RESUMO
Phytopharmaceuticals are the newly termed herbal medicine, which includes standardized extract, bioactive fraction, and phytoconstituent. They have been practiced to cure, treat, and mitigate diseases. Phytopharmaceuticals have many health benefits, but their therapeutic efficacy is limited due to poor absorption, low bioavailability, and early elimination profile. A novel phospholipid complex is a newly introduced patented technology developed to incorporate the standardized plant extracts/fractions or water-soluble phytoconstituents into phospholipids to produce lipid compatible molecular complex, called phytosome, which improves their absorption and bioavailability. In herbal formulations, phytosome is the most advanced dosage form that has an upgraded absorption rate and enhanced pharmacokinetics compared with conventional products. The phospholipid complex results from hydrogen bonding between phospholipids and phytoconstituents, offering the maximum incorporation of herbal active ingredients into the lipidic layer and core. The increased therapeutic efficacy is due to the formation of amphiphilic phospholipid-complex of herbal medicine. This review highlights the role of phospholipids on delivery of herbal bioactives and natural extracts with particular emphasis on phytosomes. Moreover, the status of bioavailabilities, commercial products, patents, and clinical trials of phytosomal systems of phytopharmaceuticals were addressed.
Assuntos
Disponibilidade Biológica , Ensaios Clínicos como Assunto , Fosfolipídeos , Extratos Vegetais , Humanos , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Animais , Compostos Fitoquímicos/farmacocinética , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Patentes como Assunto , Sistemas de Liberação de MedicamentosRESUMO
Protein and peptide-based drugs have greater therapeutic efficacy and potential application and lower toxicity compared to chemical entities in long-term use within optimum concentration as they are easily biodegradable due to biological origin. While oral administration is preferable, most of these substances are currently administered intravenously or subcutaneously. This is primarily due to the breakdown and poor absorption in the GI tract. Hence, ongoing research is focused on investigating absorption enhancers, enzyme inhibitors, carrier systems, and stability enhancers as potential strategies to facilitate the oral administration of proteins and peptides. Investigations have been directed towards advancing novel technologies to address gastrointestinal (GI) barriers associated with protein and peptide medications. The current review intensifies formulation and stability approaches for oral protein & peptide drug delivery systems with all significant parameters intended for patient safety. Notably, certain innovative technologies have been patented and are currently undergoing clinical trials or have already been introduced into the market. All the approaches stated for the administration of protein and peptide drugs are critically discussed, having their current status, future directions, and recent patents published in the last decades.
Assuntos
Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Patentes como Assunto , Peptídeos , Proteínas , Humanos , Peptídeos/administração & dosagem , Administração Oral , Sistemas de Liberação de Medicamentos/métodos , Proteínas/administração & dosagem , Proteínas/farmacocinética , AnimaisRESUMO
Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.
Assuntos
Canabinoides , Portadores de Fármacos , Nanopartículas , Humanos , Canabinoides/química , Canabinoides/administração & dosagem , Canabinoides/uso terapêutico , Canabinoides/farmacologia , Canabinoides/farmacocinética , Portadores de Fármacos/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Disponibilidade Biológica , Maconha Medicinal/uso terapêutico , Maconha Medicinal/administração & dosagem , Maconha Medicinal/química , Maconha Medicinal/farmacocinética , Animais , Sistemas de Liberação de Medicamentos/métodos , Solubilidade , Nanotecnologia/métodos , Patentes como AssuntoRESUMO
Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, ß-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, ß-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, ß-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010-present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.
Assuntos
Antineoplásicos , Desenho de Fármacos , Neoplasias , Humanos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto , Animais , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/antagonistas & inibidores , Estrutura Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases Associadas a Fase S/antagonistas & inibidores , Proteínas Quinases Associadas a Fase S/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismoRESUMO
Type-2 diabetes mellitus (T2DM) is a complicated long-term disorder associated with metabolism that is identified by insulin resistance, imbalance in glucose regulation and reduced secretion of insulin. GLP-1(Glucagon-like peptide-1) is an incretin mimetic that has excellent effects on the regulation of blood glucose levels and also the management of disorders associated with vital organs. GLP-1 agonist is an effective class of drug for the treatment of type-2 diabetes mellitus and associated complications. Liraglutide is one of the potent drugs of this class having similar effects as biological GLP-1. This review includes clinical trials and patents related to the pharmaceutical formulation, synthesis and biological action of liraglutide.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Liraglutida , Patentes como Assunto , Liraglutida/uso terapêutico , Liraglutida/farmacologia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , AnimaisRESUMO
Three-dimensional (3D) printing is one of the most flexible technologies for preparing tablets, offering controlled drug release profiles. The current patent describes the preparation of immediate-release 3D-printed tablets of hydrochlorothiazide to improve disintegration and dissolution profile. The patent involves the preparation of drug-loaded filament via hot-melt extrusion and utilizing the same filaments for printing 3D-printed tablets using fused deposition modeling. The tablets were printed with different shapes and sizes by incorporating channels within the tablet spaces, termed as gaplets. The introduction of channels within the tablet design improves the disintegration and dissolution profile of the drug significantly. The morphological characteristic of 3D-printed tablets was studied by using scanning electron microscopy and revealed the presence of gaplets in the tablets.
[Box: see text].
Assuntos
Liberação Controlada de Fármacos , Patentes como Assunto , Impressão Tridimensional , Comprimidos , Hidroclorotiazida/química , Hidroclorotiazida/administração & dosagem , Solubilidade , Preparações de Ação Retardada/química , Composição de Medicamentos/métodosRESUMO
A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
Assuntos
Patentes como Assunto , Patentes como Assunto/legislação & jurisprudência , Humanos , Pesquisa Biomédica , Desenvolvimento de Medicamentos/legislação & jurisprudênciaRESUMO
The glucokinase enzyme (belongs to the hexokinase family) is present in liver cells and ß-cells of the pancreas. Glucokinase acts as a catalyst in the conversion of glucose-6-phosphate from glucose which is rate-limiting step in glucose metabolism. Glucokinase becomes malfunctional or remains inactivated in diabetes. Glucokinase activators are compounds that bind at the allosteric site of the glucokinase enzyme and activate it. This article highlights the patent and recent research papers history with possible SAR from year 2014-2023. The data comprises the discussion of novel chemotypes (GKAs) that are being targeted for drug development and entered into clinical trials. GK activators have attracted massive interest since successful results have been reported from clinical trials data.
[Box: see text].
Assuntos
Glucoquinase , Hipoglicemiantes , Patentes como Assunto , Glucoquinase/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Animais , Ativadores de Enzimas/farmacologia , Ativadores de Enzimas/uso terapêutico , Ativadores de Enzimas/química , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Bromodomain-containing protein 4 (BRD4), an important epigenetic reader, is closely associated with the pathogenesis and development of many diseases, including various cancers, inflammation, and infectious diseases. Targeting BRD4 inhibition or protein elimination with small molecules represents a promising therapeutic strategy, particularly for cancer therapy. AREAS COVERED: The recent advances of patented BRD4 degraders were summarized. The challenges, opportunities, and future directions for developing novel potent and selective BRD4 degraders are also discussed. The patents of BRD4 degraders were searched using the SciFinder and Cortellis Drug Discovery Intelligence database. EXPERT OPINION: BRD4 degraders exhibit superior efficacy and selectivity to BRD4 inhibitors, given their unique mechanism of protein degradation instead of protein inhibition. Excitingly, RNK05047 is now in phase I/II clinical trials, indicating that selective BRD4 protein degradation may offer a viable therapeutic strategy, particularly for cancer. Targeting BRD4 with small-molecule degraders provides a promising approach with the potential to overcome therapeutic resistance for treating various BRD4-associated diseases.
Assuntos
Antineoplásicos , Proteínas de Ciclo Celular , Desenvolvimento de Medicamentos , Neoplasias , Patentes como Assunto , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Antineoplásicos/farmacologia , Terapia de Alvo Molecular , Proteólise/efeitos dos fármacos , Descoberta de Drogas , Proteínas que Contêm BromodomínioRESUMO
INTRODUCTION: c-Jun N-terminal kinase (JNK) regulates various biological processes through the phosphorylation cascade and is closely associated with numerous diseases, including inflammation, cardiovascular diseases, and neurological disorders. Therefore, JNKs have emerged as potential targets for disease treatment. AREAS COVERED: This review compiles the patents and literatures concerning JNK inhibitors through retrieving relevant information from the SciFinder, Google Patents databases, and PubMed from 2015 to the present. It summarizes the structure-activity relationship (SAR) and biological activity profiles of JNK inhibitors, offering valuable perspectives on their potential therapeutic applications. EXPERT OPINION: The JNK kinase serves as a novel target for the treatment of neurodegenerative disorders, pulmonary fibrosis, and other illnesses. A variety of small-molecule inhibitors targeting JNKs have demonstrated promising therapeutic potential in preclinical studies, which act upon JNK kinases via distinct mechanisms, encompassing traditional ATP competitive inhibition, covalent inhibition, and bidentate inhibition. Among them, several JNK inhibitors from PregLem SA, Celegene SA, and Xigen SA have accomplished the early stage of clinical trials, and their results will guide the development and indications of future JNK inhibitors.
Assuntos
Desenvolvimento de Medicamentos , Proteínas Quinases JNK Ativadas por Mitógeno , Patentes como Assunto , Inibidores de Proteínas Quinases , Humanos , Animais , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Terapia de Alvo Molecular , Desenho de FármacosRESUMO
INTRODUCTION: EphA2 is a tyrosine kinase receptor and is considered a promising target in cancer. Different approaches are used to target EphA2 receptor, and a lot of preclinical data demonstrate the potential exploitation of this receptor in clinical oncology for diagnosis and cancer therapy, including immunotherapy. AREAS COVERED: In this review, we have summarized the recent patents involving the EphA2 targeting in cancer. For this aim, we used the patent database Patentscope covering the time period of 2018-present. Preclinical and clinical data of the inventions were considered when published on peer reviewed journals. Moreover, the clinicalTrial.gov identifiers (NCT numbers) were included when available. For an easier and more immediate reading, we classify the patents in different categories, considering the nature (aptamers, small molecules, antibodies, peptides, antigens and chimeric antigen receptors) of the inventions exploiting EphA2 in clinical oncology. EXPERT OPINION: Despite the availability of a plethora of chemically diverse agents, there are no approved anticancer drugs targeting EphA2 yet. However, these intellectual properties, some of which supported by strong preclinical evidence, keep the hope that, after more than 30 years from its discovery, we will finally see the first EphA2 targeting agent approved in clinical oncology.
Assuntos
Antineoplásicos , Imunoterapia , Terapia de Alvo Molecular , Neoplasias , Patentes como Assunto , Receptor EphA2 , Humanos , Receptor EphA2/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Antineoplásicos/farmacologia , Imunoterapia/métodos , Desenvolvimento de MedicamentosRESUMO
Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors (HPIs). Here, we analyze the first patent application from Gilead in this field, which pursued a me-too approach combining elements from an old Bayer together with a recent Medshine HPI application (which covers the Phaeno Therapeutics drug candidate HN0037). The asset was contributed to Assembly Biosciences, where it is under development as ABI-1179 at the investigational new drug (IND) enabling stage for high-recurrence genital herpes. A structure proposal for indolinoyl derivative ABI-1179 is presented, showing its potential opportunities and limitations compared to other HPIs.
Assuntos
Antivirais , DNA Helicases , DNA Primase , Herpes Simples , Patentes como Assunto , Humanos , Antivirais/farmacologia , DNA Primase/antagonistas & inibidores , DNA Helicases/antagonistas & inibidores , Herpes Simples/tratamento farmacológico , Herpes Simples/virologia , Animais , Simplexvirus/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Herpes Genital/tratamento farmacológico , Herpes Genital/virologia , Farmacorresistência Viral , Proteínas ViraisRESUMO
INTRODUCTION: Mitogen-activated protein kinase (MEK) is one of the important components of Ras/Raf/MEK/ERK signaling pathway, transduces signal for cell growth, differentiation, and development. Deregulation of MEK leads to a wide variety of cancer; hence, MEK is considered as potential therapeutic targets for the treatment of cancer. The MEK1/2 inhibitors in combination with other inhibitors showed better therapeutic outcomes in various malignancies including resistant or relapsed or refractory cancer. AREAS COVERED: A comprehensive patent literature from the year 2016 to May 2024 on MEK inhibitors in oncology, their combination products and structural insights have been reviewed through searching relevant information in PubMed, Scopus, Espacenet, Web of Science, World Intellectual Property Organization and Google Patent databases. EXPERT OPINION: Overexpression and mutation of MEK have been reported to cause a wide variety of cancers especially resistant cancers. The MEK1/2 inhibitors in combination with other kinase (BRaf/KRas/PI3K) inhibitors showed significant anti-proliferative activity. Other combination of MEK inhibitor with PD-1, DYRK1, EGFR, BTK and/or VEGF inhibitors, etc. showed promising results in many cancers including colorectal, pancreatic, gastrointestinal, solid tumor, breast cancer, melanoma and multiple myeloma, etc. The dual or multi-targeted approaches of these combinations showed better and precise treatment of patients with resistant cancer.
Assuntos
Antineoplásicos , Neoplasias , Patentes como Assunto , Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/enzimologia , Antineoplásicos/farmacologia , Animais , Desenvolvimento de Medicamentos , Terapia de Alvo Molecular , Resistencia a Medicamentos Antineoplásicos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologiaRESUMO
A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
Assuntos
Patentes como Assunto , Patentes como Assunto/legislação & jurisprudência , Humanos , Pesquisa Biomédica , Desenvolvimento de Medicamentos/legislação & jurisprudênciaRESUMO
The release of active agents in tumors rather than normal tissues, limits systemic exposure and toxicities. Targeting over-expressed esterase enzyme in the tumor microenvironment can selectively release immune-active agents like Programmed Death-1 (PD-1) and PD-1 ligand inhibitors from ester-sensitive lipid nanocarriers, offering a novel approach compared with conventional therapies. PD-1 and PD-L1 association cause T-cell inactivation, whereas blocking their association improves their cytotoxic mechanism. The patent application US2022/0080051-A1 discloses a novel immune-active agent conjugated with lipid to form a nanocarrier for esterase-sensitive release. These nanocarriers selectively enter leaky vasculature of tumors through enhanced permeability and retention effect, undergo ester cleavage to release agents, and are reported to increase bioavailability by 24 times. Further, with other agents or alone it achieves targeted synergistic cancer therapy. Also, the current patent spotlight delves into the crucial formulation considerations necessary for obtaining successful approval of lipidic nano products from relevant regulatory authorities.
[Box: see text].
Assuntos
Antineoplásicos , Portadores de Fármacos , Esterases , Lipídeos , Nanopartículas , Humanos , Nanopartículas/química , Nanopartículas/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Lipídeos/química , Lipídeos/administração & dosagem , Esterases/metabolismo , Animais , Patentes como Assunto , Neoplasias/tratamento farmacológico , Liberação Controlada de FármacosRESUMO
INTRODUCTION: Covalent drugs contain electrophilic groups that can react with nucleophilic amino acids located in the active sites of proteins, particularly enzymes. Recently, there has been considerable interest in using covalent drugs to target non-catalytic amino acids in proteins to modulate difficult targets (i.e. targeted covalent inhibitors). Covalent compounds contain a wide variety of covalent reacting groups (CRGs), but only a few of these CRGs are present in FDA-approved covalent drugs. AREAS COVERED: This review summarizes a 2020-23 patent landscape analysis that examined trends in the field of covalent drug discovery around targets and organizations. The analysis focused on patent applications that were submitted to the World International Patent Organization and selected using a combination of keywords and structural searches based on CRGs present in FDA-approved drugs. EXPERT OPINION: A total of 707 patent applications from >300 organizations were identified, disclosing compounds that acted at 71 targets. Patent application counts for five targets accounted for ~63% of the total counts (i.e. BTK, EGFR, FGFR, KRAS, and SARS-CoV-2 Mpro). The organization with the largest number of patent counts was an academic institution (Dana-Farber Cancer Institute). For one target, KRAS G12C, the discovery of new drugs was highly competitive (>100 organizations, 186 patent applications).
Assuntos
Aprovação de Drogas , Descoberta de Drogas , Patentes como Assunto , United States Food and Drug Administration , Humanos , Estados Unidos , Animais , Preparações Farmacêuticas/química , Desenvolvimento de MedicamentosRESUMO
The digitalization of low-carbon energy technologies (LCET) provides important technical support for the transition to a greener energy system. Digitalization addresses the phenomenon of the growing application of information and communications technologies (ICT) across the economy, which is regarded as the technology convergence between ICT and other technologies. Scholars have revealed the signs that LCET and ICT are becoming increasingly interlinked, which raises the challenges for predicting and identifying the technology opportunities for innovations in the converged technology area. To address the challenges, this paper proposes a collaborative filtering approach to identify the digitalization technology opportunity of low-carbon energy technologies using patent classification and patent citation information. We applied the proposed collaborative filtering approach using a large LCET patent dataset derived from the United States Patent and Trademark Office (USPTO). The results indicate that the proposed method can effectively identify digitalization technology opportunities of LCET, and the current LCET digitalization technology opportunities identified based on this approach are mainly concentrated in the Energy storage field. The advantages of the proposed approach are that its underlying data are more readily available and its technical complexity is relatively lower, and thus, more replicable for other technology fields.
Assuntos
Patentes como Assunto , Carbono/química , Estados Unidos , Tecnologia DigitalRESUMO
With the rapid development of digital technology, digital technology innovation has become a core driver of China's economic development. Thus, this study uses A-share listed companies from 2003 to 2021 as the research sample. The digital patents of firms are identified to portray the level of digital technology innovation by matching the digital economy industry classification code, national economy industry classification code, and IPC number. Considers the economic effect of digital technology innovation from the perspective of firm market value. It is found that digital technology innovation significantly contributes to the increase in firm market value, and this finding still holds when robustness tests are performed. Mechanistic tests have shown that digital technology innovation affects firm market value by driving digital transformation, promoting productivity, and enhancing market profitability. Further analysis reveals that digital technology innovation has a more significant effect on increasing firm market value for large, non-state, capital-intensive, technology-intensive and low internal control costs firms. This study verifies the enabling effect of digital technology innovation on the development of the real economy at the micro level, and provides insights for the optimization of China's digital technology innovation policies and the formulation of firms' digital development strategies.