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CN-117298439-B - GLP-1 polypeptide microneedle patch and preparation method thereof

CN117298439BCN 117298439 BCN117298439 BCN 117298439BCN-117298439-B

Abstract

The application discloses a GLP-1 polypeptide drug microneedle and a preparation method thereof, wherein the microneedle comprises PVP, NVP, a photoinitiator and a GLP-1 receptor agonist, the preparation method comprises the steps of firstly dissolving a certain amount of PVP in NVP to prepare a solution with proper specific gravity and viscosity, then adding the photoinitiator and the GLP-1 receptor agonist into the solution to form a liquid system which is uniformly suspended as much as possible, secondly filling the suspension into a microneedle mould, polymerizing the NVP into solid PVP through ultraviolet irradiation, and forming the solid PVP into the geometry of the microneedle under the limitation of the mould. Then spreading a little NVP on the micro needle back layer, covering the micro needle back layer with a plastic film, irradiating with ultraviolet light again to crosslink the plastic film and PVP micro needle into a whole, and stripping the micro needle out of the mould. The application has the advantages that PVP is used for preparing NVP solution with proper specific gravity and viscosity, so that the subsequently added medicine is uniformly suspended in the solution, the uniformity of the medicine carrying quantity of the micro-needle is further improved, the medicine carrying quantity is improved, and the improvement of the medicine effect and the consistency of the medicine effect are facilitated.

Inventors

  • Hang Congrong

Assignees

  • 南通微臻医药科技有限公司

Dates

Publication Date
20260505
Application Date
20231007

Claims (7)

  1. 1. A GLP-1 polypeptide microneedle patch is characterized in that a main constituent of a microneedle substrate is polyvinylpyrrolidone (PVP), the polyvinylpyrrolidone (PVP) is from two parts, PVP for adjusting specific gravity and viscosity of a solution is firstly added, PVP polymerized by N-vinylpyrrolidone (NVP) through ultraviolet irradiation is further contained in the microneedle substrate, the microneedle substrate also contains a photoinitiator and non-polymerized NVP, the microneedle body is of a conical structure, and a medicament in the microneedle body is a GLP-1 receptor agonist.
  2. 2. A method for preparing the GLP-1 polypeptide microneedle patch according to claim 1, which comprises the following steps: Preparing a solution: a) Dissolving polyvinylpyrrolidone (PVP) in N-vinyl pyrrolidone (NVP) to prepare a solution with specific gravity and viscosity; b) Dissolving a certain amount of photoinitiator in the solution; c) Adding GLP-1 receptor agonist into the solution to prepare uniform suspension of GLP-1 receptor agonist; (II) microneedle preparation: d) Uniformly suspending GLP-1 receptor agonist in a vacuum environment, filling the suspension into micropores of a microneedle mould, and removing redundant suspension; e) Irradiating with ultraviolet light to polymerize the liquid NVP in the micropores into solid PVP micropins; f) Spreading a small amount of NVP containing a photoinitiator on the needle surface of the microneedle mould; g) Spreading a layer of plastic film on the NVP liquid film, and slightly pressing; h) Irradiating with ultraviolet light to polymerize NVP in the interlayer into PVP, and tightly crosslinking the drug-containing PVP microneedle and the plastic film; i) And stripping the GLP-1 polypeptide microneedle from the mould.
  3. 3. The method for preparing a GLP-1 polypeptide microneedle patch according to claim 2, wherein the GLP-1 receptor agonist is one of liraglutide, exenatide or semraglutide.
  4. 4. The method for preparing a GLP-1 polypeptide microneedle patch according to claim 2, wherein the NVP added in step f) is added with a photoinitiator at a concentration of 1.5% w/v.
  5. 5. The method for preparing a GLP-1 polypeptide microneedle patch according to claim 2, wherein the height of the microneedle is 150-2000 μm.
  6. 6. The method for preparing a GLP-1 polypeptide microneedle patch according to claim 2 or 5, wherein the shape of the microneedle is conical or pyramid.
  7. 7. The method for preparing a GLP-1 polypeptide microneedle patch according to claim 6, wherein the shape of the microneedle is rectangular pyramid.

Description

GLP-1 polypeptide microneedle patch and preparation method thereof Technical Field The invention relates to the technical field of medicines, in particular to a GLP-1 polypeptide microneedle patch and a preparation method thereof. Background At present, microneedle patches have received great attention as an innovative drug delivery system that can achieve rapid, convenient, painless drug delivery by delivering drugs directly to the shallow layer beneath the skin through microneedles of a tiny cone-shaped structure thereon. However, microneedle patches also have some limitations. In general, the drug loading is small, the uniformity of drug loading is poor, the preparation technology is complex, mass production is difficult to realize, and the serious lack of biosafety auxiliary materials is a main reason that the drug microneedle is not commercially available so far. The invention utilizes NVP to dissolve or suspend the drug, and polymerize NVP into PVP solid state microneedles under the catalysis of a photoinitiator and the limitation of a microneedle negative mould. The method has the obvious advantages that firstly, the preparation process is simple, the drug microneedle product is obtained in tens of minutes, almost all the known processes can be completed after more than 24 hours, and secondly, the main auxiliary material PVP is a very safe biodegradable material and is widely used for preparing drugs. The disadvantage of this approach is that most drugs have less solubility in NVP, and thus the drug loading of microneedles made from a homogeneous solution of drug and NVP is less than therapeutic. Therefore, it is desirable to increase the drug loading of the microneedles obtained by this method and ensure that the uniformity of drug loading meets the requirements of current drug administration regulations. Disclosure of Invention The invention aims to increase the drug loading capacity of the micro-needle and ensure that the uniformity of the drug loading capacity meets the requirements of the current drug management regulations. The objective case of NVP as a solvent to solubilize drugs is that NVP has little solubility for many drugs, and thus the drug loading is quite small when microneedles are made from a homogeneous clear drug-containing solution. After dissolution saturation is reached in the NVP solution, the excess drug forms a suspension with the NVP in solid form. Then the micro-needle is manufactured by taking the suspension as a starting material, and the drug loading is greatly increased. However, the specific gravity of NVP is 1.04 (25 ℃), and most solid drugs have a specific gravity greater than that of NVP, so that the drugs in the suspension generally settle, and the drug content in different parts of the suspension is very uneven. Microneedles made from suspensions with non-uniform drug loading have poor drug loading uniformity. The dynamic reasons for the sedimentation of suspended matters in the solution are that firstly, the buoyancy of the solution to the suspended matters is not equal to the gravitational force. When the specific gravity of the suspended matter is greater than or less than that of the solution, the suspended matter will settle or float, and the specific gravity of the matter is the measure of the relation, and when the acting force of the solvent to the surface of the suspended matter is greater than the gravitational force or the floating force, the suspended matter will still stand still in the solution and the solution viscosity will be the measure of the relation. Therefore, adjusting the specific gravity and viscosity of the solution is one of measures to increase the drug loading and to ensure the uniformity of the drug loading. For pharmaceutical preparations, it is also necessary to make the materials involved the less and the better, the safer. NVP is polymerized into PVP under ultraviolet light, PVP is a biosafety substance which is approved as a pharmaceutical adjuvant at the earliest, the specific gravity is 1.144, and the viscosity of the PVP aqueous solution with the concentration is determined to be rapidly increased along with the increase of the polymerization degree (molecular weight) of PVP. Therefore, the purpose of adjusting the specific gravity and the viscosity of the solution is realized by adding a certain amount of PVP into NVP, and the added PVP and PVP polymerized by illumination after the PVP form a microneedle matrix together, so that no new auxiliary materials are generated. The inventors' conception thus far envisages the implementation of a logical closed loop and was verified as viable through the following experiments. The technical scheme and the specific steps adopted by the invention are as follows: Preparing a solution: a) Dissolving polyvinylpyrrolidone (PVP) in N-vinyl pyrrolidone (NVP) to prepare a solution with specific gravity and viscosity; b) Dissolving a certain amount of photoinitiator in the solution; c) Adding