KR-102961209-B1 - Pharmaceutical composition for preventing or treating hydrocephalus or ventriculomegaly due to periventricular ciliary dysfunction

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of hydrocephalus comprising inavogliflozin as an active ingredient. Since hydrocephalus caused by an increase in cerebrospinal fluid or ventriculopathy resulting from periventricular ciliary dysfunction requires a large amount of energy to maintain cerebrospinal fluid homeostasis, mitochondrial function is important. Inavogliflozin exhibits excellent effects in the prevention and treatment of hydrocephalus or ventriculopathy resulting from periventricular ciliary dysfunction by protecting and enhancing mitochondrial function in brain tissues related to the production and circulation of cerebrospinal fluid.

Inventors

• 강슬기
• 박아름
• 지혜영
• 박준석
• 최지수
• 허준영
• 이민정
• 김태완

Assignees

• 주식회사 대웅제약

Dates

Publication Date

20260507

Application Date

20250430

Claims (4)

1. A pharmaceutical composition for the prevention or treatment of hydrocephalus or ventriculomegaly due to periventricular ciliary dysfunction, comprising enavogliflozin as an active ingredient.
2. In paragraph 1, The above pharmaceutical composition is for oral or parenteral administration, A pharmaceutical composition for the prevention or treatment of hydrocephalus or ventriculomegaly caused by periventricular ciliary dysfunction.
3. In paragraph 1, A single dose of inabogliflozin is 0.1 mg to 0.5 mg, A pharmaceutical composition for the prevention or treatment of hydrocephalus or ventriculomegaly caused by periventricular ciliary dysfunction.
4. In paragraph 1, The above pharmaceutical composition is administered once a day, A pharmaceutical composition for the prevention or treatment of hydrocephalus or ventriculomegaly caused by periventricular ciliary dysfunction.

Description

Pharmaceutical composition for preventing or treating hydrocephalus or ventriculomegaly due to periventricular ciliary dysfunction comprising inabogliflozin The present invention relates to a pharmaceutical composition for the prevention or treatment of hydrocephalus or ventriculomegaly caused by periventricular ciliary dysfunction comprising inabogliflozin as an active ingredient. Hydrocephalus refers to a pathological condition in which the ventricles expand due to the abnormal accumulation of cerebrospinal fluid (CSF), leading to increased intracranial pressure (ICP) or compression of brain tissue, which in turn causes neurological symptoms. While CSF plays a role in protecting the brain and spinal cord, supplying nutrients, and removing waste products, abnormalities in its circulation, absorption, or production processes result in abnormal accumulation, causing hydrocephalus. The treatment of hydrocephalus aims to alleviate the abnormal accumulation of cerebrospinal fluid and relieve symptoms. Surgical treatments such as ventriculoperitoneal shunt (VP Shunt) and endoscopic third ventriculostomy (ETV) are performed clinically; among these, ventriculoperitoneal shunt is the most widely used treatment method, which involves inserting a catheter into the ventricle to drain excess CSF into the abdominal cavity. Since hydrocephalus can lead to permanent nerve damage or be life-threatening if not treated promptly, accurate diagnosis and appropriate treatment are essential. However, aside from surgical treatment, no pharmacological treatment for hydrocephalus has yet been established. While drugs such as acetazolamide or digoxin can be used to inhibit CSF production, these treatments play only an adjunctive role. Meanwhile, sodium-glucose co-transporters (SGLTs) are glucose transport proteins; SGLT-1 is expressed in the small intestine, liver, kidneys, and heart, while SGLT-2 is expressed primarily in the kidneys. SGLT-2 inhibitors are a new class of antidiabetic drugs that increase glucose excretion through insulin-independent mechanisms by reducing glucose reabsorption in proximal nephrons. Furthermore, SGLT-2 inhibitors have been reported to reduce mortality and hospitalization rates related to cardiovascular aging diseases independently of blood glucose control. In addition, while various pharmacological effects of SGLT-2 inhibitors are being studied, no research has yet been reported regarding the prevention or treatment of hydrocephalus using SGLT-2 inhibitors. Figure 1 shows the results of measuring the mitochondrial oxygen consumption rate (OCR) after treating choroid plexus epithelial cells (EPCP-4) with inabogliflozin. The top of Figure 1 shows the change in mitochondrial oxygen consumption rate over time according to the treatment concentration of inabogliflozin, and the bottom of Figure 1 shows the oxygen consumption rates in the basal respiration, ATP production, and maximal respiration phases according to the treatment concentration of inabogliflozin. Figure 2 shows a Western blot image (Figure 2a) showing the expression level of mitochondrial respiratory complex proteins after treating choroid plexus epithelial cells (EPCP-4) with inabogliflozin, and a graph (Figure 2b) quantifying the results. Figure 3 shows the results of measuring the mitochondrial oxygen consumption rate (OCR) after treating choroid plexus epithelial cells (EPCP-4) with inabogliflozin, dapagliflozin, or empagliflozin for 48 or 72 hours. Figure 3a shows the change in mitochondrial oxygen consumption rate over time (top of Figure 3a) and the oxygen consumption rates during basal respiration, ATP production, and maximal respiration (bottom of Figure 3a) when the three drugs were treated at a concentration of 1 μM for 48 hours. Figure 3b shows the change in mitochondrial oxygen consumption rate over time (top of Figure 3b) and the oxygen consumption rates during basal respiration, ATP production, and maximal respiration (bottom of Figure 3b) when three drugs were treated at a concentration of 1 μM for 72 hours. FIG. 4a illustrates the protocol of the mouse behavior experiment according to Example 2-1, and FIG. 4b shows the results of analyzing the overall movement of the mouse using software through an open-field test, with the graph at the bottom of FIG. 4b showing the total distance traveled by the mouse. FIG. 4c shows the results of analyzing the horizontal grid test, displaying the hanging time (left graph) and successful steps (right graph), respectively. Figure 5a shows a table scoring neurological damage based on mouse behavior. Figure 5b shows the results of measuring the neurological scores of mice according to the treatment concentration of inabogliflozin. Figure 6 shows Western blot images (Figure 6a) showing the expression levels of mitochondrial respiratory complex proteins in mouse brain tissue after treating mice with inabogliflozin at different concentrations, and a graph (Figure 6b) quantifying the results. Figur