CN102178660A - Micropore type Granisetron hydrochloride transdermal sticking film and preparation method thereof - Google Patents
Micropore type Granisetron hydrochloride transdermal sticking film and preparation method thereof Download PDFInfo
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- CN102178660A CN102178660A CN2011100986549A CN201110098654A CN102178660A CN 102178660 A CN102178660 A CN 102178660A CN 2011100986549 A CN2011100986549 A CN 2011100986549A CN 201110098654 A CN201110098654 A CN 201110098654A CN 102178660 A CN102178660 A CN 102178660A
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Abstract
The invention provides a micropore type Granisetron hydrochloride transdermal sticking film and a preparation method thereof. The micropore type Granisetron hydrochloride transdermal sticking film comprises a microporous high-permeability sticking system layer, a Granisetron compound-containing medicament-storing film-forming system layer, a backlining layer and an anti-sticking layer, wherein the microporous high-permeability sticking system layer and the Granisetron compound-containing medicament-storing film-forming system layer are compounded with each other; the backlining layer is compounded on one side of the Granisetron compound-containing medicament-storing film-forming system layer; and the anti-sticking layer is compounded on one side of the microporous high-permeability sticking system layer. An animal test proves that a Granisetron compound-containing micropore type hydrochloride transdermal sticking film administration system can sustain medicament release and skin permeating for 1 to 3 days. In the administration system, medicaments are released through skin to enter a human body to exert medicament effect; stable blood concentration can be maintained; taking frequency is reduced; obedience and compliance of patients are reduced; due to the transdermal route, first pass effect of the medicaments from the gastrointestinal tract to the liver through an oral route is avoided; higher bioavailability is achieved; and remarkable advantages are achieved on medical application.
Description
Technical field
The present invention relates to a kind of transdermal pad pasting that contains Granisetron Hydrochloride and preparation method thereof.
Background technology
Granisetron Hydrochloride is to be developed in the mid-80 by Britain Beecham company at first.1991, first 3mg injection Kytri1 is pushed to the city in South Africa by Smithkline-Beecham (SB) company after merging.So far, comprise 1mg oral tablet, 1mg injection, Granisetron Hydrochloride more than 40 countries and regions listing in the whole world such as American and Britain, method, day, moral, meanings.
Studying data at home and abroad shows that Granisetron Hydrochloride has the receptor-selective of height.Itself and 5-HT
3The affinity of receptor is and other receptor such as 5-HT
1, 5-HT
2, dopamine D
1, D
1, histamine H
1, Benzodiazepine and opiate receptor 4000～10000 times of affinity.Toxicity research thinks that Granisetron Hydrochloride can reach good antiemetic effect when low dose, and side effect is very little.Pharmacokinetic shows that Granisetron Hydrochloride is at the intravital half-life (T of patient
1/2) be 9h, healthy people is 4h; Old people T
1/2Be 7.7h, young people is 4.9h.Granisetron Hydrochloride excretes by feces and urine with 7-hydroxyl Granisetron Hydrochloride and other metabolite form mainly at liver metabolism.The plasma clearance of the impaired or metastatic liver cancer of liver function reduces, during renal insufficiency removing power be just often 1/4.Orally observe very high first pass metabolism, absolute bioavailability is 60%.
China is populous, and annual newfound malignant tumor patient number has exceeded 1,600,000, and the nausea and vomiting that chemotherapy, radiotherapy cause is one of serious side effects that makes doctor and patient's worry always, and novel antiemetic is had urgent demand.Because the serious gastrointestinal reaction of patient, the compliance of oral administration is relatively poor; Simultaneously because the higher metabolism that was subjected to of Granisetron Hydrochloride causes oral administration biaavailability lower; And the very inconvenience of drug administration by injection form, therefore, the new formulation of exploitation transdermal administration approach can address the above problem more satisfactoryly.
Chinese patent CN101455650A discloses granisetron patch and the method for making thereof that a kind of skin irritation is little, stick the suitable percutaneous dosing of performance.Claim is characterised in that, on a face of the backing layer that medicine is not had permeability, be laminated with by acrylic acid-2-ethyl caproite 60～70 weight % and vinylpyridine and iron the transdermal formulation layer that copolymer, myristic acid isopropyl ester, lauric acid diethanolamine and the granisetron weight ratio 100: 5～20: 1～10: 5～10 of alkane ketone 40～30 weight % are formed, the 72h application on human skin accumulation maximum absorption that exsomatizes only is 290 μ g/cm in the embodiment
2, Transdermal absorption usefulness is lower, does not reach therapeutic purposes.
Chinese patent CN1747724A discloses a kind of binding agent patch that is used for the granisetron transdermal administration, comprises the acryloid cement that contains nonacid nucleophilic part, and wherein the granisetron percentage by weight needs 4～8%, just can keep the requirement that continues Transdermal absorption.Although described in Patent right requirement 14, this patch stores 1 month and does not observe crystalline polamer under room temperature and pressure, but because granisetron concentration is higher in forming, (condition is 40 ℃ ± 2 ℃ of temperature in acceleration, relative humidity 75% ± 5%RH) test 1 month, just crystallization occurs, and this acceleration environment is similar to the hot climate in 3 months summers, so the preparation stability that should form is undesirable.
Summary of the invention
One of purpose of the present invention provides a kind of micropore height and oozes the system of pasting, to overcome the above-mentioned defective that prior art exists.
Two of purpose of the present invention provides a kind of pore type Granisetron Hydrochloride transdermal pad pasting and method for making thereof.
Described micropore height oozes the described micropore height of the system of pasting and oozes the system of pasting and be made up of the component of following parts by weight percentage ratio:
Transdermal penetrating agent 0.1%～60%
Porogen 0.5%～60%
Preferably, described slight hole height oozes the system of pasting and is made up of the component of following parts by weight percentage ratio:
Transdermal penetrating agent 5%～30%
Porogen 4%～40%
Described transdermal penetrating agent is selected from sulfoxide class, pyrrolones, alcohols, terpenes, amine, phosphide class, laurocapram, poloxamer, sodium laurylsulfate, fatty acid or fatty acid ester;
Described sulfoxide class is selected from dimethyl sulfoxide or Kui ylmethyl sulfoxide;
Described pyrrolones comprises 2-pyrrolidone, 5-methyl-2-pyrrolidone, 1, and 5-dimethyl-2-pyrrolidone, N-methyl pyrrole iron alkane ketone (NMP);
Described alcohols comprises isopropyl alcohol, ethanol, propylene glycol, glycerol, n-octyl alcohol or n-dodecanol; Described terpenes comprises eucalyptole, limonene or orange blossom tree alcohol;
Described amine comprises carbamide, dodecyl-N or dimethylaminoethyl; Described phosphide class comprises lecithin, fabaceous lecithin or phosphatidyl glycerol;
Described fatty acid comprises oleic acid or lauric acid; Described fatty acid ester comprises lauryl alcohol lactate (LA), isopropyl myristate (IPM), propylene glycol dipelargonate or ethyl sebacate;
Most preferred, the transdermal penetrating agent is selected from myristic acid isopropyl ester (IPM), azone (Azone), lauryl alcohol lactate (LA) or N-Methyl pyrrolidone (NMP);
Described binding agent is hydrophobicity polyethylene, polypropylene, ethylene/propene copolymer, ethene/acrylic ester copolymer, ethylene, polyisobutylene, butyl rubber, polyprene, polyacrylate, silicone copolymer, styrene-isoprene-phenylethene triblock copolymer, ethylene-butadiene-styrene triblock copolymer, Hydrogenated SBS or polyurethane, optimization polypropylene acid esters or silicone pressure-sensitive adhesive;
Described porogen is pure dissolubility hydrophilic macromolecule, comprise cellulose derivative such as hydroxypropyl cellulose, copolyvidone, low molecular weight polyvinyl pyrrolidone, preferred molecular weight is 80,000～500,000 hydroxypropyl cellulose (HPC) or polyvinylpyrrolidone (PVP-K12, PVP-K15)
Described porogen also can be the mixture of above-mentioned pure dissolubility hydrophilic macromolecule and pure dissolubility organic salt such as sodium acetate, and weight ratio is: pure dissolubility hydrophilic macromolecule: pure dissolubility organic salt ratio 1～5: 1;
The selection of described porogen through evidence, has only the material of pure dissolubility can be dissolved in ethanol in preparation technology, the back is well compatible with above-mentioned hydrophobic pressure sensitive adhesive, mixes coating evenly, forms equally distributed micropore, its pore size 20～200 μ m, porosity is 10%～50%;
Pore type Granisetron Hydrochloride transdermal pad pasting of the present invention comprises that mutual compound micropore height oozes the storage medicine film forming delivery systme layer pasting system layer and contain the granisetron chemical compound, the backing layer of storage medicine film forming delivery systme layer one side that be compounded in described granisetron chemical compound and be compounded in the micropore height and ooze the adherent layer of pasting system layer one side;
The described storage medicine film forming delivery systme layer that contains the granisetron chemical compound is made up of the component of following parts by weight percentage ratio:
Preferably, the described storage medicine film forming delivery systme layer that contains the granisetron chemical compound is made up of the component of following parts by weight percentage ratio:
Above percentages of ingredients sum is 100%.
Described granisetron acid group salt includes but not limited to Granisetron Hydrochloride, sulphuric acid granisetron, phosphoric acid granisetron, acetic acid granisetron, fumaric acid granisetron material, tartaric acid granisetron or citric acid granisetron;
Described film former is selected from more than one in polyethylene, polypropylene, ethylene/propene copolymer, ethene/acrylic ester copolymer, ethylene, acrylic copolymer, silicone copolymer or polyurethane, gelatin, Resina persicae, arabic gum, alginic acid (sodium), chitosan, agar, polyvinyl alcohol compounds, polyoxyethylene, cellulose derivative or the copolyvidone;
Be preferably, film former is ethylene, acrylic copolymer, polyvinyl alcohol, polyoxyethylene or copolyvidone chemical compound;
Described plasticizer is more than one in glycerol, propylene glycol or the sorbitol;
The mixture of preferably glycerine and glycerol-sorbitol, weight ratio are 1～3: 1;
The agent of described pH dash adjustment is a triethanolamine, and perhaps triethanolamine and hydrogen-oxygen salt are as the compositions of sodium hydroxide or potassium hydroxide; Be preferably, triethanolamine-hydrogen-oxygen salt system, weight ratio is 1～5: 1;
The material of described backing layer is 9832 polyurethane film adhesive tapes of 3M company, and the drenched thoroughly oxygen performance of this material is good, and dermal respiration is unobstructed, can not cause malaise symptoms such as allergy, pruritus; And this material has autohension, can closely be combined with each other with storage medicine film forming medicine-releasing system;
Described adherent layer for the surface through organosilicon polymer or contain the polycarbonate membrane of perfluorinated alkyl polymer treatment, as 1022 polyester films of handling through fluorine of 3M company;
It is 20～50 μ m that the micropore height oozes the thickness of pasting system layer, and it is 1: 1.1～2 that the micropore height oozes the thickness ratio of pasting system layer and the storage medicine film forming delivery systme layer that contains the granisetron chemical compound;
The preparation method of described pore type Granisetron Hydrochloride transdermal pad pasting comprises the steps:
(1) porogen and transdermal penetrating agent are dissolved in the solvent, 2000～10000rpm stirred 0.5～1 hour, obtained transparent dissolving or dispersive liquid;
Described solvent is selected from more than one in ethanol, methanol, acetone or the ethyl acetate, and in the solvent, the weight content of porogen and transdermal penetrating agent is 10～90%;
(2) add the pressure-sensitive adhesive mixture, 2000～10000rpm stirred 0.5～2 hour, obtained the gluing body, the gluing body is coated on the anti-glutinous layer, and coating thickness is 10～25mm, 70～90 ℃ of dryings 10～30 minutes, acquisition has been coated with the micropore height and has oozed the anti-glutinous layer of pasting system layer, and is standby;
(3) granisetron or its acid group salt are dissolved in the solvent, 2000～10000rpm stirred 0.5～2 hour, obtained to contain medicine liquid, and in the solvent, the weight content of granisetron or its acid group salt is 5～30%;
Described solvent is selected from more than one in ethanol, methanol, water or the dichloromethane;
(4) in above-mentioned medicinal liquid, add filmogen, swelling 0.5～24 hour, acquisition contains the semi-solid solution of medicine;
(5) add plasticizer in above-mentioned semi-solid solution, the speed with 2000～10000rpm stirred 0.5～2 hour simultaneously;
(6) add the agent of pH dash adjustment in above-mentioned semi-solid solution, mix, the degassing obtains the pastille intermediate;
Above-mentioned pastille intermediate is coated on the backing layer, coating thickness 20～50mm, 60～80 ℃ of dryings 0.5～2 hour obtain to be coated with the backing layer of the storage medicine film forming delivery systme layer that contains the granisetron chemical compound;
(7) it is compound the micropore height of the product of step (2) to be oozed the storage medicine film forming delivery systme layer that contains the granisetron chemical compound of the product of pasting system layer and step (6), promptly obtains product.
When transdermal patch of the present invention uses, it can be attached on the intact skin of human body, dosage is three days 1 time, and each 1 is 5～50cm with area
2For suitable.
Pore type Granisetron Hydrochloride transdermal pad pasting provided by the invention, pressure-sensitive adhesive layer can help product closely to paste skin, and the transdermal penetrating agent that wherein contains helps to open skin passage, the Transdermal absorption of significantly increasing medicament; The micropore that possess hydrophilic property macromolecule porogen forms on the pressure-sensitive adhesive layer, pore size 20～200 μ m, porosity is 10%～50%, more helps discharging of medicine of internal layer (storage medicine film forming controlled release layer) and enters skin.Internal layer is also adopted in this invention in addition---and storage medicine film forming controlled release layer is used for medicine carrying and the stable release of control medicine.Because the dissolubility of Granisetron Hydrochloride in hydrophobic pressure sensitive adhesive is extremely limited, is easy to crystallize, it is unstable to cause drug release to absorb.The opposite dissolubility of medicine in the hydrophilic film material is bigger, and thermodynamic activity is stable, and dissolving is dispersed in the filmogen, reaches the purpose of the constant release of control medicine.Above-mentioned just 2 independent effective systems can make the preparation of Chinese medicine percentage by weight be lower than 4%, and concentration is not high, and pharmaceutical preparation is parallel at high temperature, low temperature, the cross matching accelerated test is investigated does not all have the crystalline polamer of observing, and preparation stability is good; And greatly reduced drug dose, saved production cost; The present invention is different from that transdermal penetrating agent and medicine often are mixed in the conventional formulation, reduces medicine stability easily, and is opposite; adopt two and separate independently system, give full play to function separately, not only help stability of formulation, safety; and Transdermal absorption amount height, only 5～50cm
2Can satisfy the absorbed dose of 3～4mg/d, and keep 2～5 days constant Transdermal absorption, fully satisfy clinical treatment effectiveness.
Animal experiment proves, the pore type transdermal pad pasting drug-supplying system that contains the granisetron chemical compound of the present invention, drug release that can continue 1～3 day and transdermal.Be released into by skin at this drug-supplying system Chinese medicine and bring into play drug effect in the human body, can keep stable blood drug level simultaneously, reduce and take frequency, increase patient's compliance and compliance; Transdermal route has been avoided the first pass effect of drug oral through gastrointestinal tract and liver simultaneously, has higher bioavailability, has clear superiority on medical applications.
Description of drawings
Fig. 1 is a transdermal film structure sketch map.
Fig. 2 is the accumulation transdermal test in vitro rate diagram of medicine in 3 days in embodiment 13～18 preparations.
The specific embodiment
Referring to Fig. 1, pore type Granisetron Hydrochloride transdermal pad pasting of the present invention comprises that mutual compound micropore height oozes the storage medicine film forming delivery systme layer 2 pasting system layer 1 and contain the granisetron chemical compound, the backing layer 3 of storage medicine film forming delivery systme layer 2 one side that are compounded in described granisetron chemical compound and be compounded in the micropore height and ooze the adherent layer 4 of pasting system layer 1 one sides.
Among the embodiment, the material of described backing layer is 9832 polyurethane film adhesive tapes of 3M company; Described adherent layer is 1022 polyester films through the fluorine processing of 3M company.
Among the embodiment, as do not have special explanation, the ratio of material is weight ratio.
The micropore height oozes the prescription of pasting system layer 1 and sees Table 1.
Solvent: embodiment 1 is an acetone, and in the solvent, the weight content of porogen and transdermal penetrating agent is 33%; Embodiment 2 is a methanol, and the weight content of porogen and transdermal penetrating agent is 45%; Embodiment 3 is an ethyl acetate, and the weight content of porogen and transdermal penetrating agent is 66%; Embodiment 4 is an ethanol, and the weight content of porogen and transdermal penetrating agent is 38%; Embodiment 5 is ethanol and ethyl acetate (1: 1, weight ratio), and the weight content of porogen and transdermal penetrating agent is 88%; Embodiment 6 is an ethanol, and the weight content of porogen and transdermal penetrating agent is 75%.
Table 1
The prescription that embodiment 7～12 contains the storage medicine film forming delivery systme layer 2 of granisetron chemical compound sees Table 2.
Solvent: embodiment 7 is an ethanol, and embodiment 8 is a methanol, and embodiment 9 is a water, and embodiment 10 is second alcohol and water (concentration of ethanol is 85%, volume), and embodiment 11 is an ethanol, and embodiment 12 is a dichloromethane;
Table 2
Embodiment 13～18
The foregoing description 1～6 and embodiment 7～12 are coated with by the thickness of embodiment 13～18 respectively, drying, compound, see Table 3.
Table 3
The preparation method of embodiment 13:
(1) porogen and transdermal penetrating agent are dissolved in the solvent, 2000rpm stirred 1 hour, obtained transparent dissolving or dispersive liquid;
(2) add the pressure-sensitive adhesive mixture, 2000 stirred 1 hour, obtained the gluing body, and the gluing body is coated on the anti-glutinous layer, and 70 ℃ of dryings 30 minutes have obtained to be coated with the micropore height and oozed the anti-glutinous layer 4 of pasting system layer 1, and are standby;
(3) granisetron or its acid group salt are dissolved in the solvent, 2000rpm stirred 2 hours, obtained to contain medicine liquid;
(4) in above-mentioned medicinal liquid, add filmogen, swelling 12 hours, acquisition contains the semi-solid solution of medicine;
(5) add plasticizer in above-mentioned semi-solid solution, the speed with 2000rpm stirred 2 hours simultaneously;
(6) add the agent of pH dash adjustment in above-mentioned semi-solid solution, mix, the degassing obtains the pastille intermediate;
Above-mentioned pastille intermediate is coated on the backing layer, and 60 ℃ of dryings 1 hour obtain to be coated with the backing layer of the storage medicine film forming delivery systme layer that contains the granisetron chemical compound;
(7) it is compound the micropore height of the product of step (2) to be oozed the storage medicine film forming delivery systme layer that contains the granisetron chemical compound of the product of pasting system layer and step (6), promptly obtains product.
The preparation method of embodiment 14:
(1) porogen and transdermal penetrating agent are dissolved in the solvent, 10000rpm stirred 0.5 hour, obtained transparent dissolving or dispersive liquid;
(2) add the pressure-sensitive adhesive mixture, 10000rpm stirred 0.5 hour, obtained the gluing body, and the gluing body is coated on the anti-glutinous layer, and 90 ℃ of dryings 10 minutes have obtained to be coated with the micropore height and oozed the anti-glutinous layer 4 of pasting system layer 1, and are standby;
(3) granisetron or its acid group salt are dissolved in the solvent, 10000rpm stirred 0.5 hour, obtained to contain medicine liquid;
(4) in above-mentioned medicinal liquid, add filmogen, swelling 4 hours, acquisition contains the semi-solid solution of medicine;
(5) add plasticizer in above-mentioned semi-solid solution, the speed with 10000rpm stirred 0.5 hour simultaneously;
(6) add the agent of pH dash adjustment in above-mentioned semi-solid solution, mix, the degassing obtains the pastille intermediate;
Above-mentioned pastille intermediate is coated on the backing layer, and 80 ℃ of dryings 0.5 hour obtain to be coated with the backing layer of the storage medicine film forming delivery systme layer that contains the granisetron chemical compound;
(7) it is compound the micropore height of the product of step (2) to be oozed the storage medicine film forming delivery systme layer that contains the granisetron chemical compound of the product of pasting system layer and step (6), promptly obtains product.
The preparation method of all the other embodiment is all identical with embodiment 13.
Embodiment 19
(Zheng Jun democracy is compiled according to " percutaneous dosing novel form ", People's Health Publisher's publication) method that provides in, adopt the Franz diffusion cell, choose with the immediate isolated pig skin of application on human skin and carry out the transdermal test in vitro test, measure the infiltration rate of the preparation of embodiment 13～18 at isolated pig skin, result such as table 4, the embodiment preparation accumulation transdermal test in vitro speed in 3 days is seen Fig. 2.
The transdermal test in vitro speed of the different embodiment Chinese medicines of table 4
Embodiment 21
By high temperature, parallel, the intersection accelerated test of low temperature, investigate the crystallization situation of embodiment 13～18 medicines, the result is as shown in table 5, and prescription preparation of Chinese medicine stability is better, and no crystallization is separated out.
The result is investigated in the test of table 5. drug crystallization
Annotate: the no crystallization of "-" expression.
The above results shows, pore type Granisetron Hydrochloride transdermal pad pasting provided by the invention, can effectively realize the lasting transdermal of medicine long period, keep constant blood drug level, and the preparation percutaneous absorption rate is fast, Transdermal absorption amount height, preparation does not have crystallization through accelerated test separates out, and has stable, characteristics of high efficiency.
Claims (14)
1. the micropore height oozes the described micropore height of the system of pasting and oozes the system of pasting, and it is characterized in that, is made up of the component of following parts by weight percentage ratio:
Transdermal penetrating agent 0.1%～60%
Binding agent 1%～95%
Porogen 0.5%～60%.
2. micropore height according to claim 1 oozes the described micropore height of the system of pasting and oozes the system of pasting, and it is characterized in that, is made up of the component of following parts by weight percentage ratio:
Transdermal penetrating agent 5%～30%
Binding agent 50%～90%
Porogen 4%～40%.
3. micropore height according to claim 1 and 2 oozes the described micropore height of the system of pasting and oozes the system of pasting, it is characterized in that described transdermal penetrating agent is selected from sulfoxide class, pyrrolones, alcohols, terpenes, amine, phosphide class, laurocapram, poloxamer, sodium laurylsulfate, fatty acid or fatty acid ester;
Described sulfoxide class is selected from dimethyl sulfoxide or Kui ylmethyl sulfoxide;
Described pyrrolones comprises 2-pyrrolidone, 5-methyl-2-pyrrolidone, 1, and 5-dimethyl-2-pyrrolidone, N-methyl pyrrole iron alkane ketone (NMP);
Described alcohols comprises isopropyl alcohol, ethanol, propylene glycol, glycerol, n-octyl alcohol or n-dodecanol; Described terpenes comprises eucalyptole, limonene or orange blossom tree alcohol;
Described amine comprises carbamide, dodecyl-N or dimethylaminoethyl; Described phosphide class comprises lecithin, fabaceous lecithin or phosphatidyl glycerol;
Described fatty acid comprises oleic acid or lauric acid; Described fatty acid ester comprises lauryl alcohol lactate (LA), isopropyl myristate (IPM), propylene glycol dipelargonate or ethyl sebacate;
Described binding agent is hydrophobicity polyethylene, polypropylene, ethylene/propene copolymer, ethene/acrylic ester copolymer, ethylene, polyisobutylene, butyl rubber, polyprene, polyacrylate, silicone copolymer, styrene-isoprene-phenylethene triblock copolymer, ethylene-butadiene-styrene triblock copolymer, Hydrogenated SBS or polyurethane;
Described porogen is the mixture of pure dissolubility hydrophilic macromolecule, pure dissolubility hydrophilic macromolecule and pure dissolubility organic salt; Described pure dissolubility hydrophilic macromolecule is hydroxypropyl cellulose, copolyvidone or polyvinylpyrrolidone.
4. micropore height according to claim 3 oozes the described micropore height of the system of pasting and oozes the system of pasting, it is characterized in that, described porogen is a molecular weight 80,000～500,000 hydroxypropyl cellulose or, polyvinylpyrrolidone PVP-K12 or polyvinylpyrrolidone PVP-K15.
5. micropore height according to claim 3 oozes the described micropore height of the system of pasting and oozes the system of pasting, it is characterized in that, described pure dissolubility organic salt is sodium acetate, and the weight ratio of pure dissolubility hydrophilic macromolecule and pure dissolubility organic salt is: pure dissolubility hydrophilic macromolecule: pure dissolubility organic salt ratio 1～5: 1.
6. pore type Granisetron Hydrochloride transdermal pad pasting, it is characterized in that, comprise that each described micropore height of mutual compound claim 1～5 oozes the storage medicine film forming delivery systme layer pasting system layer and contain the granisetron chemical compound, the backing layer of storage medicine film forming delivery systme layer one side that be compounded in described granisetron chemical compound and be compounded in the micropore height and ooze the adherent layer of pasting system layer one side.
7. pore type Granisetron Hydrochloride transdermal pad pasting according to claim 6 is characterized in that, the described storage medicine film forming delivery systme layer that contains the granisetron chemical compound is made up of the component of following parts by weight percentage ratio:
8. pore type Granisetron Hydrochloride transdermal pad pasting according to claim 6 is characterized in that, the described storage medicine film forming delivery systme layer that contains the granisetron chemical compound is made up of the component of following parts by weight percentage ratio:
Above percentages of ingredients sum is 100%.
9. according to each described pore type Granisetron Hydrochloride transdermal pad pasting of claim 6～8, it is characterized in that described granisetron acid group salt includes but not limited to Granisetron Hydrochloride, sulphuric acid granisetron, phosphoric acid granisetron, acetic acid granisetron, fumaric acid granisetron material, tartaric acid granisetron or citric acid granisetron;
Described film former is selected from more than one in polyethylene, polypropylene, ethylene/propene copolymer, ethene/acrylic ester copolymer, ethylene, acrylic copolymer, silicone copolymer or polyurethane, gelatin, Resina persicae, arabic gum, alginic acid (sodium), chitosan, agar, polyvinyl alcohol compounds, polyoxyethylene, cellulose derivative or the copolyvidone;
Described plasticizer is more than one in glycerol, propylene glycol or the sorbitol;
The agent of described pH dash adjustment is a triethanolamine, and perhaps triethanolamine and hydrogen-oxygen salt are as the compositions of sodium hydroxide or potassium hydroxide.
10. pore type Granisetron Hydrochloride transdermal pad pasting according to claim 9 is characterized in that described plasticizer is the mixture of glycerol and glycerol-sorbitol, and weight ratio is 1～3: 1.
11. pore type Granisetron Hydrochloride transdermal pad pasting according to claim 9 is characterized in that the agent of described pH dash adjustment is triethanolamine-hydrogen-oxygen salt system, weight ratio is 1～5: 1.
12., it is characterized in that it is 1: 1.1～2 that the micropore height oozes the thickness ratio of pasting system layer and the storage medicine film forming delivery systme layer that contains the granisetron chemical compound according to each described pore type Granisetron Hydrochloride transdermal pad pasting of claim 9～11.
13. pore type Granisetron Hydrochloride transdermal pad pasting according to claim 12 is characterized in that it is 20～50 μ m that the micropore height oozes the thickness of pasting system layer.
14. the preparation method according to each described pore type Granisetron Hydrochloride transdermal pad pasting of claim 9～13 is characterized in that, comprises the steps:
(1) porogen and transdermal penetrating agent are dissolved in the solvent, 2000～10000rpm stirred 0.5～1 hour, obtained transparent dissolving or dispersive liquid;
Described solvent is selected from more than one in ethanol, methanol, acetone or the ethyl acetate, and in the solvent, the weight content of porogen and transdermal penetrating agent is 10～90%;
(2) add the pressure-sensitive adhesive mixture, 2000～10000rpm stirred 0.5～2 hour, obtained the gluing body, the gluing body is coated on the anti-glutinous layer, and coating thickness is 10～25mm, 70～90 ℃ of dryings 10～30 minutes, acquisition has been coated with the micropore height and has oozed the anti-glutinous layer of pasting system layer, and is standby;
(3) granisetron or its acid group salt are dissolved in the solvent, 2000～10000rpm stirred 0.5～2 hour, obtained to contain medicine liquid, and in the solvent, the weight content of granisetron or its acid group salt is 5～30%;
Described solvent is selected from more than one in ethanol, methanol, water or the dichloromethane;
(4) in above-mentioned medicinal liquid, add filmogen, swelling 0.5～24 hour, acquisition contains the semi-solid solution of medicine;
(5) add plasticizer in above-mentioned semi-solid solution, the speed with 2000～10000rpm stirred 0.5～2 hour simultaneously;
(6) add the agent of pH dash adjustment in above-mentioned semi-solid solution, mix, the degassing obtains the pastille intermediate;
Above-mentioned pastille intermediate is coated on the backing layer, coating thickness 20～50mm, 60～80 ℃ of dryings 0.5～2 hour obtain to be coated with the backing layer of the storage medicine film forming delivery systme layer that contains the granisetron chemical compound;
(7) it is compound the micropore height of the product of step (2) to be oozed the storage medicine film forming delivery systme layer that contains the granisetron chemical compound of the product of pasting system layer and step (6), promptly obtains product.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11466115B2 (en) | 2018-06-01 | 2022-10-11 | 3M Innovative Properties Company | Porous membranes including triblock copolymers |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1747724A (en) * | 2003-02-05 | 2006-03-15 | 思特肯有限公司 | Transpigranisetron |
| CN1771918A (en) * | 2005-11-01 | 2006-05-17 | 中国人民解放军第二军医大学 | Granisetron cataplasm and its preparation method |
| CN101455650A (en) * | 2007-12-06 | 2009-06-17 | 考司美德制药株式会社 | Percutaneous absorption patch and its production method |
| CN101721394A (en) * | 2008-10-29 | 2010-06-09 | 大连理工大学 | Granisetron and/or hydrochloride patch thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1747724A (en) * | 2003-02-05 | 2006-03-15 | 思特肯有限公司 | Transpigranisetron |
| CN1771918A (en) * | 2005-11-01 | 2006-05-17 | 中国人民解放军第二军医大学 | Granisetron cataplasm and its preparation method |
| CN101455650A (en) * | 2007-12-06 | 2009-06-17 | 考司美德制药株式会社 | Percutaneous absorption patch and its production method |
| CN101721394A (en) * | 2008-10-29 | 2010-06-09 | 大连理工大学 | Granisetron and/or hydrochloride patch thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11466115B2 (en) | 2018-06-01 | 2022-10-11 | 3M Innovative Properties Company | Porous membranes including triblock copolymers |
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| CN102178660B (en) | 2012-08-08 |
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