KR100515479B1 - medicine delivering film for treating ophthalmology disease - Google Patents
medicine delivering film for treating ophthalmology disease Download PDFInfo
- Publication number
- KR100515479B1 KR100515479B1 KR10-2003-0003345A KR20030003345A KR100515479B1 KR 100515479 B1 KR100515479 B1 KR 100515479B1 KR 20030003345 A KR20030003345 A KR 20030003345A KR 100515479 B1 KR100515479 B1 KR 100515479B1
- Authority
- KR
- South Korea
- Prior art keywords
- film
- drug delivery
- drug
- treatment
- glycerol
- Prior art date
Links
Classifications
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K1/00—Lift valves or globe valves, i.e. cut-off apparatus with closure members having at least a component of their opening and closing motion perpendicular to the closing faces
- F16K1/16—Lift valves or globe valves, i.e. cut-off apparatus with closure members having at least a component of their opening and closing motion perpendicular to the closing faces with pivoted closure-members
- F16K1/18—Lift valves or globe valves, i.e. cut-off apparatus with closure members having at least a component of their opening and closing motion perpendicular to the closing faces with pivoted closure-members with pivoted discs or flaps
- F16K1/22—Lift valves or globe valves, i.e. cut-off apparatus with closure members having at least a component of their opening and closing motion perpendicular to the closing faces with pivoted closure-members with pivoted discs or flaps with axis of rotation crossing the valve member, e.g. butterfly valves
- F16K1/221—Lift valves or globe valves, i.e. cut-off apparatus with closure members having at least a component of their opening and closing motion perpendicular to the closing faces with pivoted closure-members with pivoted discs or flaps with axis of rotation crossing the valve member, e.g. butterfly valves specially adapted operating means therefor
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K27/00—Construction of housing; Use of materials therefor
- F16K27/02—Construction of housing; Use of materials therefor of lift valves
- F16K27/0209—Check valves or pivoted valves
- F16K27/0218—Butterfly valves
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K31/00—Actuating devices; Operating means; Releasing devices
- F16K31/44—Mechanical actuating means
- F16K31/53—Mechanical actuating means with toothed gearing
- F16K31/535—Mechanical actuating means with toothed gearing for rotating valves
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K31/00—Actuating devices; Operating means; Releasing devices
- F16K31/44—Mechanical actuating means
- F16K31/60—Handles
- F16K31/602—Pivoting levers, e.g. single-sided
Landscapes
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 인공수정체와 수정체 후낭 사이에 삽입되어, 안질환, 특히 후발성 백내장의 예방치료에 적합한 안질환 치료용 약물전달필름에 관한 것으로서, 상기 약물전달필름은 키토산과 글리세롤의 혼합물로 이루어진 필름 내에 유효량의 투명성 안질환 치료약물이 함유되어 이루어진 것을 특징으로 한다.The present invention relates to a drug delivery film for the treatment of eye diseases, which is inserted between the intraocular lens and the lens posterior capsule and is suitable for the prophylaxis of ocular diseases, particularly late cataracts, wherein the drug delivery films are formed in a mixture of chitosan and glycerol. An effective amount of the transparent eye disease therapeutic drug is contained.
Description
본 발명은 안질환 치료용 약물전달필름 및 그 제조방법에 관한 것으로서, 보다 상세하게는, 안질환 치료용 약물, 특히 후발성 백내장 예방치료용 약물을 함유한 채 인공수정체와 수정체 후낭 사이에 삽입되는 안질환 치료용 약물전달필름 및 그 제조방법에 관한 것이다.The present invention relates to a drug delivery film for treating ocular disease and a method for manufacturing the same, and more particularly, to be inserted between the intraocular lens and the capsular bag while containing a drug for treating ocular disease, particularly a drug for preventing the treatment of late cataract. The present invention relates to a drug delivery film for treating eye diseases, and a method of manufacturing the same.
현재, 인체의 내부조직에 직접 접촉하여 질병치료에 이용되는 약물전달시스템의 개발은 여러 치료분야에서 크게 증가되고 있는 추세이다.Currently, the development of a drug delivery system that is used in the treatment of diseases by directly contacting the internal tissues of the human body is increasing in many therapeutic fields.
하지만, 이러한 증가세에도 불구하고, 안과에서 안질환의 치료에 이용될 수 있는 약물전달시스템의 개발은 눈이라는 조직의 특성상 타분야에 비해 저조하다.However, despite this increase, the development of drug delivery systems that can be used for the treatment of eye diseases in ophthalmology is poor compared to other fields due to the characteristics of the tissue of the eye.
전통적으로, 안과 치료약물의 형태는 90% 이상이 점안약 형태를 취하고 있으며, 이러한 점안 형태의 약물 투여는 대다수의 안과질병(이하, 안질환으로 칭함)의 치료가 수용성 안약에 의존한다는 점과 이에 따른 약물손실이 크다는 점에서 문제점이 존재한다.Traditionally, more than 90% of ophthalmic drugs are in the form of eye drops, and the administration of these eye drops depends on the fact that the treatment of most ophthalmic diseases (hereinafter referred to as eye diseases) depends on water-soluble eye drops. The problem lies in the high drug loss.
안과의 약물전달시스템의 개발이 어려운 이유 중 하나는 안질환의 치료에 있어서 시각의 확보라는 중요하고도 까다로운 문제점을 안고 있기 때문이며, 결과적으로, 안과의 약물전달시스템 개발은 타분야의 약물전달시스템과 차별화될 수밖에 없다.One of the reasons why the development of ophthalmic drug delivery system is difficult is because of the important and difficult problem of securing vision in the treatment of ocular disease. As a result, the development of ophthalmic drug delivery system is not the same as other drug delivery system. There is no choice but to differentiate.
따라서, 안질환의 치료를 위한 새로운 약물전달시스템의 개발은 눈 조직과 약물의 접촉시간을 증대시켜 약물효과를 늘리고, 약물의 지속적인 방출을 가능하게 하고, 부반응을 감소시키고, 치료회수를 감소시키고, 특히, 눈에 있어서 가장 중요한 환자의 시야가 확보되어지도록 이루어져야 한다.Therefore, the development of a new drug delivery system for the treatment of eye diseases increases the contact time between the eye tissue and the drug to increase the drug effect, enable the continuous release of the drug, reduce side reactions, reduce the number of treatments, In particular, the eyes of the patient most important to the eyes should be secured.
안질환 중 하나인 후발성 백내장은, 백내장 수술의 한 방법으로 수정체낭 적출 후 남겨진 수정체 후낭에 다시 혼탁이 생기는 경우 및 외상성 백내장 안에 수정체 물질이 모두 흡수되고 전낭과 후낭만 남겨진 경우에, 후낭과 전낭에 다시 혼탁이 형성되어 나타나는 것이다.Posterior cataract, one of the eye diseases, is a method of cataract surgery, in which the turbidity of the capsular bag after recapture of the capsular bag is again turbid and when all the lens material is absorbed in the traumatic cataract and only the anterior and posterior capsules are left. Turbidity is formed again.
현재의 의약기술로는 혼탁된 수정체를 투명화시킬 수 있는 백내장 치료약이 없기 때문에 외과적 수술이 불가피하며, 따라서, 백내장 수술 후 남아 있는 수정체의 후낭은 항상 혼탁이 생길 수 있다. 이 때문에, 인공 수정체 삽입후 3~5년 정도가 지나면 약 50%의 환자에게서 후발성 백내장이 생기는 것으로 알려져 있다.Surgical operation is inevitable because current medical technology does not have a cataract therapeutic agent that can make a cloudy lens clear, so that the posterior capsule of the lens remaining after cataract surgery can always become cloudy. For this reason, about 3 to 5 years after implantation of the lens, it is known that about 50% of patients develop late cataracts.
후발성 백내장의 경우, 시력에 장애가 되면, 수술로써 동공부의 혼탁된 막에 인위적인 구멍을 만들어서 빛이 통과되도록 해주는데, 이러한 시술 방법은 재낭법(discission)이라 일컬어진다.In the case of late cataracts, when the vision is impaired, surgery creates an artificial hole in the cloudy membrane of the pupil to allow light to pass through. This procedure is called discission.
최근에는, 외과적 수술을 하지 않고서도, 네오디뮴 야그 레이저(Neodymium YAG Laser)를 이용하여 혼탁된 후낭에 구멍을 만들어 주는 치료 방법이 후발성 백내장의 치료에 이용되고 있는데, 이는 안압의 상승과 인공수정체의 훼손에 의한 시력확보의 문제점 등 부작용을 수반한다.In recent years, a treatment method that creates a hole in the clouded posterior capsule using neodymium YAG laser without surgical operation has been used for the treatment of late cataract, which is an increase in intraocular pressure and intraocular lens. It is accompanied by side effects such as problems of securing eyesight due to impairment.
이에 대해, 본 발명자는 안질환 치료를 위한, 특히 후발성 백내장의 예방치료를 위한 약물전달 시스템으로 이용 가능한 안질환 치료용 약물전달필름을 개발하게 되었는데, 이 약물전달필름은 부반응을 거의 일으킴 없이 생체에 적합한 생분해성 천연고분자 물질에 안질환 치료용 약물이 함유됨으로써 만들어진다.In this regard, the present inventors have developed a drug delivery film for treating ocular disease, which can be used as a drug delivery system for the treatment of eye diseases, in particular for the prophylactic treatment of late cataracts. It is made by the inclusion of a drug for the treatment of eye diseases in a biodegradable natural polymer material suitable for use.
따라서, 본 발명의 제 1 목적은, 새로운 형태의 생분해성 천연고분자 물질에 기존의 안질환 치료약물이 함유되어 이루어진 것으로서, 눈 조직과 약물의 접촉시간이 증대되고, 약물의 지속적인 방출이 가능하며, 환자의 시야 확보가 가능한 안질환 치료용 약물전달필름 및 그 제조방법을 제공하는 것이다.Therefore, the first object of the present invention is that a new type of biodegradable natural polymer material contains an existing eye disease treatment drug, which increases the contact time between the eye tissue and the drug, and enables continuous release of the drug. The present invention provides a drug delivery film for treating eye diseases and a method of manufacturing the same that can secure a patient's field of view.
또한, 본 발명의 제 2 목적은, 새로운 형태의 생분해성으로 천연고분자 물질에 기존의 후발성 백내장용 약물이 함유되어 이루어지는 것으로서, 눈 조직과 약물의 접촉시간이 증대되고, 약물의 지속적인 방출이 가능하며, 환자의 시야 확보가 가능한 안질환 치료용 약물전달필름을 제공하는 것이다. In addition, the second object of the present invention is to form a new form of biodegradable natural polymer material containing the existing late-end cataract drug, the contact time between the eye tissue and the drug is increased, and the drug can be continuously released And, to provide a drug delivery film for the treatment of eye diseases that can ensure the patient's field of view.
상술한 제 1 목적을 달성하기 위해, 본 발명에 따른 안질환 치료용 약물전달필름은 키토산과 글리세롤의 혼합물로 이루어진 필름 내에 유효량의 투명성 안질환 치료약물이 함유되어 이루어진 것을 특징으로 한다.In order to achieve the first object described above, the drug delivery film for treating eye diseases according to the present invention is characterized in that an effective amount of a transparent eye disease therapeutic drug is contained in a film consisting of a mixture of chitosan and glycerol.
상술한 본 발명의 제 2 목적은 상기 키토산과 글리세롤의 혼합물로 이루어진 필름 내에 후발성 백내장의 치료예방용도의 수정체상피세포 증식억제 또는 사멸 약물이 함유됨으로써 달성된다.The second object of the present invention described above is achieved by containing a lens epithelial cell proliferation inhibitor or a killing drug for preventing the treatment of late cataract in a film consisting of a mixture of chitosan and glycerol.
또한, 상기 본 발명에 따른 안질환 치료용 약물전달필름은 키토산: 글리세롤 중량비가 1:0.2 내지 1:1.2, 더 바람직하게는 1:0.7 내지 1:1이 되도록 혼합된 혼합물을 유효량의 투명성 안질환 치료약물과 혼합하여 주조하는 주조단계와; 상기 주조된 혼합물을 건조하는 단계를 포함하여 이루어지는 것을 특징으로 한다.In addition, the drug delivery film for treating eye diseases according to the present invention is a mixture of chitosan: glycerol weight ratio 1: 0.2 to 1: 1.2, more preferably 1: 0.7 to 1: 1 effective amount of transparent eye disease Casting with mixing with the therapeutic drug; It characterized in that it comprises the step of drying the cast mixture.
여기에서, 상기 글리세롤이 상기 키토산: 글리세롤 중량비 1:0.2보다 적게 첨가되면, 최종적으로 제조된 약물전달필름의 경도가 커지고 투명도가 떨어지게 되며, 상기 글리세롤이 상기 키토산: 글리세롤 중량비 1:1.2보다 많이 첨가되면 최종적으로 제조된 약물전달필름의 이용시 키토산이 생분해되는 시간이 줄어들어 지속적인 약물전달효과가 떨어지는 문제가 야기된다. Here, when the glycerol is added less than the weight ratio of the chitosan: glycerol 1: 0.2, the hardness of the finally produced drug delivery film is increased and the transparency is lowered, if the glycerol is added more than the weight ratio of chitosan: glycerol 1: 1.2 Finally, the use of the prepared drug delivery film reduces the time to decompose chitosan biodegradation causes a problem that the continuous drug delivery effect is reduced.
한편, 본 발명에 따라 제작된 상기 약물전달필름은 약물전달물질로서의 물성측정을 거쳐 이용되며, 이용시 약물전달필름 내에서 함유된 약물이 서서히 방출됨으로써 안질환 치료, 특히 후발성 백내장의 억제에 기여한다.On the other hand, the drug delivery film prepared according to the present invention is used through the measurement of physical properties as drug delivery material, and when used, the drug contained in the drug delivery film is gradually released, thereby contributing to the treatment of eye diseases, in particular suppression of late cataracts. .
이 때, 상기 약물전달필름에 의해 코팅된 인공수정체의 굴절률 변화에 대한 측정이 이루어져야 할 것이다. At this time, the measurement of the refractive index change of the intraocular lens coated by the drug delivery film should be made.
이하에서는 본 발명의 바람직한 실시예가 설명될 것이며, 이하의 실시예들 중, 실시예 1 및 실시예 2는 함수율 및 분해율의 평가를 위해 안질환 치료약물을 함유하지 않은 채 제작된 필름에 대한 실시예이고, 실시예 3 및 실시예 4는 안질환 치료약물이 함유된 채 제작된 약물전달 필름에 대한 실시예이다.Hereinafter, a preferred embodiment of the present invention will be described, and among the following examples, Examples 1 and 2 are examples of films produced without containing ophthalmic drugs for evaluation of moisture content and decomposition rate. Example 3 and Example 4 are examples of the drug delivery film prepared while containing the eye disease treatment drug.
<실시예 1><Example 1>
0.5% 아세트산에 용해하여 여과를 한 1% 키토산 용액과 3차 증류수에 1% 농도로 용해한 글리세롤 용액을 1:1의 중량비로 혼합하고, 그 혼합용액을 200㎕씩 주조하여 무균상태에서 2~3일 동안 자연건조하여 키토산/글리세롤 필름을 제작하였다.1% chitosan solution dissolved in 0.5% acetic acid and glycerol solution dissolved in 1% concentration in tertiary distilled water were mixed at a weight ratio of 1: 1, and 200 µl each of the mixed solution was cast in a sterile state. Natural drying for 1 day to produce a chitosan / glycerol film.
<실시예 2><Example 2>
0.5% 아세트산에 용해하여 여과를 한 1% 키토산 용액과 3차 증류수에 1% 농도로 용해한 글리세롤 용액을 1:0.7의 중량비로 혼합하고, 그 혼합용액을 200㎕씩 주조하여 무균상태에서 2~3일 동안 자연건조하여 키토산/글리세롤 필름을 제작하였다.1% chitosan solution dissolved in 0.5% acetic acid and glycerol solution dissolved in 3% distilled water at 1% concentration were mixed at a weight ratio of 1: 0.7, and 200 µl of the mixed solution was cast in a sterile state. Natural drying for 1 day to produce a chitosan / glycerol film.
<실시예3>Example 3
0.5% 아세트산에 용해하여 여과를 한 1% 키토산 용액과 3차 증류수에 1% 농도로 용해한 글리세롤 용액을 1:1의 중량비로 혼합하고, 그 얻어진 혼합물에 5-플루오로우라실(5-fluorouracil;5FU)을 0.4mg/㎖ 농도로 혼합한 후에 상기 실시예 1 및 상기 실시예 2와 동일한 방법으로 주조하여 후발성 백내장 예방치료용 약물전달필름을 제작하였다.A 1% chitosan solution dissolved in 0.5% acetic acid and filtered and a glycerol solution dissolved in 1% concentration in tertiary distilled water were mixed in a weight ratio of 1: 1, and 5-fluorouracil (5-FU) was added to the obtained mixture. ) Was mixed at a concentration of 0.4 mg / ㎖ and cast in the same manner as in Example 1 and Example 2 to prepare a drug delivery film for the treatment of late cataracts.
<실시예4>Example 4
0.5% 아세트산에 용해하여 여과를 한 1% 키토산 용액과 3차 증류수에 1% 농도로 용해한 글리세롤 용액을 1:0.7의 중량비로 혼합하고, 그 얻어진 혼합물에 5-플루오로우라실(5-fluorouracil;5FU)을 0.4mg/㎖ 농도로 혼합한 후에 상기 실시예 1 및 상기 실시예 2와 동일한 방법으로 주조하여 후발성 백내장 예방치료용 약물전달필름을 제작하였다.A 1% chitosan solution dissolved in 0.5% acetic acid and filtered and a glycerol solution dissolved in 1% concentration in tertiary distilled water were mixed in a weight ratio of 1: 0.7, and 5-fluorouracil (5-FU) was added to the resulting mixture. ) Was mixed at a concentration of 0.4 mg / ml and then cast in the same manner as in Example 1 and Example 2 to prepare a drug delivery film for the treatment of late cataract.
<실험예1; 함수율 측정>Experimental Example 1; Moisture Content Measurement>
함수율의 측정은 실시예 1 및 실시예 2에 따라 각각 제작된 필름의 초기 중량(Wi)을 측정한 다음, 그 필름들 각각을 인산완충식염수(PBS) 10㎖에 담아 37℃에서 24시간 동안 팽윤시킨 후 행해졌다.The water content was measured by measuring the initial weight (W i ) of each of the films produced according to Examples 1 and 2, and then each of the films in 10 ml of phosphate buffered saline (PBS) for 24 hours at 37 ℃ After swelling.
팽윤된 필름들 각각의 습시료 중량(Wt)을 측정하고, 재건조 후 무게(Wd)를 측정하여, 아래의 수학식 1에 대입하여 함수율을 각각 계산하였으며, 그 계산된 함수율은 첨부된 도 1의 그래프에 도시되고 표 1에 표시되어졌다.The wet sample weight (W t ) of each of the swollen films was measured, and the weight (W d ) after redrying was measured, and the water content was calculated by substituting the following Equation 1, and the calculated water content was It is shown in the graph of FIG. 1 and shown in Table 1.
<실험예2; 분해율 측정>Experimental Example 2; Decomposition Rate Measurement>
실시예 1 및 실시예 2에 따라 각각 제작된 필름을 40㎖의 인산완충식염수(PBS)에 각각 넣어 37℃에서 방치한 후, 일정시간마다 그 필름들 각각의 건조무게를 측정하였다.Each of the films prepared according to Example 1 and Example 2 were put in 40 ml of phosphate buffered saline (PBS), respectively, and left at 37 ° C., and then the dry weights of the films were measured at regular intervals.
이 때, 초기중량(Wi)에 대해 일정시간마다 측정된 건조무게(Wt)의 비율을 하기 수학식 2에 대입하여 분해율을 계산하고, 그 분해율의 평균치를 표 2에 표시하고 도 2에 도시하였다.At this time, the decomposition ratio was calculated by substituting the ratio of the dry weight (W t ) measured at regular intervals with respect to the initial weight (W i ) in the following Equation 2, and the average value of the decomposition ratio is shown in Table 2 and shown in FIG. Shown.
<실험예3; 약물 방출율 측정>Experimental Example 3; Drug Release Rate Measurement>
실시예3 및 실시예4를 따라 제작된 안질환 치료용 약물전달필름의 약물 방출속도를 측정하기 위하여, 상기 약물전달필름들이 80μg의 5FU를 함유하도록 준비하고, 그 준비된 약물전달필름들을 5㎖의 인산완충식염수(PBS)에 넣은 후 37℃에 방치하면서 5FU를 방출시킨 후 일정시간마다 샘플링하여 HPLC로 5FU의 방출량(Wo)을 측정하였다.In order to measure the drug release rate of the drug delivery film for treating eye diseases prepared according to Examples 3 and 4, the drug delivery films were prepared to contain 80 μg of 5FU, and the prepared drug delivery films were prepared in 5 ml. 5FU was released while being placed in phosphate buffered saline (PBS) at 37 ° C. and then sampled at regular intervals to measure the release amount (W o ) of 5FU by HPLC.
약물의 방출율은 약물전달필름이 처음 갖는 5FU 80μg에 대해 일정시간 간격으로 방출된 5FU 양을 하기 수학식 3에 대입하여 계산되어졌고, 그 계산된 방출율은 표 3에 표시되고 도 3에 도시되어졌다.The release rate of the drug was calculated by substituting the amount of 5FU released at regular intervals for the first 5FU 80μg of the drug delivery film into Equation 3 below, and the calculated release rate is shown in Table 3 and shown in FIG. 3. .
<실험예4; 필름의 독성평가>Experimental Example 4; Toxicity Evaluation of Films>
실시예 1 및 실시예 2에 따라 제작되어 약물을 함유하지 않는 필름 자체의 세포독성을 측정하기 위해, 필름의 독성평가가 이루어졌다.In order to measure the cytotoxicity of the film itself which was prepared according to Examples 1 and 2 and did not contain a drug, the toxicity evaluation of the film was made.
수정체 상피세포(Human Lens Epithelial B-3 Cell)를 75cm2 배양 플라스크("Nalge Nunc International"사로부터 구입)에 뉴욕(New), 그랜드 아이슬랜드(Grand Island) 소재의 "Invitrogen"사로부터 구입한 20% 우태아혈청(FBS)을 사용하여 37℃의 5% 이산화탄소 배양기에 배양하였고, 세포가 70~80% 정도 자랄 때까지 배지를 매일 바꾸어 주어 웰-플레이트(well-plate;"Nalge Nunc International"사로부터 구입)에 5×104 로 분주한 후, 37℃ 5% 이산화탄소 배양기에서 다시 26시가 배양하였다.20% purchased from Human Lens Epithelial B-3 Cells from "Invitrogen", Grand Island, New York, in a 75 cm 2 culture flask (purchased from "Nalge Nunc International") Incubated in fetal calf serum (FBS) in a 5% carbon dioxide incubator at 37 ° C., changing the medium daily until cells grew to 70-80%, from a well-plate (“Nalge Nunc International”). 5 × 10 4 , and 26 hours were cultured again at 37 ° C. in a 5% carbon dioxide incubator.
배지의 FBS 농도를 20%에서 1%로 바꾸어주고 다시 24시간 배양 후 실시예 1 및 실시예 2에 따라 제작된 필름을 우태아혈청(FBS)이 없는 배지에 넣어 주었다. 그 후, 37℃에서 24시간 배양한 후, 세포 생존율의 측정을 통한 상기 필름들의 독성평가를 위해 MTT 평가분석법을 수행하였다. The FBS concentration of the medium was changed from 20% to 1%, and after 24 hours of incubation, the films prepared according to Examples 1 and 2 were placed in fetal calf serum (FBS) -free medium. Then, after 24 hours incubation at 37 ℃, MTT assay was performed for the toxicity evaluation of the films by measuring the cell viability.
이에 따라, 인산완충식염수(PBS)에 MTT를 5mg/㎖ 되도록 녹여 웰(well)에 담겨있는 500㎖ 배지양의 1/10인 50㎕ 넣고 1시간 30분 동안 5% 이산화탄소 37℃ 배양기에서 배양하였다. 그리고, 각 웰에 담겨있는 배지, 필름 및 MTT를 진공흡입기로 제거하고 웰에 이소프로필알콜(isoprophylalcohol)에 0.04M Hcl을 녹인 용액을 200㎕ 넣어 플레이트에 붙어 있는 세포를 수집하여 150㎕을 96웰-플레이트(96well-plate;"Nalge Nunc International"사로부터 구입)에 옮긴 후 엘리사 판독기(ELISA reader; Molecular Device, spectra max 250)로 570nm에서 흡광도를 측정하여 세포의 수를 확인하였다. Accordingly, MTT was dissolved in phosphate-buffered saline (PBS) to 5 mg / ml, and 50 μl of 1/10 of the 500 ml medium contained in the well was added thereto, followed by incubation in a 37% incubator at 5% carbon dioxide for 1 hour and 30 minutes. . In addition, the medium, film and MTT contained in each well were removed by a vacuum inhaler, and 200 μl of a solution in which 0.04 M Hcl was dissolved in isopropyl alcohol (isoprophylalcohol) was collected in a well. The number of cells was confirmed by transferring to 96-plate (purchased from "Nalge Nunc International") and absorbance at 570nm with an ELISA reader (Molecular Device, spectra max 250).
실시예 1 및 실시예 2로 제작된 필름의 자체 세포 독성은, 상기 필름이 넣어진 채 12시간, 24시간, 그리고 48시간 배양된 처리군과, 필름을 넣지 않은 대조군이 하기 수학식 4를 이용한 세포의 숫적생존율(세포 생존율)의 계산을 통해 비교 평가되어졌다. Self-cytotoxicity of the films prepared in Examples 1 and 2, the treatment group incubated for 12 hours, 24 hours, and 48 hours with the film, and the control group without the film using the following equation (4) Comparative evaluation was made by calculating the numerical survival rate (cell viability) of the cells.
평가결과, 실시예 1 및 실시예 2로 제작된 필름 모두 세포에 대한 독성이 없는 것으로 평가되어졌고, 이는 도 4에 잘 도시되어 있다.As a result of the evaluation, both the films produced in Examples 1 and 2 were evaluated to be non-toxic to cells, which is well illustrated in FIG. 4.
<실험예 5; 상피세포의 억제효과 평가>Experimental Example 5; Evaluation of Inhibitory Effect of Epithelial Cells>
실시예 3 및 실시예 4에 따라 제작된 약물전달필름이 후발성 백내장 치료용도로 사용될 경우, 그 약물전달필름에 의한 상피세포의 억제효과, 즉 후발성 백내장의 예방효과를 평가하기 위해, 상피세포의 억제효과에 대한 평가가 이루어졌다.When the drug delivery films prepared according to Examples 3 and 4 are used for the treatment of late cataracts, in order to evaluate the inhibitory effect of epithelial cells by the drug delivery films, that is, the preventive effect of late cataracts, The inhibitory effect of
본 실험예 5는 앞선 실험예 4와 모든 조건을 같게 하고, 다만 실시예 1 및 실시예 2에 따라 제작된 필름 대신 실시예 3 및 실시예 4에 따라 제작된 필름이 이용되었다.In Experimental Example 5, all the conditions were the same as in Experimental Example 4, except that the films produced according to Examples 3 and 4 were used instead of the films prepared according to Examples 1 and 2.
상기 상피세포의 억제효과에 대한 평가, 즉 후발성 백내장의 예방효과는, 실시예 3 및 실시예 4에 따라 제작된 필름이 넣어진 채 12시간, 24시간, 그리고 48시간 배양된 처리군과, 필름을 넣지 않은 대조군이 상기 수학식 4를 이용한 세포의 숫적생존율(세포 생존도)의 계산을 통해 비교 평가되어졌다. Evaluation of the inhibitory effect of the epithelial cells, that is, the preventive effect of late cataract, the treatment group incubated for 12 hours, 24 hours, and 48 hours with the films prepared according to Examples 3 and 4, The control without the film was compared and evaluated by calculating the numerical survival rate (cell viability) of the cells using the equation (4).
평가결과, 실시예 3 및 실시예 4 필름이 넣어진 처리군의 세포생존량이 필름이 넣어지지 않은 대조군의 세포생존량에 대해 약 40% 정도에 불과하였고, 이러한 결과는 도 5에 잘 도시되어 있다. As a result of the evaluation, the cell viability of the treatment group containing the Example 3 and Example 4 film was only about 40% of the cell survival of the control group without the film, which is well shown in FIG. .
이상에서 살펴본 바와 같이, 본 발명에 따른 안질환 치료용 약물전달필름은 생분해되는 키토산에 의해 지속적인 약물방출을 가능하게 하면서도 글리세롤에 의해 경도 및 투명도가 충분히 보장되어 안과치료에 적합하게 이용될 수 있는 효과를 갖는다. As described above, the drug delivery film for treating ocular disease according to the present invention enables continuous drug release by chitosan which is biodegradable, while having sufficient hardness and transparency by glycerol, which can be suitably used for ophthalmic treatment. Has
또한, 본 발명에 따른 안질환 치료용 약물전달필름은 함수율, 분해율, 약물 방출율 면에서 안질환 치료, 특히 후발성 백내장의 예방치료에 적합하고, 매개체 역할을 하는 키토산/글리세롤 자체의 독성이 없어 인체에 무해하다는 효과를 갖는다.In addition, the drug delivery film for treating eye diseases according to the present invention is suitable for the treatment of eye diseases, in particular for the prevention of late cataracts in terms of water content, decomposition rate and drug release rate, and does not have the toxicity of chitosan / glycerol itself, which acts as a mediator. Harmless to
특히, 본 발명에 따라 제조된 안질환 치료용 약물전달필름은 용액 내에서 그 형태가 크게 변하지 않기 때문에 인공수정체와 수정체 후낭 사이에 삽입된 후 그 위치를 이탈하거나 주변조직에 영향을 주지 않는 효과를 갖는다. In particular, the drug delivery film for treating ophthalmic diseases prepared according to the present invention does not significantly change its shape in solution, so it is effective between the lens and the posterior capsular capsule after it is inserted into the intraocular lens. Have
도 1은 본 발명에 따른 약물전달필름의 함수율을 도시한 그래프.1 is a graph showing the water content of the drug delivery film according to the present invention.
도 2는 본 발명에 따른 약물전달필름의 분해율을 도시한 그래프.Figure 2 is a graph showing the decomposition rate of the drug delivery film according to the present invention.
도 3은 본 발명에 따른 약물전달필름의 약물 방출율을 평가하여 도시한 그래프. Figure 3 is a graph showing the evaluation of the drug release rate of the drug delivery film according to the present invention.
도 4는 본 발명에 따른 약물전달필름의 필름독성을 평가하여 도시한 그래프Figure 4 is a graph showing the evaluation of the film toxicity of the drug delivery film according to the present invention
도 5는 본 발명에 따른 약물전달필름의 상피세포 사멸/억제 효과를 도시한 그래프. Figure 5 is a graph showing the epithelial cell killing / suppression effect of the drug delivery film according to the present invention.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2003-0003345A KR100515479B1 (en) | 2003-01-17 | 2003-01-17 | medicine delivering film for treating ophthalmology disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2003-0003345A KR100515479B1 (en) | 2003-01-17 | 2003-01-17 | medicine delivering film for treating ophthalmology disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20040066316A KR20040066316A (en) | 2004-07-27 |
| KR100515479B1 true KR100515479B1 (en) | 2005-09-15 |
Family
ID=37356159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2003-0003345A KR100515479B1 (en) | 2003-01-17 | 2003-01-17 | medicine delivering film for treating ophthalmology disease |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100515479B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220096403A (en) | 2020-12-31 | 2022-07-07 | (주)네오비젼 | Contact lens with sustained drug release ability and manufacturing method thereof |
| KR20230080701A (en) | 2021-11-30 | 2023-06-07 | (주)네오비젼 | Contact lens for drug delivery |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102176486B1 (en) * | 2019-06-14 | 2020-11-10 | 동국대학교 산학협력단 | Method for Preparing an Ophathalmic Drug Carrier Based on Hyaluronic Acid |
-
2003
- 2003-01-17 KR KR10-2003-0003345A patent/KR100515479B1/en not_active IP Right Cessation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220096403A (en) | 2020-12-31 | 2022-07-07 | (주)네오비젼 | Contact lens with sustained drug release ability and manufacturing method thereof |
| KR20230080701A (en) | 2021-11-30 | 2023-06-07 | (주)네오비젼 | Contact lens for drug delivery |
| KR20230081995A (en) | 2021-11-30 | 2023-06-08 | (주)네오비젼 | Manufacturing method contact lens for drug delivery |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20040066316A (en) | 2004-07-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230404961A1 (en) | Ophthalmic compositions and methods for treating eyes | |
| Küchle et al. | Occurrence of pseudoexfoliation following penetrating keratoplasty for keratoconus. | |
| AU2009308017A1 (en) | Ophthalmic compositions useful for improving visual acuity | |
| US6376543B1 (en) | Secondary cataract inhibitor | |
| KR20210010638A (en) | Compositions for use in treating eye disorders using dipyridamole | |
| KR100515479B1 (en) | medicine delivering film for treating ophthalmology disease | |
| Mannis et al. | The effect of fluorouracil on the corneal endothelium | |
| RU2513997C1 (en) | Combined ophthalmic preparation presented in form of eye drops and containing polyhexamethylene guanidine and taurine | |
| US9254289B2 (en) | Methods for treating eye disorders using dipyridamole | |
| EP3682867B1 (en) | Lutein-containing ophthalmic composition | |
| CN112891326B (en) | Natamycin-loaded alginic acid gel medicine film and preparation method thereof | |
| Coles | Effects of antibiotics on the in vitro rabbit corneal endothelium. | |
| Donn | Aphakic bullous keratopathy treated with prosthokeratoplasty: an analysis of 34 consecutive cases | |
| Kaul et al. | An insight into ocular insert | |
| CN107970211A (en) | Preoperative cornea flushing liquor, preparation method and applications | |
| KR20050095077A (en) | Sustained release collagen film for treating ophthalmology disease and the method for producing thereof | |
| ZARĘBSKA et al. | Histological changes in the retina in experimental alloxan-induced diabetes in rabbits | |
| RU2135127C1 (en) | Solution "vizitin" for prophylaxis and treatment of patient with sickness and damage of cornea | |
| Gandhi et al. | A review on: ocular inserts a novel drug delivery system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| N231 | Notification of change of applicant | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20120716 Year of fee payment: 8 |
|
| FPAY | Annual fee payment |
Payment date: 20130710 Year of fee payment: 9 |
|
| LAPS | Lapse due to unpaid annual fee | ||
| FPAY | Annual fee payment |
Payment date: 20160405 Year of fee payment: 11 |
|
| R401 | Registration of restoration | ||
| FPAY | Annual fee payment |
Payment date: 20160908 Year of fee payment: 12 |
|
| LAPS | Lapse due to unpaid annual fee |