TW202038928A - Suspension compositions of multi-target inhibitors - Google Patents

Suspension compositions of multi-target inhibitors Download PDF

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TW202038928A
TW202038928A TW108102789A TW108102789A TW202038928A TW 202038928 A TW202038928 A TW 202038928A TW 108102789 A TW108102789 A TW 108102789A TW 108102789 A TW108102789 A TW 108102789A TW 202038928 A TW202038928 A TW 202038928A
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淑伶 丁
古丹 木胡里
丹霞 湯
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開曼群島商艾葳控股有限公司
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Abstract

This disclosure relates to aqueous suspension formulations of multi-target inhibitors. These formulations can be locally administered to target tissues such as eyes, prostate, problems that may potentially be solved by the present disclosure are to (1) provide an injectable dosage form that allows direct delivery of a multi-target inhibitor to the proximity of the diseased tissue, (2) be compatible with the tissue of the site of administration, (3) form a drug reservoir at the administration site to allow prolonged supply of the drug to the diseased tissue, and thus reduce dosing frequency, (4) the release rate of the drug from the reservoir is such that above therapeutic level of the drug in the diseased tissue is achievable, (5) have physicochemical properties that are suitable for clinical uses, (6) be terminally sterilizable so that safety risk due to contamination of micro-organisms can be minimized, and (7) have a stability profile suitable for long term storage and distribution.

Description

多目標抑製劑的懸浮液組合物Suspension composition of multi-target inhibitor

本發明關於一種多目標抑制劑的水性懸浮液配方。這些配方可局部地施予如眼睛、前列腺及皮膚的目標組織，以用於皮膚、眼科、泌尿生殖系統疾病的治療。The present invention relates to an aqueous suspension formulation of a multi-target inhibitor. These formulas can be topically administered to target tissues such as eyes, prostate and skin for the treatment of skin, ophthalmology, and genitourinary diseases.

低溶解度多目標抑制劑對於配方成藥學上可接受的可注射懸浮液可為具有挑戰性的。一些理由如下： 1、懸浮液為分散的系統，其為本質上熱力學不穩定的。藥學上的懸浮液通常為固體懸浮在液體中。固體顆粒可沉降或結塊，造成使用前再懸浮的困難性。在儲存期間若所配方的多晶型並非最熱力學穩定的型態，固體可能經歷多型態的轉化(polymorphic transformation)。此外，由於奧斯華熟化現象(Ostwald ripening phenomenon)，顆粒的大小可變大。該現象能夠導致在粒度分布中明顯的位移及經由改變溶解率改變產品的生物可用率。因此，達到具有可接受的物理穩定性的懸浮液為具有挑戰性的。 2、用於非腸胃懸浮液的藥學上可接受之賦形劑係受限的。為了減少熱力學不穩定性，可期望合併懸浮劑、濕潤劑、黏度增強劑、界面活性劑、凝聚劑等。不幸的是，這些功能性賦形劑許多沒有用於藥學上非腸胃之用途的足夠歷史紀錄。 3、為了生產符合商業和監管標準的無菌產品，製造非腸胃的懸浮液可能需要高度專業化的設施、設備及和製造程序。Low solubility multi-target inhibitors can be challenging to formulate into a pharmaceutically acceptable injectable suspension. Some reasons are as follows: 1. The suspension is a dispersed system, which is thermodynamically unstable in nature. Pharmaceutical suspensions are usually solids suspended in liquids. Solid particles can settle or agglomerate, making it difficult to resuspend before use. If the formulated polymorph is not the most thermodynamically stable during storage, the solid may undergo polymorphic transformation. In addition, due to the Ostwald ripening phenomenon, the size of the particles may become larger. This phenomenon can cause a significant shift in the particle size distribution and change the bioavailability of the product by changing the dissolution rate. Therefore, achieving a suspension with acceptable physical stability is challenging. 2. The pharmaceutically acceptable excipients used for parenteral suspensions are limited. In order to reduce thermodynamic instability, it may be desirable to combine suspending agents, wetting agents, viscosity enhancers, surfactants, flocculants, etc. Unfortunately, many of these functional excipients do not have sufficient historical records for pharmaceutical non-gastric uses. 3. In order to produce sterile products that meet commercial and regulatory standards, manufacturing parenteral suspensions may require highly specialized facilities, equipment, and manufacturing procedures.

一些實施例包括用於藉由施予水性懸浮液至人類或動物來治療及/或防止局部疾病/異常的組合物(例如水性懸浮液)及方法。活性成分可沉積在施予的位置並隨時間釋放用於局部作用。該配方應用於如阿西替尼(axitinib)、尼達布尼(nintedanib)、吡非尼酮(pirfenidone)、瑞司瓜特(riociguat)、索拉非尼(sorafenib)、舒尼替尼(sunitinib)、樂瓦替尼(lenvatinib)、瑞格菲尼(regorafenib)、普納替尼(ponatinib)及帕唑帕尼(pazopanib)的多目標抑制劑。Some embodiments include compositions (e.g., aqueous suspensions) and methods for treating and/or preventing local diseases/abnormalities by administering aqueous suspensions to humans or animals. The active ingredient can be deposited at the site of administration and released over time for local effect. The formula is applied to such as axitinib (axitinib), nintedanib (nintedanib), pirfenidone (pirfenidone), riociguat (riociguat), sorafenib (sorafenib), sunitinib ( Sunitinib), lenvatinib (lenvatinib), regorafenib (regorafenib), ponatinib (ponatinib) and pazopanib (pazopanib) multi-target inhibitors.

一些實施例包括藥學組合物，其包含：包含藥學上可接受的載體及至少一種多目標抑制劑的水性懸浮液(方便起見本文稱為「主題配方(subject formulation)」)。一些藥學上可接受的載體包括懸浮劑、濕潤劑、緩衝液系統及/或滲透劑。Some embodiments include pharmaceutical compositions comprising: an aqueous suspension comprising a pharmaceutically acceptable carrier and at least one multi-target inhibitor (referred to herein as a "subject formulation" for convenience). Some pharmaceutically acceptable carriers include suspending agents, wetting agents, buffer systems, and/or penetrants.

一些實施例包括治療皮膚異常、眼科異常或泌尿生殖系統異常的方法，其包含：施予有效劑量的主題配方，以治療患有皮膚異常、眼科異常或泌尿生殖系統異常的主體。Some embodiments include a method of treating skin abnormalities, ophthalmological abnormalities or urogenital system abnormalities, which comprises: administering an effective dose of the subject formulation to treat a subject suffering from skin abnormalities, ophthalmological abnormalities or urogenital system abnormalities.

一些實施例包括多目標抑制劑用於製造藥學組合物的用途，以用於皮膚異常、眼科異常或泌尿生殖系統異常的治療。在一些實施例中，所製造的藥學組合物為主題配方。Some embodiments include the use of multi-target inhibitors for the manufacture of pharmaceutical compositions for the treatment of skin abnormalities, ophthalmological abnormalities or urogenital system abnormalities. In some embodiments, the manufactured pharmaceutical composition is the subject formulation.

將目標藥物遞送至局部組織可較全身性藥物施予為佳。其可被用來改善局部藥物的曝露及降低全身性副作用。有一些關於可改善結果的局部藥物遞送的考量。例如，若具有適當局部耐受性及安全性之藥物遞送至局部組織的方法係藉由患者或從業醫師(medical practitioners)能輕易地施予可為有益的。若劑型及劑量係為適合用於目標組織的量並提供有效的疾病管理亦為有用的。藥物釋放超過一段相當的時間亦可為可期待的。Delivery of the target drug to local tissues can be better than systemic drug administration. It can be used to improve local drug exposure and reduce systemic side effects. There are some considerations regarding local drug delivery that can improve outcomes. For example, it may be beneficial if a method of delivering drugs with appropriate local tolerance and safety to local tissues can be easily administered by patients or medical practitioners. It is also useful if the dosage form and dose are suitable for the target tissue and provide effective disease management. Drug release over a considerable period of time can also be expected.

令人驚訝地，一些主題配方經由局部施加提供足夠量的活性劑至目標組織且對於治療皮膚、眼科或泌尿生殖系統係有效的。Surprisingly, some of the subject formulations provide a sufficient amount of active agent to target tissues via topical application and are effective for treating the skin, ophthalmology, or genitourinary system.

一些主題配方包括具有一定的水溶解度的多目標抑制劑之懸浮液組合物，例如大約10 mg/ml及以下。Some subject formulations include suspension compositions of multi-target inhibitors with certain water solubility, for example, about 10 mg/ml and below.

主題配方與人類及動物的組織可生物相容。一些配方可為化學及物理穩定的，且可於儲存時可再懸浮以重得均勻性。一些配方可經受最終滅菌(terminal sterilization)而不損失其物化完整性。一些配方具有低內毒素以及顆粒物質汙染。一些主題配方可使用醫療上常用的針規大小被注射至局部組織中。本文所描述的一些配方具有經證實之可接受的穩定性曲線(stability profile)且可修正的用於長期儲存及配送。The subject formula is biocompatible with human and animal tissues. Some formulations can be chemically and physically stable, and can be resuspended during storage to restore uniformity. Some formulations can withstand terminal sterilization without losing their physical and chemical integrity. Some formulations have low endotoxin and particulate matter contamination. Some topical formulas can be injected into local tissues using needle gauge sizes commonly used in medical treatment. Some of the formulations described herein have proven and acceptable stability profiles and can be modified for long-term storage and distribution.

一些實施例關於藥學上水性懸浮液配方組合物，其可包含藥學上可接受的載體及至少一種多目標抑制劑。Some embodiments relate to a pharmaceutical aqueous suspension formulation composition, which may include a pharmaceutically acceptable carrier and at least one multi-target inhibitor.

除非另有指出，任何藉由結構、名稱或任何其他包括游離鹼、游離酸、藥學上可接受的鹽、 替代的固體型態(如多形體(polymorphs)、溶劑合物(solvates)、水合物(hydrates)等)鏡像異構物、互變異構物、前藥或任何其他化學種類的方式對本文化合物如多目標抑制劑的提及在如本文所述使用化合物的條件下，可迅速轉化為本文所述的化合物。Unless otherwise indicated, any solid forms (such as polymorphs, solvates, hydrates) that include free bases, free acids, pharmaceutically acceptable salts, alternative solid forms (such as polymorphs, solvates), (hydrates), etc.) Spiegelmers, tautomers, prodrugs, or any other chemical species referred to the compounds herein, such as multi-target inhibitors, can be quickly converted to The compounds described herein.

在本文所描述的這些懸浮液中之活性成分的物理型態可為固體，其可為非晶質(amorphous)或多形體。固體活性成分可具有任何合適的顆粒大小，如介於約0.1~100µm、約1~20µm或約1~10µm之間。The physical form of the active ingredients in the suspensions described herein may be solid, which may be amorphous or polymorphic. The solid active ingredient can have any suitable particle size, such as between about 0.1-100 µm, about 1-20 µm, or about 1-10 µm.

有益的的多目標抑制劑之非限制性實例及它們物化型態和水溶解度資訊示於表1中。Non-limiting examples of useful multi-target inhibitors and their physical and chemical forms and water solubility information are shown in Table 1.

表1：多目標抑制劑的實例：結構、物化型態及水溶解度 多目標抑制劑 化學型態 物理型態及 多形體 分子量 (g/ 莫耳 ) 水溶解度 結構 阿西替尼 游離鹼 固體， 型態IV 386 2 µg/mL

Figure 02_image001
尼達布尼 游離鹼 固體 539 9 µg/mL
Figure 02_image003
 吡非尼酮 吡啶酮 固體 185 3 mg/mL
Figure 02_image005
 瑞司瓜特 游離鹼 固體 422 8 µg/mL
Figure 02_image007
 索拉非尼半甲苯磺酸鹽(Sorafenib Hemi Tosylate) 鹽 固體， 型態A 636 6 µg/mL
Figure 02_image009
 舒尼替尼   游離鹼 固體， 型態I 398 7 µg/mL
Figure 02_image011
 樂瓦替尼 游離鹼 固體， 型態B 426 4 µg/mL
Figure 02_image013
 瑞格菲尼 游離鹼 Solid 482  
Figure 02_image015
 普納替尼 游離鹼 Solid 532  
Figure 02_image017
 帕唑帕尼 游離鹼 Solid 437  
Figure 02_image019
 Table 1: Examples of multi-target inhibitors: structure, physical and chemical form and water solubility Multi-target inhibitor Chemical form Physical form and polymorphism Molecular weight (g/ mole ) Water solubility structure Axitinib Free base Solid, type IV 386 2 µg/mL
Figure 02_image001
 Nidabuni Free base solid 539 9 µg/mL
Figure 02_image003
 Pirfenidone Pyridone solid 185 3 mg/mL
Figure 02_image005
 Risgut Free base solid 422 8 µg/mL
Figure 02_image007
 Sorafenib Hemi Tosylate (Sorafenib Hemi Tosylate) salt Solid, type A 636 6 µg/mL
Figure 02_image009
 Sunitinib Free base Solid, type I 398 7 µg/mL
Figure 02_image011
 Lovatinib Free base Solid, form B 426 4 µg/mL
Figure 02_image013
 Regfini Free base Solid 482
Figure 02_image015
 Pranatinib Free base Solid 532
Figure 02_image017
 Pazopanib Free base Solid 437
Figure 02_image019

藥學上可接受的載體可包含至少一種合適的懸浮劑、至少一種合適的如濕潤劑的界面活性劑、至少一種合適的緩衝液系統及/或至少一種合適的滲透劑。懸浮劑可為羧甲基纖維素鈉(sodium carboxymethylcellulose)、纖維素(cellulose)或多種纖維素的混合物。濕潤劑可為藥學上可接受的非離子型界面活性劑，如聚山梨醇酯80 (polysorbte 80)。緩衝液系統可為藥學上可接受用於非腸胃(parenteral)配方的緩衝液系統，以控制pH接近生理的pH。緩衝液系統可為磷酸鹽緩衝液。滲透劑可包含氯化鈉(sodium chloride)及/或甘油(glycerin)。The pharmaceutically acceptable carrier may comprise at least one suitable suspending agent, at least one suitable surfactant such as a wetting agent, at least one suitable buffer system, and/or at least one suitable penetrant. The suspending agent may be sodium carboxymethylcellulose, cellulose or a mixture of multiple celluloses. The humectant may be a pharmaceutically acceptable non-ionic surfactant, such as polysorbte 80 (polysorbte 80). The buffer system may be a pharmaceutically acceptable buffer system for parenteral formulations to control the pH close to physiological pH. The buffer system can be a phosphate buffer. The osmotic agent may include sodium chloride and/or glycerin.

一些主題配方可進一步包含合適的防腐劑(preservative)，如苯甲醇(benzyl alcohol)。一些實施例可進一步包含附加的成分，如黏度增強劑、穩定劑、螯合劑、抗氧化劑、有機物或共溶劑。Some subject formulations may further include suitable preservatives, such as benzyl alcohol. Some embodiments may further include additional ingredients, such as viscosity enhancers, stabilizers, chelating agents, antioxidants, organics, or co-solvents.

多目標抑制劑可以任何在主題配方中合適的濃度或含量存在，如以組合物的總含量的重量計，約0.01~20%、0.01~10%、約0.01~8%、約0.1~4%、約4~8%、約0.01~3%、約0.01~2%、約2~4%、約0.01~0.5%、約0.5~1%、約1~1.5%、約1.5~2%、約0.01~1%、約1~2%、約2~3%、約3~4%、約4~5%、約5~6%、約6~7%、約7~8%、約8~9%、約9~10%、約0.01~3%、約3~5%、約5~10%。The multi-target inhibitor can be present in any suitable concentration or content in the subject formulation, such as about 0.01-20%, 0.01-10%, about 0.01-8%, about 0.1-4% based on the weight of the total content of the composition. , About 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2%, about 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7%, about 7~8%, about 8~ 9%, about 9~10%, about 0.01~3%, about 3~5%, about 5~10%.

在一些實施例中，在主題配方中的多目標抑制劑為阿西替尼(axitinib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is axitinib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為尼達布尼(nintedanib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is nintedanib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為吡非尼酮(pirfenidone)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is pirfenidone, which is based on the weight of the total content of the composition at about 0.01-10%, 0.01-8%, or about 0.1%. 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為瑞司瓜特(riociguat)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is riociguat, which is based on the weight of the total content of the composition at about 0.01-10%, 0.01-8%, or about 0.1%. 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為索拉非尼(sorafenib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is sorafenib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為舒尼替尼(sunitinib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is sunitinib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為樂瓦替尼(lenvatinib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is lenvatinib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為瑞格菲尼(regorafenib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is regorafenib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為普納替尼(ponatinib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is ponatinib, which is based on the weight of the total content of the composition at about 0.01~10%, 0.01~8%, about 0.1~ 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

在一些實施例中，在主題配方中的多目標抑制劑為帕唑帕尼(pazopanib)，其以組合物的總含量的重量計，以約0.01~10%、0.01~8%、約 0.1~4%、約 4~8%、約 0.01~3%、約 0.01~2%、約 2~4%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%或約7~8%的濃度或含量存在。In some embodiments, the multi-target inhibitor in the subject formulation is pazopanib, which is based on the weight of the total content of the composition at about 0.01-10%, 0.01-8%, or about 0.1%. 4%, about 4~8%, about 0.01~3%, about 0.01~2%, about 2~4%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% , About 0.01~1%, about 1~2%, about 2~3%, about 3~4%, about 4~5%, about 5~6%, about 6~7% or about 7~8% concentration Or content exists.

多目標抑制劑(如阿西替尼、尼達布尼、吡非尼酮、瑞司瓜特、索拉非尼、舒尼替尼、樂瓦替尼、瑞格菲尼、普納替尼或帕唑帕尼)可如所需藉由注射施予(如前述段落中的含量)，或以大約每周地至大約每2年的間隔施予，如約1周、約 2 周、約 3 周、約 4 周、約 5 周、約 6 周、約 7 周、約 8 周、約 9 周、約 10 周、約 11 周、約 12 周、約 13 周、約 14 周、約 15 周、約 16 周、約 17 周、約 18 周、約 19 周、約 20 周、約 21 周、約 22 周、約 23 周、約 24 周、約 25 周、約 26 周、約 27 周、約 28 周、約 29 周、約 30 周、約 31 周、約 32 周、約 33 周、約 34 周、約 35 周、約 36 周、約 37 周、約 38 周、約 39 周、約 40 周、約 41 周、約 42 周、約 43 周、約 44 周、約 45 周、約 46 周、約 47 周、約 48 周、約 49 周、約 50 周、約 51 周、約 52 周、約1 個月、約 2 個月、約 3 個月、約 4 個月、約 5 個月、約 6 個月、約 7 個月、約 8 個月、約 9 個月、約 10 個月、約 11 個月、約 12 個月、約 18 個月、約 24 個月等的間隔。Multi-target inhibitors (such as axitinib, nindabuni, pirfenidone, risguat, sorafenib, sunitinib, levatinib, regafeni, punatinib Or pazopanib) can be administered by injection as needed (as in the amount in the preceding paragraph), or at an interval of about weekly to about every 2 years, such as about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 13 weeks, about 14 weeks, about 15 weeks , About 16 weeks, about 17 weeks, about 18 weeks, about 19 weeks, about 20 weeks, about 21 weeks, about 22 weeks, about 23 weeks, about 24 weeks, about 25 weeks, about 26 weeks, about 27 weeks, about 28 weeks, about 29 weeks, about 30 weeks, about 31 weeks, about 32 weeks, about 33 weeks, about 34 weeks, about 35 weeks, about 36 weeks, about 37 weeks, about 38 weeks, about 39 weeks, about 40 weeks , About 41 weeks, about 42 weeks, about 43 weeks, about 44 weeks, about 45 weeks, about 46 weeks, about 47 weeks, about 48 weeks, about 49 weeks, about 50 weeks, about 51 weeks, about 52 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about Intervals of 11 months, about 12 months, about 18 months, about 24 months, etc.

前述段落中的治療(例如像是阿西替尼、尼達布尼、吡非尼酮、瑞司瓜特、索拉非尼、舒尼替尼、樂瓦替尼、瑞格菲尼、普納替尼或帕唑帕尼的多目標抑制劑以上述的含量及間隔施予)可以所需的時長持續使用，如僅有一次或至少約2周、至少約 3 周、至少約 4 周、至少約 5 周、至少約 2 個月、至少約 3 個月、至少約 6 個月、至少約 9 個月、至少約 12 個月、至少約 2 年、至少約 3 年、至少約 4 年、至少約 5 年、至少約 10 年或至少約20年。The treatments in the preceding paragraphs (e.g., axitinib, nindabuni, pirfenidone, rissgut, sorafenib, sunitinib, levatinib, regfinib, prafenid Natinib or pazopanib multi-target inhibitors are administered at the above levels and intervals) can be used continuously for as long as required, such as only once or at least about 2 weeks, at least about 3 weeks, at least about 4 weeks , At least about 5 weeks, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 12 months, at least about 2 years, at least about 3 years, at least about 4 years , At least about 5 years, at least about 10 years, or at least about 20 years.

主題配方可選擇性地含有懸浮劑或添加以幫助如固體顆粒的顆粒懸浮於水性溶劑中的試劑。懸浮劑可為包括雙聚合物或其衍生物的聚合物、或礦物。合適的懸浮劑之實例包括藻酸鹽(alginate)、甲基纖維素(methylcellulose)、羥乙基纖維素(hydroxyethylcellulose)、羧基甲基纖維素(carboxymethylcellulose)、羧基甲基纖維素鈉(sodium carboxymethylcellulose)、微晶型纖維素(microcrystalline cellulose)、阿拉伯膠(acacia gum)、西黃蓍膠(tragacanth)、黃原膠(xanthan gum)、皂土(bentonite)、卡波姆(carbomer)、可拉膠(carrageenan)、粉狀纖維素(powdered cellulose)、明膠(gelatin)等。The subject formulation may optionally contain a suspending agent or an agent added to help particles such as solid particles suspend in an aqueous solvent. The suspending agent may be a polymer including a dipolymer or a derivative thereof, or a mineral. Examples of suitable suspending agents include alginate, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose , Microcrystalline cellulose, acacia gum, tragacanth, xanthan gum, bentonite, carbomer, kola gum (carrageenan), powdered cellulose, gelatin, etc.

懸浮劑(例如羧基甲基纖維素鈉的羧基甲基纖維素、纖維素、纖維素的混合物等)可在主題配方中以任何合適的濃度或含量存在，如以總組合物的重量計，約0.1~10%、約 0.2~3%、約 3~6%、約 6~10%、約 0.1~1%、約 1~2%、約 2~3%、約 3~4%、約 4~5%、約 5~6%、約 6~7%、約 7~8%、約 8~9%、約 9~10%。在一些實施例中，懸浮劑為如羧基甲基纖維素鈉的羧基甲基纖維素。在一些實施例中，懸浮劑為纖維素。在一些實施例中，懸浮劑為多種纖維素的混合物。Suspending agents (for example, carboxymethyl cellulose of sodium carboxymethyl cellulose, cellulose, cellulose mixtures, etc.) may be present in the subject formulation at any suitable concentration or content, such as about the weight of the total composition. 0.1~10%, about 0.2~3%, about 3~6%, about 6~10%, about 0.1~1%, about 1~2%, about 2~3%, about 3~4%, about 4~ 5%, about 5~6%, about 6~7%, about 7~8%, about 8-9%, about 9~10%. In some embodiments, the suspending agent is carboxymethylcellulose such as sodium carboxymethylcellulose. In some embodiments, the suspending agent is cellulose. In some embodiments, the suspending agent is a mixture of multiple celluloses.

主題配方可選擇性的含有濕潤劑以藉由水性溶液幫助改善低溶解度的多目標抑制劑的濕潤性。合適的濕潤劑可包括共溶劑、水溶助劑(hydrotropes)、界面活性劑及其類似物。在一些實施例中，濕潤劑為藥學上可接受的界面活性劑，如非離子型界面活性劑，例如環氧烷類界面活性劑(alkylene oxide based surfactant) (如環氧乙烷-環氧丙烷嵌段共聚物(ethylene oxide--propylene oxide block copolymer)、脂肪酸聚環氧乙烷(fatty acid polyethylene oxide)、如聚山梨醇酯的糖基聚氧化乙烯(sugar based polyethylene oxide)等)、如氧化胺(amine oxide)或甜菜鹼(betaine)的兩性界面活性劑(amphoteric surfactant)、如烷基硫酸鹽(alkyl sulfate)、烷基苯磺酸鹽(alkylbenzenesulfonate)、烷基醚硫酸鹽(alkylether sulfate)等的陰離子界面活性劑(anionic surfactant)，或如四級胺(quaternary amine)化合物的陽離子界面活性劑(cationic surfactant)。在一些實施例中，濕潤劑為藥學上可接受的非離子型界面活性劑。在一些實施例中，濕潤劑為如聚山梨醇酯80的聚山梨醇酯。The subject formulation can optionally contain a wetting agent to help improve the wettability of the low-solubility multi-target inhibitor through the aqueous solution. Suitable wetting agents may include co-solvents, hydrotropes, surfactants, and the like. In some embodiments, the wetting agent is a pharmaceutically acceptable surfactant, such as a non-ionic surfactant, such as an alkylene oxide based surfactant (such as ethylene oxide-propylene oxide Block copolymer (ethylene oxide--propylene oxide block copolymer), fatty acid polyethylene oxide (fatty acid polyethylene oxide), sugar based polyethylene oxide (sugar based polyethylene oxide) such as polysorbate, etc.), such as oxidation Amphoteric surfactants of amine oxide or betaine, such as alkyl sulfate, alkylbenzenesulfonate, alkylether sulfate And other anionic surfactants, or cationic surfactants such as quaternary amine compounds. In some embodiments, the humectant is a pharmaceutically acceptable non-ionic surfactant. In some embodiments, the humectant is a polysorbate such as polysorbate 80.

主題配方可選擇性的含有任何合適含量的界面活性劑(例如聚山梨醇酯80)，如主題配方的總重量的約0.02~5%、約 0.02~3%、約 3~5%、約 0.2~1%、約 1~2%、約 2~3%、約 0.2~1%、約 1~1.5%、約 1.5~2%、約 2~2.5%或約2.5~3%。The subject formulation can optionally contain any suitable content of surfactant (for example, polysorbate 80), such as about 0.02~5%, about 0.02~3%, about 3~5%, about 0.2 of the total weight of the subject formulation. ~1%, about 1~2%, about 2~3%, about 0.2~1%, about 1~1.5%, about 1.5~2%, about 2~2.5% or about 2.5~3%.

主題配方可選擇性的含有緩衝液系統。合適的緩衝液系統包括檸檬酸鹽(citrate)、磷酸鹽(phosphate)、碳酸鹽(carbonate)、重碳酸鹽(bicarbonate)、硼酸鹽(borate)等。可使用任何合適濃度的緩衝液(例如磷酸鹽緩衝液)，如主題配方的總重量的約0.01~5%、約 0.1~2%、約 0.1~0.2%、約 0.2~0.4%、約 0.4~0.6%、約 0.6~0.8%、約 0.8~1%、約 0.01~0.5%、約 0.5~1%、約 0.01~1%、約 1~2%、約 2~3%、約 3~4%或約4~5%。The subject formula can optionally contain a buffer system. Suitable buffer systems include citrate, phosphate, carbonate, bicarbonate, borate and the like. Any suitable concentration of buffer (such as phosphate buffer) can be used, such as about 0.01~5%, about 0.1~2%, about 0.1~0.2%, about 0.2~0.4%, about 0.4~ of the total weight of the subject formulation. 0.6%, about 0.6 to 0.8%, about 0.8 to 1%, about 0.01 to 0.5%, about 0.5 to 1%, about 0.01 to 1%, about 1 to 2%, about 2 to 3%, about 3 to 4% Or about 4~5%.

主題配方可具有任何合適的pH，如pH接近或約略為其遞送到的組織之pH，例如約5~9、約 6~8、約 5~7、約 7~9、約 5~6、約 6~7、約 7~8、約 8~9、約 7~7.2、約 7.2~7.4、約 7.4~7.6、約 7.6~7.8、約 7.8~8等。The subject formulation may have any suitable pH, such as a pH close to or approximately the pH of the tissue to which it is delivered, for example, about 5-9, about 6-8, about 5-7, about 7-9, about 5-6, about 6 to 7, about 7 to 8, about 8 to 9, about 7 to 7.2, about 7.2 to 7.4, about 7.4 to 7.6, about 7.6 to 7.8, about 7.8 to 8, etc.

主題配方可選擇性地含有如右旋糖(dextrose)、甘油、甘露醇(mannitol)、氯化鈉等的滲透劑。可使用任何合適濃度的滲透劑(例如氯化鈉或甘油)，如主題配方的總重量的約0.01~2%、約 0.1~1%、約 0.1~0.5%、約 0.5~1%、約 0.01~0.2%、約 0.2~0.4%、約 0.4~0.6%、約 0.6~0.8%、約 0.8~1%、約 0.5%或約0.75%。The subject formulation can optionally contain penetrants such as dextrose, glycerin, mannitol, sodium chloride and the like. Any suitable concentration of penetrant (such as sodium chloride or glycerin) can be used, such as about 0.01 to 2%, about 0.1 to 1%, about 0.1 to 0.5%, about 0.5 to 1%, about 0.01 of the total weight of the subject formulation. ~0.2%, about 0.2 to 0.4%, about 0.4 to 0.6%, about 0.6 to 0.8%, about 0.8 to 1%, about 0.5%, or about 0.75%.

主題配方可選擇性地含有防腐劑，如酚(phenol)、間甲酚(m-cresol)、如對羥苯甲酸甲酯(methylparaben)、對羥苄酸丙酯(propylparaben)、羥苯甲酸丁酯(butylparaben)的對羥苯甲酸酯類(paraben)、米吡氯銨(myristyl gamma-picolinium chloride)、羥基氯苯胺(benzalkonium chloride)、氯化本索寧(benzethonium chloride)、苯甲醇(benzyl alcohol)、2-苯氧乙醇(2-penoxyethanol)、氯丁醇(chlorobutanol)、乙汞硫柳酸鈉(thimerosal)、苯基汞鹽(phenymercuric salts)等。可使用任何合適濃度的防腐劑(例如苯甲醇)，如主題配方的總重量的約0.01~2%、約 0.5~2%、約 0.01~0.2%、約 0.2~0.4%、約 0.4~0.6%、約 0.6~0.8%、約 0.8~1%、約 1~1.2%、約 1.2~1.4%、約 1.4~1.6%、約 1.6~1.8%、約 1.8~2%、約 0.01~0.5%、約 0.5~1%、約 1~1.5%、約 1.5~2%或約0.9%。The theme formula can optionally contain preservatives, such as phenol, m-cresol, methylparaben, propylparaben, and butyl paraben Parabens of butylparaben, myristyl gamma-picolinium chloride, benzalkonium chloride, benzethonium chloride, benzyl alcohol ), 2-penoxyethanol, chlorobutanol, thimerosal, phenymercuric salts, etc. Any suitable concentration of preservative (such as benzyl alcohol) can be used, such as about 0.01 to 2%, about 0.5 to 2%, about 0.01 to 0.2%, about 0.2 to 0.4%, about 0.4 to 0.6% of the total weight of the subject formulation , About 0.6~0.8%, about 0.8~1%, about 1~1.2%, about 1.2~1.4%, about 1.4~1.6%, about 1.6~1.8%, about 1.8~2%, about 0.01~0.5%, about 0.5~1%, about 1~1.5%, about 1.5~2% or about 0.9%.

主題配方可具有特性為當注射入如兔子或人類的哺乳類之前列腺約7 天、10天、15天、20天、30天、40天、50天、 60天或更久之後，多目標抑制劑(如阿西替尼、尼達布尼、吡非尼酮、瑞司瓜特、索拉非尼、舒尼替尼、樂瓦替尼、瑞格菲尼、普納替尼或帕唑帕尼)在前列腺組織中的濃度為至少約0.1 µg/g、至少 0.5 µg/g、至少約 1 µg/g、至少約 5 µg/g或至少約10 µg/g。The subject formulation may have characteristics such that when injected into the prostate of mammals such as rabbits or humans for about 7 days, 10 days, 15 days, 20 days, 30 days, 40 days, 50 days, 60 days or more, a multi-target inhibitor (E.g. axitinib, nindabuni, pirfenidone, risguat, sorafenib, sunitinib, levatinib, regafini, punatinib or pazopa The concentration of Ni) in prostate tissue is at least about 0.1 µg/g, at least 0.5 µg/g, at least about 1 µg/g, at least about 5 µg/g, or at least about 10 µg/g.

主題配方可具有特性為當注射入如兔子或人類的哺乳類之眼內約7 天、10天、15天、20天、30天、40天、50天、 60天或更久之後，多目標抑制劑(如阿西替尼、尼達布尼、吡非尼酮、瑞司瓜特、索拉非尼、舒尼替尼、樂瓦替尼、瑞格菲尼、普納替尼或帕唑帕尼)在如玻璃體(vitreous humor)、視網膜(retina)、脈絡膜(choroid)等的後眼部組織(posterior ocular tissue)的濃度為至少約0.1 µg/g、至少約0.5 µg/g、至少約 1 µg/g、至少約 5 µg/g或至少約10 µg/g。The subject formulation may have the characteristic of multi-target inhibition when injected into the eyes of mammals such as rabbits or humans for about 7 days, 10 days, 15 days, 20 days, 30 days, 40 days, 50 days, 60 days or more. (E.g. axitinib, nindabuni, pirfenidone, risguat, sorafenib, sunitinib, levatinib, regafini, punatinib or pazol (Pani) in posterior ocular tissues such as vitreous humor, retina, choroid, etc., at a concentration of at least about 0.1 µg/g, at least about 0.5 µg/g, at least about 1 µg/g, at least about 5 µg/g, or at least about 10 µg/g.

在一些實施例中，皮膚異常包括但不限制於痤瘡疤(acne scar)、皮膚疤(skin scar)、皺紋(wrinkle)、浮肉(cellulite)及真皮腫瘤性纖維化(dermal neoplastic fibrosis)、疤痕性禿髮(scarring alopecia)、血管病變(vasculopathy)、脈管炎(vasculitis)、傷口癒合(wound healing)、過剩的燒傷傷口癒合(exuberant burn wound healing)、糖尿病足症候群(diabetic foot syndrome)、硬皮症(scleroderma)、關節纖維化(arthrofibrosis)、Peyronie氏病(Peyronie's disease)、Dupuytren氏攣縮(Dupuytren's contracture)及黏連性肩關節囊炎(adhesive capsulitis)。In some embodiments, skin abnormalities include but are not limited to acne scars, skin scars, wrinkles, cellulite and dermal neoplastic fibrosis, scars Scarring alopecia, vasculopathy, vasculitis, wound healing, exuberant burn wound healing, diabetic foot syndrome, hard Dermatosis (scleroderma), joint fibrosis (arthrofibrosis), Peyronie's disease (Peyronie's disease), Dupuytren's contracture (Dupuytren's contracture) and adhesive capsulitis (adhesive capsulitis).

在一些實施例中，眼科異常包括但不限制於脈絡膜新生血管相關疾病(choroidal neovascularization associated disease)、年齡相關黃斑點退化(age-related macular degeneration)、角膜透明度受損(compromised corneal transparency)、角膜瘢痕形成(cornea scar formation)、翼狀胬肉(pterygia)、前部白內障形成(anterior cataract formation) 、與青光眼濾過手術(glaucoma filtration surgery)相關的狀況、青光眼(glaucoma)、與雷射屈光眼角膜切除術(photorefractive keratectomy)相關的狀況、與雷射原位層狀眼角膜成塑形(laser in situ keratomileusis)相關的狀況、與前視網膜及視網膜前膜收縮相關的異常(disorder related to contraction of the pre- and epiretinal membranes)、增殖性玻璃體視網膜病變(proliferative vitreoretinopathy)、增生性糖尿病視網膜病變(proliferative diabetic retinopathy)、糖尿病性黃斑水腫(diabetic macular edema)、與近視性脈絡膜新生血管相關的異常(disorder related myopic choroidal neovascularization)、網膜靜脈阻塞(retinal vain occlusion)、視網膜下纖維增生(sub-retinal fibrosis)、視網膜下瘢痕(sub-retinal scarring)、脈絡膜相關的異常(choroidal membrane related disorder)、視網膜神經膠瘤病(retinal gliosis)、視網膜前膜相關的異常(epiretinal membrane related disorder)及膠質瘢痕形成(glial scar formation)。In some embodiments, ophthalmic abnormalities include, but are not limited to, choroidal neovascularization associated disease, age-related macular degeneration, compromised corneal transparency, and corneal scarring. Cornea scar formation, pterygia, anterior cataract formation, conditions related to glaucoma filtration surgery, glaucoma, and laser refractive cornea Conditions related to photorefractive keratectomy, conditions related to laser in situ keratomileusis (laser in situ keratomileusis), disorder related to contraction of the anterior retina and epiretinal membrane pre- and epiretinal membranes, proliferative vitreoretinopathy, proliferative diabetic retinopathy, diabetic macular edema, and disorder related to myopic choroidal neovascularization myopic choroidal neovascularization, retinal vain occlusion, sub-retinal fibrosis, sub-retinal scarring, choroidal membrane related disorder, retinal glioma Disease (retinal gliosis), epiretinal membrane related disorder (epiretinal membrane related disorder) and glial scar formation.

在一些實施例中，泌尿生殖系統異常包括但不限制於良性前列腺增生(benign prostate hyperplasia)、下尿道症狀(lower urinary tract symptom)、良性前列腺腫大(benign prostatic enlargement)、膀胱出口阻塞(bladder outlet obstruction)、間質性膀胱炎相關的異常(overactive bladder related disorder)、攝護腺炎(prostatitis)、前列腺上皮內瘤形成(prostatic intraepithelial neoplasia)、神經性膀胱症後群(neurogenic bladder syndrome)、前列腺癌(prostate cancer)、尿失禁(urinary incontinence)、及骨盆疼痛(pelvic pain)。In some embodiments, abnormalities in the urogenital system include but are not limited to benign prostate hyperplasia, lower urinary tract symptom, benign prostatic enlargement, bladder outlet obstruction (bladder outlet) obstruction, overactive bladder related disorder, prostatitis, prostatic intraepithelial neoplasia, neurogenic bladder syndrome, prostate Cancer (prostate cancer), urinary incontinence (urinary incontinence), and pelvic pain (pelvic pain).

在一些實施例中，主題配方包含阿西替尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes axitinib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含尼達布尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes nintedabni, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含吡非尼酮，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes pirfenidone, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含瑞司瓜特，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes Ressgut, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含索拉非尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes sorafenib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含舒尼替尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes sunitinib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含樂瓦替尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes levatinib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含瑞格菲尼，且主題配方用於治療痤瘡疤。In some embodiments, the theme formula includes rigafini, and the theme formula is used to treat acne scars.

在一些實施例中，主題配方包含普納替尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes prnatinib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含帕唑帕尼，且主題配方用於治療痤瘡疤。In some embodiments, the subject formulation includes pazopanib, and the subject formulation is used to treat acne scars.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療皮膚疤。In some embodiments, the theme formula includes nintedabni and the theme formula is used to treat skin scars.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療皮膚疤。In some embodiments, the theme formula includes Ressgut and the theme formula is used to treat skin scars.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含 舒尼替尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療皮膚疤。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat skin scars.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療皮膚疤。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat skin scars.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療皺紋。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療皺紋。In some embodiments, the theme formula includes nintedabni and the theme formula is used to treat wrinkles.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療皺紋。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療皺紋。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療皺紋。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療皺紋。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療皺紋。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療皺紋。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat wrinkles.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療皺紋。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat wrinkles.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療皺紋。In some embodiments, the theme formula includes pazopanib and the theme formula is used to treat wrinkles.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療浮肉。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat floating meat.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療浮肉。In some embodiments, the theme formula includes nintedabney and the theme formula is used to treat floating meat.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療浮肉。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat floating meat.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療浮肉。In some embodiments, the theme formula includes Ressguat and the theme formula is used to treat floating meat.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療浮肉。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat floating meat.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療浮肉。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat floating flesh.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療浮肉。In some embodiments, the theme formula includes levatinib and the theme formula is used to treat floating meat.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療浮肉。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat floating meat.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療浮肉。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat floating meat.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療浮肉。In some embodiments, the theme formula includes pazopanib and the theme formula is used to treat floating meat.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation comprises nintedabni and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes Regalfinil and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療真皮腫瘤性纖維化。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat dermal neoplastic fibrosis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療疤痕性禿髮。In some embodiments, the theme formula includes nintedabni and the theme formula is used to treat scarring alopecia.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療疤痕性禿髮。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat scarring alopecia.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療疤痕性禿髮。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat scarring alopecia.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療血管病變。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療血管病變。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療血管病變。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat vascular disease.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療脈管炎。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat vasculitis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療傷口。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療傷口。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療傷口。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat wounds.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療過剩的燒傷傷口。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat excess burn wounds.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療糖尿病足症候群。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat diabetic foot syndrome.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes nintedabney and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療硬皮症。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat scleroderma.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療關節纖維化。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat joint fibrosis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation comprises Ressguat and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes Regalfinil and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療Peyronie氏病。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat Peyronie's disease.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes Pranatinib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療Dupuytren氏攣縮。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat Dupuytren's contracture.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation contains nintedabni and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療黏連性肩關節囊炎。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat adhesive capsulitis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes Regalfinil and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療脈絡膜新生血管相關疾病。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat choroidal neovascularization related diseases.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes nintedabney and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation comprises Ressguat and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療年齡相關黃斑點退化。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat age-related macular degeneration.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation comprises nintedabni and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療角膜透明度受損。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat impaired corneal transparency.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療角膜瘢痕形成。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat corneal scarring.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療翼狀胬肉。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat pterygium.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes nintedabney and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療前部白內障形成。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat anterior cataract formation.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat glaucoma filtration surgery related abnormalities.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療與青光眼濾過手術相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat abnormalities associated with glaucoma filtration surgery.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療青光眼。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療青光眼。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療青光眼。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat glaucoma.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療青光眼。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat glaucoma.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat conditions associated with laser refractive keratectomy.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat conditions associated with laser refractive keratectomy.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat conditions related to laser refractive keratectomy.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療與雷射屈光眼角膜切除術相關的狀況。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat conditions associated with laser refractive keratectomy.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat laser in situ lamellar corneal shaping related abnormalities.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat laser in situ lamellar corneal shaping-related abnormalities.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat laser in situ lamellar corneal shaping related abnormalities.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat laser in situ lamellar corneal shaping related abnormalities.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat laser in situ lamellar corneal shaping related abnormalities.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat laser in situ lamellar corneal shaping-related abnormalities.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat laser in situ lamellar corneal shaping-related abnormalities.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat laser in situ lamellar corneal shaping related abnormalities.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat laser in situ lamellar corneal shaping-related abnormalities.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療雷射原位層狀眼角膜成塑形相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat laser in situ lamellar corneal shaping-related abnormalities.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat abnormalities related to contraction of the anterior retina and epiretinal membrane

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含普納替尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療與前視網膜及視網膜前膜收縮相關的異常In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat abnormalities related to anterior retina and epiretinal membrane contraction

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation comprises nintedabni and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療增殖性玻璃體視網膜病變。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat proliferative vitreoretinopathy.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療增生性糖尿病視網膜病變。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat proliferative diabetic retinopathy.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療糖尿病性黃斑水腫。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat diabetic macular edema.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療與近視性脈絡膜新生血管相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat abnormalities associated with myopic choroidal neovascularization.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療網膜靜脈阻塞。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat omental vein obstruction.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療視網膜下纖維增生。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat subretinal fibrosis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation comprises Ressgut and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療視網膜下瘢痕。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat subretinal scars.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療脈絡膜相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat choroidal-related abnormalities.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療視網膜神經膠瘤病。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat glioma disease.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes Resgut and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療視網膜前膜相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat epiretinal membrane-related abnormalities.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療膠質瘢痕形成。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat glial scar formation.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療良性前列腺增生。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat benign prostatic hyperplasia.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療下尿道症狀。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat lower urinary tract symptoms.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療良性前列腺腫大。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat benign prostatic enlargement.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes Pranatinib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療膀胱出口阻塞。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat bladder outlet obstruction.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat abnormalities associated with interstitial cystitis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat abnormalities associated with interstitial cystitis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat abnormalities associated with interstitial cystitis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation contains levatinib and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation contains prnatinib and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療間質性膀胱炎相關的異常。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat abnormalities related to interstitial cystitis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療攝護腺炎。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat prostatitis.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療攝護腺炎。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat prostatitis.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes Pranatinib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療前列腺上皮內瘤形成。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat prostate intraepithelial neoplasia.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation contains Regalfinil and the subject formulation is used to treat the neurogenic bladder syndrome.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療神經性膀胱症後群。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat neurogenic bladder syndrome.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes Regalfinil and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes Pranatinib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療前列腺癌。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat prostate cancer.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes Ressguat and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes rigafini and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療尿失禁。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat urinary incontinence.

在一些實施例中，主題配方包含阿西替尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes axitinib and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含尼達布尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes nintedabni and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含吡非尼酮且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes pirfenidone and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含瑞司瓜特且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes Ressgut and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含索拉非尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes sorafenib and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含舒尼替尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes sunitinib and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含樂瓦替尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes levatinib and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含瑞格菲尼且主題配方用於治療骨盆疼痛。In some embodiments, the theme formula includes rigafini and the theme formula is used to treat pelvic pain.

在一些實施例中，主題配方包含普納替尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes prnatinib and the subject formulation is used to treat pelvic pain.

在一些實施例中，主題配方包含帕唑帕尼且主題配方用於治療骨盆疼痛。In some embodiments, the subject formulation includes pazopanib and the subject formulation is used to treat pelvic pain.

表2~4為一些主題配方的非限制性實例：Tables 2~4 are some non-limiting examples of themed formulations:

表2：用於多目標抑制劑的懸浮液組合物 成分 等級 濃度 (w/w) 多目標抑制劑 n/a 1~8%或0.01~3% 懸浮劑，例如羧甲基纖維素、纖維素或纖維素的混合物 USP 0.1~10 % 或0.2~3% (例如0.5%) 濕潤劑，例如 界面活性劑 NF 0.02~5% (例如 0.05%) 緩衝液系統 USP 0.2~0.4% 氯化鈉 USP 0.4~0.6% 1N 氫氧化鈉 NF 調整pH至7.4 注射用水 USP qs Table 2: Suspension composition for multi-target inhibitors ingredient grade Concentration (w/w) Multi-target inhibitor n/a 1~8% or 0.01~3% Suspending agents, such as carboxymethyl cellulose, cellulose or a mixture of cellulose USP 0.1~10% or 0.2~3% (e.g. 0.5%) Wetting agents, such as surfactants NF 0.02~5% (e.g. 0.05%) Buffer system USP 0.2~0.4% Sodium chloride USP 0.4~0.6% 1N sodium hydroxide NF Adjust pH to 7.4 Water for Injection USP qs

表3：用於多目標抑制劑的懸浮液組合物 成分 等級 濃度 (w/w) 多目標抑制劑 n/a 0.01~3% 羧甲基纖維素，低黏度 USP 0.1~10 % 或 0.2~3% (例如 0.5%) 聚山梨醇酯80 NF 0.02~5% (例如 0.05%) 磷酸氫二鈉七水合物(Sodium phosphate dibasic heptahydrate) USP 0.27% 磷酸二氫鈉單水合物(Sodium phosphate monobasic monohydrate) USP 0.03% 氯化鈉 USP 0.5% 1N 氫氧化鈉 NF 調整pH至7.4 注射用水 USP qs Table 3: Suspension composition for multi-target inhibitors ingredient grade Concentration (w/w) Multi-target inhibitor n/a 0.01~3% Carboxymethyl cellulose, low viscosity USP 0.1~10% or 0.2~3% (e.g. 0.5%) Polysorbate 80 NF 0.02~5% (e.g. 0.05%) Sodium phosphate dibasic heptahydrate USP 0.27% Sodium phosphate monobasic monohydrate USP 0.03% Sodium chloride USP 0.5% 1N sodium hydroxide NF Adjust pH to 7.4 Water for Injection USP qs

表4：用於多目標抑制劑的懸浮液組合物 成分 等級 濃度 (w/w) 多目標抑制劑 n/a 0.01~3% 羧甲基纖維素，低黏度 USP 1% 聚山梨醇酯80 NF 0.05% 磷酸氫二鈉七水合物   USP 0.27% 磷酸二氫鈉單水合物   USP 0.03% 氯化鈉 USP 0.75% 1N 氫氧化鈉 NF 調整pH至7.4 注射用水 USP qs Table 4: Suspension composition for multi-target inhibitors ingredient grade Concentration (w/w) Multi-target inhibitor n/a 0.01~3% Carboxymethyl cellulose, low viscosity USP 1% Polysorbate 80 NF 0.05% Disodium hydrogen phosphate heptahydrate USP 0.27% Sodium dihydrogen phosphate monohydrate USP 0.03% Sodium chloride USP 0.75% 1N sodium hydroxide NF Adjust pH to 7.4 Water for Injection USP qs

表5：用於多目標抑制劑的懸浮液組合物 成分 等級 濃度 (w/w) 多目標抑制劑 n/a 0.01~10%，較佳為0.01~3% 羧甲基纖維素，低黏度 USP 1% 聚山梨醇酯80 NF 0.05% 磷酸氫二鈉七水合物   USP 0.27% 磷酸二氫鈉單水合物   USP 0.03% 氯化鈉 USP 0.75% Benzyl alcohol NF 0.5~2% (例如 0.9%) 1N 氫氧化鈉 NF 調整pH至7.4 注射用水 USP qs Table 5: Suspension composition for multi-target inhibitors ingredient grade Concentration (w/w) Multi-target inhibitor n/a 0.01~10%, preferably 0.01~3% Carboxymethyl cellulose, low viscosity USP 1% Polysorbate 80 NF 0.05% Disodium hydrogen phosphate heptahydrate USP 0.27% Sodium dihydrogen phosphate monohydrate USP 0.03% Sodium chloride USP 0.75% Benzyl alcohol NF 0.5~2% (e.g. 0.9%) 1N sodium hydroxide NF Adjust pH to 7.4 Water for Injection USP qs

實例1~3描述一些主題配方的物理測試結果Examples 1~3 describe the physical test results of some topic formulations

實例1Example 1

多目標抑制劑懸浮液：顆粒大小、pH、滲透壓及可注射性 多目標抑制劑 API 原料 PSD* 配方懸浮液( Formulated Suspension) 粒度分布 pH 滲透壓 可注射性 (Syringeability) 阿西替尼 D90: 9.9 D50: 5.5 D90: 15.6 D50: 5.8 7.6 206 通過 25G 尼達布尼 D90: 105 D50: 68 D90: 35 D50: 22 7.6 207 通過23G 吡非尼酮 D90:74 D50: 57 D90: 72 D50: 44 7.6 312 通過23G 瑞司瓜特 D90: 29 D50: 16 D90: 17 D50: 9 7.6 201 通過27G 索拉非尼半甲苯磺酸鹽 D90: 39 D50: 18 D90: 20 D50: 11 7.3 216 通過27G 舒尼替尼 D90:52 D50: 25 D90: 26 D50: 12 7.6 201 通過25G 樂瓦替尼 D90: 346 D50: 164 D90: 25 D50: 7 7.6 201 通過27G ＊PSD：粒度分布；D90為90%樣品質量小於的粒徑；D50為50%樣品質量小於的粒徑。Multi-target inhibitor suspension: particle size, pH, osmotic pressure and injectability Multi-target inhibitor API raw material PSD* Formulation suspension (Formulated Suspension) Particle size distribution pH Osmotic pressure Injectable (Syringeability) Axitinib D90: 9.9 D50: 5.5 D90: 15.6 D50: 5.8 7.6 206 Pass 25G Nidabuni D90: 105 D50: 68 D90: 35 D50: 22 7.6 207 Through 23G Pirfenidone D90:74 D50: 57 D90: 72 D50: 44 7.6 312 Through 23G Risgut D90: 29 D50: 16 D90: 17 D50: 9 7.6 201 Pass 27G Sorafenib Hemitosylate D90: 39 D50: 18 D90: 20 D50: 11 7.3 216 Pass 27G Sunitinib D90:52 D50: 25 D90: 26 D50: 12 7.6 201 Pass 25G Lovatinib D90: 346 D50: 164 D90: 25 D50: 7 7.6 201 Pass 27G *PSD: particle size distribution; D90 is the particle size smaller than 90% of the sample mass; D50 is the particle size smaller than 50% of the sample mass.

實例2Example 2

多目標抑制劑懸浮液：最終滅菌法及穩定性 多目標抑制劑 最終滅菌法 配方懸浮液 （ 標示主張(labeled claim) 的%) 之分析 起始 6 周 (40˚C/75%RH) 4 個月 (40˚C/75%RH) 阿西替尼 伽瑪照射 102.0 100.7 97.8 98.5 95.2 100.9 高壓釜 (Autoclave) 98.7 (頂部) 100.1 (底部) 未測試 101.2 (頂部)# 103.2 (底部)# 尼達布尼 伽瑪照射 101.8 103.0 98.1 99.7 90.0 97.9 高壓釜 96.0 未測試 未測試 吡非尼酮 伽瑪照射 90.9 97.2 89.9 95.7 91.5 94.9 高壓釜 未測試 未測試 未測試 瑞司瓜特 伽瑪照射 101.9 100.6 98.7 98.0 99.9 99.7 高壓釜 未測試 未測試 未測試 索拉非尼半甲苯磺酸鹽 伽瑪照射 98.9 101.6 100.7 100.4 99.9 99.6 高壓釜 未測試 未測試 未測試 舒尼替尼 伽瑪照射 96.7 95.1 98.9 96.5 100.0 95.6 高壓釜 未測試 未測試 未測試 樂瓦替尼 伽瑪照射 101.4 102.4 99.2 99.8 99.8 100.2 高壓釜 99.0 未測試 未測試 #在3個月測試而非4個月Multi-target inhibitor suspension: terminal sterilization and stability Multi-target inhibitor Terminal sterilization (% Label claim (labeled claim)) of a suspension formulation of Analysis Start 6 weeks (40˚C/75%RH) 4 months (40˚C/75%RH) Axitinib Gamma irradiation 102.0 100.7 97.8 98.5 95.2 100.9 Autoclave 98.7 (top) 100.1 (bottom) Not tested 101.2 (top) # 103.2 (bottom) # Nidabuni Gamma irradiation 101.8 103.0 98.1 99.7 90.0 97.9 Autoclave 96.0 Not tested Not tested Pirfenidone Gamma irradiation 90.9 97.2 89.9 95.7 91.5 94.9 Autoclave Not tested Not tested Not tested Risgut Gamma irradiation 101.9 100.6 98.7 98.0 99.9 99.7 Autoclave Not tested Not tested Not tested Sorafenib Hemitosylate Gamma irradiation 98.9 101.6 100.7 100.4 99.9 99.6 Autoclave Not tested Not tested Not tested Sunitinib Gamma irradiation 96.7 95.1 98.9 96.5 100.0 95.6 Autoclave Not tested Not tested Not tested Lovatinib Gamma irradiation 101.4 102.4 99.2 99.8 99.8 100.2 Autoclave 99.0 Not tested Not tested #Test in 3 months instead of 4 months

本文所描述的一些藥學組合物顯示在局部組織中遞送維持一段延長時間的治療有效濃度。基於這些活性成分的全身性半衰期和清除率，這些延長的組織曝露將是不可能的。例如，在男性中阿西替尼的最終血漿半衰期為2~5小時(Rugo et al, 2005)、尼達布尼為9.5小時(US label)、樂瓦替尼為30小時(Yamada 2011)以及瑞格菲尼為28小時(US label)。Some of the pharmaceutical compositions described herein have been shown to deliver therapeutically effective concentrations in local tissues for an extended period of time. Based on the systemic half-life and clearance rate of these active ingredients, these extended tissue exposures will be impossible. For example, in men, the final plasma half-life of axitinib is 2 to 5 hours (Rugo et al, 2005), nintedabni is 9.5 hours (US label), and levatinib is 30 hours (Yamada 2011) and Regefini is 28 hours (US label).

實例3Example 3

耐受性、療效及眼內分布將用大鼠在雷射誘導脈絡膜新生血管模式中評估。在大鼠眼睛中一次玻璃體內注射或每日三次滴眼液滴注(eyedrop instillation) 後22天，在大鼠眼睛後段中看到良好的療效及高組織濃度。Tolerability, efficacy and intraocular distribution will be evaluated in rats in the laser-induced choroidal neovascularization model. 22 days after one intravitreal injection or three times a day eyedrop instillation in the rat eye, a good therapeutic effect and high tissue concentration were seen in the posterior segment of the rat eye.

在此22天研究中，在新生血管的發展中檢驗了多目標(即多目標激酶)抑制劑尼達布尼及樂瓦替尼的局部施予之效果。載體及正對照組也包含在本研究中。雌性棕色諾威(Brown Norway)大鼠分成7個個別的處理組(treatment groups)。在第1天時，對所有動物使用520 nm 熱雷射執行雷射處理，以在每眼產生共三個損傷。在第2~21天，每日三次執行載體、1% 尼達布尼或1% 樂瓦替尼的雙側外用施予(topical administration)。在第3天，執行載體、每眼5 μg大鼠抗VEGF抗體、每眼50 μg尼達布尼或每眼50 µg樂瓦替尼的雙側玻璃體內注射。In this 22-day study, the effects of topical administration of multi-target (ie, multi-target kinase) inhibitors nindabni and levatinib were tested in the development of neovascularization. The vehicle and the positive control group are also included in this study. Female Brown Norway rats were divided into 7 individual treatment groups. On day 1, 520 nm thermal laser was used to perform laser treatment on all animals to produce a total of three injuries in each eye. On days 2 to 21, topical administration of vehicle, 1% nintedabni or 1% levatinib was administered three times a day. On day 3, perform a bilateral intravitreal injection of vehicle, 5 μg rat anti-VEGF antibody per eye, 50 μg nitaburib per eye, or 50 μg levatinib per eye.

在第22天，對所有動物執行螢光血管造影(fluorescein angiography)並使用圖像分析軟體(Image J)測定損傷大小/區域。如第1圖所示，當經由玻璃體內注射遞送時，相較於那些載體處裡的眼睛，尼達布尼及樂瓦替尼的處理顯著的降低損傷大小。此外，樂瓦替尼的玻璃體內注射相較於那些正對照組大鼠抗VEGF的處理亦顯著的降低損傷大小。On the 22nd day, fluorescein angiography was performed on all animals and image analysis software (Image J) was used to determine the size/area of the lesion. As shown in Figure 1, when delivered by intravitreal injection, the treatment of nintedabni and levatinib significantly reduced the size of the lesion compared to those in the eyes of the carrier. In addition, the intravitreal injection of levatinib also significantly reduced the damage size compared to those treated with anti-VEGF in the positive control group.

測試化合物在眼部組織及血漿中的濃度在大鼠中玻璃體內注射或滴眼液施予之後藉由LCMS-MS測量。尼達布尼及其代謝物以及樂瓦替尼的血漿濃度示於第2圖。尼達布尼及其代謝物以及樂瓦替尼的眼部濃度示於第3圖。這些結果顯示一次單一玻璃體內注射能夠在眼睛後側產生組織濃度是可相較於或更高於超過21天每日三次滴眼液的那些。滴眼液施予在如結膜(conjunctival)的眼部表面產生較玻璃體內注射高的藥物濃度。每日三次滴眼液施予較單次玻璃體內注射在血漿中維持較高的濃度。The concentration of the test compound in ocular tissues and plasma is measured by LCMS-MS after intravitreal injection or eye drops administration in rats. The plasma concentrations of nintedabni and its metabolites and levatinib are shown in Figure 2. The ocular concentrations of nintedabni and its metabolites and levatinib are shown in Figure 3. These results show that a single intravitreal injection can produce tissue concentrations on the back of the eye that are comparable to or higher than those of three eye drops daily for more than 21 days. Eye drops administered to the surface of the eye, such as conjunctival, produce a higher drug concentration than intravitreal injection. Three times daily administration of eye drops maintains a higher concentration in plasma than a single intravitreal injection.

研究結果證實尼達布尼及樂瓦替尼的單次玻璃體內注射或每日三次眼部滴注超過20天能夠抑制脈絡膜新生血管的效果，並在眼部組織中維持治療有效濃度。The results of the study confirmed that a single intravitreal injection of nintedabni and levatinib or three ocular instillations daily for more than 20 days can inhibit the effect of choroidal neovascularization and maintain a therapeutically effective concentration in the ocular tissues.

實例4Example 4

此研究評估尼達布尼及樂瓦替尼在眼睛後段超過42天的耐受性及配方的分散性。對荷蘭黑帶兔(Dutch Belted rabbit)施予1%懸浮液的單一50 µL 玻璃體給藥。在研究期間定期進行臨床、崔氏(Draize)及眼科檢查以及眼底成像(fundus imaging)。對所有動物執行劑量後及緊接著最終時間點前的視網膜電描記術(Electroretinography，ERG)。This study evaluated the tolerability of nintedabni and levatinib in the posterior segment of the eye over 42 days and the dispersion of the formulation. A single 50 µL vitreous administration of 1% suspension was administered to Dutch Belted rabbits. Regular clinical, Draize and ophthalmological examinations and fundus imaging were performed during the study period. Electroretinography (ERG) was performed on all animals after the dose and immediately before the final time point.

在ERG中沒有顯著的配方相關的副作用(例如眼部刺激、眼壓變化)及不良反應。There are no significant formula-related side effects (such as eye irritation, changes in intraocular pressure) and adverse reactions in ERG.

經尼達布尼及樂瓦替尼懸浮液處理的眼睛之眼底成像指出單次玻璃體內注射在給藥的當天內導致中間玻璃體具有大的球狀蓄積(globular depot)。注射後的2天內，觀察到球團(bolus)萎縮且在一些情況下在中間玻璃體內如條紋出現。該蓄積及條紋的大小隨時間持續減小，但在給藥後到第42天維持存在(第4及5圖)。Fundus imaging of eyes treated with nindabuni and levatinib suspension indicated that a single intravitreal injection resulted in a large globular depot in the middle vitreous within the day of administration. Within 2 days after the injection, atrophy of the bolus was observed and in some cases appeared as stripes in the intermediate vitreous. The size of the accumulation and streaks continued to decrease over time, but remained there until the 42nd day after administration (Figures 4 and 5).

對於尼達布尼，在給藥後第29天及42天的視網膜及脈絡膜中的組織濃度維持非常高，高於1 μg/gm。眼睛前段的組織(即虹膜睫狀體及水狀液(aqueous humor))具有較後組織(即玻璃體、視網膜及脈絡膜)低得多的尼達布尼濃度。在結膜組織(conjunctival tissue)中的濃度大多在檢測極限下。在第42天大約4~7%的玻璃體劑量維持在玻璃體中。尼達布尼的全身性血漿濃度在數天內相對穩定，即在第29天及第42天分別為0.252 (0.286)及0.348 (0.235) ng/mL。For nintedabni, the tissue concentration in the retina and choroid on the 29th and 42nd days after administration remained very high, higher than 1 μg/gm. The tissues of the anterior segment of the eye (i.e., iris ciliary body and aqueous humor) have a much lower concentration of nintedabni than the posterior tissues (i.e. vitreous body, retina, and choroid). The concentration in conjunctival tissue is mostly below the detection limit. About 4 to 7% of the vitreous dose is maintained in the vitreous on day 42. The systemic plasma concentration of nintedabni was relatively stable within a few days, namely 0.252 (0.286) and 0.348 (0.235) ng/mL on day 29 and day 42, respectively.

對於樂瓦替尼，在給藥後第29天及42天的視網膜及脈絡膜中的組織濃度維持非常高，大約高於1 μg/gm。水狀液具有較在後組織的那些(即玻璃體、視網膜及脈絡膜)低得多的濃度。在第29及42天大約9~17%及3~9%的玻璃體劑量維持在玻璃體中。樂瓦替尼的全身性血漿濃度在數天內相對穩定，即在第29天及第42天分別為4.94及3.91 ng/mL。For levatinib, the tissue concentration in the retina and choroid remained very high on the 29th and 42nd days after administration, approximately higher than 1 μg/gm. The aqueous fluid has a much lower concentration than those of the posterior tissues (i.e. vitreous, retina, and choroid). Approximately 9-17% and 3-9% of the vitreous dose was maintained in the vitreous on days 29 and 42. The systemic plasma concentration of lovatinib was relatively stable within a few days, that is, 4.94 and 3.91 ng/mL on day 29 and day 42 respectively.

實例5Example 5

此研究評定當藉由在眼睛中每日三次局部眼部滴注施予超過10天時阿西替尼、尼達布尼、吡非尼酮、瑞司瓜特、索拉非尼及樂瓦替尼 (0.3% w/w)的局部耐受性及眼部分布。每一處理組使用5至7隻雄性紐西蘭白兔(New Zealand White Rabbits)。每眼每日三次持續10天接受到35µL的載體或各藥物(0.3%)的滴眼液。在第11天的最後劑量後犧牲動物，並將眼睛摘除以及收集血漿及眼部組織。藉由LC-MS/MS測量這些化合物的組織及血漿濃度。This study assessed that when axitinib, nindabuni, pirfenidone, risguate, sorafenib, and levat were administered by topical ocular instillation three times a day in the eye for more than 10 days The local tolerability of tinib (0.3% w/w) and the distribution of the eye. Each treatment group uses 5 to 7 male New Zealand White Rabbits. Each eye received 35μL of vehicle or each drug (0.3%) eye drops three times a day for 10 days. The animals were sacrificed after the last dose on day 11, the eyes were removed and plasma and ocular tissues were collected. The tissue and plasma concentrations of these compounds were measured by LC-MS/MS.

這些化合物在各組織中的眼部組織濃度示於第6至8圖。0.3% w/w的各藥物的局部滴注遞送高藥物濃度至結膜及角膜的前組織，且在兔子的脈絡膜及視網膜中有顯著的濃度。當在眼睛中維持此程度的藥物曝露，觀察到非常輕微或中等的結膜阻塞及腫脹。在10天觀察期的整個過程中這些阻塞及腫脹的程度於各組之間係非常相似(包括載體對照組)。The ocular tissue concentrations of these compounds in each tissue are shown in Figures 6 to 8. The local infusion of each drug of 0.3% w/w delivers high drug concentration to the anterior tissues of the conjunctiva and cornea, and there is a significant concentration in the choroid and retina of rabbits. When this degree of drug exposure is maintained in the eye, very slight or moderate conjunctival obstruction and swelling are observed. The degree of these obstruction and swelling during the entire 10-day observation period was very similar between the groups (including the vehicle control group).

在第11天阿西替尼及尼達布尼的血漿濃度平均值(±SD)係低於檢測極限，以及尼達布尼的代謝物為1.09 (±0.14) ng/mL，以及樂瓦替尼為98.5 (±11) ng/mL。On the 11th day, the average plasma concentration (±SD) of axitinib and nindabuni was below the detection limit, and the metabolite of nindabuni was 1.09 (±0.14) ng/mL, and lovati Ni is 98.5 (±11) ng/mL.

研究結果指出以0.3% w/w每日三次局部滴注各藥物持續10天可達到在眼部組織中的治療有效濃度，且具有在眼睛中良好的局部耐受性及安全性的低血漿濃度。The results of the study indicate that the local instillation of each drug at 0.3% w/w three times a day for 10 days can achieve the therapeutically effective concentration in the ocular tissue, and has a low plasma concentration with good local tolerance in the eye and safety .

實例6Example 6

此研究評估當藉由在紐西蘭白兔(每組n=6)的眼睛中局部眼部滴注施予時，載體、阿西替尼、吡非尼酮、索拉非尼及樂瓦替尼的局部耐受性以及阿西替尼、索拉非尼及樂瓦替尼 (0.3% w/w)的眼部分布。每右眼每日三次持續5天接受到35µL的載體或各藥物(0.3% w/w)的滴眼液。在給藥第5天犧牲動物，並將眼睛摘除。藉由LC-MS/MS測量選定化合物的眼部及血漿濃度。This study evaluated the vehicle, Axitinib, Pirfenidone, Sorafenib and Leva when administered by local ocular infusion in the eyes of New Zealand white rabbits (n=6 per group) The local tolerability of tinib and the ocular distribution of axitinib, sorafenib and levatinib (0.3% w/w). Each right eye received 35 µL of vehicle or each drug (0.3% w/w) eye drops three times a day for 5 days. The animals were sacrificed on the 5th day of administration and the eyes were removed. The eye and plasma concentrations of the selected compound were measured by LC-MS/MS.

這些研究組別中的動物在研究的整個過程中呈現正常的體重增加。右眼的眼部檢驗並沒有顯示明顯的發現。在研究期間所有組別的所有動物的平均總體檢驗分數接近於基線值。使用Tonovet探針測量眼壓(IOP)。得到6個連續的測量值並記錄示於顯示器上的平均IOP。在實驗期間所有組別中右眼的IOPs維持接近略高於基線。The animals in these study groups showed normal weight gain throughout the study. Eye examination of the right eye did not show obvious findings. The average overall test score of all animals in all groups during the study period was close to the baseline value. Tonovet probe is used to measure intraocular pressure (IOP). Obtain 6 consecutive measurements and record the average IOP shown on the display. During the experiment, the IOPs of the right eye in all groups remained close to slightly higher than the baseline.

這些藥物的眼部組織濃度列於第9至11圖。0.3% w/w阿西替尼、索拉非尼及樂瓦替尼的局部滴注遞送高藥物濃度至結膜、鞏膜(sclera)及角膜的前組織，且在兔子的脈絡膜及視網膜中有顯著的濃度。The eye tissue concentrations of these drugs are listed in Figures 9-11. The local infusion of 0.3% w/w axitinib, sorafenib, and levatinib delivers high drug concentrations to the conjunctiva, sclera and anterior tissues of the cornea, and is significant in the choroid and retina of rabbits concentration.

在投藥的第5天阿西替尼、索拉非尼及樂瓦替尼劑量的血漿濃度平均值(±SD)係為0.29 (0.15)、5.09 (±1.27) ng/mL及131 (±24) ng/mL。The mean plasma concentrations (±SD) of the doses of axitinib, sorafenib, and levatinib on the 5th day of administration were 0.29 (0.15), 5.09 (±1.27) ng/mL and 131 (±24 ) ng/mL.

上述實例顯示本文鑑定的化合物之眼科應用可達到產生治療效果的足夠濃度，同時維持良好的眼部耐受性及安全性。The above examples show that the ophthalmic application of the compounds identified herein can achieve a sufficient concentration to produce a therapeutic effect, while maintaining good ocular tolerance and safety.

實例7Example 7

探討阿西替尼及尼達布尼在單一皮內注射0.1%及1%懸浮液至尤卡坦小型豬(Yucatan minipigs)背部後的藥物動力學。每個注射的劑量體劑為0.1 mL。使用LCMS/MS法測量超過28天在注射位置及在遠離注射位置2cm的表皮及真皮中的藥物濃度。To investigate the pharmacokinetics of axitinib and nindabuni after a single intradermal injection of 0.1% and 1% suspension into the back of Yucatan minipigs. The body dose per injection is 0.1 mL. The LCMS/MS method was used to measure the drug concentration at the injection site and in the epidermis and dermis 2 cm away from the injection site over 28 days.

對於阿西替尼及尼達布尼，在注射後超過28天於皮膚表皮及真皮中具有顯著的藥物濃度。這些濃度在0.1%及1%的劑量之間具有劑量依賴性(dose dependent)。在注射位置的藥物濃度顯著高於遠離注射位置2cm的那些，指出局部皮內注射即形成藥物蓄積(drug depot)，並從注射位置隨時間延長藥物擴散。For axitinib and nindabuni, there are significant drug concentrations in the skin epidermis and dermis more than 28 days after injection. These concentrations are dose dependent between the 0.1% and 1% doses. The drug concentration at the injection site is significantly higher than those at 2 cm away from the injection site, indicating that local intradermal injection forms a drug depot and prolongs the drug diffusion from the injection site over time.

在收集自遠離注射位置2cm的皮膚樣品中，0.1%及1% 皮內注射後超過28天的平均阿西替尼濃度的範圍在表皮中為4.5~55.2及42.3~723 ng/gm以及在真皮中為1.2~8及2.9~150 ng/gm。In the skin samples collected 2cm away from the injection site, 0.1% and 1% of the average axitinib concentration over 28 days after intradermal injection ranged from 4.5 to 55.2 and 42.3 to 723 ng/gm in the epidermis and in the dermis. The medium is 1.2~8 and 2.9~150 ng/gm.

在收集自遠離注射位置2cm的皮膚樣品中，0.1%及1% 皮內注射後超過28天的平均尼達布尼濃度的範圍在表皮中為2.3~26.3及11.6~687 ng/gm以及在真皮中為0.5~5及1.8~40.3 ng/gm。In the skin samples collected 2cm away from the injection site, the range of 0.1% and 1% of the average nintedabni concentration over 28 days after intradermal injection was 2.3~26.3 and 11.6~687 ng/gm in the epidermis and in the dermis. The medium is 0.5~5 and 1.8~40.3 ng/gm.

總的來說，阿西替尼或尼達布尼的0.1%或1% 懸浮液之單一皮內注射能夠在注射的位置達到顯著的藥物蓄積。每種藥物將從此局部蓄積向外擴散至鄰近的皮膚區域，並在28天整個期間中維持顯著高的且治療上有意義的濃度。In general, a single intradermal injection of 0.1% or 1% suspension of axitinib or nindabuni can achieve significant drug accumulation at the injection site. Each drug will accumulate locally and diffuse outward to adjacent skin areas, and maintain a significantly high and therapeutically meaningful concentration throughout the 28-day period.

實例8Example 8

此研究評定在Wistar大鼠(每個處理組n=6~7)中前列腺內注射後阿西替尼、索拉非尼、吡非尼酮及瑞司瓜特的藥物動力學及分布。在此42天的研究中，阿西替尼、索拉非尼及瑞司瓜特以1% w/w 懸浮液，以及吡非尼酮以2.5% 懸浮液在第15天及第29天以單次前列腺內注射(總體積0.2 mL)施予。使用LCMS/MS法測量在血漿及前列腺中的測試化合物之濃度並示於表5及表6中。This study evaluated the pharmacokinetics and distribution of axitinib, sorafenib, pirfenidone, and risguat after intraprostatic injection in Wistar rats (n=6-7 in each treatment group). In this 42-day study, axitinib, sorafenib, and risguat were used in a 1% w/w suspension, and pirfenidone was used in a 2.5% suspension on the 15th and 29th days. A single intraprostatic injection (total volume 0.2 mL) was administered. The LCMS/MS method was used to measure the concentration of the test compound in plasma and prostate and shown in Table 5 and Table 6.

表5 ：在大鼠中前列腺內注射後的血漿濃度(ng/mL) 處理 研究天 時間 平均值 SEM 阿西替尼 15 24h 1.72 0.23 29 24h 1.49 0.16 42 0h 0.33 0.03 索拉非尼 15 24h 84.3 8.74 29 24h 83.1 10.82 42 0h 20.4 2.29 吡非尼酮 15 24h 0.381 0.09 29 24h 0.454 0.13 42 0h BLQ NA 瑞司瓜特 15 24h 3.25 0.38 29 24h 4.89 0.36 42 0h 2.26 0.27 Table 5: Plasma concentration (ng/mL) after intraprostatic injection in rats deal with Research day time average value SEM Axitinib 15 24h 1.72 0.23 29 24h 1.49 0.16 42 0h 0.33 0.03 Sorafenib 15 24h 84.3 8.74 29 24h 83.1 10.82 42 0h 20.4 2.29 Pirfenidone 15 24h 0.381 0.09 29 24h 0.454 0.13 42 0h BLQ NA Risgut 15 24h 3.25 0.38 29 24h 4.89 0.36 42 0h 2.26 0.27

表6：在大鼠中前列腺內注射後的前列腺濃度(µg/gm) 處理 平均值 SEM 阿西替尼 718 287 索拉非尼 892 255 吡非尼酮 0.014 0.004 瑞司瓜特 492 286 Table 6: Prostate concentration (µg/gm) after intraprostatic injection in rats deal with average value SEM Axitinib 718 287 Sorafenib 892 255 Pirfenidone 0.014 0.004 Risgut 492 286

研究結果指出，在阿西替尼、瑞司瓜特及索拉非尼的單一前列腺內注射後，從前列腺至全身循環中有延長的藥物釋放。在第二次每兩周一次的阿西替尼、瑞司瓜特及索拉非尼之前列腺內注射後兩周，在前列腺中的藥物濃度維持高的。The results of the study indicated that after a single intra-prostatic injection of Axitinib, Resguate, and Sorafenib, there was a prolonged drug release from the prostate to the systemic circulation. Two weeks after the second intra-prostatic injection of Acitinib, Resguat, and Sorafenib once every two weeks, the drug concentration in the prostate remained high.

實例9Example 9

此研究探討在Wistar大鼠(每個處理組n=5~7)中前列腺內注射後尼達布尼、舒尼替尼及樂瓦替尼的藥物動力學及分布。在此32天的研究中，每個化合物以1% w/w 懸浮液在第1天及第18天以單次前列腺內注射(總體積0.4 mL)施予。使用LCMS/MS法測量在血漿及前列腺中的測試化合物之濃度並示於表12至表15中。This study explored the pharmacokinetics and distribution of ninababinib, sunitinib and levatinib after intraprostatic injection in Wistar rats (n=5-7 in each treatment group). In this 32-day study, each compound was administered in a 1% w/w suspension as a single intraprostatic injection (total volume 0.4 mL) on day 1 and day 18. The LCMS/MS method was used to measure the concentration of the test compound in plasma and prostate and are shown in Table 12 to Table 15.

研究結果證實在前列腺的背外側及腹葉中有顯著的藥物濃度。在第32天，約在第二次前列腺內注射後兩周，在前列腺中維持顯著含量的測試化合物，指出藥物滯留的延長。各藥物的血漿濃度較其前列腺濃度低得多，主要是由於藥物從前列腺蓄積緩慢擴散至全身循環。The results of the study confirmed that there are significant drug concentrations in the dorsolateral and ventral lobes of the prostate. On day 32, approximately two weeks after the second intra-prostatic injection, a significant amount of the test compound was maintained in the prostate, indicating prolonged drug retention. The plasma concentration of each drug is much lower than its prostate concentration, mainly due to the slow diffusion of the drug from the prostate to the systemic circulation.

實例10Example 10

此研究的目的為評估當經由皮內注射施予阿西替尼、尼達布尼、索拉非尼及樂瓦替尼至迷你豬沿線性切口的背部皮膚時的懸浮液配方。The purpose of this study was to evaluate the formulation of the suspension when axitinib, nindabuni, sorafenib and levatinib were administered via intradermal injection to the back skin of mini-pigs along a linear incision.

對4隻雄性迷你豬給藥。每隻動物經由沿著10個傷口的每一個的邊緣皮內注射給藥一次(背部的各側5個傷口[垂直於脊柱]，離脊柱大約3公分長及3公分寬)。對於每個傷口位置總體積為0.8 mL，圍繞各傷口位置經由8次0.1 mL 皮內注射 (在傷口的兩側以一次注射/公分)施予阿西替尼、尼達布尼、樂瓦替尼及載體對照組物質(vehicle control article)。每個傷口位置總體積為1.6 mL，經由相同的方法以每次注射0.2 mL的體積施予索拉非尼。載體控制物質為用於測試物質阿西替尼、尼達布尼、樂瓦替尼及索拉非尼的載體。The drug was administered to 4 male mini pigs. Each animal was given an intradermal injection along the edges of each of the 10 wounds (5 wounds on each side of the back [perpendicular to the spine], approximately 3 cm long and 3 cm wide from the spine). For each wound position, the total volume is 0.8 mL. Axitinib, Nidabuni, and Lovati are administered through 8 times of 0.1 mL intradermal injections (one injection/cm on both sides of the wound) around each wound position. Nepal and carrier control substances (vehicle control article). The total volume of each wound site was 1.6 mL, and sorafenib was administered by the same method in a volume of 0.2 mL per injection. The carrier control substance is the carrier used for the test substances axitinib, nindabuni, levatinib and sorafenib.

以顯微鏡評估發炎的廣義測量，其包括炎性細胞浸潤(inflammatory cell infiltrate)、纖維蛋白沉澱(fibrin deposition)、纖維增生(fibroplasia)、表皮增生(epithelial hyperplasia)及組織壞死(tissue necrosis)的區域。在對照組傷口位置的發炎嚴重性隨著時間為輕微至中等(傷後第4、7、9及29天)。所有測試試劑處理的傷口在第4天時評級為輕微，且相較於對照組隨時間沒有一致差異(consistent difference)。Microscopic evaluation of inflammation is a broad measure that includes areas of inflammatory cell infiltrate, fibrin deposition, fibroplasia, epidermal hyperplasia, and tissue necrosis. The severity of inflammation at the wound site in the control group was mild to moderate over time (days 4, 7, 9 and 29 after injury). All wounds treated with test reagents were graded as mild on day 4, and there was no consistent difference over time compared to the control group.

結果總結於第16圖中。超過29天在顯微鏡下，載體處理的傷口位置示出輕微至中等的發炎、中等至無的真皮暫時性基模(provisional matrix)、極小至輕微的真皮纖維增生、明顯至極小的皮下組織纖維增生、輕微至明顯的皮下組織混合細胞浸潤、極小至無的表皮增生、極小至無的真皮纖維蛋白、及中等至極小的SMA染色。阿西替尼示出輕微至中等的發炎、明顯至中等的真皮暫時性基模、無至輕微的真皮纖維增生、無至中等的皮下組織纖維增生、中等至極小的皮下組織混合細胞浸潤、極小至輕微的表皮增生、輕微至中等的真皮纖維蛋白及極小至中等的SMA染色。尼達布尼示出輕微至中等的發炎、明顯的真皮暫時性基模、無至輕微的真皮纖維增生、無至中等的皮下組織纖維增生、輕微至明顯的皮下組織混合細胞浸潤、極小至中等的表皮增生、輕微至中等的真皮纖維蛋白及無至中等的SMA染色。索拉非尼示出中等至極小的發炎、輕微至無的真皮暫時性基模、極小至輕微的真皮纖維增生、極小至中等的皮下組織纖維增生、輕微至明顯的皮下組織混合細胞浸潤、無表皮增生、極小至無的真皮纖維蛋白及輕微至極小的SMA染色。樂瓦替尼示出輕微至明顯的發炎、明顯至極小的真皮暫時性基模、極小至輕微的真皮纖維增生、中等至極小的皮下組織纖維增生、輕微至嚴重的皮下組織混合細胞浸潤、輕微至無的表皮增生、極小至輕微的真皮纖維蛋白及輕微的SMA染色。The results are summarized in Figure 16. Under the microscope for more than 29 days, the position of the wound treated with the carrier showed mild to moderate inflammation, moderate to no temporary provisional matrix of the dermis, minimal to slight dermal fiber proliferation, and obvious to minimal subcutaneous tissue fiber proliferation. , Slight to obvious mixed cell infiltration of subcutaneous tissue, minimal to no epidermal hyperplasia, minimal to no dermal fibrin, and moderate to minimal SMA staining. Axitinib shows mild to moderate inflammation, obvious to moderate temporary dermal matrix, no to slight dermal fibrosis, no to moderate subcutaneous tissue fibrous hyperplasia, moderate to very small subcutaneous tissue mixed cell infiltration, very small To slight epidermal hyperplasia, slight to moderate dermal fibrin and very small to moderate SMA staining. Nidabni shows mild to moderate inflammation, obvious temporary dermal matrix, no to slight dermal fibrosis, no to moderate subcutaneous tissue fibrous hyperplasia, mild to obvious subcutaneous tissue mixed cell infiltration, minimal to moderate Epidermal hyperplasia, mild to moderate dermal fibrin and no to moderate SMA staining. Sorafenib showed moderate to minimal inflammation, mild to no temporary dermal matrix, minimal to slight dermal fibrosis, minimal to moderate subcutaneous tissue fibrous hyperplasia, slight to obvious subcutaneous tissue mixed cell infiltration, no Epidermal hyperplasia, minimal to no dermal fibrin, and slight to minimal SMA staining. Levatinib showed mild to obvious inflammation, obvious to very small temporary dermal matrix, very small to slight dermal fibrosis, moderate to very small subcutaneous tissue fibrous hyperplasia, mild to severe subcutaneous tissue mixed cell infiltration, slight To none of the epidermal hyperplasia, minimal to slight dermal fibrin and slight SMA staining.

綜上所述，這些結果建議經阿西替尼(2% 懸浮液)、尼達布尼(2% 懸浮液)、索拉非尼(1% 懸浮液)及樂瓦替尼(2% 懸浮液)處理的傷口相較於載體處理控制組傷口展現肉芽組織形成的延滯以及肌纖維母細胞的延長存在。懸浮液配方能夠在一段長的期間(例如至少一個月)維持顯著高的且治療上有意義的濃度。In summary, these results suggest that axitinib (2% suspension), nindabuni (2% suspension), sorafenib (1% suspension) and levatinib (2% suspension) Compared with the wounds in the vehicle-treated control group, the wounds treated with liquid) showed delayed granulation tissue formation and extended presence of myofibroblasts. The suspension formulation can maintain a significantly high and therapeutically meaningful concentration for a long period of time (for example, at least one month).

雖然以有限數量的實例說明一些實施例，所屬技術領域具有通常知識者應理解的是在不脫離本發明的範圍的情況下可能存在其他修飾及變化。因此，所保護的範圍不應限制於任何特定的實例或實施例。Although some embodiments are illustrated with a limited number of examples, those skilled in the art should understand that there may be other modifications and changes without departing from the scope of the present invention. Therefore, the scope of protection should not be limited to any specific example or embodiment.

無no

第1圖繪示在大鼠脈絡膜新生血管模式中新生血管性損傷的降低，其中VH=載體對照組，NTDH=尼達布尼，LVTN=樂瓦替尼。Figure 1 shows the reduction of neovascular injury in the rat choroidal neovascularization model, where VH=vehicle control group, NTDH=nitaburi, and LVTN=levatinib.

第2圖繪示尼達布尼及其代謝物及樂瓦替尼的血漿濃度(ng/mL)(平均值 +/- SEM，n=6)。Figure 2 shows the plasma concentration (ng/mL) of nindabni and its metabolites and levatinib (mean +/- SEM, n=6).

第3A圖繪示在兩眼中一次單一玻璃體內注射(intravitreal injection)尼達布尼後第二天(IVT)尼達布尼及其代謝物在眼部組織中的濃度(ng/mL或ng/gm)。Figure 3A shows the concentration of nintedabni and its metabolites in ocular tissues (ng/mL or ng/i) on the second day (IVT) after a single intravitreal injection (intravitreal injection) in both eyes. gm).

第3B圖繪示在第3~21天每日三次10 µl 1% 尼達布尼的滴眼液後尼達布尼及其代謝物在眼部組織中的濃度(ng/mL或ng/gm)。Figure 3B shows the concentration (ng/mL or ng/gm) of nintedabni and its metabolites in the eye tissue after 10 µl 1% nintedabnid eye drops three times a day from day 3 to 21 ).

第3C圖繪示在兩眼中一次單一玻璃體內注射樂瓦替尼後第二天(IVT)樂瓦替尼在眼部組織中的濃度(ng/mL或ng/gm)。Figure 3C shows the concentration (ng/mL or ng/gm) of lovatinib in the ocular tissue on the second day (IVT) after a single intravitreal injection of lovatinib in both eyes.

第3D圖繪示在第3~21天每日三次10 µl 1% 樂瓦替尼的滴眼液後樂瓦替尼及其代謝物在眼部組織中的濃度(ng/mL或ng/gm)。Figure 3D shows the concentration of levatinib and its metabolites in eye tissues (ng/mL or ng/gm) after 10 µl 1% levatinib eye drops three times a day from day 3 to 21 ).

第4圖繪示在單一玻璃體內注射尼達布尼懸浮液後兔眼睛的代表影像。Figure 4 shows a representative image of a rabbit eye after nintedabni suspension was injected into a single intravitreal.

第5圖繪示在單一玻璃體內注射樂瓦替尼懸浮液後兔眼睛的代表影像。Figure 5 shows a representative image of rabbit eyes after intravitreal injection of levatinib suspension.

第6圖繪示在兔子的眼部組織中阿西替尼的平均濃度(ng/gm)。Figure 6 shows the average concentration (ng/gm) of axitinib in the eye tissues of rabbits.

第7圖繪示在兔子的眼部組織中尼達布尼及其代謝物的平均濃度(ng/gm)。Figure 7 shows the average concentration (ng/gm) of nintedabni and its metabolites in the eye tissues of rabbits.

第8圖繪示在兔子的眼部組織中樂瓦替尼的平均濃度(ng/gm)。Figure 8 shows the average concentration (ng/gm) of levatinib in the eye tissues of rabbits.

第9圖繪示在兔子的眼部組織中阿西替尼的平均濃度(ng/gm)。Figure 9 shows the average concentration (ng/gm) of Axitinib in the eye tissue of rabbits.

第10圖繪示在兔子的眼部組織中索拉非尼的平均濃度(ng/gm)。Figure 10 shows the average concentration of sorafenib (ng/gm) in the eye tissues of rabbits.

第11圖繪示在兔子的眼部組織中樂瓦替尼的平均濃度(ng/gm)。Figure 11 shows the average concentration (ng/gm) of levatinib in the eye tissues of rabbits.

第12圖繪示在大鼠中前列腺內注射後尼達布尼及其代謝物的血漿濃度(ng/mL)。Figure 12 shows the plasma concentration (ng/mL) of nintedabni and its metabolites after intraprostatic injection in rats.

第13圖繪示在大鼠中前列腺內注射後樂瓦替尼的血漿濃度(ng/mL)。Figure 13 shows the plasma concentration (ng/mL) of lovatinib after intraprostatic injection in rats.

第14圖繪示在大鼠中前列腺內注射後尼達布尼及其代謝物在背外側(dorsolateral)及腹葉(ventral lobe)中的濃度(μg/gm)。Figure 14 shows the concentration (μg/gm) of nintedabni and its metabolites in the dorsolateral and ventral lobe after intraprostatic injection in rats.

第15圖繪示在大鼠中前列腺內注射後樂瓦替尼在背外側及腹葉中的濃度(μg/gm)。Figure 15 shows the concentration (μg/gm) of levatinib in the dorsolateral and ventral lobes after intraprostatic injection in rats.

第16圖繪示在以阿西替尼、尼達布尼、索拉非尼、樂瓦替尼及載體處理的染色傷口中的纖維增生(真皮及皮下組織)、真皮纖維蛋白(dermis fibrin)及α平滑肌肌動蛋白(alpha sma)的組織學評估之總結。Figure 16 shows fibrosis (dermis fibrin) and dermal fibrin (dermis fibrin) in stained wounds treated with axitinib, nindabuni, sorafenib, levatinib and vehicle And a summary of histological evaluation of alpha smooth muscle actin (alpha sma).

Claims (20)

一種藥學組合物，其包含： 包含藥學上可接受的載體及至少一種多目標抑制劑的水性懸浮液。A pharmaceutical composition comprising: An aqueous suspension comprising a pharmaceutically acceptable carrier and at least one multi-target inhibitor. 如申請專利範圍第1項所述之藥學組合物，其中該藥學上可接受的載體包含懸浮劑。The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable carrier comprises a suspending agent. 如申請專利範圍第2項所述之藥學組合物，其中該懸浮劑為羧甲基纖維素、纖維素或多種纖維素的混合物。The pharmaceutical composition according to item 2 of the scope of patent application, wherein the suspending agent is carboxymethyl cellulose, cellulose or a mixture of multiple celluloses. 如申請專利範圍第1項、第2項或第3項所述之藥學組合物，其中該藥學上可接受的載體包含濕潤劑。The pharmaceutical composition according to item 1, item 2 or item 3 of the scope of patent application, wherein the pharmaceutically acceptable carrier comprises a wetting agent. 如申請專利範圍第1項、第2項、第3項或第4項所述之藥學組合物，其中該藥學上可接受的載體包含緩衝系統。The pharmaceutical composition according to item 1, item 2, item 3 or item 4 of the scope of the patent application, wherein the pharmaceutically acceptable carrier comprises a buffer system. 如申請專利範圍第1項、第2項、第3項、第4項或第5項所述之藥學組合物，其中該藥學上可接受的載體包含滲透劑。The pharmaceutical composition according to item 1, item 2, item 3, item 4 or item 5 of the scope of the patent application, wherein the pharmaceutically acceptable carrier comprises a penetrant. 如申請專利範圍第1項、第2項、第3項、第4項、第5項或第6項所述之藥學組合物，其中該多目標抑制劑為該組合物之總重量的約0.01%至約20%。The pharmaceutical composition described in item 1, item 2, item 3, item 4, item 5 or item 6 of the scope of patent application, wherein the multi-target inhibitor is about 0.01 of the total weight of the composition % To about 20%. 如申請專利範圍第7項所述之藥學組合物，其中該多目標抑制劑為該組合物之總重量的約0.01%至約8%。The pharmaceutical composition according to claim 7, wherein the multi-target inhibitor is about 0.01% to about 8% of the total weight of the composition. 如申請專利範圍第8項所述之藥學組合物，其中該多目標抑制劑為該組合物之總重量的約0.01%至約10%。The pharmaceutical composition according to claim 8, wherein the multi-target inhibitor is about 0.01% to about 10% of the total weight of the composition. 如申請專利範圍第1項、第2項、第3項、第4項、第5項、第6項、第7項、第8項或第9項所述之藥學組合物，其中該組合物為可注射的。Such as the pharmaceutical composition described in item 1, item 2, item 3, item 4, item 5, item 6, item 7, item 8 or item 9 of the scope of patent application, wherein the composition It is injectable. 如申請專利範圍第1項、第2項、第3項、第4項、第5項、第6項、第7項、第8項、第9項或第10項所述之藥學組合物，其中該多目標抑制劑包含阿西替尼(axitinib)、尼達布尼(nintedanib)、吡非尼酮(pirfenidone)、瑞司瓜特(riociguat)、索拉非尼(sorafenib)、舒尼替尼(sunitinib)、樂瓦替尼(lenvatinib)、瑞格菲尼(regorafenib)、普納替尼(ponatinib)、帕唑帕尼(pazopanib)或其組合物。Such as the pharmaceutical composition described in item 1, item 2, item 3, item 4, item 5, item 6, item 7, item 8, item 9 or item 10 of the scope of patent application, Among them, the multi-target inhibitor includes axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitin Sunitinib, lenvatinib, regorafenib, ponatinib, pazopanib, or a combination thereof. 如申請專利範圍第11項所述之藥學組合物，其中該多目標抑制劑為尼達布尼。The pharmaceutical composition according to claim 11, wherein the multi-target inhibitor is nintedabni. 如申請專利範圍第11項所述之藥學組合物，其中該多目標抑制劑為樂瓦替尼。The pharmaceutical composition according to claim 11, wherein the multi-target inhibitor is levatinib. 如申請專利範圍第11項所述之藥學組合物，其中該多目標抑制劑為阿西替尼。The pharmaceutical composition according to claim 11, wherein the multi-target inhibitor is axitinib. 如申請專利範圍第11項所述之藥學組合物，其中該多目標抑制劑為舒尼替尼。The pharmaceutical composition according to claim 11, wherein the multi-target inhibitor is sunitinib. 如申請專利範圍第11項所述之藥學組合物，其中該多目標抑制劑為瑞格菲尼。The pharmaceutical composition according to claim 11, wherein the multi-target inhibitor is Regefinil. 一種治療皮膚異常、眼科異常或泌尿生殖系統異常的方法，其包含：施予有效劑量的如申請專利範圍第1、2、3、4、5、6、7、8、9、10、11、12、13、14、15或16項所述的藥學組合物，以治療患有皮膚異常、眼科異常或泌尿生殖系統異常的主體。A method for treating skin abnormalities, ophthalmological abnormalities or urogenital system abnormalities, comprising: administering an effective dose of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, The pharmaceutical composition according to item 12, 13, 14, 15 or 16, for treating subjects suffering from skin abnormalities, ophthalmological abnormalities or abnormalities of the urogenital system. 如申請專利範圍第17項所述的方法，其中該主體患有皮膚異常，該皮膚異常包含：痤瘡疤(acne scar)、皮膚疤(skin scar)、皺紋(wrinkle)、浮肉(cellulite)及真皮腫瘤性纖維化(dermal neoplastic fibrosis)、疤痕性禿髮(scarring alopecia)、血管病變(vasculopathy)、脈管炎(vasculitis)、過剩的燒傷傷口癒合(exuberant burn wound healing)、糖尿病足症候群(diabetic foot syndrome)、硬皮症(scleroderma)、關節纖維化(arthrofibrosis)、Peyronie氏病(Peyronie's disease)、Dupuytren氏攣縮(Dupuytren's contracture)、黏連性肩關節囊炎(adhesive capsulitis)或其組合。The method according to claim 17, wherein the subject suffers from skin abnormalities, and the skin abnormalities include: acne scars, skin scars, wrinkles, cellulite, and Dermal neoplastic fibrosis (dermal neoplastic fibrosis), scarring alopecia (scarring alopecia), vasculopathy (vasculopathy), vasculitis (exuberant burn wound healing), diabetic foot syndrome (diabetic) foot syndrome), scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, adhesive capsulitis, or a combination thereof. 如申請專利範圍第17項所述的方法，其中該主體患有眼科異常，該眼科異常包含：脈絡膜新生血管相關疾病(choroidal neovascularization associated disease)、年齡相關黃斑點退化(age-related macular degeneration)、角膜透明度受損(compromised corneal transparency)、角膜瘢痕形成(cornea scar formation)、翼狀胬肉(pterygia)、前部白內障形成(anterior cataract formation)、青光眼濾過手術(glaucoma filtration surgery)、青光眼(glaucoma)、雷射屈光眼角膜切除術(photorefractive keratectomy)、雷射原位層狀眼角膜成塑形(laser in situ keratomileusis)、與前視網膜及視網膜前膜收縮相關的異常(disorder related to contraction of the pre- and epiretinal membranes)、增殖性玻璃體視網膜病變(proliferative vitreoretinopathy)、增生性糖尿病視網膜病變(proliferative diabetic retinopathy)、糖尿病性黃斑水腫(diabetic macular edema)、與近視性脈絡膜新生血管相關的異常(disorder related myopic choroidal neovascularization)、網膜靜脈阻塞(retinal vain occlusion)、視網膜下纖維增生(sub-retinal fibrosis)、視網膜下瘢痕(sub-retinal scarring)、脈絡膜相關的異常(choroidal membrane related disorder)、視網膜神經膠瘤病(retinal gliosis)、視網膜前膜相關的異常(epiretinal membrane related disorder)、膠質瘢痕形成(glial scar formation)或其組合。The method according to item 17 of the scope of application, wherein the subject has an ophthalmological abnormality, and the ophthalmic abnormality includes: choroidal neovascularization associated disease, age-related macular degeneration, Compromised corneal transparency, cornea scar formation, pterygia, anterior cataract formation, glaucoma filtration surgery, glaucoma , Laser refractive keratectomy (photorefractive keratectomy), laser in situ lamellar cornea shaping (laser in situ keratomileusis), abnormalities related to contraction of the anterior retina and epiretinal membrane (disorder related to contraction of the pre- and epiretinal membranes, proliferative vitreoretinopathy, proliferative diabetic retinopathy, diabetic macular edema, disorder related to myopic choroidal neovascularization myopic choroidal neovascularization, retinal vain occlusion, sub-retinal fibrosis, sub-retinal scarring, choroidal membrane related disorder, retinal glioma Disease (retinal gliosis), epiretinal membrane related disorder, glial scar formation, or a combination thereof. 如申請專利範圍第17項所述的方法，其中該主體患有泌尿生殖系統異常，該泌尿生殖系統異常包含：良性前列腺增生(benign prostate hyperplasia)、下尿道症狀(lower urinary tract symptom)、良性前列腺腫大(benign prostatic enlargement)、膀胱出口阻塞(bladder outlet obstruction)、間質性膀胱炎相關的異常(overactive bladder related disorder)、攝護腺炎(prostatitis)、前列腺上皮內瘤形成(prostatic intraepithelial neoplasia)、神經性膀胱症後群(neurogenic bladder syndrome)、前列腺癌(prostate cancer)、尿失禁(urinary incontinence)、骨盆疼痛(pelvic pain)或其組合。The method according to item 17 of the scope of patent application, wherein the subject has an abnormality of the urinary and reproductive system, and the abnormality of the urinary and reproductive system includes: benign prostate hyperplasia, lower urinary tract symptom, and benign prostate Enlargement (benign prostatic enlargement), bladder outlet obstruction (bladder outlet obstruction), overactive bladder related disorder, prostatitis (prostatitis), prostatic intraepithelial neoplasia (prostatic intraepithelial neoplasia) , Neurogenic bladder syndrome, prostate cancer, urinary incontinence, pelvic pain, or a combination thereof.
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