CN104587260B - The composition of bamboo-leaves flavones and chitosan oligosaccharide, its preparation method and application - Google Patents
The composition of bamboo-leaves flavones and chitosan oligosaccharide, its preparation method and application Download PDFInfo
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- CN104587260B CN104587260B CN201510042918.7A CN201510042918A CN104587260B CN 104587260 B CN104587260 B CN 104587260B CN 201510042918 A CN201510042918 A CN 201510042918A CN 104587260 B CN104587260 B CN 104587260B
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- bamboo
- leaves flavones
- chitosan oligosaccharide
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- composition
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Abstract
The present invention provides the healthy product composition containing bamboo-leaves flavones and chitosan oligosaccharide, the formulation of the composition is any pharmaceutical dosage form of acceptable in pharmacy, wherein described bamboo-leaves flavones also include its pharmaceutically acceptable salt or solvate, its combination also includes bamboo-leaves flavones and chitosan oligosaccharide single preparation is respectively prepared, and two kinds of single preparations are packaged in same medicine box；Invention further provides the preparation method of the composition; and the application in the medicine of antiatherosclerosis is prepared, the application in preparation improves myocardial ischemia and improves cerebral ischemia, protects the medicine of heart and brain cell, reducing blood lipid, preventing and treating cardiovascular and cerebrovascular disease.
Description
Technical field
The present invention relates to a kind of healthy product composition, and its preparation method and application, specifically bamboo-leaves flavones and chitosan oligosaccharide
Composition, with and its preparation method and application.It is healthy product composition of the present invention, including but not limited to medicine, medical
Food, health food or functional food, ordinary food etc..
Background technology
Bamboo-leaves flavones, it is that the biology with physiologically active 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, improve cerebral ischemia, regulation blood fat, reduce the effect of blood viscosity, there is preventing and treating cardiovascular and cerebrovascular disease, anti-oxidant, anti-inflammatory
And the function that regulation is immune, when human body lacks, easily cause heart and cerebral function not entirely, the production of the disease such as vascular sclerosis
It is raw.
Chitosan oligosaccharide:Also referred to as Chitosan poly oligosaccharide, chitosan oligomer, it is using chitosan as raw material, is refined into through enzymolysis process, point
Sub- amount≤3200Da, is the basic amine group oligosaccharide of unique positively charged cation in nature, and its molecular weight is low, water-soluble
Get well, be easily absorbed by the body, bioactivity height, having reducing blood lipid, protection cardiac muscle cell, regulation immune（Humoral immunity and cell are exempted from
Epidemic disease）, protection function of intestinal canal, protection liver function, Green Tea Extract peroxidatic reaction of lipid, it is antitumor, hypoglycemic, promote calcium uptake
Acted on bone health etc., it is particularly significant for health.
Bamboo-leaves flavones or chitosan oligosaccharide have been machined on various health foods, such as capsule, tablet, it has not been found that the leaf of bamboo
The composition of flavones and chitosan oligosaccharide.
Detrimental effect is, on the one hand, the stability of bamboo-leaves flavones is simultaneously bad, especially in water environment, the processing of preparation
During, often in aqueous environment, and use and carried out under heating condition, the degraded of bamboo-leaves flavones is exacerbated, to preparation
It is safe to use to bring unfavorable and hidden danger；On the other hand, acted on the effect of bamboo-leaves flavones relatively weak, it usually needs with compound form
Improve the effect of its curative effect.
The content of the invention
Inventor surprisingly has found, the combination of bamboo-leaves flavones and chitosan oligosaccharide, is on the one hand advantageous to the stability of bamboo-leaves flavones,
On the other hand, its curative effect of medication is also improved.
It is an object of the invention to provide a kind of healthy product composition containing bamboo-leaves flavones and chitosan oligosaccharide, the bamboo-leaves flavones
Also include its pharmaceutically acceptable salt or solvate.
It is a further object to provide the preparation method of above-mentioned composition；
The invention further relates to application of the above-mentioned composition in medicine, medical usage.
The present composition includes two kinds of combinations：
A kind of combination is that have bamboo-leaves flavones and chitosan oligosaccharide in the form of compound preparation, and the agent of the medicine
Type is any pharmaceutical dosage form of acceptable in pharmacy.Using corresponding pharmaceutical carrier or auxiliary material, using different preparation works
Skill may be manufactured without same compound medicinal formulation.It should be appreciated that compound preparation refers to using bamboo-leaves flavones and chitosan oligosaccharide as medicine
Active ingredient and single preparation is made, can be acceptable any pharmaceutical dosage form in pharmacy, preferred oral formulations, example
Such as oral solution, tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet, etc.), hard capsule (bag
Include capsulae enterosolubilis), soft capsule, granule, pill, micropill preparation (including enteric-coated micro-pill), pill, dry suspensoid agent, dry syrup
Agent, powder, oral administration mixed suspension and the formulation such as oral quick-release or 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 drip-feed)；Also include ointment, gel, emulsion agent, the latex of external preparation for skin
Agent, patch, etc.；Can also be the formulations such as quick-release, the slow-release controlled-release of any of the above formulation, 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..Especially, 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 (including injection
Powder-injection and parenteral solution)；
Another combination is that bamboo-leaves flavones and chitosan oligosaccharide are respectively prepared into single preparation, when in use, Huan Zheke
With successively medication successively, medication simultaneously after can also the preparation of separated bamboo-leaves flavones be mixed with the preparation of chitosan oligosaccharide, with most
Reach the purpose using composition of medicine of the present invention eventually, it is necessary to, in order to facilitate patient medication and represent drug regimen
Feature, two kinds of single preparations should be packaged in same medicine box；Further, bamboo-leaves flavones are individually to make with chitosan oligosaccharide
During agent, both pharmaceutical dosage forms can with identical or different, as bamboo-leaves flavones piece and chitosan oligosaccharide tablet medicament composition,
Bamboo-leaves flavones capsule and chitosan oligosaccharide capsule pharmaceutical composition, bamboo-leaves flavones piece and chitosan oligosaccharide capsule pharmaceutical composition, bamboo-leaves flavones
Capsule and the formulation such as chitosan oligosaccharide tablet medicament composition or the quick-release of any of the above formulation, slow-release controlled-release, such as orally
Dispersible tablet, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Especially
Ground, prepared by means known in the art preferably for prepare pharmacy on use oral solution, tablet (including dispersible tablet,
Slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), injection
Agent (including powder ampoule agent for 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 component 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, bamboo-leaves flavones and chitosan oligosaccharide can be administered in the form of either alone or in any combination, preferably by bamboo-leaves flavones and chitosan oligosaccharide simultaneously
Administration is sequentially administered with independent medicine type, is most preferably administered simultaneously.
It is preferred that give the drug regimen of the present invention in the form of single combination preparation, such as oral solution, tablet, in tablet
Special is double-layer tablets, chewable tablets, for another example capsule, pulvis or granule, liquid preparation, spirituosity pharmaceutical solutions, medicinal tea, etc.
Deng.
Particularly, the pharmaceutical composition provided by the invention containing bamboo-leaves flavones and chitosan oligosaccharide, when pharmaceutical dosage form be tablet,
During the solid pharmaceutical preparations such as capsule, pulvis or granule, wherein bamboo-leaves flavones or chitosan oligosaccharide be with composition made of micronized form,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are crushed by low-temperature airflow broken wall crushing technology, its powder size is more than 800 mesh, excellent
Powder size is selected in 800~1000 mesh, or even the granularity of preferably powder is more than 1000 mesh.
Another aspect of the present invention provides bamboo-leaves flavones and chitosan oligosaccharide with existing for the ratio of the drug dose to act synergistically
Present invention combination.
Another aspect of the present invention provides bamboo-leaves flavones with chitosan oligosaccharide with the combination of arbitrary proportion, preferably with synergy
Present invention combination existing for the ratio of dosage, either preferably with chitosan oligosaccharide can protect bamboo-leaves flavones stability in the formulation or
The ratio for improving the dosage of stability of the said preparation in preparation process is processed is present in combination of the present invention, and bamboo-leaves flavones are few with shell
Sugar is using weight ratio as (0.1~5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.2~4.5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.3~4.5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.4~4.5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.5~4):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.7~3.5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.8~3.3):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (0.9~3):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (1~2.8):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (1.2~2.7):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (1.3~2.6):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (1.4~2.5):1 ratio combination,
It is preferred that bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as (1.5~2.5):1 ratio combination,
Specifically, for example preferred bamboo-leaves flavones and chitosan oligosaccharide are using weight ratio as 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、2.1:1、2.2:1、2.3:1、2.4:1、2.5:1、2.6:1、2.7:1、2.8:1、2.9:1、3:1、3.1:1、
3.2:1、3.3:1、3.4:1、3.5:1、3.6:1、3.7:1、3.8:1、3.9:1、4:1、4.1:1、4.2:1、4.3:1、4.4:1、
4.5:1、4.6:1、4.7:1、4.8:1、4.9:1、5:1, etc..
The bamboo-leaves flavones also include its pharmaceutically acceptable salt or solvate, and bamboo-leaves flavones and shell are few in composition
The dosage of sugar can typically use and show that the amount for treating or preventing action effect is than advantageous during its exclusive use.
The dosage that bamboo-leaves flavones are orally applicable is generally daily 100~2500mg levels of being grown up and gives the compound, preferably
Daily 200~2000mg singles give the compound at twice, for example, 250mg, 300mg, 400mg, 500mg, 600mg,
800mg, 1000mg, 1500mg, 1800mg, 2000mg, and the chitosan oligosaccharide of effective dose is given, such as 100mg, 200mg,
300mg, 400mg, 500mg, 600mg, 800mg, 1000mg, 1800mg, 2000mg, etc..
It should be appreciated that the composition of the invention containing bamboo-leaves flavones and chitosan oligosaccharide, can also optionally contain other medicines
Thing functional component, such as the red sage root, Ligusticum wallichii, ginkgo leaf, safflower or their extract.
Preferably, the pharmaceutical composition of bamboo-leaves flavones and chitosan oligosaccharide, wherein it is preferred that in per unit preparation containing 50~
2000mg bamboo-leaves flavones and 50~1000mg chitosan oligosaccharides,
For example, contain 50~500mg bamboo-leaves flavones and 50~200mg chitosan oligosaccharides in per unit preparation,
For example, contain 200~500mg bamboo-leaves flavones and 100~200mg chitosan oligosaccharides in per unit preparation；
Specifically, contain 100mg bamboo-leaves flavones and 50mg chitosan oligosaccharides in per unit preparation,
Or contain 125mg bamboo-leaves flavones and 125mg chitosan oligosaccharides in per unit preparation,
Or contain 150mg bamboo-leaves flavones and 50mg chitosan oligosaccharides in per unit preparation,
Or contain 200mg bamboo-leaves flavones and 100mg chitosan oligosaccharides in per unit preparation,
Or contain 250mg bamboo-leaves flavones and 125mg chitosan oligosaccharides in per unit preparation,
Or contain 500mg bamboo-leaves flavones and 125mg chitosan oligosaccharides, etc. in per unit preparation.
Although the active component of drug regimen can be given in the form of chemical raw material, preferably given in the form of Pharmaceutical composition
Give.Pharmaceutical composition of the present invention includes bamboo-leaves flavones and the chitosan oligosaccharide, and one or more pharmaceutically acceptable carriers
Or the drug regimen of the invention of excipient.These carriers must be acceptable, you can it is compatible with other components of formula, and
It is nontoxic to its recipient.When individually giving each component of said composition, they are typically individually Pharmaceutical composition form.Remove
Be otherwise noted, the signified composition of the present invention refer to the drug regimen containing bamboo-leaves flavones and chitosan oligosaccharide or wherein bamboo-leaves flavones with
The composition of the drug regimen of each component of chitosan oligosaccharide.
Preferably, the combination of bamboo-leaves flavones and chitosan oligosaccharide usually unit dosage form has one or more pharmaceutically
The Pharmaceutical composition of acceptable carrier, the bamboo-leaves flavones and the dosage of chitosan oligosaccharide contained in conventional unit formulation are in above institute
It is clear and definite in stating.
Using corresponding, different pharmaceutical carrier and preparation technology, 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 formulation, ensure medicine safely, effectively with the factor such as stable, and the physics and chemistry according to different pharmaceutical dosage forms and medicine itself
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 pharmaceutical carrier is applied in combination, optionally including excipient or diluent, such as microcrystalline cellulose, mannitol, plant fat
End, lactose, pregelatinized starch, starch, dextrin, calcium phosphate, calcium monohydrogen phosphate, hydroxypropyl methyl cellulose, sucrose, dextran,
Poloxamer, sodium chloride, sorbierite, glucose, fructose, water, polyethylene glycol, propane diols, glycerine, cyclodextrin and its derivative,
Etc.；For oral solid formulation, it is also an option that property includes adhesive, such as PVP (polyvinylpyrrolidone), first
Base cellulose, hydroxymethyl cellulose, HPMC, hydroxypropyl cellulose, hydroxyethyl cellulose, gelatin, guar gum, Huang
Virgin rubber, etc.；Also include lubricant, such as magnesium stearate, stearic acid, talcum powder, stearyl fumarate, dodecyl sulphate
Sodium, etc.；Also optionally include disintegrant, such as sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose
Plain sodium, PVPP, Ac-Di-Sol, crosslinked carboxymethyl fecula sodium, pregelatinized starch, etc.；
Also optionally include surfactant or cosolvent, such as lauryl sodium sulfate, Tween-80, etc.；It can also wrap
Include pH values conditioning agent or buffer or cosolvent, for example, phosphate buffer, citric acid, sodium citrate, acetate buffer,
Watery hydrochloric acid, lactic acid, sodium carbonate, sodium hydroxide, alkaline organic compound, such as arginine, lysine, meglumine, tromethamine, etc.
Deng；Also optionally include preservative, such as sodium benzoate, potassium sorbate, methyl p-hydroxybenzoate, P-hydroxybenzoic acid
Propyl ester, etc.；Also optionally include stabilizer and antioxidant, such as metal chelating agent selects ethylenediamine tetra-acetic acid and its salt
(mosatil, natrium adetate) etc., sodium sulfite, sodium pyrosulfite, vitamin C, vitamin E, etc.；Also it may be selected
Property includes taste conditioning agent, such as maltitol, fructose, sucrose, saccharin sodium, flavoring orange essence, strawberry essence, etc.；In addition
It may also include other conventional, appropriate additives.Can be film bag it is also understood that when agent type is tablet or capsule
Clothing.For the material of film coating, including suitable coating agent, such as HPMC, hydroxyethyl cellulose, hydroxypropyl
Cellulose, hydroxypropyl methylcellulose phthalate (enteric-coating material), etc.；Plasticizer, such as poly- second can also be included
Glycol, triethyl citrate, etc.；Also optionally include suitable solubilizer, such as Polyoxyethylene Sorbitan Monooleate；It can also include
Suitable pigment, such as titanium dioxide, various iron oxide, pink pigment, etc..It should be appreciated that above-mentioned " optionally wrap
Include " refer to optionally select to use, can also be without using.
Particularly, the pharmaceutical composition of bamboo-leaves flavones of the present invention and the chitosan oligosaccharide, bamboo-leaves flavones and chitosan oligosaccharide
Chemical composition can be different on medicament releasing pattern, such as bamboo-leaves flavones can be sustained or the form of controlled release occurs, and shell is few
Sugar can also be sustained or the form of controlled release occurs, to improve bamboo-leaves flavones and time difference of the chitosan oligosaccharide in terms of action or metabolism
Caused blood concentration does not act synergistically.
In the present patent application, " composition " refer to described one or more compounds or its physiologically/can pharmaceutically connect
The salt or prodrug received, with other chemical compositions, such as the mixing that physiologically/pharmaceutically acceptable carrier or excipient are formed
Thing, the purpose of pharmaceutical composition are advantageous for the administration of medicine, carrying, preservation；" administration " mentioned here refers to prevent
Or treatment disease and to organism（Including patient or healthy population）Deliver described compound, its pharmaceutically useful salt or its is molten
Agent compound；" the per unit preparation " refers to the preparation unit of minimum package or minimum form of medication, such as each bottle of oral administration solution,
Each capsule, each tablet or pill, each bag of granule or pulvis, each injection or parenteral solution, each bottle of note
Penetrate agent or parenteral solution, each piece of suppository, each bottle of eye drops, each pipe ointment, etc..
Another aspect, it has been found that when bamboo-leaves flavones are applied in combination with chitosan oligosaccharide, it shows unexpected excellent
Point, the especially drug regimen show outstanding, unexpected in improvement myocardial ischemia and improvement cerebral ischemia, protection heart and brain
The effect of cell.Preferably, the pharmaceutical composition of bamboo-leaves flavones and chitosan oligosaccharide of the present invention, heart and brain blood is treated or prevented for preparing
The medicine of pipe disease, the application in the medicine of antiatherosclerosis is prepared, and myocardial infarction, cerebral apoplexy occurs reducing
Or the application of risk caused by angiocardiopathy, it is particularly, thin for improving myocardial ischemia and improving cerebral ischemia, protection heart and brain
Born of the same parents, reducing blood lipid, preventing and treating cardiovascular and cerebrovascular disease, etc..
Therefore, another aspect, the present invention, which provides, a kind of to be improved myocardial ischemia and improves cerebral ischemia, protection heart and brain cell
Pharmaceutical composition, it contains bamboo-leaves flavones and chitosan oligosaccharide, wherein the bamboo-leaves flavones also include its pharmaceutically acceptable salt or
Solvate, the chitosan oligosaccharide also include its pharmaceutically acceptable salt or solvate.It will be appreciated by those skilled in the art that
, it is this to improve myocardial ischemia and improve cerebral ischemia, protect in the pharmaceutical composition of heart and brain cell, bamboo-leaves flavones and chitosan oligosaccharide
Combination, the dosage ratio in per unit preparation and content, foregoing content is just the same with the present invention.
Further, present invention also offers bamboo-leaves flavones and the preparation method of the pharmaceutical composition of chitosan oligosaccharide, it includes
Bamboo-leaves flavones and chitosan oligosaccharide are mixed with pharmaceutically acceptable pharmaceutical carrier and acceptable any medicine in pharmacy is made
Preparation, such as bamboo-leaves flavones and chitosan oligosaccharide mix (dry granulating machine processing), wet method with pharmaceutical carrier dry powder blend, dry granulation
Granulation mixing is (with water or ethanol solution wet granulation), liquid or semisolid mixing (content, the dripping pill dropping liquid of such as soft capsule
Mixing) etc., preferable pharmaceutical dosage form be tablet (including dispersible tablet, enteric coatel tablets, chewable tablets, oral disnitegration tablet, effervescent tablet etc.),
It is hard capsule (including capsulae enterosolubilis), soft capsule, granule, pill, micropill preparation (including enteric-coated micro-pill), pill, dry-mixed
Suspension, oral solution, dry syrup, powder, oral administration mixed suspension and the formulation such as oral quick-release or sustained release or controlled release, note
Penetrate and be can also be with powder-injection (including the filling powder of Injectable sterile, freeze drying powder injection), aqueous solution injection, injection with Portugal
Grape sugar, sodium chloride, fructose, inverted sugar, xylitol or maltose etc. use as the intravenous injection of osmotic pressure regulator (including quiet
Arteries and veins is injected and drip-feed) the aqueous solution or the formulation such as the quick-release of any of the above formulation, slow-release controlled-release, such as mouth
The dispersible tablet of clothes, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets, born of the same parents rise particle, etc..Especially
Ground, prepared by means known in the art preferably for prepare tablet (including dispersible tablet, slow-release tablet, the intestines used in pharmacy
Molten, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, spansule), oral solution, injection
Agent (including powder ampoule agent for injection and parenteral solution) etc.；Or
The bamboo-leaves flavones and the preparation method of the pharmaceutical composition of chitosan oligosaccharide that the present invention also provides, it is included bamboo-leaves flavones
Single pharmaceutical preparation is mixed and made into pharmaceutically acceptable pharmaceutical carrier respectively with chitosan oligosaccharide, and by two kinds of single medicines
Thing preparation is packaged in same medicine box, and preferable pharmaceutical dosage form is that (including dispersible tablet, enteric coatel tablets, chewable tablets, oral cavity collapse tablet
Solve piece, effervescent tablet etc.), hard capsule (including capsulae enterosolubilis), soft capsule, granule, pill, (including enteric is micro- for micropill preparation
Ball), pill, dry suspensoid agent, oral solution, dry syrup, powder, oral administration mixed suspension and oral quick-release or sustained release
Or the formulation such as controlled release, powder ampoule agent for injection (including the filling powder of Injectable sterile, freeze drying powder injection), aqueous solution injection, note
Penetrate agent and can also be using glucose, sodium chloride, fructose, inverted sugar, xylitol or maltose etc. and be used as the quiet of osmotic pressure regulator
Arteries and veins injection uses the aqueous solution of (including intravenous injection and drip-feed).Can also be the quick-release of any of the above formulation, sustained release,
The formulations such as controlled release, for example, oral dispersible tablet, sustained release tablets, spansule, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets,
Effervescence granular, etc..Especially, prepared by means known in the art preferably for prepare pharmacy on use tablet (including
Dispersible tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral disnitegration tablet, special-shaped tablets), capsule (including soluble in the stomach, enteric, sustained release glue
Capsule), oral solution, injection (including powder ampoule agent for injection and parenteral solution) etc..
Preferably, the present invention provides a kind of liquid composite containing bamboo-leaves flavones, chitosan oligosaccharide and water, the bamboo-leaves flavones
With chitosan oligosaccharide using weight ratio as (0.1~5):1 ratio combination, the content of the composition reclaimed water are more than 70% with weight ratio meter,
Further, the above-mentioned liquid composite containing bamboo-leaves flavones, chitosan oligosaccharide and water of the present invention, can also contain sweetener, institute
State sweetener and be selected from xylitol, stevioside, fructose, glucose, sucrose, Sucralose, D-sorbite, fructose syrup, albumen
At least one of sugar, Aspartame, acesulfame potassium, stachyose, neotame, honey, polyglucose.
Further, the present invention provides a kind of preparation method of the liquid composite containing bamboo-leaves flavones, chitosan oligosaccharide and water,
It includes：Bamboo-leaves flavones, chitosan oligosaccharide are mixed with water and uniform liquid is made, the content of its reclaimed water is more than with weight ratio meter
70%；Particularly, the present invention provides a kind of preparation method of the liquid composite containing bamboo-leaves flavones, chitosan oligosaccharide and water, and it is wrapped
Include：
(1) dispensing：Bamboo-leaves flavones, chitosan oligosaccharide are weighed by formula, is added in purified water, is stirred and is uniformly dispersed, constant volume
To required output；
(2) dissolve：PH adjusting agent is added in the liquid prepared in (1), making the pH of liquid, stirring is equal 5.5~7.0
Solution that is even, being clarified；
(3) filling, sterilizing：Solution to be filtered through 500~1000 mesh, vacuum outgas is canned, sealing, and at 85~135 DEG C
Under the conditions of sterilize 4 seconds~35 minutes；
(4) pack, examine, produce product of the present invention；
The pH adjusting agent includes following one or more compositions：Arginine, lysine, meglumine, tromethamine, hydrogen-oxygen
Change sodium, potassium hydroxide.
Further, the present invention also provides bamboo-leaves flavones and the composition of chitosan oligosaccharide is used to prepare treatment or prevention heart and brain
Application in the medicine of vascular diseases, the application in the medicine of antiatherosclerosis is prepared, and preparing reduction
Applied in the medicine of myocardial infarction, cerebral apoplexy or risk caused by angiocardiopathy, particularly, improve myocardial ischemia for preparing
With improve cerebral ischemia, protection heart and brain cell, reducing blood lipid, prevent and treat application in the medicine of cardiovascular and cerebrovascular disease.
It has been found that when bamboo-leaves flavones are applied in combination with chitosan oligosaccharide, it shows the advantages of unexpected, especially the medicine
Thing combination show it is outstanding, unexpected improve myocardial ischemia and improve cerebral ischemia, protect heart and brain cell effect, with
And the effect in antiatherosclerosis.Preferably, the pharmaceutical composition of bamboo-leaves flavones and chitosan oligosaccharide of the present invention, it is anti-dynamic preparing
Application in the medicine of pulse atherosclerosis, in improvement myocardial ischemia and improvement cerebral ischemia is prepared, protect the medicine of heart and brain cell
Application.
For embodiment in the implementation process of the present invention, those of ordinary skill in the art are not departing from the present invention's
Caused various embodiments and modification are obvious and are easy to perform on the basis of scope and spirits.It is logical
Cross the following examples to be further elaborated with come application to the present invention etc., it is not intended that limit of the embodiment to the present invention
System.
Embodiment 1, bamboo-leaves flavones chitosan oligosaccharide oral administration solution and its preparation
Recipe quantity by weight percentage, contains：
Bamboo-leaves flavones 0.5%~2.5%, preferably 0.8%,
Chitosan oligosaccharide 0.5%~5%, preferably 2%,
Sucralose 0~0.05%, preferably 0.015%,
Appropriate arginine, pH to 4.5~7.5 is adjusted,
Purified water adds to 100%；
Prepare：(1) dispensing：Bamboo-leaves flavones, chitosan oligosaccharide are weighed by formula, is added in purified water, is stirred and is uniformly dispersed,
It is settled to required output；
(2) dissolve：Arginine is added in the liquid prepared in (1), makes the pH of liquid 4.5~7.5, preferably
PH6.5, Sucralose is added, is completely dissolved, stirs, the solution clarified；
(3) filling, sterilizing：Solution to be filtered through 500~1000 mesh, vacuum outgas is canned, sealing, and at 85~135 DEG C
Under the conditions of sterilize 4 seconds~35 minutes, sterilized 4~10 seconds preferably under the conditions of 135 DEG C；
(4) pack, examine, produce bamboo-leaves flavones chitosan oligosaccharide oral administration solution.
Embodiment 2, bamboo-leaves flavones chitosan oligosaccharide oral administration solution and its preparation
Recipe quantity by weight percentage, contains：
Bamboo-leaves flavones 0.5%~2%, preferably 1%,
Chitosan oligosaccharide 0.5%~2.5%, preferably 1%,
Fructose 0~10%, preferably 7%,
Glucose 0~10%, preferably 7%,
Appropriate lysine, pH to 4.5~7.5 is adjusted,
Purified water adds to 100%；
Prepare：(1) dispensing：Bamboo-leaves flavones, chitosan oligosaccharide are weighed by formula, is added in purified water, is stirred and is uniformly dispersed,
It is settled to required output；
(2) dissolve：Lysine is added in the liquid prepared in (1), is completely dissolved, is stirred, the solution clarified,
Fructose, glucose are added, is stirred after being completely dissolved, makes the pH of liquid in 4.5~7.5, preferably pH6.5；
(3) filling, sterilizing：Solution to be filtered through 500~1000 mesh, vacuum outgas is canned, sealing, and at 85~135 DEG C
Under the conditions of sterilize 4 seconds~35 minutes, sterilized 4~10 seconds preferably under the conditions of 135 DEG C；
(4) pack, examine, produce bamboo-leaves flavones chitosan oligosaccharide oral administration solution.
Embodiment 3, bamboo-leaves flavones chitosan oligosaccharide tablet and its preparation
Recipe quantity by weight percentage, contains：
50~100g of bamboo-leaves flavones,
50~80g of chitosan oligosaccharide,
100~160g of mannitol,
50~85g of calcium monohydrogen phosphate,
10~18g of sodium carboxymethyl starch,
2.5% hydroxypropyl cellulose aqueous solution is appropriate,
5~8g of magnesium stearate,
Prepare：Bamboo-leaves flavones, chitosan oligosaccharide, mannitol, calcium monohydrogen phosphate, sodium carboxymethyl starch are crossed into 100 mesh sieves respectively, by place
Side amount weigh after, first bamboo-leaves flavones and chitosan oligosaccharide are well mixed, obtain A mixed-powders, it is stand-by, separately by sodium carboxymethyl starch with
Calcium monohydrogen phosphate is well mixed by the equivalent method of progressively increasing, and is then well mixed with mannitol, obtains B mixed-powders, then by A mixed powders
End is well mixed with B mixed-powders, adds 2.5% hydroxypropyl cellulose aqueous solution and softwood is made, and crosses the granulation of 24 mesh sieves, and 60 DEG C dry
After dry, 20 mesh sieve whole grains, the magnesium stearate of recipe quantity added, is mixed, is pressed into 1000, produces.
Embodiment 4, bamboo-leaves flavones chitosan oligosaccharide chewable tablets and its preparation
Recipe quantity by weight percentage, contains：
50~100g of bamboo-leaves flavones,
80~150g of chitosan oligosaccharide,
100~300g of xylitol,
300~900g of vegetable fat powder,
5~8g of magnesium stearate,
Prepare：Using the direct mixed pressuring plate of dry method, bamboo-leaves flavones, chitosan oligosaccharide are crossed into 100 mesh sieves respectively, weighed by recipe quantity
Afterwards, first bamboo-leaves flavones and chitosan oligosaccharide are well mixed, obtain A mixed-powders, it is stand-by, separately xylitol is mixed with vegetable fat powder
It is even, B mixed-powders are obtained, then A mixed-powders are well mixed with B mixed-powders, add the magnesium stearate of recipe quantity, are mixed
It is even, 1000 are pressed into, produces bamboo-leaves flavones chitosan oligosaccharide chewable tablets.
Embodiment 5, bamboo-leaves flavones chitosan oligosaccharide capsule and its preparation
Recipe quantity by weight percentage, contains：
50~200g of bamboo-leaves flavones,
80~150g of chitosan oligosaccharide,
50~100g of mannitol,
50~100g of pregelatinized starch,
5~10g of sodium carboxymethyl starch,
70% ethanol solution of 3% polyvinylpyrrolidone is appropriate,
2~5g of magnesium stearate,
Prepare：Bamboo-leaves flavones, chitosan oligosaccharide, mannitol, pregelatinized starch, sodium carboxymethyl starch are crossed into 100 mesh sieves respectively, pressed
After recipe quantity weighs, first bamboo-leaves flavones and chitosan oligosaccharide are well mixed, obtain A mixed-powders, it is stand-by；Separately by mannitol, pre- glue
Change starch, sodium carboxymethyl starch are well mixed, and are obtained B mixed-powders, are then sufficiently mixed A mixed-powders and B mixed-powders
Uniformly, softwood is made in 70% ethanol solution for adding the polyvinylpyrrolidone of the aqueous solution 3%, crosses the granulation of 20 mesh sieves, 60 DEG C of drying, does
Particle crosses 18 mesh sieve whole grains, and stiffened fatty acid magnesium is well mixed, and fills to 1000 capsules, produces.
The stability study of embodiment 6, bamboo-leaves flavones of the present invention and chitosan oligosaccharide composition
Fully according to the preferred amounts formula of embodiment 1, bamboo-leaves flavones chitosan oligosaccharide solution is made by the preparation method；Separately
Outside, chitosan oligosaccharide being replaced with sucrose, the preferred amounts formula of other compositions and embodiment 1 is just the same, using same preparation method,
Bamboo-leaves flavones sucrose solution is obtained, the heating of two kinds of solution is boiled and thawing 3 times repeatedly, respectively the general flavone before and after contrast operation
Content and states of matter change, analyze and compare its stability.The measure of general flavone content uses aluminum nitrate natrium nitrosum colorimetric method, with
Rutin is standard specimen, is determined at 510nm wavelength, as a result such as table 1 below.
Table 1
| Compare content | General flavone content | 20min is boiled in heating | Thawing 3 times repeatedly |
| Bamboo-leaves flavones chitosan oligosaccharide solution prepared by embodiment 1 | Decline 0.91% | Without significant change | Without significant change |
| Bamboo-leaves flavones sucrose solution | Decline 7.69% | A small amount of Precipitation | More Precipitation, liquid layered, irregular colour are even |
As can be seen from Table 1, the stability of bamboo-leaves flavones of the present invention and chitosan oligosaccharide composition solution is significantly higher than conventional bamboo
Leaf flavonoids solution, show that chitosan oligosaccharide has the function that very significantly to protect bamboo-leaves flavones stability（p<0.001）, prevent it
Degraded；In addition, also there is good protective effect for the stability of the states of matter of solution.
Effect of the composition of embodiment 7, bamboo-leaves flavones and chitosan oligosaccharide in terms of myocardial ischemia is improved
Animal：SD rats, male and female half and half, 160~190g of body 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, is opening chest on the left of breastbone at 3,4 ribs, 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 bamboo-leaves flavones 10mg/kg, chitosan oligosaccharide 10mg/kg, bamboo-leaves flavones and chitosan oligosaccharide are not given（1:1）Composition
L0mg/kg, each administration group successive administration carried out myocardial infarction and ischemia model in the 4th day, given respectively after modeling success oral after 3 days
Gavage bamboo-leaves flavones 10mg/kg, chitosan oligosaccharide 10mg/kg, bamboo-leaves flavones and chitosan oligosaccharide（1:1）Composition l0mg/kg, after administration
180min, heart is removed immediately, with normal saline flushing, weigh and whole-heartedly weigh (g), atrium and major blood vessel are cut off along coronary sulcus,
Satisfactory room weight (g), ventricle is placed in refrigerator after freezing, below heart ligature, parallel to coronary artery ditch equably by ventricle
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 nitro tetrazole
In blue (N-BT) dye liquor, taken out in 37 DEG C of water baths after constant temperature dyeing 15min, normal myocardium dye is skipper, and infarcted region is myocardium
It is then not colored or light yellow.Draw the infarcted region, non-infarcted region and cavity scope on every myocardium two sides.It is every with paper-cut method, measurement
The infarcted region on piece cardiac muscle two sides and the weight (mg) of normal myocardium, the gross weight for weighing up 5 are ventricle gross weight (mg).Respectively
Calculate whole-heartedly infarcted region, ventricle group infarcted region, the myocardial infarction percentage of Zha Xia areas infarcted region（%）, compare between group and examined with t,
It the results are shown in Table 2.
Influence of the composition of the bamboo-leaves flavones of table 2 and chitosan oligosaccharide to rats with myocardial ischemia myocardial infarct size
(, %, n=8)
| Group | Infarcted region/whole-heartedly | Infarcted region/ventricle | Infarcted region/Zha Xiaqu |
| Model control group | 22.31±4.76 | 25.64±5.41 | 28.75±5.30 |
| Bamboo-leaves flavones group | 11.65±4.18 | 14.68±4.53 | 17.18±4.86 |
| Chitosan oligosaccharide group | 17.61±4.12 | 18.97±5.06 | 21.76±5.23 |
| Bamboo-leaves flavones and chitosan oligosaccharide（1:1）Composition group | 8.52±3.19 | 10.83±3.52 | 14.89±3.57 |
Conclusion：The composition of bamboo-leaves flavones and chitosan oligosaccharide of the present invention can show in the animal model of SD myocardial ischemia in rats
Writing reduces infarct size, shows the good effect for improving myocardial ischemia, protecting cardiac muscle cell；Relative to model control group,
The composition group of bamboo-leaves flavones and chitosan oligosaccharide has highly significant difference, p<0.01；Relative to bamboo-leaves flavones group and chitosan oligosaccharide group,
Also there is very significant difference, p<0.05.Show that pharmaceutical composition of the present invention is improving myocardial ischemia, protecting cardiac muscle cell's
Outstanding role.
Effect of the composition of embodiment 8, bamboo-leaves flavones and chitosan oligosaccharide in terms of antiatherosclerosis
Research is compared using rat aorta atherosis model.
Method：Using feeding high lipid food and the method for vitamine D3 joint modeling, rat aorta atherosis is built
Model, modeling rat is randomly divided into blank group, model group, bamboo-leaves flavones group administration group, chitosan oligosaccharide group administration group, bamboo-leaves flavones
With chitosan oligosaccharide composition administration group, every group 8.
Experiment packet：
（1）Blank group：Base particle feed is fed with；
（2）Model group：Modeling feed (cholesterol of+2% lard of base particle feed+1%)；
（3）Bamboo-leaves flavones group administration group：Modeling feed feeding+bamboo-leaves flavones（15mg/kg）；
（4）Chitosan oligosaccharide group administration group：Modeling feed feeding+chitosan oligosaccharide（15mg/kg）；
（5）Bamboo-leaves flavones and chitosan oligosaccharide composition administration group：Modeling feed feeding+bamboo-leaves flavones and chitosan oligosaccharide composition
（1:1）（15mg/kg）.
Modeling method：One time a day, successive administration 8 weeks, administration group and model group continue to be fed with high fat feeding during administration
Material, and gavage is given modeling medicine propylthiouracil and formed with accelerating model；Blank group is fed with basal feed.
The histopathologic examination of Lipid Plaque：After the modeling phase terminates, each group rat aorta vascular specimen is taken, longitudinal direction
Split, normal saline flushing, be placed in 10% neutral formalin fixed.Sample application image analysis-e/or determining after Sudan IV dyes
Aortic tunica intima Lipid Plaque area percentage (ratio of Lipid Plaque area and the blood vessel gross area).As a result such as table 3 below.
Table 3
Conclusion：The composition of bamboo-leaves flavones and chitosan oligosaccharide of the present invention can show in model of experimental atherosclerosis in rats is formed
Writing reduces atherosclerotic plaques ratio, relative to model group, has highly significant difference, p<0.01, and it is better than bamboo
Leaf flavones group administration group and chitosan oligosaccharide group administration group, p<0.05.Illustrate the combination of compositions of bamboo-leaves flavones and chitosan oligosaccharide of the present invention
In terms of thing has the function that notable antiatherosclerosis, myocardial infarction, cerebral apoplexy or angiocardiopathy occurs for reducing in this
Caused risk it is significant.
The composition of bamboo-leaves flavones and chitosan oligosaccharide described in embodiment 9, embodiment 1 to embodiment 5 should following aspects
With：
The medicine for the treatment of or prevention cardiovascular and cerebrovascular disease is being prepared, and myocardial infarction, cerebral apoplexy or the heart occurs reducing
Application in the medicine of risk caused by vascular diseases；
Application in the medicine of antiatherosclerosis is prepared；
Improve myocardial ischemia preparing and improve cerebral ischemia, protection heart and brain cell, reducing blood lipid, preventing and treating cardiovascular and cerebrovascular disease
Application in medicine.
Claims (1)
1. a kind of bamboo-leaves flavones chitosan oligosaccharide oral administration solution, its recipe quantity by weight percentage, contain：
Bamboo-leaves flavones 0.8%,
Chitosan oligosaccharide 2%,
Sucralose 0.015%,
Appropriate arginine, pH to 6.5 is adjusted,
Purified water adds to 100%；
Prepare：(1) dispensing：Bamboo-leaves flavones, chitosan oligosaccharide are weighed by formula, is added in purified water, is stirred and is uniformly dispersed, constant volume
To required output；
(2) dissolve：Arginine is added in the liquid prepared in (1), the pH for making liquid is 6.5, adds Sucralose, completely
Dissolving, stirs, the solution clarified；
(3) filling, sterilizing：Solution is filtered through 500~1000 mesh, vacuum outgas is canned, sealing, is sterilized under the conditions of 135 DEG C
4~10 seconds；
(4) pack, examine, produce.
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| CN104922145B (en) * | 2015-05-25 | 2018-05-01 | 福州乾正药业有限公司 | Composition of γ-aminobutyric acid and chitosan oligosaccharide and its preparation method and application |
| CN104840800B (en) * | 2015-06-08 | 2018-05-22 | 福州乾正药业有限公司 | Bamboo-leaves flavones and the composition of γ-aminobutyric acid and its preparation method and application |
| CN107441114A (en) * | 2017-05-26 | 2017-12-08 | 宁夏医科大学 | Chitosan oligosaccharide treats the pharmaceutical applications of neonatal hypoxic ischemic encephalopathy |
| CN107568737A (en) * | 2017-08-07 | 2018-01-12 | 天津科技大学 | Improve the water-soluble method with inoxidizability of aurantiamarin using chitosan oligosaccharide |
| CN108888672A (en) * | 2018-08-12 | 2018-11-27 | 白东跃 | Composition and its preparation method and application containing swan-mussel polysaccharide and precious Rogor |
| CN109430878B (en) * | 2018-10-19 | 2022-04-05 | 天津科技大学 | Rutin chitosan oligosaccharide compound and preparation method and application thereof |
| CN111671719A (en) * | 2020-06-18 | 2020-09-18 | 广东药科大学 | Chitosan oligosaccharide composition and preparation method and application thereof |
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Effective date of registration: 20231110 Address after: Building 22, Yard 1, Jinghai Fifth Road, Beijing Economic and Technological Development Zone (Tongzhou), Daxing District, Beijing, 100176 Patentee after: BEIJING ABACE BIOTECHNOLOGY Co.,Ltd. Patentee after: Angel Biomed 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. |