104 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 discovery and application of immune checkpoint inhibitors (ICI) have significantly promoted cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. To explore novel adjuvant treatment options, we performed fecal microbiota transplantation (FMT) of healthy donors on 10 GI cancer patients with resistance to anti-PD-(L) 1 treatment. The combination of FMT and anti-PD1 treatment was well tolerated and no serious adverse reaction was observed. Two out of 10 patients restored clinical responsiveness to anti-PD1 after FMT. Clinical benefits were shown to be associated with better colonization of co-occurred immunogenic microbes from donors, alongside activated immune status reflected by the peripheral immune cell population. Moreover, we identified microbial signatures of ICI responsiveness and validated in an independent cohort. Our study demonstrates the feasibility of FMT as a potential adjuvant therapy for ICI irresponsive GI cancer patients and laid a foundation for LBP / consortia development to enhance ICI efficacy.

Provided herein is, among other things, is a method of treating cancer using an improved intermittent dosing regimen for Azenosertib, or a pharmaceutically acceptable salt thereof, administration to achieve a highly efficacious, safe and tolerable dosing regimen to treat many different types of cancers. In one aspect, the method of treating cancer comprises administering a daily dose of Azenosertib, or a pharmaceutically acceptable salt thereof, (e.g., greater than about 350 mg) in accordance with an improved intermittent dosing cycle, wherein the intermittent dosing cycle comprises one or more dosing weeks with each dosing week comprising between about 2-7 consecutive dosing days and between about 1-7 days without dosing. In some embodiments, the intermittent dosing cycle is repeated wherein the dosing weeks are separated by a break of one, two or more weeks. In some aspects, Azenosertib, or a pharmaceutically acceptable salt thereof, is administered as a combination therapy.

Provided are a recombinant cat allergen, a pharmaceutical composition therefor, a preparation method therefor, and a use thereof. Compared with naturally extracted allergen products, the recombinant cat allergen has multiple advantages in desensitization immunotherapy and allergen diagnosis for cat allergic diseases. For example, high purity and high uniformity are achieved; a pure protein / peptide having specified properties and quality is defined; the allergenicity, immunogenicity, and tolerability of the allergen are predetermined; production is performed according to GMP standards; the production of a specified quantity and concentration in a reproducible manner is enabled; product standardization and quality controllability are achieved; regulatory requirements for modern pharmaceuticals and vaccines are met; and when used for diagnosis, the allergen can identify allergen molecules that truly cause allergic reactions and reveal cross-reactivity, and when used for treatment, the allergen enables targeted allergen immunotherapy for a patient, avoiding the influence of non-allergenic substances in an extract, improving the safety, and facilitating precise diagnosis, precise administration, etc.

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.

Chronic obstructive pulmonary disease is a major clinical challenge mostly due to cigarette smoke exposure and affects more than 200 million people. The inventors tested if exposure to the Bordetella pertussis BPZE1 strain could modulate outcomes of chronic exposure to cigarette smoke in mice. In particular, they showed in mice chronically exposed to cigarette smoke that preventive and / or curative vaccination using BPZE1 could limit the lung inflammation and strongly contribute to the prevention of lung function decline. BPZE1 vaccination modulated pulmonary antigen presenting cells (macrophages and dendritic cells) to switch the immune response, by decreasing the IL-17 inflammatory pathway involved in the pathology of COPD itself, and by favouring a tolerogenic response (IL-10). Together, the data show that vaccination with BPZE1 of mice chronically exposed to cigarette smoke limits the development of chronic obstructive pulmonary disease outcomes and thus represents an interesting therapy.

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.

Disclosed is a method for treating thyroid cancer by using a fibroblast activation protein inhibitor modified with radiolabeled truncated Evans blue. The drug demonstrates good safety and tolerability in thyroid cancer patients, offering excellent therapeutic prospects in the treatment of thyroid cancer.

The invention belongs to the technical field of biological medicine, and particularly relates to application of coniferyl aldehyde in preparation of anti-cancer drugs. The invention discloses application of coniferyl aldehyde in preparation of anti-cancer drugs, coniferyl aldehyde can significantly inhibit invasion and migration ability of hepatocellular carcinoma cells, cancer cells cannot break through primary parts through key links such as interference of movement and adhesion of the cancer cells and degradation of extracellular matrixes, invasion of tumors to surrounding tissues is reduced, and the anti-cancer effect is improved. The occurrence rate of remote metastasis is reduced, the non-metastasis lifetime of the patient is prolonged, and more treatment time and survival opportunities are won for the patient; a large number of cell experiments and animal experiments prove that the medicine has no obvious liver and kidney toxicity under the treatment dosage, the tolerance of a patient to treatment is improved, the smooth proceeding of the treatment process is guaranteed, and the living quality of the patient is effectively improved.

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.

The invention provides a traditional Chinese medicine composition for treating myelosuppression. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 45-55 parts of astragalus membranaceus, 20-30 parts of glossy privet fruit, 15-25 parts of rubia yunnanensis, 45-55 parts of caulis spatholobi, 20-30 parts of polygonum cuspidatum, 15-25 parts of radix ranunculi ternati and 25-35 parts of wild buckwheat. The invention further provides a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition disclosed by the invention has the effects of strengthening the body resistance, tonifying deficiency and enhancing the immune function of a patient, improves the tolerance of a tumor patient to an anti-tumor drug, and is particularly suitable for prognosis treatment of a lung cancer patient with deficiency of both qi and yin. The traditional Chinese medicine composition can improve the myelosuppression symptom after anti-tumor medicine treatment (such as chemoradiotherapy), has the effects of increasing the capacity of white blood cells, red blood cells, blood platelets, bone marrow DNA, hematopoietic stem cells or / and hematopoietic tissues and treating cancer fatigue and / or consumptive disease, and plays the optimal effect at a low dosage. The preparation method is simple and is suitable for large-scale production, popularization and application.

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.

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 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 dual therapy involving tumor stroma-binding IL-7 and IL-12 variants led to synergistic antitumor efficacy through suppression of immune exhaustion and promotion of immune memory without compromised tolerability. The disclosure describes a polypeptide comprising an IL-7 polypeptide, or a functional fragment thereof, linked to a extracellular matrix (ECM)-affinity domain. Also described is a nucleic acid encoding a polypeptide of the disclosure and cells comprising the polypeptide(s) or nucleic acid(s) of the disclosure.