CN102406615B - The former times how sour salmaterol chitosan nanoparticle preparation that a kind of wheat germ agglutinin is modified - Google Patents
The former times how sour salmaterol chitosan nanoparticle preparation that a kind of wheat germ agglutinin is modified Download PDFInfo
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Abstract
The present invention relates to medical art, is the former times how sour salmaterol chitosan nanoparticle preparation and preparation method thereof that a kind of wheat germ agglutinin is modified.The present invention adopts ionic cross-linking to prepare former times how sour salmaterol chitosan nano; And utilize alveolar epithelium to there is the feature of specific sugar receptor N-Acetyl-D-glucosamine, make the former times how sour salmaterol chitosan nano that wheat germ agglutinin is modified, to be combined by the specific sugar receptor N-Acetyl-D-glucosamine of wheat germ agglutinin with alveolar epithelium, make former times how sour salmaterol chitosan nano have guiding alveolar membrane targeting.External sugared binding tests result shows, the former times how sour salmaterol chitosan nano that wheat germ agglutinin is modified has the advantage of guiding alveolar membrane, thus can reduce dosage, reduces toxic and side effects; The valid density time that the slow release of medicine makes medicine maintain in pulmonary is long, strengthens therapeutic effect.Invention formulation can be used for the medicine preparing treatment asthma, chronic bronchitis or chronic obstructive pulmonary disease.
Description
Technical field
The present invention relates to medical art, is the former times how sour salmaterol chitosan nanoparticle preparation and preparation method thereof that a kind of wheat germ agglutinin is modified.
Background technology
Along with the quickening of life style urbanization process, asthma prevalence increases gradually, and this will bring huge economy and burden on society undoubtedly.Former times, how sour salmaterol was a kind of long-acting adrenoceptor agonists, also be a bronchiectasis medicine with anti-inflammatory activity, to Nocturnal patient, there is good therapeutical effect, as relievining asthma, the choice drug of antiinflammatory, it is the important breakthrough first over nearly more than 20 years in treating asthma, is mainly used in treating asthma, chronic bronchitis and chronic obstructive pulmonary disease.
At present conventional is clinically how sour salmaterol aerosol of a kind of former times (former times how sour salmaterol aerosol: Harbin Hui Li pharmaceutcal corporation, Ltd), it is with suction administration, after in medicine suction body, the reservation of pulmonary and deposition limited, how sour salmaterol cannot concentrate in pulmonary and play curative effect former times, and delivery time is short, and dosage is large, easy generation toxic and side effects, very unfavorable for the asthma patient at night-time attack or aggravation.
Make pharmaceutical carrier with nanoparticle, there is the advantages such as entrapment efficiency is high, slow releasing pharmaceutical.Chitosan is a kind of positively charged hy-drophilic polysaccharide that chitin obtains through deacetylated process, and have good biocompatibility, biodegradable and bio-adhesive characteristic, chitosan nano is widely used as pharmaceutical carrier.The common preparation method of chitosan nano has the sedimentation method, covalent cross-linking method, ionic cross-linking and emulsified solvent dispensing volatile method etc., wherein ionic cross-linking (refers to: Zheng AP, Wang JC, Lu WL, et al.Thymopentin-loaded pH-sensitive chitosan nanoparticles for oral administration:preparation, characterization, and pharmacodynamics.J Nanosci Nanotechnol, 2006, 6 (9-10): 2936-2944.) be utilize the sodium polyphosphate had no side effect carry out ion induction gelation to chitosan and prepare a kind of method of nanoparticle, this reaction condition is gentle, do not use any organic solvent.But so far there are no by how sour for former times salmaterol is prepared into the report of nano particle preparations.
Agglutinin is a kind of glycoprotein of nonimmunogenic or sugared special body, particularly comes from the vegetalitas wheat germ agglutinin almost non-immunogenicity of Fructus Hordei Germinatus.Agglutinin alternative identifies surface of cell membrane glycan molecule or receptor spline structure, thus combine with glycosylation biomembrane, therefore, Phytoagglutinin modified medicament carrier system can mediate through cell adhesion effect, be conducive to breaking through epithelium membranes barriers (to refer to: (1) Lis H, Sharon N.Lectins asmolecules and as tools [J] .Annual Review of Biochemistry, 1986, 55:35-67. (2) Ezpeleta I, Arangoa MA, Irache JM, et al.Preparation of Ulex europaeuslectin-gliadin nanoparticle conjugates and their interaction with gastrointestinalmucus [J] .Int J Pharm, 1999, 191:25-32. (3) Sharma A, Sharma S, Khuller GK.Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolizedantitubercular drug carriers for treatment of tuberculosis [J] .J AntimicrobChemother, 2004, 54:761-766. (4) Fei YB, Li FQ, Li L, et al.Lectin-modifiedtransmucosal microspheres drug delivery system [J] .Pharm Care & Res (pharmaceutical services and research), 2010, 10:142-145.).
Summary of the invention
The object of this invention is to provide the former times how sour salmaterol chitosan nanoparticle preparation that a kind of wheat germ agglutinin with long-acting, controlled release, targeting and division of day and night pharmacology regulating and controlling effect is modified.
The present invention take sodium tripolyphosphate as cross-linking agent, adopts ionic cross-linking to prepare former times how sour salmaterol chitosan nano; And utilize alveolar epithelium to there is the feature of specific sugar receptor N-Acetyl-D-glucosamine, how sour for former times salmaterol chitosan nano is carried out wheat germ agglutinin modification, make the former times how sour salmaterol chitosan nano that wheat germ agglutinin is modified, to be combined by the specific sugar receptor N-Acetyl-D-glucosamine of wheat germ agglutinin with alveolar epithelium, make former times how sour salmaterol chitosan nano have guiding alveolar membrane targeting.
The preparation method of invention formulation is as follows:
One, component and proportioning:
Preferred:
Two, preparation process:
1) chitosan solution is prepared
By proportioning, chitosan is scattered in appropriate 0.05 ~ 1% (v/v) dilute acetic acid aqueous solution (preferably 0.1 ~ 0.5% (v/v) dilute acetic acid aqueous solution), overnight swelling, make chitosan solution;
2) sodium tripolyphosphate solution is prepared
By proportioning, sodium tripolyphosphate is dissolved in appropriate distilled water, mixes and obtain sodium tripolyphosphate solution;
3) former times how sour salmaterol solution is prepared
Under the condition of about 40 DEG C heating, by proportioning, how sour for former times salmaterol is dissolved in ethanol in proper amount, obtains former times how sour salmaterol solution;
4) by proportioning by 3) in former times how sour salmaterol Solution Dispersion in 2) in sodium tripolyphosphate solution in, make the sodium tripolyphosphate solution containing former times how sour salmaterol;
Or, by proportioning by 3) in former times how sour salmaterol Solution Dispersion in 1) in chitosan solution in, make the chitosan solution containing former times how sour salmaterol;
5) former times how sour salmaterol chitosan nano colloidal solution is prepared
Continuing magnetic force stir under, by proportioning by 2) in sodium tripolyphosphate solution slowly drip in 4) in containing former times how sour salmaterol chitosan solution in, react 10 minutes, obtain former times how sour salmaterol chitosan nano colloidal solution;
Or, continuing magnetic force stir under, by proportioning by 4) in containing former times how sour salmaterol sodium tripolyphosphate solution slowly drip in 1) in chitosan solution in, react 10 minutes, obtain former times how sour salmaterol chitosan nano colloidal solution;
Above-mentioned obtained be former times how sour salmaterol chitosan nanoparticle preparation (it is modified without wheat germ agglutinin);
6) surface amino groups of former times how sour salmaterol chitosan nano is activated
By proportioning to 5) in former times add appropriate 0.1 ~ 1% (v/v) glutaraldehyde water solution (preferably 0.2 ~ 0.5% (v/v) glutaraldehyde water solution) in how sour salmaterol chitosan nano colloidal solution, mixing jolting makes the surface amino groups of former times how sour salmaterol chitosan nano activate, unreacted glutaraldehyde is separated with phosphate buffer (pH 7.4), glutaraldehyde (to prevent its crosslinked agglutinin) unnecessary in abandoning supernatant after high speed centrifugation, obtains the former times how sour salmaterol chitosan nano colloidal solution that surface amino groups has activated;
7) wheat germ lectin cellulose solution is prepared
By proportioning, wheat germ agglutinin is dissolved in appropriate phosphate buffer (pH 7.4), obtains wheat germ lectin cellulose solution;
8) the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified is prepared
By 7) in wheat germ lectin cellulose solution join 6) in former times of having activated of surface amino groups in how sour salmaterol chitosan nano colloidal solution, whirlpool mixes, at room temperature hatch 24 hours altogether, unconjugated wheat germ agglutinin in abandoning supernatant after high speed centrifugation, obtains the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified.
The preparation of the chitosan nanoparticle preparation that the wheat germ agglutinin that this method can also be used for other drug is modified.
Detect through laser particle size analyzer, former times prepared by the present invention how sour salmaterol chitosan nano particle size range be 200 ~ 300nm, transmission electron microscope results display nanoparticle outward appearance rounding rule.External sugared binding tests result shows, the former times how sour salmaterol chitosan nano that the wheat germ agglutinin that the present invention obtains is modified has the advantage of guiding alveolar membrane, thus can reduce dosage, reduces toxic and side effects; The valid density time that the slow release of medicine makes medicine maintain in pulmonary is long, strengthens therapeutic effect.Invention formulation can be used for the medicine preparing treatment asthma, chronic bronchitis or chronic obstructive pulmonary disease.
Detailed description of the invention
Now in conjunction with the embodiments, the present invention is described in detail
Embodiment 1 prepares the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified
1) chitosan 150mg is dissolved in the dilute acetic acid aqueous solution of 100mL 0.2%, obtains chitosan solution;
2) under the condition of 40 DEG C of heating, how sour for 5mg former times salmaterol (Wuhan Yi Tai Science and Technology Ltd., lower same) is dissolved in 1ml dehydrated alcohol, obtains the alcoholic solution of former times how sour salmaterol;
3) 25mg sodium tripolyphosphate is dissolved in 15ml distilled water, and adds the alcoholic solution of former times how sour salmaterol wherein, must containing the sodium tripolyphosphate solution of former times how sour salmaterol;
4) under the continuing magnetic force stirring of 600 revs/min, slowly dripped in chitosan solution by the sodium tripolyphosphate solution containing former times how sour salmaterol, Keep agitation 10 minutes, obtains former times how sour salmaterol chitosan nano colloidal solution;
5) in former times how sour salmaterol chitosan nano colloidal solution, add the glutaraldehyde water solution of 3ml 0.1% (v/v), jolting mixes 6 hours, to activate the amino on chitosan nano surface, then phosphate buffer (pH 7.4 is used, lower same) be separated unreacted glutaraldehyde, high speed centrifugation (10000rpm, 30 minutes, lower with) and glutaraldehyde unnecessary in abandoning supernatant;
6) wheat germ agglutinin (wheat germ agglutinin is got, Medicago, lower same) 2mg, be dissolved in 1mL phosphate buffer (pH 7.4, lower same) in, this wheat germ lectin cellulose solution is joined the former times after the activation of above-mentioned surface amino groups in how sour salmaterol chitosan nano colloidal solution, whirlpool mixes, 24 hours are hatched under room temperature condition, high speed centrifugation (10000rpm, 30 minutes, lower with) unconjugated wheat germ agglutinin in abandoning supernatant afterwards, collect the colloidal solution of lower floor, obtain the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified.
Embodiment 2 prepares the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified
1) chitosan 500mg is dissolved in the dilute acetic acid aqueous solution of 100mL 0.5%, obtains chitosan solution;
2) under the condition of 40 DEG C of heating, how sour for 50mg former times salmaterol is dissolved in 2ml dehydrated alcohol, obtains the alcoholic solution of former times how sour salmaterol, and added in chitosan solution, must containing the chitosan solution of former times how sour salmaterol;
3) 100mg sodium tripolyphosphate is dissolved in 15ml distilled water, obtains sodium tripolyphosphate solution;
4) under the continuing magnetic force stirring of 600 revs/min, slowly dripped by sodium tripolyphosphate solution in the chitosan solution containing former times how sour salmaterol, Keep agitation 10 minutes, obtains former times how sour salmaterol chitosan nano colloidal solution;
5) in former times how sour salmaterol chitosan nano colloidal solution, add the glutaraldehyde water solution of 3ml 0.3% (v/v), jolting mixes 6 hours, to activate the amino on chitosan nano surface, then unreacted glutaraldehyde is separated with phosphate buffer, high speed centrifugation glutaraldehyde unnecessary in abandoning supernatant;
6) wheat germ agglutinin 10mg is got, be dissolved in 2mL phosphate buffer, this wheat germ lectin cellulose solution is joined the former times after the activation of above-mentioned surface amino groups in how sour salmaterol chitosan nano colloidal solution, whirlpool mixes, 24 hours are hatched under room temperature condition, unconjugated wheat germ agglutinin in abandoning supernatant after high speed centrifugation, collects the colloidal solution of lower floor, obtains the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified.
Embodiment 3 prepares the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified
1) chitosan 900mg is dissolved in the dilute acetic acid aqueous solution of 100mL 0.8%, obtains chitosan solution;
2) under the condition of 40 DEG C of heating, how sour for 300mg former times salmaterol is dissolved in 20ml dehydrated alcohol, obtains the alcoholic solution of former times how sour salmaterol;
3) 200mg sodium tripolyphosphate is dissolved in 15ml distilled water, and adds the alcoholic solution of former times how sour salmaterol wherein, must containing the sodium tripolyphosphate solution of former times how sour salmaterol;
4) under the continuing magnetic force stirring of 600 revs/min, slowly dripped in chitosan solution by the sodium tripolyphosphate solution containing former times how sour salmaterol, Keep agitation 10 minutes, obtains former times how sour salmaterol chitosan nano colloidal solution;
5) in former times how sour salmaterol chitosan nano colloidal solution, add the glutaraldehyde water solution of 3ml 0.6% (v/v), jolting mixes 6 hours, to activate the amino on chitosan nano surface, then unreacted glutaraldehyde is separated with phosphate buffer, high speed centrifugation glutaraldehyde unnecessary in abandoning supernatant;
6) wheat germ agglutinin 30mg is got, be dissolved in 3mL phosphate buffer, this wheat germ lectin cellulose solution is joined the former times after the activation of above-mentioned surface amino groups in how sour salmaterol chitosan nano colloidal solution, whirlpool mixes, 24 hours are hatched under room temperature condition, unconjugated wheat germ agglutinin in abandoning supernatant after high speed centrifugation, collects the colloidal solution of lower floor, obtains the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified.
Tablets in vitro is tested:
Wheat germ agglutinin prepared by embodiment 2 modify former times how sour salmaterol chitosan nanoparticle preparation and the former medicine of former times how sour salmaterol carry out the contrast experiment of tablets in vitro time, experimentation is as follows:
1) former times of a certain amount of wheat germ agglutinin being modified how sour salmaterol chitosan nanoparticle preparation and the former medicine of former times how sour salmaterol respectively in bag filter, two ends are tightened, and are placed in two tool plug wide mouthed bottles respectively;
2) in above-mentioned two tool plug wide mouthed bottles, add 100ml 0.5% sodium dodecyl sulfate solution (w/v) respectively as release medium, vibrate on 37 DEG C of constant-temperature tables, rotating speed is 120rmin
-1;
3) respectively at 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h and 18h timing sampling, every sub-sampling 1ml, adds the above-mentioned release medium of same volume;
4) by each sampling liquid respectively through 0.22 μm of filtering with microporous membrane, get subsequent filtrate high performance liquid chromatography sample introduction, by standard curve calculate former times how sour salmaterol concentration, obtain medicine accumulative releasing degree.
Tablets in vitro result of the test: reach 94.31% when the vitro cumulative release percent of the former medicine 4h of former times how sour salmaterol is 72.62%, 12h, effective acting time is 12h; And the vitro cumulative release percent of the former times how sour salmaterol chitosan nano 4h that wheat germ agglutinin that the present invention obtains is modified reaches 89.16% when being 51.05%, 18h, effective acting time can reach more than 18h.Show that the former times how sour salmaterol chitosan nano that the wheat germ agglutinin that the present invention obtains is modified has obvious slow release effect.Nano particle preparations experimental technique prepared by embodiment 1 and 3 is the same, and result is substantially consistent.
Tablets in vitro experimental technique refers to: Lin AH, Liu YM, Ping QN.Free amino groups onthe surface of chitosan nanoparticles and its characteristics [J] .Acta Pharm Sin (Acta Pharmaceutica Sinica), 2007,42:323-328.
External sugared binding tests:
Former times prepared by embodiment 2 how sour salmaterol chitosan nanoparticle preparation and the former times how sour salmaterol chitosan nanoparticle preparation modified of wheat germ agglutinin carry out the contrast experiment that external sugar combines, GenBank AF178428-derived protein GI 7682468 can be combined with agglutinin, take GenBank AF178428-derived protein GI 7682468 as substrate, after the former times how sour salmaterol chitosan nanoparticle preparation that in former times how sour salmaterol chitosan nanoparticle preparation and wheat germ agglutinin are modified hatches certain hour altogether with substrate GenBank AF178428-derived protein GI 7682468 respectively, measure its combination rate to GenBank AF178428-derived protein GI 7682468 respectively; Add competitive inhibitor N-Acetyl-D-glucosamine again, after hatching certain hour altogether, again measuring the combination rate of two kinds of preparations and GenBank AF178428-derived protein GI 7682468 respectively, illustrating that the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified has the specificity be combined with N-Acetyl-D-glucosamine by adding the former times how sour salmaterol chitosan nanoparticle preparation that before and after N-Acetyl-D-glucosamine, wheat germ agglutinin is modified with the change of substrate GenBank AF178428-derived protein GI 7682468 combination rate.Experimentation is as follows:
1) respectively by former times how sour salmaterol chitosan nanoparticle preparation 5ml that former times how sour salmaterol chitosan nanoparticle preparation 5ml and wheat germ agglutinin are modified, 3h is hatched altogether with the phosphate buffer 1 ml room temperature of the GenBank AF178428-derived protein GI 7682468 containing 200 μ g, supernatant is got after centrifugal (10000rpm, 15min);
2) gel chromatography analytic process is adopted (to refer to: Usui S, Mizuno T, Okazaki M, et al.Evaluation of a gel-permeation high-performance liquid chromatographyfor determining triglyceride levels in serum major lipoproteins, comparedwith the ultracentrifugation/precipitation method [J] .Clin Biochem, 2009, 42:114-117.) measure unconjugated GenBank AF178428-derived protein GI 7682468 amount in supernatant, according to measured value and the difference adding total amount, calculate above-mentioned two parts of preparations to the combination rate of GenBank AF178428-derived protein GI 7682468, result: former times, how sour salmaterol chitosan nano was 55% with the combination rate of GenBank AF178428-derived protein GI 7682468, wheat germ agglutinin modify after former times how sour salmaterol chitosan nano be 88.32% with the combination rate of GenBank AF178428-derived protein GI 7682468,
3) in above-mentioned two parts of preparations, respectively add 10 μm of ol N-Acetyl-D-glucosamines again, through whirlpool mixing, place 3h and make association reaction reach balance;
4) centrifugal (10000rpm, 15min), gel chromatography analytic process is adopted again to measure unconjugated GenBank AF178428-derived protein GI 7682468 amount in supernatant, according to measured value and the difference adding total amount, calculate above-mentioned two parts of preparations to the combination rate of GenBank AF178428-derived protein GI 7682468, result: former times, how sour salmaterol chitosan nano was 54% with the combination rate of GenBank AF178428-derived protein GI 7682468, wheat germ agglutinin modify after former times how sour salmaterol chitosan nano be 63.86% with the combination rate of GenBank AF178428-derived protein GI 7682468.
Experimental result shows: after adding N-Acetyl-D-glucosamine, former times, how sour salmaterol chitosan nano had almost no change with when not adding N-Acetyl-D-glucosamine with the combination rate of GenBank AF178428-derived protein GI 7682468 compared with the combination rate of GenBank AF178428-derived protein GI 7682468, and wheat germ agglutinin modify after former times, how sour salmaterol chitosan nano did not more add N-Acetyl-D-glucosamine with the combination rate of GenBank AF178428-derived protein GI 7682468 time significantly decline with the combination rate of GenBank AF178428-derived protein GI 7682468,63.86% is down to by 88.32%, illustrate that the former times how sour salmaterol chitosan nano after wheat germ agglutinin modification can be combined with the N-Acetyl-D-glucosamine added, show that wheat germ agglutinin can by N-Acetyl-D-glucosamine Competitive assays with the combination of GenBank AF178428-derived protein GI 7682468, reflect wheat germ agglutinin modify after former times how sour salmaterol chitosan nano to the sugared binding specificity of N-Acetyl-D-glucosamine, so the former times how sour salmaterol chitosan nano after wheat germ agglutinin modification can be enriched in alveolar membrane, thus reach the effect of targeting pulmonary.Nano particle preparations experimental technique prepared by embodiment 1 and 3 is the same, and result is substantially consistent.
Preparation technology of the present invention is simple, former times how sour salmaterol chitosan nanoparticle preparation after wheat germ agglutinin is modified can be combined with alveolar epithelium specific sugar receptor N-Acetyl-D-glucosamine, promote that medicine is in the gathering of alveolar membrane, thus reach the effect of targeting pulmonary, improve drug bioavailability, reduce dosage, reduce toxic and side effects.
Claims (6)
1. wheat germ agglutinin modify a former times how sour salmaterol chitosan nanoparticle preparation, it is characterized in that component and proportioning as follows:
2. wheat germ agglutinin modify a former times how sour salmaterol chitosan nanoparticle preparation, it is characterized in that component and proportioning as follows:
3. wheat germ agglutinin modify a former times how sour salmaterol chitosan nanoparticle preparation, it is characterized in that component and proportioning as follows:
4. described in claim 1,2 or 3 wheat germ agglutinin modify former times how sour salmaterol chitosan nanoparticle preparation preparation method, step is as follows:
1) chitosan solution is prepared
By proportioning, chitosan is scattered in 0.05 ~ 1%v/v dilute acetic acid aqueous solution, overnight swelling, make chitosan solution; Prepare sodium tripolyphosphate solution
By proportioning, sodium tripolyphosphate is dissolved in appropriate distilled water, mixes and obtain sodium tripolyphosphate solution;
2) former times how sour salmaterol solution is prepared
Under the condition of heating, by proportioning, how sour for former times salmaterol is dissolved in ethanol in proper amount, obtains former times how sour salmaterol solution;
3) by proportioning by how sour for former times salmaterol Solution Dispersion in 2) in, make the polyphosphoric acids sodium solution containing former times how sour salmaterol;
Or, by proportioning by how sour for former times salmaterol Solution Dispersion in 1) in, make the chitosan solution containing former times how sour salmaterol;
4) the chitosan nano colloidal solution of former times how sour salmaterol is prepared
Under continuing magnetic force stirs, by proportioning by 2) solution slowly drips in 4) in the chitosan solution containing former times how sour salmaterol in, react 10 minutes, obtain the chitosan nano colloidal solution of former times how sour salmaterol;
Or, under continuing magnetic force stirs, by proportioning by 4) in containing former times how sour salmaterol polyphosphoric acids sodium solution be added dropwise to 1) in liquid, react 10 minutes, obtain former times how sour salmaterol chitosan nano colloidal solution;
5) surface amino groups of former times how sour salmaterol chitosan nano is activated
By proportioning to 5) in add appropriate 0.1 ~ 1%v/v glutaraldehyde water solution in obtained nanoparticle colloidal solution, mixing jolting makes the surface amino groups of chitosan nano activate, unreacted glutaraldehyde is separated with phosphate buffer, glutaraldehyde unnecessary in abandoning supernatant after high speed centrifugation, obtains the former times how sour salmaterol chitosan nano colloidal solution that surface amino groups has activated;
6) wheat germ lectin cellulose solution is prepared
By proportioning, wheat germ agglutinin is dissolved in phosphate buffer, obtains wheat germ lectin cellulose solution;
7) the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified is prepared
Former times wheat germ lectin cellulose solution being added above-mentioned surface amino groups activated is in how sour salmaterol chitosan nano colloidal solution, whirlpool mixes, at room temperature hatch 24 hours altogether, unconjugated agglutinin in abandoning supernatant after high speed centrifugation, obtains the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin is modified.
5. modify by wheat germ agglutinin according to claim 4 former times how sour salmaterol chitosan nanoparticle preparation preparation method, chitosan is scattered in 0.1 ~ 0.5%v/v dilute acetic acid aqueous solution when it is characterized in that preparing chitosan solution, when activating the surface amino groups of former times how sour salmaterol chitosan nano, the concentration of glutaraldehyde water solution is 0.2 ~ 0.5%v/v.
6. the former times how sour salmaterol chitosan nanoparticle preparation that wheat germ agglutinin described in claim 1 or 2 or 3 is modified treats the application in asthma, chronic bronchitis or chronic obstructive pulmonary disease in preparation.
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