CN101292961A - Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere - Google Patents
Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere Download PDFInfo
- Publication number
- CN101292961A CN101292961A CNA200810039132XA CN200810039132A CN101292961A CN 101292961 A CN101292961 A CN 101292961A CN A200810039132X A CNA200810039132X A CN A200810039132XA CN 200810039132 A CN200810039132 A CN 200810039132A CN 101292961 A CN101292961 A CN 101292961A
- Authority
- CN
- China
- Prior art keywords
- acid
- acetic acid
- polylactic acid
- ferulic
- ferulic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of ferulic acid polylactic acid-glycolic acid copolymer microspheres, including the following steps: 1) the polylactic acid-glycolic acid copolymer PLGA is dissolved in organic solvent, and then the ferulic acid is added for ultrasound dissolution as an organic phase; 2) under the condition of stirring, the organic phase is gradually added into polyvinyl alcohol PVA water solution as the aqueous phase, and then electrolyte is added for continuous stirring under room temperature until the organic solvent fully volatilizes, and after centrifugation, washing and freeze-drying, the ferulic acid polylactic acid-glycolic acid copolymer PLGA microspheres can be obtained. The microspheres have round shape and even grain size distribution. The average grain diameter is below 10 micron, the drug loading is up to 12.6 percent and the entrapment rate is about 75 percent. As a drug carrier, the microsphere of the invention has a good biocompatibility.
Description
Technical field
The invention belongs to anti-oxidation medicine microsphere preparation field, particularly relate to a kind of preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere.
Background technology
The chemical name of ferulic acid (Ferulic Acid) is a 4-hydroxy 3-methoxybenzene acrylic acid, extensively is present in the Chinese medicines such as Radix Angelicae Sinensis, Rhizoma Chuanxiong, Resina Ferulae; Ferulaic acid content is also higher in raw-food material such as coffee, chinese cymbidium bean, rice husk, bagasse, beet pulp, Testa Tritici and Testa oryzae.
At present, ferulic acid in the purposes in fields such as medicine, food, cosmetics more and more widely.Ferulic acid is the Natural antioxidant of generally acknowledging, also is international in recent years cognitive anti-cancer material, causes that common people gaze at.Ferulic acid has good antioxidant activity, hydrogen peroxide, superoxide radical, hydroxy radical, peroxidating nitroso-group is all had intensive scavenging action, and can regulate physiological function, suppresses to produce the enzyme of free radical, increases the activity of removing the free radical enzyme.
Except that being widely used in pharmaceuticals industry, ferulic acid also enlarges day by day in the application of food service industry.Ferulic acid can be used as the precursor substance of synthesis of vanillin, by microbial enzyme ferulic acid is changed into vanillin; Because ferulic acid has antioxidant activity and bacteriostasis, ferulic acid also can be used as the antisepsis antistaling agent of food, and safety non-toxic; Ferulic acid also little by little is applied to prepare food glue and edible packing membrane as cross-linking agent; In addition, it promotes that as antioxidant and function material can be applicable in the motion food.Microsphere has excellent biological compatibility as pharmaceutical carrier, can change interior distribution of body of medicine, improves the Drug therapy index, reduces toxic and side effects, is subjected to paying attention to widely and deep research.Research report is made anti-oxidation medicine the oxidation resistance that can improve medicine behind the microsphere significantly.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere.This method with U.S. FDA authentication the degradability biocompatible material that can be used for human body---polylactic acid-hydroxide acetic acid copolymer (PLGA) prepares ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere as carrier, this microsphere can be used as the pharmaceutical carrier of anti-oxidation medicine, can change interior distribution of body of medicine, improve the Drug therapy index, reduce toxic and side effects.
The preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere of the present invention comprises the following steps:
(1) polylactic acid-hydroxide acetic acid copolymer (PLGA) is dissolved in the organic solvent, adds ferulic acid again, ultrasonic dissolution is as organic facies;
(2) under stirring condition, organic facies is slowly added in polyvinyl alcohol (PVA) aqueous solution as water, add electrolyte then, continue to be stirred to organic solvent under the room temperature and volatilize fully, centrifugal, washing, lyophilization promptly get ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere.
Described polylactic acid-hydroxide acetic acid copolymer specification is lactic acid (LA): the weight ratio of glycolic (GA) is 50: 50, and molecular weight Mr is 20000; LA: GA=50: 50, Mr=40000; LA: GA=75: 25, Mr=20000; LA: GA=75: 25, Mr=40000, the concentration of polylactic acid-hydroxide acetic acid copolymer PLGA in organic facies is 40～60mg/ml.
Organic solvent in the described step (1) is an acetonitrile.
The concentration of described ferulic acid in organic facies is 5～20mg/ml.
The specification of the polyvinyl alcohol in the described step (2) is PVA-124, and the mole percent of alcoholysis degree is 98～99%, and average degree of polymerization n is 2400～2500, and the polyvinyl alcohol water solution mass concentration is 0.5%～1.5%.
Electrolyte in the described step (2) is a sodium chloride, and the mass concentration in the PVAC polyvinylalcohol aqueous solution is 2%～5%.
Described organic facies is 1: 20～1: 30 with volume ratio as the PVAC polyvinylalcohol aqueous solution of water.
Mixing speed in the described step (2) is 600～1000rpm.
The mean diameter of described ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere is below 10 μ m.
Beneficial effect of the present invention:
(1) the polylactic acid-hydroxide acetic acid copolymer PLGA of usefulness of the present invention has excellent biological compatibility and biodegradability, and implant into body can reach slow release effect preferably;
(2) Zhi Bei microsphere is by observation by light microscope, and the form rounding is evenly distributed, and the entrapment efficiency of microsphere is about 75%, and medicament contg can reach 12.6%;
(3) experiment shows that the ferulic acid microsphere has good oxidation resistance.
Description of drawings
Fig. 1 is the microphotograph of the ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere of preparation;
The standard curve of Fig. 2 ferulic acid alcoholic solution.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
(1) preparation of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere
Accurately take by weighing polylactic acid-hydroxide acetic acid copolymer PLGA (LA: GA=50: 50, Mr=20000) 100mg is dissolved in the 2ml acetonitrile, adds ferulic acid 20mg again, ultrasonic dissolution is as organic facies; Preparation 60ml 0.5%PVA aqueous solution adds 1.5gNaCl, again as water.Under stirring condition (800rpm), (1ml/min) joins aqueous phase to organic facies slowly, continues to stir 24h under the room temperature, centrifugalize then, and with distilled water washing 3 times, lyophilization promptly gets ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere.
(2) form of microsphere and grain size
By the microsphere photo (Fig. 1) that optical microscope is taken, can see that the microsphere that institute gets has good rounded form.The mean diameter that records microsphere with laser particle size determination instrument is 8.101 microns.
(3) medicament contg and entrapment efficiency determination
A. the mensuration of ferulic acid maximum absorption wavelength
For determining mensuration wavelength with the determined by ultraviolet spectrophotometry ferulaic acid content, with UV-2102PC type ultraviolet-uisible spectrophotometer the maximum absorption wavelength of ferulic acid is measured in the research, determination step is: precision takes by weighing the 20mg ferulic acid, dissolve with ethanol solution with 95%, alcoholic solution with 95% is a blank, in 200～400nm catch cropping UV scanning, just can obtain maximum absorption wavelength is 310nm.Get blank microsphere 5mg, add 95% alcoholic solution standardize solution,, about 300nm, do not have uv absorption, therefore, select 310nm as the ultraviolet detection wavelength by above-mentioned condition scanning.
B. standard curve preparation
Precision takes by weighing the 50mg ferulic acid, and the dissolve with ethanol solution with 95% is transferred to standardize solution in the 50ml volumetric flask, gets the ferulic acid contrast liquid of 1.000mg/ml.The accurate contrast liquid 0.05,0.1,0.15,0.2,0.25 of drawing, 0.3ml, the ethanol with 95% is settled to 5ml respectively in test tube.Measure absorbance according to spectrophotography in the maximum absorption wave strong point of ferulic acid.And be that vertical coordinate, absorbance are that standard curve such as Fig. 2 that abscissa mapping obtains the ferulic acid alcoholic solution shows with ferulic acid concentration.Obtaining absorbance A by linear regression to the regression equation of ferulic acid concentration C is: A=18.343C+0.1947, R
2=0.9998.
C. the calculating of medicament contg and envelop rate
Precision takes by weighing 10mg ferulic acid PLGA microsphere, and adds 10ml 95% ethanol in test tube, ultrasonic add heat damage 1h after, use the microporous filter membrane sucking filtration, the accurate filtrate 1ml that draws is a blank with 95% ethanol, record at the 310nm place, the substitution regression equation also calculates, and just can obtain ferulaic acid content is 12.1%.The envelop rate that just can calculate ferulic acid in the microsphere preparation process according to following formula is 73.5% then.
The theoretical content of ferulic acid in the actual content/microsphere of ferulic acid in envelop rate=microsphere
(4) ferulic acid antioxidation in vitro evaluation
Ferulic acid microsphere and ferulic acid are added in the 50g Oleum Arachidis hypogaeae semen with different ratios, and according to the Schaal Oven Method, results of regular determination peroxide value (POV) value the results are shown in Table 1.The induction time of Oleum Arachidis hypogaeae semen sample that adds antioxidant is all greater than the induction time of blank sample.The protection coefficient (PF value) of every group of addition ferulic acid microsphere and ferulic acid illustrates that all greater than 1 they have antioxidation to Oleum Arachidis hypogaeae semen.But the ferulic acid microsphere is stronger to the antioxidation of Oleum Arachidis hypogaeae semen.
Table 1 is the comparison to the Oleum Arachidis hypogaeae semen oxidation resistance of ferulic acid microsphere and ferulic acid
Claims (9)
1. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere comprises the following steps:
(1) polylactic acid-hydroxide acetic acid copolymer PLGA is dissolved in the organic solvent, adds ferulic acid again, ultrasonic dissolution is as organic facies;
(2) under stirring condition, organic facies is slowly added in the PVAC polyvinylalcohol aqueous solution as water, add electrolyte then, continue to be stirred to organic solvent under the room temperature and volatilize fully, centrifugal, washing, lyophilization promptly get ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere.
2. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: described polylactic acid-hydroxide acetic acid copolymer specification is lactic acid LA: the weight ratio of glycolic GA is 50: 50, and molecular weight Mr is 20000; LA: GA=50: 50, Mr=40000; LA: GA=75: 25, Mr=20000; LA: GA=75: 25, Mr=40000;
The concentration of polylactic acid-hydroxide acetic acid copolymer PLGA in organic facies is 40～60mg/ml.
3. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: the organic solvent in the described step (1) is an acetonitrile.
4. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: the concentration of described ferulic acid in organic facies is 5～20mg/ml.
5. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1, it is characterized in that: the specification of the polyvinyl alcohol in the described step (2) is PVA-124, the mole percent of alcoholysis degree is 98～99%, average degree of polymerization n is 2400～2500, and the polyvinyl alcohol water solution mass concentration is 0.5%～1.5%.
6. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: the electrolyte in the described step (2) is a sodium chloride, and the mass concentration in the PVAC polyvinylalcohol aqueous solution is 2%～5%.
7. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: described organic facies is 1: 20～1: 30 with volume ratio as the PVAC polyvinylalcohol aqueous solution of water.
8. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: the mixing speed in the described step (2) is 600～1000rpm.
9. the preparation method of ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere according to claim 1 is characterized in that: the mean diameter of described ferulic acid polylactic acid-hydroxide acetic acid copolymer PLGA microsphere is below 10 μ m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810039132XA CN101292961A (en) | 2008-06-18 | 2008-06-18 | Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810039132XA CN101292961A (en) | 2008-06-18 | 2008-06-18 | Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101292961A true CN101292961A (en) | 2008-10-29 |
Family
ID=40063670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200810039132XA Pending CN101292961A (en) | 2008-06-18 | 2008-06-18 | Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101292961A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITRM20110195A1 (en) * | 2011-04-18 | 2011-07-18 | Galdi Maria Rosa | PLA-BASED ACTIVE SYSTEMS FOR CREATING SEMI-RIGID AND FLEXIBLE FLEXIBLE PACKAGING, BIODEGRADABLE |
| CN104448356A (en) * | 2014-12-13 | 2015-03-25 | 浙江大学 | Blank PLGA microspheres and preparation method thereof |
| CN110496105A (en) * | 2019-08-07 | 2019-11-26 | 澳门科技大学 | A kind of microball preparation and preparation method thereof carrying S- S-propargyl-cysteine |
| CN110885381A (en) * | 2019-12-27 | 2020-03-17 | 蚌埠天成包装科技股份有限公司 | Catechin graft modified starch, degradable preservative film and preparation method thereof |
-
2008
- 2008-06-18 CN CNA200810039132XA patent/CN101292961A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITRM20110195A1 (en) * | 2011-04-18 | 2011-07-18 | Galdi Maria Rosa | PLA-BASED ACTIVE SYSTEMS FOR CREATING SEMI-RIGID AND FLEXIBLE FLEXIBLE PACKAGING, BIODEGRADABLE |
| CN104448356A (en) * | 2014-12-13 | 2015-03-25 | 浙江大学 | Blank PLGA microspheres and preparation method thereof |
| CN110496105A (en) * | 2019-08-07 | 2019-11-26 | 澳门科技大学 | A kind of microball preparation and preparation method thereof carrying S- S-propargyl-cysteine |
| CN110496105B (en) * | 2019-08-07 | 2021-09-14 | 澳门科技大学 | S-propargyl cysteine-loaded microsphere preparation and preparation method thereof |
| CN110885381A (en) * | 2019-12-27 | 2020-03-17 | 蚌埠天成包装科技股份有限公司 | Catechin graft modified starch, degradable preservative film and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Rajabzadeh-Khosroshahi et al. | Chitosan/agarose/graphitic carbon nitride nanocomposite as an efficient pH-sensitive drug delivery system for anticancer curcumin releasing | |
| Zhang et al. | Creation of highly stable selenium nanoparticles capped with hyperbranched polysaccharide in water | |
| Başaran et al. | Chitosan nanoparticles for ocular delivery of cyclosporine A | |
| CN105853365B (en) | A kind of silica-chitosan for having both pH responsiveness and folate-targeted and loading ursolic acid-folic acid nano material and application | |
| CN110090223A (en) | Solid dispersions of beta glucan and preparation method thereof | |
| Di et al. | Engineering synthetic insulin-secreting cells using hyaluronic acid microgels integrated with glucose-responsive nanoparticles | |
| CN108670960A (en) | A kind of hyaluronic acid oligosaccharide-chitosan microball and the preparation method and application thereof containing Docetaxel | |
| CN101292961A (en) | Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere | |
| Songsurang et al. | Mucoadhesive drug carrier based on functional-modified cellulose as poorly water-soluble drug delivery system | |
| Chen et al. | Encapsulation of Phloretin in a ternary Nanocomplex prepared with Phytoglycogen–Caseinate–pectin via electrostatic interactions and chemical cross-linking | |
| CN109044963B (en) | A kind of preparation method of the nano-hydrogel of injection pH sensibility | |
| CN103585113B (en) | Apigenin polylactic acid sustained release microsphere and preparation method thereof | |
| Bensouiki et al. | Evaluation of anti-inflammatory activity and in vitro drug release of ibuprofen-loaded nanoparticles based on sodium alginate and chitosan | |
| CN101305985B (en) | Preparation method of coffee acid polylactic acid copolymer nanometer microsphere | |
| Campos et al. | Preparation and characterisation of Dextran-70 hydrogel for controlled release of praziquantel | |
| Halevas et al. | Evaluation of the hemocompatibility and anticancer potential of poly (ε-Caprolactone) and poly (3-Hydroxybutyrate) microcarriers with encapsulated chrysin | |
| Yingying et al. | pH-Sensitive ε-polylysine/polyaspartic acid/zein nanofiber membranes for the targeted release of polyphenols | |
| Yao et al. | Effect of solvents on forming poly (butyl-2-cyanoacrylate) encapsulated paeonol nanocapsules | |
| Ilić-Stojanović et al. | Biomedical applications of thermosensitive hydrogels for controlled/modulated piroxicam delivery | |
| CN101696278B (en) | Preparation method of Trolox- chitosan self-assembly nano-particles | |
| CN103989746B (en) | A kind of broussoflavone nanometer formulation and preparation method thereof | |
| CN107693488B (en) | Fat-soluble medicine submicron capsule glucose injection and preparation method thereof | |
| Lin et al. | Glycol chitin/PAA hydrogel composite incorporated bio-functionalized PLGA microspheres intended for sustained release of anticancer drug through intratumoral injection | |
| CN110051652A (en) | PLGA/FK506 medicament-carrying nano-microsphere and its preparation method and application | |
| CN113521311B (en) | Bimodal imaging-guided polymersome with tumor targeting function and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20081029 |