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CN-121971410-A - Treprostinil soluble microcrystalline patch and preparation method thereof

CN121971410ACN 121971410 ACN121971410 ACN 121971410ACN-121971410-A

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and discloses a treprostinil soluble microcrystalline patch and a preparation method thereof. The existing treprostinil mainly depends on intravenous injection or subcutaneous injection, and the administration mode needs professional medical staff to operate, so that pain is brought to patients, and the problems of infection risk, inconvenience in long-term administration and the like exist. The invention provides a treprostinil soluble microcrystalline patch and a preparation method thereof. The patch is of a layered structure and comprises a backing layer, a microcrystal array layer, an adhesive layer and a protective layer, wherein the microcrystal array layer is composed of treprostinil, biodegradable high polymer matrix materials and auxiliary materials. The preparation method comprises dissolving the above components in solvent to form microcrystalline stock solution, injecting into a mold, vacuum drying to solidify microcrystalline, and laminating with the above layers of materials. The microcrystalline patch provided by the invention can penetrate the skin cuticle painlessly and noninvasively, realizes efficient and continuous transdermal administration of treprostinil, and solves a plurality of defects of the existing administration mode of treprostinil.

Inventors

  • GUO YANQING
  • CAI PEIYAN
  • CAO YUNSHAN

Assignees

  • 山西省第五人民医院(山西省老年医院)

Dates

Publication Date
20260505
Application Date
20260119

Claims (10)

  1. 1. A treprostinil soluble microcrystalline patch, wherein the patch is a layered structure comprising, in order from top to bottom: A backing layer; A microcrystalline array layer comprising a therapeutically effective amount of treprostinil and at least one biodegradable polymeric matrix material; An adhesive layer; And (3) a protective layer.
  2. 2. A treprostinil soluble microcrystalline patch according to claim 1, wherein said biodegradable polymeric matrix material is one or more of hyaluronic acid, chondroitin sulfate, polyvinylpyrrolidone.
  3. 3. A treprostinil soluble microcrystalline patch according to claim 1, wherein the treprostinil is 0.5% to 5.0% by weight and the biodegradable polymeric matrix material is 3.0% to 10.0% by weight based on the total weight of the microcrystalline array layer.
  4. 4. A treprostinil soluble microcrystalline patch according to claim 1, wherein the crystallites in the microcrystalline array layer are pyramidal, conical or cylindrical.
  5. 5. A treprostinil soluble microcrystalline patch according to claim 1, wherein said microcrystalline array layer further comprises excipients comprising plasticizers and pH adjusting agents.
  6. 6. The treprostinil soluble microcrystalline patch of claim 5, wherein the plasticizer is glycerol or propylene glycol and the pH adjustor is triethanolamine or sodium hydroxide.
  7. 7. The treprostinil soluble microcrystalline patch according to claim 1, wherein the backing layer is made of polyester, polypropylene or polyimide and has a thickness of 50 μm to 200 μm, and the adhesive layer is a medical pressure-sensitive adhesive layer having a thickness of 30 μm to 100 μm.
  8. 8. A method of preparing a treprostinil soluble microcrystalline patch according to any of claims 1-7, comprising the steps of: s1, preparing a microcrystal stock solution, dissolving the biodegradable polymer matrix material in a solvent, adding treprostinil and auxiliary materials, uniformly mixing, and filtering to obtain the microcrystal stock solution; s2, preparing a microcrystal array, filling the microcrystal stock solution into a mould with a microneedle groove, and removing redundant microcrystal stock solution; s3, drying and curing, namely drying the die filled with the microcrystal stock solution, removing the solvent, and curing and forming microcrystals to obtain a cured microcrystal array; s4, laminating and assembling, namely laminating the cured microcrystal array with the backing layer, the adhesive layer and the protective layer to obtain the treprostinil soluble microcrystal patch.
  9. 9. The method of preparing a treprostinil soluble microcrystalline patch according to claim 8, wherein in step S3, the drying process is vacuum drying at a drying temperature of 30 ℃ to 50 ℃, a vacuum of-0.1 MPa to-0.08 MPa, and a drying time of 12 hours to 48 hours.
  10. 10. Use of a treprostinil soluble microcrystalline patch according to any of claims 1-10 in the manufacture of a medicament for the treatment of pulmonary arterial hypertension.

Description

Treprostinil soluble microcrystalline patch and preparation method thereof Technical Field The invention relates to the technical field of pharmaceutical preparations, in particular to a treprostinil soluble microcrystalline patch and a preparation method thereof. Background Pulmonary arterial hypertension (Pulmonary Arterial Hypertension, PAH) is a fatal cardiovascular disease characterized by progressive increases in pulmonary vascular resistance, ultimately leading to right heart failure and patient death. Treprostinil (Treprostinil) is one of the important drugs for the treatment of PAH as a stable prostacyclin analogue. However, existing treprostinil administration modes rely primarily on subcutaneous injections or intravenous infusions. The subcutaneous injection often causes pain and reaction at the injection site, so that the tolerance of patients is extremely poor, the intravenous infusion needs to be implanted into a central venous catheter, great pain and inconvenience are brought to the patients, serious complications such as thrombus and infection are easily caused, and the life quality, the treatment compliance and the long-term curative effect of the patients are seriously affected. Transdermal administration is used as a non-invasive administration mode, so that the first pass effect of the liver and gastrointestinal tract degradation of oral administration can be effectively avoided, meanwhile, the pain and risk caused by injection administration are avoided, and the convenience and compliance of the administration of patients are obviously improved. However, the stratum corneum, the outermost layer of human skin, is the primary barrier to transdermal absorption of drugs, and most drugs are difficult to passively diffuse through the stratum corneum to achieve effective therapeutic concentrations. The soluble microcrystal patch is used as a novel transdermal drug delivery technology, the skin cuticle is pierced painlessly and minimally invasively through the micron-sized soluble microcrystal array, a temporary pore canal is formed on the skin surface layer, and the drug is absorbed by capillary vessels along with microcrystal dissolution and release to enter the systemic circulation, so that the transdermal efficiency of the drug can be effectively improved, and meanwhile, the defect of traditional injection is avoided. At present, the application of soluble microcrystalline patches to treprostinil is blank. Therefore, the development of a soluble microcrystalline patch capable of realizing efficient, painless and sustained delivery of treprostinil has great clinical significance and commercial value. Disclosure of Invention The invention aims to provide a treprostinil soluble microcrystalline patch and a preparation method thereof, which are used for solving the problems in the background technology. The main design idea of the invention is as follows: Based on the technical problems, the invention aims to provide a treprostinil soluble microcrystalline patch and a preparation method thereof. Painless, high-efficiency and continuous transdermal administration of treprostinil is realized through the microcrystalline patch, and medication compliance, safety and life quality of patients with pulmonary arterial hypertension are obviously improved. Meanwhile, the preparation method has simple process, mild condition and easy mass production, and can ensure the form, mechanical strength and drug stability of the microcrystal. In order to achieve the above purpose, the present invention provides the following technical solutions: in one aspect, the invention provides a treprostinil soluble microcrystalline patch, wherein the patch is of a layered structure and comprises the following components in sequence from top to bottom: A backing layer; A microcrystalline array layer comprising a therapeutically effective amount of treprostinil and at least one biodegradable polymeric matrix material; An adhesive layer; And (3) a protective layer. Further preferably, the biodegradable polymer matrix material is one or more of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone. Further preferably, the treprostinil is 0.5% to 5.0% by weight and the biodegradable polymer matrix material is 3.0% to 10.0% by weight based on the total weight of the microcrystalline array layer. Further preferably, the crystallites in the crystallite array layer are pyramidal, conical or cylindrical. Further preferably, the microcrystalline array layer further comprises an auxiliary material, wherein the auxiliary material comprises a plasticizer and a pH regulator. Further preferably, the plasticizer is glycerol or propylene glycol, and the pH regulator is triethanolamine or sodium hydroxide. Further preferably, the backing layer is made of polyester, polypropylene or polyimide and has a thickness of 50 μm to 200 μm, and the adhesive layer is a medical pressure-sensitive adhesive layer having a thickness of 30 μm to 100