CN104719910A - Solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and preparation method of solid dispersion combination and application in preparation of solid dispersion combination - Google Patents

Solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and preparation method of solid dispersion combination and application in preparation of solid dispersion combination Download PDF

Info

Publication number
CN104719910A
CN104719910A CN201510183570.3A CN201510183570A CN104719910A CN 104719910 A CN104719910 A CN 104719910A CN 201510183570 A CN201510183570 A CN 201510183570A CN 104719910 A CN104719910 A CN 104719910A
Authority
CN
China
Prior art keywords
egcg
starch
preparation
glycitols material
glycitols
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201510183570.3A
Other languages
Chinese (zh)
Other versions
CN104719910B (en
Inventor
张耿元
王保红
唐湘成
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Runtong Changda Pharmaceutical Technology Co.,Ltd.
Original Assignee
FUZHOU QIANZHENG PHARMACEUTICAL Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by FUZHOU QIANZHENG PHARMACEUTICAL Co Ltd filed Critical FUZHOU QIANZHENG PHARMACEUTICAL Co Ltd
Priority to CN201510183570.3A priority Critical patent/CN104719910B/en
Publication of CN104719910A publication Critical patent/CN104719910A/en
Application granted granted Critical
Publication of CN104719910B publication Critical patent/CN104719910B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—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
    • 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
    • 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
    • A61K9/1617—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
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • 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
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a solid alcohol solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and sugar alcohols. The sugar alcohols include one or more ingredients comprising fructose, newtol, fructo-oligose, xylooligosaccharide, polydextrose, mannitol, cane sugar, glucose, resistant dextrin, sorbitol, maltose, isomalt, mannose oligomer, carbo wax, dextrin, cyclodextrin, hydroxyl-lpropyl-beta-cyclodextrin, microcrystalline cellulose, carboxymethylcellulose, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, proteoglycan, sucralose, aspartame, acesulfame, stachyose, neotame and stevioside, and the sugar alcohols and the EGCG are in (12-80):1 in proportion by weigth. The invention further provides a preparation method of the solid dispersion combination and application in preparation of the solid dispersion combination. By the aid of the solid dispersion combination, the EGCG is effectively improved in stability.

Description

EGCG solid dispersion composition 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, the specifically composition of the solid dispersions of EGCG, with and its preparation method and application.Healthy product composition of the present invention, includes but not limited to medicine, nutritious health product, medical food, special diet, health food or functional food, bread and cheese etc.
Background technology
EGCG, i.e. Epigallo-catechin gallate (EGCG), structural formula is as follows,
，
EGCG is a kind of native compound that extracting and developing obtains from green tea; it is the most efficient active monomer component in Tea Polyphenols; there is good security and physiological activity widely; research shows; EGCG has the infringement of antitumor, antiviral, antibacterial, immunity moderation, Green Tea Extract, anti-oxidant, anti-oxidation stress, antithrombus formation, anti arteriosclerosis, neuroprotective system, antiangiogenic, protection cardiovascular and cerebrovascular and antiinflammatory action, very important for health.
But, disadvantageously, the less stable of EGCG, is vulnerable to the impact of the factors such as temperature, water, pH, especially in liquid environment, 7 days are deposited, its hydrolysis/degradation rate reaches more than 17%, even if in the solid state, although stability can improve relatively, but it is more responsive for temperature, progressively can degrade under thermal environment, have a strong impact on the exploitation of product quality and EGCG preparation/product, preparation, storage, circulation etc. for product bring serious harmful effect.
Inventor is in the further rear discovery of research; EGCG is again under solid state; unstability for heat stems from pressed powder and self contains a small amount of water or the water be free in air is adsorbed on EGCG molecule; under thermal environment; accelerate the hydrolysis process of EGCG; therefore, suppressing EGCG hydrolysis under solid state (as particle, powder), is the important means of its stability of protection.
Summary of the invention
Inventor surprisingly finds, owing to containing more hydroxyl in EGCG molecular structure, when EGCG mixes with glycitols material, EGCG molecule can form hydrogen bond with the molecule of glycitols material, has intermolecular Van der Waals force, improves the heat endurance of EGCG;
Nonetheless, the mixed system of EGCG and glycitols material can improve the degree of heat stability of EGCG, sometimes also more difficultly reach preparation or product in long-term storage and ensure the requirement of product quality, therefore inventor is found by further creationary research, when EGCG and glycitols material reach the ratio of certain proportioning and form mixed system, especially when the weight proportion of glycitols material and EGCG is greater than 12:1, EGCG molecule " can be flooded " by a large amount of glycitols materials or is surrounded, the thermal energy of glycitols material meeting peptizaiton on EGCG molecule, the energy of heat is dredged from EGCG molecule and comes, thus improve and further increase the stability of EGCG to heat.By the effect of above-mentioned two aspects, the heat endurance of EGCG well can be improved.
Based on above research and practice, the invention provides the technology contents of following aspect:
First aspect, provide the solid dispersions of EGCG and glycitols material, and preparation method thereof, composition application and preparation;
Second aspect, provides the solid dispersions of a kind of EGCG and glycitols material and other pharmaceutical carrier, and its preparation method, application.
" solid dispersions " of EGCG of the present invention refers to and EGCG high uniformity is scattered in solid carrier (dispersion material), a kind of decentralized system existed in solid form such as, formed in glycitols material, or be made up the decentralized system of solid pharmaceutical preparation further of decentralized system, the latter is as granule, pulvis; Its objective is and EGCG is fully contacted with glycitols material, mix and disperses.
First aspect, the object of this invention is to provide the solid dispersion composition of a kind of EGCG and glycitols material, described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, and glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 65) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (35 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (40 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (50 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (55 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (60 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 35) with weight ratio: the ratio combination of 1;
Concrete, such as preferably glycitols material and EGCG take 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 combines.
Present invention also offers three kinds of preparation methods of the solid dispersions of EGCG and glycitols material:
Method one. dry pigmentation, the method comprises: get EGCG and glycitols material respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mix according to equal increments, or dry granulation, dry, whole grain, optionally can pulverize further, and obtain solid dispersions, wherein said glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside,
Method two. wet granulation process, the method comprises: EGCG is dissolved in ethanol or ethanol-water solution, this dissolution homogeneity is sprayed on glycitols material, carry out wet granulation, softwood processed, granulate, dry, whole grain, optionally can pulverize further, namely solid dispersions is obtained, wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside,
Method three. solvent method, the method comprises: get EGCG and glycitols material, add solvent, stirring makes EGCG and glycitols substance dissolves or is scattered in solvent, from this mixture, desolventizing is removed after mixing, and it is dry, pulverize and obtain solid dispersions, wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, described solvent selected from ethanol, water (such as distilled water or purified water) or ethanol water.In above-mentioned preparation, Rotary Evaporators can be taked to steam except desolventizing and dry method to remove, remove under reduced pressure, drying under reduced pressure, vacuum drying, freeze drying, spraying dry, fluidized bed drying, one or more in heating, drying.
The above-mentioned preparation method of the present invention all can by EGCG and described glycitols material dispersed, the solid dispersions obtained, pressed powder or the particle of high degree of dispersion, EGCG is highly dispersed in glycitols material, under the state of the blended dispersion of glycitols material, GCG molecule can form hydrogen bond with the molecule of glycitols material, there is intermolecular Van der Waals force, improve the heat endurance of EGCG, in addition, when the weight proportion of glycitols material and EGCG is greater than 12:1, EGCG molecule " can be flooded " by a large amount of glycitols materials or is surrounded, the thermal energy of glycitols material meeting peptizaiton on EGCG molecule, the energy of heat is dredged from EGCG molecule and comes, thus improve and further increase the stability of EGCG to heat.
The invention provides and by the solid dispersions of the administration of any appropriate EGCG of the present invention and glycitols material, but usually can pass through oral route.In order to carry out this kind of application, the solid dispersions of EGCG and glycitols material can be prepared as acceptable any pharmaceutical dosage form in pharmacy by adding suitable pharmaceutical carrier, and but, the exact form of said composition depends on form of medication naturally.
Further, present invention also offers the purposes of the solid dispersions of above-mentioned EGCG and glycitols material, i.e. the application of the solid dispersions of above-mentioned EGCG and glycitols material in the preparation compositions preparing different dosage form.
Second aspect, provides the solid dispersions of a kind of EGCG and glycitols material and the solid dispersion composition of other pharmaceutical carrier, and its preparation method, the pharmaceutical dosage form of described composition is any pharmaceutical dosage form of acceptable in pharmacy, wherein said glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, and glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 65) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (35 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (40 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (50 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (55 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (60 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 35) with weight ratio: the ratio combination of 1,
Concrete, such as preferably glycitols material and EGCG take 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 combines, and further, use corresponding pharmaceutical carrier or auxiliary material, adopt different preparation technologies to can be made into different compound medicinal formulations.Be to be understood that, compound preparation refers to makes independent preparation using the solid dispersions of EGCG and glycitols material as medicament active composition, it can be any pharmaceutical dosage form that pharmacy can accept, preferred oral preparation, such as granule, pulvis, dry suspensoid agent, tablet (comprises dispersing tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet, Deng), hard capsule (comprising capsulae enterosolubilis), pill, micropill preparation (comprising enteric-coated micro-pill), pill, dry syrup, powder, oral solution, oral administration mixed suspension, and oral quick-release or the formulation such as slowly-releasing or controlled release, etc., also can be the formulation such as quick-release, slowly-releasing, controlled release of above various formulation, such as oral dispersing 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, by means known in the art preparation, be preferred for preparing oral solution, tablet (comprising dispersing tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (comprise stomach is molten, enteric, spansule) that pharmacy uses.
Usually can give the active component of drug regimen with the solid dispersions form of EGCG and glycitols material, but preferably give with Pharmaceutical composition form.Pharmaceutical composition of the present invention comprises the solid dispersions of EGCG and glycitols material, and the drug regimen of the present invention of one or more pharmaceutically acceptable carriers or excipient.These carriers must be acceptable, can with other component compatibility of formula, and nontoxic to its recipient; Use corresponding, different pharmaceutical carriers and preparation technology, pharmaceutical composition of the present invention can be made different pharmaceutical dosage forms.What those skilled in the art were appreciated that is, these pharmaceutical carriers be become various formulation for the ease of production and processing, guarantee medicine safe, effectively with the factor such as to stablize, and to select according to the physicochemical property of different pharmaceutical dosage forms and medicine self.The choice for use of pharmaceutical carrier is that those of skill in the art of the present invention know with apparent.
Be to be understood that, for oral agents, according to method well known in the art, usually according to the pharmaceutical carrier that different medicaments is selected or combinationally used, optionally comprise excipient or diluent, such as microcrystalline cellulose, sweet mellow wine, vegetable fat powder, lactose, pregelatinized starch, starch, dextrin, cyclodextrin, HP-β-CD, calcium phosphate, calcium monohydrogen phosphate, hydroxypropyl methylcellulose, sucrose, dextran, poloxamer, sodium chloride, sorbierite, glucose, FOS, xylo-oligosaccharide, polydextrose, Oligomeric manna sugar, solid polyethylene glycol (such as PEG-4000, polyethylene glycol-12000, PEG-4000, Polyethylene glycol-2000 etc.), resistant dextrin, fructose, water, propane diols, glycerine, cyclodextrin, HP-β-CD and derivative thereof, coffee, milk powder, plant protein powder, etc., for oral solid formulation, optionally can also comprise adhesive, such as PVP (polyvinylpyrrolidone), methylcellulose, CMC, HPMC, pregelatinized starch, sodium carboxymethyl starch, hydroxypropyl cellulose, hydroxyethylcellulose, gelatin, guar gum, xanthans, etc., also comprise lubricant, such as dolomol, stearic acid, talcum powder, stearyl fumarate, lauryl sodium sulfate, etc., also optionally comprise disintegrant, such as sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, PVPP, Ac-Di-Sol, crosslinked carboxymethyl fecula sodium, pregelatinized starch, etc., also optionally comprise surfactant or cosolvent, such as lauryl sodium sulfate, Tween-80, etc., also can comprise pH value conditioning agent or buffer or cosolvent, such as phosphate buffer, citric acid, natrium citricum, acetate buffer, watery hydrochloric acid, lactic acid, sodium carbonate, NaOH, alkaline organic compound, as arginine, lysine, meglumine, tromethamine, etc., also optionally comprise anticorrisive agent, such as Sodium Benzoate, potassium sorbate, methyl p-hydroxybenzoate, propylparaben, etc., also optionally comprise stabilizing agent and antioxidant, such as metal chelating agent selects ethylenediamine tetra-acetic acid and salt (mosatil, natrium adetate) etc. thereof, sodium sulfite, sodium pyrosulfite, vitamin C, vitamin E, etc., also optionally comprise taste conditioning agent, such as maltitol, fructose, sucrose, saccharin sodium, flavoring orange essence, strawberry essence, etc., that also can comprise other routine in addition, appropriate additive.It is also understood that agent type be tablet or capsule time, can be film dressing.For the material of film dressing, comprise applicable coating agent, such as HPMC, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate (enteric-coating material), etc.; Also can comprise plasticizer, such as polyethylene glycol, triethyl citrate, etc.; Also optionally comprise suitable solubilizer, as Polyoxyethylene Sorbitan Monooleate; Also can comprise suitable pigment, as titanium dioxide, various iron oxide, pink pigment, etc.Should be appreciated that above-mentioned " optionally comprising " refers to namely can optionally choice for use, also can not use.
In the present patent application, " composition " refers to EGCG and other chemical composition, and such as, on physiology/mixture that formed of pharmaceutically acceptable carrier or excipient, the object of pharmaceutical composition is conducive to the using of medicine, carries, preserves; " administration " mentioned here refer in order to prevent or disease therapy and to organism (comprising patient or healthy population) deliver described in change EGCG or its solid dispersions.
Further, present invention also offers the preparation method of the pharmaceutical composition of the solid dispersions containing EGCG and glycitols material, it comprises and the solid dispersions of EGCG and glycitols material and pharmaceutically acceptable pharmaceutical carrier is mixed and make acceptable any pharmaceutical preparation in pharmacy, the solid dispersions of such as EGCG and glycitols material and pharmaceutical carrier dry powder blend, dry granulation mixing (dry granulating machine process), wet granulation mixing (with water or ethanolic solution wet granulation), liquid or semisolid mixes (as the content of soft capsule, dripping pill dropping liquid mixes) etc., preferred pharmaceutical dosage form is granule, dry suspensoid agent, tablet (comprises dispersing tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet etc.), hard capsule (comprising capsulae enterosolubilis), oral solution, dry syrup, powder, soft capsule, pill, micropill preparation (comprising enteric-coated micro-pill), pill, and oral quick-release or the formulation such as slowly-releasing or controlled release, also can be the quick-release of above various formulation, slowly-releasing, the formulations such as controlled release, such as oral dispersing 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, by means known in the art preparation, be preferred for preparing tablet (comprising dispersing tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (comprise stomach is molten, enteric, spansule), oral solution etc. that pharmacy uses.
Preferably, the invention provides a kind of granule containing the solid dispersions of EGCG and glycitols material, described glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1;
Preferred glycitols material and EGCG are (15 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 65) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (35 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (40 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 60) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 55) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (50 ~ 80) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (55 ~ 75) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (60 ~ 70) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (15 ~ 50) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (20 ~ 45) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred glycitols material and EGCG are (30 ~ 35) with weight ratio: the ratio combination of 1;
Concrete, such as preferably glycitols material and EGCG take 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 combines,
Wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside,
Further, its preparation method comprises: glycitols material is crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this dissolution homogeneity is sprayed in the mixture of glycitols material and makes softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: get EGCG, glycitols material, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Have now found that, the solid dispersions of EGCG of the present invention and glycitols material, the stability of EGCG is improved by the factor of two aspects, the Van der Waals force that EGCG and glycitols thing of the present invention form intermolecular hydrogen bonding on the one hand, improve the heat endurance of EGCG, that EGCG and glycitols material reach the ratio of certain proportioning and form mixed system on the other hand, especially when the weight proportion of glycitols material and EGCG is greater than 12:1, EGCG molecule " can be flooded " by a large amount of glycitols materials or is surrounded, the thermal energy of glycitols material meeting peptizaiton on EGCG molecule, the energy of heat is dredged from EGCG molecule and comes, thus improve and further increase the stability of EGCG to heat.By the effect of above-mentioned two aspects, the heat endurance of EGCG well can be improved; In addition, glycitols material of the present invention and EGCG form solid dispersions, can also improve the bitter taste that composition EGCD when oral brings, and improve the property followed used.
Inventor studies by experiment, devise for the pure powder of EGCG, glycitols material and EGCG are 1:1 according to weight proportion respectively, 3:1, 7:1, 10:1, 12:1, 15:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, the ratio of 80:1 makes solid dispersions, often kind of solid dispersions samples 8 (n=8) respectively, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, content drop-out value is less, illustrate that stability is higher, data statistics software process, experimental result finds: 1, the stability of the EGCG in the solid dispersions of EGCG and glycitols material is higher than the pure powder of EGCG, and along with the increase of glycitols material and EGCG weight proportion, stability improves more obvious, 2, when the weight proportion of glycitols material and EGCG is more than or equal to 12:1, the weight that the raising of stability is significantly higher than glycitols material and EGCG is joined for solid dispersions during 10:1, and has significant difference (p<0.05), 3 and when the weight of glycitols material and EGCG connects nearly 80:1, the increase rate curve of its stability tends towards stability, imply that its stability substantially no longer improves when the weight proportion of glycitols material and EGCG is greater than 80:1.
More than study, embody creativeness of the present invention, this is for extremely important in the link such as preparation, storage, circulation of its preparation by EGCG, and the raising for product quality or quality is very favourable.
detailed description of the inventionin implementation process of the present invention, those of ordinary skill in the art are not departing from the scope of the present invention various embodiment that the basis with Spirit Essence produces and are modifying apparent and be easily carry out.By the following examples application of the present invention etc. done and illustrate further, but do not represent embodiment limitation of the present invention.
The solid dispersions of embodiment 1, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 10%, is preferably 3%,
Fructose or xylitol 90% ~ 99%, be preferably fructose 97%;
Its preparation method comprises: fructose or xylitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, takes by recipe quantity, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood in fructose or xylitol, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, fructose or xylitol, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG as blank product, and fructose and EGCG be 5:1 proportioning according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 1.
Table 1 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.50%
With reference to product 1.79%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 2, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 10%, is preferably 2.5%,
FOS 90% ~ 99%, is preferably 97.5%;
Its preparation method comprises: FOS is crossed 80 mesh sieves, preferred mistake 100 order, takes by recipe quantity, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood in FOS, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, FOS, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule, FOS also has certain functional in addition, such as, improve gut flora.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG and shine product as to blank, and using FOS and EGCG according to weight ratio be 5:1 proportioning with and the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 2.
Table 2 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.41%
With reference to product 1.55%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to blank product and with reference to product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 3, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 5%, is preferably salt 2%,
Oligomeric manna sugar or xylo-oligosaccharide 5% ~ 25%, be preferably Oligomeric manna sugar 10%,
D-sorbite 70% ~ 94%, is preferably 88%;
Its preparation method comprises: by Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite mistake 80 mesh sieves respectively, preferred mistake 100 order, mixes, separately EGCG is dissolved in ethanol-water solution, preferably 75% ethanolic solution, this spray solution is made softwood, wet granulation, 45 ~ 70 DEG C of dryings in the mixture of Oligomeric manna sugar or xylo-oligosaccharide and D-sorbite, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule, Oligomeric manna sugar or xylo-oligosaccharide also have certain functional in addition, such as, improve gut flora.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG product in contrast, and be 5:1 proportioning according to the Oligomeric manna sugar of optimizing prescriptions amount in the present embodiment and the mixture of D-sorbite proportioning and EGCG according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 3.
Table 3 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.44%
With reference to product 1.60%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 4, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 6%, is preferably 3%,
Isomalt 85% ~ 96%, is preferably 92%,
Sodium carboxymethyl starch 3% ~ 10%, is preferably 5%;
Its preparation method comprises: isomalt, sodium carboxymethyl starch are crossed 80 mesh sieves respectively, preferred mistake 100 order, mixes, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood, wet granulation, 45 ~ 70 DEG C of dryings in the mixture of isomalt and sodium carboxymethyl starch, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, isomalt, sodium carboxymethyl starch, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG product in contrast, and be 5:1 proportioning according to the isomalt of optimizing prescriptions amount proportioning in the present embodiment and the mixture of sodium carboxymethyl starch and EGCG according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 4.
Table 4 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.51%
With reference to product 1.72%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 5, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 2% ~ 10%, is preferably 6%,
Sucrose or glucose 75% ~ 95%, be preferably sucrose 89%,
Starch 2% ~ 8%, is preferably 2%,
Sodium carboxymethyl starch 3% ~ 10%, is preferably 3%;
Its preparation method comprises: EGCG, sucrose or glucose, sodium carboxymethyl starch are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, equal increments mixes, separately starch purified water is made starch slurry, this starch slurry is added in the mixed-powder of EGCG, sucrose or glucose, sodium carboxymethyl starch and make softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, pack, sealing, to obtain final product;
Or its preparation method comprises: get EGCG, sucrose or glucose, starch, sodium carboxymethyl starch respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG product in contrast, and according to the sucrose of optimizing prescriptions amount proportioning in the present embodiment, the mixture of starch and sodium carboxymethyl starch and EGCG are 5:1 proportioning according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 5.
Table 5 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.62%
With reference to product 1.83%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 6, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 10%, is preferably 2%,
Sweet mellow wine 45% ~ 65%, is preferably 55%,
Lactose 35% ~ 55%, is preferably 43%;
Its preparation method comprises: sweet mellow wine, lactose are crossed 80 mesh sieves respectively, and preferred mistake 100 order, after taking by recipe quantity, mix, separately EGCG is dissolved in ethanol-water solution, is preferably dissolved in 75% ethanolic solution, this dissolution homogeneity is sprayed in the mixture of sweet mellow wine and lactose and makes softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, sweet mellow wine, lactose, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG product in contrast, and be 5:1 proportioning according to the sweet mellow wine of optimizing prescriptions amount proportioning in the present embodiment and the mixture of lactose and EGCG according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 6.
Table 6 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.57%
With reference to product 1.73%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.
The solid dispersions of embodiment 7, EGCG and glycitols material and preparation thereof
Recipe quantity by weight percentage, contains:
EGCG 1% ~ 5%, is preferably salt 3%,
PEG-4000 5% ~ 25%, is preferably 10%,
D-sorbite 70% ~ 94%, is preferably 88%;
Its preparation method comprises: PEG-4000, D-sorbite are crossed 80 mesh sieves respectively, preferred mistake 100 order, mixes, separately EGCG is dissolved in ethanol-water solution, preferably 75% ethanolic solution, this spray solution is made softwood, wet granulation, 45 ~ 70 DEG C of dryings in the mixture of PEG-4000 and D-sorbite, whole grain, packaging or pack, sealing, to obtain final product;
Or its preparation method comprises: take EGCG, PEG-4000, D-sorbite, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
Further, can be optionally tablet by the solid dispersion preparation in the present embodiment, or fillingly in Capsules shell, make capsule, PEG-4000 also has certain functional in addition, such as, improve constipation.
Stability test: get the solid dispersions that the optimizing prescriptions in the present embodiment obtains, separately get the pure powder of EGCG product in contrast, and be 5:1 proportioning according to the PEG-4000 of optimizing prescriptions amount in the present embodiment and the mixture of D-sorbite proportioning and EGCG according to weight ratio and with the obtained solid dispersions of same procedure as with reference to product, often kind of a sample samples 8 (n=8), the data result detected is averaged, by Accelerated stability test (at 40 DEG C, under humidity 75% condition) place 2 months, sampling detects, HPLC method is adopted to detect the content of EGCG in each sample, and result was compared with 0 day, draw the content drop-out value of 2 months some EGCG, data statistics software process, detection method: adopt high effective liquid chromatography for measuring content, using 0.1 phosphoric acid and acetonitrile as mobile phase, sample size 20 μ L, column temperature 28 DEG C, determined wavelength 273nm, retention time is greater than 7min.Result of the test is in table 7.
Table 7 stability test result
Sample (n=8 averages) EGCG content drop-out value
The present embodiment solid dispersions 0.46%
With reference to product 1.59%
Blank product 2.13%
Result shows, the solid dispersions that the present embodiment is obtained, and the content drop-out value of its EGCG lower than to reference to product and blank product in the same old way, and has the significance difference opposite sex, and the solid dispersion composition embodying EGCG of the present invention has significant stability.

Claims (10)

  1. The solid dispersion composition of 1.EGCG and glycitols material, described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, and glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1, preferred glycitols material and EGCG are (15 ~ 50) with weight ratio: the ratio combination of 1.
  2. 2. the preparation method of solid dispersion composition according to claim 1, it comprises:
    Get EGCG and glycitols material respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mix according to equal increments, or dry granulation, dry, whole grain, optionally can pulverize further, and obtain solid dispersions, wherein said glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, or,
    EGCG is dissolved in ethanol or ethanol-water solution, this dissolution homogeneity is sprayed on glycitols material, carry out wet granulation, softwood processed, granulate, dry, whole grain, optionally can pulverize further, namely solid dispersions is obtained, wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, or,
    Get EGCG and glycitols material, add solvent, stirring makes EGCG and glycitols substance dissolves or is scattered in solvent, from this mixture, desolventizing is removed after mixing, and it is dry, pulverize and obtain solid dispersions, wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, described solvent selected from ethanol, water or ethanol water, describedly Rotary Evaporators can be taked to steam except desolventizing and dry method to remove, remove under reduced pressure, drying under reduced pressure, vacuum drying, freeze drying, spraying dry, fluidized bed drying, one or more in heating, drying.
  3. 3. the solid dispersions of EGCG and glycitols material and a solid dispersion composition for other pharmaceutical carrier, the pharmaceutical dosage form of described composition is any pharmaceutical dosage form of acceptable in pharmacy, wherein said glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside, and glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1.
  4. 4. one kind contains the granule of the solid dispersions of EGCG and glycitols material, described glycitols material and EGCG are (12 ~ 80) with weight ratio: the ratio combination of 1, and preferred glycitols material and EGCG are (15 ~ 50) with weight ratio: the ratio combination of 1, wherein said described glycitols material comprises one or more compositions following: fructose, xylitol, FOS, xylo-oligosaccharide, polydextrose, sweet mellow wine, 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 etc.), dextrin, cyclodextrin, HP-β-CD, microcrystalline cellulose, carboxymethyl cellulose, HPMC, pregelatinized starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, knob is sweet, stevioside,
    Its preparation method comprises: glycitols material is crossed 80 mesh sieves respectively, and preferred mistake 100 order, after taking by recipe quantity, mix, separately EGCG is dissolved in ethanol-water solution, is preferably dissolved in 75% ethanolic solution, this dissolution homogeneity is sprayed in the mixture of glycitols material and makes softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product; Or its preparation method comprises: get EGCG, glycitols material, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
  5. 5. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 1%～10%，
    Fructose or xylitol 90% ~ 99%;
    Its preparation method comprises: fructose or xylitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, takes by recipe quantity, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood in fructose or xylitol, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
    Or its preparation method comprises: take EGCG, fructose or xylitol, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
  6. 6. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 1%～10%，
    FOS 90% ~ 99%;
    Its preparation method comprises: FOS is crossed 80 mesh sieves, preferred mistake 100 order, takes by recipe quantity, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood in FOS, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
    Or its preparation method comprises: take EGCG, FOS, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
  7. 7. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 1%～5%，
    Oligomeric manna sugar or xylo-oligosaccharide 5% ~ 25%,
    D-sorbite 70% ~ 94%;
    Its preparation method comprises: by Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite mistake 80 mesh sieves respectively, preferred mistake 100 order, mixes, separately EGCG is dissolved in ethanol-water solution, preferably 75% ethanolic solution, this spray solution is made softwood, wet granulation, 45 ~ 70 DEG C of dryings in the mixture of Oligomeric manna sugar or xylo-oligosaccharide and D-sorbite, whole grain, packaging or pack, sealing, to obtain final product;
    Or its preparation method comprises: take EGCG, Oligomeric manna sugar or xylo-oligosaccharide, D-sorbite, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
  8. 8. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 1%～6%，
    Isomalt 85% ~ 96%,
    Sodium carboxymethyl starch 3% ~ 10%;
    Its preparation method comprises: isomalt, sodium carboxymethyl starch are crossed 80 mesh sieves respectively, preferred mistake 100 order, mixes, separately EGCG is dissolved in ethanol-water solution, be preferably dissolved in 75% ethanolic solution, this spray solution is made softwood, wet granulation, 45 ~ 70 DEG C of dryings in the mixture of isomalt and sodium carboxymethyl starch, whole grain, packaging or pack, sealing, to obtain final product;
    Or its preparation method comprises: take EGCG, isomalt, sodium carboxymethyl starch, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
  9. 9. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 2%～10%，
    Sucrose or glucose 75% ~ 95%,
    Starch 2% ~ 8%,
    Sodium carboxymethyl starch 3% ~ 10%;
    Its preparation method comprises: EGCG, sucrose or glucose, sodium carboxymethyl starch are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, equal increments mixes, separately starch purified water is made starch slurry, this starch slurry is added in the mixed-powder of EGCG, sucrose or glucose, sodium carboxymethyl starch and make softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, pack, sealing, to obtain final product;
    Or its preparation method comprises: get EGCG, sucrose or glucose, starch, sodium carboxymethyl starch respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, pack, sealing, to obtain final product.
  10. 10. a solid dispersion composition for EGCG and glycitols material, its recipe quantity by weight percentage, contains:
    EGCG 1%～10%，
    Sweet mellow wine 45% ~ 65%,
    Lactose 35% ~ 55%;
    Its preparation method comprises: sweet mellow wine, lactose are crossed 80 mesh sieves respectively, and preferred mistake 100 order, after taking by recipe quantity, mix, separately EGCG is dissolved in ethanol-water solution, is preferably dissolved in 75% ethanolic solution, this dissolution homogeneity is sprayed in the mixture of sweet mellow wine and lactose and makes softwood, wet granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product;
    Or its preparation method comprises: take EGCG, sweet mellow wine, lactose, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, mixes according to equal increments, or dry granulation, 45 ~ 70 DEG C of dryings, whole grain, packaging or pack, sealing, to obtain final product.
CN201510183570.3A 2015-04-19 2015-04-19 EGCG solid dispersion compositions with heat endurance and its preparation method and application Active CN104719910B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510183570.3A CN104719910B (en) 2015-04-19 2015-04-19 EGCG solid dispersion compositions with heat endurance and its preparation method and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510183570.3A CN104719910B (en) 2015-04-19 2015-04-19 EGCG solid dispersion compositions with heat endurance and its preparation method and application

Publications (2)

Publication Number Publication Date
CN104719910A true CN104719910A (en) 2015-06-24
CN104719910B CN104719910B (en) 2017-07-28

Family

ID=53444772

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510183570.3A Active CN104719910B (en) 2015-04-19 2015-04-19 EGCG solid dispersion compositions with heat endurance and its preparation method and application

Country Status (1)

Country Link
CN (1) CN104719910B (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105462845A (en) * 2015-10-29 2016-04-06 安徽农业大学 Tea polyphenol or EGCG and beta-CD clathrate compound and method for preparing general solid medium rich in tea polyphenol or EGCG
CN109589323A (en) * 2018-12-11 2019-04-09 福州乾正药业有限公司 Nervonic acid and the solid dispersion composition of EGCG and its preparation method and application
CN110477377A (en) * 2019-08-02 2019-11-22 大连医诺生物股份有限公司 The molten type of the mouth of the ingredient containing non-fat-soluble directly drinks powder and preparation method thereof
CN111297918A (en) * 2020-05-04 2020-06-19 福州乾正药业有限公司 Composition of EGCG and cordyceps militaris extract and preparation method and application thereof
CN111372581A (en) * 2017-11-23 2020-07-03 巴黎公共救济院 Epigallocatechin gallate solution
CN111955749A (en) * 2020-08-31 2020-11-20 浙江新维士生物科技有限公司 Composition of dietary fiber particles and preparation process thereof
CN114366717A (en) * 2022-01-11 2022-04-19 四川农业大学 Enteric solid dispersion particle based on EGCG nano-particle, preparation method and application thereof
CN116420874A (en) * 2023-04-26 2023-07-14 仙乐健康科技股份有限公司 A composition without bitter taste and product comprising the same

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1739499A (en) * 2005-09-05 2006-03-01 中山大学 (-)-epigallocatechin gallate solid dispersion and its prepn and application
CN1939296A (en) * 2005-09-29 2007-04-04 中国人民解放军军事医学科学院毒物药物研究所 Theapolyphenol composition and its preparation
CN101028253A (en) * 2001-07-30 2007-09-05 Dsmip资产有限公司 Composition comprising epigallocatechin gallate
CN102028633A (en) * 2009-09-30 2011-04-27 Exax调色剂株式会社 Egcg/polyester resin complex, process for preparing the same and cosmetic composition comprising the same
CN102217756A (en) * 2011-04-26 2011-10-19 杭州市农业科学研究院 Epigallocatechin gallate effervescent tablet and preparation method thereof
JP2012072061A (en) * 2009-01-29 2012-04-12 Eisai R & D Management Co Ltd New composition
CN102924929A (en) * 2012-10-03 2013-02-13 中南大学 Nanoparticles for encapsulating polyphenol active substances and preparation method thereof
CN104356406A (en) * 2014-10-31 2015-02-18 中南大学 Method for coating polyphenol material with gelatin-polysaccharide graft

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101028253A (en) * 2001-07-30 2007-09-05 Dsmip资产有限公司 Composition comprising epigallocatechin gallate
CN1739499A (en) * 2005-09-05 2006-03-01 中山大学 (-)-epigallocatechin gallate solid dispersion and its prepn and application
CN1939296A (en) * 2005-09-29 2007-04-04 中国人民解放军军事医学科学院毒物药物研究所 Theapolyphenol composition and its preparation
JP2012072061A (en) * 2009-01-29 2012-04-12 Eisai R & D Management Co Ltd New composition
CN102028633A (en) * 2009-09-30 2011-04-27 Exax调色剂株式会社 Egcg/polyester resin complex, process for preparing the same and cosmetic composition comprising the same
CN102217756A (en) * 2011-04-26 2011-10-19 杭州市农业科学研究院 Epigallocatechin gallate effervescent tablet and preparation method thereof
CN102924929A (en) * 2012-10-03 2013-02-13 中南大学 Nanoparticles for encapsulating polyphenol active substances and preparation method thereof
CN104356406A (en) * 2014-10-31 2015-02-18 中南大学 Method for coating polyphenol material with gelatin-polysaccharide graft

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
马雅钦，等: "燕麦β-葡聚糖-表没食子儿茶素没食子酸酯", 《食品科学》 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105462845A (en) * 2015-10-29 2016-04-06 安徽农业大学 Tea polyphenol or EGCG and beta-CD clathrate compound and method for preparing general solid medium rich in tea polyphenol or EGCG
CN111372581A (en) * 2017-11-23 2020-07-03 巴黎公共救济院 Epigallocatechin gallate solution
US20200375939A1 (en) * 2017-11-23 2020-12-03 Assistance Publique - Hopitaux De Paris Epigallocathechin gallate solution
US11938113B2 (en) * 2017-11-23 2024-03-26 Assistance Publique—Hopitaux de Paris Epigallocathechin gallate solution
CN109589323A (en) * 2018-12-11 2019-04-09 福州乾正药业有限公司 Nervonic acid and the solid dispersion composition of EGCG and its preparation method and application
CN110477377A (en) * 2019-08-02 2019-11-22 大连医诺生物股份有限公司 The molten type of the mouth of the ingredient containing non-fat-soluble directly drinks powder and preparation method thereof
CN111297918A (en) * 2020-05-04 2020-06-19 福州乾正药业有限公司 Composition of EGCG and cordyceps militaris extract and preparation method and application thereof
CN111955749A (en) * 2020-08-31 2020-11-20 浙江新维士生物科技有限公司 Composition of dietary fiber particles and preparation process thereof
CN114366717A (en) * 2022-01-11 2022-04-19 四川农业大学 Enteric solid dispersion particle based on EGCG nano-particle, preparation method and application thereof
CN116420874A (en) * 2023-04-26 2023-07-14 仙乐健康科技股份有限公司 A composition without bitter taste and product comprising the same

Also Published As

Publication number Publication date
CN104719910B (en) 2017-07-28

Similar Documents

Publication Publication Date Title
CN104719910A (en) Solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and preparation method of solid dispersion combination and application in preparation of solid dispersion combination
EP2180882B2 (en) Solid matrix pharmaceutical preparation
CN101141961B (en) Stable particular pharmaceutical composition of solifenacin or salt thereof
EP3135300B1 (en) Disintegrating particle composition including microfibrous cellulose
EP2979697A1 (en) Oral administration preparation with masked bitterness of silodosin
CN105362240A (en) Orally disintegrating tablet
CN104922143B (en) The composition and its preparation method and application of EGCG and chitosan oligosaccharide
CN104784197A (en) EGCG and beta-glucan composition, and preparation method, and medical application thereof
EP3225256B1 (en) Disintegrative particle composition including pulverized lactose or granulated lactose
CN105078910A (en) Freeze-dried oral preparation containing elopiprazole and preparation method of freeze-dried oral preparation
CN111297918A (en) Composition of EGCG and cordyceps militaris extract and preparation method and application thereof
CN109589323A (en) Nervonic acid and the solid dispersion composition of EGCG and its preparation method and application
EP4257119A1 (en) Olaparib solid dispersion composition with improved stability and bioavailability
CN104825441A (en) EGCG and gamma-aminobutyric acid composition, and preparation method and applications thereof
CN104546667A (en) Solid dispersion containing posaconazole and preparation method thereof
JP2020518611A (en) Compositions with improved water solubility and bioavailability
CA2253769C (en) Pharmaceutical compositions comprising fenofibrate
CN104739776A (en) Solid dispersion composition of levocarnitine as well as preparation method and medical application of solid dispersion composition
CN104248769B (en) A kind of lurasidone medicine composition and preparation method thereof
WO2007049626A1 (en) Oral solid preparation containing cabergoline
JP6456377B2 (en) Tablets containing sake yeast
KR20130062691A (en) Rapid solid dispersion oral compsition for using wheat bran
KR20170001786A (en) Preparation method for pharmaceutical composition comprising Pelargonium sidoides extracts
WO2021100728A1 (en) 6,7-unsaturated-7-carbamoyl morphinan derivative-containing solid formulation
JPWO2005000358A1 (en) Stabilizer

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20180503

Address after: 211100 169 general road, Jiangning economic and Technological Development Zone, Nanjing, Jiangsu

Patentee after: Nanjing Shuang Ke Pharmaceutical Development Co., Ltd.

Address before: 350008 Jinshan Industrial Concentration Zone, 6 Lane Road, Jianxin Town, Cangshan District, Fuzhou, Fujian, two, Cangshan, 25.

Patentee before: Fuzhou Qianzheng Pharmaceutical Co., Ltd.

TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20220126

Address after: 210000 first, second and third floors of building a, Mingjia science and technology building, No. 99 Shengli Road, Jiangning District, Nanjing, Jiangsu Province (Jiangning Development Zone)

Patentee after: Nanjing Runtong Changda Pharmaceutical Technology Co.,Ltd.

Address before: 211100 169 general road, Jiangning economic and Technological Development Zone, Nanjing, Jiangsu

Patentee before: NANJING SHUANGKE PHARMACEUTICAL DEVELOPMENT Co.,Ltd.

TR01 Transfer of patent right