KR101791399B1 - Oral disintegrating film comprising diagnosis agent and preparation method thereof - Google Patents
Oral disintegrating film comprising diagnosis agent and preparation method thereof Download PDFInfo
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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Abstract
The present invention relates to a preparation for oral disintegration film comprising a photosensitizer and a method for producing the same, wherein the preparation of the oral disintegration film comprising the modified photosensitizer according to the present invention satisfies the required physical properties and the solubility And the photosensitizer maintains hydrophilicity and has excellent elution and absorption rate in the body, so that it can be useful as a formulation for diagnosing diseases.
Description
The present invention relates to a preparation for oral disintegration film containing a diagnostic agent and a method for preparing the same, and specifically to a preparation for oral disintegration film comprising a modified diagnostic agent, a water-soluble polymer and a solubilizing agent, and can be used as a diagnostic or therapeutic agent for cancer.
Recently, changes in eating habits and lifestyle changes have increased cancer incidence in the gastrointestinal tract. Recent advances in medical technology have greatly improved the treatment of cancer, but the most important thing is finding cancer early. Therefore, various studies have been actively carried out for early diagnosis.
Several methods have been developed to diagnose these cancers, but the most widely used and accurate method is the biopsy. However, biopsy has many difficulties in obtaining, analyzing and treating actual tumor tissue. In addition, if the location of the tumor is accurately detected through a general endoscope, it is difficult to diagnose the disease because the disease progresses and the tissue can be visually confirmed. Therefore, it is highly dependent on the doctor's experience and judgment. Positron Emission Tomography (PET) is a diagnostic method for other cancers, and image discrimination is possible in cancer progression, malignancy, metastatic site diagnosis, etc. However, Should be administered.
Many researches have been made to overcome these problems. Among them, research and development on early detection technology of cancer that can be confirmed by eyes using fluorescence signal due to the issue of optical diagnosis of cancer using molecular imaging technology .
Many kinds of fluorescence materials to be used for such diagnosis are being studied as a new diagnostic fluorescent material. Photosensitizer is a substance that generates singlet oxygen or free radicals due to chemical reaction caused by abundant oxygen and external light in the body when light is irradiated from the outside. When irradiated with a laser, an oxygen or free radical generated in the body acts to destroy the cells, and fluorescence emitted from the photodynamic agent enables the diagnosis of cancer.
Currently known photosensitizers are porphyrin derivatives, chlorin, bacteriochlorin, phthalocyanine, and 5-aminolevulinic acid derivatives. Among them, porphyrin-based photosensitizers Photofin ® and Photogem ® , which use the hematophorphyrin derivative (HpD), are currently in commercial use and are being used clinically.
In addition, retinal circulation microangiography using a known fluorescent dye such as fluorescein, fluorescamine and riboflavin is known (see U.S. Patent No. 4945239). It is also known to use cyanine compounds, including indocyanine green (hereinafter abbreviated as ICG), which are used to measure liver function and cardiac function as fluorescent contrast agents (Neurosurgery, 35, 930 (1994) SPIE, 2389, 789-797 (1995)).
However, the photosensitizer as a diagnostic reagent to date has encountered problems such as photodegradability and poor solubility in the development stage, and thus it is difficult to develop it.
Accordingly, the inventors of the present invention have been studying a formulation that can be easily administered and can be administered directly into the gastrointestinal tract while improving the poor solubility of a photosensitizer combined with a substance capable of specifically diagnosing cancer, . Oral disintegrating film preparations are easy to administer and can be taken without drinking water. In addition, it is convenient for patients who can not swallow tablets or capsules due to pediatric, elderly, dementia, dysphagia, etc., and has the advantage of directly administering a diagnostic agent into the gastrointestinal tract.
The inventors of the present invention have found that a preparation of oral disintegrating film according to the present invention can directly administer a diagnostic substance into the gastrointestinal tract while satisfying required physical properties and increasing the solubility of a photosensitizer having cancer specificity as an active ingredient in water, .
It is an object of the present invention to provide an oral disintegrating film preparation comprising a modified photosensitizer, a water-soluble polymer and a solubilizing agent.
Another object of the present invention is to provide a method for producing the oral disintegrating film preparation.
In order to achieve the above object,
The present invention relates to a modified photosensitizer, which is characterized in that [photosensitizer] - [biocompatible polymer] - [linker] - [target specific ligand]
Water soluble polymers; And
Solubilizing agents;
And an oral disintegrating film.
The present invention also provides a modified photosensitizer which is characterized in that the solubilizing agent and the [photosensitizer] - [biocompatible polymer] - [linker] - [target specific ligand] (Step 1);
Adding a water-soluble polymer to the mixed solution obtained in step 1 (step 2); And
(3) applying the mixture obtained in the step 2 on a hydrophobic film and then drying the mixture.
The oral disintegrating film formulation containing the modified photosensitizer according to the present invention satisfies the required physical properties, has excellent solubility of the photosensitizer, maintains the hydrophilic property of the photosensitizer, and has excellent elution and absorption in the body. Therefore, As described herein.
Hereinafter, the present invention will be described in detail.
The present invention relates to a modified photosensitizer, which is characterized in that [photosensitizer] - [biocompatible polymer] - [linker] - [target specific ligand]
Water soluble polymers; And
Solubilizing agents;
And an oral disintegrating film.
The oral disintegrating film preparation according to the present invention may further comprise at least one pharmaceutically acceptable additive such as a plasticizer, a lubricant, a sweetener, a flavoring agent, a pigment, a preservative, and the like. As the above-mentioned pharmaceutically acceptable additives, for example, those disclosed in Korean Patent No. 10-1462018 can be used.
In the oral disintegrating film preparation according to the present invention, the modified photosensitizer acts as an active ingredient for the diagnosis or treatment of a specific disease, and is characterized in that [photosensitizer] - [biocompatible polymer] - [linker] Ligand] are sequentially chemically bonded to each other and one or more [biocompatible polymer] - [linker] - [target specific ligand] can be substituted for [photosensitizer].
In the oral disintegrating film preparation according to the present invention, the water-soluble polymer may be 500-1500 parts by weight and the solubilizing agent may be 10-200 parts by weight based on 1 part by weight of the modified photosensitizer. Preferably, the water-soluble polymer may be 600-1000 parts by weight and the solubilizing agent may be 50-150 parts by weight based on 1 part by weight of the modified photosensitizer. More preferably, the water-soluble polymer may be 700-900 parts by weight and the solubilizing agent may be 90-110 parts by weight based on 1 part by weight of the modified photosensitizer.
If the amount of the water-soluble polymer is less than 500 parts by weight based on 1 part by weight of the modified photosensitizer, the inherent hydrophobicity of the photosensitizer becomes relatively larger than the hydrophilic property of the hydrophilic water-soluble polymer, If the amount is more than 1500 parts by weight, the size or thickness of the film preparation itself becomes large, and the disintegration rate of the modified photo-sensitizer having a large molecular weight may be delayed, resulting in a problem that the film is not absorbed into the body.
When the amount of the solubilizing agent is less than 10 parts by weight based on 1 part by weight of the modified photosensitizer, it is difficult to solubilize the modified photosensitizer. Thus, uniformity is not ensured and dissolution is delayed due to insolubilization. If the amount exceeds 200 parts by weight, the disintegrating film formulation is not formed to such an extent that the tensile force can not be measured due to the agglomerated physical properties of the preparation even after the drying process.
The photosensitizer may be broadly classified into a porphyrin-based compound and a nonporphyrins compound in the form of a free base or a metal complex.
The porphyrin-based compounds include porphyrins compounds, reduced porphyrins compounds in which at least one pyrrole constituting porphyrin is reduced to pyrroline, chlorins compounds, bacteriocin Porphyrin analogues such as bacteriochlorins compounds, phthalocyanines compounds and the like can be used. In addition, a desired substance can be prepared by introducing a functional group such as a carboxylic acid into the side chain structure by various synthesis methods.
Examples of the non-porphyrin compound include hypericins dyes, rhodamines dyes, rose bengal dyes, psoralens dyes, phenothiazinium dyes, Merocyanine dyes and the like can be used.
In the present invention, the photosensitizer is preferably a tetrapyrrole derivative, more preferably a cyclopentadiene derivative, and still more preferably a phthalocyanine compound. An example of the phthalocyanine compound is the compound used in Production Example 1 of the present invention.
As a preferable example, the [photosensitizer] - [biocompatible polymer] - [linker] in the modified photosensitizer is a compound represented by the following formula (1) ] Can be used.
In Formula 1,
n is an integer of 10-200, preferably 20-60, more preferably 40-50.
Examples of the biocompatible polymer include polyethyleneglycol, dextran, chitosan, glycol chitosan, poly-L-lysine, polyaspartic acid, poly (N-2- (hydroxypropyl) methacrylamide) (Styrene-co-maleic anhydride), poly (styrene-co-maleic anhydride), and the like can be used, and polyethylene glycol is preferably used. More preferably, Of polyethylene glycol may be used, but the present invention is not limited thereto.
As the linker, there can be used maleimide, n-hydroxysuccinimide (NHS), etc. in which N is substituted with a C 1-10 linear or branched alkylcarboxylic acid, preferably N is a C 1-10 Of linear or branched alkylcarboxylic acid substituted maleimide may be used, but the present invention is not limited thereto.
The target specific ligand can be selected from peptides, DNA, RNA, RNAi, platamer, PNA, antibody, folic acid, protein and the like depending on the disease to be diagnosed or treated.
Examples of the peptides include RGD peptides binding to? V? 3 integrin, CGNSNPKSC peptides binding to gastric endothelial cells, VHSPNKK peptides targeting vascular cell adhesion molecule-1 (VCAM-1), MMPs A CTTHWGFTLC peptide targeting matrix metalloproteinase-2 (MMP-9), a SGKGPRQITAL peptide targeting matrix metalloproteinase-9 (MMP-9), a SGRSA peptide binding to uropain plasminogen activator (uPA), a urokinase-type plasminogen activator receptor targeting FSRYLWS peptide, but not limited thereto.
In the oral disintegrating film preparation according to the present invention, the water-soluble polymer serves as a matrix of the film preparation.
Examples of the water-soluble polymer include pregelatinized starch, hydroxypropylmethylcellulose (HPMC), pullulan, gelatin, pectin, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyvinylalcohol, polyacrylic acid, Carboxymethyl cellulose, carboxyvinyl polymer, polyethylene glycol, methyl cellulose, polyvinyl pyrrolidone, maltodextrin, woodlite (methacrylic acid), carrageenan, modified starch, casein, whey protein isolate (WPI) soy protein isolate, gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum, agar and the like, preferably pregelatinized starch) and hydroxypropylmethylcellulose (HPMC) may be used in combination, but the present invention is not limited thereto.
In the oral disintegrating film preparation according to the present invention, the solubilizing agent may be macrogolglycerol ricinoleate (also referred to as Polyoxyl-35 castor oil, trade name: Cremophor TM EL (Cremophor TM EL)], macrogol-glycerol-hydroxy-stearate (macrogolglycerol hydroxystearate) [polyoxyl becomes now called to as -40 castor oil (polyoxyl-40 castor oil), trade name Crescent mode pore TM RH 40 (Cremophor TM RH 40 )] , polyoxyalkylene block of ethylene and polyoxypropylene copolymer (polyoxyethylene / polyoxypropylene block co-polymer ) [ trade name: poloxamer TM F-127 (poloxamer TM F -127), poloxamer TM F-188 (poloxamer TM F -188 ), etc.], sorbitan monooleate (sorbitan monooleate) [e.g., span TM 80 (span TM 80), etc.], and polysorbates (polysorbate) [trade name: tween TM 20 (tween TM 20), tween TM 80, and the like (tween TM 80), etc.], preferably Although available crushers all pores, and not to limit it.
The oral disintegrating film preparation according to the present invention is preferably used for diagnosing or treating cancer, and the cancer may be selected from the group consisting of digestive, urinary, reproductive, respiratory, circulatory, brain and nervous system cancer. More particularly, the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer, colon cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, uterine cancer, ovarian cancer, rectal cancer, gastric cancer, colon cancer, breast cancer, fallopian tube carcinoma, endometrial carcinoma , Cancer of the uterine cervix, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small bowel cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute From the group consisting of leukemia, lymphocytic lymphoma, bladder cancer, renal or ureteral cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system (CNS) tumor, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma and pituitary adenoma But is not limited thereto.
The oral debonding film preparation according to the present invention satisfied all of the physical properties (see Experimental Example 1) and showed excellent solubility of the modified photosensitizer (see Experimental Example 2).
Accordingly, the preparation of the oral disintegrating film comprising the modified photosensitizer according to the present invention satisfies the required physical properties, has excellent solubility of the photosensitizer, maintains the hydrophilic property of the photosensitizer, May be useful as formulations for disease diagnosis.
Method
The present invention relates to a method of dissolving a modified photosensitizer, which is characterized in that a solubilizing agent and a [photosensitizer] - [biocompatible polymer] - [linker] - [target specific ligand] (Step 1);
Adding a water-soluble polymer to the mixed solution obtained in step 1 (step 2); And
(3) applying the mixture obtained in the step 2 on a hydrophobic film and then drying the mixture.
In the production method according to the present invention, the step 1 is a step in which a solubilizing agent and a [photosensitizer] - [biocompatible polymer] - [linker] - [target specific ligand] Characterized in that the modified photosensitizer is dissolved.
The aqueous solvent used in step 1 may be used alone or in combination with water, such as water, phosphate buffer, physiological saline, alcohol having 1-4 carbon atoms, acetonitrile, dimethylsulfoxide, etc., But is not limited thereto.
Here, the solubilizing agent and the modified photosensitizer are as described in detail herein.
In the production method according to the present invention, the step 2 is a step of adding a water-soluble polymer to the mixed solution obtained in the step 1.
In the step 2, one or more pharmaceutically acceptable additives such as a plasticizer, a lubricant, a sweetener, a flavoring agent, a pigment, a preservative and the like may be further added.
In the production method according to the present invention, the step 3 is a step of applying the mixture obtained in the step 2 on the hydrophobic film and then drying the mixture.
In the step 3, a degassing process may be added to remove the bubbles of the mixture obtained in the step 2. That is, step 3 may be carried out by first carrying out the deaeration process of the mixture obtained in step 2, then applying it on the hydrophobic film, and then drying it.
As the hydrophobic film, a plastic film commonly used in the field of oral disintegration film preparation, for example, a polyethylene terephthalate film (PET film) can be used, but the present invention is not limited thereto.
The drying process can be carried out until the drying loss of the finally obtained oral disintegration film preparation is 1-8% by weight, preferably 2-4% by weight.
Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.
< Manufacturing example 1> [ Phthalocyanine derivative]-[ PEG149 ] - [ Maleimide Derivative] - [peptide] conjugate (hereinafter referred to as PC-PEG-Mal-Pep conjugate)
Step 1: [ Phthalocyanine derivative]-[ PEG149 ] Conjugate (hereinafter referred to as PC-PEG conjugate)
After dissolving 77 mg of NHS (N-Hydroxysuccinimide) and 139 mg of N, N'-dicyclohexylcarbodiimide (DCC) in 50 ml of dimethylsulfoxide (DMSO) at room temperature, polyethylene glycol (PEG) (PC) was prepared by mixing 2 g of S-149 (SunBio, P2AM-6) with 262 mg of phthalocyanine derivative (PC) and reacting for 24 hours to prepare a PC-PEG conjugate.
Separation and purification of PC-PEG conjugate
Hydrophobic chromatography (sephadex LH-20) was performed to selectively isolate and purify only the 1: 2 equivalent of the conjugate of PC-PEG conjugate prepared above. First, a solution of PC-PEG conjugate dissolved in methanol at a concentration of 5 mg / ml was injected into the hydrophobic chromatography. The ratio of water to methanol was varied from 5: 5 to 1: 9, The resulting product was recovered. The recovered product was freeze-dried after removing methanol with a concentrator to obtain a PC-PEG conjugate.
Step 2: [ Phthalocyanine derivative]-[ PEG149 ] - [ Maleimide Derivative] (hereinafter referred to as PC-PEG-Mal conjugate)
Then, 10 mg of NHS and 18 mg of dicyclohexylcarbodiimide were dissolved in 10 ml of dimethylsulfoxide (DMSO) and 14 mg of maleimide (molecular weight 217.11) was added to the PC-PEG conjugate obtained in Step 1 at room temperature For 24 hours. The reaction mixture was filtered and dialyzed against distilled water for 3 days using a dialysis membrane (Spectra / Por, mol. Wt. Cutoff size, 1,000) to remove dimethyl sulfoxide and impurities. After dialysis and freeze-drying, a PC-PEG-Mal conjugate was obtained.
Step 3: Preparation of [phthalocyanine derivative] - [PEG149] - [maleimide derivative] - [peptide] conjugate (hereinafter referred to as PC-PEG-Mal-Pep conjugate)
0.1 mg of target specific peptide, N-terminal-SSSPIQGSWTWENGK (Cys) WTWKGIIRLEQC terminal, was dissolved in 0.05 mL of distilled water, 0.05 mL of TCEP (Tri-2-carboxyethyl) phosphine hydrochloride bead was added and reacted for 1 hour. The reaction was centrifuged at 1000 xg for 1 min to separate only the supernatant. The supernatant was dried under reduced pressure for 2 hours, and the obtained material was dissolved in 0.4 mL of dimethylsulfoxide. 26 mg of the PC-PEG-Mal conjugate obtained in Step 2 was added and reacted for 6 hours. The reaction product was dried under reduced pressure to obtain a PC-PEG-Mal-Pep conjugate.
The obtained PC-PEG-Mal-Pep was separated and purified by HPLC (C18 high performance liquid chromatography column and Agilent 1100 series HPLC system (Agilent, Santa Clara, CA)).
< Example 1 to 4> Oral Disintegration Preparation of Film Formulation
A 5 cm 2 oral disintegrating film preparation containing the PC-PEG-Mal-Pep conjugate prepared in Preparation Example 1 was prepared according to the ingredients and composition ratio shown in Table 1 below. The PC-PEG-Mal-Pep conjugate prepared in Preparation Example 1 was dissolved in an aqueous solution in which a solubilizing agent was dissolved, and then the other ingredients listed in Table 1 were added and mixed uniformly. The resulting mixture was stirred under vacuum for about 2 hours to remove air bubbles. The degassed mixture was applied to a PET film (Enterpack) to a constant thickness, and then dried at 70 캜 until the loss on drying reached 3%. The obtained film preparation was cut into a size of 5 cm 2 to prepare a disintegrating oral film preparation.
(Water-soluble polymer)
< Comparative Example 1 > PC-PEG- Mal -Pep < / RTI > conjugate and saline
0.025 mg of the PC-PEG-Mal-Pep conjugate prepared in Preparation Example 1 was added to 5 mL of physiological saline to prepare a composition.
< Comparative Example 2 > Preparation of oral disintegrating film formulation without solubilizing agent
A disintegrating film formulation containing no solubilizing agent was prepared in the same manner as in Example 1, according to the ingredients and contents in Table 2 below.
(Per 5 cm 2 size, mg)
≪ Experimental Example 1 > Property evaluation
Tensile strength, disintegration time, and moisture content tests were conducted to evaluate the physical properties of the preparation of the oral disintegrating film containing a photosensitizer prepared in Examples 1 to 4 of the present invention.
Specifically, when the tensile strength of the film is less than 300 g / cm 2 when the oral disintegration film is produced, the film is torn or broken at the time of cutting and packaging. Therefore, the tensile strength is measured by the tensile test and the disintegration test and the moisture content 10, and the results thereof are shown in Table 3. < tb >< TABLE >
(g / cm 2 )
(second)
(%)
As shown in Table 3, the inventive oral debonding film formulations prepared in Examples 1 to 4 exhibited excellent physical properties in terms of tensile strength, disintegration speed and moisture content.
Therefore, the oral disintegrating film preparation according to the present invention is excellent in physical properties, and thus may be useful as an oral disintegrating film preparation containing a photosensitizer as an active ingredient.
< Experimental Example 2> Evaluation of solubility
In order to evaluate the solubility of the oral disintegration film, the film prepared in Example 1 was added to 5 mL of physiological saline, and the result was compared with Comparative Example 1. Each solution was centrifuged, and the supernatant was taken and the content of photosensitizer was measured according to the following conditions to calculate the solubility. The results are shown in Table 4.
Specifically, the content of the photosensitizer dissolved in the oral disintegrating film preparation was measured using a fluorescent plate reader (Spark 10M absorbance, fluorescence, Hum / Multi-functional microplate reader, Tecan) at a peak of Excitation 570 nm / Emission 630 nm Were measured and evaluated.
As shown in Table 4, since the content of the photosensitizer is significantly higher in Example 1 than in Comparative Examples 1 and 2, the preparation of the oral disintegrating film of the present invention exhibits high solubility and is kept hydrophilic .
Therefore, the oral disintegrating film preparation according to the present invention may be useful as a preparation for oral disintegration film containing a photosensitizer as an active ingredient, since the photosensitizer is kept hydrophilic and has high solubility.
Claims (16)
Water soluble polymers; And
Polysorbate as a solubilizing agent;
Lt; / RTI >
The photosensitizer is a phthalocyanine compound,
The biocompatible polymer may be selected from the group consisting of polyethylene glycol, dextran, chitosan, glycol chitosan, poly-L-lysine, polyaspartic acid, poly (N-2- (hydroxypropyl) methacrylamide) Ether-co-maleic anhydride), and poly (styrene-co-maleic anhydride)
The linker is N-hydroxysuccinimide or N-hydroxysuccinimide in which N is a linear or branched alkylcarboxylic acid substituted with C 1-10 ,
Wherein the target specific ligand is any one selected from the group consisting of peptide, DNA, RNA, RNAi, platemaker, PNA, antibody, folic acid, and protein.
Wherein said oral disintegrating film preparation further comprises at least one pharmaceutically acceptable additive selected from the group consisting of plasticizers, lubricants, sweeteners, flavors, pigments, and preservatives.
Wherein the modified photosensitizer is capable of substituting one or more [biocompatible polymer] - [linker] - [target specific ligand] in the [photosensitizer].
Wherein the water-soluble polymer is 500-1500 parts by weight and the solubilizing agent is 10-200 parts by weight based on 1 part by weight of the modified photosensitizer.
In the modified photosensitizer, [photosensitizer] - [biocompatible polymer] - [linker] is a compound represented by the following formula (1)
Wherein the target specific ligand is bound to the maleimide group in the compound of formula (1): < EMI ID =
[Chemical Formula 1]
(In the formula 1,
n is an integer of 10-200).
These peptides include RGD peptide binding to? V? 3 integrin, CGNSNPKSC peptide binding to gastric endothelial cells, VHSPNKK peptide targeting vascular cell adhesion molecule-1 (VCAM-1), MMP-2 (SGPGQR) peptide targeting mMP-9 (matrix metalloproteinase-9), SGRSA peptide binding to uPA (urokinase plasminogen activator), and uPAR (urokinase-type plasminogen activator receptor) Wherein the peptide is any one selected from the group consisting of FSRYLWS peptide as a target.
The water-soluble polymer may be selected from the group consisting of pregelatinized starch, hydroxypropylmethylcellulose (HPMC), pullulan, gelatin, pectin, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyvinylalcohol, polyacrylic acid, carboxy The present invention also relates to a method for producing a soybean protein isolate (soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, soybean protein isolate, protein isolate, gluten, acacia gum, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum and agar. .
Adding a water-soluble polymer to the mixed solution obtained in step 1 (step 2); And
Applying the mixture obtained in the step 2 on the hydrophobic film and then drying (step 3)
The photosensitizer is a phthalocyanine compound,
The biocompatible polymer may be selected from the group consisting of polyethylene glycol, dextran, chitosan, glycol chitosan, poly-L-lysine, polyaspartic acid, poly (N-2- (hydroxypropyl) methacrylamide) Ether-co-maleic anhydride), and poly (styrene-co-maleic anhydride)
The linker is N-hydroxysuccinimide or N-hydroxysuccinimide in which N is a linear or branched alkylcarboxylic acid substituted with C 1-10 ,
Wherein the target specific ligand is any one selected from the group consisting of peptides, DNA, RNA, RNAi, platamer, PNA, antibody, folic acid, and protein. Gt;
Wherein the solvent of step 1 is at least one selected from the group consisting of water, a phosphate buffer solution, physiological saline, an alcohol having 1 to 4 carbon atoms, acetonitrile, and dimethylsulfoxide.
Wherein at least one pharmaceutically acceptable additive selected from the group consisting of plasticizers, lubricants, sweeteners, flavors, pigments, and preservatives is further added in step 2 above.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102182630B1 (en) * | 2019-12-19 | 2020-11-24 | 김진왕 | Eco-friendly smart photosensitizers and photobiomodulation of stem cell therapy agent using the same |
| WO2022203316A1 (en) * | 2021-03-22 | 2022-09-29 | 선바이오(주) | Mouth rinse composition including polyethylene glycol derivative as active ingredient for alleviating xerostomia |
| JP2023522286A (en) * | 2021-03-22 | 2023-05-30 | ソンバイオ・インコーポレイテッド | Oral rinse composition for alleviating xerostomia containing a polyethylene glycol derivative as an active ingredient |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101970214B1 (en) * | 2017-07-17 | 2019-08-27 | 이화여자대학교 산학협력단 | Organometallic compound, their self-assembly and composition for diagnosis or treatment of tumors comprising the same |
| KR102044515B1 (en) * | 2019-08-20 | 2019-11-14 | 이영환 | Sustained release type orally disintegrating film with excellant oral mucoadhesion and the manufacturing method thereof |
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| KR101493168B1 (en) * | 2013-10-11 | 2015-02-13 | 가톨릭대학교 산학협력단 | pH sensitive conjugates for photodynamic therapy having nano-pin structure and method thereof |
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| KR101183732B1 (en) | 2010-04-16 | 2012-09-17 | 가톨릭대학교 산학협력단 | Conjugate of acetylated polysccharide and photosensitizer for photodynamic diagnosis or therapy and process of preparation thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR102182630B1 (en) * | 2019-12-19 | 2020-11-24 | 김진왕 | Eco-friendly smart photosensitizers and photobiomodulation of stem cell therapy agent using the same |
| WO2021125611A1 (en) * | 2019-12-19 | 2021-06-24 | 김진왕 | Eco-friendly smart photosensitizer and photo-stem cell therapy product comprising same |
| US11654195B2 (en) | 2019-12-19 | 2023-05-23 | Jin Wang KIM | Eco-friendly smart photosensitizer and photo-stem cell therapy product comprising same |
| WO2022203316A1 (en) * | 2021-03-22 | 2022-09-29 | 선바이오(주) | Mouth rinse composition including polyethylene glycol derivative as active ingredient for alleviating xerostomia |
| JP2023522286A (en) * | 2021-03-22 | 2023-05-30 | ソンバイオ・インコーポレイテッド | Oral rinse composition for alleviating xerostomia containing a polyethylene glycol derivative as an active ingredient |
| JP7454880B2 (en) | 2021-03-22 | 2024-03-25 | ソンバイオ・インコーポレイテッド | Oral rinse composition for alleviating xerostomia containing a polyethylene glycol derivative as an active ingredient |
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