KR20080016372A - Use of methylene blue for treatment of retinal damage and protection of retina - Google Patents

Use of methylene blue for treatment of retinal damage and protection of retina Download PDF

Info

Publication number
KR20080016372A
KR20080016372A KR1020060078432A KR20060078432A KR20080016372A KR 20080016372 A KR20080016372 A KR 20080016372A KR 1020060078432 A KR1020060078432 A KR 1020060078432A KR 20060078432 A KR20060078432 A KR 20060078432A KR 20080016372 A KR20080016372 A KR 20080016372A
Authority
KR
South Korea
Prior art keywords
methylene blue
retina
retinal
administered
theophylline
Prior art date
Application number
KR1020060078432A
Other languages
Korean (ko)
Other versions
KR100816670B1 (en
Inventor
조영
주천기
최준섭
김경아
Original Assignee
국방과학연구소
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 국방과학연구소 filed Critical 국방과학연구소
Priority to KR1020060078432A priority Critical patent/KR100816670B1/en
Publication of KR20080016372A publication Critical patent/KR20080016372A/en
Application granted granted Critical
Publication of KR100816670B1 publication Critical patent/KR100816670B1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A formulation comprising methylene blue is provided to be effective for inhibiting retinotoxic effect induced by the increase of cGMP, specifically inhibiting the retinotoxic effect by theophylline. A formulation for treating retinal damage and protecting retina comprises methylene blue as an effective ingredient, wherein the retinal damage is caused by cyclic GMP(cGMP) increased by inhibiting phosphodiesterase(PDE) and 1-2 mg/kg of the methylene blue is administered into the retina through oral administration, instillation or injection.

Description

망막 손상 치료 및 망막 보호하기 위한 메틸렌블루의 용도{USE OF METHYLENE BLUE FOR TREATMENT OF RETINAL DAMAGE AND PROTECTION OF RETINA}USE OF METHYLENE BLUE FOR TREATMENT OF RETINAL DAMAGE AND PROTECTION OF RETINA}

도 1은 정상인 망막 (A), 테오필린(30 mg/kg)만 투여된 망막 (B), 테오필린(50 mg/kg)만 투여된 망막 (C)에서의 독성을 관찰한 것이다. Figure 1 shows the toxicity in normal retina (A), retina (B) administered only theophylline (30 mg / kg), retina (C) administered only theophylline (50 mg / kg).

도 2(A)는 RT-PCR 분석에 의하여 테오필린에 의한 유전자 발현 변화를 나타낸 것이고, 도 2(B)는 웨스턴 블롯 분석에 의하여 테오필린에 의한 단백질 발현 변화를 나타낸 것이다. Figure 2 (A) shows the change in gene expression by theophylline by RT-PCR analysis, Figure 2 (B) shows the change in protein expression by theophylline by Western blot analysis.

도 3은 정상인 망막 (A), 메틸렌블루(2 mg/kg)만 투여된 망막 (B), 테오필린(50mg/kg)만 투여된 망막 (C), 테오필린(50 mg/kg)과 메틸렌블루(2 mg/kg)가 동시 투여 된 망막 (D)에서 망막보호 효과를 관찰한 것이다. 3 shows normal retina (A), retina (B) administered only methylene blue (2 mg / kg), retina (C) administered only theophylline (50 mg / kg), theophylline (50 mg / kg) and methylene blue ( 2 mg / kg) was observed in the retina (D) with co-administration.

도 4는 메틸렌블루 망막보호효과를 전자현미경으로 촬영한 사진이다. A와 D: 정상인 망막, B와 E: 테오필린 투여된 망막, C와 F: 테오필린과 메틸렌블루 동시 투여된 망막.4 is a photograph taken with an electron microscope of the methylene blue retinal protective effect. A and D: normal retina, B and E: theophylline administered retina, C and F: theophylline and methylene blue co-administered retina.

도 5는 테오필린에 의한 망막 손상과 메틸렌블루에 의한 보호 작용의 모식도를 나타낸 것이다. Figure 5 shows a schematic diagram of the retinal damage caused by theophylline and the protective action by methylene blue.

본 발명은 메틸렌블루 (methylene blue)를 유효 성분으로 하는 망막 손상 치료 및 망막 보호용 억제제에 관한 것이다. 구체적으로는 테오필린 (theophylline)에 의하여 이인산에스터라제가 억제됨으로써 야기되는 망막 손상을 치료하거나 망막을 보호하는 억제제에 관한 것이다. The present invention relates to an inhibitor for the treatment of retinal damage and retinal protection using methylene blue as an active ingredient. Specifically, the present invention relates to an inhibitor for treating retinal damage or protecting the retina caused by the inhibition of diphosphate esterase by theophylline.

망막은 연속된 3개의 신경원이 연접 결합된 구조를 기본으로 한다. 제1차 신경원은 광수용 세포로 그 외절 (막대 세포와 원뿔 세포) 에는 광감수성 색소가 함유되어 있고 광자극을 수용기 전압으로 바꾸는 역할을 하고 있다. 제 2 차 신경원은 양극 세포로 그 말초성 돌기는 막대 및 원뿔 세포와 그 기저부에 연접 결합하고 중추성 돌기 (축삭)는 세 번째의 망막 신경절 세포와 연접 결합한다. 이 두 번째 신경원에는 수평 양극 신경원, 원뿔 양극 신경원 및 막대 양극 세포로 구별된다. 제3차 신경원인 망막 신경절 세포는 망막 신경 세포층을 구성하며 그 축삭은 망막 원판을 향해 달려 원판에서 굵은 신경 섬유(시신경)를 형성한다. 신경절 세포층은 망막의 대부분의 부위에서 단층이지만 측두부에서는 2층으로 되어 있다. 광수용 세포층 (receptor layer)은 색소층과 막대 및 원뿔 세포층으로 이루어지고, 구성 신경인 광수용 세포는 외절, 내절, 세포체, 수상 돌기를 포함한다.The retina is based on a contiguous structure of three consecutive neurons. The primary neurons are photoreceptive cells whose extremities (bar cells and cones) contain photosensitive pigments and convert photostimuli into receptor voltages. The secondary neurons are bipolar cells, whose peripheral processes connect with rods and cones and their bases, while the central processes (axons) connect with third retinal ganglion cells. This second neuron is divided into horizontal bipolar neurons, conical bipolar neurons and rod bipolar cells. Retinal ganglion cells, the third neurons, make up the retinal nerve cell layer, and the axons run toward the retinal disc to form coarse nerve fibers (optic nerves) in the disc. Ganglion cell layers are monolayers in most areas of the retina, but two layers in the temporal region. Photoreceptor cell layer (receptor layer ) The photoreceptor cells, which are composed of a pigment layer, rod and cone cell layers, and constitutive neurons, include extinctions, internal incisions, cell bodies, and dendrites.

망막의 손상 중 광수용세포 손상에서 일어나는 주요 원인은 중 하나는 PDE 억제와 구아닐릴 사이클라제(Guanylyl cylase)에 의한 사이클링 GMP(cGMP)의 증가에 의한 것이고 세포사멸 인자(Caspase, Bax, P53)의 발현에 의하여 고사한다.(이 부분과 관련하여 추가하실 내용이 있으시면 기재하여 주십시오)One of the main causes of photoreceptor damage during retinal injury is due to PDE inhibition and increased cycling GMP (cGMP) by guanylyl cyclase and the effects of apoptosis factors (Caspase, Bax, P53). (Please write if you have any additional information regarding this part.)

한편, 천식의 치료제로 사용되고 있는 테오필린 (theophylline)은 약물의 부작용 때문에 사용 용량이 제한되어 있고, 과량 복용에 의한 독성이 많이 보고되어 있으며, 독성은 조직 및 기관에 따라 다양한 임상적 특징을 나타낸다. 예컨대, 심각한 위장관, 심장혈관계 및 신장 부작용뿐만 아니라 중추신경계 부작용 등의 단점이 있다. 또한, 이 독성에서의 분자 생물학적 특징은 cGMP의 증가를 포함한다. 즉, 이인산에스터라제 억제제인 테오필린에 의하여 cGMP가 증가한다고 할 것이다. On the other hand, theophylline (theophylline), which is used as a therapeutic agent for asthma, has a limited use dose due to side effects of the drug, and there are many reports of toxicity due to overdose, and toxicity has various clinical characteristics depending on tissues and organs. For example, there are disadvantages such as severe gastrointestinal, cardiovascular and kidney side effects as well as central nervous system side effects. In addition, molecular biological characteristics in this toxicity include an increase in cGMP. That is, cGMP is increased by theophylline, a diphosphate esterase inhibitor.

따라서, 본 발명자들은 테오필린 등에 의한 망막 손상, 즉 망막 독성을 cGMP생성을 억제함으로써 치유할 수 있다고 생각하였다. 이에 대하여 연구한 결과, 메트헤모글로빈혈증 및 환원제로 사용되고 있으며, cGMP를 생성하는 구아닐릴 사이클라제 (guanylyl cyclase)의 활성을 억제하는 메틸렌블루 (methylene blue)가 cGMP가 증가하는 PDE 억제제 중독에 대한 해독제로 이용할 수 있다는 것을 발견하여 본 발명을 완성하였다. Therefore, the present inventors thought that retinal damage caused by theophylline or the like, that is, retinal toxicity, can be cured by inhibiting cGMP production. As a result of this study, methylene blue, which is used as methemoglobinemia and reducing agent, and inhibits the activity of guanylyl cyclase, which produces cGMP, has been shown to prevent PDE inhibitor poisoning, which increases cGMP. The present invention has been completed by discovering that it can be used as an antidote.

본 발명은 망막 손상을 치료하고 망막을 보호하기 위하여 메틸렌블루를 유효 성분으로 사용하는 망막 손상 치료 및 망막 보호용 제제를 제공하는 것을 목적으로 한다.An object of the present invention is to provide an agent for the treatment of retinal damage and retinal protection using methylene blue as an active ingredient to treat retinal damage and to protect the retina.

본 발명은 메틸렌블루를 유효 성분으로 하는 망막 손상 치료 및 망막 보호용 제제에 관한 것이다. 본 발명의 메틸렌블루를 유효 성분으로 하는 망막 손상 치료 및 망막 보호용 제제는 메틸렌블루의 새로운 용도를 제공한다.The present invention relates to an agent for the treatment of retinal damage and retinal protection using methylene blue as an active ingredient. The agent for the treatment of retinal damage and retinal protection using methylene blue as an active ingredient of the present invention provides a new use of methylene blue.

또한, 본 발명은 메틸렌블루를 1 내지 2 mg/kg(0.2%)의 양으로 망막에 투여하는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제에 관한 것이다.The present invention also relates to a retinal injury treatment and retinal protective agent, characterized in that the methylene blue is administered to the retina in an amount of 1 to 2 mg / kg (0.2%).

본 발명에서 망막 손상은 포스포디에스터라제(phosphodiesterase, PDE)를 억제하고, 이로 인하여 증가된 사이클릭 GMP (cGMP)에 의하여 일어날 수 있다. 특히, 망막 손상 및 중독은 포스포디에스터라제의 억제제인 테오필린에 의하여 일어날 수 있다. Retinal damage in the present invention inhibits phosphodiesterase (PDE) and can be caused by increased cyclic GMP (cGMP). In particular, retinal damage and poisoning can be caused by theophylline, an inhibitor of phosphodiesterase.

망막 손상 기작은 도 5의 모식도의 오른쪽 개요에서 알 수 있다. 즉, 구아닐릴 사이클라제 (guanylyl cyclase)가 활성화되면 사이클릭 GMP의 합성이 증가하게 되고, 이로 인하여 시토졸의 나트륨과 칼슘 농도가 증가하여 망막의 광수용 세포가 손상 받게 되는 것이다. The mechanism of retinal damage can be seen in the right outline of the schematic diagram of FIG. 5. That is, when guanylyl cyclase is activated, the synthesis of cyclic GMP increases, thereby increasing the sodium and calcium concentrations of the cytosol and damaging the photoreceptor cells of the retina.

본 발명은 이러한 망막 손상을 치료 또는 망막을 보호하기 위하여, 메틸렌블루를 이용하였다. 도 5의 모식도 왼쪽 개요에 나타낸 바와 같이, 결국 망막 독성을 일으키는 구아닐릴 사이클라제의 활성이 메틸렌블루에 의하여 차단됨으로써, 사이클릭 GMP의 합성을 중지시킬 수 있었다. 따라서, 이러한 기작에 의하여 망막을 보호하는 효과를 얻을 수 있다. The present invention uses methylene blue to treat such retinal damage or to protect the retina. As shown in the schematic diagram on the left of FIG. 5, the activity of guanylyl cyclase, which eventually causes retinal toxicity, was blocked by methylene blue, thereby stopping the synthesis of cyclic GMP. Therefore, the effect of protecting the retina can be obtained by such a mechanism.

본 발명에서 메틸렌블루는 1 내지 2 mg/kg의 양으로 망막에 투여되는 것을 특징으로 한다. 메틸렌블루의 양이 1 mg/kg 미만인 경우 망막을 보호하는 효과가 미미하다. 메틸렌블루 2 mg/kg은 생체 내에 들어갈 수 있는 최대량에 해당한다. Methylene blue in the present invention is characterized in that it is administered to the retina in an amount of 1 to 2 mg / kg. If the amount of methylene blue is less than 1 mg / kg, the effect of protecting the retina is minimal. Methylene blue 2 mg / kg corresponds to the maximum amount that can enter the living body.

메틸렌블루를 망막보호를 위하여 투여하는 방법으로는 주사용, 경구용과 점안액용으로 구분할 수 있다.Methylene blue may be administered for retinal protection by injection, oral use, and eye drops.

주사용 메틸렌블루 용액은 생리식염수, BSS(Balanced salt solution)에 5 mg/㎖ (0.5%)으로 용해시킨 후 혈관 주사하며, 투여량이 하루에 최종 2 mg/kg이 되도록 한다.Injectable methylene blue solution is dissolved in physiological saline, BSS (Balanced salt solution) at 5 mg / ml (0.5%), and then vascularally injected, so that the final dose is 2 mg / kg per day.

경구용 메틸렌블루는 생리식염수 또는 음용수에 10 mg/㎖(1%)을 녹여 20 ㎖를 복용한다.      Oral methylene blue dissolves 10 mg / ml (1%) in saline or drinking water and takes 20 ml.

점안액(안약)용 메틸렌블루 용액은 인공 누액 (Alcon co. 또는 삼일제약) 또는 생리식염수, BSS(Balanced salt solution)에 0.01%로 용해시켜 점안제로 만들어 투여한다.    The methylene blue solution for eye drops (eye drops) is dissolved in artificial lacrimal fluid (Alcon co. Or Samil Pharmaceuticals) or physiological saline, BSS (Balanced salt solution) in 0.01% and administered as eye drops.

이하에서는 본 발명을 실시예에 의하여 자세히 설명하고자 한다. 그러나, 실시예에 의하여 본 발명의 범위가 제한되는 것은 아니다. Hereinafter, the present invention will be described in detail by examples. However, the scope of the present invention is not limited by the examples.

[실시예]EXAMPLE

실시예Example 1. 테오필린에 의한 망막 손상 확인 실험 1. Experiment for retinal damage caused by theophylline

본 연구를 위하여 흰쥐를 이용한 동물모델을 사용하였으며, 망막 및 광수용 세포의 변화를 관찰하였다. 테오필린에 대한 독성은 테오필린을 30 mg/kg과 50 mg/kg의 양으로 각각 투여하고, 24시간 후에 망막 광수용 세포의 손상을 광학 현미경으로 관찰하였다. 망막 광수용 세포의 외절과 내절의 형태 변형 및 퇴화를 유도하였다 (도1). 이러한 실험에 의하여, 테오필린이 망막을 손상시킨다는 것을 확인할 수 있었다. For this study, an animal model using rats was used and changes of retina and photoreceptor cells were observed. Toxicity to theophylline was administered with theophylline in amounts of 30 mg / kg and 50 mg / kg, respectively, and after 24 hours the damage of retinal photoreceptive cells was observed under an optical microscope. Morphological modification and degeneration of extinction and extinction of retinal photoreceptor cells were induced (FIG. 1). These experiments confirmed that theophylline damages the retina.

단백질 및 유전자 발현의 변화를 관찰하기 위하여 단백질 면역 항체 반응인 웨스턴 블롯 분석법과 역전사 증폭법인 역전사-PCR법을 사용하였다. 유전자 발현의 변화는 테오필린 투여 후 1, 3, 5일에 관찰하고, 그 결과를 도 2에 나타내었다. 도 2에서 알 수 있는 바와 같이, 테오필린 즉, 포스포디에스터라제(phosphodiesterase, PDE) 억제에 의한 망막 손상은 망막 구아닐릴 사이클라제 (retinal guanylyl cyclase, ret-GC) 및 세포질 구아닐릴 사이클라제(soluble guanylyl cyclase, sGC)를 모두 증가시켰다. 또한 cGMP에 의하여 활성화되는 cGK (즉, 단백질 키나아제 G, PKG)의 발현도 증가시켰다. 이에 비하여 대조군에 해당하는 액틴 및 α-튜불린은 변화가 없어, 다른 단백질에 영향을 미치지 않는 것으로 볼 수 있다. 상기의 실험 및 관찰에 의하여 테오필린이 망막을 손상시키며, 구아닐릴 사이클라제 및 cGMP를 증가시키고, 이것이 망막 광수용 세포의 손상에 주요 작용을 한다는 것을 알 수 있었다. Western blot analysis, a protein immune antibody response, and reverse transcription-PCR, a reverse transcription amplification method, were used to observe changes in protein and gene expression. Changes in gene expression were observed 1, 3, and 5 days after theophylline administration, and the results are shown in FIG. 2. As can be seen in FIG. 2, retinal damage by theophylline, ie, phosphodiesterase (PDE) inhibition, was observed between retinal guanylyl cyclase (ret-GC) and cytoplasmic guanylyl. Both soluble guanylyl cyclase (sGC) was increased. It also increased the expression of cGK (ie, protein kinase G, PKG) activated by cGMP. In contrast, actin and α-tubulin, which correspond to the control, do not change, and thus, do not affect other proteins. Experiments and observations showed that theophylline damages the retina, increases guanylyl cyclase and cGMP, and this plays a major role in damaging retinal photoreceptor cells.

실시예Example 2. 메틸렌블루에 의한 망막 손상 억제 실험 2. Methylene Blue-induced Retinal Damage Inhibition Experiment

망막의 형태학적 관찰을 위하여 광학 현미경과 전자 현미경을 이용하여 관찰하였다. 테오필린에 의한 독성을 억제하기 위하여 구아닐릴 사이클라제(guanylyl cyclase) 억제제인 메틸렌블루(Methylene blue)를 2 mg/kg의 양으로 투여하였다. 그 결과, 메틸렌블루만 투여된 망막에서는 독성이 관찰되지 않아, 정상의 망막과 같았다 (도3). 이로 인하여 망막 손상이 억제된 것을 알 수 있었다. For the morphological observation of the retina, observation was carried out using an optical microscope and an electron microscope. In order to suppress the toxicity by theophylline, guanylyl cyclase inhibitor, methylene blue, was administered in an amount of 2 mg / kg. As a result, no toxicity was observed in the retina administered only methylene blue, which was the same as that of the normal retina (FIG. 3). This revealed that retinal damage was suppressed.

메틸렌블루의 보호 효과를 전자 현미경으로 관찰하였다. 그 결과 광수용 세포의 손상이 억제되고 정상과 같은 광수용 세포의 형태가 유지되는 것을 관찰하였다 (도4).The protective effect of methylene blue was observed with an electron microscope. As a result, it was observed that damage to the photoreceptive cells was suppressed and the morphology of the photoreceptive cells as normal was maintained (FIG. 4).

이 연구에 의하여, 메틸렌블루의 테오필린 독성에 대한 망막 광수용 세포의 보호 효과를 관찰하였으며, 메틸렌블루가 cGMP 증가성 망막 손상에 보호 효과가 있음을 확인하였다.This study observed the protective effect of retinal photoreceptor cells on theophylline toxicity of methylene blue and confirmed that methylene blue had a protective effect on cGMP-increasing retinal damage.

메틸렌블루를 유효 성분으로 하는 본 발명은 망막 손상, 그 중에서도 cGMP증가로 인한 망막 독성을 억제하는데 효과가 있다. 구체적으로는, 테오필린에 의한 망막 독성을 억제할 수 있다.The present invention using methylene blue as an active ingredient is effective in suppressing retinal toxicity due to retinal damage, especially cGMP. Specifically, retinal toxicity caused by theophylline can be suppressed.

Claims (10)

메틸렌블루 (methylene blue)를 유효 성분으로 하는 망막 손상 치료 및 망막 보호용 제제. Retinal injury treatment and retinal protective agent containing methylene blue as an active ingredient. 제1항에 있어서, 상기 망막 손상은 포스포디에스터라제(phosphodiesterase, PDE)를 억제하여 증가된 사이클릭 GMP (cGMP)에 의한 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제. The method of claim 1, wherein the retinal injury is due to increased cyclic GMP (cGMP) by inhibiting phosphodiesterase (PDE). 제2항에 있어서, 상기 포스포디에스터라제의 억제는 테오필린에 의하여 이루어지는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 억제제. The inhibitor of claim 2, wherein the inhibition of the phosphodiesterase is by theophylline. 제1항 내지 제3항에 있어서, 상기 메틸렌블루는 1 내지 2 mg/kg의 양으로 망막에 투여되는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제. The method of claim 1, wherein the methylene blue is administered to the retina in an amount of 1 to 2 mg / kg. 제1항 내지 제3항에 있어서, 상기 메틸렌블루는 경구투여, 점안 그리고 주사 방법으로 망막에 투여되는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제. The agent for the treatment of retinal injury and retinal protection according to claim 1, wherein the methylene blue is administered to the retina by oral administration, instillation and injection. 제5항에 있어서, 메틸렌블루 용액을 생리식염수, BSS(Balanced salt solution)에 용해시킨 후, 그 혼합물을 혈관 주사하는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제. The method of claim 5, wherein the methylene blue solution is dissolved in physiological saline, BSS (Balanced salt solution), and then the mixture is vascularly injected. 제6항에 있어서, 상기 혼합물의 투여량은 1일당 2 mg/kg인 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제.The agent for treating retinal injury and protecting retina according to claim 6, wherein the dosage of the mixture is 2 mg / kg per day. 제5항에 있어서, 메틸렌블루를 생리식염수 또는 음용수에 녹여 그 혼합물을 경구 투여하는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제.The method of claim 5, wherein the methylene blue is dissolved in physiological saline or drinking water and the mixture is orally administered. 제8항에 있어서, 상기 혼합물의 투여량은 1일당 20 ㎖인 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제.The method of claim 8, wherein the dosage of the mixture is 20 ml per day. 제5항에 있어서, 메틸렌블루를 인공 누액 또는 생리식염수, BSS(Balanced salt solution)에 용해시켜 그 혼합물을 점안제로 투여하는 것을 특징으로 하는 망막 손상 치료 및 망막 보호용 제제.The method of claim 5, wherein the methylene blue is dissolved in artificial lacrimal fluid, physiological saline, BSS (Balanced salt solution), and the mixture is administered as an eye drop.
KR1020060078432A 2006-08-18 2006-08-18 Use of methylene blue for treatment of retinal damage and protection of retina KR100816670B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020060078432A KR100816670B1 (en) 2006-08-18 2006-08-18 Use of methylene blue for treatment of retinal damage and protection of retina

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020060078432A KR100816670B1 (en) 2006-08-18 2006-08-18 Use of methylene blue for treatment of retinal damage and protection of retina

Publications (2)

Publication Number Publication Date
KR20080016372A true KR20080016372A (en) 2008-02-21
KR100816670B1 KR100816670B1 (en) 2008-03-27

Family

ID=39384511

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020060078432A KR100816670B1 (en) 2006-08-18 2006-08-18 Use of methylene blue for treatment of retinal damage and protection of retina

Country Status (1)

Country Link
KR (1) KR100816670B1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012112918A1 (en) * 2011-02-18 2012-08-23 Allergan, Inc. Methods for treating diseases of the retina
WO2021034267A1 (en) * 2019-08-20 2021-02-25 Yin Sze Loh Formulations for use in the prevention and/or treatment of peripheral neuropathy and its associated diseases.

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5602143A (en) * 1994-12-08 1997-02-11 Allergan Method for reducing intraocular pressure in the mammalian eye by administration of guanylate cyclase inhibitors

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012112918A1 (en) * 2011-02-18 2012-08-23 Allergan, Inc. Methods for treating diseases of the retina
WO2021034267A1 (en) * 2019-08-20 2021-02-25 Yin Sze Loh Formulations for use in the prevention and/or treatment of peripheral neuropathy and its associated diseases.

Also Published As

Publication number Publication date
KR100816670B1 (en) 2008-03-27

Similar Documents

Publication Publication Date Title
Wang et al. Autophagy in glaucoma: crosstalk with apoptosis and its implications
Dahlmann-Noor et al. Strategies for optic nerve rescue and regeneration in glaucoma and other optic neuropathies
Russo et al. Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury
US20220184075A1 (en) Pharmaceutical composition containing hdac6 inhibitor as active ingredient for prevention or treatment of itching
Gur et al. Review of erectile dysfunction in diabetic animal models
KR20110042054A (en) Prophylactic or therapeutic agent for axial myopia
KR20190120197A (en) Therapeutic and Neuroprotective Peptides
Yu et al. Huperzine A lowers intraocular pressure via the M3 mAChR and provides retinal neuroprotection via the M1 mAChR: A promising agent for the treatment of glaucoma
KR100816670B1 (en) Use of methylene blue for treatment of retinal damage and protection of retina
US9561234B2 (en) Methods for treating diseases of the retina
Kobayashi et al. The relationship between the renin-angiotensin–aldosterone system and NMDA receptor-mediated signal and the prevention of retinal ganglion cell death
EP3285761B1 (en) Parthenolide and its derivatives for use in the treatment of axonal damage
DE69912304T2 (en) USE OF STAUROSPORINE DERIVATIVES FOR THE TREATMENT OF OCCULAR NEOVASCULAR DISEASES
KR20210010638A (en) Compositions for use in treating eye disorders using dipyridamole
US20180200279A1 (en) Inhibition of hsv-1-associated corneal neovascularization using inhibitors of cyclin-dependent kinase 9
Wang et al. Tongqiao Mingmu formula alleviates retinal ganglion cell autophagy through PI3K/AKT/mTOR pathway
Cooley-Themm et al. Loss of displaced starburst amacrine cells in a rat glaucoma model
KR20040014600A (en) OPTIC NERVE PROTECTING AGENTS CONTAINING α1 RECEPTOR BLOCKER AS THE ACTIVE INGREDIENT
US8481500B2 (en) Compounds having neuroprotective properties
US7468434B2 (en) Diazene-bridge crown ether lithium compounds and methods for their use
US9987242B2 (en) Treatment of Levodopa-induced Dyskinesias
KR101102229B1 (en) Use of Tyrosine Kinase Inhibitor to Treat Diabetes
US9629835B1 (en) Method for treating tau-associated diseases
CN105963287B (en) Compound and its medical usage
KR20150083167A (en) Pharmaceutical composition comprising methylene blue for treating or preventing sensorineural hearing loss

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E90F Notification of reason for final refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
FPAY Annual fee payment

Payment date: 20130228

Year of fee payment: 6

FPAY Annual fee payment

Payment date: 20140304

Year of fee payment: 7

FPAY Annual fee payment

Payment date: 20150302

Year of fee payment: 8

LAPS Lapse due to unpaid annual fee