KR-20260062409-A - COMPOSITION FOR BONE REGENERATION COMPRISING L-SERINE

Abstract

The present invention aims to provide a composition for bone regeneration. The present invention provides a composition for bone regeneration comprising L-serine and a pharmaceutically acceptable salt thereof; and a carrier.

Inventors

• 김성곤

Assignees

• 국립강릉원주대학교산학협력단

Dates

Publication Date

20260507

Application Date

20241029

Claims (6)

1. A bone regeneration composition comprising L-serine and a pharmaceutically acceptable salt thereof; and a carrier.
2. In paragraph 1, The above carrier is a biocompatible scaffold, a composition for bone regeneration.
3. In paragraph 3, The above biocompatible scaffold is a bone regeneration composition that is a sponge, collagen, autograft, allograft, xenograft, ceramic, composite material, or demineralized bone matrix.
4. In paragraph 1, The above L-serine is a bone regeneration composition that increases serine racemase expression.
5. In paragraph 1, The above L-serine is a bone regeneration composition that inhibits cathepsin K expression.
6. A pharmaceutical composition for the prevention or treatment of osteoporosis comprising L-serine and a pharmaceutically acceptable salt thereof.

Description

Composition for bone regeneration comprising L-serine The present invention relates to a bone regeneration composition comprising L-serine. Osteoporosis is a disease characterized by a decrease in bone mineral density (BMD) due to an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts. This imbalance weakens bones and increases the risk of fractures. While osteoporosis is particularly common in postmenopausal women due to accelerated bone resorption caused by hormonal changes, it is not limited to this group and can also affect men and young individuals. Patients with osteoporosis often have poor bone quality and require bone grafts to treat bone defects or fractures. Previously, it was proposed that bone grafts reinforced with osteoclast inhibitors improve bone regeneration in osteoporosis patients by reducing bone resorption and promoting bone formation. Bisphosphonates, a class of drugs that inhibit osteoclast-mediated bone resorption, have been widely used in the treatment of osteoporosis. It is known that incorporating bisphosphonates into bone graft materials improves bone formation compared to untreated control groups. However, long-term use of bisphosphonates leads to serious side effects, particularly drug-associated osteonecrosis of the jaw (MRONJ), which significantly limits their clinical application, especially in surgical procedures involving bone grafting. Therefore, there is a need for alternative osteoclast inhibitors that can promote bone regeneration without the side effects associated with bisphosphonates. Sericin, a protein derived from the silkworm Bombyx mori, has emerged as a potential candidate. Previous studies have shown that administering a sericin-based beverage to ovariectomized mouse models, an established model for postmenopausal osteoporosis, improves bone density. The key difference between sericin and other proteins is its high content of the amino acid serine. Upon ingestion, sericin is digested into amino acids and peptides, leading to increased serine levels in the bloodstream compared to other dietary proteins. Serine can play an important role in bone metabolism by reducing bone resorption through the inhibition of osteoclast differentiation and activity. In particular, studies have shown that D-serine, the D-enantiomer of serine, can inhibit osteoclast formation. However, since most serine found in nature is L-serine and is known to promote osteoclast differentiation in cell experiments, L-serine-based bone graft materials have not been previously studied. As L-serine is a naturally occurring amino acid and a normal component of the diet, it is unlikely to cause serious complications associated with bisphosphonate therapy, such as MRONJ. [Prior Art Literature] Republic of Korea Registered Patent Publication No. 10-2063962 Figure 1 shows the FT-IR results: (a) FT-IR spectra of gelatin (black), gelatin + amino acid (blue), and gel + L-serine (red). (b) IR transmittance magnified in the amide I band of the protein. (c) Second derivative transmittance of the amide I band of the protein. Figure 2 shows the XRD analysis results of gelatin-based materials containing L-serine and amino acids: (A) Comparison of X-ray diffraction (XRD) patterns of gelatin, gelatin + amino acids, and gelatin + serine with the reference diffraction pattern of L-serine (ICDD: 00-054-2280). The group containing only gelatin exhibits an amorphous structure as no distinct crystalline peak appears. The gelatin + amino acid and gelatin + serine groups show crystalline peaks, while the gelatin + serine group shows a sharp peak indicating higher crystallinity. Gaussian fitting of the XRD peaks for the gelatin + amino acid group (B) and the gelatin + serine group (C). The gelatin + serine group showed a smaller FWHM value (0.31641 ± 0.01034) compared to the gelatin + amino acid group, indicating higher crystallinity in the gelatin + serine group. Figure 3 shows the effects of D-serine on cathepsin K expression and osteoclast differentiation in RAW264.7 cells: (A) Administration of RANKL and M-CSF significantly increased cathepsin K expression in RAW264.7 cells. However, concomitant treatment with D-serine attenuated the increase in cathepsin K expression. (B) TRAP analysis results show that D-serine supplementation inhibits osteoclast differentiation induced by RANKL and M-CSF. Data are expressed as mean ± standard error. p < 0.05 indicates statistical significance compared to the control group. Figure 4 shows the results of Micro-CT analysis on bone volume (BV) and the bone volume to total volume (BV/TV) ratio of the experimental groups: BV was significantly higher in the L-serine group compared to the amino acid group (P < 0.001) and the control group (P = 0.002). Analysis of the BV/TV ratio showed that the ratio was significantly higher in the L-serine group compared to the amino acid group (P = 0.002), while there was no significant difference between the control group