26680-10-4

Usage

Uses

Used in Controlled Release Applications:
3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer is used as a controlled release material for its ability to provide a sustained and controlled release of active ingredients over an extended period. This property is particularly useful in the pharmaceutical and medical industries for drug delivery systems.
Used in Drug Delivery Systems:
In the pharmaceutical industry, 3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer is used as a component in drug delivery materials for its biodegradability and biocompatibility. It can be formulated into various forms such as microspheres, nanoparticles, or implants to improve the delivery, bioavailability, and therapeutic outcomes of drugs.
Used in Medical Devices:
3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer is also utilized in the medical device industry for the development of implantable devices, such as sutures, pins, and screws, due to its mechanical properties and biocompatibility.
Used in Tissue Engineering:
In the field of tissue engineering, 3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer serves as a scaffold material for the growth and regeneration of various tissues. Its biodegradability allows it to be gradually replaced by the body's own tissue as the healing process progresses.
Used in Packaging Industry:
3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer can be used in the packaging industry for the development of biodegradable and environmentally friendly packaging materials, reducing the environmental impact of plastic waste.
Used in Cosmetics Industry:
In the cosmetics industry, 3,6-Dimethyl-1,4-dioxane-2,5-dione homopolymer may be used as an ingredient in various cosmetic products, such as creams, lotions, and gels, for its ability to provide controlled release of active ingredients and improve product performance.

Production Methods

Lactic acid is a chiral molecule and has two optically active forms: Llactic acid and D-lactic acid. Poly(DL-lactic acid) is produced from the racemic mixture of lactic acid. Lactic acid is produced either from ethylene (petrochemical pathway) or by bacterial fermentation of D-glucose derived from food stocks. The former pathway involves an oxidation step followed by treatment with hydrogen cyanide and produces only racemic DL-lactic acid. In contrast, lactic acid produced by fermentation occurs mainly as L-lactic acid. Lowmolecular- weight poly-DL-(lactic acid) (500–10 000 Da) is produced directly from lactic acid by condensation. Higher-molecular-weight product is produced by one of two major pathways. The first involves a depolymerization of low-molecular-weight polymer into the cyclic dimer form (lactide) followed by ring-opening polymerization. Alternatively, it can be produced by a direct condensation using azeotropic distillation.

Pharmaceutical Applications

Poly(DL-lactic acid) is used in drug delivery systems in implants, injections, and oral solid dispersions. It is also used as a coating agent.

Safety

Poly(DL-lactic acid) degrades to produce lactic acid, which is considered a well-tolerated nontoxic material. Several in vitro and in vivo studies demonstrated that poly(lactic acid) in general (including poly(DL-lactic acid)) is well tolerated and does not induce a significant immune response.However, some studies have illustrated signs of a mild immune response.The FDA has also reported some rare cases of inflammatory responses in patients treated with cosmetic poly(DL-lactic acid) injections.

storage

Poly(DL-lactic acid) is stable under dry conditions. However, it typically biodegrades over a period of 10–15 months according to the molecular weight. Increasing moisture and temperature enhances biodegradation; the onset of degradation in water at 25°C is 6 months.In contrast to many other biodegradable polymers, poly(DL-lactic acid) degrades through a two-step mechanism. The primary degradation step involves the hydrolysis of the ester bonds independently of microbial activity to produce a low-molecular-weight polymer. When the molecular weight drops below 10 000, microorganisms digest the polymer into carbon dioxide and water. Poly(DL-lactic acid) is more stable than poly(L-lactic acid) or poly(D-lactic acid) alone.Poly(DL-lactic acid) should be stored in a dry inert environment at a temperature of －15°C to －20°C.

Incompatibilities

Incompatible with strong acids or alkaline materials.

Regulatory Status

Included in the FDA Inactive Ingredients Database (IM, powder, for injection, suspension, and lyophilization). Poly(DL-lactic acid) is considered as ‘not hazardous’ according to the European Directive 67/548/EEC. Included in parenteral preparations (prolongedrelease powder for suspension for subcutaneous or intramuscular injection) licensed in the UK.

Upstream product

• 849585-22-4 LACTIC ACID 
• 4511-42-6 L,L-dilactide 
• 79-33-4 L-Lactic acid 
• 2216-51-5 (-)-menthol 
• 13076-19-2 (3R,6S)-3,6-dimethyl-1,4-dioxane-2,5-dione 
• 673502-34-6 5-acetyl-3,6-dimethyl-2,3-dihydro-1,4-dioxin-2-one 
• 10326-41-7 D-Lactic acid 
• 97-64-3 ethyl 2-hydroxypropionate 
• 27871-49-4 (S)-Methyl lactate 
• 13076-17-0 D-lactide 
• 26680-10-4 3,6-dimethyl-1,4-dioxane-2,5-dione 
• 1071822-17-7 (6S)-3-methylene-6-methyl-1,4-dioxane-2,5-dione 
• 547-64-8 methyl lactate 

Downstream Products

• 52183-00-3 1,1-diphenylpropane-1,2-diol 
• 106942-22-7 lactanilide 
• 57-55-6 propylene glycol 
• 13076-19-2 (3R,6S)-3,6-dimethyl-1,4-dioxane-2,5-dione 
• 27871-49-4 (S)-Methyl lactate 
• 687-47-8 (S)-Ethyl lactate 
• 64231-47-6 (S)-2-hydroxy-propionic acid (S)- 1-ethoxycarbonyl-ethyl ester 
• 26680-10-4 3,6-dimethyl-1,4-dioxane-2,5-dione 
• 2037-15-2 Methyl 2-(2-hydroxypropionyl)propionate 
• 547-64-8 methyl lactate 
• 909025-04-3 (2S)-1-{[(2S)-1-(benzyloxy)-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-hydroxypropanoate 

Relevant academic research and scientific papers

Synthesis and characterization of a brush-like copolymer of polylactide grafted onto chitosan

A brush-like poly(DL)-lactide grafted onto chitosan as the backbone was investigated. The graft copolymerization was carried out with triethylaluminum as catalyst in toluene at 70°C. It was found that a greater lactide content in the feeding ratio results in a higher grafting percentage. FTIR spectrometry, 1H NMR, DSC scanning, and wide-angle X-ray scattering, respectively, are used to characterize these branch copolymers. A copolymer has a definite melting point when the molar feeding ratio of lactide to chitosan is more than 10:1, and the ΔH of the copolymers increases with the feed ratio of lactide to chitosan in feeding.

From meso-Lactide to Isotactic Polylactide: Epimerization by B/N Lewis Pairs and Kinetic Resolution by Organic Catalysts

B/N Lewis pairs have been discovered to catalyze rapid epimerization of meso-lactide (LA) or LA diastereomers quantitatively into rac-LA. The obtained rac-LA is kinetically polymerized into poly(l-lactide) and optically resolved d-LA, with a high stereoselectivity kL/kD of 53 and an ee of 91% at 50.6% monomer conversion, by newly designed bifunctional chiral catalyst 4 that incorporates three key elements (β-isocupreidine core, thiourea functionality, and chiral BINAM) into a single organic molecule. The epimerization and enantioselective polymerization can be coupled into a one-pot process for transforming meso-LA directly into poly(l-lactide) and d-LA.

Chemical Recycling of End-of-Life Poly(lactide) via Zinc-Catalyzed Depolymerization and Polymerization

The chemical recycling of poly(lactide) was investigated based on depolymerization and polymerization processes. Using methanol as depolymerization reagent and zinc salts as catalyst, poly(lactide) was depolymerized to methyl lactate applying microwave heating. An excellent performance was observed for zinc(II) acetate with turnover frequencies of up to 45000 h?1. In a second step the monomer methyl lactate was converted to (pre)poly(lactide) in the presence of catalytic amounts of zinc salts. Here zinc(II) triflate revealed excellent performance for the polymerization process (yield: 91 %, Mn ～8970 g/mol). Moreover, the (pre)poly(lactide) was depolymerized to lactide, the industrial relevant molecule for accessing high molecular weight poly(lactide), using zinc(II) acetate as catalyst.

In Vitro Characterization and Evaluation of the Cytotoxicity Effects of Nisin and Nisin-Loaded PLA-PEG-PLA Nanoparticles on Gastrointestinal (AGS and KYSE-30), Hepatic (HepG2) and Blood (K562) Cancer Cell Lines

The aim of this study was an in vitro evaluation and comparison of the cytotoxic effects of free nisin and nisin-loaded PLA-PEG-PLA nanoparticles on gastrointestinal (AGS and KYSE-30), hepatic (HepG2), and blood (K562) cancer cell lines. To create this novel anti-cancer drug delivery system, the nanoparticles were synthesized and then loaded with nisin. Subsequently, their biocompatibility, ability to enter cells, and physicochemical properties, including formation, size, and shape, were studied using hemolysis, fluorescein isothiocyanate (FITC), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM), respectively. Then, its loading efficiency and release kinetics were examined to assess the potential impact of this formulation for the nanoparticle carrier candidacy. The cytotoxicities of nisin and nisin-loaded nanoparticles were evaluated by using the MTT and Neutral Red (NR) uptake assays. Detections of the apoptotic cells were done via Ethidium Bromide (EB)/Acridine Orange (AO) staining. The FTIR spectra, SEM images, and DLS graph confirmed the formations of the nanoparticles and nisin-loaded nanoparticles with spherical, distinct, and smooth surfaces and average sizes of 100 and 200?nm, respectively. The loading efficiency of the latter nanoparticles was about 85–90%. The hemolysis test represented their non-cytotoxicities and the FITC images indicated their entrance inside the cells. An increase in the percentage of apoptotic cells was observed through EB/AO staining. These results demonstrated that nisin had a cytotoxic effect on AGS, KYSE-30, HepG2, and K562 cancer cell lines, while the cytotoxicity of nisin-loaded nanoparticles was more than that of the free nisin.

A study on highly concentrated lactic acid and the synthesis of lactide from its solution

Lactic acid is an important platform compound used as raw material for the production of lactide and polylactic acid. However, its concentration and composition distribution are not as simple as those of common compounds. In this work, the mass concentration distribution of highly concentrated lactic acid is determined by back titration. The components of highly concentrated lactic acid, crude lactide, and polymer after the reaction are analyzed by HPLC. Different concentrations of lactic acid solution were prepared for the synthesis of lactide and its content in the product was determined by 1H NMR analysis. We found that lactide is more easily produced from high-concentration lactic acid solution with which the condensed water is easier to release. Hence, the removal of condensed water is crucial to the formation of lactide, although it is not directly formed by esterification of two molecules of lactic acid.

Synthesis of new substituted 2,3-dihydro-1,4-dioxin-2-ones and 1,4-dioxan-2-ones

3-Alkyl-6-methyl-2,3-dihydro-1,4-dioxin-2-ones reacted with acetyl chloride in the presence of zinc(II) chloride to give the corresponding 3-alkyl-5-acetyl-6-methyl-2,3-dihydro-1,4-dioxin-2-ones. Oxidation of the latter with hydrogen peroxide in formic acid, followed by treatment with magnesium bromide, afforded 3-alkyl-6-methyl-1,4-dioxane-2,5-diones. Successive chlorination and dechlorination of 6-hydroxymethy 1-1,4-dioxan-2-ones yielded 6-methylene-1,4-dioxan-2-ones.

Effect of block lengths on the association behavior of poly(l-lactic acid)/poly(ethylene glycol) (PLA-PEG-PLA) micelles in aqueous solution

A series of poly(l-lactic acid)/poly(ethylene glycol) triblock copolymers with a PLA-PEG-PLA architecture were synthesized by a ring-opening polymerization (ROP) process. The copolymers were characterized by 1H NMR and GPC. The total number average molecular weights were in the range of 4,700-50,000, whereas the degrees of polymerization of the PLA and PEG blocks varied from 15 to 359 and from 68 to 136, respectively. The self-association of these copolymers in aqueous environment was studied by emission fluorescence spectroscopy of anilinonaphthalene probe and the critical association concentration (CAC) of the copolymers was measured. It was found that the micellization process of these copolymers was mainly determined by the length of the hydrophobic LA block, while the length of the hydrophilic PEG block had little effect. Furthermore, the low CAC values of the copolymers suggest that the copolymers form stable supramolecular structures in aqueous solutions.

Progress toward reaction monitoring at variable temperatures: a new stopped-flow NMR probe design

A stopped-flow NMR probe is described that enables fast flow rates, short transfer times, and equilibration of the reactant magnetization and temperature prior to reaction. The capabilities of the probe are demonstrated by monitoring the polymerization of lactide as catalyzed by the air-sensitive catalyst 1,3-dimesitylimidazol-2-ylidene (IMes) over the temperature range of ?30 to 40 °C. The incorporation of stopped-flow capabilities into an NMR probe permits the rich information content of NMR to be accessed during the first few seconds of a fast reaction. Copyright

Synthesis of lactide from lactic acid and its esters in the presence of rare-earth compounds

A procedure is described for the synthesis of lactide by dehydration of L-lactic acid and subsequent depolymerization of its oligomer mixture in the presence of yttrium(III) and praseodymium(III) oxides, as well as of cerium(III) chloride heptahydrate. The catalytic activity of yttrium and praseodymium sesquioxides was determined at different temperatures at the oligomerization and deoligomerization stages. Ethyl lactate was prepared in the presence of Purolite C100 MB cation exchange resin and subjected to oligomerization followed by thermal decomposition of oligoester and oligolactic acid mixture in the presence of yttrium(III) and praseodymium(III) oxides and aqueous cerium(III) chloride.

Design of a heterogeneous catalytic process for the continuous and direct synthesis of lactide from lactic acid

We present a continuous one-step reaction pathway for optically pure lactide under atmospheric conditions based on a novel SnO2-SiO2 nanocomposite catalyst. The new heterogeneous catalytic system gave a record high lactide yield of 94% with almost 100% enantioselectivity and long-term stability (>2500 h) from l-lactic acid.