KR-20260065562-A - Freeze-dried composition for long-term storage of biopharmaceuticals

Abstract

The present invention relates to a delivery vehicle for the long-term storage of biological pharmaceuticals and a method for manufacturing the same. Specifically, it relates to a delivery vehicle utilizing freeze-drying of inorganic nanoparticles for the preservation and distribution of biological pharmaceuticals containing proteins or nucleic acids as active ingredients, and a method for manufacturing the same.

Inventors

• 이효진
• 이시안
• 한상인
• 김영민

Assignees

• 한국과학기술연구원

Dates

Publication Date

20260508

Application Date

20251030

Claims (10)

1. A composition for delivering a bio-derived material comprising: a bio-derived material loaded onto porous inorganic nanoparticles; and a cryopreservative selected and combined from the group comprising sucrose, trehalose, D-mannitol, and dextran.
2. In paragraph 1, A composition for bio-derived material delivery, wherein the porous inorganic nanoparticles are selected from the group comprising porous silica nanoparticles (PSN), porous metal oxide nanoparticles such as titanium oxide or aluminum oxide, and porous carbon nanoparticles.
3. In paragraph 1, A composition for delivering bio-derived substances, wherein the above cryopreservative contains 0.025~0.1% sucrose, 0.025~0.2% trehalose, 0.025~0.1% mannitol, or 0.005~0.025% dextran.
4. In paragraph 1, The above composition is a composition for delivering bio-derived substances, further comprising a buffer selected from PBS (Phosphate Buffered Saline), Tris-HCl (Tris-Hydrochloride), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-(N-morpholino)propanesulfonic acid), or Citrate Buffer (citric acid buffer).
5. In paragraph 1, A composition for delivering a bio-derived material, wherein the bio-derived material is selected from the group comprising proteins, antibodies, genes, nucleic acid sequences, or cells.
6. In paragraph 5, A composition for delivering a bio-derived material, wherein the bio-derived material comprises a Cas9 protein or gRNA for gene editing.
7. In paragraph 5, A composition for delivering a bio-derived substance, wherein the bio-derived substance is a biological drug having preventive or therapeutic activity against disease in the body.
8. In paragraph 1, A biopharmaceutical delivery composition, wherein the above composition is freeze-dried at a temperature of -70°C to -85°C for 12 to 48 hours.
9. In paragraph 1, The above composition is a composition for delivering biological medicines that can be stored at room temperature for a period of 90 days or less.
10. A pharmaceutical composition comprising the composition for delivering biological drugs of claim 1.

Description

Freeze-dried composition for long-term storage of biopharmaceuticals The present invention relates to a delivery vehicle for the long-term storage of biological pharmaceuticals and a method for manufacturing the same. Specifically, it relates to a delivery vehicle utilizing freeze-drying of inorganic nanoparticles for the preservation and distribution of biological pharmaceuticals containing proteins or nucleic acids as active ingredients, and a method for manufacturing the same. Biological drugs, or biopharmaceuticals, refer to medicines based on living cells, tissues, microorganisms, or biologically derived materials that are utilized for the prevention, diagnosis, or treatment of diseases. They exert therapeutic effects primarily by utilizing proteins, antibodies, genes, or cells to regulate biological responses or activate the immune system. Types include protein-based therapeutics (e.g., monoclonal antibodies, plasma-derived proteins), vaccines, gene therapies, and cell therapies, and they are applied to a wide range of diseases, including autoimmune diseases, cancer, infectious diseases, genetic disorders, and rare diseases. In particular, biological drugs enable personalized treatment for diseases and play an important role in providing treatment options for conditions that are difficult to address with conventional synthetic drugs through highly specific and effective mechanisms of action. Recently developed biological drugs have disadvantages that make stability, delivery, and storage difficult and challenging due to their increasing complexity. For example, mRNA vaccines face difficulties such as requiring low-temperature (frozen) distribution due to their low stability. The following are materials used for the transport of biological drugs. - Lipid Nanoparticles (LNP): Used in RNA vaccines and the like for the protection and intracellular delivery of mRNA, aiding in stability and effective delivery. - Polymer Nanoparticles (PNP): Used to enhance the controlled release and stability of drugs, various polymer materials with biocompatibility and biodegradability are utilized. - Porous Silica Nanoparticles (PSN): Enable drug adsorption and controlled release through a large surface area, and are used to encapsulate various biological molecules. - Gold Nanoparticles: Their surfaces can be functionalized, making them suitable for drug delivery or diagnostic purposes; they are primarily applied to the delivery of anticancer drugs. - Polymeric Nanocapsules: These are carriers composed of biocompatible and biodegradable polymers that enable the protection and controlled release of drugs. Recently, freeze-drying processes have also been utilized for the long-term preservation of biopharmaceuticals. However, even in this case, problems arise, such as reduced efficacy due to changes in vaccine antigen structure and surface charge, functional degradation caused by the instability of protein degradation pathways, phase separation and aggregation of lipid nanoparticles (LNPs), changes in the particle size and shape of polymer nanoparticles (PNPs), and effects resulting from stress on the capsid proteins and lipid membranes of viral particles. Figure 1 is a TEM image of a porous silica nanoparticle freeze-dried formulation containing the biopharmaceutical of the present invention and a diagram comparing the characteristics of porous silica nanoparticles before and after freeze-drying. Figure 2 shows the results of an experiment to select the optimal combination of cryopreservative and buffer in the manufacturing process of a porous silica nanoparticle freeze-dried formulation containing the biopharmaceutical of the present invention. Figure 3 shows the dispersion stability and cell viability confirmed by analyzing the size and surface charge of each particle synthesized using a cryopreservation agent under optimized conditions. Figure 4 shows the results of comparing the retention of activity of biopharmaceuticals contained in freeze-dried formulations of lipid nanoparticles (LNP) and porous inorganic nanoparticles (PSN) through GFP gene expression. Figure 5 shows the experimental results confirming the long-term storage efficiency of a porous silica nanoparticle freeze-dried formulation containing a biopharmaceutical in cells. Figure 6 shows the results of analyzing the in vivo tumor-targeted gene editing and GFP knockout efficiency using freeze-dried porous inorganic nanoparticles. Hereinafter, embodiments are described in detail to specifically explain the present specification. However, the embodiments according to the present specification may be modified in various different forms, and the scope of the present specification is not to be interpreted as being limited to the embodiments described below. The embodiments of the present specification are provided to more completely explain the present specification to those with average knowledge in the art. Experimental Example 1. Preparation of a lyophilized f