Benzyl Atropine Eye Drops With pH-Controlled Aqueous Stability
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Solution Overview
Problem
Current treatments for myopia, such as native atropine, require high doses that cause debilitating side effects and are unstable in aqueous solutions with physiological pH, necessitating a stable pharmacological agent for myopia prevention and progression reduction.
Innovation Solution
Aqueous pharmaceutical solutions comprising benzyl atropine, a pharmaceutically acceptable salt, or prodrug, along with buffers and solubilizing agents, maintaining a pH of 4 to 5 and concentration of 0.01 to 0.2%, to stabilize the compound and enhance its efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of native atropine are used to reduce myopia progression, then the effectiveness in preventing myopia is improved, but debilitating side effects such as pupillary dilation and light sensitivity occur
Solution Approach 1:
The patent modifies the chemical structure of atropine by adding a benzyl group to create benzyl atropine, which changes the pharmacological parameters to achieve myopia control at lower doses with reduced side effects. This structural parameter change allows the compound to maintain therapeutic efficacy while improving the safety profile by reducing pupillary dilation and light sensitivity effects.
Solution Approach 2:
The invention creates a composite pharmaceutical composition containing benzyl atropine combined with specific excipients including buffers (phosphate, citrate, or acetate at pH 4-5), solubilizing agents (polysorbate 80, polyethylene glycol 400, or hydroxypropyl-beta-cyclodextrin), and tonicity agents (sodium chloride, mannitol, or sorbitol). This composite formulation enhances stability and efficacy while minimizing side effects.
2Ease of operation
If native atropine is used in aqueous solutions with physiological pH, then it can be administered as a pharmacological agent, but it decomposes into tropic acid and tropine making it nonviable for treatment
Solution Approach 1:
The patent changes the pH parameter of the aqueous solution to a lower range (pH 4-5) and modifies the chemical structure of atropine to benzyl atropine. This parameter change prevents hydrolysis decomposition that occurs at physiological pH, thereby maintaining compound stability in aqueous solution while preserving administerability.
Solution Approach 2:
The patent introduces buffers (phosphate, citrate, or acetate) as intermediary substances that maintain the pH at 4-5, preventing the decomposition of benzyl atropine. These buffer intermediaries stabilize the solution environment to protect the active compound from hydrolysis while allowing aqueous administration.
3Reliability
If benzyl atropine is formulated in aqueous solution with pH 4-5 and appropriate excipients, then stability and efficacy are improved, but the formulation complexity increases
Solution Approach 1:
The patent employs excipients that serve multiple functions simultaneously: buffers (phosphate, citrate, or acetate) maintain pH and provide ionic strength; solubilizing agents (polysorbate 80, polyethylene glycol 400, or hydroxypropyl-beta-cyclodextrin) enhance drug solubility and stability; and tonicity agents (sodium chloride, mannitol, or sorbitol) adjust osmolarity. This multi-functionality reduces the need for additional separate components, managing formulation complexity while ensuring stability and efficacy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation provides a stable and effective treatment for myopia, reducing progression with minimal side effects by using benzyl atropine in a pH-controlled aqueous solution.
Implementation Method 1
maintaining a pH of 4 to 5 and concentration of 0.01 to 0.2%
Implementation Method 2
along with buffers and solubilizing agents
Data Source
AI summary
The present disclosure is directed, in part, to aqueous pharmaceutical solutions comprising benzyl atropine or a pharmaceutically acceptable salt or prodrug thereof, at least one buffer, at least one tonicity agent, and at least one solubilizing agent, processes of preparing an aqueous solution comprising benzyl atropine, the products of such processes, and methods of preventing myopia, treating myopia, reducing myopia progression, or preventing myopia progression in a subject in need thereof, by administering to the eye of the subject a therapeutically effective amount of such an aqueous pharmaceutical solution.