189072-06-8

Upstream product

• 868-77-9 2-methyl-2-propenoic acid 2-hydroxyethyl ester 
• 15687-27-1 ibuprofen 
• 71381-91-4 (+/-)-2-(4-isobutylphenyl)propanoyl chloride 

Relevant academic research and scientific papers

PH-Responsive nanoparticles based on ibuprofen prodrug as drug carriers for inhibition of primary tumor growth and metastasis

Cancer metastases represent a major determinant of mortality in patients with cancer. Cyclooxygenase-2 (COX-2) and its metabolites play important roles in tumor growth and metastasis. Overexpression of COX-2 have been found in various types of cancers including melanoma. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used to inhibit COX-2 and can be a promising additive for the management of aggressive cancers. A novel pH-sensitive drug delivery carrier based on PEG-derivatized ibuprofen, MPEG-PHEI, was synthesized for dual delivery of anticancer agents and NSAIDs. This amphiphilic and biodegradable copolymer could self-assemble into core-shell nanoparticles (NPs) and the hydrophobic doxorubicin (DOX) could be loaded into the core of the nanoparticles. DOX-loaded MPEG-PHEI nanoparticles (DOX/NPs) could release DOX in endosome microclimate via micelle collapse and ibuprofen via ester bond hydrolysis. In vitro DOX/NPs showed comparable cytotoxicity to DOX·HCl and comparable inhibition of COX-2 to ibuprofen. More importantly, DOX/NPs revealed a significant in vivo therapeutic efficacy in both experimental subcutaneous tumors and lung metastasis model while decreasing the toxicity of DOX. This study demonstrated the advantages of combining NSAIDs with chemotherapy agents and provided a novel nanoparticle system for both primary and metastatic tumor treatment.

Synthesis of hydrophilic intra-articular microspheres conjugated to ibuprofen and evaluation of anti-inflammatory activity on articular explants

The main limitation of current microspheres for intra-articular delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is a significant initial burst release, which prevents a long-term drug delivery. In order to get a sustained delivery of NSAIDs without burst, hydrogel degradable microspheres were prepared by co-polymerization of a methacrylic derivative of ibuprofen with oligo(ethylene-glycol) methacrylate and poly(PLGA-PEG) dimethacrylate as degradable crosslinker. Microspheres (40-100 μm) gave a low yield of ibuprofen release in saline buffer (≈2% after 3 months). Mass spectrometry analysis confirmed that intact ibuprofen was regenerated indicating that ester hydrolysis occurred at the carboxylic acid position of ibuprofen. Dialysis of release medium followed by alkaline hydrolysis show that in saline buffer ester hydrolysis occurred at other positions in the polymer matrix leading to the release of water-soluble polymers (>6-8000 Da) conjugated with ibuprofen showing that degradation and drug release are simultaneous. By considering the free and conjugated ibuprofen, 13% of the drug is released in 3 months. In vitro, ibuprofen-loaded MS inhibited the synthesis of prostaglandin E2 in articular cartilage and capsule explants challenged with lipopolysaccharides. Covalent attachment of ibuprofen to PEG-hydrogel MS suppresses the burst release and allows a slow drug delivery for months and the cyclooxygenase-inhibition property of regenerated ibuprofen is preserved.

DRUG FORMULATIONS

The invention relates to methods of producing solid drug formulations using advanced manufacturing techniques, such as 3D printing, where there is a requirement for low viscosity. The invention uses a photo-reactive material in liquid form, the photo-reactive material comprising: (a) prodrug monomer that comprises an active pharmaceutical ingredient in a prodrug form, in which the active pharmaceutical ingredient is releasably attached to a polymerisable group via a releasable covalent bond, and, optionally, (b) diluent monomer that comprises a polymerisable group.

Ibuprofen sustained release microsphere as well as preparation method and application thereof

The invention relates to the technical field of sustained-release medicines, in particular to an ibuprofen sustained-release microsphere as well as a preparation method and application thereof. The preparation method of the ibuprofen sustained release microspheres provided by the invention comprises the following steps: mixing ibuprofen, thionyl chloride and a catalyst, and carrying out substitution reaction to obtain 2-(4-isobutylphenyl)propionyl chloride; mixing the 2-(4-isobutylphenyl)propionyl chloride and hydroxyethyl methylacrylate, and carrying out an esterification reaction, so as to obtain 2-((2-(4-isobutylphenyl) propionyl) oxy)ethylmethacrylate; under the action of an emulsifier and an initiator, subjecting the 2-((2-(4-isobutylphenyl)propionyl)oxy)ethylmethacrylate, methyl methacrylate and ethylene glycol dimethacrylate to a polymerization reaction, so as to obtain the ibuprofen sustained release microspheres. The ibuprofen sustained-release microsphere prepared by the invention not only has a better sustained-release effect, but also can improve the bioavailability of ibuprofen.

Implantable bio-resorbable polymer

The present invention relates to a polymer obtained from the polymerization of: (i) at least one monomer of formula (I) (CH2═CR1)CO—K (I) wherein: K represents 0-Z or NH—Z, Z representing (CR2R3)m—CH

IMPLANTABLE SWELLABLE BIO-RESORBABLE POLYMER

The present invention relates to a polymer obtained from the polymerization of: (i) at least one monomer of formula (I) (CH2═CR1)CO—K (1) wherein: K represents O—Z or NH—Z, Z representing (CR2R3)m-CH3, (CH2—CH2—O)m-H, (CH2—CH2—O)m-CH3, (CH2)m-NR4R5 with m representing an integer from 1 to 30; R1, R2, R3, R4 and R5 independently represent H or a C1-C6 alkyl; (ii) at least between 0.1 and 50% mol, advantageously between 1 and 30% mol, more advantageously between 1 and 20 mol % of a cyclic monomer having a exomethylene group of formula (II) wherein: R6, R7, R8 and R9 represent independently H or a C5-C7 aryl group or R6 and R9 are absent and R7 and R8 form together with the carbon atom on which they are bonded a C5-C7 aryl group; i and j represent independently an integer chosen between 0 and 2; X represents either O or X is not present and in this latter case, CR6R7 and CR8R9 are linked via a single bond C—C and (iii) at least one bio-resorbable block copolymer cross-linker.