KR102656260B1 - Ophthalmic composition comprising moxifloxacin - Google Patents
Ophthalmic composition comprising moxifloxacin Download PDFInfo
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- 239000000203 mixture Substances 0.000 title claims abstract description 109
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 title claims abstract description 26
- 229960003702 moxifloxacin Drugs 0.000 title claims abstract description 21
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 19
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 19
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 17
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 17
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000007951 isotonicity adjuster Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims 1
- 239000003889 eye drop Substances 0.000 abstract description 16
- 230000003111 delayed effect Effects 0.000 abstract description 11
- 229940012356 eye drops Drugs 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 238000011156 evaluation Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 7
- 230000035807 sensation Effects 0.000 description 7
- 229960005112 moxifloxacin hydrochloride Drugs 0.000 description 6
- IDIIJJHBXUESQI-DFIJPDEKSA-N moxifloxacin hydrochloride Chemical compound Cl.COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 IDIIJJHBXUESQI-DFIJPDEKSA-N 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 201000007032 bacterial conjunctivitis Diseases 0.000 description 4
- 201000007717 corneal ulcer Diseases 0.000 description 4
- 206010023332 keratitis Diseases 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229940034215 vigamox Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000006172 buffering agent Substances 0.000 description 3
- 201000003265 lymphadenitis Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 229940054534 ophthalmic solution Drugs 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010042928 Syringomyelia Diseases 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 230000001934 delay Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000000887 hydrating effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- -1 pH adjusters Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004397 blinking Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000007287 cheilitis Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000478 corneal permeability Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 1
- 229960004224 tyloxapol Drugs 0.000 description 1
- 229920001664 tyloxapol Polymers 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 목시플록사신 또는 이의 염, 히드록시에틸 셀룰로오스 및 폴리비닐알코올을 포함하는 우수한 점안감을 제공하면서도 우수한 지속력과 지연 방출 효과를 나타내는, 안정성 및 치료 효과가 우수한 안과용 조성물에 관한 것이다.The present invention relates to an ophthalmic composition containing moxifloxacin or a salt thereof, hydroxyethyl cellulose, and polyvinyl alcohol, which provides excellent eye drops and exhibits excellent durability and delayed release effect, and has excellent stability and therapeutic effect.
Description
본 발명은 목시플록사신 또는 이의 염을 포함하는 안과용 조성물에 관한 것이다.The present invention relates to an ophthalmic composition containing moxifloxacin or a salt thereof.
목시플록사신(moxifloxacin)은 플루오르퀴놀론계 항균제의 한 종류로서, 그람 양성균 및 그람 음성균 모두에 효과가 있는 광역 항생 물질이고, 세균의 DNA를 분리하는데 필요한 토포이소머라아제 등을 막아 세포 복제를 저해한다. 목시플록사신은 세균성 결막염, 검판선염, 각막염(각막궤양포함) 등의 치료와, 안과 수술 전/후의 무균화 요법 등에 널리 이용되고 있다. 염증의 치료를 위해서는 일반적으로 적어도 1일 3회로 처방되고, 안과 수술을 위해서는 1일 5회까지 점안하는 것으로 처방되고 있다.Moxifloxacin is a type of fluoroquinolone antibacterial agent. It is a broad-spectrum antibiotic that is effective against both gram-positive and gram-negative bacteria. It inhibits cell replication by blocking topoisomerase, which is necessary to isolate bacterial DNA. . Moxifloxacin is widely used in the treatment of bacterial conjunctivitis, adenitis syrinx, keratitis (including corneal ulcers), and aseptic therapy before and after ophthalmic surgery. For the treatment of inflammation, it is generally prescribed at least three times a day, and for ophthalmic surgery, it is prescribed to be instilled up to five times a day.
점안제는 눈물 또는 깜빡임으로 인해 투여 약물의 손실이 많으나 1회당 투여할 수 있는 부피가 제한적이고, 약물의 각막 투과성을 향상시키는 데에도 한계가 있다. 이러한 이유로, 치료에 유효한 양으로서 약물이 투여되기 위해서 점안제의 다수 회 점안이 필수적이다.Eye drops cause a lot of loss of administered drug due to tears or blinking, but the volume that can be administered per time is limited, and there is also a limit to improving the corneal permeability of the drug. For this reason, multiple application of eye drops is essential to administer the drug in a therapeutically effective amount.
점안제의 생체 이용률을 향상시키는 보편적인 일 방법으로서, 약물의 지연 방출을 위해 점도를 증가시키는 것을 고려할 수 있다. 다만, 점도가 매우 높은 겔제는 액상 제제에 비해 눈에 투여하기 어려운 단점이 있고, 투여 시 작열감, 이물감 등의 나쁜 점안감 때문에 복약 순응도를 낮추게 된다.As a common way to improve the bioavailability of eye drops, increasing the viscosity for delayed release of the drug can be considered. However, gel formulations with very high viscosity have the disadvantage of being difficult to administer to the eyes compared to liquid formulations, and poor eye sensations such as burning and foreign body sensation upon administration reduce medication compliance.
이에, 보관 시 성상, 물리/화학적 성질, 유효성분의 함량 등을 유지하는 안정성을 갖고, 우수한 점안감을 유지하면서도 목시플록사신을 지연 방출시키는 새로운 점안제의 개발이 필요하다.Accordingly, there is a need to develop a new eye drop that has stability that maintains the properties, physical/chemical properties, and active ingredient content during storage, and that delays the release of moxifloxacin while maintaining an excellent eye feel.
본 발명은 점도와 같은 물리/화학적 성질, 성상, 유효성분의 함량 등이 보관 시에 안정적으로 유지되고, 우수한 점안감을 제공하면서도, 약물을 지연 방출시키는, 목시플록사신 또는 이의 염을 포함하는 안과용 조성물을 제공한다.The present invention is an ophthalmic treatment containing moxifloxacin or a salt thereof, which maintains stable physical/chemical properties such as viscosity, properties, content of active ingredients, etc. during storage, provides excellent eye drops, and delays drug release. Provides a composition for
본 발명에 따른 안과용 조성물은 목시플록사신 또는 이의 염; 히드록시에틸 셀룰로오스(hydroxyethyl cellulose, HEC); 및 폴리비닐알코올(polyvinyl alcohol, PVA)을 포함한다.The ophthalmic composition according to the present invention includes moxifloxacin or a salt thereof; hydroxyethyl cellulose (HEC); and polyvinyl alcohol (PVA).
본 발명의 실시예들에 있어서, '목시플록사신'은 하기 화학식 1로 표시되는 화합물을 의미한다.In the embodiments of the present invention, 'moxifloxacin' refers to a compound represented by the following formula (1).
<화학식 1><Formula 1>
본 발명의 실시예들에 있어서, 목시플록사신 염은 목시플록사신 염산염을 포함할 수 있다.In embodiments of the invention, the moxifloxacin salt may include moxifloxacin hydrochloride.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 목시플록사신 또는 이의 염을 안과용 조성물 전체 부피에 대하여 0.01 w/v% 이상, 0.1 w/v% 이상, 0.2 w/v% 이상, 0.3 w/v% 이상, 0.4 w/v% 이상 또는 0.5 w/v% 이상으로 포함할 수 있고, 5 w/v% 이하, 3 w/v% 이하, 1.5 w/v% 이하, 1 w/v% 이하, 0.9 w/v% 이하, 0.8 w/v% 이하, 0.7 w/v% 이하 또는 0.6 w/v% 이하로 포함할 수 있다. In embodiments of the present invention, the ophthalmic composition contains moxifloxacin or a salt thereof in an amount of 0.01 w/v% or more, 0.1 w/v% or more, 0.2 w/v% or more, or 0.3 w/v% or more, based on the total volume of the ophthalmic composition. It may contain more than w/v%, more than 0.4 w/v%, or more than 0.5 w/v%, less than 5 w/v%, less than 3 w/v%, less than 1.5 w/v%, 1 w/v % or less, 0.9 w/v% or less, 0.8 w/v% or less, 0.7 w/v% or less, or 0.6 w/v% or less.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 목시플록사신 또는 이의 염을 안과용 조성물 전체 부피에 대하여 0.01 내지 5 w/v%, 0.1 내지 3 w/v%, 0.1 내지 1.5 w/v%, 0.1 내지 1 w/v% 또는 0.3 내지 1 w/v%로 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains moxifloxacin or a salt thereof in an amount of 0.01 to 5 w/v%, 0.1 to 3 w/v%, 0.1 to 1.5 w/v based on the total volume of the ophthalmic composition. %, 0.1 to 1 w/v%, or 0.3 to 1 w/v%.
본 발명의 실시예들에 있어서, 본 발명의 안과용 조성물은 목시플록사신을 유리 염기로서 약 0.5 w/v%에 상당하는 양으로 포함할 수 있다. 예를 들어, 상기 안과용 조성물 중에 목시플록사신 염산염의 양은 0.5 내지 0.6 w/v%이고, 구체적으로는 0.545 w/v%일 수 있으며, 이는 0.5 w/v% 목시플록사신에 해당한다.In embodiments of the present invention, the ophthalmic composition of the present invention may contain moxifloxacin as a free base in an amount equivalent to about 0.5 w/v%. For example, the amount of moxifloxacin hydrochloride in the ophthalmic composition may be 0.5 to 0.6 w/v%, specifically 0.545 w/v%, which corresponds to 0.5 w/v% moxifloxacin.
본 발명의 실시예들에 있어서, 상기 안과용 조성물에 포함되는 HEC 및 PVA는 안과용 조성물의 점도를 제어하고 점도 안정성을 향상시키는 동시에 약물을 지연 방출시킬 수 있다.In embodiments of the present invention, HEC and PVA included in the ophthalmic composition can control the viscosity of the ophthalmic composition, improve viscosity stability, and delay the release of the drug.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 HEC를 안과용 조성물 전체 부피에 대하여 0.1 w/v% 이상, 0.2 w/v% 이상, 0.3 w/v% 이상, 0.4 w/v% 이상, 0.5 w/v% 이상으로 포함할 수 있고, 5 w/v% 이하, 3 w/v% 이하, 1 w/v% 이하, 0.9 w/v% 이하, 0.8 w/v% 이하, 0.7 w/v% 이하, 0.6 w/v% 이하로 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains HEC in an amount of 0.1 w/v% or more, 0.2 w/v% or more, 0.3 w/v% or more, or 0.4 w/v% or more based on the total volume of the ophthalmic composition. , may contain more than 0.5 w/v%, less than 5 w/v%, less than 3 w/v%, less than 1 w/v%, less than 0.9 w/v%, less than 0.8 w/v%, 0.7 w It can be included in amounts below /v% and below 0.6 w/v%.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 HEC를 안과용 조성물 전체 부피에 대하여 0.1 내지 5 w/v%, 0.1 내지 1 w/v%, 0.1 내지 0.8 w/v%, 0.2 내지 0.8 w/v%, 0.3 내지 0.8 w/v%, 0.1 내지 0.6 w/v%, 0.2 내지 0.6 w/v%, 0.3 내지 0.6 w/v%로 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains HEC in an amount of 0.1 to 5 w/v%, 0.1 to 1 w/v%, 0.1 to 0.8 w/v%, 0.2 to 0.8 w/v%, based on the total volume of the ophthalmic composition. It may include w/v%, 0.3 to 0.8 w/v%, 0.1 to 0.6 w/v%, 0.2 to 0.6 w/v%, and 0.3 to 0.6 w/v%.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 PVA를 안과용 조성물 전체 부피에 대하여 0.1 w/v% 이상, 0.2 w/v% 이상, 0.3 w/v% 이상, 0.4 w/v% 이상, 0.5 w/v% 이상으로 포함할 수 있고, 5 w/v% 이하, 3 w/v% 이하, 1 w/v% 이하, 0.9 w/v% 이하, 0.8 w/v% 이하, 0.7 w/v% 이하, 0.6 w/v% 이하로 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains PVA in an amount of 0.1 w/v% or more, 0.2 w/v% or more, 0.3 w/v% or more, or 0.4 w/v% or more based on the total volume of the ophthalmic composition. , may contain more than 0.5 w/v%, less than 5 w/v%, less than 3 w/v%, less than 1 w/v%, less than 0.9 w/v%, less than 0.8 w/v%, 0.7 w It can be included in amounts below /v% and below 0.6 w/v%.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 PVA를 안과용 조성물 전체 부피에 대하여 0.1 내지 5 w/v%, 0.1 내지 1 w/v%, 0.1 내지 0.8 w/v%, 0.2 내지 0.8 w/v%로 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains PVA in an amount of 0.1 to 5 w/v%, 0.1 to 1 w/v%, 0.1 to 0.8 w/v%, 0.2 to 0.8 w/v%, based on the total volume of the ophthalmic composition. Can be included as w/v%.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 0.2 내지 0.8 w/v%의 HEC 및 0.2 내지 0.8 w/v%의 PVA를 포함할 수 있고, 0.3 내지 0.6 w/v%의 HEC 및 0.2 내지 0.8 w/v%의 PVA를 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition may include 0.2 to 0.8 w/v% of HEC and 0.2 to 0.8 w/v% of PVA, and 0.3 to 0.6 w/v% of HEC and 0.2% of PVA. It may contain from 0.8 w/v% of PVA.
본 발명의 실시예들에 있어서, 상기 안과용 조성물의 점도는 500 cps 이하, 구체적으로는 250 cps 이하일 수 있다. 본 발명에서의 점도는, 회전점도계(예, Brookfield)를 이용하여 스핀들 62(spindle 62), 약 20℃ 조건에서 Torque 값이 최대한 100%가 되는 속도에서 측정된 점도를 의미한다. 본 발명의 조성물의 점도는 단일원통형 회전점도계 및 스핀들 62을 이용하여 측정 시 500 cps 이하, 400 cps 이하, 300 cps 이하, 250 cps 이하, 240 cps 이하, 230 cps 이하, 220 cps 이하, 210 cps 이하일 수 있으며, 30 cps 이상, 40 cps 이상, 50 cps 이상, 100 cps 이상, 140 cps 이상, 150 cps 이상, 170 cps 이상, 180 cps 이상일 수 있다. 본 발명의 조성물 점도는 단일원통형 회전점도계 및 스핀들 62을 이용하여 측정 시 30 내지 500 cps, 50 내지 500 cps, 50 내지 300 cps, 50 내지 250 cps, 50 내지 240 cps, 50 내지 230 cps, 50 내지 220 cps, 50 내지 210 cps 일 수 있다. 본 발명의 조성물 점도는 단일원통형 회전점도계 및 스핀들 62을 이용하여 측정 시 바람직하게는 250 cps 이하, 240 cps 이하, 230 cps 이하, 220 cps 이하, 210 cps 이하일 수 있으며, 50 내지 250 cps, 50 내지 240 cps, 50 내지 230 cps, 50 내지 220 cps, 50 내지 210 cps 일 수 있다.In embodiments of the present invention, the viscosity of the ophthalmic composition may be 500 cps or less, specifically 250 cps or less. Viscosity in the present invention refers to the viscosity measured using a rotational viscometer (e.g. Brookfield) at spindle 62, at a speed at which the torque value reaches 100% at maximum under conditions of about 20°C. The viscosity of the composition of the present invention is 500 cps or less, 400 cps or less, 300 cps or less, 250 cps or less, 240 cps or less, 230 cps or less, 220 cps or less, and 210 cps or less when measured using a single cylindrical rotational viscometer and spindle 62. It can be 30 cps or higher, 40 cps or higher, 50 cps or higher, 100 cps or higher, 140 cps or higher, 150 cps or higher, 170 cps or higher, and 180 cps or higher. The viscosity of the composition of the present invention is 30 to 500 cps, 50 to 500 cps, 50 to 300 cps, 50 to 250 cps, 50 to 240 cps, 50 to 230 cps, 50 to 50 cps when measured using a single cylindrical rotational viscometer and spindle 62. It may be 220 cps, 50 to 210 cps. The viscosity of the composition of the present invention, when measured using a single cylindrical rotational viscometer and spindle 62, is preferably 250 cps or less, 240 cps or less, 230 cps or less, 220 cps or less, 210 cps or less, and 50 to 250 cps, 50 to 50 cps. It may be 240 cps, 50 to 230 cps, 50 to 220 cps, or 50 to 210 cps.
본 발명의 안과용 조성물에 따르면, HEC 및 PVA를 포함함으로써 안과용 조성물의 점도, 물리/화학적 성질, 유효성분의 함량 등이 보관 시에 안정적으로 유지되고, 우수한 점안감을 제공하면서 목시플록사신 또는 이의 염을 지연 방출시킬 수 있다.According to the ophthalmic composition of the present invention, by including HEC and PVA, the viscosity, physical/chemical properties, content of active ingredients, etc. of the ophthalmic composition are maintained stably during storage, and while providing excellent eye drop sensation, moxifloxacin or Its salts can be released with a delay.
본 발명의 조성물의 삼투압은 250 mOsmol/kg 내지 350 mOsmol/kg일 수 있으며, 구체적으로 270 mOsmol/kg 내지 330 mOsmol/kg일 수 있으나, 이에 제한되는 것은 아니다. 삼투압이 상기 범위 이내인 경우 안구 자극 및 통증 발생을 방지할 수 있다.The osmotic pressure of the composition of the present invention may be 250 mOsmol/kg to 350 mOsmol/kg, specifically 270 mOsmol/kg to 330 mOsmol/kg, but is not limited thereto. If the osmotic pressure is within the above range, eye irritation and pain can be prevented.
본 발명의 실시예들에 있어서, 상기 안과용 조성물의 pH는 6 이상, 6.4 이상일 수 있고, 8.5 이하, 8 이하, 7.6 이하일 수 있다. 예를 들어, 상기 안과용 조성물의 pH는 6 내지 8.5, 6.4 내지 8, 또는 6.4 내지 7.6일 수 있다.In embodiments of the present invention, the pH of the ophthalmic composition may be 6 or higher, 6.4 or higher, and 8.5 or lower, 8 or lower, or 7.6 or lower. For example, the pH of the ophthalmic composition may be 6 to 8.5, 6.4 to 8, or 6.4 to 7.6.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 완충제, pH 조절제, 용해보조제 및 등장화제 등의 첨가제 중 선택된 1 이상의 첨가제를 더 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition may further include one or more additives selected from the group consisting of buffering agents, pH adjusters, solubilizers, and tonicity agents.
본 발명의 실시예들에 있어서, 완충제는 아세트산, 인산, 붕산 및/또는 이들의 염 등을 사용할 수 있으며, 이에 제한되는 것은 아니다. 완충제는 적절한 pH의 유지를 위해 적절한 양으로 첨가될 수 있다.In embodiments of the present invention, the buffering agent may be acetic acid, phosphoric acid, boric acid, and/or salts thereof, but is not limited thereto. Buffering agents may be added in appropriate amounts to maintain appropriate pH.
본 발명의 실시예들에 있어서, pH 조절제는 염산, 수산화나트륨 등을 사용할 수 있다. pH 조절제는 적절한 범위의 pH를 얻기 위하여 필요한 양으로 사용될 수 있다.In embodiments of the present invention, the pH adjuster may be hydrochloric acid, sodium hydroxide, or the like. The pH adjuster may be used in the amount necessary to obtain a pH in an appropriate range.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 용해보조제로서 폴리소르베이트, 옥시놀, 티록사폴 등의 알킬 아릴 폴리에테르 알콜, 폴록사머, 폴리에톡실화 피마자유, 폴리에톡실화 수소화 피마자유 등을 포함할 수 있다.In embodiments of the present invention, the ophthalmic composition contains alkyl aryl polyether alcohols such as polysorbate, oxynol, and tyroxapol, poloxamer, polyethoxylated castor oil, and polyethoxylated hydrogenated castor as a solubilizing agent. May include freedom, etc.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 등장화제로서 염화나트륨, 당알콜 등을 사용할 수 있으나 이에 제한되는 것은 아니다.In embodiments of the present invention, the ophthalmic composition may use sodium chloride, sugar alcohol, etc. as an isotonic agent, but is not limited thereto.
본 발명의 안과 조성물은 투명한 성상을 갖는 액상의 점안용 조성물일 수 있다. 본 발명의 실시예들에 있어서 본 발명의 안과 조성물은 수성 매질로 물을 포함할 수 있고, 구체적으로는 안과용 제제의 제조에 적합한 멸균 정제수, 주사용수 등일 수 있다.The ophthalmic composition of the present invention may be a liquid ophthalmic composition with transparent properties. In embodiments of the present invention, the ophthalmic composition of the present invention may contain water as an aqueous medium, and specifically may be sterilized purified water, water for injection, etc. suitable for the production of ophthalmic preparations.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 20℃ 내지 55℃의 온도에서 보관 시 점도가 크게 변하지 않고 안정적으로 유지될 수 있다.In embodiments of the present invention, the ophthalmic composition can be stably maintained without significant change in viscosity when stored at a temperature of 20°C to 55°C.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 세균성 결막염, 검판선염, 각막염(각막궤양포함) 등의 치료와, 안과수술 전/후의 무균화 요법에 유용하게 사용될 수 있다.In embodiments of the present invention, the ophthalmic composition can be usefully used in the treatment of bacterial conjunctivitis, adenitis syrinx, keratitis (including corneal ulcers), and sterilization therapy before and after ophthalmic surgery.
본 발명의 실시예들에 있어서, 상기 안과용 조성물은 1일 1회 내지 3회 투여될 수 있다. 예를 들면, 상기 안과용 조성물은 1일 1회, 2회 또는 3회 투여될 수 있다. 예를 들면, 상기 안과용 조성물은 1일 2회 투여될 수 있다.In embodiments of the present invention, the ophthalmic composition may be administered once to three times per day. For example, the ophthalmic composition may be administered once, twice or three times per day. For example, the ophthalmic composition can be administered twice a day.
본 발명의 안과용 조성물은 우수한 점안감을 제공하면서 우수한 지속력과 지연 방출 효과를 나타낼 수 있다. 이에 따라, 세균성 결막염, 검판선염, 각막염(각막궤양포함) 등의 치료와, 안과수술 전/후의 무균화 요법을 위해서 본 발명에 따른 안과용 조성물의 투여 횟수를 감소시킬 수 있다.The ophthalmic composition of the present invention can exhibit excellent durability and delayed release effect while providing excellent eye relief. Accordingly, the number of administrations of the ophthalmic composition according to the present invention can be reduced for the treatment of bacterial conjunctivitis, adenitis sebum, keratitis (including corneal ulcers), and sterilization therapy before and after ophthalmic surgery.
또한, 상기 안과용 조성물은 유효성분의 함량, pH, 점도 등 물리화학적 특성 등이 잘 유지되어 우수한 안정성을 갖는다. 따라서 본 발명의 안과용 조성물은 장기간 동안 안정한 상태를 유지할 수 있어, 안전하게 안구에 투여될 수 있고, 부작용 없이 우수한 치료 효과를 나타낼 수 있다.In addition, the ophthalmic composition has excellent stability as the physicochemical properties such as content of active ingredients, pH, and viscosity are well maintained. Therefore, the ophthalmic composition of the present invention can maintain a stable state for a long period of time, can be safely administered to the eye, and can exhibit excellent therapeutic effects without side effects.
즉, 본 발명의 안과용 조성물은 우수한 지연 방출 효과를 가짐으로써 1일 1회 내지 3회, 구체적으로 1일 2회 투여만으로 우수한 치료 효과를 제공할 수 있을 뿐만 아니라, 점도 등과 같은 조성물의 물리적 특성이 장기간 유지될 수 있어 우수한 점안감 및 안정성을 가지는 안과용 조성물을 제공할 수 있다.That is, the ophthalmic composition of the present invention has an excellent delayed-release effect, so that it can provide an excellent therapeutic effect only by administration once to three times a day, specifically twice a day, as well as physical properties of the composition such as viscosity, etc. Since this can be maintained for a long period of time, it is possible to provide an ophthalmic composition with excellent eye relief and stability.
본 발명의 안과용 조성물은 점안제일 수 있다.The ophthalmic composition of the present invention may be an eye drop.
본 발명에 따른 안과용 조성물의 제조 방법은, 목시플록사신 또는 이의 염, HEC 및 PVA를 포함하는 혼합 용액을 준비하는 단계를 포함한다.The method for producing an ophthalmic composition according to the present invention includes preparing a mixed solution containing moxifloxacin or a salt thereof, HEC, and PVA.
본 발명의 실시예들에 있어서, 상기 혼합 용액을 준비하는 단계는, 목시플록사신 또는 이의 염, HEC 및 PVA을 물에 혼합함으로써 수행될 수 있다.In embodiments of the present invention, the step of preparing the mixed solution may be performed by mixing moxifloxacin or its salt, HEC, and PVA in water.
본 발명의 실시예들에 있어서, 상기 혼합 용액은 멸균 공정이 수행된 용액일 수 있다.In embodiments of the present invention, the mixed solution may be a solution in which a sterilization process has been performed.
본 발명의 실시예들에 있어서, 상기 혼합 용액을 준비하는 단계는, HEC 및 PVA을 물에 수화시켜 제1 용액을 제조하는 단계, 목시플록사신 또는 이의 염을 물에 용해시켜 제2 용액을 제조하는 단계 및 제1 및 제2 용액을 혼합하여 혼합 용액을 제조하는 단계를 포함할 수 있다.In embodiments of the present invention, the step of preparing the mixed solution includes preparing a first solution by hydrating HEC and PVA in water, and preparing a second solution by dissolving moxifloxacin or a salt thereof in water. It may include preparing a mixed solution by mixing the first and second solutions.
본 발명의 실시예들에 있어서, 상기 혼합 용액을 준비하는 단계에서의 제1 용액, 제2 용액 및 혼합 용액은, 각각 독립적으로 완충제, pH 조절제, 용해보조제, 등장화제 등의 첨가제를 더 포함할 수 있다.In embodiments of the present invention, the first solution, the second solution, and the mixed solution in the step of preparing the mixed solution may each independently further include additives such as a buffer, a pH adjuster, a solubilizing agent, and an isotonic agent. You can.
본 발명에 따른 안과용 조성물의 제조 방법에서, 목시플록사신 또는 이의 염, HEC 및 PVA, 그리고 추가되는 첨가제들 및 추가 유효 성분은 앞서 설명한 바와 실질적으로 동일하므로, 중복되는 상세한 설명은 생략한다.In the method for producing an ophthalmic composition according to the present invention, moxifloxacin or its salt, HEC and PVA, and added additives and additional active ingredients are substantially the same as described above, and thus detailed overlapping descriptions are omitted.
본 발명의 안과용 조성물은 우수한 점안감을 제공하면서 우수한 지속력과 지연 방출 효과를 나타낼 수 있다. 이에 따라, 세균성 결막염, 검판선염, 각막염(각막궤양포함) 등의 치료와, 안과수술 전/후의 무균화 요법을 위해서 본 발명에 따른 안과용 조성물의 투여 횟수를 감소시킬 수 있다.The ophthalmic composition of the present invention can exhibit excellent durability and delayed release effect while providing excellent eye relief. Accordingly, the number of administrations of the ophthalmic composition according to the present invention can be reduced for the treatment of bacterial conjunctivitis, cheilitis, keratitis (including corneal ulcers), and sterilization therapy before and after ophthalmic surgery.
또한, 본 발명의 안과용 조성물은 유효성분의 함량, pH, 점도 등 물리화학적 특성 등이 잘 유지되어 우수한 안정성을 가지며, 적정 범위의 점도를 유지한다. 따라서 본 발명의 안과용 조성물은 장기간 동안 안정한 상태를 유지할 수 있어 안전하게 안구에 투여될 수 있고, 부작용 없이 우수한 치료 효과를 나타낼 수 있다.In addition, the ophthalmic composition of the present invention has excellent stability by maintaining the physicochemical properties such as the content of the active ingredient, pH, and viscosity, and maintains the viscosity in an appropriate range. Therefore, the ophthalmic composition of the present invention can maintain a stable state for a long period of time, can be safely administered to the eye, and can exhibit excellent therapeutic effects without side effects.
도 1은 실험예 2에 따른 지연 방출 평가 결과이다.
도 2는 실험예 4에 따른 지연 방출 평가 결과이다.
도 3은 실험예 5에 따른 점안감 평가 결과이다.Figure 1 shows the delayed release evaluation results according to Experimental Example 2.
Figure 2 shows the delayed release evaluation results according to Experimental Example 4.
Figure 3 shows the results of evaluating eye drop sensation according to Experimental Example 5.
이하, 실험예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실험예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실험예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through experimental examples. These experimental examples are only for illustrating the present invention, and it will be obvious to those skilled in the art that the scope of the present invention is not to be construed as limited by these experimental examples.
제조예 1: 안과용 조성물의 제조Preparation Example 1: Preparation of ophthalmic composition
하기 표 1에 기재된 성분 및 함량에 따라 조성물을 제조하였다. 각 성분은 안과용 조성물 전체 부피에 대해서 하기 표 1에 기재된 함량(w/v%)이 되도록 혼합하였다. 구체적으로, 고온(약 80~90℃)의 멸균 정제수에 히드록시에틸 셀룰로오스, 폴리비닐알코올 및 염화나트륨을 수화 및 용해시킨 후, 고온고압 멸균하여 용액 1을 제조하였다. 약 30℃의 멸균 정제수에 목시플록사신 염산염, 티록사폴, 붕산 및 솔비톨을 용해시킨 후 제균 여과하여 용액 2를 제조하였다. 상기 용액 1 및 용액 2를 혼합한 후 pH를 7.4로 조정하여 조성물 1을 제조하였다. 조성물 2는 폴리비닐알코올을 제외하고 조성물 1과 동일하게 제조하였다. 조성물 1 및 2의 삼투압은 약 300 mOsmol/kg였다.A composition was prepared according to the ingredients and contents listed in Table 1 below. Each component was mixed to obtain the content (w/v%) shown in Table 1 below with respect to the total volume of the ophthalmic composition. Specifically, Solution 1 was prepared by hydrating and dissolving hydroxyethyl cellulose, polyvinyl alcohol, and sodium chloride in sterilized purified water at high temperature (about 80-90°C) and then sterilizing it at high temperature and pressure. Solution 2 was prepared by dissolving moxifloxacin hydrochloride, tyloxapol, boric acid, and sorbitol in sterilized purified water at about 30°C and then filtering for sterilization. Composition 1 was prepared by mixing Solution 1 and Solution 2 and adjusting the pH to 7.4. Composition 2 was prepared in the same manner as Composition 1 except for polyvinyl alcohol. The osmotic pressure of Compositions 1 and 2 was about 300 mOsmol/kg.
[표 1][Table 1]
실험예 1. 점도 안정성 평가Experimental Example 1. Viscosity stability evaluation
상기 조성물 1 및 2를 가혹 조건(55℃, 75%)에서 4주 동안 보관하면서 조성물의 점도를 측정하였다. 점도는 회전 점도계 (Brookfield 점도계)를 이용하고, 스핀들 62(spindle 62), 20±1.0℃의 조건에서 Torque 값이 최대한 100%가 되는 속도로 측정하였다.Compositions 1 and 2 were stored under harsh conditions (55°C, 75%) for 4 weeks and the viscosity of the compositions was measured. Viscosity was measured using a rotational viscometer (Brookfield viscometer), spindle 62, and 20 ± 1.0°C at a speed where the torque value reached 100% as much as possible.
그 결과 조성물 1은 가혹 조건에서 4주 보관한 후에도 점도가 안정적으로 유지된 반면, 조성물 2의 점도는 매우 높을 뿐만 아니라 4주 보관 후 점도가 많이 감소하여 안정하지 않음을 확인하였다(표 2).As a result, it was confirmed that the viscosity of Composition 1 remained stable even after being stored for 4 weeks under harsh conditions, while the viscosity of Composition 2 was not only very high, but also significantly decreased after 4 weeks of storage, making it unstable (Table 2).
[표 2][Table 2]
실험예 2. 지연 방출 평가Experimental Example 2. Delayed release evaluation
반투과성막(Float-A-lyzer)과 용출기(SOTAX TM)를 이용하여 상기 조성물 1과 시판제품 비가목스 점안액(목시플록사신 염산염 0.545 w/v% 포함)의 시간에 따른 유효성분의 방출양상을 관찰하였다. 구체적으로 반투과성막에 조성물 1 또는 비가목스 점안액을 넣고 STF(Stimulated Tear Fluid) 용액이 들어 있는 용출기에 넣어 유효성분의 방출량을 액체 크로마토그램을 이용하여 측정하였다.The release pattern of the active ingredient over time of Composition 1 and the commercial product Bigamox ophthalmic solution (containing 0.545 w/v% of moxifloxacin hydrochloride) was measured using a semi-permeable membrane (Float-A-lyzer) and an eluent (SOTAX TM). observed. Specifically, Composition 1 or Vigamox ophthalmic solution was added to a semi-permeable membrane and placed in an eluent containing a Stimulated Tear Fluid (STF) solution, and the amount of active ingredient released was measured using a liquid chromatogram.
그 결과, 본 발명의 조성물 1이 비가목스 점안액에 비하여 유효성분의 방출이 지연되는 것을 확인하였다(도 1).As a result, it was confirmed that Composition 1 of the present invention delayed the release of the active ingredient compared to Vigamox eye drop (Figure 1).
제조예 2. 안과용 조성물의 제조Preparation Example 2. Preparation of ophthalmic composition
상기 조성물 1과 동일한 방법으로 하기 표 2에 기재된 성분 및 함량(w/v%)에 따라 조성물 3 내지 7을 제조하였다.Compositions 3 to 7 were prepared in the same manner as Composition 1, according to the ingredients and contents (w/v%) shown in Table 2 below.
[표 3][Table 3]
실험예 3. 점도 안정성 평가Experimental Example 3. Viscosity stability evaluation
상기 조성물 3 내지 7을 가혹 조건(55℃, 75%)에서 4주 동안 보관하면서 실험예 1과 동일한 방법으로 조성물의 점도를 측정하였다.The compositions 3 to 7 were stored under harsh conditions (55°C, 75%) for 4 weeks, and the viscosity of the compositions was measured in the same manner as in Experimental Example 1.
그 결과, 가혹 조건에서 4주 보관한 후에도 조성물 3 내지 7의 점도가 안정하게 유지됨을 확인하였다(표 4).As a result, it was confirmed that the viscosity of compositions 3 to 7 remained stable even after being stored for 4 weeks under harsh conditions (Table 4).
[표 4][Table 4]
실험예 4. 지연 방출 평가Experimental Example 4. Delayed release evaluation
실험예 2와 동일한 방법으로 상기 조성물 3 내지 7과 시판제품 비가목스 점안액(목시플록사신 염산염 0.545 w/v%% 포함)의 시간에 따른 유효성분의 방출양상을 관찰하고 그 결과를 도 2에 나타내었다.In the same manner as in Experimental Example 2, the release pattern of the active ingredient over time of the compositions 3 to 7 and the commercial product Bigamox ophthalmic solution (containing 0.545 w/v%% moxifloxacin hydrochloride) was observed, and the results are shown in Figure 2. It was.
그 결과, 본 발명의 조성물 3 내지 7이 시판제품 비가목스 점안액에 비하여 유효성분의 방출이 지연되는 것을 확인하였다(도 2).As a result, it was confirmed that compositions 3 to 7 of the present invention delayed the release of active ingredients compared to the commercially available Vigarmox eye drops (FIG. 2).
실험예 5. 점안감 평가Experimental Example 5. Evaluation of eye drop sensation
상기 조성물 1 내지 6의 점안감을 평가하였다. 6명의 성인을 대상으로 조성물을 양안에 각 1방울 점안하여 점안감을 평가하였다. The compositions 1 to 6 were evaluated for eye relief. The feel of the composition was evaluated by instilling 1 drop into each eye of 6 adults.
점안감은 하기 표 5의 기준에 따라 이물감 및 시야 흐림 정도를 평가하였다.The degree of foreign body sensation and blurred vision was evaluated according to the standards in Table 5 below.
[표 5][Table 5]
그 결과, 도 3과 같이, 조성물 2 대비 조성물 1 및 3 내지 6의 점안감이 현저히 더 우수함을 확인하였다.As a result, as shown in Figure 3, it was confirmed that compositions 1 and 3 to 6 had significantly better eye drop sensation compared to composition 2.
실험예 6. 안정성 평가Experimental Example 6. Stability evaluation
상기 조성물 1의 안정성 평가를 위해 가혹 조건(55℃, 75%)에서 4주 동안 보관하면서 조성물의 pH, 삼투압, 유효성분(목시플록사신)의 함량 및 유연물질의 발생량을 측정하였다.To evaluate the stability of Composition 1, the pH, osmotic pressure, content of the active ingredient (moxifloxacin), and amount of related substances generated were measured while stored for 4 weeks under harsh conditions (55°C, 75%).
[표 6][Table 6]
그 결과, 본 발명의 조성물은 가혹 조건에 장기 보관 시에도 pH 및 삼투압의 큰 변화가 없고, 유효성분의 함량이 안정적으로 유지되며, 유연물질 발생량도 적어 우수한 안정성을 가지는 바, 안과용 조성물로 사용하기에 적절한 것을 확인하였다(표 6).As a result, the composition of the present invention has no significant change in pH and osmotic pressure even when stored for a long time under harsh conditions, the content of the active ingredient is maintained stably, and the amount of related substances generated is low, so it has excellent stability and is used as an ophthalmic composition. The following was confirmed to be appropriate (Table 6).
실험예 7. 생체 이용률 평가Experimental Example 7. Bioavailability evaluation
New Zealand White Rabbit에 비가목스 점안액(목시플록사신 염산염 0.545 w/v% 포함) 또는 상기 조성물 1을 1회 점안하고, 1일 동안 안방수와 눈물에서의 약물 동태시험을 수행하였다. Vimgox eye drops (containing moxifloxacin hydrochloride 0.545 w/v%) or Composition 1 were administered once to a New Zealand White Rabbit, and a pharmacokinetic test was performed on the aqueous humor and tears for 1 day.
[표 7][Table 7]
상기 표 7에서 확인할 수 있는 바와 같이, 안방수와 눈물에서 조성물 1의 AUC는 비가목스 점안액 대비 각각 2.13배 및 2.16배 높게 나타났다(표 7). 이러한 결과를 통해 본 발명의 조성물이 비가목스 점안액에 비해 생체 이용률이 매우 우월한 것을 확인하였다.As can be seen in Table 7, the AUC of Composition 1 in aqueous humor and tears was 2.13 and 2.16 times higher than that of Vigamox eye drops, respectively (Table 7). Through these results, it was confirmed that the composition of the present invention has very superior bioavailability compared to Vigamox eye drops.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시예일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. will be. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (11)
히드록시에틸 셀룰로오스(hydroxyethyl cellulose); 및
폴리비닐알코올(polyvinyl alcohol)을 포함하는,
안과용 조성물.
Moxifloxacin or a salt thereof;
hydroxyethyl cellulose; and
Containing polyvinyl alcohol,
Ophthalmic composition.
안과용 조성물.
The method of claim 1, wherein moxifloxacin or a salt thereof is contained in an amount of 0.01 to 5 w/v% based on the total volume of the composition.
Ophthalmic composition.
안과용 조성물.
The method of claim 1, comprising 0.1 to 5 w/v% of hydroxyethyl cellulose based on the total volume of the composition.
Ophthalmic composition.
안과용 조성물.
The method of claim 1, comprising 0.2 to 0.6 w/v% of hydroxyethyl cellulose based on the total volume of the composition.
Ophthalmic composition.
안과용 조성물.
The method of claim 1, wherein polyvinyl alcohol is contained in an amount of 0.1 to 5 w/v% based on the total volume of the composition.
Ophthalmic composition.
안과용 조성물.
The method of claim 1, wherein polyvinyl alcohol is contained in an amount of 0.2 to 0.8 w/v% based on the total volume of the composition.
Ophthalmic composition.
The ophthalmic composition of claim 1, wherein the composition has a viscosity of 500 cps or less.
The ophthalmic composition of claim 1, wherein the composition has a viscosity of 250 cps or less.
The ophthalmic composition according to claim 1, wherein the pH is between 6 and 8.5.
The ophthalmic composition according to claim 1, wherein the ophthalmic composition is a transparent liquid.
안과용 조성물.The method of claim 1, wherein the ophthalmic composition contains at least one additive selected from a buffer, a pH adjuster, an isotonic agent, and a solubilizing agent.
Ophthalmic composition.
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| US20020193370A1 (en) * | 1998-09-30 | 2002-12-19 | Gerald Cagle | Antibiotic compositions for treatment of the eye, ear and nose |
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| KR20010075138A (en) | 1998-09-30 | 2001-08-09 | 제임스 에이. 아노 | Antibiotic compositions for treatment of the eye, ear and nose |
| US20020193370A1 (en) * | 1998-09-30 | 2002-12-19 | Gerald Cagle | Antibiotic compositions for treatment of the eye, ear and nose |
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