CN-122005421-A - Hydrobromic acid voltammetric acid implant based on 3D printing technology and preparation method and application thereof

Abstract

The invention discloses a hydrobromic acid volt-sulfur sitagliptin implant based on a 3D printing technology and a preparation method and application thereof, relates to the technical field of pharmaceutical preparations, adopts a melt extrusion deposition printing technology, takes polylactic acid with excellent biocompatibility as a drug carrier material and hydrobromic acid volt-sulfur sitagliptin as a model drug, and realizes accurate molding of the implant by constructing a customized three-dimensional model, carrying out adaptive screening on an auxiliary material system and drug loading, and optimizing key 3D printing process parameters such as filling distance, layer thickness, printing needle diameter, printing path and the like. The preparation method has the advantages of simple operation, low energy consumption, short production period, controllable process and the like, and the prepared implant has good biocompatibility, can realize long-term (40-80 days) stable release of the medicament, and improves medication compliance of patients.

Inventors

• HE YE
• WANG SILING
• ZHOU MENGYUE
• ZHAO QINFU
• XIE SHUQIONG

Assignees

• 沈阳药科大学

Dates

Publication Date

20260512

Application Date

20260204

Claims (10)

1. 1. The preparation method of the photovoltaic thioxetine hydrobromide implant based on the 3D printing technology is characterized by comprising the following steps of: Establishing a three-dimensional model of the implant, namely establishing a three-dimensional model of the implant of the hydrobromide voltaic thioxetine with preset size, shape and internal structure by utilizing computer aided design software, and exporting a model file into a standard printable format; preparing a mixed material, namely precisely weighing a prescription amount of the raw material medicine of the voethidine hydrobromide and a medicine carrier slow-release material, mixing, grinding, sieving with a 80-200 mesh standard sieve, and drying to constant weight; And 3D printing the hydrobromic acid volt-sulfur-filled implant, namely adding the mixed material into a charging barrel of a 3D printer, setting printing parameters, starting the printer, heating and melting the material in the charging barrel, extruding wires through a screw nozzle, depositing the wires on a printing platform layer by layer according to a preset three-dimensional model, and cooling and solidifying to obtain the hydrobromic acid volt-sulfur-filled implant.
2. 2. The method for preparing the printed prothioxetine hydrobromide implant based on the 3D technology according to claim 1, wherein the three-dimensional model of the prothioxetine hydrobromide implant constructed by 3D modeling software comprises, but is not limited to, a solid cylinder, a cylindrical internal cylindrical cavity, a cylindrical internal rectangular cavity and the like.
3. 3. The preparation method of the 3D technology-based printed volt-sulfur-acid-salt implant is characterized in that the drug carrier slow-release material is selected from one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polyglycolic acid and polycaprolactone, the weight average molecular weight of the polylactic acid is 10000-190000 daltons, and the intrinsic viscosity is 0.74 ml/g-130 ml/g.
4. 4. The preparation method of the 3D printing technology-based implant of the photovoltaic thioxetine hydrobromide is characterized in that the weight ratio of the photovoltaic thioxetine hydrobromide to the polylactic acid is (30-60) (70-40).
5. 5. The preparation method of the 3D printing technology-based implant of the invention is characterized in that the material mixing mode is dry grinding and mixing, and the grinding and mixing time is 10-50 min.
6. 6. The method for preparing the applicator based on the 3D printing technology according to claim 1, wherein the setting of the 3D printing basic parameters comprises a heating temperature of a metal cylinder for loading materials of 100-180 ℃, a wire-out speed of 0.01 mm/s-0.08 mm/s and a printing platform temperature of 25-55 ℃.
7. 7. The preparation method of the hydrobromic acid volt-sulfur statin implant based on the 3D printing technology according to claim 1 is characterized in that filling parameters are set on 3D printer software, a filling mode is linear filling, a filling interval is 0.20-0.50 mm, a filling initial angle is 0-90 degrees, a rotating angle is 0-90 degrees, the rotating times are 0-2 times, slicing parameters are set on the printing software, the layer thickness of an implant three-dimensional model is 0.20-0.30 mm, the layer number is 15-10 layers, the single-stage layer height is 3 mm, and the diameter of a printing needle head is 0.20-0.50 mm.
8. 8. A fumace implant prepared by the method of any one of claims 1-7.
9. 9. Use of the voltammetrin hydrobromide implant of claim 8 in the preparation of an antidepressant.
10. 10. The use according to claim 9, wherein the implant is a depot formulation for subcutaneous implantation.

Description

Hydrobromic acid voltammetric acid implant based on 3D printing technology and preparation method and application thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a 3D printing technology-based applicator for a tembotrions hydrobromide, and a preparation method and application thereof. Background The temmoxidectin hydrobromide (VXT) is a novel multimode antidepressant, plays an antidepressant role by inhibiting mechanisms such as reuptake of 5-hydroxytryptamine, regulation of 5-hydroxytryptamine receptor and the like, has the advantages of definite curative effect, slight adverse reaction and the like, and becomes a first-line medicament for clinically treating depression. The hydrobromic acid voltammetric acid is initially developed by the cooperation of northbound pharmacy and Wuta, is first approved in the United states in 2013 for major depressive disorder, and enters the Chinese market in 2017, 11. The main dosage form of the hydrobromide in the domestic market at present is an oral tablet, the conventional administration mode is oral once a day, and depression symptoms can be effectively controlled, but the long-term treatment still has obvious limitations that depression patients often have symptoms such as reduced cognitive functions, low emotion and the like, and the conditions of missed administration and forgetting to take medicine are easy to occur, so that the blood concentration is lower than the effective treatment level, the recurrence risk of illness is increased, and particularly for patients with severe depression, a more stable administration mode is needed to ensure the treatment effect. In the field of drug delivery, the implant is used as a long-acting drug delivery formulation, has the core advantages of realizing the sustained release of the drug in the body, reducing the drug delivery frequency, improving the drug compliance of patients and being particularly suitable for the disease scenes needing long-term treatment. The accurate regulation and control of the drug release behavior is a key core for the research and development of the implant, and parameters such as the release rate, the release period, the release curve morphology and the like directly influence the treatment effect and the medication safety. The traditional preparation method of the solid drug-carrying implant mainly comprises (1) a melt extrusion method, namely heating and melting a drug and a carrier material, extruding and forming the drug and the carrier material into a column shape, a rod shape and the like through an extruder, and cooling the drug-carrying implant to obtain the implant. (2) And hot pressing, in which the medicine and the carrier material are mixed, heated to a molten state, and placed into a die for pressing and forming. (3) The solvent casting process includes dissolving or dispersing medicine in organic solvent, adding carrier material to dissolve, mixing, pouring into mold and volatilizing solvent to obtain the implant. However, the method has some limitations, the drug release rate of the implant mainly depends on the degradation speed or diffusion characteristic of the material, and the drug release is difficult to regulate and control. As an additive manufacturing technology, 3D printed medicines are manufactured with the advantages of high precision, individuation and complex structure, and significant progress has been made in the field of medicine manufacturing in recent years, and the 3D printed medicines are becoming an important means for developing and producing new medicines. The 3D printing medicine technology provides feasibility for preparing the hydrobromic acid volt-sulfur sitagliptin implant for treating depression, wherein the 3D printing medicine technology adopts a discrete-stacking core forming principle, namely a three-dimensional model of the preparation is firstly split into innumerable thin layers, and then the preparation is completed in a mode of stacking materials layer by layer, so that a new path is provided for accurate manufacturing of the implant. The technology can flexibly construct various implant morphologies such as solid cylinder, cylinder built-in cylindrical cavity, cylinder built-in rectangular cavity and the like through customizing design of implant macroscopic morphology, change the contact area of a drug and body fluid, diffusion path and degradation rate of the implant in vivo by means of morphological difference, optimize the combination effect of the drug and a carrier and the corrosion characteristic of a matrix through reasonably screening and regulating and controlling the types, proportion and drug loading of auxiliary materials, and match with accurate regulation and control of printing parameters (such as filling spacing, layer thickness, printing needle diameter, printing path and the like), optimize the density and pore distribution of a microstructure