Summary of the invention
The object of this invention is to provide a kind of medicine-carrying method of medicine eluting balloon catheter, the method can make medication coat evenly, firmly, and drug release fast and stable.
The technical solution used in the present invention is:
A medicine-carrying method for medicine eluting balloon catheter, comprises the following steps:
1. first sacculus is carried out to swelling treatment, the time of swelling treatment is 0.5h-3h; 2. adopt airless spraying technology by the balloon surface being sprayed on by the mixed liquor of curative drug, additive and solvent composition after swelling, natural air drying 10-30 minute.
In described mixed liquor, the ratio of weight and number of solvent, curative drug, additive is 10-90:0.5-30:5-60.
1. step carries out sacculus solution that swelling treatment uses is any one in methyl formate, ethyl acetate, Ethyl formate, methyl acetate, propyl formate, methyl propionate, ethyl propionate, phenylacetate, 1-Octyl acrylate and essence of Niobe, or two or more mixing in them.
Step 2. described curative drug is fat-soluble medicine.
Described fat-soluble medicine is any one in the derivant of paclitaxel, rapamycin and two kinds of medicines, or two or more mixing in them.
Step 2. described additive is epoxy resin, acrylic acid, polyurethane, UV glue, alpha-cyanoacrylate, Iopromide, any one in polycarbodiimide, or two or more mixing in them.
Step 2. described solvent is at least one and the mixture of water in ethanol, methanol, acetone, isopropyl alcohol, acetonitrile, ethyl acetate, methyl formate, and the mass concentration of described solvent is 50%-90%.
Advantage and effect that the present invention has are:
The medicine-carrying method of a kind of medicine eluting balloon catheter of the present invention can make medication coat evenly, firmly, and drug release fast and stable.
Utilize normal experiment method, medicament elution sacculus prepared by embodiment of the present invention 1-13 carries out drug release experiment, observes the medicine-releasing performance of medicinal balloon, and result is as table 1:
Table 1:
| Numbering | Drug release rate (%) |
| Embodiment 1 | 86 |
| Embodiment 2 | 79 |
| Embodiment 3 | 92 |
| Embodiment 4 | 82 |
| Embodiment 5 | 84 |
| Embodiment 6 | 72 |
| Embodiment 7 | 76 |
| Embodiment 8 | 82 |
| Embodiment 9 | 75 |
| Embodiment 10 | 88 |
| Embodiment 11 | 86 |
| Embodiment 12 | 79 |
| Embodiment 13 | 75 |
From said medicine release rate data, in embodiment, all medicament elution sacculus release rate in drug release experiment is all higher than 70%, there is good medicine-releasing performance, particularly in embodiment 3, taking ethyl acetate as swelling solution, swelling time is 1 hour, and during taking mass concentration as 60% aqueous acetone solution as spray solution, taking paclitaxel as fat-soluble medicine, taking UV glue as additive, the medicament elution sacculus of preparation drug release rate under these conditions, up to 92%, is significantly better than the medicament elution sacculus of preparing in other embodiment.
Detailed description of the invention
Embodiment 1:
A medicine-carrying method for medicine eluting balloon catheter, comprises the following steps:
1. first sacculus is carried out to swelling treatment: sacculus is placed in to solution submergence 1h, makes it swelling.It is any one in methyl formate, ethyl acetate, Ethyl formate, methyl acetate, propyl formate, methyl propionate, ethyl propionate, phenylacetate, 1-Octyl acrylate and essence of Niobe that sacculus is carried out to solution that swelling treatment uses, or two or more mixing in them.
2. the mixed liquor that preparation contains curative drug, additive, solvent; Swelling sacculus is placed on airless spraying instrument, utilizes airless spraying technology that mixed solution is coated in to balloon surface, natural air drying 10min.Wherein:
In described mixed liquor, the ratio of weight and number of solvent, curative drug, additive is 10-90:0.5-30:5-60.
Described curative drug is any one in the derivant of paclitaxel, rapamycin and two kinds of medicines, or two or more mixing in them.
Described additive is epoxy resin, acrylic acid, polyurethane, UV glue, alpha-cyanoacrylate, Iopromide, any one in polycarbodiimide, or two or more mixing in them.
Described solvent is at least one and the mixture of water in ethanol, methanol, acetone, isopropyl alcohol, acetonitrile, ethyl acetate, methyl formate, and the mass concentration of described solvent is 50%-90%.
The solvent of mixed liquor is methanol aqueous solution in the present embodiment, and fat-soluble medicine is everolimus, and additive is polycarbodiimide, and the mass concentration of methanol aqueous solution is 50%.
The ratio of weight and number of methanol aqueous solution, everolimus, polycarbodiimide is: 10:30:60.
Described in the present embodiment, the sacculus of medicine eluting balloon catheter can be equal diameter, can be also to straighten footpath, irregularly shaped, can be used for coronary artery, also can be used for peripheral blood vessel.The material of described sacculus is polyethylene or nylon or block polyetheramides macromolecular material.
Embodiment 2:
The difference of the present embodiment and embodiment 1 is:
It is methyl acetate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 30min.
The step 2. solvent of the mixed liquor of middle preparation is acetonitrile solution, and fat-soluble medicine is rapamycin, and additive is acrylic acid, and the time of natural air drying is 30min.The mass concentration of acetonitrile solution is 90%.
Acetonitrile solution, rapamycin, acrylic acid ratio of weight and number are 90:0.5:5.
Embodiment 3:
The difference of the present embodiment and embodiment 1 is:
It is ethyl acetate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 1 hour.
The step 2. solvent of the mixed liquor of middle preparation is aqueous acetone solution, and fat-soluble medicine is paclitaxel, and additive is UV glue, and the time of natural air drying is 25min.The mass concentration of aqueous acetone solution is 60%.
The ratio of weight and number of aqueous acetone solution, paclitaxel, UV glue is 50:15:30.
Embodiment 4:
The difference of the present embodiment and embodiment 1 is:
It is essence of Niobe that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 3h.
The step 2. solvent of the mixed liquor of middle preparation is isopropanol water solution, and fat-soluble medicine is Docetaxel, and additive is alpha-cyanoacrylate, and the time of natural air drying is 20min.The mass concentration of isopropanol water solution is 70%.
The ratio of weight and number of isopropanol water solution, Docetaxel, alpha-cyanoacrylate is 30:20:40.
Embodiment 5:
The difference of the present embodiment and embodiment 1 is:
It is methyl propionate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 2h.
The step 2. mixed liquor solvent of middle preparation is isopropanol water solution, and fat-soluble medicine is albumin paclitaxel, and additive is Iopromide, and the time of natural air drying is 10min.The mass concentration of isopropanol water solution is 80%.
The ratio of weight and number of isopropanol water solution, albumin paclitaxel, Iopromide is 70:10:20.
Embodiment 6:
The difference of the present embodiment and embodiment 1 is:
It is ethyl propionate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 1h.
The step 2. solvent of the mixed liquor of middle preparation is ethanol water, and fat-soluble medicine is everolimus, and additive is epoxy resin, and the time of natural air drying is 15min.
Ethanol water, everolimus, weight epoxy portion rate are 10:30:60.
Embodiment 7:
The difference of the present embodiment and embodiment 1 is:
It is 1-Octyl acrylate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 2h.
Step is the mixed liquor of middle preparation 2.: solvent is ethanol, methanol, acetone, isopropyl alcohol, acetonitrile, ethyl acetate and methyl formate mixture aqueous solution, in mixture aqueous solution, the ratio of weight and number of ethanol, methanol, acetone, isopropyl alcohol, acetonitrile, ethyl acetate and methyl formate is 1:1:1:1:1:1:1, and the mass concentration of solvent aqueous solution is 90%.Fat-soluble medicine is the mixture of paclitaxel, rapamycin, everolimus, Docetaxel, albumin paclitaxel, in this mixture, the ratio of weight and number of each medicine is 1:1:1:1:1, additive is epoxy resin and acrylic acid mixture, epoxy resin and acrylic acid ratio of weight and number are 1:1, and the time of natural air drying is 20min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 90:0.5:5.
Embodiment 8:
The difference of the present embodiment and embodiment 1 is:
It is propyl formate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 40min.
Step is the mixed liquor of middle preparation 2.: solvent is methyl formate aqueous solution, and the mass concentration of methyl formate aqueous solution is 50%.Fat-soluble medicine is the mixture of rapamycin and paclitaxel, and the ratio of weight and number of rapamycin and paclitaxel is 1:1.Additive is the mixture of UV glue, alpha-cyanoacrylate and Iopromide, and the ratio of weight and number of UV glue, alpha-cyanoacrylate and Iopromide is 1:1:1, and the time of natural air drying is 30min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 80:20:10.
Embodiment 9:
The difference of the present embodiment and embodiment 1 is:
It is Ethyl formate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 1.5h.
The step 2. solvent of the mixed liquor of middle preparation is ethyl acetate aqueous solution, and the mass concentration of ethyl acetate aqueous solution is 60%.Fat-soluble medicine is the mixture of everolimus and albumin paclitaxel, and in this mixture, the ratio of weight and number of each medicine is 1:1, and additive is polyurethane, and the time of natural air drying is 10min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 60:50:50.
Embodiment 10:
The difference of the present embodiment and embodiment 1 is:
It is ethyl propionate that step carries out by sacculus the solution that swelling treatment uses in 1., and swelling Immersion time is 2.5h.
Step is the mixed liquor of middle preparation 2.: solvent is the mixture aqueous solution of acetonitrile, ethyl acetate and methyl formate, and the ratio of weight and number of acetonitrile, ethyl acetate and methyl formate is 1:1:1, and the mass concentration of solvent aqueous solution is 80%.Fat-soluble medicine is the mixture of paclitaxel, everolimus and rapamycin, in this mixture, the ratio of weight and number of each medicine is 1:1:1, additive is epoxy resin, acrylic acid, polyurethane, UV glue, alpha-cyanoacrylate, the mixture of Iopromide and polycarbodiimide, epoxy resin, acrylic acid, polyurethane, UV glue, alpha-cyanoacrylate, the ratio of weight and number of Iopromide and polycarbodiimide is 1:1:1:1:1:1:1, and the time of natural air drying is 15min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 10:30:60.
Embodiment 11:
The difference of the present embodiment and embodiment 1 is:
It is the mixed solution of methyl formate, ethyl acetate, Ethyl formate, methyl acetate, propyl formate, methyl propionate, ethyl propionate, phenylacetate, 1-Octyl acrylate and essence of Niobe that step carries out by sacculus the solution that swelling treatment uses in 1., and in mixed solution, the ratio of weight and number of methyl formate, ethyl acetate, Ethyl formate, methyl acetate, propyl formate, methyl propionate, ethyl propionate, phenylacetate, 1-Octyl acrylate and essence of Niobe is 1:1:1:1:1:1:1:1:1:1.Swelling Immersion time is 1h.
Step is the mixed liquor of middle preparation 2.: solvent is the aqueous solution of methanol and acetone mixture, and the ratio of weight and number of methanol and acetone is 1; 1, the mass concentration of solvent aqueous solution is 80%.Fat-soluble medicine is the mixture of rapamycin and everolimus, in this mixture, the ratio of weight and number of each medicine components is 1:1, additive is the mixture of epoxy resin, acrylic acid, polyurethane and UV glue, the ratio of weight and number of epoxy resin, acrylic acid, polyurethane and UV glue is 1:1:1:1, and the time of natural air drying is 10min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 15:6:60.
Embodiment 12:
The difference of the present embodiment and embodiment 1 is:
It is the mixed solution of propyl formate and methyl propionate that step carries out by sacculus the solution that swelling treatment uses in 1., and in mixed solution, the ratio of weight and number of propyl formate and methyl propionate is 1:1, and swelling Immersion time is 30min.
The step 2. mixed liquor solvent of middle preparation is acetone, isopropanol mixture aqueous solution, and the ratio of weight and number of acetone, isopropyl alcohol is 1:1, and the mass concentration of solvent aqueous solution is 50%.Fat-soluble medicine is the mixture of rapamycin and albumin paclitaxel, and in this mixture, each drug weight portion rate is 1:1, and additive is acrylic acid, and the time of natural air drying is 30min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 70:25:45.
Embodiment 13: the difference of the present embodiment and embodiment 1 is:
It is the mixed solution of Ethyl formate, methyl acetate, ethyl propionate and phenylacetate that step carries out by sacculus the solution that swelling treatment uses in 1., in mixed solution, the ratio of weight and number of Ethyl formate, methyl acetate, ethyl propionate and phenylacetate is 1:1:1:1, and swelling Immersion time is 30min.
The step 2. mixed liquor solvent of middle preparation is the aqueous solution of isopropyl alcohol, acetonitrile and ethyl acetate mixture, and the ratio of weight and number of isopropyl alcohol, acetonitrile and ethyl acetate is 1:1:1, and the mass concentration of solvent aqueous solution is 80%.Fat-soluble medicine is the mixture of rapamycin, Docetaxel albumin paclitaxel and everolimus, and in this mixture, the ratio of weight and number of each medicine is 1:1:1:1, and additive is acrylic acid mixed liquor, and the time of natural air drying is 30min.
In described mixed liquor, the ratio of weight and number of solvent, fat-soluble medicine, additive is 50:5:12.