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Preparation method and application of GelMA hydrogel for locally slow-releasing Abaloparatide or related polypeptides

A hydrogel, topical technology, used in medical science, prosthesis, tissue regeneration, etc., to achieve good biocompatibility and promote biological behavior.

Inactive Publication Date: 2019-07-05
博志生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no research on the use of this hydrogel as a drug carrier for parathyroid hormones, such as Abaloparatide, PTH 1-34 Peptide small molecule

Method used

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  • Preparation method and application of GelMA hydrogel for locally slow-releasing Abaloparatide or related polypeptides
  • Preparation method and application of GelMA hydrogel for locally slow-releasing Abaloparatide or related polypeptides
  • Preparation method and application of GelMA hydrogel for locally slow-releasing Abaloparatide or related polypeptides

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preparation example Construction

[0033] The preparation method of the GelMA hydrogel capable of local sustained release of Abaloparatide or related polypeptide analogs of the present invention comprises the following steps:

[0034] (1) Weigh methacrylic anhydride gelatin (GelMA) monomer and dissolve it in PBS solution, the mass fraction of GelMA is 5-30%, shake and dissolve at 37-50°C and avoid light for 15-20min;

[0035] (2) Take the LAP blue photoinitiator and mix it with the GelMA solution prepared in step (1) at room temperature and avoid light, and the mass fraction of the LAP photoinitiator in the solution is 0.1% to 1%. Use a sterile filter to dissolve the solution Filter into a sterile centrifuge tube;

[0036] (3) Abaloparatide or PTH 1-34 Dissolve in PBS solution, then add dropwise to the solution in step (2), mix ultrasonically for 20-60 minutes at room temperature, let stand for 3-24 hours, and then use a blue light source (excitation wavelength 400-490nm) to irradiate the mixed solution for 3-...

Embodiment 1

[0041] Preparation of GelMA hydrogel for local sustained release of Abaloparatide:

[0042] (1) Weigh 0.25g of GelMA monomer and dissolve it in 5ml of PBS solution, shake and dissolve at 37°C for 15min (under dark conditions), and prepare a GelMA solution with a mass fraction of 5%;

[0043] (2) Weigh 0.005g of LAP blue photoinitiator and add it to the solution of (1) above and mix evenly (under dark conditions), then filter the solution into a new sterile centrifuge tube with a 0.22 μm filter membrane.

[0044] (3) Dissolve Abaloparatide in PBS solution, then add it dropwise to the above GelMA solution and mix it ultrasonically for 20 minutes. The final concentration of Abaloparatide in the solution is 0.5mg / mL. After standing for 3 hours, use a blue light source (excitation wavelength 405nm) to irradiate Mix the solution and solidify into a gel after 3s. By scanning electron microscope (SEM) test ( image 3 ) It can be seen that Abaloapratide is attached to the hydrogel gr...

Embodiment 2

[0046] Preparation of GelMA hydrogel for local sustained release of Abaloparatide:

[0047] (1) Weigh 0.25g of GelMA monomer and dissolve it in 5ml of PBS solution, shake and dissolve at 37°C for 15min (under dark conditions), and prepare a GelMA solution with a mass fraction of 5%;

[0048] (2) Weigh 0.005g of LAP blue photoinitiator and add it to the solution of (1) above and mix evenly (under dark conditions), then filter the solution into a new sterile centrifuge tube with a 0.22 μm filter membrane.

[0049] (3) Dissolve Abaloparatide in PBS solution, then add it dropwise to the above GelMA solution and mix it ultrasonically for 40 minutes. The final concentration of Abaloparatide in the solution is 0.5 mg / mL. After standing for 10 hours, use blue light source (excitation wavelength 405nm) to irradiate Mix the solution and let it solidify into a gel for 5s.

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Abstract

The present invention relates to a preparation method and an application of a GelMA hydrogel for locally slow-releasing Abaloparatide or related polypeptides. Gel methacrylate anhydride monomers are weighed to be dissolved in a PBS solution, and the dissolved methacrylate anhydride gelatin monomers are oscillated and dissolved at 37-50 DEG C in the dark; a lithium phenyl-2,4,6-trimethylbenzoylphosphonate blue light initiator is weighed to be mixed with the prepared GelMA solution at room temperature in the dark, and the solution is filtered into a sterile centrifuge tube with a sterile filter;and the related polypeptides or Abaloparatide is added to the sterile centrifuge tube containing the solution, and then the mixed solution is irradiated with a blue light source and cured into the hydrogel of any shapes. Effective entrapment and release of the Abaloparatide and PTH1-34 drugs are conducted and a cumulative release rate reaches approximately 86% on the 12th day. The hydrogel is also applied in cavity locally filled stent materials or applied for repairing and filling bone defects caused by osteoporotic fractures.

Description

technical field [0001] The invention relates to a preparation method of a GelMA hydrogel which can locally and slowly release Abaloparatide or related polypeptide analogues, and the hydrogel can be used as a bone defect filling material. Background technique [0002] Abaloparatide is a parathyroid hormone-related protein [PTHrP(1-34)] analogue, which has 76% homology with PTHrP(1-34), and PTH 1-34 With 41% homology, it can bind to parathyroid receptor 1, thereby regulating metabolism and promoting bone formation, which is used for the treatment of postmenopausal women at risk of osteoporosis (Tella S H, Kommalapati A, Correa R. Profile of Abaloparatide and Its Potential in the Treatment of Postmenopausal Osteoporosis [J]. Cureus, 2017, 9(5): e1300). On April 28, 2017, the FDA approved Tymlos (abaloparatide) for the treatment of postmenopausal osteoporosis in women, providing patients with a new strategy for the treatment of osteoporosis. Clinical trials have shown that the...

Claims

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Application Information

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IPC IPC(8): A61L27/52A61L27/22A61L27/58
CPCA61L27/222A61L27/227A61L27/52A61L27/58A61L2430/02C08L89/00
Inventor 谭宝玉宁梓妤李朝阳吕维加
Owner 博志生物科技有限公司
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