KR102083503B1 - Pharmaceutical composition and kit for preventing or treating cystic disease, and method using the same - Google Patents

Abstract

According to one aspect, a pharmaceutical composition, a kit, and a method for preventing or treating cystic disease using the same are provided. According to this, the cyst can be safely and simply removed, recurrence can be prevented, and side effects can be minimized. Also provided are methods of screening candidate agents for preventing or treating cystic disease. According to this, candidate microorganisms effective for removing the cyst can be screened by simulating the microenvironment of the actual cyst.

Description

Pharmaceutical composition and kit for preventing or treating cystic disease, and method using the same

Pharmaceutical compositions for preventing or treating cystic diseases, kits, methods for preventing or treating cystic diseases using the same, and methods for screening candidate substances for preventing or treating cystic diseases.

A cyst is a pouch with a film (or membrane) and contents that is distinct from surrounding tissue. The contents in the cyst coat may be liquid or semisolid substances derived from the human body, and the capsule of the cyst consists of cells constituting the cyst and collagen around the cells. Cysts can occur anywhere in the kidneys, ovaries, liver, breasts, and skin. Typically, once a cyst is formed, it does not go away unless it is removed by surgery and lasts for life. Most cysts are benign and do not have a significant impact on health, but they can sometimes be cancerous or precancerous (the stages before cancer) and can mean severe underlying disease. For example, in the case of polycystic kidney disease, cysts develop and the pain increases as the size of the cyst increases, leading to cyst-related complications such as hypertension and abnormal kidney function, which may lead to kidney failure.

Cyst cure or decompression (Sclerotherapy of cyst) is a treatment method that chemically destroys the cyst coat after inhaling the contents of the cyst. The cyst was removed using a hardening liquid drug used for vascular treatment, but there were side effects such as recurrence of the cyst, extreme pain, and infection. In addition, there is a method of administering a curing agent in the form of a liquid (foam), there is a problem in that it is difficult to maintain the form of the foam and the side effects caused by the existing curing liquid.

Therefore, there is a need to develop a foam-type cyst-curable drug that can be used for cystic sclerotherapy, and to develop a method for preventing or treating cystic disease using the same.

Provided are pharmaceutical compositions for preventing or treating cystic diseases.

Kits for preventing or treating cystic disease are provided.

Provided are methods for preventing or treating cystic disease.

Methods of screening candidate agents for preventing or treating cystic disease are provided.

One aspect provides pharmaceutical compositions for preventing or treating cystic diseases, including sclerosant agents, osmotic agents, and photosensitizers.

The pharmaceutical composition may be in the form of a foam. The pharmaceutical composition may comprise a medical gas. The gas is, for example, sterile air, carbon dioxide, or oxygen.

The term "sclerosant agent" refers to a substance that, when administered to a structure such as a cyst or blood vessel, causes them to contract. The curing agent may induce protein denaturation and destroy cell membranes. The curing agent of claim 1, wherein the curing agent is polydocanol, sodium tetradecyl sulphate, sodium morrhuate, ethanolamine oleate, minocycline hydro It may be selected from the group consisting of minocycline hydrochloride, N-butyl cyanoacrylate, and iodized oil. The polydocanol may be a mixture of macrogol monolauryl ethers of formula C ₁₂ C ₂₅ (OCH ₂ CH ₂ ) _n OH with an average value of n of 9. The polydocanol is laureth 9, macrogol lauryl ether, lauromacrogol, PEG-9 lauryl alcohol, POE-9 lauryl alcohol, dodecyl polyethylene glycol ether (Dodecylpolyethyleneglycolether), hydroxyl polyethoxy dodecane (Hydroxyl polyethoxy dodecane), or may also be called Oxypolyethoxy dodecane (Oxypolyethoxydodecane). The concentration of the curing agent in the pharmaceutical composition is about 0.1% (v / v) to about 10% (v / v), about 0.2% (v / v) to about 8% (v / v), about 0.5% ( v / v) to about 6% (v / v), about 1% (v / v) to about 4% (v / v), or about 2% (v / v) to about 3% (v / v) Can be.

The osmotic agent may be a substance that induces cell dehydration or damage to the cell by inducing cell dehydration. The osmotic agent may be selected from the group consisting of glycerol, sodium chloride solution, and dextrose-containing sodium chloride. The concentration of the osmotic agent in the pharmaceutical composition is about 0.1% (v / v) to about 20% (v / v), about 0.5% (v / v) to about 18% (v / v), about 1% (v / v) to about 16% (v / v), about 2% (v / v) to about 15% (v / v), about 5% (v / v) to about 15% (v / v) , About 6% (v / v) to about 14% (v / v), about 7% (v / v) to about 13% (v / v), about 8% (v / v) to about 12% ( v / v), about 9% (v / v) to about 11% (v / v), or about 10% (v / v) to about 11% (v / v).

The photosensitizer may be a material that exhibits a light sensitive reaction. The photosensitizer may denature cell membranes or proteins by photochemical reactions. The photosensitizer rose bengal, fluorescein, eosin blue, methylene blue, erythrosin blue, riboflavin, porphyrin, phthalocyanine (phthalocyanine), and tetrapyrrole (tetrapyrrole). The concentration of the photosensitizer in the pharmaceutical composition is about 0.1% (v / v) to about 10% (v / v), about 0.1% (v / v) to about 9% (v / v), about 0.1% ( v / v) to about 8% (v / v), about 0.1% (v / v) to about 7% (v / v), about 0.1% (v / v) to about 6% (v / v), About 0.1% (v / v) to about 5% (v / v), about 0.1% (v / v) to about 4% (v / v), about 0.1% (v / v) to about 3% (v / v), about 0.1% (v / v) to about 2% (v / v), about 0.1% (v / v) to about 1% (v / v), about 0.1% (v / v) to about 0.9% (v / v), about 0.1% (v / v) to about 0.8% (v / v), about 0.1% (v / v) to about 0.7% (v / v), about 0.1% (v / v) to about 0.6% (v / v), about 0.1% (v / v) to about 0.5% (v / v), about 0.1% (v / v) to about 0.4% (v / v), about 0.1 % (v / v) to about 0.3% (v / v), or about 0.1% (v / v) to about 0.2% (v / v).

The pharmaceutical composition may be a pharmaceutical composition for injection.

The cystic diseases include polycystic kidney disease, polycystic ovary syndrome (PCOS), medulla cystic kidney disease, cysts of the jaw, periodontal cysts, periodontal cysts, dental cysts, and periodontal Gaitus cyst, Nasopalatine duct cyst, Polycystic liver disease, Congenital liver fibrosis, Degenerative hepatitis, Biliary hamartomas, Caroli disease, Choledochal cysts, Cholangiopancreatic hyperplasia Species (Bile duct hamartoma), cystic hygroma, breast cyst, cutaneous cyst, and cystic bronchiectasis.

The term "prevention" refers to any action that inhibits or delays the development of cystic disease by administration of the pharmaceutical composition. The term "treatment" refers to any action in which symptoms of cystic disease improve or benefit altered by administration of the pharmaceutical composition.

The pharmaceutical composition may include a sclerosant agent, an osmotic agent, and a photosensitizer in an effective amount. The term "effective amount" refers to an amount sufficient to exert the effect of prophylaxis or treatment when administered to a subject in need thereof. The effective amount may be appropriately selected by those skilled in the art according to the cell or individual to be selected. Factors including the severity of the disease, the age, weight, health, sex of the patient, the sensitivity of the patient to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, the drug in combination with the composition used, or other medical fields. Can be determined according to well-known factors. The effective amount is about 0.1 μl to about 1 mL, about 5 μl to about 100 μl, about 10 μl to about 80 μl, about 20 μl to about 60 μl, about 20 μl to about 40 μl, per ml of the pharmaceutical composition, Or about 30 μl.

The pharmaceutical composition may comprise a pharmaceutically acceptable carrier. The carrier is used in the sense including excipients, diluents or adjuvants. The carrier is, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pi It may be selected from the group consisting of rolidone, water, saline, buffers such as PBS, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, and mineral oil. The composition may comprise fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, or combinations thereof.

The pharmaceutical composition may be prepared in any formulation according to conventional methods. The composition may be formulated, for example, in a parenteral formulation (eg injection). In addition, the compositions may be prepared in systemic or topical formulations.

The pharmaceutical composition may be administered in a conventional manner via the oral, transdermal, subcutaneous, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, topical, or intradermal routes. The dosage of the pharmaceutical composition may be, for example, from about 0.001 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 10 mg / kg, or about 0.1 mg / kg to about 1 mg / on an adult basis. It may be in the range of kg. The administration is once a day, twice to 24 times a day, once to twice a day, once to six times a week, once to ten times a week, once to 15 times a three weeks. , Once to three times a week, or once to twelve times a year.

Another aspect includes a pharmaceutical composition of claim 1 comprising a curing agent, an osmotic agent, and a photosensitizer; And

Provided are kits for preventing or treating cystic disease, including syringes.

The kit may further comprise a one-way valve, a two-switch, a three-way tap, or a combination thereof. The kit may further comprise a stopcock or a luer connector.

Another aspect includes preparing a pharmaceutical composition according to one aspect in the form of a foam; And

A method of preventing or treating cystic disease is provided, comprising contacting the pharmaceutical composition in foam form with the membrane of the cyst by administering the pharmaceutical composition in foam form to the interior of the cyst.

The method comprises the step of preparing the pharmaceutical composition according to one aspect in the form of a foam.

By adding a medical gas to the pharmaceutical composition can be prepared in the form of a foam. The medical gas is as described above.

The foam form can be prepared using methods known in the art (eg, Tessari method).

The method comprises administering the pharmaceutical composition in foam form to the interior of the cyst to contact the membrane of the cyst with the pharmaceutical composition in foam form.

The cyst may be a film or membrane of the cyst from which the internal stock solution of the cyst is removed. The pharmaceutical composition in foam form may be in contact with the interior of the cyst coating to cure the cyst coating. The cyst may be a cyst present in vitro or in vivo in the subject. The subject may be a mammal, for example human, cow, horse, pig, dog, sheep, goat or cat.

The pharmaceutical composition may be administered parenterally. The method of administration can be, for example, the oral, transdermal, subcutaneous, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, topical, intranasal, intratracheal, or intradermal routes. The composition may be administered systemically or locally, and may be administered alone or in combination with other pharmaceutically active compounds. The dosage is, for example, in the range of about 0.001 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 10 mg / kg, or about 0.1 mg / kg to about 1 mg / kg on an adult basis. Can be. The administration can be administered once daily, multiple times daily, or once a week, once every two weeks, once every three weeks, or once every four weeks to once a year.

The method may further include irradiating light to the cyst containing the pharmaceutical composition therein. The pharmaceutical composition may adsorb the cyst coat via photochemical tissue crosslinking. The light may be a laser, an infrared wave, a two photon laser, or a combination thereof. The laser may be Light Amplification by the Stimulated Emission of Radiation. The laser can be light having a wavelength of about 500 nm to about 600 nm, about 510 nm to about 580 nm, 520 nm to about 560 nm, 530 nm to about 540 nm, or about 532 nm.

Another aspect includes preparing a foam formulation by adding a test substance to a pharmaceutical composition according to one aspect;

Place the foam formulation in the upper chamber of the transwell chamber and place cyst or cystic cells on the lower side of the insert of the transwell, or place the foam formulation in the lower portion of the transwell chamber. Placing the cyst or cystic cells in an upper chamber of a transwell chamber to contact the pharmaceutical composition with the cystic cells; And

Preventing cystic disease, comprising screening a test substance effective for removing the cyst by measuring the removal of the cyst, survival of the cystic cells, Lactate dehydrogenase (LDH) activity, or a combination thereof Or a method of screening candidate substances for treatment.

The method includes adding a test substance to a pharmaceutical composition according to one aspect to prepare a foam formulation.

The foam formulations can be prepared using methods known in the art (eg, Tessari method).

The method places the foam formulation in the upper chamber of the transwell chamber and places the cyst or cystic cell in the lower side of the insert of the transwell, or the foam formulation in the lower chamber of the transwell chamber and the cyst or cystic Positioning the cells in an upper chamber of a transwell chamber to contact the pharmaceutical composition with the cystic cells.

When the foam formulation is placed in the upper chamber of the transwell chamber and the cyst or cystic cells are placed on the lower surface of the insert of the transwell, it can be called by two-dimensional in vitro hardening and the foam formulation contacts the interior of the cyst's coating. You can simulate what you do.

When the foam formulation is placed in the lower chamber of the transwell chamber and the cyst or cystic cells are placed in the upper chamber of the transwell chamber, it can be called three-dimensional in vitro sclerotherapy and the three-dimensional contact of the cyst and foam formulation I can copy it.

The transwell chamber refers to a chamber including a microporous membrane at a lower end thereof. The transwell chamber is also referred to as a transwell upper chamber or transwell insert. The microporous membrane is a support through which a substance such as a buffer, a cellular material, or a culture medium penetrates but a cell cannot penetrate. The pore size of the microporous membrane may be appropriately adopted by those skilled in the art, for example, 0.4 μm to 0.8 μm. For example, microporous membranes are polycarbonates, polyesters, and collagen-coated polytetrafluoroethylene. The transwell chamber is widely used in the art and may be a commercially available product.

The method comprises screening a test material effective for removing the cyst by measuring the removal of the cyst, the survival rate of the cystic cells, the Lactate dehydrogenase (LDH) activity, or a combination thereof.

The method may further comprise irradiating the cyst or cystic cell and foam formulation with light. The light is as described above.

Pharmaceutical compositions, kits for preventing or treating cystic diseases, and methods of preventing or treating cystic diseases using the same, according to one aspect, can safely and simply remove cysts and prevent recurrence. The side effects can be minimized. In addition, by using a method of screening a candidate material for preventing or treating cystic disease, it is possible to screen a candidate material effective for removing the cyst by simulating the microenvironment of the actual cyst.

FIG. 1A is a photograph of a syringe for producing a polydocanol-containing foam by the Tessari method, and FIGS. 1B and 1C are schematic diagrams showing two-dimensional in vitro cyst hardening therapy.
Figure 2a is a graph showing the concentration of polydocanol foam and LDH activity (percentage ratio of LDH activity of each experimental group to LDH activity of the positive control) after contacting the foam formulation containing glycerol with the cells. FIG. 2B is a green image of living cells through live and dead imaging of live cells after two-dimensional in vitro sclerotherapy. Figure 2c is a result of treating the cured foam solution using the existing CCK-8 method, a graph that did not give a significant result (N / A: not available (not available)).
Figure 3 shows cells for time (minutes) when contacted with cells with a foam formulation containing 3% (v / v) polydocanol and 0.1% (v / v) to 10% (v / v) of rose bengal. It is a graph showing the survival rate (percent ratio of each experimental group to the positive control).
4 is a graph showing the retention time of 3% (v / v) polydocanol foam formulations containing 0% (v / v) glycerol (negative control) to 20% (v / v) glycerol.
FIG. 5A is a schematic diagram measuring the extent and rate at which collagen fibrillogenesis occurs over time when a 532 nm laser is injected according to Rose Bengal contained in collagen (a: negative control, b: 1 minute in cancer conditions). Laser scan at 532 nm, c: confirm collagen fibrosis), FIGS. 5B and 5C are graphs of the measurement results.
FIG. 6A is an experimental schematic diagram showing how the cyst-curable foam diffused from collagen gel penetrates rose bengal over time, and FIG. 6B is a graph of the measurement results.

It will be described in more detail through the following examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1. Curable Foam Composition for Cyst Decompression in Kidney Disease

1. Screening of Cyst-Curable Foam Formulations in 2-D In Vitro Foam Forms

When cyst sclerotherapy is performed, a curable foam is administered inside the cyst's coat. Cells were attached to the cross-section under the transwell insert and simulated in the transwell upper chamber to simulate in vitro the contact of the curable foam with the cyst's coat.

Specifically, 1% (v / v), 2% (v / v), and 3% (v / v) polydocanol solution (diluted with distilled water or phosphate buffered saline (PBS) (when treating cells)) Polidocanol, Asclera®, Merz Aesthetics) were prepared. Polydocanol solution was added to a 5 ml syringe polydocanol solution. Foam formulations were prepared by using the Tessari method, ie double syringes, and passing through 10 syringes so that the ratio of air to solution was 1: 4 (FIG. 1A).

Transwell inserts were preincubated with MEM cell culture medium for about 30 minutes (FIG. 1B (i)). The transwell insert was turned upside down on the 6-well plate. Maddin-Darby Canine Kidney (MDCK) cells, which are the cells that make up the kidney cyst, were prepared. 2.5 x 10 ⁴ Cell suspensions containing MDCK cells were seeded on the underside of the transwell membrane (top side of the inverted transwell insert) (FIG. 1B (ii)). The transwell inserts on which the cells were placed were incubated in the incubator for about 30-40 minutes, after which the transwell inserts were placed in 24-well plates (FIG. 1B (iii)). 600 μl of cell culture medium was added to the transwells placed in 24-well plates.

100 μl of the prepared polydocanol foam was added to the transwell insert and incubated for 1 minute (FIG. 1B (iv)). Then, the transwell insert loaded with polydocanol foam was removed. Twenty-four wells of total cell cultures were collected and centrifuged to collect cell cultures containing no cells.

10 μl of cell culture was added to a 96 well plate and 100 μl of Lactate dehydrogenase (LDH) assay solution (50: 1 = LDH buffer: water soluble tetrazolium salt (WST)). Was added. After the plate was incubated for about 30 minutes in dark conditions, the absorbance at 450 nm was measured using a Microplate reader. As a control, a cell culture obtained before treatment of the foam (negative control) and 100 [mu] l of the lysis buffer provided in the LDH assay kit were added to the transwell insert and a cell culture obtained (positive control) after 1 minute was used.

LDH activity was calculated using the measured absorbance and the following equation.

Equation

LDH is an enzyme present in the cytoplasm that normally does not pass through the cell membrane and is not excreted out of the cell, but is released into the medium when the cell membrane is damaged or the cell dies. Thus, LDH activity in the medium is proportional to the number of cells in which cells die or are injured and exhibit cytotoxicity.

A graph showing LDH activity (percent ratio of LDH activity of each experimental group to LDH activity of positive control group) according to the concentration of polydocanol foam is shown in FIG. 2A. As shown in Figure 2a, as the concentration of polydocanol foam increased, the cytotoxicity was increased.

In addition, to confirm the increase in cytotoxicity, the actual cell imaging results are shown in FIG. 2B. As shown in FIG. 2B, the cells killed by the foam treatment fell down by gravity and did not remain in the imaging photograph.

In addition to the increase in the concentration of polydocanol foam, when the treatment was developed by the development of a new foam, such as mixing glycerol in the foam, the effect was also very significantly different from other high results (Fig. 2a). These results were impossible with the CCK-8 assay, one of the existing cytotoxicity experiments (Fig. 2c). Thus, it was confirmed that the experimental method for screening cyst curable foam formulations in foam form in vitro works effectively.

2. rose Bengal  Confirmation of Cytotoxicity

Additives may be added to polydocanol to produce curable foam formulations that are more potent in removing cysts. As an additive, a photosensitizer is for photochemically binding to the collagen layer of the cyst coat, and Rose Bengal may be used as the photosensitizer.

Before using Rose Bengal in the curable foam formulation, the cytotoxicity of Rose Bengal was confirmed. Specifically, Rose Bengal (Sigma Aldrich) was added to distilled water to prepare a Rose Bengal solution of 0.1% (v / v) to 10% (v / v). The prepared rose bengal solution was added to MDCK cells and incubated for 0.1 to 60 minutes. Cell viability (percentage of each experimental group relative to the positive control group) was then measured using a CCK-8 assay kit (Dojindo Molecular Technologies, Inc.). Measured cell viability is shown in FIG. 3.

As shown in Figure 3, Rose Bengal was confirmed that there is no cytotoxic up to a concentration of 10% (v / v).

3. Stability of glycerol-containing cyst curable foams

In order to verify the stability or retention time of the foam, the time for half of the prepared foam formulation to return to the original solution state was measured.

Specifically, 3% (v / v) polydocanol foam formulations containing 0% (v / v) glycerol (negative control) to 15% (v / v) glycerol were prepared, as described in Example 1.2. . In order to simulate the physiological environment of the human body, the retention time of the foam formulation in a chamber at about 37 ° C. was measured, and the results are shown in FIG. 4.

As shown in FIG. 4, foam formulations containing 10% (v / v) glycerol were the most stable. In addition, foam formulations containing 10% (v / v) glycerol have about twice as good foam formulations containing glycerol as the cell membrane destabilizing effect (LDH activity), so glycerol-containing foam formulations are curable for cyst decompression. It confirmed that it was excellent as a foam composition.

4. Determination of collagen fibrosis and permeability of cyst curable foam

(1) Confirmation of collagen fibrosis

A mixture of 2.2 mg / ml collagen prepared with different concentrations of rose bengal was prepared (a of FIG. 5a). The prepared mixture was injected with a laser of wavelength 532 mn for 1 minute under dark conditions (b of FIG. 5a). To confirm the collagen fibrosis level, the mixture was kept at 37 ° C. constant temperature and absorbance at wavelength 315 nm was measured (c in FIG. 5A). The results are shown in FIGS. 5B and 5C.

As shown in FIGS. 5B and 5C, as the concentration of rose bengal increased with time, collagen fibrosis level increased. Therefore, it was confirmed that collagen fibrosis increased as the concentration of Rose Bengal increased.

(2) glycerol and rose Bengal  Permeability Measurement of Cyst Curable Foams Contained

When the actual foam was administered to the tissue, it was determined how the rose bengal contained in the foam could penetrate the surrounding tissue, that is, collagen.

Specifically, as described in Example 1.2, containing 0.1% (v / v) glycerol to 10% (v / v) glycerol and 0.1% (v / v) to 1.0% (v / v) rose bengal. A 3% (v / v) polydocanol foam formulation was prepared.

Collagen was added to the 96-well plate and the collagen was incubated at about 37 ° C. for about 30 minutes to gel. The prepared foam formulation was placed on the gelled collagen on the collagen layer containing rose bengal. It was left at room temperature for about 1 minute to about 30 minutes. Then, the absorbance at wavelength 548 nm was measured and the height of the rose bengal layer was measured.

The height of the stained collagen layer according to the concentration of rose bengal in the polydocanol foam is shown in Figure 6b. As shown in FIG. 6B, the cyst curable foams containing glycerol and rose bengal spread over time to increase the height of the dyed collagen layer. When the polydocanol foam was treated to the cyst membrane for about 10 minutes, it was confirmed that the cyst membrane could be adsorbed to each other by causing collagen fibrosis of the cyst membrane.

Thus, for in vivo application, the stock solution of the cyst can be removed with minimal incision and the prepared curable foam can be injected into the cyst. The injected foam hardens the cyst's film and can be left until the foam's photosensitizer sufficiently stains the cyst's film. Thereafter, the foam can be removed and irradiated with a laser or the like to adsorb the coating of the cyst through photochemical tissue crosslinking, thereby removing the cyst.

Claims (15)

As a pharmaceutical composition for preventing or treating cystic disease, including a sclerosant agent, an osmotic agent, and a photosensitizer,
The osmotic agent is selected from the group consisting of glycerol, sodium chloride solution, and dextrose-containing sodium chloride,
The concentration of the osmotic agent in the pharmaceutical composition is greater than 5% (v / v) to 15% (v / v). The pharmaceutical composition of claim 1, which is in the form of a foam. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition comprises a medical gas. The method of claim 1, wherein the curing agent polydocanol (polidocanol), sodium tetradecyl sulphate (sodium tetradecyl sulphate), sodium morrhuate, ethanolamine oleate (minoolamine oleate), minocycline hydrochloride (Minocycline hydrochloride), N-butyl cyanoacrylate (N-butyl cyanoacrylate), and iodide oil (Iodized oil) is a pharmaceutical composition selected from the group consisting of. delete The method of claim 1, wherein the photosensitive agent is rose bengal, fluorescein, eosin blue, methylene blue, erythrosin blue, riboflavin, porphyrin (porphyrin), phthalocyanine, and tetrapyrrole (tetrapyrrole). The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is for injection. The method according to claim 1, wherein the cystic disease is polycystic kidney disease (Polycystic kidney disease), polycystic ovary syndrome (PCOS), Medullary cystic kidney disease (Medullary cystic kidney disease), cysts of the jaw, periodontal cyst, periodontal cyst, Dental cysts, periodontal gait cysts, Nasopalatine duct cyst, polycystic liver disease, congenital liver fibrosis, degenerative hepatitis, Biliary hamartomas, Caroli disease, Choledochal cyst cysts), bile duct hamartoma, cystic hygroma, breast cyst, cutaneous cyst, and cystic bronchiectasis. A pharmaceutical composition of claim 1 comprising a curing agent, an osmotic agent, and a photosensitizer,
The osmotic agent is selected from the group consisting of glycerol, sodium chloride solution, and dextrose-containing sodium chloride,
The pharmaceutical composition wherein the concentration of the osmotic agent in the pharmaceutical composition is greater than 5% (v / v) to 15% (v / v); And
A kit for preventing or treating cystic disease, including a syringe. The kit of claim 9, wherein the kit further comprises a one-way valve, a two-switch, a three-way tap, or a combination thereof. Preparing a pharmaceutical composition of claim 1 in foam form; And
Administering the pharmaceutical composition in foam form to the interior of a cyst of a mammal, except for humans, to contact the membrane of the cyst with the pharmaceutical composition in foam form,
A method for preventing or treating cystic disease in mammals other than humans. The method of claim 11, wherein the method further comprises irradiating light to the cyst containing the pharmaceutical composition therein. The method of claim 12, wherein the light is a laser, an infrared wave, a two photon laser, or a combination thereof. Preparing a foam formulation by adding a test substance to the pharmaceutical composition of claim 1;
Placing the foam formulation in an upper chamber of the transwell chamber and placing cyst or cystic cells in the lower surface of the insert of the transwell, or
Placing the foam formulation in a lower chamber of the transwell chamber and placing a cyst or cystic cell in an upper chamber of the transwell chamber to contact the cystic cell with the pharmaceutical composition; And
Screening for a test substance effective to remove the cyst, by measuring the removal of the cyst, the survival rate of the cystic cells, the Lactate dehydrogenase (LDH) activity, or a combination thereof.
A method of screening candidate substances for preventing or treating cystic disease. The method of claim 14, wherein the method further comprises irradiating the cyst or cystic cells with the foam formulation.

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