WO2018052185A1 - Forme posologique pour film oculaire comprenant de la cyclosporine - Google Patents

Forme posologique pour film oculaire comprenant de la cyclosporine Download PDF

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Publication number
WO2018052185A1
WO2018052185A1 PCT/KR2017/007426 KR2017007426W WO2018052185A1 WO 2018052185 A1 WO2018052185 A1 WO 2018052185A1 KR 2017007426 W KR2017007426 W KR 2017007426W WO 2018052185 A1 WO2018052185 A1 WO 2018052185A1
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WIPO (PCT)
Prior art keywords
dosage form
film
unit dosage
eye
cyclosporin
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PCT/KR2017/007426
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English (en)
Korean (ko)
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김상욱
김정태
이홍기
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주식회사 코아팜바이오
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Publication of WO2018052185A1 publication Critical patent/WO2018052185A1/fr

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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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on

Definitions

  • the present invention relates to a formulation for administering cyclosporin to the eye. Specifically, it relates to solid dosage forms for delivering an accurate single dose of cyclosporin to the eye. More specifically, the present invention relates to a film formulation for delivering an accurate single dose of cyclosporin to the eye, and specifically, a film in which the cyclosporin is in the form of a solid solution, which has a burning sensation such as a burning sensation when administered to the eye. To a new formulation that has been removed.
  • Dry eye syndrome (dry eye disease, dry eye disease, or dry eye syndrome) is an organic disorder that results in a lack of tear production or the tear film that protects the mucous membranes disappears faster than normal, resulting in damage to the eye's surface, resulting in foreign bodies, discomfort or stinging in the eyes. Is a syndrome that makes you feel irritation symptoms.
  • a common method of treating dry eye syndrome is to administer artificial tears (artificial tears) containing small amounts of water-soluble polymers to help retain water.
  • artificial tears artificial tears
  • the International Dry Eye Workshop held in 1995, included the scope of dry eye due to inflammatory changes on the ocular surface. Patients with inflammatory changes on the ocular surface usually have increased T-lymphocytes and high levels of inflammatory mediators such as cytokines.
  • Eye drops based on cyclosporine A include Restasis®, released by Allergan Inc., Irvine, CA, USA, which contains 0.05% cyclosporin A. Restasis® is a drug approved for use in patients in the United States in 1983 whose tears have been suppressed because of inflammation caused by keratoconjunctivitis sicca.
  • Restasis® is an eye drop in emulsion formulations that is administered to the eye twice a day, one drop every 12 hours.
  • the above product contains glycerin, castor oil, polysorbate 80, carbomer copolymer type A and purified water as preparation additives in addition to 0.05% of the main component cyclosporine, and the pH of the preparation is 6.5-8.0. The pH was adjusted with sodium hydroxide to maintain. In addition, the osmotic pressure of the formulation is maintained at 230-320 mOsmol / kg to reduce eye irritation.
  • eye drops are liquid aseptics applied to eye tissues such as conjunctival sac or solid aseptics used when dissolved or suspended when used.
  • eye drops collectively refer to formulations which are liquid or liquid when administered.
  • the ophthalmic ointment is listed in the eleventh amendment of the Korean Pharmacopoeia, which is defined as a semi-solid sterile agent applied to eye tissues such as conjunctival sac.
  • the eye drop includes both an emulsion and a suspension, which are liquid formulations, including an aqueous solution of the drug, and a semi-solid agent such as an ointment.
  • Ophthalmic ointment as an alternative formulation of eye drops has the advantage of increasing the retention in the eye, while ophthalmic ointment is blurred in the eye due to the characteristics of the ophthalmic ointment, which mainly blurs the field of vision during the administration of eye drops and also uses oily base such as petrolatum. It does not wash well, so it does not look good and affects the recovery of vision.
  • Thin film formulations are for oral administration of drugs and are used in oral mucoadhesive formulations for absorption through the gastrointestinal tract or for delivery of the drug to the systemic circulation for a long time.
  • Such film formulations are generally considered to be safe formulations because they dissolve very quickly in an aqueous environment by using soluble polymers as film formers, and the polymers themselves are not absorbed due to their large molecular weight.
  • We use thin film formulations to deliver drugs to the eye so that the dosage can be kept constant by applying a film of constant size to the eye, and if the film dissolves within seconds in the eye, it will not interfere with the field of vision and the administered formulation.
  • the present invention has been derived in consideration of the possibility that the risk of falling down can be excluded.
  • a novel formulation capable of administering cyclosporin to the eye it is an object of the present invention to provide a formulation in which an accurate single dose of cyclosporin can be delivered to the eye and the burning sensation is removed. More specifically, to provide a film formulation containing a single dose of cyclosporine, and to provide a formulation with no burning sensation by using no surfactant and preservatives.
  • the present invention discloses the following means.
  • a unit dosage form comprising cyclosporin is disclosed, wherein the unit dosage form is a film administered to the eye.
  • the unit formulation is characterized in that the unit formulation does not contain a surfactant.
  • the unit dosage form is characterized in that it does not contain a preservative.
  • the unit formulation is polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylmethyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, benzalkonium chloride, alginic acid or sodium alginate
  • a unit dosage form comprising at least one polymer selected from the group consisting of pectin, xanthan gum, xyloglucan gum and hyaluronic acid as a film forming polymer.
  • the unit dosage form is disclosed, wherein the unit dosage form comprises an amount equal to a single dose of cyclosporin.
  • the cyclosporin is disclosed in the unit dosage form, characterized in that dissolved in the form of a solid solution in the unit dosage form.
  • a unit formulation in which the film-forming polymer of the unit formulation is PVA.
  • the unit dosage form is disclosed wherein the cyclosporine is dissolved in the form of a solid solution in the PVA matrix.
  • an accurate single dose of cyclosporin can be administered, and the burning sensation caused by other eye drops including cyclosporin is eliminated.
  • the film of the present invention is suitable for administration to the eye, and also has suitable physical properties for handling.
  • 1 is an evaluation of the burning sensation of one embodiment according to the present invention in a healthy rabbit.
  • FIG. 2 is a view of the surface of one embodiment according to the invention.
  • film formulation as a means of administering drugs to the eye is not common.
  • the most common means for delivering drugs to the eye are liquids such as eye drops or semisolids such as ophthalmic ointments.
  • administering a solid preparation, such as a film may give the patient a feeling of foreign substance coming into the eye, and may also cause unnecessary eye irritation due to the physical properties of the solid preparation. Accordingly, commercially available film formulations as ocular dosage forms have not been known to date.
  • microemulsions are thermodynamically unstable and can cause phenomena such as aggregation, sedimentation, creaming, particle growth or coalescence, and breakage of liquid-liquid dispersion, which is also pointed out as a cause of burning sensation.
  • the above castor oil has a short storage period.
  • nanoemulsions such as nanoemulsions have been attempted to reduce particles to nanosized size (Korea Patent No. 1008189), but nanoemulsions are expensive for high-pressure homogenizers and microfluidizers for manufacturing. In addition to the need for machines, there is a possibility of deterioration during the process, which is not suitable for mass production due to effort and cost.
  • the present inventors have focused on improving the causes that can cause a burning sensation during ocular administration, such as the essential combination of surfactants or instability of particles.
  • a burning sensation such as the essential combination of surfactants or instability of particles.
  • all studies have been limited to eye drop formulations, focusing on the selection of solvents similar in composition to tears so as not to give a burning sensation, and on means for uniformly dispersing poorly soluble cyclosporin in the selected solvent. did.
  • preservatives In the case of eye drops, due to the limitation of liquid formulations, preservatives must be added to prepare a unit dosage form that can be used several times. Preservatives without preservatives are recommended to be discarded within 7-8 hours, even if the drug remains after use because of biological contamination. On the other hand, containing the preservative may prevent the contamination of biological bacteria due to the opening and closing of the eye drop container, it may be possible to use for about 30 days, but the preservative may cause allergies, etc., may be harmful to the human body.
  • the present inventors have tried to improve gastric discomfort through the introduction of a new formulation film. In other words, there was no case of blocking the use of preservatives and at the same time discard the excess drug.
  • a surfactant when included in the eye drop as a means for solubilizing cyclosporin, a burning sensation occurs.
  • Restasis ® it can be used in combination with artificial tears or other anti-inflammatory drugs in refractory dry eyes and can reduce the number of eye drops and inhibit the use of other anti-inflammatory drugs.
  • the patient feels burning or eye pain, and thus, many patients cannot fill a long period of time, for example, about 3 months.
  • the present inventors have formulated cyclosporine in the form of a film using a solid property without using a solubilizer or surfactant used to solubilize the cyclosporin as a means of eliminating the burning sensation, which is a serious side effect of the cyclosporine preparation.
  • the present invention was created by obtaining a new knowledge that the stimulus is removed.
  • the formulation was designed so that it does not contain a preservative, and the dosage amount is set correctly so that the case of discarding the drug remaining after use does not occur. The storage stability was then invented to be improved when compared with eye drops.
  • the invention is characterized in the formulation. Cyclosporine is an active ingredient, and all of the medicines marketed as ophthalmic inflammation, such as increased tear production or dry keratoconjunctivitis, consist of eye drops. However, the present invention is a film.
  • the efficacy, effect, usage and dosage of the present invention may be the same as conventional cyclosporine-containing eye drops.
  • the eye drops are set at an interval of about 12 hours once a day and twice a day. At this time, the concentration of the above drop was 0.5 mg of cyclosporin per ml, which is 0.05%.
  • the usage and dosage of the present invention can be configured to be biologically equivalent to the bioavailability.
  • a certain amount of polymer is required to maintain the shape of the film. At this time, there may be a difference in the burning sensation given to the eyes depending on the type of the polymer. Since film formulations have been developed only for oral administration, the choice of polymer was evaluated according to criteria such as disintegration in the oral cavity, the degree of bitterness masking, retention of post-production properties, and ease of manufacturing process. However, in the present invention, since the administration site is an eyeball, it is necessary to evaluate the physical properties of the polymer on a completely different basis.
  • Polyvinyl alcohol polyvinylpyrrolidone, hydroxypropylmethyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, benzalkonium chloride, alginic acid or sodium alginate, pectin, xanthan gum, xyl
  • PVA polyvinyl alcohol
  • PVA polyvinyl alcohol
  • the polymer may be uniformly dispersed in the cyclosporine, there is a manufacturing advantage such that the film does not occur, such as cracks that can occur in the film manufacturing process such as drying after transport or application of the manufacturing solution.
  • the thin film to give a quick absorption of the active ingredient and less heterogeneity to the eye if you want to produce a thin film should be a relatively high content of the active ingredient. At this time, if the content of the active ingredient is high concentration may cause problems such as layer separation of the film preparation, non-homogenization of the active ingredient, but the above polymer was able to block such a problem because it is in harmony with a specific drug called cyclosporin .
  • the viscosity and blending amount of the polymer can be selected through the routine experiments in consideration of the rapid disintegration in the eye, cracks in the appearance of the film production, causing wrinkles, and the like.
  • Plasticizer may be added to the above polymer.
  • glycerin, sorbitol, polyethylene glycol, propylene glycol, triethyl citrate, and the like may be adopted.
  • propylene glycol may be preferable in combination with the above specific polymer and cyclosporine.
  • the present invention is characterized in that no surfactant is added to the preparation of conventional eye drops or poorly soluble drugs.
  • a surfactant such as polysorbate must be inevitably mixed in order to obtain a preparation or to consider the efficiency of dissolution and absorption after oral administration.
  • the inventors have found for the first time that a specific polymer film forming agent enables homogeneous dispersion of cyclosporin, so that the particles of cyclosporin can be uniformly implemented in the film formulation even without a surfactant.
  • this invention can mix
  • the present invention can dissolve or disperse cyclosporin in a solution consisting of a polymer, a solvent, and a plasticizer, degass the solution solution using an ultrasonic disperser, and then produce a film according to a known casting method.
  • the film according to the present invention is excellent in storage stability and biological stability (contamination by bacteria) even without formulating preservatives compared to eye drops, and enables homogeneous dispersion of cyclosporin even without a surfactant, and gives a sense of foreign body (Quick disintegration), less burning sensation, and ease of use compared to eye drops (when compared to eye drops, one-dose recommended dose can be administered to the eye with exactly no external loss, and there is no need to discard the remaining drug after use). great. Moreover, productivity is also preferable when considering the frequency of film separation, cracking, etc. in a film manufacturing process.
  • cyclosporin is dissolved or dispersed in a solution consisting of various polymers, solvents and plasticizers using a magnetic stirrer. Thereafter, the solution was degassed using a sonicator, and the solution was cast to a suitable substrate to prepare a film. The prepared film was further cut to a size of 0.5 cm x 0.5 cm to obtain a final result.
  • Example 1 Example 2 Example 3 Example 4 Example 5 Film base PVA 1 PVP 2 HPMC 3 CMC-Na 4 Sodium alginate 5 usage 0.69mg 0.69mg 0.69mg 0.69mg 0.69mg 0.69mg Plasticizer Propylene glycol Propylene glycol Propylene glycol Propylene glycol usage 0.075ml 0.075ml 0.075ml 0.075ml 0.075ml 0.075ml Main drug Cyclosporin A Cyclosporin A Cyclosporin A Cyclosporin A Cyclosporin A usage 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg 0.015mg
  • Comparative Examples 1 and 2 Film preparation containing cyclosporin
  • Comparative Example 1 Comparative Example 2 Film base Pullulan Maltodextrin usage 1.4mg 2.2mg Plasticizer Propylene glycol Propylene glycol usage 0.075ml 0.075ml Main drug Cyclosporin A Cyclosporin A usage 0.015mg 0.015mg
  • Recitasis ® Commercially available Recitasis ® was used as a reference example.
  • Example 1 The film prepared in Example 1 was administered to one eye of a rabbit against 10 healthy rabbits, and then contrasted with the other eye not receiving the film, before, immediately after, and after the administration of cyclosporine. After 24 hours, the corneal clouding, the extent of clouding cornea, conjunctival redness, conjunctival edema, and discharge were assessed. Evaluation of the experiment is shown in FIG.
  • the eyes of the rabbits to which the cyclosporin film was administered did not have any visible corneal haze before and 24 hours after the administration, and no visible redness or edema was observed in the conjunctiva of the rabbit. No emissions from eye abnormalities could be observed throughout the eye area.
  • Example 1 For the film prepared in Example 1, 10 healthy adults were subjected to sensory evaluation for burning sensation after applying the film to the cornea. At this time, the subjects were blinded in all the tests. The results were evaluated according to the following evaluation criteria and the test results were shown.
  • Example 1 Reference Example 1 Subject score (10) One 3 One 4 One 4 One 3 One 4 One 5 One 4 One 3 One 4 One 4 Average One 3.8
  • the disintegration time of the film containing the cyclosporin prepared in Example 1 was measured to determine how long it could melt in the eye. After adding 5 mm of artificial tears to a Petri dish in a 37-degree environment, drop a sheet of 0.5cm x 0.5cm on the surface of the water and observe the shape of the film while visually observing the dissolution of the film over time. The disintegration time was evaluated by measuring the time taken until it was impossible. The evaluation results of the experiment are shown in Table 4.
  • the films prepared by the formulations of Examples 1 to 5 were all dissolved within 35 seconds in artificial tears, and in particular, the film of Example 1 exhibited a disintegration rate much faster than that of other films. .
  • the thickness, weight and weight deviation, tensile strength and elongation of the film were measured.
  • an average value was obtained by measuring three times at room temperature using a Digimatic Caliper 500.
  • the weight of the prepared film was measured three times with chemical balance to obtain the average weight and the weight deviation.
  • the tensile strength of the film divided by the cross-sectional area of the material when the film was pulled by an external force was measured. The tensile strength of the film was measured, and the strain between the marks was measured. Elongation was obtained.
  • Table 5 shows the results of evaluating the physical properties of the film prepared in Example 1.
  • Example 1 Comparative Example 1 Thickness (mm) 0.010 ⁇ 0.00 0.03 ⁇ 0.01 Weight (mg) 0.72 ⁇ 0.057 1.41 ⁇ 0.029 Tensile Strength (N / mm 2 ) 26.37 ⁇ 1.34 9.31 ⁇ 0.021 Elongation (%) 165.21 ⁇ 3.93 20.29 ⁇ 1.01
  • Example 2 In order to observe the surface morphology of the film prepared in Example 1 and the presence of drug crystals, an optical microscope (MIC LX400, Bimeince, Suwon, Korea) and a field emission scanning electron microscope (Field Emission Electron Microscopy, FE-SEM, SIGMA, Carl Zeiss, Germany). To observe the field emission scanning microscope, the surface of the film sample was platinum treated, and then the surface shape, lamination defects and the presence of drug particles were observed under the voltage condition of 20kV. The form and surface observation results of the film prepared in Example 1 are shown in FIG. 2. As shown in FIG.

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Abstract

La présente invention concerne une forme posologique unitaire comprenant de la cyclosporine et qui est caractérisée en ce que la forme posologique unitaire comprend la même quantité qu'une dose de cyclosporine, que la cyclosporine est dissoute et présente à l'état de solution solide, et que la forme posologique unitaire est un film destiné à l'application à l'œil.
PCT/KR2017/007426 2016-09-13 2017-07-12 Forme posologique pour film oculaire comprenant de la cyclosporine WO2018052185A1 (fr)

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KR10-2016-0117835 2016-09-13
KR1020160117835A KR20180030323A (ko) 2016-09-13 2016-09-13 사이클로스포린의 안구필름 제형

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111358771A (zh) * 2020-04-14 2020-07-03 沈阳药科大学 一种硫酸阿托品眼用膜剂及其制备方法
WO2024059952A1 (fr) * 2022-09-23 2024-03-28 Madd Ophthalmics Ltd. Systèmes d'administration de médicament muco-adhésif et méthodes d'utilisation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120022574A (ko) * 2010-07-30 2012-03-12 주식회사종근당 사이클로스포린 에이 함유 점안제 조성물
KR101587412B1 (ko) * 2014-10-17 2016-01-21 주식회사 휴온스 사이클로스포린 및 트레할로스를 포함하는 안과용 조성물
KR101587385B1 (ko) * 2015-07-29 2016-01-21 국제약품공업주식회사 사이클로스포린 함유 무자극성의 안약조성물 및 편리한 제조방법
KR101635915B1 (ko) * 2016-02-15 2016-07-04 삼천당제약주식회사 사이클로스포린과 히알루론산 또는 이의 염을 포함하는 수용액 형태의 안과용 조성물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120022574A (ko) * 2010-07-30 2012-03-12 주식회사종근당 사이클로스포린 에이 함유 점안제 조성물
KR101587412B1 (ko) * 2014-10-17 2016-01-21 주식회사 휴온스 사이클로스포린 및 트레할로스를 포함하는 안과용 조성물
KR101587385B1 (ko) * 2015-07-29 2016-01-21 국제약품공업주식회사 사이클로스포린 함유 무자극성의 안약조성물 및 편리한 제조방법
KR101635915B1 (ko) * 2016-02-15 2016-07-04 삼천당제약주식회사 사이클로스포린과 히알루론산 또는 이의 염을 포함하는 수용액 형태의 안과용 조성물

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JIANG, W. ET AL.: "Preparation of Cyclosporine A Eye Film.", CHINESE JOURNAL OF HOSPITAL PHARMACY, 2008, pages 357 - 360, Retrieved from the Internet <URL:http://en.cnki.com.cn/Article_en/CJFDTotal-ZGYZ200805013.htm> *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111358771A (zh) * 2020-04-14 2020-07-03 沈阳药科大学 一种硫酸阿托品眼用膜剂及其制备方法
CN111358771B (zh) * 2020-04-14 2023-01-10 沈阳药科大学 一种硫酸阿托品眼用膜剂及其制备方法
WO2024059952A1 (fr) * 2022-09-23 2024-03-28 Madd Ophthalmics Ltd. Systèmes d'administration de médicament muco-adhésif et méthodes d'utilisation

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