Гексаметилендиизоцианат синоним

Environmental, Behavior, Fate, Routes, and Pathways

HDI is an industrial chemical that is not known to occur naturally. All of the potential exposures to this compound are associated with the production, handling, use, and disposal of HDI and HDI-containing products or materials. HDI may be found in air near areas where spray paints containing it as a hardening agent are applied. HDI vapor is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 16–48 h. Because of its relatively short atmospheric half-life and possible rapid hydrolysis, it is not expected that HDI will be transported to long distances in air. HDI is not expected to leach or adsorb onto solids due to its rapid degradation reaction with water. Because of these reactions, it is not expected that HDI will bioconcentrate in aquatic organisms or bioaccumulate in the food chain. Because of the rapid hydrolysis of HDI in water and moist soil, neither volatilization from these media nor leaching from soil or sediment should be important partitioning processes. Further, HDI would also not be expected to partition onto suspended solids and sediment in water.

Environmental Fate and Behavior

HDI is not readily soluble (low mg l⁻¹ range) in water. However, upon contact with water, reactivity is rapid with a half-life of 0.23 h at 23 °C. This nonhomogeneous reaction is expected to produce principally polyureas. In the occupational environment, an aerosol can be formed by nebulization; however, with a vapor pressure of 0.007 hPa, HDI is expected to exist in the ambient atmosphere in its vapor state. As a vapor, HDI is expected to degrade in the atmosphere by reaction with hydroxyl radicals (half-life approximately 2 days). In direct contact with water, its rapid hydrolysis reduces the likelihood for HDI to bioaccumulate in the aquatic compartment or transfer to groundwater. Therefore, the rapid hydrolysis in an aquatic environment and relatively rapid degradation in atmosphere limits the ability of this substance to be bioaccumulative or persistent.

HDI – Hexamethylene Diisocyanate

4.38.5.22 Polyurethanes

Texter and Ziemer¹⁶⁶ created polyurethanes via FP in microemulsions. Chen et al.¹⁶⁷ created epoxy-polyurethane hybrid networks frontally. Pot lives were on the order of hours. Hu et al.¹⁶⁸ frontally prepared urethane–acrylate copolymers in DMSO using persulfate as the initiator. Chen et al.⁹² studied FP of poly(propylene oxide) glycol, 2,4-toluene diisocyanate, and 1,4-butanediol with the catalyst stannous caprylate in dimethylbenzene. At room temperature, bulk polymerization did not occur quickly, and the pot life could be extended to 6 h if the solution was cooled to 10 °C. Mariani et al.¹⁶⁹ prepared diurethane diacrylates.

26.6 Toxicity of isocyanates

Commonly used isocyanates include toluene diisocyanate (TDI), methylenediphenyl diisocyanate (MDI), naphthalene diisocyanate (NDI), and hexamethylene diisocyanate (HDI). All isocyanates are toxic (Rye, 1973) to varying degrees; TDI seems to be the most toxic.

The National Institute of Occupational Safety and Health in the United States projected as early as 1978 that approximately 50,000–100,000 workers would be exposed to these chemicals within 2 years (NIOSH, 1978). The routine method of exposure of workers to isocyanates is by inhalation, and their toxicity is greater following inhalation than following oral ingestion; isocyanates that produce both pulmonary and sensory irritation are more toxic than those that cause only sensory irritation (Weyel et al., 1982).

Collagen

As the most abundant protein in the body, collagen is a major component of musculoskeletal tissues, the skin, and blood vessels. Collagen can be easily cross-linked using chemicals, such as aldehydes, carbodiimides, hexamethylene diisocyanate, and epoxy compounds; elevated temperatures; or high-energy irradiation. Cross-linked collagen is used as scaffolds for tissue engineering and drug delivery vehicles. The drug release profile from collagen matrices can be manipulated by varying the physical properties, such as density, porosity, and degradation kinetics. Cross-linked collagen has also been used as a vehicle for delivery of absorbed/adsorbed bioactive proteins, such as recombinant human bone morphogenetic protein-2 (INFUSE® (Medtronic)).

10.24.3.2.1(i) Automotive coatings

Two-component PUR systems have made major inroads into the market for transportation vehicle and automotive refinishing. Their main advantages for such applications are their fast curing and their outstanding final properties, such as weather stability, scratch resistance, and gloss. In such cases, use is predominantly made of systems comprising HDI and IPDI polyisocyanates in combination with polyacrylates and polyesters. By incorporating amine reactive thinners, coatings can be formulated with a particularly high-solids content.

4.3.2.16 Triblock Copolymer

This copolymer may be of either ABA type (two polymeric chains of the same type separated end to end by another type of polymeric chain) or ABC type (all three chains of this type of copolymer having a different polymeric material attached end to end in A-B-C manner). ABA type of triblock copolymer may be prepared by using diblock copolymer as an initiator molecule. Hwang et al. have prepared a powdered form of PEG-b-PCL-b-PEG triblock copolymer with the help of hexamethylene diisocyanate (HDI) as conjugating material. It could be understood into two steps where in the first step, It may form a diblock copolymer having a probable structure somewhat like PEG-PCL-OH but when further copolymerization occurs with the help of HDI as the conjugating material it further may lead to the formation of PEG-PCL-PEG. ABA type triblock copolymer may also be prepared by using a bifunctional initiator molecule (Hwang et al., 2005).

The preparation of A-B-C type of copolymer, which contains three different blocks (A, B, and C) may be affected by three major parameters: degree of polymerization, volume proportion of all three materials, and sequence of all three segments (ABC, BCA, or CAB) of the ABC-type triblock copolymer. Kaneko et al. have prepared poly[styrene-b-(ethylene-alt-propylene)-b-(methyl methacrylate)] (SEPM) and ABC type triblock copolymer, and have reported two types of morphology, that is, knitting and ladder type (Kaneko et al., 2006).

6.2 Antitumor Drug-Delivery Systems

Since DOX became a frontline drug used for chemotherapy treatment, a considerable number of studies have investigated the effects of DOX-loaded hydrogel nanocomposites in the treatment of different cancer types. Studies have demonstrated promising results for hydrogel systems containing Fe₃O₄ nanoparticles [174], silica nanoparticles [175], graphene oxide [176], etc. Overall, DOX-loaded hydrogel nanocomposites have demonstrated higher therapeutic efficacy and fewer side effects compared with free DOX. Moreover, controlled- or sustained-release systems have been developed for this drug, which lead to a reduction of DOX dose and greater patient safety and compliance.

Injectable thermoresponsive hydrogel nanocomposites of DOX were prepared by incorporating hexamethylene diisocyanate (HDI)–Pluronic F-127 (PF-127) copolymers in an HA matrix. The copolymer molecules, which are characterized by an amphiphilic nature, self-assemble into micelles in aqueous solutions (particle size from 100 to 200 nm). The release of DOX from the hydrogel nanocomposite was sustained over 28 days and it was completed after 30 days. A release rate of about 20 μg DOX/day was demonstrated. This release profile could maintain a high local concentration of DOX in the tissues affected by cancer for a long time period. Unlike the outer corona layer of the hydrogel, the inner core layers result in a slower diffusion rate of DOX due to the dense structure of the polymer. In antitumor activity assays, the tumor volume was evaluated in a nude mouse model considering different treatments (free DOX, DOX-loaded HDI–PF-127/HA hydrogel, DOX-loaded PF-127/HA hydrogel, and phosphate-buffered saline). The tumor volume was decreased by up to 70% with the DOX-loaded HDI–PF-127/HA hydrogel nanocomposite, while it was increased by about 210% and 250% with free DOX and PF-127/HA hydrogel, respectively. Once the hydrogel nanocomposite presented a sustained release over 28 days and a slower degradation rate compared with other treatments, these findings could explain its higher antitumor activity [38].

pH-responsive hydrogel nanocomposites have also been investigated for a targeted delivery of anticancer drugs in the intestine or colon. Hou and coworkers [177], for example, prepared pH-sensitive hydrogel nanocomposites containing graphene oxide (GO), azoaromatic crosslinks, and PVA for colon drug delivery. The freeze–thaw technique was used to prepare the hydrogels, and curcumin (CUR), an active constituent of turmeric, was used as the anticancer drug. Once the pH directly affected the system performance, swelling index and drug release assays were performed in pH 1.2, 6.8, and 7.4 to mimic drug transport in different gastrointestinal tract regions. The swelling ratio values of PVA hydrogels were approximately 400% at all pH values, while this parameter increased from 225% (pH 1.2) to 325% (pH 7.4) for GO-based hydrogel nanocomposites. At higher pH values, the carboxylic acid groups of GO became more ionized, increasing the electrostatic repulsion among the polymeric chains and, consequently, the swelling. The release of CUR from the hydrogel nanocomposites was shown to be pH dependent. Less than 10% of CUR was released from the hydrogel nanocomposites at pH 1.2, while about 20% and 50% was released at pH 6.8 and 7.4, respectively. In vivo imaging analysis showed stronger and more persistent fluorescence intensity for nanocomposite hydrogels in the colon compared with PVA hydrogels and control solutions. Based on these findings, the authors suggested that the hydrogel nanocomposite could protect the drug from the stomach and small intestine environment until it reached the proximal colon. In pharmacokinetic analyses, hydrogel nanocomposites showed higher AUC (3.15-fold) as well as lower t_1/2 (5.65-fold) and clearance rate (6.62-fold) compared with a CUR suspension, which was used as the control. In summary, GO/PVA-based hydrogel nanocomposites were shown to be a potential oral dosage form for colon cancer treatment since the target was achieved appropriately [177].

Chemical Cross-Linking of ECM Scaffolds

The use of chemicals to cross-link tissue-derived biomaterials is a commonly employed strategy for the prevention of degradation and/or masking of cellular epitope remaining within the decellularized material (Badylak, 2004; Jarman-Smith et al., 2004; Liang et al., 2004). Cross-linking reagents include glutaraldehyde, carbodiimide, and hexamethylene diisocyanate, among others (Vasudev et al., 2000). Due to the rapid degradation which has been observed following in vivo placement of many ECM-derived materials and subsequent loss of mechanical integrity, chemical cross-linking has been used to prevent or retard degradation and thereby the loss of mechanical integrity. The lack of degradation, while often purported to be an advantage in certain applications, is now recognized to prevent the process of constructive remodeling (Valentin et al., 2006, 2009, 2010; Brown et al., 2012b). Chemical cross-linking has also been employed to mask potentially immunogenic elements within nondecellularized and decellularized tissue-based grafts, and is commonly employed in the manufacture of porcine heart valves for human applications (Huelsmann et al., 2012). However, and as described above, not all cellular components within an ECM scaffold material have been associated with poor outcomes, particularly if present only in small amounts. The chemical changes to biological ligands caused by cross-linking can remove much of the beneficial bioactivity which is a major advantage of these biomaterials (Brown et al., 2010). Further, and as discussed in the following section, chemical cross-linking prevents the release of growth factors and bioactive peptides generated by parent molecule degradation.