65 results about "Tolerability" patented technology

Disclosed herein are methods and compositions for preventing or reducing adverse events associated with administration of a RAS(ON) inhibitors. Thus, disclosed are compositions and methods for treating or preventing RAS(ON) inhibitor therapy-associated rash or mucositis. The methods involve administering a compound that binds to cyclophilin A (CypA) to compete with a RAS(ON) inhibitor for CypA binding, thereby reducing tri-complex formation in non-tumor tissues. These approaches may improve the tolerability of RAS(ON) inhibitor therapies without compromising efficacy.

The present invention relates to an ophthalmic composition in the form of an aqueous solution containing levofloxacin or salt or derivative thereof and ketorolac or salt or derivative. The present invention relates to an ophthalmic composition in the form of an aqueous solution containing levofloxacin or salt or derivative thereof and ketorolac or salt or derivative thereof, for use in a method for the treatment of conjunctivitis and for the prevention or treatment of inflammation or prevention of infection after cataract surgery in a subject, according to a dosage regimen that improves patient compliance and tolerability and enables the prevention and treatment of intermediate / antibiotic-resistant infections.

The present invention relates to a compound of formula (I), which is a phosphate ester of apomorphine, or a pharmaceutically acceptable salt thereof. The apomorphine phosphate ester according to the invention exhibits remarkably advantageous properties as a therapeutic, including a favorable tolerability, an improved side effect profile, particularly a reduced occurrence of skin nodule formation and panniculitis when administered subcutaneously, as well as pharmacokinetic and metabolic properties rendering it particularly well-suited as an apomorphine prodrug. The invention further relates to the compound of formula (I) for use as a medicament, particularly for use in the treatment of Parkinson's disease.

This invention relates to antibody-drug conjugates and their uses. An antibody-drug conjugate having a structure represented by formula (I) is provided: Ab-(L-D) n (I), wherein Ab is an antibody against the interleukin-6 receptor or an antigen-binding fragment thereof, said antibody or antigen-binding fragment comprising at least one light chain and at least one heavy chain as described herein, and the use of the antibody-drug conjugate. The antibody-drug conjugate of the present invention can significantly reduce the dosage, improve patient tolerability, and reduce adverse reactions.

Disclosed herein are methods of administering compositions comprising a mixture of salts that induce purgation of the colon and are useful to cleanse the colon. Furthermore, the disclosed methods prevent degradation of PEG and allow for cleansing of the colon without the use of adjunct laxatives, including stimulant laxatives such as bisacodyl. The disclosed methods are superior to the prior art in that they allow for higher tolerability, improved safety, lower volumes, and improved patient compliance.

Provided herein are methods of treating, preventing, or reducing conditions and / or side effects associated with anti-cancer agents (e.g., chemotherapeutic agents) via administration of a non-naturally occurring melanocortin analog prior to, during, and / or after administration of the anti-cancer agents. The methods reduce adverse effects associated with the anti-cancer agent, such as anorexia, weight loss, muscle mass loss, fat mass loss, wasting, reduced appetite, and loss of appetite, thereby enhancing tolerance of the anti-cancer agents and survival of the subject having cancer or having a disease or condition that is not cancer but is treated, reduced, or prevented by administration of an anti-cancer agent.

The invention discloses a process for synergistically inhibiting melanoma by carrying low-dose paclitaxel on nanoparticles based on immunoregulation. According to the invention, hyaluronic acid functionalized albumin nanoparticles are combined with low-dose paclitaxel, the tumor targeting property of the drug is improved by utilizing a nanotechnology, and meanwhile, the tumor immune microenvironment is regulated and the anti-tumor immune effect is enhanced by activating an STING pathway. Through the combination, the treatment effect of the medicine is improved, the side effect of the medicine is remarkably reduced, and a new strategy is provided for tumor treatment. High-efficiency delivery of low-dose paclitaxel is realized through the nano-carrier, the drug dosage is reduced, the toxicity is reduced, meanwhile, the antitumor activity of the paclitaxel is retained, a new thought is provided for clinical application of traditional chemotherapeutic drugs, the tolerance and life quality of patients are expected to be improved, polarization of M1 type macrophages is promoted by activating an STING pathway, and the antitumor activity of the paclitaxel is improved. Interferon and other inflammatory factors are released, CD8 + T cells are recruited and activated, and therefore the anti-tumor effect is achieved.

Disclosed herein are methods of administering compositions comprising a mixture of salts that induce purgation of the colon and are useful to cleanse the colon. Furthermore, the disclosed methods prevent degradation of PEG and allow for cleansing of the colon without the use of adjunct laxatives, including stimulant laxatives such as bisacodyl. The disclosed methods are superior to the prior art in that they allow for higher tolerability, improved safety, lower volumes, and improved patient compliance.

This invention relates to the field of appropriate immunotherapy for activating the immune response in patients. More specifically, the present invention relates to negative anti-EPO function modulators useful as active ingredients in pharmaceutical compositions for immunomodulatory strategies in therapies (e.g., cancer immunotherapy, therapies for infectious and inflammatory diseases) or for activating the immune system, enhancing cell-based or pharmacological or vaccine-based immunotherapy, and stimulating the immune system response of patients as needed. In particular, the present invention also describes how to restore the immune response in pathological conditions such as cancer and refractory infections, for example, by enhancing and ensuring therapeutic access to immunotherapy strategies by products consisting of EPO pathway inhibitors that can function as active pharmaceutical ingredients in vaccine compositions that stimulate the immune response in cancer, infectious diseases, and inflammatory diseases and be delivered to patients, thereby eliminating "tolerogenic" stimulation.

The present invention provides a composition of nebivolol and amlodipine, comprising nebivolol, amlodipine and a pharmaceutical excipient. The nebivolol comprises one or more of nebivolol, a pharmaceutically acceptable salt thereof, and a solvate thereof. The amlodipine comprises one or more of amlodipine, a pharmaceutically acceptable salt thereof, and a solvate thereof. The pharmaceutical excipient is selected from one or more of a filler, a binder, a disintegrant, a lubricant, and a glidant. The composition does not contain a colorant and a film coating. The compound preparation of the present invention has good stability, and is beneficial to improving the antihypertensive efficacy, enhancing safety and tolerability, and reducing side effects. Compared to monotherapy, the present invention reduces the number of administered medications and improves the compliance of patients, is beneficial to improving the medication compliance of the elderly patients and individuals with dysphagia, maintains a stable plasma drug concentration, maintains long-term stable blood pressure in hypertensive patients, prevents the patients from discontinuing medication arbitrarily, and prevents disease recurrence and the progression of severe complications.

To provide a combination for gastric cancer therapy which brings about enhanced therapeutic effects and reduced side effects.SOLUTION: Gastric cancer patients treated daily with the combination of the minelide prodrug and paclitaxel experienced significant negative side effects and cancer progression. Combination therapy of paclitaxel with a minelide prodrug administered according to the new regimen resulted in significantly improved therapeutic outcomes. The new dosing regimen comprises a 28-day cycle in which the minelide prodrug is administered once daily on days 1-5, 8-12, and 15-19 of the cycle, and paclitaxel is administered once daily on days 1, 8, and 15 of the cycle. The new dosing regimen was shown to be effective for treating gastric cancer and well tolerated in human patients.SELECTED DRAWING: Figure 5A

The invention relates to an API5 antigen epitope and an antibody specifically binding to the API5 antigen epitope or an antigen binding fragment thereof. The API5 epitopes according to the present invention elicit resistance, tolerance or non-responsiveness of cancer to anti-cancer drugs more strongly than other regions or epitopes present in the API5 protein. Therefore, the antibody or the antigen-binding fragment thereof that binds to the API5 epitope has an excellent cancer cell killing effect and an excellent tumor proliferation or growth inhibition effect, and particularly has an excellent anti-cancer effect on cancers that are resistant, tolerant or non-responsive to existing anti-cancer drugs.

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing or treating progressive hearing loss of large vestibular aqueduct syndrome as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from fructus psoraleae, herba cistanche, rhizoma drynariae, poria peel, polyporus umbellatus, cortex mori radicis, plantain herb, radix salviae miltiorrhizae, ligusticum wallichii, caulis spatholobi and honey-fried licorice root. The traditional Chinese medicine composition disclosed by the invention has the effects of tonifying kidney and strengthening primordial qi, and tonifying spleen and promoting urination, and is mainly used for preventing or treating patients with progressive hearing loss caused by large vestibular aqueduct syndrome. Compared with western medicine glucocorticoid, the traditional Chinese medicine composition has no adverse reaction, the health risk is reduced, and the treatment tolerance and compliance of patients are improved. A standardized scheme for preventing or treating progressive hearing loss of large vestibular aqueduct syndrome by traditional Chinese medicine is formed, clinical popularization is facilitated, more patients are benefited, a reference basis is provided for subsequent research, and related medical research is promoted.

The invention discloses application of a VCP inhibitor combined with an STING agonist in preparation of a medicine for treating colorectal cancer, and belongs to the technical field of biological medicines. The regulation and control effect of the VCP on a cGAS-STING signal channel is proved, and the anti-tumor immunity driven by the cGAS-STING can be enhanced by pharmacological inhibition of the VCP, so that the VCP inhibitor is put forward to be applied to anti-tumor treatment as an STING agonist anti-tumor sensitizer. The VCP inhibitor can enhance the treatment effect of the STING agonist on the colorectal cancer through the drug synergistic effect, and the combined treatment tolerance is good. The invention provides the application of the VCP inhibitor and the STING agonist in preparing the medicine for treating the colorectal cancer, provides a new way for clinical transformation for treating the colorectal cancer, and has an application value.

Intravesical devices are provided that are wholly deployable within the bladder of a patient in need of treatment and are well tolerated by the patient. The device may include an elastic body having a retention shape having (i) dimensions that provide intravesical mobility and that prevent voiding of the medical device through the urethra, and (ii) dimensions, buoyancy, or both, that exclude the medical device from entering the orifices of the ureters. The elastic body may exert a maximum acting force less than 1 N when compressed to a shape with a maximum dimension in any dimension of 3 cm. The device may include a drug for controlled release within the bladder, for treatment of the bladder or a regional tissue. Methods of treatment are also provided that include selecting a patient in need of treatment in the bladder where tolerability of the treatment is a primary concern.

Methods and compositions relate to managing chimeric antigen receptor T (CAR T) cell therapy-associated diarrhea in human subjects undergoing such therapy for colorectal cancer (CRC) are disclosed. The CAR T cells target a CRC-associated antigen, such as Guanylate Cyclase C (GCC) or Carcinoembryonic Antigen (CEA). The methods comprise administering a prophylactic regimen to the subject post-infusion of CAR T cells. This regimen includes agents such as vedolizumab, infliximab, or prophylactic budesonide. Subjects are monitored for diarrhea development and severity based on predefined clinical criteria, including stool frequency or stool volume. The methods may further involve a tiered therapeutic algorithm for treating occurring diarrhea, potentially utilizing corticosteroids or antithymocyte globulin (ATG). These approaches aim to reduce the incidence, duration, and severity of CAR T induced diarrhea, thereby improving patient safety and treatment tolerability.

The present disclosure provides methods for treating or managing fibromyalgia and its associated symptoms in a subject in need hereof characterized by an early onset of one or more of: (1) a reduction in widespread pain characterized by about 0.3 or more difference in the LS mean change in the NRS Pain Score; (2) a reduction in sleep disturbance characterized by about 2.9 or more difference in the LS Mean change in PROMIS Sleep Disturbance T-score; (3) a reduction in fatigue characterized by about 2.0 or more difference in the LS Mean change in PROMIS Fatigue T-score; or (4) an improved sleep quality characterized by about 0.5 or more difference in the LS Mean change in NRS Sleep Quality Score, each as compared to placebo, comprising administering to a subject in need thereof 2.8 mg or 5.6 mg cyclobenzaprine HCl once daily in one or more dosage units by transmucosal administration. The present disclosure also provides methods for preventing or avoiding one or more of a clinically meaningful change in mean weight, a clinically meaningful change in mean systolic blood pressure or mean diastolic blood pressure, or a decline in sexual functioning in conjunction with treating or managing fibromyalgia or its associated symptoms in a subject in need thereof, the treatment or management being characterized by the transmucosal administration of cyclobenzaprine HCl in one or more dosage units (e.g., a first dosage unit or a second dosage unit). The cyclobenzaprine HCl of these methods is in the form of a mannitol eutectic (e.g., a 75%±2% by weight cyclobenzaprine HCl and 25%±2% by weight β-mannitol eutectic) and the one or more dosage units further comprise a basifying agent.

Disclosed herein are methods of administering compositions comprising a mixture of salts that induce purgation of the colon and are useful to cleanse the colon. Furthermore, the disclosed methods prevent degradation of PEG and allow for cleansing of the colon without the use of adjunct laxatives, including stimulant laxatives such as bisacodyl. The disclosed methods are superior to the prior art in that they allow for higher tolerability, improved safety, lower volumes, and improved patient compliance.

The invention discloses application of licoflavone A in resisting viral hepatitis B, and belongs to the technical field of medicine application. The licoflavone A is used for treating viral hepatitis B. The licoflavone A used in the invention shows good safety and tolerance in HepG2.2. 15 and HepG2.A64 cells, can play a role in resisting HBV under the condition of no obvious cytotoxicity, and has significant advantages compared with interferon drugs in the prior art with long treatment course, large side effect and poor tolerance.

The invention relates to an effect of limited uptake of arachidonic acid (AA) in preparation of a chemotherapy sensitizer, and particularly relates to an application of the arachidonic acid (AA) in preparation of the chemotherapy sensitizer. A large number of researches find that the AA content is extremely related to the colorectal cancer chemotherapy resistance, the high level of AA has negative correlation with the colorectal cancer chemotherapy sensitivity, the AA can be used for predicting the colorectal cancer chemotherapy tolerance and sensitivity degree, and early evaluation is provided for the relation of preoperative treatment of a patient. Meanwhile, AA uptake is limited, for example, AA transporter SLC27A4 is inhibited, an important function of colorectal cancer chemotherapy sensitization is achieved, correspondingly, the tolerance of a patient to colorectal cancer chemotherapy can be reduced by reducing the level of AA in a body, the chemotherapy treatment effect is improved, the survival rate of the patient is prolonged, and prognosis is improved. The invention provides sufficient scientific basis and theoretical basis for exploring new colorectal cancer diagnosis, prognosis judgment and treatment molecular targets and developing new targeted drugs, is helpful for better realizing accurate treatment, and has important social value and scientific significance.

The invention relates to an application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer, and particularly relates to the following aspects: (1) osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and shows a remarkable curative effect in treatment of non-small cell lung cancer (NSCLC) patients carrying specific EGFR mutation; (2) chidamide is a novel oral HDACi, can induce cell apoptosis, cell cycle arrest and cell growth inhibition, and shows good tolerance and antitumor activity in various cancer types; and (3) chidamide is taken as an epigenetic regulating agent and can be in synergistic effect with osimertinib, so that the capability of killing lung cancer cells is enhanced. The invention belongs to the technical field of medicines, and particularly provides application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer.

The application provides a traditional Chinese medicine external application method for reducing the risk of fistula fibrosis in dialysis patients, relates to the technical field of clinical application of traditional Chinese medicine, is suitable for the prevention of autologous arteriovenous fistula fibrosis of maintenance hemodialysis patients, can effectively reduce the incidence of complications such as fistula peripheral tissue fibrosis and vascular stenosis, and prolongs the service life of the fistula. The drug stability and skin permeability are improved through optimization of adjuvants, and based on the grouping intervention of maintenance hemodialysis patients, the fistula blood flow and fibrosis improvement are evaluated in combination with color Doppler ultrasound. The application takes the principles of promoting blood circulation to remove blood stasis, dredging collaterals and resolving knots, and detoxification and swelling reduction as the therapeutic principles, prepares a fistula protection ointment by screening and optimizing a traditional Chinese medicine formula, realizes the effects of improving local microcirculation of the fistula, inhibiting fibrous tissue proliferation and reducing inflammatory reactions through external application intervention, thereby reducing the incidence of fistula fibrosis and related complications, prolonging the fistula patency time, simultaneously reducing the treatment cost, and improving the patient tolerance and life quality.

The present disclosure relates to compositions and methods for treating cancer comprising the administration of TLR7 / 8 agonist-containing compositions at dosages effective to elicit anti-tumor activity yet maintaining advantageous safety and tolerability profiles.

The application discloses a traditional Chinese medicine composition for treating overactive bladder (OAB) with kidney yang deficiency, a preparation method and application thereof. The composition is composed of three medicinal materials of fennel, cherokee rose and stir-baked dodder seed, and is formulated according to an optimal ratio. The composition improves the symptoms of frequent urination caused by OAB according to the TCM syndrome differentiation and treatment concept. The composition has the advantages of simple prescription, exact curative effect, no obvious toxic and side effects, simple medicine, easy quality control, low cost, reduced medical burden of patients, saved traditional Chinese medicine resources, and the like. The composition can obviously improve the urination indexes, OABSS scores and TCM syndrome scores of patients, improve the life quality of patients, has few adverse reactions, good tolerance and no drug dependence, and can significantly repair the bladder function of model rats and reduce the urination frequency. The product is prepared by adopting a volatile oil inclusion, alcohol extraction and water extraction combination and spray drying granulation process. The product contains 42 kinds of chemical components, mainly flavones and phenolic acids, has obvious comprehensive advantages, and has good industrialization and clinical application prospects.

An open-label, Phase I, first-in-human (FIH) multicenter, clinical study is / was conducted in multiple parts to establish the safety, tolerability and pharmacokinetic / pharmacodynamic (PK / PD) profile (with and without food) and early signs of efficacy of tuvuseritib (M1774) as monotherapy and in combination with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib.

The invention provides a tolerance evaluation system and method for medicines in an intelligent medicine box, and the method comprises the steps: extracting a medication behavior feature vector and a physiological feature vector from the weight change data of the medicines in the intelligent medicine box and a physiological signal after a target patient takes medicines, and determining the fusion features of the tolerance evaluation of the medicines; recognizing the dependency relationship between the medication event of the target patient and the physiological signal according to the fusion feature and the metabolic half-life period of the drug; combining the drug metabolism data of the target patient with a knowledge graph of drug action in the intelligent drug box to determine drug tolerance feature nodes of the target patient in the drug use process; and determining a drug tolerance tensor when the target patient takes drugs according to the tolerance feature node in combination with the dependency relationship, and generating a drug tolerance evaluation map according to the drug tolerance tensor and the current metabolic data of the target patient. According to the technical scheme provided by the invention, the dynamic association between the medication event of the target patient and the continuous physiological metabolism response in the drug tolerance evaluation can be identified.

A pharmaceutical composition comprising azilsartan medoxomil potassium and a calcium channel blocker, a method for preparing same, and use thereof are provided. Azilsartan medoxomil potassium and the calcium channel blocker are formulated into a compound formulation, thus improving the blood pressure lowering efficacy, improving safety and tolerability, and reducing adverse effects. Azilsartan medoxomil potassium can ameliorate peripheral edema caused by amlodipine by means of expanding peripheral venous vessels, while amlodipine can ameliorate adverse effects such as vasogenic edema, dry cough, and the like caused by azilsartan medoxomil potassium.

Through virtual screening based on molecular docking, molecular dynamics simulation, free energy calculation and experimental verification, it is found for the first time that benfotiamine can efficiently antagonize P2Y14R, and the IC50 value of benfotiamine reaches 0.31 nM. Experimental results show that benfotiamine can significantly relieve inflammatory reactions of a DSS-induced mouse colitis model and an MSU-induced gouty arthritis model, and the action mechanism of benfotiamine is closely related to inhibition of activation of NLRP3 inflammasomes. Benfotiamine is used as a vitamin B1 derivative clinically applied for a long time and has good safety and tolerance. The invention provides a brand new pharmacological action target and indication direction, realizes new use of old medicines, is beneficial to shortening the research and development period of medicines and reducing the development cost, and has important application prospects and economic and social values in the field of treatment of inflammatory diseases.

The present invention relates to a pharmaceutical composite formulation containing candesartan, amlodipine, and indapamide as active ingredients for preventing or treating hypertension. By including candesartan, amlodipine, and indapamide at low doses, the pharmaceutical composite formulation according to the present invention can reduce side effects that may occur due to excessive blood pressure reduction, and can be utilized as a composite formulation for preventing or treating hypertension owing to sufficient tolerability and excellent blood pressure-lowering effects.

The present invention provides a pharmaceutical composition containing azilsartan medoxomil potassium and a calcium channel blocker, as well as a method for preparing and using the same. The development of a combination formulation using azilsartan medoxomil potassium and a calcium channel blocker is advantageous in terms of improving antihypertensive effects, improving safety and tolerability, and reducing side effects. Azilsartan medoxomil potassium can alleviate amlodipine-induced peripheral edema by dilating peripheral venous blood vessels, while amlodipine can alleviate adverse reactions such as angioedema and dry cough caused by azilsartan medoxomil potassium. Compared with single drugs, the advantages of combination drugs include: (1) reducing medication dosage and improving patient compliance; (2) improving compliance for elderly people and those with dysphagia; and (3) preventing frequent fluctuations in blood drug concentrations, maintaining stable blood drug concentrations, stabilizing blood pressure in hypertensive patients over the long term, and reducing the side effects of each drug. (4) Avoid patients discontinuing medication on their own, and prevent disease recurrence and progression of malignant complications.