CN108403633A - It is a kind of that there is the high stable type pterostilbene soluble type compound and preparation method thereof for providing faintly acid Micellar Microenvironment - Google Patents
It is a kind of that there is the high stable type pterostilbene soluble type compound and preparation method thereof for providing faintly acid Micellar Microenvironment Download PDFInfo
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- CN108403633A CN108403633A CN201810282857.5A CN201810282857A CN108403633A CN 108403633 A CN108403633 A CN 108403633A CN 201810282857 A CN201810282857 A CN 201810282857A CN 108403633 A CN108403633 A CN 108403633A
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- pterostilbene
- rebaudioside
- compound
- glycyrrhizic acid
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- 230000004580 weight loss Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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Abstract
The present invention discloses a kind of high stable type pterostilbene soluble type compound for having and providing faintly acid Micellar Microenvironment, including pterostilbene is main ingredient, it is characterised in that further include Rebaudioside A and glycyrrhizic acid is excipient substance, the pterostilbene and Rebaudioside A mass ratio are 1:15‑1:Between 30, the glycyrrhizic acid and Rebaudioside A mass ratio are 1:3‑1:Between 6, pterostilbene compound prepared by the present invention, in aqueous solution Rebaudioside A spontaneously form Micellar Solubilization pterostilbene, pterostilbene solubility reaches 13mg/ml, and micella grain size is small and uniform, medicine stability is good, also significantly improves pterostilbene oral administration biaavailability, while Rebaudioside A has anti-diabetic, anti-inflammatory isoreactivity, so that pterostilbene compound has collaboration pharmacological activity well, the pterostilbene compound preparation process of the present invention is simple, is suitble to industrialized production, has good economy.
Description
Technical field
The present invention relates to a kind of pterostilbene soluble type compounds, more particularly to a kind of to have offer faintly acid Micellar Microenvironment
High stable type pterostilbene soluble type compound and preparation method thereof.
Background technology
Pterostilbene (Pterostilbene, CAS 537-42-8) is a kind of from red sandalwood, blueberry, grape and flower palmitic acid
The active ingredient of the plants such as wood has the function of anticancer, anti-inflammatory, anti-oxidant and analgestic.Numerous studies show pterostilbene at present
There is preferable effect in the treatment and protection of skin disease, especially in anti-oxidant equal fields.Pterostilbene has prevention painstaking effort
A variety of pharmacological activity such as pipe disease, antitumor, anti-oxidant have good medical value, great exploitation potential.Newest research
Show that there is the extensive pharmacological activities such as significant anti-oxidant, anti-inflammatory, removing free radical because of pterostilbene, in treatment diabetes
And its in terms of complication, as diabetic keratopathy has broad application prospects.And pterostilbene is as green chip basket
The natural extract of the certain kind of berries also has prodigious effect in terms of anti-aging.But there is following deficiency in pterostilbene, seriously affect it and open
Hair and utilization：(1) water-soluble is poor, and pterostilbene is in water phase at 20 DEG C, and solubility is about 0.03mg/ml in water；(2) molecule
Structural instability contains phenolic hydroxyl group in pterostilbene molecular structure, and phenolic hydroxyl group is extremely unstable, this just determines the steady of pterostilbene
It is qualitative very poor, it is especially extremely unstable in aqueous solution, it is easy oxidation；(3) half-life short, saturating biomembrane poor performance take orally
Etc. bioavilabilities it is extremely low.These above-mentioned deficiencies, seriously limit pterostilbene in clinic such as injection and Orally taken health article
With the application in the fields such as cosmetics.Therefore, it is necessary to further explore a kind of economic and effective novel pterostilbene preparation or
Product.
Pterostilbene has very strong anti-oxidant and anti-inflammatory activity in the polyphenol compound being currently known.Pterostilbene is
The dimethyl ether analog of polyphenol compound resveratrol, there are many identical biological activities, including antioxygen with resveratrol
Change, it is anti-inflammatory, the effects that anti-diabetic, anticancer, neuroprotection.But studies have shown that pterostilbene has better lipophilic than resveratrol
Property, the oral administration biaavailability of pterostilbene is higher 20%-80% than resveratrol, this may be because resveratrol exists widely
II phase was metabolized, and for resveratrol there are three hydroxyl, glucuronidation and sulphation on hydroxyl cause resveratrol half-life period to contract
Short, bioavilability is low.And hydroxyl there are one methide pterostilbenes, lipophilicity increase, membrane permeability enhancing, have more preferable
Metabolic stability, bioactivity enhancing.But the phenolic hydroxyl group in pterostilbene molecular structure is extremely unstable, and pterostilbene is extremely poor
Water-soluble and unstability seriously limits its application.The present inventor is compared by experiment, finds existing document at present
Report and technology cannot meet the requirement of pterostilbene eye drip solubility and its aqueous stability.Application for a patent for invention number
201410505366.4 " a kind of pterostilbene compositions and preparation method thereof " disclose a kind of using pterostilbene, stearyl fumarate
The mass ratio 1 of sodium and L-Carnosine：1：The composition of 1 structure significantly improves the oral administration biaavailability of pterostilbene, but should
Technology disclosed in patent of invention can not be solved there is no pterostilbene solubility in aqueous solution and its aqueous stability is solved
The certainly aqueous solution preparation demand of the clinical demands such as eye drops can not also solve application of the pterostilbene in fields such as some beverage industries
Demand.
Insoluble drug solubility can be improved using Nano medication delivery technique, pharmaceutical aqueous solution stability is improved, carry
High oral administration biaavailability.Currently used ophthalmically acceptable Nano medication delivery system such as micella, nanoparticle etc. mainly uses polyethylene
Caprolactam-polyvinyl acetate-ethylene glycol copolymer (PVCL-PVA-PEG), polyglycolic acid (PGA), polylactic acid
(PLA), the copolymer (PLGA) of hydroxyacetic acid and lactic acid, glycolide-lactide-caprolactone ternary atactic copolymer (PGLC)
Deng, itself it is only a kind of carrier, without therapeutic effect, and these artificial synthesized polymeric carrier materials, because existing
The problems such as degradability, there are some potential safety problemss for long-time service.As can using natural extract matter, especially naturally extract
As a kind of novel carriers, this carrier can play the role of building Nano medication delivery system small-molecule substance, improve drug
Stability, enhancing cornea drug absorption improve curative effect.The natural small molecule substance reported at present has ginseng soap as carrier
Glycosides (application for a patent for invention number 201310155639.2), Stevioside (modern food science and technology, 2014,30 (1):115-119；J
Agric Food Chem,2013,61(18):4433-4440) etc..The natural small molecule substance of above-mentioned existing research and report is made
It can meet for carrier and the Polyphenols chemicals such as resveratrol, curcumin are contained, but the present inventor passes through Experimental comparison, hair
Now ginsenoside, the Stevioside of existing document report cannot meet pterostilbene eye drip solubility and its stabilized aqueous solution at present
The requirement of property.This is because containing phenolic hydroxyl group in pterostilbene molecular structure, could only keep stablizing under slant acidity microenvironment,
Ginsenoside, Stevioside etc. in above-mentioned existing document report cannot maintain the weak acid microenvironment needed for drug molecule, to it
The pterostilbene contained does not have good stabilization.Therefore, it is necessary to select a kind of weakly acidic natural small molecule substance itself, make
It can maintain the faintly acid microenvironment needed for pterostilbene, improve the stability of drug molecule, maintain its pharmacological activity, while can also
Effectively encapsulating pterostilbene, to improve the solubility and its stability of pterostilbene in aqueous solution.
Rebaudioside A (Rebaudioside A, CAS registration number 58543-16-1, molecular formula C44H70O23, molecular weight
967.03) it is to be extracted from the leaf of feverfew Stevia Rebaudia (plant is referred to as STEVIA REBAUDIANA in China)
A kind of glucosides is widely used in as a kind of new type natural sweetener in the production of food, beverage, seasoning.In South America
There is centuries history using STEVIA REBAUDIANA as medicinal herbs and for sugar.In recent years studies have shown that Rebaudioside A have strong anti-oxidation
Activity (Saravanan R, Ramachandran V.Modulating efficacy of Rebaudioside A, a
diterpenoid on antioxidant and circulatory lipids in experimental diabetic
rats.Environ Toxicol Pharmacol.2013,36(2):472-83), meanwhile, Rebaudioside A has strong anti-glycosuria
The effects that sick, anti-inflammatory, immunological regulation (V,S,N,et al.Insight into anti-
diabetic effect of low dose of stevioside.Biomed Pharmacother.2017,90:216-
221).The present inventor the study found that Rebaudioside A can significantly solubilized pterostilbene, improve pterostilbene stability, and significantly improve purple
Wingceltis stilbene oral administration biaavailability.And from the leaf of feverfew Stevia Rebaudia (plant is referred to as STEVIA REBAUDIANA in China)
In another ingredient Stevioside (also known as steviol glycoside, CAS the registration number 57817-89-7, molecular formula C that extract38H60O18,
Molecular weight 804.87), then fail to have the function that while improving pterostilbene water solubility and its stability.
Invention content
The object of the present invention is to provide a kind of high stable type pterostilbene soluble type for having and providing faintly acid Micellar Microenvironment
Compound improves pterostilbene stability of molecule, improves solubility, improves and improves the bioavilability after oral medication, and carries
The bin stability of high pterostilbene, meanwhile, the carrier of structure pterostilbene compound is the small-molecule substance of two kinds of natural safety,
Having the effects that anti-diabetic, anti-inflammatory, immunological regulation so that its pterostilbene compound built has the function of synergy,
For example, the drug effect of enhancing pterostilbene treatment diabetic complication such as diabetic keratopathy and cornea neuropathy.Meanwhile it is purple
Wingceltis stilbene improves water solubility, after improving its stability in aqueous solution, can expand pterostilbene in food industry and field
Using for example, for health oral solution etc..
Another object of the present invention is to provide the preparation method of above-mentioned pterostilbene compound.
The technology of the present invention is conceived：Pterostilbene has the specific pharmacology such as anti-oxidant, anti-inflammatory, anti-diabetic and neuroprotection
Activity, but pterostilbene molecular structure is extremely unstable, be insoluble in water, the problems such as oral administration biaavailability is low seriously limits purple
Application of the wingceltis stilbene in the fields such as clinical drug therapy, food industry, and the phenolic hydroxyl group in pterostilbene molecular structure, it is extremely unstable
It is fixed, easily Oxidative inactivation in aqueous solution.And the stability of pterostilbene is improved, especially improve its stabilization in aqueous solution
Property, it can significantly expand its clinical application (for example, the aqueous solution preparations such as injection, eye drops can be prepared into) and its in health food
The application (for example, oral solution etc. can be prepared into) in equal fields.Pterostilbene is built by nanometer system using Nano medication delivery system
Agent will be such that pterostilbene stability significantly improves because of advantage specific to of Nano medication delivery system itself, improve oral bio
Availability heightens the effect of a treatment.And use biologically active Small-molecule compounds as the load of structure pterostilbene nanometer formulation
Body, pterostilbene can then be further enhanced also because carrier has pharmacological activity by not only acting as effectively structure myricetin nanometer formulation
Pharmacological effect.The present inventor has similar glue the study found that Rebaudioside A can spontaneously form in aqueous solution with glycyrrhizic acid
The nanostructure of beam, plays the effect of solubilized pterostilbene, and because Rebaudioside A itself has strong anti-oxidative activity, can play guarantor
The not oxidized inactivation of pterostilbene contained is protected, and glycyrrhizic acid is weakly acidic, can provide the faintly acid micella for maintaining pterostilbene to stablize
Interior microenvironment.The pterostilbene solution of the mixed micelle of Rebaudioside A and glycyrrhizic acid solubilising, i.e. pterostilbene mixed micelle solution, surely
Qualitative to significantly improve, further experiment finds that pterostilbene mixed micelle solution has the oral administration biaavailability that increases significantly, carries
The validity effect of high pterostilbene treatment diabetic keratopathy.
Technical scheme of the present invention：A kind of pterostilbene soluble type compound, including pterostilbene are main ingredient, it is further characterized in that
Including Rebaudioside A and glycyrrhizic acid as excipient substance, the pterostilbene main ingredient and Rebaudioside A excipient substance mass ratio are 1:
15-1:Between 30, two kinds of excipient substance mass ratioes of the glycyrrhizic acid and Rebaudioside A are 1:3-1:Between 6.
The Rebaudioside A (Rebaudioside A) is that (plant is in China by feverfew Stevia Rebaudia
Referred to as STEVIA REBAUDIANA) leaf in a kind of glucosides (CAS registration numbers for extracting:58543-16-1, molecular formula:C44H70O23, point
Son amount:967.03), Rebaudioside A purity >=98%.The glycyrrhizic acid (Glycyrrhizic acid) is that legume is sweet
Root extract (the CAS registration numbers of grass:1405-86-3, molecular formula:C42H62O16, molecular weight:822.93), glycyrrhizic acid purity >=
97%.
The preparation method of the eye drops of the present invention is as follows：Pterostilbene and Rebaudioside A, glycyrrhizic acid are dissolved into absolute ethyl alcohol
In, by 40 DEG C of water-bath rotatory vacuum ethanol evaporations (recyclable ethyl alcohol), solid powder is formed inside container up to the present invention
Pterostilbene compound.Preparation process is simple, environmentally protective, is suitable for industrialization large-scale production.
The preparation method of above-mentioned pterostilbene micelle complex, pterostilbene compound obtained are highly soluble in water, and solubility can
Up to 13mg/ml, pterostilbene compound spontaneously forms micella after being dissolved in water, and micella particle size range is between 6~15nm.
Above-mentioned pterostilbene micelle complex is also applied for filling suitable for being further prepared into the aqueous solution preparations such as oral solution
It is encapsulated or directly packed at powder.
The preparation method of above-mentioned pterostilbene micelle complex, preparation process and simple for process is easy to operate, dry without spraying
Dry equal large-scale instrument and equipments, are suitable for industrialized production, are also very applicable for the clean chemical industry of pharmacy corporation or food enterprise etc.
Industry produces.
Pterostilbene compound prepared by the present invention, because in aqueous solution, composite materials Rebaudioside A can be certainly with glycyrrhizic acid
Assembling forms micella, rapid solubilisation pterostilbene so that pterostilbene has good dissolubility, the solubility of pterostilbene in aqueous solution
Up to 13mg/ml, and micella grain size is minimum, and distribution is uniform, and medicine stability is good.The pterostilbene compound not only improves
Stability of the pterostilbene in aqueous solution state, can also significantly increase oral administration biaavailability, experimental result table of the invention
It is bright, before prepared by the oral administration biaavailability of the pterostilbene compound of the patent of the present invention of same dose after rat oral gavage
2.3 times of pterostilbene ordinary powder, while the Rebaudioside A anti-diabetic, anti-inflammatory isoreactivity and the glycyrrhizic acid that have have
Anti-inflammatory, immunological regulation isoreactivity makes pterostilbene compound have good synergistic treatment diabetic complication such as diabetic keratopathy
The drug effect of keratopathy and cornea neuropathy.Therefore, pterostilbene compound of the invention has good economy.
Description of the drawings
Fig. 1 be administered 8 weeks after to each group diabetic mice corneal nerve sensitivity analysis figure.
Specific implementation mode
Below in conjunction with the accompanying drawings and by specific embodiment come present invention be described in more detail.
Embodiment 1：
50mg pterostilbenes, 900mg Rebaudioside A, 300mg glycyrrhizic acids are placed in 100mL round-bottomed flasks, be added 50mL without
Water-ethanol, fully after dissolving, 40 DEG C of water-bath rotatory vacuums evaporate absolute ethyl alcohol and recycle ethyl alcohol, obtain pterostilbene and rebaudioside
A, the evenly dispersed pterostilbene compound of glycyrrhizic acid.
Embodiment 2：
20mg pterostilbenes, 300mg Rebaudioside A, 50mg glycyrrhizic acids are placed in 100mL round-bottomed flasks, be added 50mL without
Water-ethanol, fully after dissolving, 40 DEG C of water-bath rotatory vacuums evaporate absolute ethyl alcohol and recycle ethyl alcohol, obtain pterostilbene and rebaudioside
A, the evenly dispersed pterostilbene compound of glycyrrhizic acid.
Embodiment 3：
100mg pterostilbenes, 3000mg Rebaudioside A, 750mg glycyrrhizic acids are placed in 100mL round-bottomed flasks, 50mL is added
Absolute ethyl alcohol, fully after dissolving, 40 DEG C of water-bath rotatory vacuums evaporate absolute ethyl alcohol and recycle ethyl alcohol, obtain pterostilbene and Rui Baodi
The evenly dispersed pterostilbene compound of glycosides A, glycyrrhizic acid.
Experiment effect example 1：The pterostilbene compound solubility property and its aqueous stability of the present invention measures.
Experimental drug：Pterostilbene compound (prepared by embodiment 1, be set as experimental group).
Control drug：Using 1 preparation method of patent Example of the present invention, but it is not added with glycyrrhizic acid, remaining preparation process one
It causes, the pterostilbene compound (being set as control drug 1) of preparation；Using a kind of " the pterostilbene combination of application number 201410505366.4
Object and preparation method thereof ", using the mass ratio 1 of pterostilbene, sodium stearyl fumarate and L-Carnosine：1：The composition of 1 structure is (right
According to drug 2)；Pterostilbene ordinary powder (control drug 3).
Experimental method：Excessive experimental drug, control drug 1, control drug 2, control drug 3 are taken, brown glass is sealed in
In glass bottle, 5ml water is added, vortex oscillation is after one hour, absorption liquid, after 0.22 μm of filtering with microporous membrane, will filter gained
Solution is divided into two parts, and portion is using 100 times of methanol dissolvings and dilution, and high effective liquid chromatography for measuring concentration, another is loaded on saturating
In bright vial, it is positioned over room temperature (not being protected from light), 24 as a child afterwards by after 0.22 μm of filtering with microporous membrane of liquid, efficient liquid
Phase chromatography measured concentration, and calculate medicament contg and degradation percentage.
The experimental results showed that the amount that experimental drug (i.e. pterostilbene compound) vortex oscillation dissolves after one hour is 13mg/
Ml using 1 preparation method of patent Example of the present invention, but is not added with glycyrrhizic acid, remaining preparation process is consistent, the pterostilbene of preparation
The amount that compound (being set as control drug 1) vortex oscillation dissolves after one hour is 12.1mg/ml, using application number
201410505366.4 " a kind of pterostilbene compositions and preparation method thereof ", using pterostilbene, sodium stearyl fumarate and left-handed flesh
The mass ratio 1 of peptide：1：The amount that composition (control drug 2) vortex oscillation of 1 structure dissolves after one hour is 0.4mg/ml, red sandalwood
The amount that stilbene ordinary powder (control drug 2) vortex oscillation dissolves after one hour is 0.028mg/ml.Illustrate prepared by the technology of the present invention
Pterostilbene compound significantly improve and improve pterostilbene solubility property, and use Rebaudioside A also can be solubilized well merely
Pterostilbene.Avoid light place is not after 24 hours for experimental drug (i.e. pterostilbene compound) aqueous solution room temperature, pterostilbene content in solution
It is the 91% of initial soln, using 1 preparation method of patent Example of the present invention, but is not added with glycyrrhizic acid, remaining preparation process one
It causes, the pterostilbene compound (being set as control drug 1) of preparation, avoid light place is not after 24 hours for aqueous solution room temperature, red sandalwood in solution
Stilbene content only has the 36% of initial soln concentration, and using pterostilbene, the mass ratio 1 of sodium stearyl fumarate and L-Carnosine：
1：Avoid light place 24 is not small for the composition (control drug 2) and pterostilbene ordinary powder (control drug 3) aqueous solution room temperature of 1 structure
Shi Hou, pterostilbene content only has the 2.5% of initial soln concentration in solution, illustrates that pterostilbene prepared by the technology of the present invention is compound
Object significantly improves the stability with improvement pterostilbene aqueous solution, although and using Rebaudioside A also can be solubilized purple well merely
Wingceltis stilbene, but aqueous stability is poor.
Experiment effect example 2：The pterostilbene compound of the present invention is used for STZ induction type diabetic mice ocular complications
Validity.
Experimental drug：Pterostilbene compound (prepared by embodiment 1, be set as experimental group).
Control drug：Using application number 201410505366.4 " a kind of pterostilbene composition and preparation method thereof ", use
The mass ratio 1 of pterostilbene, sodium stearyl fumarate and L-Carnosine：1：The composition (control drug 1) of 1 structure, pterostilbene is common
Powder (control drug 2).
Experimental animal and experimental method：Because the diabetic mice of STZ inductions is similar to people's non-proliferative phase as compared with what is generally acknowledged
Diabetic retinopathy model, this part content are studied using this model.C57BL/6 mouse are selected, it is male, 6-8 weeks
Age, 18~25 grams of weight (are bought from Beijing Vital River Experimental Animals Technology Co., Ltd.).Animal is randomly divided into two groups, one group
Mouse is injected intraperitoneally after preparing STZ solution using the citrate buffer (pH 4.5) of fresh configuration, continuously injects 5
It, the 8th day (after a week) after last time (the 5th injection) measures blood glucose to every mouse, continuous to measure 3 days, STZ notes
It penetrates group blood glucose value and thinks the success of Type I diabetes model more than 300mg/dL (16.7mmol/L).It is after model success, mouse is random
It is divided into 4 groups (i.e. experimental group, 1 group of control, control 2 groups, blank control groups), every group 12, given low is 25mg/kg weight
(determination of gastric infusion dosage combination document report), before gavage, respectively by 2 groups of experimental group, 1 group of control and control pterostilbenes dissolvings
Or be dispersed in water, it is configured to a concentration of 2.5mg/ml of pterostilbene, gavage volume is 0.1ml/10g weight (i.e. 25mg pterostilbenes
Per kilogram mouse weight dosage gavage), blank control group gavage gives the physiological saline of respective volume, and daily gavage is primary, even
Continue gavage 8 weeks, the weight, fasting blood-glucose, corneal sensitivity of diabetic mice are measured after 8 weeks gavages.
The experimental results showed that the mouse of saline control group STZ intraperitoneal injection modeling, gradually show drink, more foods,
The diabetes classical symptom such as diuresis, weight loss, glucostasis maintain higher level, and weight is relatively low compared with normal mouse, table
Bright modeling success.And the weight and blood glucose target of experimental group (pterostilbene compound) mouse are then substantially better than pterostilbene composition
(control drug 1) and pterostilbene ordinary powder (control drug 2) group (table 1).The corneal sensitivity of mouse is detected, as a result such as Fig. 1
Shown, STZ modeling diabetic mice saline control group corneal sensitivities are remarkably decreased (compared to normal mouse, P<
0.05) the pterostilbene compound oral medication group of patent of the present invention, is used, mouse cornea susceptibility, which then significantly improves, (to be compared
In normal mouse, P>0.05), 2 groups of 1 group of STZ modeling diabetic mices control and control, the improvement of mouse cornea susceptibility are not shown
It writes (compared to normal mouse, P<0.05).
Table 1 is normal and diabetic mice in sample point weight and blood sugar test (N=12)
Experiment effect example 3：The pterostilbene compound Oral Administration in Rats bioavilability test experience of the present invention.
Experimental drug：Pterostilbene compound (prepared by embodiment 1, be set as experimental group).
Control drug：Using application number 201410505366.4 " a kind of pterostilbene composition and preparation method thereof ", use
The mass ratio 1 of pterostilbene, sodium stearyl fumarate and L-Carnosine：1：The composition (control drug 1) of 1 structure；Pterostilbene is common
Powder (control drug 2).
Experimental animal and experimental method：24 SD rats are selected, male, (purchase is logical from Beijing dimension for 290~310 grams of weight
Li Hua experimental animals Technology Co., Ltd.).Animal is randomly divided into three groups, every group 8, tests preceding overnight fasting, will be real before gavage
Drug, control drug 1 and control drug 2 is tested to be dissolved or dispersed in water with 1mg/ml concentration respectively, with 1ml/100g weight into
Row gavage (i.e. 10mg pterostilbenes per kilogram rat body weight dosage gavage), 0.25,0.5,1,2,4,6,8,12 and upon administration
24 hours, tail vein took blood 0.25ml, and anticoagulant heparin, centrifugal separation plasma, High Performance Liquid Chromatography/Mass Spectrometry instrument detects purple in blood sample
Wingceltis stilbene concentration, the processing of DAS2.0 softwares and analysis pharmacokinetic parameter.
Experimental result is as shown in table 1, the C of experimental groupmaxIt is significantly higher than 1 group of (P of control drug<And 2 groups of control drug 0.05)
(P<0.05), the AUC of experimental group0-24hAlso it is significantly better than 1 group of (P of control drug<And 2 groups of (P of control drug 0.05)<0.05) it, reaches
Peak time shortens, and illustrates that there is the pterostilbene compound of the present invention faster oral absorption, better oral organism-absorbing to utilize
Degree.
2 oral drugs kinetic parameter of table
| Pharmacokinetic parameter | Experimental group | Control drug 1 | Control drug 2 |
| Cmax(μg/mL) | 0.35±0.031 | 0.241±0.23 | 0.137±0.021 |
| Tmax(h) | 1 | 2 | 2 |
| AUC0-24h(μg/mL) | 73.64±3.97 | 51.76±2.15 | 32.09±0.45 |
The above embodiments merely illustrate the technical concept and features of the present invention, and the protection model of the present invention can not be limited with this
It encloses.It is all any equivalent transformation or modification made according to the spirit of the present invention, should all cover within the scope of the present invention.
Claims (4)
1. a kind of having the high stable type pterostilbene soluble type compound for providing faintly acid Micellar Microenvironment, including based on pterostilbene
Medicine, it is characterised in that further include Rebaudioside A and glycyrrhizic acid be excipient substance, the pterostilbene main ingredient and Rebaudioside A drug
Auxiliary material mass ratio is 1:15-1:Between 30, the glycyrrhizic acid and Rebaudioside A mass ratio are 1:3-1:Between 6.
2. pterostilbene compound as described in claim 1, it is characterised in that Rebaudioside A (the CAS registration numbers 58543-
16-1, molecular formula C44H70O23, molecular weight 967.03) and purity >=98%, glycyrrhizic acid (the CAS registration numbers:1405-86-3, point
Minor:C42H62O16, molecular weight:822.93) purity >=97%.
3. a kind of preparation method of pterostilbene compound as described in claim 1, it is characterised in that include the following steps：It will be purple
Wingceltis stilbene main ingredient and Rebaudioside A are dissolved in glycyrrhizic acid medicine auxiliary material in absolute ethyl alcohol, pass through rotatory vacuum evaporative removal ethyl alcohol
To obtain the final product.
4. the preparation method of pterostilbene compound as claimed in claim 3, it is characterised in that pterostilbene compound obtained can
It is self-assembly of micella after being quickly dissolved in water, micella particle size range is between 6-15nm.
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| CN201810282857.5A CN108403633A (en) | 2018-04-02 | 2018-04-02 | It is a kind of that there is the high stable type pterostilbene soluble type compound and preparation method thereof for providing faintly acid Micellar Microenvironment |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110538094A (en) * | 2019-09-27 | 2019-12-06 | 华南理工大学 | Pterostilbene @ cyclodextrin inclusion compound with homogeneous hydrophilicity and multi-dimensional stability and preparation method thereof |
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2018
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110538094A (en) * | 2019-09-27 | 2019-12-06 | 华南理工大学 | Pterostilbene @ cyclodextrin inclusion compound with homogeneous hydrophilicity and multi-dimensional stability and preparation method thereof |
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