pill, micropill preparation (including enteric-coated micro-pill), pill, dried molassed Starch agent, powder, oral solution, oral administration mixed suspension and the formulation such as oral quick-release or sustained release or controlled release, etc.；Can also The formulations such as quick-release, the slow-release controlled-release of any of the above formulation, such as oral dispersible tablet, sustained release tablets, spansule, enteric coatel tablets, Effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Especially, prepared by means known in the art preferably for system The oral solution that is used in standby pharmacy, tablet (including dispersible tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, Special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule).
The active component of drug regimen can be generally given in EGCG and glycitols material solid dispersions form, but it is excellent Choosing is given in Pharmaceutical composition form.Solid dispersions of the Pharmaceutical composition of the present invention comprising EGCG with glycitols material, and The drug regimen of the invention of one or more pharmaceutically acceptable carriers or excipient.These carriers must be acceptable , you can it is compatible and nontoxic to its recipient with other components of formula；Use corresponding, different pharmaceutical carriers and preparation Technique, pharmaceutical composition of the present invention can be made different pharmaceutical dosage forms.What those skilled in the art were appreciated that Be, these pharmaceutical carriers be for the ease of produce and process into various formulations, ensure medicine safely, effectively with the factor such as stable, And selected according to the physicochemical property of different pharmaceutical dosage forms and medicine itself.The selection of pharmaceutical carrier using be the present invention Technical staff in field knows and obvious.
It should be appreciated that for oral agents, according to method well known in the art, being selected generally according to different medicaments or group Close the pharmaceutical carrier used, optionally including excipient or diluent, such as microcrystalline cellulose, mannitol, vegetable fat powder, breast Sugar, pregelatinized starch, starch, dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, calcium phosphate, calcium monohydrogen phosphate, hydroxypropyl methyl fiber It is element, sucrose, dextran, poloxamer, sodium chloride, sorbierite, glucose, FOS, xylo-oligosaccharide, polydextrose, low Poly- mannose, solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, poly- second two Alcohol -2000 etc.）, resistant dextrin, fructose, water, propane diols, glycerine, cyclodextrin, hydroxypropyl-β-cyclodextrin and its derivative, coffee Coffee, milk powder, plant protein powder, etc.；For oral solid formulation, it is also an option that property includes adhesive, such as PVP (polyvinylpyrrolidone), methylcellulose, hydroxymethyl cellulose, HPMC, pregelatinized starch, carboxymethyl form sediment Powder sodium, hydroxypropyl cellulose, hydroxyethyl cellulose, gelatin, guar gum, xanthans, etc.；Also include lubricant, such as it is stearic Sour magnesium, stearic acid, talcum powder, stearyl fumarate, lauryl sodium sulfate, etc.；Also optionally include disintegrant, Such as sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, PVPP, crosslinking carboxylic Sodium carboxymethylcellulose pyce, crosslinked carboxymethyl fecula sodium, pregelatinized starch, etc.；Also optionally include surfactant or help Solvent, such as lauryl sodium sulfate, Tween-80, etc.；PH values conditioning agent or buffer or cosolvent are may also include, Such as phosphate buffer, citric acid, sodium citrate, acetate buffer, watery hydrochloric acid, lactic acid, sodium carbonate, sodium hydroxide, alkali Property organic compound, such as arginine, lysine, meglumine, tromethamine, etc.；Also optionally include preservative, for example Sodium benzoate, potassium sorbate, methyl p-hydroxybenzoate, propylparaben, etc.；Also optionally include stable Agent and antioxidant, such as metal chelating agent is from ethylenediamine tetra-acetic acid and its salt (mosatil, natrium adetate), Asia Sodium sulphate, sodium pyrosulfite, vitamin C, vitamin E, etc.；Also optionally include taste conditioning agent, such as maltose Alcohol, fructose, sucrose, saccharin sodium, flavoring orange essence, strawberry essence, etc.；It additionally can include other conventional, appropriate additions Agent.It is also understood that can be film coating when agent type is tablet or capsule.For the material of film coating, including it is adapted to Coating agent, such as HPMC, hydroxyethyl cellulose, hydroxypropyl cellulose, HPMC O-phthalic Acid esters (enteric-coating material), etc.；Plasticizer, such as polyethylene glycol, triethyl citrate, etc. can also be included；It is also optional Selecting property include suitable solubilizer, such as Polyoxyethylene Sorbitan Monooleate；Suitable pigment, such as titanium dioxide, various oxygen can also be included Change iron, pink pigment, etc.." optionally including " refers to can optionally select to use it should be appreciated that above-mentioned, Can be without using.
In the present patent application, " composition " refers to EGCG and other chemical compositions, for example physiologically/pharmaceutically acceptable Carrier or the mixture of excipient formation, the purpose of pharmaceutical composition are advantageous for the administration of medicine, carrying, preserved；Here institute " administration " said refer in order to prevent or treat disease and to organism（Including patient or healthy population）Deliver described change EGCG or its solid dispersions.
Further, present invention also offers the pharmaceutical composition containing EGCG and the solid dispersions of glycitols material Preparation method, it includes mixing EGCG with the solid dispersions and pharmaceutically acceptable pharmaceutical carrier of glycitols material and making Acceptable any pharmaceutical preparation on into pharmacy, such as EGCG and glycitols material solid dispersions and pharmaceutical carrier dry powder Mixing, dry granulation mixing (dry granulating machine processing), wet granulation mix (with water or ethanol solution wet granulation), liquid or Semisolid mixing (content of such as soft capsule, the mixing of dripping pill dropping liquid), preferred pharmaceutical dosage form is granule, dry-mixed outstanding Agent, tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet etc.), hard capsule (including capsulae enterosolubilis), Oral solution, dry syrup, powder, soft capsule, pill, micropill preparation (including enteric-coated micro-pill), pill and oral The formulations such as quick-release, the slow-release controlled-release of the formulation such as quick-release or sustained release or controlled release or any of the above formulation, such as it is oral Dispersible tablet, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Especially, Prepared by means known in the art preferably for prepare tablet (including dispersible tablet, slow-release tablet, the enteric used in pharmacy Piece, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), oral solution etc..
It is preferred that, the present invention provides a kind of granule containing EGCG Yu the solid dispersions of glycitols material, the sugar Alcohols material is with EGCG using weight ratio as (12~80):1 ratio combination；
It is preferred that glycitols material and EGCG are using weight ratio as (15~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~65):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (35~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (40~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~60):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~55):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (50~80):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (55~75):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (60~70):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (15~50):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (20~45):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (25~40):1 ratio combination,
It is preferred that glycitols material and EGCG are using weight ratio as (30~35):1 ratio combination；
Specifically, for example preferred glycitols material and EGCG are using weight ratio as 12:1、13:1、14:1、15:1、16:1、17: 1、18:1、19:1、20:1、21:1、22:1、23:1、24:1、25:1、26:1、27:1、28:1、29:1、30:1、31:1、32:1、 33:1、34:1、35:1、36:1、37:1、38:1、39:1、40:1、41:1、42:1、43:1、44:1、45:1、46:1、47:1、 48:1、49:1、50:1、51:1、52:1、53:1、54:1、55:1、56:1、57:1、58:1、59:1、60:1、61:1、62:1、 63:1、64:1、65:1、66:1、67:1、68:1、69:1、70:1、71:1、72:1、73:1、74:1、75:1、76:1、77:1、 78:1、79:1 or 80:1 equal proportion is combined；
Wherein described glycitols material includes following one or more compositions：It is fructose, xylitol, FOS, low It is xylan, polydextrose, mannitol, sucrose, glucose, resistant dextrin, D-sorbite, maltose, isomalt, oligomeric Mannose, solid polyethylene glycol（Such as PEG-4000, polyethylene glycol -12000, PEG-4000, polyethylene glycol - 2000 etc.）, it is dextrin, cyclodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pre- Gelling starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, wood Sugar, neotame, stevioside；
Further, its preparation method includes：Glycitols material is crossed into 80 mesh sieves respectively, 100 mesh are preferably crossed, by recipe quantity After weighing, it is well mixed, EGCG is separately dissolved in ethanol-water solution, 75% ethanol solution is preferably dissolved in, the solution is uniform Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack are made in the mixture for being sprayed on glycitols material, it is close Envelope, is produced；
Or, its preparation method includes：EGCG, glycitols material are taken, 80 mesh sieves were crushed respectively, 100 mesh sieves are preferably crossed, It is well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, pack or pack, sealing is produced.
It has been found that EGCG of the present invention and glycitols material solid dispersions, EGCG is improved by both sides factor Stability, the Van der Waals force for being on the one hand EGCG with glycitols thing of the present invention formation intermolecular hydrogen bonding improves On the other hand EGCG heat endurance is EGCG and glycitols material reaches the ratio necessarily matched and forms mixed system, especially It is that glycitols material and EGCG weight proportion is more than 12:When 1, EGCG molecules can by substantial amounts of glycitols material " flooding " or It is surrounded, glycitols material meeting peptizaiton acts on the energy of heat from EGCG molecules in the thermal energy on EGCG molecules Dredge and come, so as to improve the stability for further increasing EGCG to heat.Acted on by above-mentioned both sides, can be well Improve EGCG heat endurance；In addition, glycitols material of the present invention and EGCG formation solid dispersions, moreover it is possible to improve composition and exist The bitter taste that EGCD is brought when oral, improves the property followed used.
Inventor is devised for the pure powder of EGCG, glycitols material and EGCG respectively according to weight by experimental study Match as 1:1、3:1、7:1、10:1、12:1、15:1、20:1、30:1、40:1、50:1、60:1、70:1、80:1 ratio is made Solid dispersions, every kind of solid dispersions are separately sampled 8 (n=8), by Accelerated stability test (in 40 DEG C, humidity 75% Under part) to place 2 months, sampling detects the content of EGCG in each sample using HPLC methods, and result was compared with 0 day, draws 2 Individual month point EGCG content drop-out value, content drop-out value is smaller, illustrates that stability is higher, data are used at statistics software Reason, experimental result is found：1st, the stability of the EGCG in the solid dispersions of EGCG and glycitols material is higher than the pure powder of EGCG, And with the increase of glycitols material and EGCG weight proportions, stability improves more obvious；2nd, as glycitols material and EGCG Weight proportion be more than or equal to 12:When 1, the raising of stability is significantly higher than glycitols material and EGCG weight is matched somebody with somebody for 10:1 When solid dispersions, and with significant difference（p<0.05）；3 and when glycitols material and EGCG weight are with close 80:When 1, the increase rate curve of its stability tends towards stability, and imply that when the weight proportion of glycitols material and EGCG is more than 80:When 1, its stability is no longer improved substantially.
More than study, embody the present invention creativeness, this for by EGCG in preparation, storage, circulation of its preparation etc. Link is extremely important, and the raising for product quality or quality is highly beneficial.
Embodiment is in the implementation process of the present invention, and those of ordinary skill in the art are not departing from the present invention's The various embodiments produced on the basis of scope and spirits and modification are obvious and are easy to perform.It is logical Cross the following examples to be further elaborated with come application to the present invention etc., it is not intended that limit of the embodiment to the present invention System.
Embodiment 1, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~10%, preferably 3%,
Fructose or xylitol 90%~99%, preferably fructose 97%；
Its preparation method includes：Fructose or xylitol are crossed into 80 mesh sieves respectively, 100 mesh is preferably crossed, is weighed by recipe quantity, separately EGCG is dissolved in ethanol-water solution, 75% ethanol solution is preferably dissolved in, the spray solution is made in fructose or xylitol Into softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack, sealing is produced；
Or, its preparation method includes：EGCG, fructose or xylitol are weighed, 80 mesh sieves were crushed respectively, 100 are preferably crossed Mesh sieve, it is well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, pack or pack, sealing is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Blank control product, and by fructose and EGCG according to weight ratio be 5:1 matches and is made with solid dispersions made from same procedure For with reference to product, each 8 (n=8) of sampling of every kind of sample, the data result of detection is averaged, by Accelerated stability test ( 40 DEG C, under the conditions of humidity 75%) place 2 months, sampling detection, the content of EGCG in each sample is detected using HPLC methods, and will knot Fruit was compared with 0 day, drew 2 months point EGCG content drop-out value, data are handled with statistics software；Detection method：Adopt High effective liquid chromatography for measuring content is used, using 0.1 phosphoric acid and acetonitrile as mobile phase, the μ L of sample size 20,28 DEG C of column temperature detects ripple Long 273nm, retention time is more than 7min.Result of the test is shown in Table 1.
The stability test result of table 1
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.50%
With reference to product 1.79%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.
Embodiment 2, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~10%, preferably 2.5%,
FOS 90%~99%, preferably 97.5%；
Its preparation method includes：FOS is crossed into 80 mesh sieves, 100 mesh is preferably crossed, is weighed by recipe quantity, it is separately that EGCG is molten Solution is preferably dissolved in 75% ethanol solution in ethanol-water solution, and the spray solution is made into softwood, wet method system in FOS Grain, 45~70 DEG C of dryings, whole grain, packaging or pack, sealing are produced；
Or, its preparation method includes：EGCG, FOS are weighed, 80 mesh sieves were crushed respectively, 100 mesh sieves are preferably crossed, It is well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, pack or pack, sealing is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell, FOS also has certain feature in addition, for example, improve gut flora.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken According to weight ratio it is 5 to blank photo product, and by FOS and EGCG:Solid made from 1 proportioning use and same procedure disperses Body is as with reference to product, and every kind of sample respectively samples 8 (n=8), and the data result of detection is averaged, and passes through Accelerated stability test (under the conditions of 40 DEG C, humidity 75%) is placed 2 months, sampling detection, and the content of EGCG in each sample is detected using HPLC methods, and Result was compared with 0 day, 2 months point EGCG content drop-out value is drawn, data are handled with statistics software；Detection side Method：Using high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time is more than 7min.Result of the test is shown in Table 2.
The stability test result of table 2
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.41%
With reference to product 1.55%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to blank photo sample With with reference to product, and with the significance difference opposite sex, embody EGCG of the present invention solid dispersion composition have it is significant stable Property.
Embodiment 3, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~5%, preferably salt 2%,
Oligomeric manna sugar or xylo-oligosaccharide 5%~25%, preferably Oligomeric manna sugar 10%,
D-sorbite 70%~94%, preferably 88%；
Its preparation method includes：Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite are crossed into 80 mesh sieves respectively, 100 are preferably crossed Mesh, is well mixed, EGCG separately is dissolved in into ethanol-water solution, preferably 75% ethanol solution, by the spray solution in oligomeric sweet dew Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or dress are made in the mixture of sugar or xylo-oligosaccharide and D-sorbite Bag, sealing, is produced；
Or, its preparation method includes：EGCG, Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite are weighed, was crushed respectively 80 mesh sieves, preferably cross 100 mesh sieves, well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, packaging or Pack, sealing, is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell, Oligomeric manna sugar or xylo-oligosaccharide also have certain feature in addition, for example, improve gut flora.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Reference substance, and the mixture matched according to the Oligomeric manna sugar of optimizing prescriptions amount in the present embodiment and D-sorbite are pressed with EGCG It is 5 according to weight ratio:1 matches and with solid dispersions made from same procedure as reference product, each sampling 8 of every kind of sample (n= 8), the data result of detection is averaged, and is placed 2 months by Accelerated stability test (under the conditions of 40 DEG C, humidity 75%), Sampling detection, the content of EGCG in each sample is detected using HPLC methods, and result was compared with 0 day, draws 2 months points EGCG content drop-out value, data are handled with statistics software；Detection method：Using high effective liquid chromatography for measuring content, with 0.1 phosphoric acid and acetonitrile are as mobile phase, and the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time is more than 7min.Examination Test and the results are shown in Table 3.
The stability test result of table 3
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.44%
With reference to product 1.60%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.
Embodiment 4, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~6%, preferably 3%,
Isomalt 85%~96%, preferably 92%,
Sodium carboxymethyl starch 3%~10%, preferably 5%；
Its preparation method includes：Isomalt, sodium carboxymethyl starch are crossed into 80 mesh sieves respectively, 100 mesh are preferably crossed, mixed Close uniform, EGCG is separately dissolved in ethanol-water solution, 75% ethanol solution is preferably dissolved in, by the spray solution in different malt ketone Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack are made in the mixture of sugar alcohol and sodium carboxymethyl starch, it is close Envelope, is produced；
Or, its preparation method includes：EGCG, isomalt, sodium carboxymethyl starch are weighed, 80 mesh were crushed respectively Sieve, preferably crosses 100 mesh sieves, well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, packaging or dress Bag, sealing, is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Reference substance, and according in the present embodiment optimizing prescriptions amount match isomalt and sodium carboxymethyl starch mixture with EGCG is 5 according to weight ratio:1 matches and with solid dispersions made from same procedure as with reference to product, and every kind of sample respectively samples 8 Individual (n=8), the data result of detection is averaged, and 2 are placed by Accelerated stability test (under the conditions of 40 DEG C, humidity 75%) Individual month, sampling detection detected the content of EGCG in each sample using HPLC methods, and result was compared with 0 day, when drawing 2 months Between point EGCG content drop-out value, data handle with statistics software；Detection method：Contained using high effective liquid chromatography for measuring Amount, using 0.1 phosphoric acid and acetonitrile as mobile phase, the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time is more than 7min.Result of the test is shown in Table 4.
The stability test result of table 4
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.51%
With reference to product 1.72%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.
Embodiment 5, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 2%~10%, preferably 6%,
Sucrose or glucose 75%~95%, preferably sucrose 89%,
Starch 2%~8%, preferably 2%,
Sodium carboxymethyl starch 3%~10%, preferably 3%；
Its preparation method includes：EGCG, sucrose or glucose, sodium carboxymethyl starch are crossed into 80 mesh sieves respectively, 100 are preferably crossed Mesh, after being weighed by recipe quantity, equal increments are well mixed, and starch separately is made into starch slurry with purified water, the starch slurry is added Softwood is made in EGCG, sucrose or glucose, the mixed-powder of sodium carboxymethyl starch, wet granulation, 45~70 DEG C of dryings are whole Grain, is packed, and sealing is produced；
Or, its preparation method includes：EGCG, sucrose or glucose, starch, sodium carboxymethyl starch are taken respectively, respectively powder The broken mesh sieve of mistake 80, preferably crosses 100 mesh sieves, well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, dress Bag, sealing, is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Reference substance, and matched according to optimizing prescriptions amount in the present embodiment sucrose, the mixture of starch and sodium carboxymethyl starch with EGCG is 5 according to weight ratio:1 matches and with solid dispersions made from same procedure as with reference to product, and every kind of sample respectively samples 8 Individual (n=8), the data result of detection is averaged, and 2 are placed by Accelerated stability test (under the conditions of 40 DEG C, humidity 75%) Individual month, sampling detection detected the content of EGCG in each sample using HPLC methods, and result was compared with 0 day, when drawing 2 months Between point EGCG content drop-out value, data handle with statistics software；Detection method：Contained using high effective liquid chromatography for measuring Amount, using 0.1 phosphoric acid and acetonitrile as mobile phase, the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time is more than 7min.Result of the test is shown in Table 5.
The stability test result of table 5
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.62%
With reference to product 1.83%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.
Embodiment 6, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~10%, preferably 2%,
Mannitol 45%~65%, preferably 55%,
Lactose 35%~55%, preferably 43%；
Its preparation method includes：Mannitol, lactose are crossed into 80 mesh sieves respectively, 100 mesh are preferably crossed, after being weighed by recipe quantity, It is well mixed, EGCG is separately dissolved in ethanol-water solution, 75% ethanol solution is preferably dissolved in, the solution is uniformly sprayed on sweet Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack are made in the mixture of dew alcohol and lactose, sealing is produced；
Or, its preparation method includes：EGCG, mannitol, lactose are weighed, 80 mesh sieves were crushed respectively, 100 mesh are preferably crossed Sieve, it is well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, pack or pack, sealing is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Reference substance, and the mannitol and the mixture of lactose and EGCG that are matched according to optimizing prescriptions amount in the present embodiment are according to weight ratio For 5:1 matches and with solid dispersions made from same procedure as with reference to product, and every kind of sample respectively samples 8 (n=8), detection Data result is averaged, and is placed 2 months by Accelerated stability test (under the conditions of 40 DEG C, humidity 75%), sampling detection, The content of EGCG in each sample is detected using HPLC methods, and result was compared with 0 day, 2 months point EGCG content is drawn Drop-out value, data are handled with statistics software；Detection method：Using high effective liquid chromatography for measuring content, with 0.1 phosphoric acid and second Nitrile is more than 7min as mobile phase, the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time.Result of the test is shown in Table 6。
The stability test result of table 6
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.57%
With reference to product 1.73%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.
Embodiment 7, EGCG and glycitols material solid dispersions and its preparation
Recipe quantity by weight percentage, contains：
EGCG 1%~5%, preferably salt 3%,
PEG-4000 5%~25%, preferably 10%,
D-sorbite 70%~94%, preferably 88%；
Its preparation method includes：PEG-4000, D-sorbite are crossed into 80 mesh sieves respectively, 100 mesh, mixing are preferably crossed Uniformly, EGCG is separately dissolved in ethanol-water solution, preferably 75% ethanol solution, by the spray solution in PEG-4000 with Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack are made in the mixture of D-sorbite, sealing is produced；
Or, its preparation method includes：EGCG, PEG-4000, D-sorbite are weighed, 80 mesh sieves were crushed respectively, It is preferred that 100 mesh sieves are crossed, it is well mixed according to equal increments, or dry granulation, 45~70 DEG C of dryings, whole grains, pack or pack, it is close Envelope, is produced.
Further, the solid dispersions in the present embodiment can be optionally prepared as to tablet, or it is filling in Capsules Capsule is made in shell, PEG-4000 also has certain feature in addition, for example, improve constipation.
Stability test：Solid dispersions made from the optimizing prescriptions in the present embodiment are taken, the pure powder conducts of EGCG are separately taken Reference substance, and the mixture matched according to the PEG-4000 of optimizing prescriptions amount in the present embodiment and D-sorbite with EGCG is 5 according to weight ratio:1 matches and with solid dispersions made from same procedure as with reference to product, and every kind of sample respectively samples 8 Individual (n=8), the data result of detection is averaged, and 2 are placed by Accelerated stability test (under the conditions of 40 DEG C, humidity 75%) Individual month, sampling detection detected the content of EGCG in each sample using HPLC methods, and result was compared with 0 day, when drawing 2 months Between point EGCG content drop-out value, data handle with statistics software；Detection method：Contained using high effective liquid chromatography for measuring Amount, using 0.1 phosphoric acid and acetonitrile as mobile phase, the μ L of sample size 20,28 DEG C of column temperature, Detection wavelength 273nm, retention time is more than 7min.Result of the test is shown in Table 7.
The stability test result of table 7
Sample（N=8, average） EGCG content drop-out value
The present embodiment solid dispersions 0.46%
With reference to product 1.59%
Blank control product 2.13%
As a result show, solid dispersions made from the present embodiment, its EGCG content drop-out value is less than to reference to product and sky White product in the same old way, and with the significance difference opposite sex, embodying EGCG of the present invention solid dispersion composition has significant stabilization Property.

Claims (6)

1. a kind of EGCG and fructose solid dispersion composition, its recipe quantity by weight percentage, contain：
EGCG 3%,
Fructose 97%；
Its preparation method includes：Fructose is crossed into 80 mesh sieves, weighed by recipe quantity, EGCG is separately dissolved in 75% ethanol solution, by this Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack is made in spray solution in fructose, and sealing is produced.
2. a kind of EGCG and glycitols material solid dispersions, its recipe quantity by weight percentage, contain：
EGCG 2.5%,
FOS 97.5%；
Its preparation method includes：FOS is crossed into 80 mesh sieves, weighed by recipe quantity, EGCG is separately dissolved in 75% ethanol solution, Softwood, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack is made in the spray solution in FOS, is sealed, Produce.
3. a kind of EGCG and glycitols material solid dispersions, its recipe quantity by weight percentage, contain：
EGCG 2%,
Oligomeric manna sugar 10%,
D-sorbite 88%；
Its preparation method includes：Oligomeric manna sugar, D-sorbite are crossed into 80 mesh sieves respectively, is well mixed, is separately dissolved in EGCG 75% ethanol solution, softwood, wet granulation, 45 are made by the spray solution in the mixture of Oligomeric manna sugar and D-sorbite ~70 DEG C of dryings, whole grain, packaging or pack, sealing are produced.
4. a kind of EGCG and glycitols material solid dispersions, its recipe quantity by weight percentage, contain：
EGCG 3%,
Isomalt 92%,
Sodium carboxymethyl starch 5%；
Its preparation method includes：Isomalt, sodium carboxymethyl starch are crossed into 80 mesh sieves respectively, are well mixed, separately by EGCG 75% ethanol solution is dissolved in, softwood is made in the mixture of isomalt and sodium carboxymethyl starch in the spray solution, Wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack, sealing are produced.
5. a kind of EGCG and glycitols material solid dispersions, its recipe quantity by weight percentage, contain：
EGCG 6%,
Sucrose 89%,
Starch 2%,
Sodium carboxymethyl starch 3%；
Its preparation method includes：EGCG, sucrose, sodium carboxymethyl starch are crossed into 80 mesh sieves respectively, after being weighed by recipe quantity, equivalent is passed Increase well mixed, starch slurry separately is made with purified water in starch, the starch slurry is added into EGCG, sucrose, sodium carboxymethyl starch Softwood is made in mixed-powder, wet granulation, 45~70 DEG C of dryings, whole grain is packed, and sealing is produced.
6. a kind of EGCG and glycitols material solid dispersions, its recipe quantity by weight percentage, contain：
EGCG 2%,
Mannitol 55%,
Lactose 43%；
Its preparation method includes：Mannitol, lactose are crossed into 80 mesh sieves respectively, after being weighed by recipe quantity, are well mixed, separately by EGCG 75% ethanol solution is dissolved in, the solution is uniformly sprayed in the mixture of mannitol and lactose softwood is made, wet granulation, 45~70 DEG C of dryings, whole grain, packaging or pack, sealing are produced.
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