Pharmacologically active composition for the development of synthetic drugs for the treatment of neurodegenerative diseases

Abstract

An isolated pharmacologically active composition for use in the treatment of neurodegenerative diseases, the composition comprising: 0.1% to 20% (w / w) of at least one synthetic small molecule backbone selected from heteroaryl-substituted piperazine derivatives, benzothiazole derivatives or quinoline-based analogues; 50% to 95% (w / w) of at least one pharmaceutically acceptable carrier or excipient; and 0.1% to 10% (w / w) of a stabilizer, antioxidant or surfactant.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to pharmacologically active compositions for the development of synthetic drugs against neurodegenerative diseases. In particular, the invention relates to chemically prepared synthetic scaffolds of heteroaryl-substituted piperazine derivatives, benzothiazole derivatives, and quinoline analogues, formulated with pharmaceutically acceptable excipients and stabilizers for therapeutic use in diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and other diseases characterized by neuronal degeneration, protein misfolding, oxidative stress, and synaptic dysfunction. The invention further relates to a structural delivery system for formulating, stabilizing, and controlled release of the compositions into biological environments. BACKGROUND OF THE INVENTION

[0002] Neurodegenerative diseases are chronic, progressive, and often irreversible disorders of the central nervous system. These diseases are characterized by the accumulation of misfolded proteins, the formation of amyloid plaques, mitochondrial dysfunction, and metal ion-induced oxidative stress. Current therapies are largely palliative in nature and do not adequately address the underlying biochemical processes that accelerate neurodegeneration. Therefore, there is an urgent need for synthetic pharmaceuticals that can interact at the molecular level with β-amyloid fibrils, α-synuclein aggregates, tau proteins, and neurotoxic reactive oxygen species.

[0003] Naturally occurring small molecules have shown promise for neuroprotection, but their low stability, metabolic degradation, and low bioavailability limit their therapeutic implementation. Synthetic scaffolds composed of heteroaryl-substituted piperazines, benzothiazoles, and quinolines offer structural advantages, including high ligand efficiency, the ability to conjugate with electron-donating or electron-withdrawing substituents, and improved solubility. However, such molecules require precise formulation with stabilizers, carriers, and delivery vehicles to achieve controlled release and targeted neuronal uptake. The present invention provides such compositions and extends to a device or machine structure that ensures reproducible preparation, stability, and administration.

[0004] Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a class of chronic and progressive disorders that primarily affect the central nervous system and are characterized by the gradual loss of neuronal structure, function, and connectivity. The medical, social, and economic burden of these diseases is enormous, as they are associated with cognitive decline, motor dysfunction, behavioral disturbances, and ultimately, the loss of independence. Despite decades of research, effective disease-modifying therapies are still unavailable, primarily due to the multifactorial nature of these diseases.Multiple signaling pathways, including protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, impaired autophagy, and chronic neuroinflammation, interact to drive the progression of neurodegeneration, making it extremely difficult to identify a single therapeutic target or pathway for intervention.

[0005] Current therapeutic approaches can be broadly divided into symptomatic treatments, disease-modifying candidates, and supportive care strategies. Symptomatic treatments remain the most widely used and include agents such as cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists in Alzheimer's disease or dopaminergic agents and monoamine oxidase B inhibitors in Parkinson's disease. These medications temporarily alleviate cognitive decline, memory loss, or motor impairment, but do not alter the underlying neurodegenerative cascade. Their efficacy also decreases with progressive neuronal damage, and side effects such as gastrointestinal disturbances, hallucinations, cardiovascular stress, or dyskinesias further limit their clinical benefit.

[0006] Disease-modifying therapies have been intensively pursued over the past two decades, particularly in Alzheimer's disease, where β-amyloid and tau protein aggregation are central pathological hallmarks. Monoclonal antibodies targeting β-amyloid plaques, such as aducanumab and lecanemab, have attracted regulatory attention, but their clinical utility remains controversial. These biologics are associated with high costs, the requirement for intravenous administration, and the risk of adverse effects, such as amyloid-related imaging abnormalities (ARIAs), including cerebral edema and microbleeds. Furthermore, the ability of such large biomolecules to cross the blood-brain barrier is inherently limited, reducing their efficacy in achieving sufficient concentrations at sites of neuronal pathology.

[0007] Small molecule drugs targeting β-amyloid aggregation, tau phosphorylation, or neuroinflammation have also been investigated, but many have failed in late-stage clinical trials due to lack of efficacy, poor pharmacokinetics, or toxicity. For example, inhibitors of the β-secretase and γ-secretase enzymes involved in the processing of amyloid precursor protein initially showed promising results but were discontinued due to off-target effects and worsening cognitive symptoms. Similarly, tau aggregation inhibitors such as methylthioninium chloride derivatives have shown inconsistent clinical benefits and issues with bioavailability. These failures highlight the challenges associated with directly targeting complex protein folding pathways through conventional small molecule or enzyme inhibitor strategies.

[0008] In Parkinson's disease, levodopa, a dopamine precursor, remains the mainstay of therapy. It is often administered in combination with carbidopa to inhibit peripheral metabolism. Long-term levodopa therapy, although effective in the early stages of the disease, is associated with significant drawbacks, such as motor fluctuations, on-off phenomena, and dyskinesias. Deep brain stimulation has emerged as a complementary intervention for advanced cases, offering symptomatic relief by modulating basal ganglia circuitry. However, it remains invasive, expensive, and not suitable for all patients. Disease-modifying strategies to prevent α-synuclein aggregation, protect dopaminergic neurons, or reduce mitochondrial dysfunction have had little success translating preclinical studies into human trials.

[0009] Another class of therapeutic strategies focuses on reducing oxidative stress and excitotoxicity in neuronal tissue. Antioxidants such as vitamin E, coenzyme Q10, and selegiline have been investigated for their neuroprotective potential, but clinical results have been inconsistent, and most have failed to demonstrate significant benefit in large controlled trials. Part of the problem lies in the inability of many antioxidants to reach sufficient concentrations in neuronal tissue, as well as in the complexity of reactive oxygen species metabolic pathways, which are tightly regulated and difficult to modulate with single compounds. Drugs targeting excitotoxicity through glutamate receptor antagonism have also encountered limitations, as blockade of NMDA or AMPA receptors resulted in unacceptable side effects such as cognitive impairment and hallucinations.

[0010] Metal ion dyshomeostasis is also associated with neurodegenerative diseases, particularly Alzheimer's disease, where excess iron, copper, or zinc ions catalyze oxidative stress and promote β-amyloid aggregation. Chelation therapies are being investigated as a way to restore metal balance, with agents such as clioquinol and deferiprone being used in clinical trials. However, these chelators often lack selectivity, leading to systemic deficiencies of essential metal ions and associated toxicities. Their pharmacokinetic limitations and poor ability to cross the blood-brain barrier further limit their clinical efficacy.

[0011] Efforts have also been made to develop therapies based on neurotrophic factors such as nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). These agents are intended to support the survival, plasticity, and regeneration of nerve cells. However, the large protein structure of these molecules prevents efficient penetration of the blood-brain barrier, requiring invasive delivery methods such as intrathecal injections or gene therapy vectors. While biologically interesting, such approaches face significant challenges regarding safety, scalability, and cost, limiting their widespread application.

[0012] Nanotechnology-based delivery systems, including liposomes, polymeric nanoparticles, and dendrimers, have been explored to overcome some of these drawbacks by improving bioavailability and targeted drug delivery across the blood-brain barrier. While preclinical studies are promising, translation to clinical use has been slow due to challenges in mass production, reproducibility, long-term stability, and regulatory hurdles. Furthermore, the safety of long-term exposure to nanomaterials in the brain is still poorly characterized, raising concerns about potential toxicity.

[0013] Despite these shortcomings, the development of synthetic drugs is proving to be a particularly promising approach to overcome the limitations of existing therapies. Synthetic scaffolds enable precise chemical tuning of physicochemical properties such as solubility, stability, and binding affinity. They can be functionalized with electron-donating or electron-withdrawing substituents to optimize interaction with pathological proteins, or conjugated with polar side chains to improve pharmacokinetics and reduce metabolic degradation. The challenge, however, is to develop synthetic compounds that are both effective against neurodegenerative targets and sufficiently bioavailable in neuronal tissue. Many candidates have failed due to lack of water solubility, rapid liver metabolism, or the inability to cross the blood-brain barrier at effective concentrations.

[0014] Another disadvantage of existing solutions is the lack of multifunctionality. Neurodegenerative diseases have multifactorial causes and are simultaneously associated with protein aggregation, oxidative stress, mitochondrial dysfunction, synaptic impairment, and inflammation. Most current drugs are monofunctional, meaning they target a single signaling pathway, and therefore cannot halt disease progression when administered in isolation. There is a growing realization that successful interventions require compounds capable of acting on multiple pathological processes simultaneously, for example, by disrupting protein aggregation while simultaneously removing reactive oxygen species and restoring metal ion balance.

[0015] Finally, the delivery systems themselves also face significant limitations. Oral formulations are often degraded by gastric acid and first-pass metabolism, resulting in reduced bioavailability. While injectable formulations circumvent gastrointestinal degradation, they are associated with poor patient compliance, pain, and risk of infection. Even when drugs reach the systemic circulation, the blood-brain barrier remains a significant obstacle, blocking most large and hydrophilic molecules. Without strategies to improve targeted delivery, therapeutics distribute nonspecifically throughout the body, leading to undesirable side effects and failing to achieve therapeutic concentrations in neuronal tissue.

[0016] While existing solutions for neurodegenerative diseases have made incremental progress in alleviating symptoms, they remain fundamentally limited in their ability to influence disease progression. Small-molecule drugs often have issues with stability, solubility, and bioavailability. Biologics face challenges such as cost, invasiveness, and the need to cross the blood-brain barrier. Antioxidants, chelators, and neurotrophic factors have shown limited clinical success, and device-based interventions such as deep brain stimulation are applicable only in select cases. The multifactorial pathology of neurodegenerative diseases further complicates therapy, as single-target agents fail to address the complex interplay of molecular dysfunctions.These disadvantages underline the need for innovative pharmacologically active compositions and delivery systems that combine the precision of synthetic scaffolds with multifunctional activity, sustained release, and effective penetration into the central nervous system. Summary of the invention

[0017] The invention relates to an isolated pharmacologically active composition for the treatment of neurodegenerative diseases. The composition contains approximately 0.1 to 20 wt.% of at least one synthetic low-molecular-weight scaffold selected from heteroaryl-substituted piperazine derivatives, benzothiazole derivatives, or quinoline analogues. The composition also contains approximately 50 to 95 wt.% of at least one pharmaceutically acceptable carrier or excipient, as well as approximately 0.1 to 10 wt.% of a stabilizer, antioxidant, or surfactant.

[0018] In one embodiment, the heteroaryl-substituted piperazine derivative is present in an amount of about 1 to 10% (w / w) and contains a fluorinated pyridyl moiety conjugated with a methoxy-substituted phenyl group. This structural configuration is intended to enhance hydrogen bond acceptor interactions with misfolded protein residues, thus reducing aggregation and toxicity. In another embodiment, the benzothiazole derivative is present in an amount of about 0.5 to 15% (w / w) and is functionalized with an electron-donating substituent at the 6-position, which enhances π-π stacking with β-amyloid fibrils. Likewise, quinoline-based analogues may contain a tertiary amine side chain at the 4-position in an amount of approximately 2 to 12% (w / w) to improve solubility and minimize first-pass metabolism.

[0019] The composition may also contain stabilizing excipients such as cyclodextrins, liposomal carriers, or polymeric nanoparticles in an amount of about 1 to 20% (w / w) to enable sustained release and preferential transport across the blood-brain barrier. In certain embodiments, chelating moieties such as hydroxypyridinones or catechols are conjugated into the scaffold in an amount of 0.2 to 5% (w / w) to mitigate metal ion-mediated oxidative stress. The formulation may be configured as an oral dosage form and comprise about 20% to 40% (w / w) of the active scaffold, 40% to 70% (w / w) of a filler such as lactose or mannitol, and 1% to 5% (w / w) of a binder or disintegrant, enclosed in a delayed-release coating to prevent degradation in the stomach and ensure targeted release in the intestine.In addition, the composition can be co-formulated with synergistic adjuvants such as monoamine oxidase B inhibitors or acetylcholinesterase inhibitors in an amount of approximately 0.1 to 5% (w / w) to enhance the neuroprotective effect.

[0020] Another aspect of the invention is the provision of a machine structure in the form of a microfluidic formulation and delivery device for neuropharmaceuticals. This device consists of a modular housing with a reservoir for the pharmacologically active composition, a microfluidic channel system for homogenizing stabilizers and excipients, and a nanoparticle coating chamber for encapsulating active molecules in liposomal or polymeric carriers. The structure also integrates an integrated spectroscopic detector for real-time monitoring of scaffold stability, pH, and oxidation state. The device is also equipped with a programmable release module that enables precise control of drug delivery kinetics and enables administration in oral, injectable, or transdermal dosage forms.

[0021] This combined pharmaceutical composition and device system ensures not only the production of stable and bioavailable formulations, but also their reproducible and scalable delivery for therapeutic purposes.

[0022] The primary objective of the present invention is to provide pharmacologically active compositions specifically designed for the treatment of neurodegenerative diseases. These compositions overcome the deficiencies of existing therapies by offering improved stability, solubility, and bioavailability while ensuring effective penetration of the blood-brain barrier. Another objective of the invention is to create synthetic scaffolds of small molecules, including heteroaryl-substituted piperazine derivatives, benzothiazole derivatives, and quinoline-based analogues, that are chemically tailored with specific substituents to increase their binding affinity to misfolded proteins, amyloid fibrils, and other pathological aggregates involved in neurodegeneration.A further object of the invention is to provide formulations containing pharmaceutically acceptable carriers, excipients and stabilizers in defined proportions to ensure controlled release, reduced first-pass metabolism and targeted delivery to neuronal tissue.

[0023] Another aim of the invention is to integrate chelating agents into the synthetic scaffolds, such as hydroxypyridinone or catechol derivatives, which can mitigate oxidative stress caused by metal ions without disrupting systemic metal balance. Another aim of the invention is to enable multifunctional activity in a single composition that simultaneously reduces protein aggregation, oxidative stress, and mitochondrial dysfunction, thus addressing the multifactorial pathology of neurodegenerative diseases more effectively than monofunctional drugs. Another aim is to develop oral dosage forms with delayed-release coatings that resist gastric degradation and selectively release the active ingredients in the intestinal tract, thereby improving patient compliance and enhancing pharmacokinetic performance.

[0024] A key objective of the invention is to provide compositions that can be combined with synergistic adjuvants such as monoamine oxidase B inhibitors or acetylcholinesterase inhibitors to achieve additive or synergistic neuroprotective effects. A further objective is to ensure the compatibility of the pharmacological compositions with modern delivery platforms such as cyclodextrins, liposomal carriers, or polymeric nanoparticles to enable sustained release and efficient neuronal targeting. Beyond the composition itself, an objective of the invention is to provide a complementary machine structure in the form of a microfluidic formulation and delivery system capable of stabilizing, encapsulating, and programmatically releasing the active ingredients, thus enabling reproducible and scalable drug development and delivery.

[0025] The ultimate goal of the invention is to advance the development of synthetic drugs for neurodegenerative diseases by offering a scientifically rational, technically precise, and clinically practical pharmacological system that not only alleviates symptoms but also modifies disease progression, thus improving the quality of life and therapeutic outcomes for patients suffering from these debilitating diseases. Detailed description of the invention

[0026] To better understand the principles of the invention, reference is made to embodiments below and these are described in specific language. However, the scope of the invention is not limited thereby. Changes and further modifications to the system, as well as further applications of the principles of the invention, are possible, as would normally occur to one skilled in the art to which the invention pertains.

[0027] It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting thereof.

[0028] References in this specification to "one aspect," "another aspect," or similar expressions mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Therefore, the occurrences of the terms "in one embodiment," "in another embodiment," and similar expressions throughout this specification may or may not all refer to the same embodiment.

[0029] The terms "comprises," "having," or other variations thereof are intended to cover non-exclusive inclusion, such that a process or method comprising a list of steps not only includes those steps, but may also include other steps not expressly listed or inherent in such process or method. Likewise, the statement "comprises" with respect to one or more devices, subsystems, elements, structures, or components does not exclude, without further limitation, the existence of other devices, other subsystems, elements, structures, or components, or additional devices, additional subsystems, additional elements, additional structures, or additional components.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. The system, methods, and examples provided herein are for illustrative purposes only and should not be considered limiting.

[0031] Embodiments of the present disclosure are described in detail below.

[0032] The present invention provides an isolated pharmacologically active composition for use in the treatment of neurodegenerative diseases, the composition comprising: (a) about 0.1% to 20% (w / w) of at least one synthetic small molecule scaffold selected from heteroaryl-substituted piperazine derivatives, benzothiazole derivatives, or quinoline-based analogues; (b) about 50% to 95% (w / w) of at least one pharmaceutically acceptable carrier or excipient; and (c) by 0.1% to 10% (w / w) of a stabilizer, antioxidant or surfactant.

[0033] In one embodiment, the heteroaryl-substituted piperazine derivative is present in an amount of about 1% to 10% (w / w) and comprises a fluorinated pyridyl moiety conjugated to a methoxy-substituted phenyl group to increase hydrogen bond acceptor interactions with misfolded protein residues.

[0034] In one embodiment, the benzothiazole derivative is present in an amount of about 0.5% to 15% (w / w) and functionalized with an electron donor substituent at the 6-position to enhance π-π stacking interactions with β-amyloid fibrils.

[0035] In one embodiment, the quinoline-based analogue is present in an amount of about 2% to 12% (w / w) and is substituted at the 4-position with a tertiary amine side chain to increase solubility and reduce first-pass metabolic degradation.

[0036] In one embodiment, it further comprises about 1% to 20% (w / w) of a stabilizing excipient selected from cyclodextrins, liposomal carriers, or polymeric nanoparticles configured to enhance sustained release and targeted delivery to neuronal tissue.

[0037] In one embodiment, the synthetic scaffold further contains a chelating moiety selected from hydroxypyridinone or catechol derivatives present in an amount of about 0.2% to 5% (w / w) and serving to reduce metal ion-mediated oxidative stress in neuronal environments.

[0038] In one embodiment, the composition is formulated as an oral dosage form comprising: by 20% to 40% (w / w) of the pharmacologically active scaffold; by 40% to 70% (w / w) of a filler or diluent selected from lactose, microcrystalline cellulose or mannitol; and by 1% to 5% (w / w) of a disintegrant or binder with a delayed-release coating that resists degradation in the stomach and selectively releases the active ingredient in the intestinal tract.

[0039] In one embodiment, the composition is formulated together with an adjuvant selected from monoamine oxidase B inhibitors and acetylcholinesterase inhibitors present in an amount of about 0.1% to 5% (w / w) to achieve synergistic neuroprotective effects.

[0040] The present invention provides a pharmacological system comprising both a synthetic pharmacologically active composition and a microfluidic formulation and delivery system. The system is designed to overcome the limitations of existing neurodegenerative therapeutics by integrating chemical scaffolds with programmable release technologies. The composition is based on small-molecule synthetic scaffolds such as heteroaryl-substituted piperazine derivatives, benzothiazole derivatives, and quinoline analogues. Each scaffold is chemically functionalized to optimize its physicochemical properties, binding affinity, and pharmacokinetic stability.For example, heteroaryl-substituted piperazine derivatives contain a fluorinated pyridyl moiety conjugated to a methoxy-substituted phenyl group, thereby increasing hydrogen bond acceptor capacity and polar interactions with misfolded proteins such as β-amyloid fibrils. Similarly, benzothiazole derivatives are tailored with electron-donating groups at the 6-position, enhancing π-π stacking with fibrillar backbones to disrupt aggregation, while quinoline analogues are substituted at the 4-position with tertiary amine side chains to increase water solubility and reduce liver degradation.

[0041] The composition is balanced with pharmaceutically acceptable carriers and excipients in concentrations ranging from 50% to 95% (w / w) to ensure dosage stability, consistent compressibility, and compatibility with oral or injectable forms. Stabilizers, antioxidants, or surfactants are included in amounts ranging from 0.1% to 10% (w / w) to prevent degradation of the scaffold during storage and administration. Optional stabilizing excipients such as cyclodextrins, liposomal vesicles, or polymeric nanoparticles are included in amounts ranging from 1% to 20% (w / w) to encapsulate the scaffold and enable controlled release across biological barriers. Chelating agents such as hydroxypyridinones or catechols can be conjugated in concentrations of 0.2% to 5% (w / w) to selectively bind neurotoxic metal ions while sparing essential ions such as zinc, thereby reducing oxidative stress.Oral formulations are optimized with fillers such as lactose, mannitol, or microcrystalline cellulose, binders such as polyvinylpyrrolidone, and disintegrants such as croscarmellose sodium. These are all encapsulated in pH-sensitive coatings that selectively dissolve in the intestinal tract at a pH of 6.5 to 7.5. This bypasses gastric degradation and improves systemic absorption.

[0042] The second component of the invention is the microfluidic formulation and delivery device, which serves as an intelligent machine structure for processing, stabilizing, and administering the pharmacologically active compositions. The device is made of biocompatible polymers such as polycarbonate or cycloolefin copolymer and includes modular reservoirs for scaffold, excipients, and stabilizers. The reservoirs feed into a microfluidic mixing array made of polydimethylsiloxane (PDMS) with channels 50 to 200 micrometers wide. These channels are designed to operate under laminar flow conditions, maintaining Reynolds numbers below 1. This ensures precise and shear-free mixing of the scaffold with carriers and excipients. Avoiding turbulence in this environment is crucial for the stability of nanoparticle encapsulation systems and preventing mechanical denaturation of liposomal bilayers.

[0043] Downstream of the mixer is a nanoparticle encapsulation chamber, which acts as the central structural unit for encapsulating active scaffold molecules. This chamber integrates an ultrasound module operating at frequencies between 20 and 40 kHz. Ultrasonication induces controlled cavitation in the medium and promotes the self-assembly of phospholipid bilayers or polymer matrices around the scaffold molecules. This results in liposomal vesicles or nanoparticles with diameters in the range of 50 to 150 nanometers, optimized for neuronal uptake by endocytosis. Encapsulation offers the dual advantage of protecting the scaffold from enzymatic degradation and improving its transport across the blood-brain barrier.

[0044] To ensure quality and reproducibility, the device incorporates a real-time optical spectroscopy sensor in the encapsulation chamber. This sensor continuously monitors the scaffold's absorption maxima and provides direct feedback on structural integrity, stability, and concentration. The spectroscopic data is transmitted to an embedded microcontroller, which forms the control core of the programmable release module. The microcontroller integrates the sensor output with preprogrammed release parameters and modulates the activity of a piezoelectric micropump. The pump regulates dosing volumes between 1 microliter and 100 microliters per process with high precision and reproducibility.

[0045] The control system implemented in the microcontroller follows a closed-loop control system in which sensor feedback is continuously compared with reference stability thresholds. If the scaffold's absorption peak deviates beyond a defined tolerance window, the technology initiates corrective measures by adjusting the sonication amplitude, mixing rates, or micropump timing to restore formulation integrity. The release technology is time-modulated and programmable, enabling personalized delivery profiles such as pulsatile dosing, sustained infusion, or delayed release. This ensures that the drug's release kinetics can be adapted to the progression and pathology of the neurodegenerative disease being treated.

[0046] If the composition is configured for oral administration, the device produces capsules or tablets with delayed-release coatings that ensure a uniform structure and pH-dependent dissolution. For parenteral or transdermal applications, the device produces nanoparticle suspensions or encapsulated emulsions with controlled particle size and optimized zeta potential for bioavailability. The device's modular housing also features sterilizable cartridge interfaces, allowing aseptic loading and storage of the formulations for up to 30 days under ambient conditions without degradation.

[0047] The integration of composition and device offers synergistic therapeutic benefits. The synthetic scaffolds simultaneously target multiple pathological mechanisms, including protein misfolding, oxidative stress, and metal ion dyshomeostasis. The stabilizers and excipients enhance the stability and solubility of the scaffold, while the encapsulation technologies prolong release and promote neuronal targeting. The microfluidic device ensures reproducible formulation with nanoprecision and integrates real-time, closed-loop feedback to ensure formulation integrity. Together, the system ensures a multifunctional therapeutic platform that not only alleviates symptoms but also impacts disease progression in neurodegenerative diseases.

[0048] In an exemplary operation, the device is programmed to formulate a composition containing 5% (w / w) of a quinoline-based analogue with a tertiary amine side chain, 70% (w / w) lactose filler, 3% (w / w) binder, and 2% (w / w) antioxidant. The microfluidic assembly dispenses the scaffold under laminar flow within the carrier, while the encapsulation chamber encloses the scaffold in liposomes with a diameter of approximately 100 nanometers. The spectroscopic sensor confirms the structural integrity of the scaffold by monitoring its λmax at 310 nm. The microcontroller technology then initiates a pulsatile release program that releases 10 microliters every 6 hours over a 24-hour cycle. This corresponds to a sustained therapeutic plasma concentration while minimizing off-target exposure.

[0049] The pharmacologically active compositions of the invention target specific pathological features of neurodegenerative diseases. In a preferred embodiment, heteroaryl-substituted piperazine derivatives at concentrations of 1 to 10% (w / w) selectively bind to hydrophobic grooves of amyloidogenic proteins, thus reducing fibril elongation. Their fluorinated pyridyl moiety increases electron density and binding affinity, while the methoxy-substituted phenyl group introduces polar interactions that stabilize the protein-drug complex.

[0050] Benzothiazole derivatives in concentrations of 0.5 to 15% (w / w) are engineered to feature planar aromatic structures with substituents at the 6-position, thus enhancing π-π stacking interactions with β-amyloid fibrils. This structural alignment disrupts fibril aggregation while maintaining the lipophilic balance for neuronal penetration. Quinoline analogues in concentrations of 2 to 12% (w / w) are modified with tertiary amine side chains to increase water solubility, improve pharmacokinetic stability, and minimize hepatic degradation.

[0051] The formulations are optimized with pharmaceutically acceptable carriers such as lactose, mannitol, or microcrystalline cellulose to ensure compressibility for oral tablets and uniformity during capsule filling. Stabilizers such as antioxidants (ascorbic acid, tocopherols) or surfactants (polysorbates) prevent premature degradation. Encapsulation in cyclodextrins or liposomal vesicles improves delayed release and facilitates transport across the blood-brain barrier. Chelating agents such as catechols are optionally incorporated to capture neurotoxic iron or copper ions.

[0052] In an exemplary oral dosage formulation, the composition consists of 30% (w / w) of the synthetic scaffold, 60% (w / w) lactose as a diluent, 3% (w / w) cross-linked polyvinylpyrrolidone as a disintegrant, and 2% (w / w) magnesium stearate as a lubricant, encapsulated in a pH-sensitive polymer coating that dissolves at intestinal pH. The delayed-release profile bypasses gastric enzymes and ensures intestinal absorption, thereby improving systemic availability.

[0053] The associated device consists of a biocompatible polymer housing containing a container with sterile chambers for the scaffold, carrier, and stabilizer. Integrated microfluidic channels ensure laminar mixing of the ingredients at controlled flow rates, while nanoparticle coating modules enable encapsulation of the scaffold in cyclodextrin or polymeric nanocarriers. A spectroscopic sensor array monitors the scaffold's absorption maxima to confirm structural integrity prior to release. The programmable release system is controlled by a microcontroller that regulates timing, pressure, and dosage, ensuring consistency across all therapeutic administrations.

[0054] This synergistic system – consisting of the pharmacologically active compounds and the machine device – not only enables effective treatment of neurodegenerative diseases but also ensures stability, bioavailability and controlled release, thus representing a significant advance in the development of synthetic drugs.

[0055] The present invention relates to pharmacy, in particular to the development of synthetic drugs and formulation technologies for the treatment of neurodegenerative diseases. It concerns the development of pharmacologically active compositions from engineered small molecule scaffolds tailored to interact with misfolded proteins, amyloid fibrils, and other pathogenic substrates involved in neuronal degeneration. The invention also encompasses the integration of advanced drug delivery systems using stabilizing excipients, nanoparticles, liposomal carriers, and delayed-release coatings, thereby improving the solubility, stability, and targeted biodistribution of the active ingredients.Furthermore, the invention encompasses the development of a device-supported system with microfluidic structures to support the encapsulation, stabilization, and programmable release of the pharmacological compositions to ensure reproducibility and scalability of production. The invention therefore bridges the fields of medicinal chemistry, pharmaceutical formulation, neurotherapeutics, and biomedical device engineering to address the unmet need for effective and disease-modifying treatments for Alzheimer's disease, Parkinson's disease, Huntington's disease, and other progressive neurodegenerative diseases.

[0056] The foregoing description provides examples of embodiments. Those skilled in the art will recognize that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be split into multiple functional elements. Elements of one embodiment may be added to another embodiment. For example, the order of the processes described herein may be changed and is not limited to the manner described herein. Furthermore, the actions need not be implemented in the order recited; nor do all actions necessarily have to be performed. Also, actions that are not dependent on other actions may be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples. Numerous variations, whether explicitly stated in the specification or not, such asDifferences in structure, dimensions, and material use are possible. The scope of the embodiments is at least as broad as indicated in the following claims.

[0057] Advantages, further benefits, and solutions to problems have been described above with reference to specific embodiments. However, the advantages, advantages, solutions to problems, and any components that may result in an advantage, advantage, or solution occurring or becoming more apparent are not to be construed as critical, required, or essential features or components of any or all of the claims.

Claims

[1] An isolated pharmacologically active composition for use in the treatment of neurodegenerative diseases, the composition comprising: 0.1% to 20% (w / w) of at least one synthetic scaffold of small molecules selected from heteroaryl-substituted piperazine derivatives, benzothiazole derivatives or quinoline-based analogues; 50% to 95% (w / w) of at least one pharmaceutically acceptable carrier or excipient; and 0.1% to 10% (w / w) of a stabilizer, antioxidant or surfactant. [2] Composition according to claim 1, wherein the heteroaryl-substituted piperazine derivative is present in an amount of 1 to 10% (w / w) and comprises a fluorinated pyridyl residue conjugated to a methoxy-substituted phenyl group to enhance hydrogen bond acceptor interactions with misfolded protein residues. [3] Composition according to claim 1, wherein the benzothiazole derivative is present in an amount of 0.5% to 15% (w / w) and is functionalized with an electron donor substituent at the 6-position to enhance the π-π stacking interactions with β-amyloid fibrils. [4] Composition according to claim 1, wherein the quinoline-based analogue is present in an amount of about 2 to 12% (w / w) and is substituted at the 4-position with a tertiary amine side chain to increase solubility and reduce first-pass metabolic degradation. [5] Composition according to claim 1, further comprising about 1 to 20% (w / w) of a stabilizing excipient selected from cyclodextrins, liposomal carriers or polymeric nanoparticles and configured to enhance sustained release and targeted delivery to neuronal tissue. [6] Composition according to claim 1, wherein the synthetic scaffold further comprises a chelating unit selected from hydroxypyridinone or catechol derivatives and present in an amount of about 0.2% to 5% (w / w) and configured to reduce metal ion-mediated oxidative stress in neuronal environments. [7] Composition according to claim 1, wherein the composition is formulated as an oral dosage form, comprising: 20% to 40% (w / w) of the pharmacologically active scaffold; 40% to 70% (w / w) of a filler or diluent selected from lactose, microcrystalline cellulose or mannitol; and 1% to 5% (w / w) of an explosive or binder with a delayed-release coating that resists degradation in the stomach and selectively releases the active ingredient in the intestinal tract. [8] Composition according to claim 1, wherein the composition is formulated together with an adjuvant consisting of monoamine oxidase B inhibitors and acetylcholinesterase -inhibitors are selected and are present in an amount of 0.1% to 5% (w / w) to achieve synergistic neuroprotective effects.