CN101028521A - Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method - Google Patents
Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method Download PDFInfo
- Publication number
- CN101028521A CN101028521A CN 200710020993 CN200710020993A CN101028521A CN 101028521 A CN101028521 A CN 101028521A CN 200710020993 CN200710020993 CN 200710020993 CN 200710020993 A CN200710020993 A CN 200710020993A CN 101028521 A CN101028521 A CN 101028521A
- Authority
- CN
- China
- Prior art keywords
- medicine
- adjuvant
- superfine
- nuclear
- fibre
- 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.)
- Granted
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
An orally taken medicine based on electrospun superfine shell-core fibers and able to be released in colon for treating local colon disease or physiorhythmic disease is composed of the fibers consisting of the shell prepared from pH-sensitive polymer and the core prepared from the high-molecular polymer able to be specifically degraded by the unique enzyme system in colon, adhesive, and the absorption promoter, and the medicine carried by said core of fibers.
Description
Technical field
The present invention relates to a kind of oral colon positioning feed preparation, be used for the oral administration of colon local disease, physiological rhythm disease and polypeptide protein class medicine, belong to the technical field of pharmaceutical preparation based on electric spinning superfine nuclear fibre.
Background technology
Modern medicinal agents has entered drug delivery system (Drug Delivery System, DDS), it is the drug-supplying system epoch, pharmaceutical preparation is being experienced conventional formulation, long-acting and slow releasing preparation, controlled release preparation and targeting preparation after the stage, the research of various drug-supplying systems and use and made it enter the intelligent administration stage.Drug-supplying system makes the notion of pharmaceutical preparation that qualitative leap arranged, and pharmaceutical preparation no longer only is a medicine " prescription " with certain dosage form, but " device " carrying and transmit medicine.
The electrospinning silk is the spining technology of the invention thirties in 20th century, is to obtain the effective ways of nanometer to the micron diameter superfine fibre.In recent years, be subjected to the attention of researcher day by day based on the drug-supplying system of electrospinning fibre, the research work that people begin to be correlated with, but in this regard research at present is still limited, also has very big research and development space.Along with drug preparation technique develops to efficient, low toxicity direction, targeting or location release tech are one of main means, and no matter present ultra-fine electrospinning fibre is solvent spinning or milk thread, and prepared fiber does not generally have tangible medicine location releasing effect.
Route of administration and method are most important to the safety and the effectiveness of medication.Oral administration is the especially first-selected route of administration of long-term prescription of clinical administration, by designing suitable dosage form, can reach and the identical curative effect of intravascular administration (as intravenous injection), the tissue necrosis that infection, thrombosis, the drug extravasation that can avoid intravascular administration to cause causes, particularly during long term administration, can avoid the inconvenience of intravascular administration, patient dependence is good, can improve patient's quality of life, reduce medical expense.
(the Oral colon-specific drug delivery system of oral colon positioning feed system, OCDDS) be that oral route is with the class pharmaceutical preparation of drug delivery to conlon targeting release, be meant by suitable method, avoid discharging at stomach, duodenum, jejunum and ileum front end behind the drug oral, requirement is until being transported to ileocecus release again, a kind of novel drug-delivery preparation of performance part or whole body therapeutic effect.
The curative effect of medicine, promptly the height of bioavailability is the key issue of medicament design.Influence the principal element of bioavailability in the oral administration, absorption difference, liver and gastral first pass effect as medicine make some drugs most of metabolism inefficacy before arriving focus, digestive enzyme degraded destroy protein and peptide drugs etc., make the oral administration biaavailability of medicine low, thereby not only cause between individuality and difference in individual, blood concentration fluctuation is big, weak curative effect increases production cost simultaneously, increases the toxic probability of body.And OCDDS, medicine does not discharge in stomach and small intestinal, just discharge when being transported to colon, can be used for treating locality intestinal tract diseases such as colitis, colon cancer, colon parasitic disease, medicine directly acts on lesions position and does not cause the toxic and side effects of general, has avoided gastral first pass effect simultaneously; Upper gastrointestinal various protease can decompose, digest degraded and destroy protein and peptide drugs, and at the equal inactivation of a large amount of digestive enzyme of colon, the abundant lymphoid tissue of colon is oral macromolecular drug, particularly the absorption of polypeptide protein class medicine provides an effective way, can improve its oral administration biaavailability.
Colonic has a large amount of microorganisms, its concentration is equivalent to 5 orders of magnitude of gastrointestinal tract microorganism concn, surviving and surpassing 400 kinds of profitable strains, flora concentration is 1011/mL intestinal juice, some antibacterial can produce specific bacterial enzymes such as β-glucuronide enzyme, β-heteroside enzyme, cellulase, nitroreductase, azo reductase, α-dehydrogenase, Cholesterol dehydrogenase, this is the marked feature that colon is different from other parts of digestive tract, can utilize design flora flip-over type (enzymolysis type) the self-adjustable OCDDS of enzyme system of colon uniqueness; The colonic fluid pH value is higher, is about 6.5～7.5 (pH of stomach is 0.9～1.5, and small intestinal is 6.0～6.8), also can utilize gastrointestinal tract pH difference design OCDDS.In addition, colon place substance transportation speed is slow, medicine can be detained 20～30h at this, therefore there is the people to propose " colon closed-chamber " theory, be that medicine can concentrate herein, constitute " bank ", and be absorbed into blood thus, thereby can guarantee that medicine is absorbed (zero level absorption curve) with a kind of constant speed, performance " long lasting drug formulations " effect; Oral drugs are long and relatively stable through the time that digestive tract arrives colon, are generally 3～6h, so OCDDS also can utilize time-lag effect design OCDDS to be used for the treatment of the physiological rhythm disease by postponing the release method.
In sum, OCDDS all has tempting market prospect and clinical meaning at the oral administration of treatment colon local disease, physiological rhythm disease and polypeptide protein class medicine.
As one of research focus of preparation, pH dependent form, time lag type, flora flip-over type and comprehensive OCDDS all have research both at home and abroad, but the positioning performance of comprehensive all kinds of OCDDS, the complexity of technology, biocompatibility and bioavailability are the main flow that the OCDDS of self-regulated comprehensive Design will become its development in conjunction with the enzyme of gastrointestinal tract pH difference and colon uniqueness.Wherein receive the OCDDS of micro-meter scale with its distinctive advantage, become one of development focus of OCDDS, this is because its particle diameter is very little, be easy to adhere to, the increase of anelasticity when both having helped local application after oral, also help increasing the contact area and the time of contact of medicine and intestinal wall, promote drug absorption, improve bioavailability.The research of this respect at present concentrates on nanoparticle (nanoparticle) and nanosphere (microspheres), microcapsule (microcapsule) etc., and still belongs to blank both at home and abroad based on the oral colon positioning feed preparation research of electric-woven super-fine fiber.
Electric-woven super-fine fiber is applied to OCDDS, the advantage that not only has above-mentioned particulate delivery system, the superior part that its uniqueness is more arranged: (1) can power carrier material of spinning is abundant, can be according to the characteristic of medicine, seek best method and only material to reach higher drug loading, the composition of spinning liquid and proportioning can be adjusted flexibly, make the characteristics that the drug release behavior is controlled.(2) compare with existing preparation OCDDS method, electrospinning fibre is the method that " single step " obtains pharmaceutical preparation, but the cycle is short, preparation method is simple, the lower continuous production of cost.(3) preparation process gentleness, electrospinning solution uses the optimum solvent of corresponding high polymer, the compatible high polymers of matter such as selection and medicine, at room temperature be prepared, the character of the pH of electrospinning solution, ionic strength and viscosity and medicine and stability coupling, medicine can recurring structure or conformation, physicochemical property change, can not lose biological activity.(4) variation of electrospinning fibre structure and pattern also provides convenience for it is applied to OCDDS.
Oral colon positioning feed preparation based on electric-woven super-fine fiber provided by the invention, the fiber of preparation has nucleocapsid structure: medicine and carrier high polymer are made nuclear solution, enteric polymer is made shell solution, under the effect of high voltage electric field, will examine solution and become the nucleocapsid structure superfine fibre then with shell solution cospinning.Housing is rolled in nucleome inside with pharmaceutical pack, can prevent medicine hydrolysis or chance digestive enzyme degraded destruction under the stomach acidity condition, thereby improve the stability of medicine in gastrointestinal tract.Simultaneously, for the development oral colon positioning feed preparation, nucleocapsid structure can select different adjuvants to design the character of shell and nuclear respectively, makes that the oral colon positioning feed preparation of comprehensive gastrointestinal tract pH difference of development and self-adjustable is more flexible, guarantees the conlon targeting characteristic of preparation.
We select the adjuvant of safe pharmaceutically acceptable polymer as preparation.Its middle shell intends adopting pH responsive type high molecular polymer with adjuvant, and they dissolve in the environment of pH＞7.0, cause drug release, are nontoxic, the inexpensive polymer of a class, and being applied to oral colon positioning feed preparation has good prospect.Simultaneously, the enzyme that we design the uniqueness that can be produced by colon bacteria that contains proper proportion in the nucleome adjuvant is the macromolecular material of specificity degraded, they at stomach, small intestinal since the shortage of corresponding enzyme can not be degraded, the housing of fiber is the enteric polymer with suitable thickness in addition, and this just guarantees that medicine does not discharge at the harmonization of the stomach small intestinal.Like this, utilize the characteristic comprehensive Design oral colon positioning feed preparation of housing and nucleome macromolecule polymer material respectively, can reach good location releasing effect.In addition, also can contain the adjuvant of other kind in the nucleome polymer,, also can add absorption enhancer to promote to support the absorption of medicine at intestinal as intestinal pasting material, release sluggishness/accelerated material etc.Multiple adjuvant use in conjunction had both made that the oral colon positioning feed preparation of design had different drug release rates and mode according to different needs, made again on the basis of medicine conlon targeting release, increased drug absorption, effectively improved its bioavailability.
Oral colon positioning feed preparation based on the electrospinning nuclear fibre provided by the invention is prepared by the coaxial electrically spun device, rely on the electrospinning nuclear fibre, prepare OCDDS, will produce important social benefit and economic benefit with clear and definite conlon targeting release and high bioavailability.
Summary of the invention
Technical problem: the purpose of this invention is to provide a kind of oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and preparation method thereof.Said preparation can improve colon fraction medicine concentration, effectively treats colon local disease; Control polypeptide, protein medicaments and vaccine be in conlon targeting release, avoids them to be subjected to gastric acid in the upper digestive tract, pepsin and the effect of pancreas enzyme and destroyed; By the method for segmented intestine targeted delay release, treatment physiological rhythm disease.
Technical scheme: the present invention is achieved by the following technical solution:
Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre of the present invention is a form with fabric nonwoven cloth or non-woven mat, fiber is made up of medicine and adjuvant, has nucleocapsid structure; Medicine is loaded in the fiber nucleome by bag, adjuvant is biodegradable or absorbable medicinal materials, its middle shell adjuvant is the high molecular polymer of pH responsive type, and the nucleome adjuvant is the high molecular polymer and the intestinal pasting material of specificity degraded for the enzyme of the uniqueness that can be produced by colon bacteria and discharges sluggishness/accelerated material or increase supports the absorption enhancer that medicine absorbs at colon.
Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre provided by the invention is the self-regulated comprehensive Design in conjunction with gastrointestinal tract pH difference and colon specific enzymes.Have good colon positioning release feature, and can have different drug release rates and mode owing to the kind or the proportioning difference of nucleome/housing adjuvant.And housing is rolled in nucleome inside with pharmaceutical pack, can prevent medicine hydrolysis or chance digestive enzyme degraded destruction under the stomach acidity condition, thereby improve the stability of medicine in gastrointestinal tract.In addition, in nucleome, add absorption enhancer, on the basis of medicine location release, effectively improve its bioavailability to promote to support the absorption of medicine at intestinal.
The present invention is the method that " single step " obtains pharmaceutical preparation, and the medicine carrying superfine nuclear fibre of formation has certain mechanical strength and toughness, can be used as independent preparation and directly uses.
Technical scheme comprises the steps and condition:
1) with nucleome adjuvant and medicine and solvent, sonic oscillation or magnetic agitation obtain examining solution;
2) with housing adjuvant and solvent, sonic oscillation or magnetic agitation obtain shell solution;
3) under the effect of high voltage electric field, will examine solution and the coaxial cospinning of shell solution, obtain the superfine nuclear fibre of nanometer to micron diameter, medicine is loaded in nucleome inside by bag, forms the superfine nuclear fibre non-woven fabrics or the superfine nuclear fibre non-woven mat of medicine carrying;
4) superfine nuclear fibre non-woven fabrics or non-woven mat are placed on 60～80 ℃ of placement 6～24h in the vacuum drying oven, remove residual solvent wherein.
Employed solvent is the optimum solvent of emergencing copolymer mutually in step (1) and step (2), can be single solvent, or mixed solvent, or has added the single or mixed solvent of surfactant, solubilizing agent or pH regulator agent.
In the step 1), by bag be loaded in fiber examine intravital medicine for the treatment colon local disease or treatment physiological rhythm one or more medicines disease or the polypeptide protein class, as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, camptothecine, Betula platyphylla Suk. acid, paclitaxel, Ai Disha, sulfasalazine, berberine, dioctahedral smectite, ACTH, adrenocortical hormone, sulphonamides, aspirin, indometacin, theophylline, sodium cromoglicate, hydrochlorothiazide, cyclopenthiazide, chlortalidone, furosemide, reserpine, verticil, clonidine hydrochloride, nifedipine, amlodipine, prazosin, insulin, the human growth hormone, erythropoietin etc., medicine polarity is similar with adjuvant to the nucleome polymer, and both have the compatibility preferably; With adjuvant content in the fiber is the quality radix, and carrying drug ratio is 0.1～200%.
In step 1) Chinese medicine concentration is 0.01～200% of the saturation solubility of medicine in solvent; Nuclear solution nucleus is 1～100% with the mass concentration of adjuvant.
The high molecular polymer that the unique enzyme of the colon that uses in step 1) is the specificity degraded is as: azo polymer (as the azo polyurethane etc.); Polysaccharide macromolecule (as chitosan, pectin, chondroitin sulfate, cyclodextrin, glucosan, melon Auricularia glue, inulin, locust bean gum, amylose etc.).Other adjuvant sticks, discharges sluggishness/acceleration or absorb promotion as intestinal, as polyethylene glycols, polyvinylpyrrolidone class, cellulose family, polyvinyl alcohol, sodium alginate, hyaluronic acid, modified starch, polyethylene glycol oxide, cholesterol, phospholipid, polylactic acid, poly-epsilon-caprolactone, lactide, Brazil wax, carbomer, phytohemagglutinin, tween series, poloxamer, polyoxyethylene castor oil, sodium lauryl sulphate, EDTA-Na etc.Employed adjuvant is one or more the mixture in the above-mentioned material in this step.
In step 2) mesochite solution middle shell is 1～100% with the mass concentration of adjuvant.The housing adjuvant is a pH responsive type high molecular polymer, and they are one or more the mixture in the following polymers: acrylic resin (as Eudragit L, Eudragit S), cellulose acetate phthalate ester (CAP), hypromellose phthalate ester (HPMCP), Hydroxypropyl Methylcellulose Phathalate (HPMCP), carboxyethyl methylphosphinate cellulose (CMEC) etc.
The electrostatic spinning apparatus that the present invention adopts, sketch map as shown in Figure 1.Wherein
High voltage power supply: be used for producing the highfield between spinning appts and gathering-device, generally adopt the high direct voltage electrostatic generator of maximum output voltage at 30～100kV.Adopt the homemade high voltage power supply of 0～40kV among the present invention.
Gathering-device: can be metal plate, grid or cylinder etc.Utilize difform gathering-device, can be made into various non-woven fabrics products.Adopt aluminium foil as gathering-device among the present invention.
Solution storage device: can use syringe or liquid storage pipe etc., wherein fill polymer solution.Adopt 5ml glass syringe storage solutions among the present invention.
Coaxial spinning appts: spinning appts mainly is made up of the metal needle of 200 a μ l trace rifle head and a syringe, and metal needle is enclosed within micro-rifle head inside.Directly high voltage power supply is linked to each other with the metal needle of syringe, need not to insert in addition electrode.
The solution propulsion plant: solution advances to adopt installs air pump adjusting hydrostatic pressure in the solution storage device, perhaps utilize the method for the slow pushing syringe of numerical controlled machinery device, and this dual mode can be controlled flow rate of liquid in spinning process.
The controllable flow rate syringe pump that adopts 0.08um/min～87.75mm/min among the present invention is as the solution propulsion plant.
The critical component of this device is special coaxial spinning head (as shown in Figure 1), and by a metal needle, two micro-rifle heads and an adapter of plastic assemble through processing.Two micro-rifle heads link together by adapter of plastic, and metal needle bends after passing adapter of plastic, make it be embedded in micro-rifle head inside.The tube for transfusion of metal needle and certain-length links to each other, and is used for carrying nuclear solution (shown in redness among Fig. 1); Top micro-rifle head also links to each other with the tube for transfusion of certain-length, is used for carrying shell solution (shown in green among Fig. 1).Select the metal needle of different model and the flow that micro-rifle head can change nuclear solution and shell solution for use, so just can be easy to prepare the superfine fibre of different compositions, thickness.In addition, can change the length of tube for transfusion, the condition that adapts to the different experiments chamber is so that operation.
This device adopts two syringe pumps to come respectively can to change the fltting speed of nuclear solution and shell solution so easily simultaneously as the propeller of nuclear solution and shell solution, and then changes the character such as composition, thickness of superfine fibre.
This device adopts the bin of two glass syringes as nuclear solution and shell solution, can make the progradation of solution and shell solution more smooth and easy like this.
For obtaining high-quality superfine nuclear fibre, electrospinning strand spare of the present invention will suitably be controlled, and these spinning conditions comprise the design of (1) coaxial spinning appts; (2) concentration and the viscosity of nuclear solution and shell solution; (3) rate of outflow of nuclear solution and shell solution; (4) intensity of high voltage electric field and distribution.
Beneficial effect: the oral colon positioning feed based on electric spinning superfine nuclear fibre provided by the invention can reach following purpose:
1) improves colon fraction medicine concentration, effectively treat colon local disease (as colitis, Crohn ' sdisease, colon cancer, polyp of colon, fistula of colon etc.);
2) control polypeptide protein class medicine is in conlon targeting release, avoids them to be subjected to gastric acid in the upper digestive tract, pepsin and the effect of pancreas enzyme and destroyed;
3) method by segmented intestine targeted delay release, treatment physiological rhythm disease (as morning deadlock, asthma, hypertension etc.).
Electric spinning superfine nuclear fibre of the present invention mainly contains following advantage:
1) no matter electric spinning superfine drug-loading fibre in the past is solvent spinning or milk thread, and prepared fiber is not generally significantly located releasing effect.The superfine fibre of the present invention's preparation has nucleocapsid structure, utilize the pH sensitivity of housing and nucleome macromolecule polymer material, specific flora or enzyme trigger characteristic comprehensive Design conlon targeting release oral formulations, and can have different drug release rates and mode owing to the kind or the proportioning difference of adjuvant, reach good location releasing effect.In addition, in nucleome, add absorption enhancer, on the basis of medicine location release, effectively improve its bioavailability to promote to support the absorption of medicine at colon.Widened the application of electrospinning fibre, and made this application adapt to actual demand more versatile and flexiblely as drug delivery vehicle.
2) the present invention utilizes coaxial spinning appts, simultaneously with two kinds of different polymer solutions, under the high voltage electric field effect, is spun into the superfine fibre with nucleocapsid structure.Medicine is dispersed in the nucleome, and one deck housing is also wrapped up in the nucleome outside, can guarantee that like this medicine is wrapped in fibrous inside, thereby ensures that effectively the intestinal targeting positioning control that supports medicine discharges, and prevents the burst effect of medicine; Avoid medicine hydrolysis or chance digestive enzyme degraded destruction under the stomach acidity condition simultaneously, thereby improve the stability of medicine in gastrointestinal tract.
3) drug loading in the nuclear fibre of the present invention can be regulated within a large range, is radix with the quality of high molecular polymer, and carrying drug ratio reaches 0.1～200%, with the character that adapts to different pharmaceutical and the needs of different syndromes.Because under the high voltage electric field effect, fibrous solution in solidification process the quick drawing process of diameter from the millimeter to the micron has taken place, fiber has good orientation and intensity.Even drug loading reaches more than 100%, good mechanical performance is arranged also.
4) the electrospinning nuclear fibre of colon positioning release provided by the invention, its diameter in nanometer to micron dimension, compare with conventional dose, this minute yardstick dosage form has very big specific surface area, because its surperficial adhesiveness and little particle diameter, the increase of anelasticity when helping local application also helps increasing the contact area and the time of contact of medicine and intestinal wall, improves bioavailability.This superfine nuclear fibre is made non-woven fabrics or fiber felt, with other nano-medicament carrier, compare as nanometer liposome, polymer nanocomposite capsule, nanosphere, polymer micelle etc., mechanical strength is big, not needing further to be processed into other dosage form, can be used as separate dosage forms and directly use, is the method that " single step " obtains pharmaceutical dosage form, but short continuous production of cycle, technical difficulty is little, cost is low.
5) intestine target medicinal controlled release nuclear fibre preparation method provided by the invention, because nuclear solution and shell solution all use the optimum solvent of corresponding adjuvant, and the character of medicine and high polymer is compatible, thereby made full use of the advantage of electrostatic spinning technique, solution jet stretches at extremely short time inner height, organic solvent and aqueous solvent be evaporation simultaneously in the extremely short time, and medicine and high polymer are not separated, and obtains the ideal superfine nuclear fibre of drug encapsulation.
6) preparation process gentleness of the present invention at room temperature is prepared, the character of the pH of electrospinning solution, ionic strength and viscosity and medicine and stability coupling, medicine can recurring structure or conformation, physicochemical property change, can not lose biological activity.
Description of drawings
Fig. 1 is an experimental provision used in the present invention;
Fig. 2 is nuclear fibre SEM (scanning electron microscope) figure of the embodiment of the invention 1;
Fig. 3 is nuclear fibre TEM (transmission electron microscope) figure of the embodiment of the invention 1;
Fig. 4 is nuclear fibre SEM (scanning electron microscope) figure of the embodiment of the invention 2;
Fig. 5 is nuclear fibre TEM (transmission electron microscope) figure of the embodiment of the invention 2;
Fig. 6 is nuclear fibre SEM (scanning electron microscope) figure of the embodiment of the invention 3;
Fig. 7 is nuclear fibre TEM (transmission electron microscope) figure of the embodiment of the invention 3.
The specific embodiment
Further specify the present invention by the following examples, but claim of the present invention is not limited only to embodiment.
Embodiment 1:
Medicine 5-fluorouracil (5-FU) with the treatment colon cancer is a model drug, and preparation is based on the 5-FU oral colon positioning feed preparation of electric spinning superfine nuclear fibre.
Preparation is a form with the fabric nonwoven cloth, and fiber has nucleocapsid structure; 5-FU is loaded in the fiber nucleome by bag, and the housing adjuvant is polyacrylic resin (Eudragit S100), and the nucleome adjuvant is chitosan, polyvinyl alcohol and hydroxypropyl methylcellulose.With adjuvant content in the fiber is the quality radix, and carrying drug ratio is 25%.
The preparation method of preparation:
1.) with nucleome adjuvant and medicine and solvent, sonic oscillation or magnetic agitation obtain examining solution;
2.) with housing adjuvant and solvent, sonic oscillation or magnetic agitation obtain shell solution;
3.) under the effect of high voltage electric field, will examine solution and the coaxial cospinning of shell solution, obtain the superfine nuclear fibre of nanometer to micron diameter, medicine is loaded in nucleome inside by bag, forms the superfine nuclear fibre non-woven fabrics or the superfine nuclear fibre non-woven mat of medicine carrying;
4.) superfine nuclear fibre non-woven fabrics or non-woven mat are placed on 60 ℃ of placement 24h in the vacuum drying oven, remove residual solvent wherein.
In step 1), solvent is 50% aqueous acetic acid, and 5-FU concentration is 100% of its saturation solubility in solvent; Nuclear solution nucleus is 50% (chitosan: polyvinyl alcohol: hydroxypropyl emthylcellulose=7: 1: 2) with the mass concentration of adjuvant.
In step 2) in, solvent is 80% aqueous acetic acid, shell solution middle shell is 10% with the mass concentration of adjuvant.
Precision takes by weighing the superfine nuclear fibre of an amount of embodiment gained, successively discharges 2 hours respectively in simulated gastric fluid under laboratory condition, discharges 4 hours in the simulation intestinal fluid, discharges 4 hours in the simulation colonic fluid.
The result shows, fibre diameter is 300～1000nm (accompanying drawing 2), form nucleocapsid structure (accompanying drawing 3) more completely, 2 hours 5-FU discharge hardly in simulated gastric fluid, the cumulative release of 4 hours 5-FU is less than 20% in the simulation intestinal fluid, and in the simulation colonic fluid in 4 hours 5-FU can reach fully and discharge.
Embodiment 2:
To treat hypertensive medicine prazosin is model drug, and preparation is based on the prazosin oral colon positioning feed preparation of electric spinning superfine nuclear fibre.
Preparation is a form with the fabric nonwoven cloth, and fiber has nucleocapsid structure; Prazosin is loaded in the fiber nucleome by bag, and the housing adjuvant is the cellulose acetate phthalate ester, and the nucleome adjuvant is HP-, alginate, hydroxymethyl ethyl cellulose and methylcellulose.With adjuvant content in the fiber is the quality radix, and carrying drug ratio is 1%.
The preparation method of preparation:
1.) with nucleome adjuvant and medicine and solvent, sonic oscillation or magnetic agitation obtain examining solution;
2.) with housing adjuvant and solvent, sonic oscillation or magnetic agitation obtain shell solution;
3.) under the effect of high voltage electric field, will examine solution and the coaxial cospinning of shell solution, obtain the superfine nuclear fibre of nanometer to micron diameter, medicine is loaded in nucleome inside by bag, forms the superfine nuclear fibre non-woven fabrics or the superfine nuclear fibre non-woven mat of medicine carrying;
4.) superfine nuclear fibre non-woven fabrics or non-woven mat are placed on 60 ℃ of placement 24h in the vacuum drying oven, remove residual solvent wherein.
In step 1), solvent is an ethanol, and prazosin concentration is 1% of its saturation solubility in solvent; Nuclear solution nucleus is 10% (HP-: hydroxymethyl ethyl cellulose: methylcellulose: alginate=3: 5: 1: 1) with the mass concentration of adjuvant.
In step 2) in, solvent is 80% aqueous acetic acid, contains 0.5% poloxamer, shell solution middle shell is 10% with the mass concentration of adjuvant.
Precision takes by weighing the superfine nuclear fibre of an amount of embodiment gained, successively discharges 2 hours respectively in simulated gastric fluid under laboratory condition, discharges 4 hours in the simulation intestinal fluid, discharges 4 hours in the simulation colonic fluid.
The result shows, fibre diameter is 1～1.5 μ m (accompanying drawing 4), form nucleocapsid structure (accompanying drawing 5) more completely, 2 hours prazosin discharge hardly in simulated gastric fluid, the cumulative release of 4 hours prazosin is less than 8% in the simulation intestinal fluid, and in the simulation colonic fluid in 4 hours prazosin can reach fully and discharge.
Embodiment 3:
To treat hypertensive medicine prazosin is model drug, and preparation is based on the prazosin oral colon positioning feed preparation of electric spinning superfine nuclear fibre.
Preparation is a form with the fabric nonwoven cloth, and fiber has nucleocapsid structure; Prazosin is loaded in the fiber nucleome by bag, and the housing adjuvant is the cellulose acetate phthalate ester, and the nucleome adjuvant is HP-, alginate, hydroxymethyl ethyl cellulose and methylcellulose.With adjuvant content in the fiber is the quality radix, and carrying drug ratio is 200%.
The preparation method of preparation:
1.) with nucleome adjuvant and medicine and solvent, sonic oscillation or magnetic agitation obtain examining solution;
2.) with housing adjuvant and solvent, sonic oscillation or magnetic agitation obtain shell solution;
3.) under the effect of high voltage electric field, will examine solution and the coaxial cospinning of shell solution, obtain the superfine nuclear fibre of nanometer to micron diameter, medicine is loaded in nucleome inside by bag, forms the superfine nuclear fibre non-woven fabrics or the superfine nuclear fibre non-woven mat of medicine carrying;
4.) superfine nuclear fibre non-woven fabrics or non-woven mat are placed on 60 ℃ of placement 24h in the vacuum drying oven, remove residual solvent wherein.
In step 1), solvent is an ethanol, and prazosin concentration is 200% of its saturation solubility in solvent; Nuclear solution nucleus is 10% (HP-: hydroxymethyl ethyl cellulose: methylcellulose: alginate=3: 5: 1: 1) with the mass concentration of adjuvant.
In step 2) in, solvent is 80% aqueous acetic acid, contains 0.5% poloxamer, shell solution middle shell is 10% with the mass concentration of adjuvant.
Precision takes by weighing the superfine nuclear fibre of an amount of embodiment gained, successively discharges 2 hours respectively in simulated gastric fluid under laboratory condition, discharges 4 hours in the simulation intestinal fluid, discharges 4 hours in the simulation colonic fluid.
The result shows, fibre diameter is 3～10 μ m (accompanying drawings 6), form nucleocapsid structure (accompanying drawing 7) more completely, 2 hours prazosin discharge hardly in simulated gastric fluid, the cumulative release of 4 hours prazosin is less than 15% in the simulation intestinal fluid, and in the simulation colonic fluid in 4 hours prazosin can reach fully and discharge.
Claims (7)
1. the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre is characterized in that said preparation is a form with fabric nonwoven cloth or non-woven mat, fiber is made up of medicine and adjuvant, has nucleocapsid structure; Medicine is loaded in the fiber nucleome by bag, adjuvant is biodegradable or absorbable medicinal materials, its middle shell adjuvant is the high molecular polymer of pH responsive type, and the nucleome adjuvant is the high molecular polymer and the intestinal pasting material of specificity degraded for the enzyme of the uniqueness that can be produced by colon bacteria and discharges sluggishness/accelerated material or increase supports the absorption enhancer that medicine absorbs at colon.
2. the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 1, it is characterized in that, wrap be loaded in fiber examine intravital medicine for the treatment colon local disease or treat physiological rhythm one or more medicines disease or the polypeptide protein class; Medicine polarity is similar with adjuvant to the nucleome polymer, and both have the compatibility preferably; With adjuvant content in the fiber is the quality radix, and carrying drug ratio is 0.1～200%.
3. the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 1 is characterized in that, described fibre diameter is tens nanometers to tens micron; Fiber has certain mechanical strength and toughness, can be used as independent preparation directly for orally using.
4. the preparation method of the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 1 is to it is characterized in that this method is:
1.) with nucleome adjuvant and medicine and solvent, sonic oscillation or magnetic agitation obtain examining solution;
2.) with housing adjuvant and solvent, sonic oscillation or magnetic agitation obtain shell solution;
3.) under the effect of high voltage electric field, will examine solution and the coaxial cospinning of shell solution, obtain the superfine nuclear fibre of nanometer to micron diameter, medicine is loaded in nucleome inside by bag, forms the superfine nuclear fibre non-woven fabrics or the superfine nuclear fibre non-woven mat of medicine carrying;
4.) superfine nuclear fibre non-woven fabrics or non-woven mat are placed on 60～80 ℃ of placement 6～24h in the vacuum drying oven, remove residual solvent wherein.
5. the preparation method of the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 4 is characterized in that in the described step 1) that drug level is 0.01～200% of the saturation solubility of medicine in solvent; Nuclear solution nucleus is 1～100% with the mass concentration of adjuvant.
6. the preparation method of the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 4 is characterized in that described step 2) mesochite solution middle shell is 1～100% with the mass concentration of adjuvant.
7. the preparation method of the oral colon positioning feed preparation based on electric spinning superfine nuclear fibre as claimed in claim 4, it is characterized in that, in step 1) and step 2) in employed solvent be the optimum solvent of emergencing copolymer mutually, it can be single solvent, or mixed solvent, or added the single or mixed solvent of surfactant, solubilizing agent or pH regulator agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100209939A CN101028521B (en) | 2007-04-06 | 2007-04-06 | Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100209939A CN101028521B (en) | 2007-04-06 | 2007-04-06 | Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101028521A true CN101028521A (en) | 2007-09-05 |
| CN101028521B CN101028521B (en) | 2010-10-27 |
Family
ID=38714183
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100209939A Expired - Fee Related CN101028521B (en) | 2007-04-06 | 2007-04-06 | Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101028521B (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101785760A (en) * | 2010-03-25 | 2010-07-28 | 东华大学 | Spontaneously-combined chitosan medicine-carrying nano particle and preparation method thereof |
| CN102697727A (en) * | 2012-06-12 | 2012-10-03 | 东华大学 | Method for preparing self-assembly ketoprofen liposome by electrostatic spinning technology |
| CN103596620A (en) * | 2011-05-12 | 2014-02-19 | 奥托·博克保健有限公司 | Electrode comprising an embedded layer, and a method for producing same |
| CN105040279A (en) * | 2015-08-14 | 2015-11-11 | 北京化工大学 | Preparation method for core-shell structure nanofiber membrane with cyclodextrinpolypseudortaxane molecule channel on surface |
| CN106702597A (en) * | 2016-12-20 | 2017-05-24 | 华南理工大学 | Kernel-shell structural nanofiber membrane, preparation method thereof and application |
| CN106757778A (en) * | 2016-12-01 | 2017-05-31 | 华南协同创新研究院 | A kind of spacetabs type insect-pest nano fibrous membrane and preparation method and application |
| CN107447366A (en) * | 2017-08-03 | 2017-12-08 | 东华大学 | A kind of sensitive medicament-carried sustained release nano fiber films of pH and its preparation method and application |
| US20180305524A1 (en) * | 2014-11-28 | 2018-10-25 | The American University In Cairo | Inulin Nanofibers |
| CN109330977A (en) * | 2018-09-27 | 2019-02-15 | 上海理工大学 | Lipid substance-coated drug-loaded nanofiber and preparation method thereof |
| CN110468503A (en) * | 2019-08-22 | 2019-11-19 | 河南省人民医院 | A kind of composite nano-fiber membrane and its preparation method and application |
| CN115887734A (en) * | 2022-10-11 | 2023-04-04 | 北京化工大学常州先进材料研究院 | Micro-nano fiber dressing |
| CN116005290A (en) * | 2022-12-30 | 2023-04-25 | 华南理工大学 | High-hydrophobicity composite nanofiber containing functional protein as well as preparation method and application thereof |
| CN116870231A (en) * | 2023-08-03 | 2023-10-13 | 北京化工大学常州先进材料研究院 | Nanofiber dressing |
-
2007
- 2007-04-06 CN CN2007100209939A patent/CN101028521B/en not_active Expired - Fee Related
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101785760A (en) * | 2010-03-25 | 2010-07-28 | 东华大学 | Spontaneously-combined chitosan medicine-carrying nano particle and preparation method thereof |
| CN101785760B (en) * | 2010-03-25 | 2012-06-13 | 东华大学 | Spontaneously-combined chitosan medicine-carrying nano particle and preparation method thereof |
| US10347386B2 (en) | 2011-05-12 | 2019-07-09 | Ottobock Se & Co. Kgaa | Electrode comprising an embedded layer, and a method for producing same |
| CN103596620A (en) * | 2011-05-12 | 2014-02-19 | 奥托·博克保健有限公司 | Electrode comprising an embedded layer, and a method for producing same |
| CN103596620B (en) * | 2011-05-12 | 2015-10-07 | 奥托·博克保健有限公司 | There is the electrode of an embedding layer and manufacture its method |
| CN102697727B (en) * | 2012-06-12 | 2014-01-08 | 东华大学 | Method for preparing self-assembly ketoprofen liposome by electrostatic spinning technology |
| CN102697727A (en) * | 2012-06-12 | 2012-10-03 | 东华大学 | Method for preparing self-assembly ketoprofen liposome by electrostatic spinning technology |
| US20180305524A1 (en) * | 2014-11-28 | 2018-10-25 | The American University In Cairo | Inulin Nanofibers |
| CN105040279A (en) * | 2015-08-14 | 2015-11-11 | 北京化工大学 | Preparation method for core-shell structure nanofiber membrane with cyclodextrinpolypseudortaxane molecule channel on surface |
| CN105040279B (en) * | 2015-08-14 | 2017-05-03 | 北京化工大学 | Preparation method for core-shell structure nanofiber membrane with cyclodextrinpolypseudortaxane molecule channel on surface |
| CN106757778B (en) * | 2016-12-01 | 2019-04-23 | 华南协同创新研究院 | A kind of slow-release insect-pest nano fibrous membrane and the preparation method and application thereof |
| CN106757778A (en) * | 2016-12-01 | 2017-05-31 | 华南协同创新研究院 | A kind of spacetabs type insect-pest nano fibrous membrane and preparation method and application |
| CN106702597B (en) * | 2016-12-20 | 2019-06-18 | 华南理工大学 | A kind of nuclear shell structured nano tunica fibrosa and its preparation method and application |
| CN106702597A (en) * | 2016-12-20 | 2017-05-24 | 华南理工大学 | Kernel-shell structural nanofiber membrane, preparation method thereof and application |
| CN107447366A (en) * | 2017-08-03 | 2017-12-08 | 东华大学 | A kind of sensitive medicament-carried sustained release nano fiber films of pH and its preparation method and application |
| CN109330977A (en) * | 2018-09-27 | 2019-02-15 | 上海理工大学 | Lipid substance-coated drug-loaded nanofiber and preparation method thereof |
| CN109330977B (en) * | 2018-09-27 | 2022-05-13 | 上海理工大学 | Lipid substance-coated drug-loaded nanofiber and preparation method thereof |
| CN110468503A (en) * | 2019-08-22 | 2019-11-19 | 河南省人民医院 | A kind of composite nano-fiber membrane and its preparation method and application |
| CN115887734A (en) * | 2022-10-11 | 2023-04-04 | 北京化工大学常州先进材料研究院 | Micro-nano fiber dressing |
| CN116005290A (en) * | 2022-12-30 | 2023-04-25 | 华南理工大学 | High-hydrophobicity composite nanofiber containing functional protein as well as preparation method and application thereof |
| CN116005290B (en) * | 2022-12-30 | 2024-04-05 | 华南理工大学 | High-hydrophobicity composite nanofiber containing functional protein as well as preparation method and application thereof |
| CN116870231A (en) * | 2023-08-03 | 2023-10-13 | 北京化工大学常州先进材料研究院 | Nanofiber dressing |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101028521B (en) | 2010-10-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101028521B (en) | Oral colon positioning feed preparation based on electric spinning superfine nuclear fibre and its making method | |
| CN1507357A (en) | Method and compositions for enhanced delivery of bioactive molecules | |
| CN101984958A (en) | Nanoscale albendazole micropowder and preparation method thereof | |
| CN101601862A (en) | Porous-starch and derivant thereof are as the application of pharmaceutical carrier | |
| CN108912349A (en) | Polylactic acid microsphere and preparation method thereof and the application in medicament slow release | |
| CN100428957C (en) | A fibroid magnetic medicament and preparation method thereof | |
| CN100560133C (en) | Magnetic polylactic acid-phenylarsine glycolate nano microsphere and pharmaceutical applications thereof | |
| CN102293748B (en) | Oral PEGylated insulin pH-sensitive naonparticle and preparation method thereof | |
| CN113230346B (en) | A Chinese medicinal composition with anticancer effect and anticancer Chinese medicinal implant | |
| CN104337797B (en) | A kind of preparation method of the composite drug-loaded tunica fibrosa of multiple medicine integrated-type | |
| CN103784400A (en) | Novel oral micelle preparation of pegylated phosphatide-entrapped insulin | |
| CN100560060C (en) | Nano-grade medicine microball and manufacture method thereof | |
| CN1297260C (en) | Fatty acyl acetaldehyde powder projection and its preparing method | |
| CN101040847A (en) | Nanometer medicine agent produced by hydrogenated castor oil and the technique of preparing the same | |
| CN104825399B (en) | Contain reverse micelle-microsphere sustained-release preparation of CA-4 P and preparation method thereof | |
| CN1533765A (en) | Preparaton method of anticancer medicine colchicin microsphere freeze dried agent | |
| CN1285347C (en) | Kuhseng targeting preparation and its preparing method | |
| CN1621039A (en) | Targeted preparation via nose to brain of Huperzine and its derivant or its salt | |
| CN114983945B (en) | Microsphere loaded with ammonium glycyrrhetate and medical application thereof | |
| CN102757564B (en) | Preparation method and application of tree-like polyester-polyglycidol block polymer | |
| CN1947796A (en) | Chemical modified adefovir and tynofovir | |
| CN103446060B (en) | Carry Docetaxel sativum agglutinin and preparation method, pisum sativum agglutinin method of modifying and application | |
| CN100586479C (en) | Application of cyanoacrylate glycol ester in preparing medicine carrier | |
| Rana et al. | Phyto-nanotechnology for the treatment of diabetes | |
| CN106924720B (en) | Preparation method of apocynum venetum acidic polysaccharide cell-penetrating peptide oral insulin nano-composite |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101027 Termination date: 20170406 |