The evolution of smart materials has allowed researchers to incorporate stimuli adaptive polymers, metals, composites and other systems in their new innovations. From phase changing and temperature/pH sensitive materials, shape memory alloys and piezoelectric ceramics, these materials have properties that change with respect to their designed sensitive conditions, which are utilized to create novel responsive products.
This paper will provide a brief review on pH-responsive systems as well as the identification of new emerging technologies utilizing these polymers by screening patent classification codes. In addition, the top researchers on designing these new polymers will be detailed with a synopsis of their recent research activities.
Examining patent classification codes relative to a type of material or a company’s activity can be useful in obtaining competitive intelligence information on how potential threats are moving forward in a field as well as locating Universities/affiliations to collaborate with or potential licensures.
pH-responsive polymers typically behave as a function of their acidic and basic moieties in their molecular chain. Acidic-type polymers change their structure, and/or physical or chemical properties in basic media and vice versa for basic polymers. General polymers that are known to have high pH sensitivity due to their acidic groups include polyacrylic acids, polysulfonamides and polyglutamic acid while low pH sensitive polymers are typically alkyl ammonium chloride based systems.
The pH-dependent acidic/basic groups within polymeric structures can be adjusted for the creation of new polymers that degrade, swell, solubilize or contract at specific pH profiles. For the creation of new types of pH-responsive polymers, this is typically done by the incorporation of acidic/basic sensitive end, covalent, block or graft components within the polymer matrix. These chemical moieties include carboxylic, sulfonic or ammonium additions.
Within the human body, different pH profiles can exist, which explains why these types of polymers have been most reported for uses in drug delivery. The pH sensitive polymer is initially bound or encapsulated on the active ingredient and then subsequently released at a certain pH. The pH sensitivity of the polymer determines the part of the body the active ingredient treats, for example for stomach illness, in which the stomach has a low pH, or the colon, which has neutral to basic pH conditions.
Patents: Where are the Innovations?
From examination of the Cooperative Patent Classification and well as the International Patent Classification codes for patents released over the past five years on pH responsive polymers, the top applications of these polymers are in the areas:
- Medical preparations
- Oil/gas drilling
- Analyzing materials (sensors, detectors, etc)
The top affiliations disclosing novelties within these areas will be discussed as well as a summary of their recent discoveries.
The area of pharmaceuticals (A61K) continues to be one of the most researched and top invented area for uses of pH sensitive polymers. Code definitions within this set include
A61K-009 for medicinal preparations characterised by special physical form pills, solutions, emulsions, ointments
A61K-031 for medicinal preparations containing organic active ingredients
A61K-047 for medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives, inorganics.
The Council of Scientific and Industrial Research, University of Washington and Sungkyunkwan University are the most prolific researchers within this targeted space.
- Council of Scientific and Industrial Research
This affiliation has focused on pH sensitive polymers for drug delivery systems. One of their most recent US granted patents is discussed in US 8,822,605 based on a graft copolymer that does not swell or dissolve at acidic pH in the stomach but does swell and dissolve at near neutral pH in the intestinal region. The graft copolymer is based on a polyester or poly (ester-ether) backbone with a polyacrylic grafts. The pH sensitive graft copolymer is claimed to swell at neutral or slightly basic conditions and can be used as an enteric coating for extended release formulations. Their other recent patent activity by this assignee includes:
US granted patent US 8,383,153: “Poly(amidoamine) oligomer hydrogel for drug delivery and drug carrier using the same”
US patent application US 20100233264: “Temperature and pH-sensitive block copolymer having excellent safety in vivo and hydrogel and drug delivery system using thereof”
University of Washington is currently engaged in pH sensitive outer shells for coated targets, membranes and other formulations for uses with therapeutic drugs or diagnostic agents. In US patent application US 20140161893, their invention is based around a pH-responsive polymeric shell and a pH-irresponsive polymeric core. The shell is based around methacrylate copolymers that have pendant groups that change their charges as a function of pH, of which releases the target agent when the polymer charge changes. The agents that can be used include toll-like receptor agonist, a vaccine, an antigen peptide, or an imaging agent. Their other inventions include:
US patent application US 20110117668: “Self-powered smart diagnostic devices”
US patent application US 20100150952: “pH-responsive polymer carrier compositions for cytosolic protein delivery”
This University is also heavily involved in drug delivery systems but utilizes block copolymer systems in their creation. The blocks or segments within the polymer as described in US patent application US 20110150978 is a polyethylene glycol containing an acrylate pH sensitive end group and also containing a polyamino acid and a heterocyclic alkyl amine. This triblock system forms hydrophobic-hydrophilic nanomicelles with anticancer, anti-inflammatory drugs, of which the bound drugs are released at pHs of 6-7 due to polymer collapse. Other recent patents include:
US granted patent US 8,383,153: “Poly(amidoamine) oligomer hydrogel for drug delivery and drug carrier using the same”
US patent application US 20120027690: “pH-sensitive graft copolymer, manufacturing method for same, and polymer micelles using method ”
The area of medicinal preparations using these polymers is the most dominate in novelties with pH sensitive polymers. Other examples of specific uses of these polymers within the IP landscape for medicinal preparations include:
- Nano and Advanced Materials Institute US patent application 20130034589: pH-sensitive nanoparticles for oral insulin delivery; Nano and Advanced Materials Institute
- Chonbuk National University World patent application WO 2014058252: pH-sensitive block copolymer containing cinnamaldehyde derivatives, and method for preparing same for anticancer use
- Indicator Systems International US patent application US 2013064772: Infection activated wound caring compositions and devices
- Yissum Research European patent application EP 2691085: Film-forming composition for a ph-dependant sustained release of the active agent
- University of Massachusetts US patent application US 2013337566: Responsive cell culture hydrogel
An emerging application of pH sensitive polymers in earth and rock drilling (E21B) was found, with Cooperative and International patent classification codes E21B-043 defined as
“methods or apparatus for obtaining oil, gas, water, soluble or meltable materials or a slurry of minerals from wells”
being the most common classification code. Also C09K-008 defined as
“Compositions for drilling of boreholes or wells”
was also indexed for patents around this space. Rhodia and Halliburton were found to be the most active recent patenting companies.
This diverse specialty chemistry company is targeting pH sensitive polymers for multiple uses. They recently have applied for US patent application US 2014178324 on a novel pH responsive polymer made with mono-[2-ethacryloyloxy)ethyl] phthalate and/or mono-[2-(methacryloyloxy)ethyl hexahydro]phthalate. Their new polymer is claimed to be insoluble in water at a low pH’s but at higher pH’s they become swellable or soluble in water and thus exhibit thickening behavior. In hydraulic fracturing, a viscous fracturing fluid is injected at high pressures into a well to form a fracture. To keep the newly formed site open, a proppant such as sand, ceramic beads or gravel are used to keep the fracturing site open and not collapse. The combination of pH sensitive polymer with a proppant is utilized in this part of the invention to prevent such collapses from occurring. They claim other applications of the pH sensitive polymer as a thixotropic promoters in latex paints and in other emulsion systems. The company also holds other US granted patents on pH sensitive systems including US 8,637,624, US 8,505,631 and US 8,501,983 all related to pH sensitive rheology modifiers for aqueous emulsions.
Halliburton was recently granted US granted patent US 8,746,339 that relates to preventing the loss of drilling and other well treatment fluids during construction of boreholes by the use of a new pH responsive polymer. This invention relates to a N-acryloyl acid polymer formed via free radical polymerization and is claimed to bond to other particles in the formulation at low pH. This interaction is believed to be due to the N-acryloyl acid polymer having flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties. At low pH’s the side chains are able to mediate hydrogen bonds across the polymer interfaces. This hydrogen bond network allows for a newly swelled system to form, thus preventing fluid loss through the holes. Other patents in this space includes US granted patent US 6,739,806 titled “Cement compositions with improved fluid loss characteristics and methods of cementing in subterranean formation” that utilizes a pH-sensitive crosslink polymer in a cement composition.
Lehigh University is also becoming affiliated with creating new polymers in pH sensitivity. They recently have applied for US patent application US 20140262203 related to pH and other stimuli responsive polymers used to coat silica sand, silt or clay. They disclose new formulations based on alkylthiophene and other receptive systems that are used to manipulate the flowability of fluids including ones used in boreholes.
Analyzing Materials (Sensors, Detectors, etc)
Patent classification code G01N was another area receiving novelties in relation to pH sensitive polymers. Patent classification codes G01N-021 and G01N-023 were the top definitions found related to these polymers with their code definitions being respectively
“analysis through the use of optical means”
“analysis through electric, electro-chemical, or magnetic means”
G01N-033 was also found to be indexed to may patents, which can be used to identify patents analyzing materials for food, medicinal, textiles and other applications.
Within this area, pH sensitive networks release materials at a specific pH and the active material is able to be analyzed, either by imaging techniques such as nuclear or magnetic resonance. The incorporation of contrast agents and materials that illuminate under imaging techniques are being utilized within these pH sensitive networks and are released at acidic/basic or neutral pHs for medical imaging and diagnostic applications.
The University of North Texas recently applied for US patent application US 20120065614 based on stabilizing transition metal phosphors in a wide variety of stimuli-sensitive polymers. With the use pH responsive structures of poly-N-isopropylacrylamide or chitosan, the resulting nanospheres release and photoluminesce at physiological pH and temperature. Areas of use include for biological labeling, imaging, and optical sensing.
Canon USA also has shown patent activity related to a fluorescence polymer having pH sensitivity and can be created with the addition of a fluorescent dye as cited in US patent application US 2010022759. This novel structure when exposed to a between 5 to about 6, the polymer structure changes from a random coil that diffuses quickly to a helix having slowed diffusion. The fluorescence polymer can be used as a fluorescence probe to detect tumors or illnesses that have these associated pHs.
Also, US patent application US 2014004048 assigned to the University of Pennsylvania discloses iron-oxide nanoparticles that are attached to a polyglutamic dendrimer containing a pH sensitive core. The core is released as the pH of the tumor site and is able to map out the location of hypoxic tumors. University of Washington was also found to be a major player with targeting pH sensitive polymers for uses in in-vitro imaging/molecular labeling as noted in US patent application US 2012282632 and in granted patent US 7,625,764 related to microdevice/bioanalytical and microfluidic systems having a pH sensitive polymeric component.
The use of patent classification codes can be a viable tool in monitoring the future direction of a given industry, especially for specialty chemistry companies. Within pH sensitive polymers, future innovations appear to be still within pharmaceuticals, with other areas emerging including well treatment fluids and the manufacture of sensors and analytical tools. Patent code information can be useful to guide a business to identify new companies that may be able to use their class of materials or in identifying new innovating areas and markets for a business to enter with an advanced material. Also, these codes can streamline the reviewing process to locate top assignees active in certain applications, whether it is to locate possible licensures or experts in an area.