CN104825873B - Composition of EGCG and bamboo-leaves flavones and its preparation method and application - Google Patents

Abstract

The present invention provides the pharmaceutical composition containing EGCG and bamboo-leaves flavones, and the dosage form of the drug is any pharmaceutical dosage form of acceptable in pharmacy, and the EGCG is with bamboo-leaves flavones using weight ratio as (0.05~2):1 ratio combination; invention further provides the preparation methods of the composition; and prepare protection cardiovascular and cerebrovascular, protection heart and brain tissues, improve the drug of cardiac-cerebral ischemia in application, preparing the application that reduces during the drug of risk caused by myocardial infarction, cerebral apoplexy or angiocardiopathy occurs.

Description

Composition of EGCG and bamboo-leaves flavones 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 and bamboo-leaves flavones Composition, with and its preparation method and application.Health product composition of the present invention, including but not limited to drug, medical food Product, health food or functional food, ordinary food 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, is that most efficient activity is single in tea polyphenols Body ingredient has good safety and extensive physiological activity, research shows that, EGCG has antithrombus formation, resists and move Arteries and veins hardening, Green Tea Extract damage, anti-oxidant, anti-oxidation stress, antiangiogenic, adjusts immune, the protection heart at protection nervous system The cerebrovascular and anti-inflammatory, antitumor, antiviral, antibacterial action, it is particularly significant for health.

However, disadvantageously, on the one hand, EGCG is relatively simple in the mechanism of action for the treatment of cardiac and cerebral vascular diseases, lacks comprehensive It protects cardiovascular and cerebrovascular or treats the function of cardiovascular and cerebrovascular disease；On the other hand, the taste of EGCG is very bitter, limits it Application in terms of medicine food, consumer or patient are difficult to receive its bitter taste when directly oral, the compliance for applying it It is serious restricted.

Bamboo-leaves flavones are that the biology with physiological activity extracted from the leaf of bamboo of grass family Phyllostachys Ph. meyeri is yellow Ketone, it is a kind of efficient biological anti-oxidant, is nutrient needed by human, has protection cardiovascular and cerebrovascular, improves cardiac muscle and lacks Blood improves cerebral ischemia, adjusts blood fat, reduces the effect of blood viscosity, has prevention cardiovascular and cerebrovascular disease, anti-oxidant, anti-inflammatory And adjust immune function, when human body lacks, be easy to cause heart and cerebral function not entirely, the production of the diseases such as vascular sclerosis It is raw.

Invention content

The pleasantly surprised discovery of inventor combines EGCG with bamboo-leaves flavones, has good synergistic effect, especially in the protection heart The cerebrovascular protects heart and brain tissues, improves the synergistic effect of cardiac-cerebral ischemia etc. and myocardial infarction, brain soldier occurs reducing In or angiocardiopathy caused by risk effect；On the other hand, bamboo-leaves flavones can improve the bitter taste of EGCG, make consumer or Patient is easy to receive in direct take orally.

The object of the present invention is to provide a kind of pharmaceutical composition containing EGCG and bamboo-leaves flavones, the dosage form of the drug is Any pharmaceutical dosage form of acceptable in pharmacy.

It is a further object to provide the preparation methods of above-mentioned composition；

The invention further relates to application of the above-mentioned composition in drug, medical usages.

The present composition includes two kinds of combinations：

A kind of combination is that have EGCG and bamboo-leaves flavones, and the dosage form of the drug in the form of compound preparation It is any pharmaceutical dosage form of acceptable in pharmacy.Using corresponding pharmaceutical carrier or auxiliary material, using different preparation processes It can be made into different compound medicinal formulations.It should be appreciated that compound preparation refers to using EGCG and bamboo-leaves flavones as pharmaceutical activity Composition and individual preparation is made, can be acceptable any pharmaceutical dosage form in pharmacy, preferably oral preparation, such as piece Agent (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet, etc.), hard capsule (including capsulae enterosolubilis), flexible glue Wafer, pulvis, dry suspensoid agent, pill, micropill preparation (including enteric-coated micro-pill), pill, dry syrup, powder, takes orally granule Solution, oral administration mixed suspension and oral quick-release or the dosage forms such as sustained release or controlled release or injection or cutaneous permeable agent, Powder ampoule agent for injection (including the filling powder-injection of Injectable sterile, freeze drying powder injection), aqueous solution injection, injection can be with It is that intravenous injection using glucose, sodium chloride, fructose, inverted sugar, xylitol or maltose etc. as osmotic pressure regulator uses The aqueous solution of (including intravenous injection and intravenous drip)；Further include ointment, gelling agent, emulsion agent, the latex of external preparation for skin Agent, patch, etc.；Can also be the dosage forms such as quick-release, the slow-release controlled-release of any of the above dosage form, such as oral dispersible tablet, sustained release Piece, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Particularly, by known in the art Prepared by method preferably for prepare the oral solution used in pharmacy, tablet (including dispersible tablet, slow-release tablet, enteric Piece, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), injection is (including injection Powder-injection and parenteral solution).Preferred combination dosage form is oral preparation, most preferably oral granule, pulvis, dry suspensoid agent, It is tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet, etc.), hard capsule (including capsulae enterosolubilis), soft Capsule, pill, micropill preparation (including enteric-coated micro-pill), pill, dry syrup, powder, oral solution, oral administration mixed suspension Deng.

Another combination is that EGCG and bamboo-leaves flavones are respectively prepared individual preparation, and when in use, patient can be with Successively medication successively, uses after can also the preparation of separated EGCG be mixed with the preparation of bamboo-leaves flavones, simultaneously finally to reach To the purpose for using composition of medicine of the present invention, it is necessary to, in order to facilitate patient medication and represent pharmaceutical composition feature, Two kinds of individual preparations should be packaged in same pack arrangement；Further, EGCG is individually to make with bamboo-leaves flavones During agent, the pharmaceutical dosage form of the two can be identical or different, as EGCG pieces and bamboo-leaves flavones tablet medicament composition, EGCG capsules and bamboo-leaves flavones pharmaceutical capsules composition, EGCG pieces and bamboo-leaves flavones pharmaceutical capsules composition, EGCG capsules and bamboo The dosage forms such as leaf flavones tablet medicament composition or the quick-release of any of the above dosage form, slow-release controlled-release, such as oral dispersion Piece, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Particularly, by this Prepared by art-known methods preferably for prepare the tablet used in pharmacy (including dispersible tablet, slow-release tablet, enteric coatel tablets, bubble Rise piece, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), granule, pulvis, dry suspensoid agent, Pill, micropill preparation (including enteric-coated micro-pill), pill, dry syrup, powder, oral solution, injection are (including injection powder Injection and parenteral solution) etc..

It should be appreciated that the compound that the present invention combines can simultaneously or sequentially be given, these combination of compounds can be same Or different pharmaceutical composition.If be sequentially administered, the delay administration of second of active component should not reduce the active constituent group The effect of the drug mechanism of synergistic therapeutic action or collaboration between conjunction.It is also understood that no matter simultaneously or sequentially give Medicine, EGCG and bamboo-leaves flavones can be administered in the form of either alone or in any combination, preferably be administered simultaneously EGCG and bamboo-leaves flavones Or be sequentially administered with independent medicine type, most preferably it is administered simultaneously.

It is preferred that give the pharmaceutical composition of the present invention in the form of compound preparation, such as tablet, in tablet it is special be double-layer tablets, Chewable tablets, for another example capsule, granule, pulvis, dry suspensoid agent, oral solution, liquid preparation, medicinal tea, etc..

Particularly, the pharmaceutical composition provided by the invention containing EGCG and bamboo-leaves flavones, when pharmaceutical dosage form is tablet, glue When solid pharmaceutical preparations, wherein EGCG or bamboo-leaves flavones are with group made of micronized form for wafer, granule, pulvis or dry suspensoid agent Object is closed, preferably EGCG and bamboo-leaves flavones are crushed by low-temperature airflow crushing technology, and powder size is more than 800 mesh, excellent It selects powder size in 800~1000 mesh or even preferably the granularity of powder is more than 1000 mesh.

Another aspect of the present invention provides EGCG and bamboo-leaves flavones with sheet existing for the ratio of the drug dose to act synergistically Invention combination.

Another aspect of the present invention provides EGCG with bamboo-leaves flavones with the combination of arbitrary proportion, preferably with the agent of synergistic effect Present invention combination existing for the ratio of amount, EGCG is with bamboo-leaves flavones using weight ratio as (0.05~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.06~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.07~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.08~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.09~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.1~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.2~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.3~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.4~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.5~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.6~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.7~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.8~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.1~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.2~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.3~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.4~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.5~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.6~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.7~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.8~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.06~1.9):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.07~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.08~1.7):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.09~1.6):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.1~1.5):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.15~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.2~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.3~1.7):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.4~1.6):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.5~1.5):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.6~1.4):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.7~1.3):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.8~1.2):1 ratio combination；

Specifically, for example preferred EGCG and bamboo-leaves flavones are using weight ratio as 0.05:1、0.06:1、0.07:1、0.08:1、 0.09:1、0.1:1、0.2:1、0.3:1、0.4:1、0.5:1、0.6:1、0.7:1、0.8:1、0.9:1、1:1、1.1:1、1.2:1、 1.3:1、1.4:1、1.5:1、1.6:1、1.7:1、1.8:1、1.9:1、2:1, etc..

EGCG takes orally applicable dosage generally daily 50~1000mg levels of being grown up and gives the compound, preferably daily 100~800mg singles give the compound in two times, for example, 100mg, 150mg, 200mg, 250mg, 300mg, 350mg, The EGCG of 400mg, 450mg, 500mg, 550mg, 600mg, 650mg, 700mg, 750mg, 800mg, 900mg or 1000mg, And give the bamboo-leaves flavones of effective dose, preferably give the bamboo-leaves flavones of 50~2000mg, for example, 50mg, 100mg, 150mg, 200mg、250mg、300mg、350mg、400mg、450mg、500mg、550mg、600mg、650mg、700mg、750mg、 800mg、850mg、900mg、950mg、1000mg、1100mg、1200mg、1300mg、1400mg、1500mg、1600mg、 Bamboo-leaves flavones of 1700mg, 1800mg, 1900mg or 2000mg, etc..

It should be appreciated that the composition of the invention containing EGCG and bamboo-leaves flavones, can also optionally contain other medicines Effect or food function ingredient, for example, it is mannatide, lentinan, oligofructose, polyfructosan, xylo-oligosaccharide, oligomeric sweet Reveal sugar, etc..

Preferably, the pharmaceutical composition of EGCG and bamboo-leaves flavones, wherein it is preferred that in per unit preparation containing 50~ 1000mgEGCG and 50~2000mg bamboo-leaves flavones；

Specifically, contain 50mgEGCG and 50mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 550mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 650mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 750mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 850mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 950mg bamboo-leaves flavones in per unit preparation,

Or contain 50mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 160mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 550mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 650mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 750mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 850mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 950mg bamboo-leaves flavones in per unit preparation,

Or contain 100mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 550mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 650mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 750mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 850mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 950mg bamboo-leaves flavones in per unit preparation,

Or contain 150mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 550mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 650mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 750mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 850mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 950mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1100mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1200mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1300mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1400mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1500mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1600mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1700mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1800mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 1900mg bamboo-leaves flavones in per unit preparation,

Or contain 200mgEGCG and 2000mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1100mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1200mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1300mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1400mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1500mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1600mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1700mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1800mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 1900mg bamboo-leaves flavones in per unit preparation,

Or contain 250mgEGCG and 2000mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 100mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 150mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 200mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 250mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 300mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 350mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 400mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 450mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 600mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 700mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 800mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 900mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1000mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1100mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1200mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1300mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1400mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1500mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1600mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1700mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1800mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 1900mg bamboo-leaves flavones in per unit preparation,

Or contain 300mgEGCG and 2000mg bamboo-leaves flavones in per unit preparation,

Or contain 350mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 400mgEGCG and 500mg bamboo-leaves flavones in per unit preparation,

Or contain 500mgEGCG and 500mg bamboo-leaves flavones in per unit preparation.

" the per unit preparation " refers to the preparation unit of minimum package or minimum form of medication, including each capsule It is agent, each tablet or pill, each bag of granule or pulvis, each bottle of oral administration solution, each injection or parenteral solution, every One bottle of injection or parenteral solution, each piece of suppository, each bottle of eye drops, each pipe ointment, etc..

The active component of pharmaceutical composition can be usually given in the form of chemical raw material, but is preferably given in the form of Pharmaceutical composition It gives.Pharmaceutical composition of the present invention includes EGCG and bamboo-leaves flavones and one or more pharmaceutically acceptable carriers or figuration The pharmaceutical composition of the present invention of agent.These carriers must be acceptable, you can and it is compatible with other components of formula, and it is connect Receptor is nontoxic.When each component for individually giving the composition, they are generally individually Pharmaceutical composition form.Except as otherwise saying Bright, the signified composition of the present invention refers to the pharmaceutical composition containing EGCG and bamboo-leaves flavones or wherein EGCG and bamboo-leaves flavones The composition of the pharmaceutical composition of each component.

Preferably, the combination of EGCG and bamboo-leaves flavones is usually pharmaceutically may be used with one or more for unit dosage form The Pharmaceutical composition of the carrier of receiving, the EGCG and the dosage of bamboo-leaves flavones contained in common unit formulation is in the foregoing Clearly.

Using corresponding, different pharmaceutical carrier and preparation process, pharmaceutical composition of the present invention can be made different Pharmaceutical dosage form.Those skilled in the art are it will be appreciated that these pharmaceutical carriers are for the ease of producing and processing into each Kind of dosage form, ensure drug safely, effectively with factors and the physics and chemistry according to different pharmaceutical dosage forms and drug itself such as stablizing Property is selected.The selection of pharmaceutical carrier is using being that technical staff in field of the present invention is known and obvious.

It should be appreciated that for oral or injection, according to method well known in the art, selected generally according to different medicaments With or the pharmaceutical carrier that is applied in combination, optionally including excipient or diluent, such as microcrystalline cellulose, mannitol, plant Fat end, lactose, pregelatinized starch, starch, dextrin, cyclodextrin, maltodextrin, hydroxypropyl-β-cyclodextrin, calcium phosphate, phosphoric acid hydrogen Calcium, hydroxypropyl methyl cellulose, sucrose, dextran, poloxamer, sodium chloride, sorbierite, glucose, oligofructose, poly Fructose, xylo-oligosaccharide, polydextrose, Oligomeric manna sugar, solid polyethylene glycol（Such as polyethylene glycol-4000, polyethylene glycol- 12000th, polyethylene glycol-6000, Polyethylene glycol-2000 etc.）, resistant dextrin, fructose, water, propylene glycol, glycerine, coffee, milk powder, Plant protein powder, etc.；For oral solid formulation, it is also an option that property includes adhesive, such as povidone (polyethylene Pyrrolidones), methylcellulose, hydroxymethyl cellulose, hypromellose, pregelatinized starch, sodium carboxymethyl starch, hydroxypropyl Base cellulose, hydroxyethyl cellulose, gelatin, guar gum, xanthans, etc.；Further include lubricant, such as magnesium stearate, tristearin Acid, talcum powder, stearyl fumarate, lauryl sodium sulfate, etc.；Also optionally include disintegrant, such as carboxylic first Base sodium starch, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, crosslinked polyvinylpyrrolidone, cross-linked carboxymethyl fiber Plain sodium, crosslinked carboxymethyl fecula sodium, pregelatinized starch, etc.；Also optionally include surfactant or cosolvent, such as Lauryl sodium sulfate, Tween-80, etc.；It may also include pH values conditioning agent or buffer or cosolvent, such as phosphoric acid Salt buffer, citric acid, sodium citrate, acetate buffer, dilute hydrochloric acid, lactic acid, sodium carbonate, sodium hydroxide, alkalinity organise Object is closed, such as arginine, lysine, meglumine, tromethamine, etc.；Also optionally include preservative, such as benzoic acid Sodium, potassium sorbate, methyl p-hydroxybenzoate, propylparaben, etc.；Also optionally include stabilizer and resist Oxygen agent, for example, metal chelating agent select ethylenediamine tetra-acetic acid and its salt (mosatil, natrium adetate) etc., sodium sulfite, Sodium pyrosulfite, vitamin C, vitamin E, etc.；Also optionally include taste conditioning agent, such as maltitol, fructose, Sucrose, saccharin sodium, flavoring orange essence, strawberry essence, etc.；It additionally can include other conventional, appropriate additives.Should also Understand, can be film coating when agent type is tablet or capsule.For the material of film coating, including suitable coating agent, Such as hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate (enteric Coating material), etc.；It also may include plasticizer, such as polyethylene glycol, triethyl citrate, etc.；Also optionally include Suitable solubilizer, such as Polyoxyethylene Sorbitan Monooleate；It also may include suitable pigment, such as titanium dioxide, various iron oxide, pink Pigment, etc..It should be appreciated that above-mentioned " optionally including " refers to optionally select to use, can not also use.

Particularly, the chemical composition of the composition of EGCG and bamboo-leaves flavones of the present invention, EGCG and bamboo-leaves flavones is in medicine Can be different on agent releasing pattern, such as EGCG can be sustained or the form of controlled release occurs, and bamboo-leaves flavones can also be sustained or The form of controlled release occurs, to improve EGCG with bamboo-leaves flavones in the blood concentration caused by the time difference in terms of action or metabolism Do not act synergistically.

In the present patent application, " composition " refers to the EGCG or/and bamboo-leaves flavones, and other chemical compositions, such as The mixture that physiologically/pharmaceutically acceptable carrier or excipient are formed, the purpose of pharmaceutical composition are conducive to drug Using, carry, preserve；" administration " mentioned here refer in order to prevent or treat disease and to organism（Including patient or Healthy population）Deliver described compound, its pharmaceutical salt or its solvate；" the per unit preparation " refers to most parcel It is the preparation unit of dress or minimum form of medication, such as each bottle of oral administration solution, each capsule, each tablet or pill, each Bag granule or pulvis, each injection or parenteral solution, each bottle of injection or parenteral solution, each piece of suppository, each bottle of drop Ocular fluid, each pipe ointment, etc..

Another aspect, it has been found that when EGCG is applied in combination with bamboo-leaves flavones, show the advantages of unexpected, Especially the pharmaceutical composition show it is outstanding, unexpected protection cardiovascular and cerebrovascular, protection heart and brain tissues, improve heart and brain lack The synergistic effect of blood etc. and reduce myocardial infarction, cerebral apoplexy or angiocardiopathy occurs caused by risk etc. have Good synergistic function.Preferably, the pharmaceutical composition of EGCG and bamboo-leaves flavones of the present invention is used to prepare protection heart and brain blood It manages, the application in the drug of protection heart and brain tissues, improvement cardiac-cerebral ischemia, generation myocardial infarction, cerebral apoplexy or the heart is reduced preparing Application in the drug of risk caused by vascular diseases, etc..

Therefore, another aspect, the present invention provide a kind of protection cardiovascular and cerebrovascular, protection heart and brain tissues, improve cardiac-cerebral ischemia, Or the pharmaceutical composition that myocardial infarction, cerebral apoplexy or risk caused by angiocardiopathy occurs is reduced, it contains EGCG and bamboo Leaf flavones.It will be appreciated by those skilled in the art that, in pharmaceutical composition, the combination of EGCG and bamboo-leaves flavones, every list Dosage ratio and content in the preparation of position, aforementioned content is just the same with the present invention.

Further, the present invention also provides EGCG and the preparation method of the pharmaceutical composition of bamboo-leaves flavones, it includes will EGCG and bamboo-leaves flavones mix with pharmaceutically acceptable pharmaceutical carrier and acceptable any pharmaceutical preparation in pharmacy are made, Such as EGCG and bamboo-leaves flavones mix (dry granulating machine processing) with pharmaceutical carrier dry powder blend, dry granulation, wet granulation mixes It closes (with water or ethanol solution wet granulation), liquid or semisolid mixing (content of such as soft capsule, the mixing of dripping pill dropping liquid) Deng preferred pharmaceutical dosage form is tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet etc.), hard shell capsules Agent (including capsulae enterosolubilis), granule, dry suspensoid agent, oral solution, dry syrup, powder, oral administration mixed suspension, soft capsule Agent, pill, micropill preparation (including enteric-coated micro-pill), pill and oral quick-release or the dosage forms such as sustained release or controlled release, injection powder Injection (including the filling powder of Injectable sterile, freeze drying powder injection), aqueous solution injection, injection can also be with glucose, Sodium chloride, fructose, inverted sugar, xylitol or maltose etc. are used as the intravenous injection of osmotic pressure regulator and (are pushed away including vein Note and intravenous drip) aqueous solution or the dosage forms such as quick-release, slow-release controlled-release of any of the above dosage form, it is 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..Particularly, It is prepared by means known in the art preferably for prepare the tablet used in pharmacy (including dispersible tablet, slow-release tablet, enteric Piece, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), oral solution, injection (including powder ampoule agent for injection and parenteral solution) etc.；Or

The present invention also provides EGCG and bamboo-leaves flavones pharmaceutical composition preparation method, it is included EGCG and the leaf of bamboo Flavones is mixed and made into individual pharmaceutical preparation with pharmaceutically acceptable pharmaceutical carrier respectively, and by two kinds of individual drug systems Agent is packaged in same medicine box, and preferred pharmaceutical dosage form is tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, Orally disintegrating Piece, effervescent tablet etc.), hard capsule (including capsulae enterosolubilis), granule, dry suspensoid agent, dry syrup, powder, soft capsule, mouth Take solution, pill, micropill preparation (including enteric-coated micro-pill), pill, oral administration mixed suspension and oral quick-release or sustained release or control Dosage forms, powder ampoule agent for injection (including the filling powder of Injectable sterile, freeze drying powder injection), aqueous solution injection, the injection such as release It can also be the vein note using glucose, sodium chloride, fructose, inverted sugar, xylitol or maltose etc. as osmotic pressure regulator Penetrate the aqueous solution of use (including intravenous injection and intravenous drip).Can also be quick-release, the slow-release controlled-release of any of the above dosage form Etc. dosage forms, such as oral dispersible tablet, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, effervesce Particle, etc..Particularly, it is prepared by means known in the art preferably for prepare the tablet used in pharmacy (including dispersion Piece, slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), Oral solution, injection (including powder ampoule agent for injection and parenteral solution) etc..

Preferably, the present invention provides a kind of granule containing EGCG and bamboo-leaves flavones, the EGCG and bamboo-leaves flavones with Weight ratio is (0.05~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.06~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.07~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.08~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.09~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.1~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.2~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.3~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.4~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.5~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.6~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.7~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.8~1):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.1~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.2~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.3~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.4~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.5~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.6~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.7~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (1.8~2):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.06~1.9):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.07~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.08~1.7):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.09~1.6):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.1~1.5):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.15~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.2~1.8):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.3~1.7):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.4~1.6):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.5~1.5):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.6~1.4):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.7~1.3):1 ratio combination,

It is preferred that EGCG and bamboo-leaves flavones are using weight ratio as (0.8~1.2):1 ratio combination；

Specifically, for example preferred EGCG and bamboo-leaves flavones are using weight ratio as 0.05:1、0.06:1、0.07:1、0.08:1、 0.09:1、0.1:1、0.2:1、0.3:1、0.4:1、0.5:1、0.6:1、0.7:1、0.8:1、0.9:1、1:1、1.1:1、1.2:1、 1.3:1、1.4:1、1.5:1、1.6:1、1.7:1、1.8:1、1.9:1、2:1, etc.；

Also containing granule auxiliary material in the granule composite, the granule auxiliary material include it is following it is one or more into Point：Fructose, xylitol, oligofructose, polyfructosan, xylo-oligosaccharide, polydextrose, mannitol, sucrose, inverted sugar（That is grape The equal amount of mixture of sugar and fructose）, glucose, resistant dextrin, D-sorbite, maltose, isomalt, oligomeric sweet dew Sugar, solid polyethylene glycol（Such as polyethylene glycol-4000, polyethylene glycol -12000, polyethylene glycol-6000, Polyethylene glycol-2000 Deng）, dextrin, cyclodextrin, maltodextrin, hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose Element, pregelatinized starch, starch, starch sugar, lactose, vegetable fat powder, milk powder, plant protein powder, coffee, sodium carboxymethyl starch, albumen Sugar, Sucralose, Aspartame, acesulfame potassium, stachyose, neotame, stevioside, wherein the content of granule auxiliary material is with weight ratio Meter is more than 30%, and the preferably content of granule auxiliary material is more than 45% with weight ratio meter, and preferably the content of granule auxiliary material is with weight ratio Meter is more than 60%；

Further, the present invention provides a kind of preparation method of the granule containing EGCG and bamboo-leaves flavones, it includes：It will EGCG, bamboo-leaves flavones are uniformly mixed respectively with granule auxiliary material, then with ethanol water wet granulation, dry, whole grain, wherein The content of granula auxiliary material is more than 30% with weight ratio meter；Particularly, present invention offer is a kind of contains EGCG and bamboo-leaves flavones granule Preparation method, it includes：

(1) dispensing：EGCG, bamboo-leaves flavones are weighed by formula, first EGCG is added in granule auxiliary material and is uniformly mixed, then is added Enter bamboo-leaves flavones to be uniformly mixed, it is preferred to use equal increments hybrid mode is uniformly mixed；

(2) it pelletizes：By 75% ethanol solution softwood of prepared material in (1), wet granulation, 45~70 DEG C of dryings, Whole grain；

(3) it packs, examine to get granule of the present invention containing EGCG and bamboo-leaves flavones.

Further, capsule can be obtained in Capsules shell or by above-mentioned granule by above-mentioned granule is filling It is tabletted by tablet forming technique.

Further, the present invention also provides the composition of EGCG and bamboo-leaves flavones in following application：

Application in the drug for preparing protection cardiovascular and cerebrovascular, protection heart and brain tissues, improvement cardiac-cerebral ischemia；

Etc. synergistic effect, Yi Ji

Application in the drug of risk caused by preparation reduction generation myocardial infarction, cerebral apoplexy or angiocardiopathy, etc. Deng.

The composition of EGCG and bamboo-leaves flavones of the present invention have the advantages that following three aspect：

1st, bamboo-leaves flavones have special taste, and the slight bitter taste similar to Chinese medicine simultaneously has back sugariness, can improve well The bitter taste of EGCG so that oral person is easy to receive；

3rd, the composition of EGCG and bamboo-leaves flavones is in sides such as protection cardiovascular and cerebrovascular, protection heart and brain tissues, improvement cardiac-cerebral ischemias The synergistic effect in face and risk etc. caused by reduction generation myocardial infarction, cerebral apoplexy or angiocardiopathy have good Good synergistic function, for more comprehensively preventing cardiovascular and cerebrovascular disease advantageously.

For specific embodiment in the implementation process of the present invention, those of ordinary skill in the art are not departing from the present invention's The various embodiments generated on the basis of scope and spirits and modification are obvious and are easy to perform.It is logical It crosses 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, the composite tablet of EGCG and bamboo-leaves flavones and its preparation

Recipe quantity by weight percentage, contains：

EGCG 5%~25%, preferably 15%,

Bamboo-leaves flavones 10%~40%, preferably 30%,

Mannitol 20%~35%, preferably 30%,

Calcium monohydrogen phosphate 8%~20%, preferably 17%,

Sodium carboxymethyl starch 1%~10%, preferably 5%,

Appropriate hydroxypropyl cellulose aqueous solution, preferably 2.5% hydroxypropyl cellulose aqueous solution, with hydroxy propyl cellulose Element is calculated as 2%,

Magnesium stearate 0.5%~2%, preferably 1%；

Preparation method includes：EGCG, bamboo-leaves flavones, mannitol, calcium monohydrogen phosphate, sodium carboxymethyl starch are crossed into 80 mesh respectively Sieve preferably crosses 100 mesh, after being weighed by recipe quantity, is first uniformly mixed EGCG and mannitol, obtains A mixed-powders, separately by the leaf of bamboo Flavones and calcium monohydrogen phosphate are uniformly mixed, and obtain B mixed-powders, then by A mixed-powders, B mixed-powders and sodium carboxymethyl starch After mixing, it adds in 2.5% hydroxypropyl cellulose aqueous solution and softwood is made, cross 24 mesh sieve series grains, after 45~60 DEG C of dryings, 20 Mesh sieves whole grain, adds in the magnesium stearate of recipe quantity, mixing, tabletting to get.

Embodiment 2, the compound granule of EGCG and bamboo-leaves flavones and its preparation

Recipe quantity by weight percentage, contains：

EGCG 1%~10%, preferably 3%,

Bamboo-leaves flavones 1%~20%, preferably 10%,

Granule auxiliary material 85%~98%, preferably fructose 87%；

Wherein described granule auxiliary material includes following one or more ingredients：Fructose, xylitol, oligofructose, poly fruit Sugar, xylo-oligosaccharide, polydextrose, mannitol, sucrose, inverted sugar（That is the equal amount of mixture of glucose and fructose）, it is glucose, anti- Property dextrin, D-sorbite, maltose, isomalt, Oligomeric manna sugar, solid polyethylene glycol（Such as polyethylene glycol- 4000th, polyethylene glycol -12000, polyethylene glycol-6000, Polyethylene glycol-2000 etc.）, dextrin, cyclodextrin, maltodextrin, hydroxypropyl Group-beta-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, hypromellose, pregelatinized starch, starch, starch sugar, breast Sugar, vegetable fat powder, milk powder, plant protein powder, coffee, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, acesulfame potassium, Stachyose, neotame, stevioside, most preferably fructose or/and oligofructose, polyfructosan；

Preparation method includes：EGCG, bamboo-leaves flavones, granule auxiliary material are crossed to 80 mesh sieve respectively, 100 mesh is preferably crossed, presses After recipe quantity weighs, first EGCG with granule auxiliary material is uniformly mixed, then bamboo-leaves flavones are added in after mixing, with 75% second Alcoholic solution wet granulation, 45~70 DEG C of dryings, whole grain packaging, examine to get.Further, can by above-mentioned granule it is filling in Capsule or above-mentioned granule is tabletted by tablet forming technique is obtained in Capsules shell.

Embodiment 3, the compound capsule of EGCG and bamboo-leaves flavones and its preparation

Recipe quantity by weight percentage, contains：

EGCG 10%~30%, preferably 15%,

Bamboo-leaves flavones 15%~45%, preferably 40%,

Mannitol 15%~35%, preferably 26%,

Pregelatinized starch 8%~25%, preferably 12%,

Sodium carboxymethyl starch 1%~15%, preferably 5%,

The ethanol solution of polyvinylpyrrolidone is appropriate, preferably using polyvinylpyrrolidone as 1%,

Magnesium stearate 0.5%~2%, preferably 1%；

Preparation method includes：EGCG, bamboo-leaves flavones, mannitol, pregelatinized starch, sodium carboxymethyl starch are crossed 80 respectively Mesh sieves, and preferably sieves with 100 mesh sieve, after being weighed by recipe quantity, is first uniformly mixed EGCG and bamboo-leaves flavones, obtains A mixed-powders, treat With；Separately mannitol, pregelatinized starch, sodium carboxymethyl starch are uniformly mixed, obtain B mixed-powders, then by A mixed-powders with B mixed-powders, which are sufficiently mixed, uniformly, to be added in the ethanol solution of polyvinylpyrrolidone and is made softwood, crosses 20 mesh sieve series grains, 45~ 70 DEG C of drying, dry particl cross 18 mesh sieve whole grain, and stiffened fatty acid magnesium is uniformly mixed, fill to capsulae vacuus to get.

Embodiment 4, the compound granule of EGCG and bamboo-leaves flavones and its preparation

Recipe quantity by weight percentage, contains：

EGCG 1%~6%, preferably 2%,

Bamboo-leaves flavones 1%~10%, preferably 8%,

Maltodextrin 3%~10%, preferably 5%,

Other granule auxiliary materials 75%~95%, preferably fructose 85%；

Wherein described other granule auxiliary materials include following one or more ingredients：It is fructose, xylitol, oligofructose, more Fructooligosaccharides, xylo-oligosaccharide, polydextrose, mannitol, sucrose, inverted sugar（That is the equal amount of mixture of glucose and fructose）, grape Sugar, resistant dextrin, D-sorbite, maltose, isomalt, Oligomeric manna sugar, solid polyethylene glycol, dextrin, cyclodextrin, Hydroxypropyl-β-cyclodextrin, microcrystalline cellulose, carboxymethyl cellulose, hypromellose, pregelatinized starch, starch, starch Sugar, lactose, vegetable fat powder, milk powder, plant protein powder, coffee, sodium carboxymethyl starch, protein sugar, Sucralose, Aspartame, peace Match honey, stachyose, neotame, most preferably stevioside, fructose or/and oligofructose, polyfructosan；

Preparation method includes：EGCG, bamboo-leaves flavones, maltodextrin, other granule auxiliary materials are crossed to 80 mesh sieve respectively, it is excellent 100 mesh were selected, after being weighed by recipe quantity, were first uniformly mixed EGCG with maltodextrin, other granule auxiliary materials successively, Ran Houjia Enter bamboo-leaves flavones after mixing, with 75% ethanol solution wet granulation, 45~70 DEG C of dryings, whole grain packaging, examine to get.

Effect of the composition of embodiment 5, EGCG and bamboo-leaves flavones in terms of myocardial ischemia is improved

Animal：SD rats, half male and half female, 160~190g of weight.

Myocardial infarction and ischemia model：Rat urethane intraperitoneal injection of anesthesia is taken, lies on the back and is fixed on operating table, exposure tracheae is opened Lung ventilator is inserted in front, opens chest on the left of the breastbone at 3,4 rib cages, exposure heart, between left auricle of heart root and pulmonary artery circular cone with Needle threading ligation arteria coroaria sinistra, closes thoracic cavity, forms myocardial infarction and ischemia model.

Experimental method：Rat is randomly divided into model control group, administration group, wherein administration group is divided on the basis of normal feeding Oral administration gavage EGCG 6mg/kg, bamboo-leaves flavones 12mg/kg, EGCG and bamboo-leaves flavones weight ratio 1 are not given:2 composition L0mg/kg, each administration group successive administration carried out myocardial infarction and ischemia model in the 4th day, are given respectively after modeling success oral after 3 days Gavage EGCG 6mg/kg, bamboo-leaves flavones 12mg/kg, EGCG and bamboo-leaves flavones (weight ratio 1:2）Composition l2mg/kg, administration 180min afterwards removes heart immediately, with normal saline flushing, weighs and whole-heartedly weighs (g), atrium and major blood are cut off along coronary sulcus Ventricle is placed in refrigerator after freezing, in heart ligature hereinafter, being parallel to coronary artery ditch equably by the heart by pipe, satisfactory room weight (g) Room partial cross section is cut into 5, and every thickness about 1~2mm, the weight of 5 is the weight (g) in Zha Xia areas, is subsequently placed in four nitrogen of nitro It in azoles indigo plant (N-BT) dye liquor, is taken out after constant temperature dyeing 15min in 37 DEG C of water baths, normal myocardium is contaminated for skipper, the infarcted region heart Flesh is then not colored or light yellow.Draw infarcted region, non-infarcted region and the cavity range on every myocardium two sides.With paper-cut method, measure The every myocardium infarcted region on two sides and the weight (mg) of normal myocardium, the total weight for weighing up 5 are ventricle total weight (mg).Point The myocardial infarction percentage of whole-heartedly infarcted region, ventricle group infarcted region, Zha Xia areas infarcted region is not calculated（%）, comparison among groups are examined with t It tests, the results are shown in Table 1.

Influence of the composition of 1 EGCG of table and bamboo-leaves flavones to rats with myocardial ischemia myocardial infarct size

(, %, n=8)

Conclusion：The composition of EGCG and bamboo-leaves flavones of the present invention, can be significantly in the animal model of SD myocardial ischemia in rats Infarct size is reduced, shows good improvement myocardial ischemia, the effect for protecting cardiac muscle cell；Relative to model control group, The composition group of EGCG and bamboo-leaves flavones has highly significant difference, p<0.01；Relative to bamboo-leaves flavones group and EGCG groups, also have There are very significant difference, p<0.05.Show pharmaceutical composition of the present invention in the protrusion for improving myocardial ischemia, protecting cardiac muscle cell Effect.

Protective effect of the composition of embodiment 6, EGCG and bamboo-leaves flavones to cerebral ischemia-reperfusion neural cell injury

Local specific region acute cerebral ischemia in rats model is made using folder arteria cerebri media is closed, calculates dead neuronal cell Number observes the morphological change of neuron, from cell and the composition of Molecular level study EGCG and bamboo-leaves flavones in patron saint Effect through member and prevention cerebral ischemia.

Method：Wistar big white mouse, 150~200g of weight, half male and half female is random to be grouped, be divided into model group, EGCG to Medicine group, bamboo-leaves flavones administration group, EGCG and bamboo-leaves flavones composition administration group, every group 8.

First to rats underwent 10% chloral hydrate anesthesia (ip, 350mg.Kg^-1) after, skull is carefully pried open with instrument, exposure is simultaneously It closes folder arteria cerebri media and causes local specific region acute cerebral ischemia model, to close folder arteria cerebri media side as the (experiment of ischemic side Group), opposite side does not close folder as control (control group).

Each group 30min rows intraperitoneal injection drug before ischemic.All samples have drawn from representational correlation zone Domain, and fixed through 4% neutral formalin rapidly, conventional to be dehydrated, paraffin embedding, HE dyeing and HSP70 dyeing.With nerve after HE dyeing There is karyopycnosis, karyorrhexis in first cell, and karyolysis person is judged to neuronal death, and 5 high power field of view are taken in every slice, unites Meter dead cell accounts for the percentage of total cell, takes its average value.

HSP70 is one kind in HSP families, molecular weight 70KDa, its major function be protection it is various stress caused by Cellular damage and apoptosis, induction HSP70 high expression can mitigate the neure damage caused by cerebral ischemia.

Experiment packet：

（1）Model group：The isometric distilled water of intraperitoneal injection；

（3）EGCG administration groups：The isometric EGCG distilled water solutions of intraperitoneal injection, EGCG dosages 5mg/kg；

（4）Bamboo-leaves flavones administration group：The isometric bamboo-leaves flavones distilled water solution of intraperitoneal injection, bamboo-leaves flavones dosage 12mg/kg；

（5）EGCG and bamboo-leaves flavones composition administration group：The isometric EGCG of intraperitoneal injection and bamboo-leaves flavones composition (weight ratio 1:2.4) distilled water solution, EGCG and bamboo-leaves flavones composition dosage 12mg/kg.

As a result：It is shown in Table 2.

The composition of 2 EGCG of table and bamboo-leaves flavones is to cerebral morphology change, nerve cell death rate and HSP70 Expression (n=8)

As can be seen from Table 2, the composition of EGCG and bamboo-leaves flavones has good protective effect for rat cerebral ischemia, And protection brain tissue, protection nerve cell, mitigation brain tissue oedema degree, in nerve cell death rate, HSP70 expression data Aspect compared with independent EGCG administration groups, bamboo-leaves flavones administration group, has significant difference, p<0.05.Show combination of the present invention Object is in protection cardiovascular and cerebrovascular, the effect for protection heart and brain tissues, improving cardiac-cerebral ischemia, protecting heart and brain cell.

Effect of the composition of embodiment 7, EGCG and bamboo-leaves flavones to the bitter taste of improvement EGCG

It is 1 to take EGCG and bamboo-leaves flavones weight ratio:0.5、1:1、1:1.5、1:2 composition carries out bitter taste comparison.

The preparation of bitter taste reference substance：Respectively using the additive amount of maltodextrin as 0,10%, 30%, 50%, 70%, 90% EGCG original powders and the mixed uniformly powder of maltodextrin, respectively take 5g, add in 45 DEG C of hot water of 100ml, fully dissolve, and taste, point Bitter taste degree is not obtained labeled as 10.0 points, 9.0 points, 7.0 points, 5.0 points, 3.0 points, 1.0 points of bitter taste reference substance, highest It is 10.0 points, retains a decimal point, score value is higher, and characterization bitter taste is bigger.

Bitter taste comparative approach：Based on bitter taste reference substance, by 5 people to the trial test side of testing combination bitter taste Method compared with bitter taste reference substance, differentiates, gives a mark to testing combination bitter taste（Up to 10.0 points, retain one small Several points）, it is averaged, for comparing, is respectively compared the bitter taste of prepared composition.

Bitter taste compares data such as the following table 3.

Table 3

The composition of EGCG and bamboo-leaves flavones of the present invention it can be seen from 3 tables, compared with EGCG original powders, bitter taste is substantially Degree declines, and with the increase of bamboo-leaves flavones content in the composition, and bitter taste declines more；EGCG and bamboo-leaves flavones weight Than being 1:0.5、1:1 composition, bitter taste only have 60 or so the percent of EGCG original powders（p<0.05）, EGCG and the leaf of bamboo Flavones weight ratio is 1:1.5、1:2 composition, bitter taste is less than 50 the percent of EGCG original powders（p<0.01）；Display Go out the present composition has remarkable effect to the bitter taste for improving EGCG.

The application of the composition of EGCG and bamboo-leaves flavones described in embodiment 8, embodiment 1 to embodiment 4 in the following aspects：

Application in the drug for preparing protection cardiovascular and cerebrovascular, protection heart and brain tissues, improvement cardiac-cerebral ischemia；

Application in the drug of risk caused by preparation reduction generation myocardial infarction, cerebral apoplexy or angiocardiopathy.

Claims (6)

1. the pharmaceutical composition of a kind of EGCG and bamboo-leaves flavones, which is composite tablet, and recipe quantity is with weight hundred Divide than meter, contain：

EGCG 15%,

Bamboo-leaves flavones 30%,

Mannitol 30%,

Calcium monohydrogen phosphate 17%,

Sodium carboxymethyl starch 5%,

2.5% hydroxypropyl cellulose aqueous solution 2%, in terms of hydroxypropyl cellulose,

Magnesium stearate 1%；

Preparation method includes：EGCG, bamboo-leaves flavones, mannitol, calcium monohydrogen phosphate, sodium carboxymethyl starch are crossed to 80 mesh sieve respectively, After being weighed by recipe quantity, first EGCG and mannitol are uniformly mixed, obtain A mixed-powders, separately by bamboo-leaves flavones and calcium monohydrogen phosphate It is uniformly mixed, obtains B mixed-powders, then by A mixed-powders, B mixed-powders and sodium carboxymethyl starch after mixing, add in 2.5% hydroxypropyl cellulose aqueous solution is made softwood, crosses 24 mesh sieve series grains, and after 45~60 DEG C of drying, 20 mesh sieve whole grain, at addition The magnesium stearate just measured, mixing, tabletting to get.

2. the pharmaceutical composition of a kind of EGCG and bamboo-leaves flavones, which is compound granule, and recipe quantity is with weight Percentages contain：

EGCG 3%,

Bamboo-leaves flavones 10%,

Granule auxiliary material 87%；

Wherein described granule auxiliary material includes following one or more ingredients：Fructose, oligofructose, xylo-oligosaccharide, gathers xylitol Glucose, mannitol, sucrose, glucose, resistant dextrin；

Preparation method includes：EGCG, bamboo-leaves flavones, granule auxiliary material are crossed to 80 mesh sieve respectively, after being weighed by recipe quantity, first will EGCG is uniformly mixed with granule auxiliary material, then adds in bamboo-leaves flavones after mixing, with 75% ethanol solution wet granulation, 45 ~70 DEG C of dryings, whole grain packaging, examine to get.

3. the pharmaceutical composition of a kind of EGCG and bamboo-leaves flavones, which is compound capsule, and recipe quantity is with weight Percentages contain：

EGCG 15%,

Bamboo-leaves flavones 40%,

Mannitol 26%,

Pregelatinized starch 12%,

Sodium carboxymethyl starch 5%,

The ethanol solution 1% of polyvinylpyrrolidone, in terms of polyvinylpyrrolidone,

Magnesium stearate 1%；

Preparation method includes：EGCG, bamboo-leaves flavones, mannitol, pregelatinized starch, sodium carboxymethyl starch are crossed into 80 mesh respectively EGCG and bamboo-leaves flavones, after being weighed by recipe quantity, are first uniformly mixed, obtain A mixed-powders, for use by sieve；Separately by mannitol, pre- Gelling starch, sodium carboxymethyl starch are uniformly mixed, and obtain B mixed-powders, then that A mixed-powders and B mixed-powders is fully mixed Conjunction is uniform, and softwood is made in the ethanol solution for adding in polyvinylpyrrolidone, crosses 20 mesh sieve series grains, 45~70 DEG C of drying, dry particl Cross 18 mesh sieve whole grain, stiffened fatty acid magnesium is uniformly mixed, fill to capsulae vacuus to get.

4. the pharmaceutical composition of a kind of EGCG and bamboo-leaves flavones, which is compound granule, and recipe quantity is with weight Percentages contain：

EGCG 2%,

Bamboo-leaves flavones 8%,

Maltodextrin 5%,

Other granule auxiliary materials 85%；

Wherein described other granule auxiliary materials include following one or more ingredients：Fructose, xylitol, oligofructose, oligomeric wood Sugar, polydextrose, mannitol, sucrose, glucose, resistant dextrin；

Preparation method includes：EGCG, bamboo-leaves flavones, maltodextrin, other granule auxiliary materials are crossed to 80 mesh sieve respectively, by prescription After amount weighs, first EGCG with maltodextrin, other granule auxiliary materials is uniformly mixed successively, it is equal then to add in bamboo-leaves flavones mixing After even, with 75% ethanol solution wet granulation, 45~70 DEG C of dryings, whole grain packaging, examine to get.

5. claim 1 to any one described in claim 4 contains EGCG and the pharmaceutical composition of bamboo-leaves flavones is being made Application in the standby drug for improving myocardial ischemia.

6. claim 1 to any one described in claim 4 contains EGCG and the pharmaceutical composition of bamboo-leaves flavones is being made Application in the drug of standby protection ischemic cranial nerve cell.