Lyophilized cell cultures of Trametes hirsuta yield aldehydes from alkenes, representing a biotransformation alternative to ozonolysis.
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The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.
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There are several methods to prepare unilamellar liposomes and the protocols differ based on the type of desired unilamellar vesicles. Different lipids can be bought either dissolved in chloroform or as lyophilized lipids. In the case of lyophilized lipids, they can be solubilized in chloroform. Lipids are then mixed with a desired molar ratio.
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Liquid controls are more convenient than lyophilized (freeze-dried) controls because they do not have to be reconstituted, minimizing pipetting error.
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In 1983 Sailer described a new operative procedure in which lyophilized cartilage of organ donors is used as a replacement for patients’ bones.Sailer, H.F., Transplantation of Lyophilized Cartilage in Maxillofacial Surgery: Experimental Foundations and Clinical Success, Basel 1983 In the following decades the material has been tried and tested for reconstructions of all types in the region of the skull, jaws and the face.Sailer, H.F., Longterm Results after Implantation of different lyophilized Bones & Cartilage for Reconstruction in Craniofacial Surgery, in: A.G. Montoya, Monduzzi Bologna, 1992, p. 69-72 This saves the patient from undergoing a second operation for removal of bones and cartilage.
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Rationale Design of Stable Lyophilized Protein Formulations: Some Practical Advice, Carpenter et al, Pharmaceutical Research, Vol 14, No.8, 1977 Before administration, a lyophilized drug is reconstituted as a liquid before being administered. This is done by combining a liquid diluent with the freeze-dried powder, mixing, then injecting. Reconstitution usually requires a reconstitution and delivery system to ensure that the drug is correctly mixed and administered.
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Institute of Molecular Genetics: Translation of As with all lyophilized peptides, it needs refrigeration to remain stable within sterile water solutions, such as bacteriostatic water concentrations.
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Lyophilized drugs are stored in vials, cartridges, dual chamber syringes, and prefilled mixing systems. Lyophilization, or freeze drying, is a process that removes water from a liquid drug creating a solid powder, or cake. The lyophilized product is stable for extended periods of time and could allow storage at higher temperatures. In protein formulations, stabilizers are added to replace the water and preserve the structure of the molecule.
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In particular, it is used to prepare collagen sponges: collagen is dissolved into acidic solutions of acetic acid or hydrochloric acid that are cast into a mold, frozen with liquid nitrogen and then lyophilized.
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Examples of lyophilized biological products include many vaccines such as live measles virus vaccine, typhoid vaccine, and meningococcal polysaccharide vaccine groups A and C combined. Other freeze-dried biological products include antihemophilic factor VIII, interferon alfa, anti-blood clot medicine streptokinase, and wasp venom allergenic extract. Many bio- pharmaceutical products based on therapeutic proteins such as monoclonal antibodies require lyophilization for stability. Examples of lyophilized biopharmaceuticals include blockbuster drugs such as etanercept (Enbrel by Amgen), infliximab (Remicade by Janssen Biotech), rituximab, and trastuzumab (Herceptin by Genentech).
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If the solution doesn't contain any other soluble component than the protein in question the protein can be lyophilized (dried). This is commonly done after an HPLC run. This simply removes all volatile components, leaving the proteins behind.
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After fermentation, the polysaccharides are purified, formulated, and lyophilized using preservatives and stabilizers to make a vaccine product. The vaccine cannot protect from other serogroups of N. meningitidis and cannot completely eliminate the chance of infection by these serogroups.
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In many instances the decision to pretreat a product is based on theoretical knowledge of freeze-drying and its requirements, or is demanded by cycle time or product quality considerations.J. Jeff Schwegman (2009) "Basic Cycle Development Techniques for Lyophilized Products".
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Rotasiil is lyophilized pentavalent vaccine. It contain human bovine reassortant strains of rotavirus serotypes G1, G2, G3, G4 and G9. This is world's first thermostable vaccine which can be stored without refrigeration at or below 25 °C. Rotasiil is recently launched in India.
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Many different materials have been used in the past, including fascia lata, Lyodura (lyophilized human dura), Gore-Tex, Zenoderm (porcine skin dermis),Gerinec, A., & Slezakova, G. (2001). Posterior scleroplasty in children with severe myopia. Bratisl Lek Listy, 102(2), 73-78. animal tendons, and donor's or cadaver’s sclera.
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The proteins elute according to their hydrophobicity. After purification by HPLC the protein is in a solution that only contains volatile compounds, and can easily be lyophilized. HPLC purification frequently results in denaturation of the purified proteins and is thus not applicable to proteins that do not spontaneously refold.
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Dr. Hugenholtz and colleagues from the University of Queensland in Australia, have completed shotgun sequencing of lyophilized cells of V. chlorellavourus strain Gromov B, Mamkaeva K. 1980. Proposal of a new genus Vampirovibrio for chlorellavorus bacteria previously assigned to Bdellovibrio. Mikrobiologia 49:165–167. in culture with Chlorella vulgaris.
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This powder is easy to reconstitute. The lyophilized product has to be packaged without any oxygen. It has a shelf life of two years. Concluding, the treatment of lyophilization (freeze dried) of donkey's milk demonstrated that the natural colour, flavours, nutrients, bioactive substances of the fresh donkey milk are retained.
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Lyophilized 5% w/v sucrose cake in a pharmaceutical glass vial Pharmaceutical companies often use freeze-drying to increase the shelf life of the products, such as live virus vaccines, biologics and other injectables. By removing the water from the material and sealing the material in a glass vial, the material can be easily stored, shipped, and later reconstituted to its original form for injection. Another example from the pharmaceutical industry is the use of freeze drying to produce tablets or wafers, the advantage of which is less excipient as well as a rapidly absorbed and easily administered dosage form. Freeze-dried pharmaceutical products are produced as lyophilized powders for reconstitution in vials and more recently in prefilled syringes for self-administration by a patient.
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The available treatment for hemophilia at the time included transfusion of large volumes of fresh frozen plasma to replenish the missing clotting factors. Cryoprecipitate, and later in 1970, lyophilized factor VIII concentrates became available for the treatment of hemophilia A.Lusher JM. Development and introduction of recombinant factor VIII--a clinician's experience. Haemophilia 2012;18:483-6.
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Urist made the key discovery that demineralized, lyophilized segments of bone induced new bone formation when implanted in muscle pouches in rabbits. This discovery was published in 1965 by Urist in Science. Urist proposed the name "Bone Morphogenetic Protein" in the scientific literature in the Journal of Dental Research in 1971. Bone induction is a sequential multistep cascade.
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The cDNA coding for rasburicase was cloned from a strain of Aspergillus flavus. Rasburicase is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent.
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It is a strongly cationic glycoprotein, and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose.
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These are also called injectable formulations and are used with intravenous, subcutaneous, intramuscular, and intra-articular administration. The drug is stored in liquid or if unstable, lyophilized form. Many parenteral formulations are unstable at higher temperatures and require storage at refrigerated or sometimes frozen conditions. The logistics process of delivering these drugs to the patient is called the cold chain.
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The cold chain can interfere with delivery of drugs, especially vaccines, to communities where electricity is unpredictable or nonexistent. NGOs like the Gates Foundation are actively working to find solutions. These may include lyophilized formulations which are easier to stabilize at room temperature. Most protein formulations are parenteral due to the fragile nature of the molecule which would be destroyed by enteric administration.
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Pentamidine isethionate for injection is commercially available as a lyophilized, white crystalline powder for reconstitution with sterile water or 5% Dextrose. After reconstitution, the mixture should be free from discoloration and precipitation. Reconstitution with sodium chloride should be avoided due to formation of precipitates. Intravenous solutions of pentamidine can be mixed with intravenous HIV medications like zidovidine and intravenous heart medications like diltiazem.
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Differences may be the use of disintegrating aids, such as crospovidone, and binding agents that aid in mouth feel, such as microcrystalline cellulose. Primarily, ODTs contain some form of sugar such as mannitol, which typically serves as the major diluent of the ODTs, and is also the primary contributor to the smooth and creamy mouth feel of most ODTs. Lyophilized ODT formulations may use proprietary technologies but can produce a tablet that has a faster disintegration rate, for example the Zydis ODT typically dissolves in the mouth in less than 5 seconds without water and Lyophilized Freeze drying tablets - ODT typically dissolves in the mouth in few seconds depending on the molecules and strength. ODTs are available in HPDE bottles (Parcopa) or individually sealed in blister packs to protect the tablets from damage, moisture, and oxidation.
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Hwang K, Hwang JH, et al. Experimental study of autologous cartilage, acellular cadaveric dermis, lyophilized bovine pericardium, and irradiated bovine tendon: applicability to nasal tip plasty. J Craniofac Surg 2007;18(3):551–8 Article on Pubmed Examples of ECM biomaterials that meet these requirements and have been successfully used to create gTissue include SurgiMend,SurgiMend, TEI Biosciences Inc. Website TissueMend,TissueMend, Stryker Orthopaedics Website and Durepair.
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Purified chymopapain is the main component of the injection, composed basically of 20 mg in five millilitres. It is provided in vials containing 10.000 units of the lyophilized agent with 0.37 mg of disodium edetate, 3.5 mg of cysteine hydrochloride monohydrate and 1.0 mg of bisulfide. All of them work as stabilisers and activators. Sodium hydroxide is in charge of adjusting the PH of the solution.
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The FDA label indication is "For the treatment of lymphoma in dogs". Rabacfosadine can be used in dogs with lymphoma new to treatment and in dogs that are no longer responding to conventional chemotherapy. It comes in the form of a sterile, lyophilized powder that is reconstituted and administered as a 30-minute intravenous infusion. Infusions are given once every three weeks for up to five treatments.
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It is fitted out with modern technological and support equipment made by the leading European manufacturers. In 2013 the investment project on anticancer medicines production, in the form of lyophilized powders and solutions for injections was launched. A new building was erected to implement this project. The new capacities and production lines of high-performance drugs for complex polychemotherapy of oncologic diseases, including oncohematologic ones were set up.
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Donkey milk can be freeze dried to preserve the biological quality of the milk, and so preserve its nutritional, functional and cosmetic properties. This is possible because in freeze drying the milk is frozen and brought under vacuum at low temperatures. During this process the water is removed by sublimation. The result is approximately ten percent of dry matter that is called lyophilized (or freeze dried) donkey milk.
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The antigen for the FTA-ABS test is whole bacteria. The bacteria cannot be cultured on laboratory media, so the organisms used are a lyophilized suspension of T. pallidum extracted from rabbit testicular tissue. This is spread over and fixed to a slide. Patient serum is mixed with an absorbent (the "ABS" part of the test) containing an extract of a non- pathogenic treponeme, Treponema phagedenis biotype Rieter.
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Freeze-drying is also used in manufacturing of raw materials for pharmaceutical products. Active Pharmaceutical Product Ingredients (APIs) are lyophilized to achieve chemical stability under room temperature storage. Bulk lyophilization of APIs is typically conducted using trays instead of glass vials. Cell extracts that support cell-free biotechnology applications such as point-of-care diagnostics and biomanufacturing are also freeze-dried to improve stability under room temperature storage.
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CinnoVex is the trade name of recombinant Interferon beta-1a, which is manufactured as biosimilar/biogeneric in Iran. It is produced in a lyophilized form and sold with distilled water for injection. Cinnovex was developed at the Fraunhofer Society in collaboration with CinnaGen, and is the first therapeutic protein from a Fraunhofer laboratory to be approved as biogeneric / biosimilar medicine. There are several clinical studies to prove the similarity of CinnoVex and Avonex.
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Decellularized ECM biomaterials can be further processed into a fine powder and then lyophilized (freeze-dried). This powder can then be mixed with collagenase to form an ECM derived hydrogel (self-healing hydrogels). These hydrogels are then used in cell culture to help maintain cell phenotype and increase cell proliferation. Cells cultured on ECM hydrogels maintain their phenotype better than cells cultured on other substrates such as matrigel or type 1 collagen.
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An egg-layer, a typical adult female can lay 300,000 eggs in a single spawn. Although carp typically spawn in the spring, in response to rising water temperatures and rainfall, carp can spawn multiple times in a season. In commercial operations, spawning is often stimulated using a process called hypophysation, where lyophilized pituitary extract is injected into the fish. The pituitary extract contains gonadotropic hormones which stimulate gonad maturation and sex steroid production, ultimately promoting reproduction.
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The use of cross-linked enzyme crystals (CLECs) as industrial biocatalysts was pioneered by Altus Biologics in the 1990s. CLECs proved to be significantly more stable to denaturation by heat, organic solvents and proteolysis than the corresponding soluble enzyme or lyophilized (freeze-dried) powder. CLECs are robust, highly active immobilized enzymes of controllable particle size, varying from 1 to 100 micrometer. Their operational stability and ease of recycling, coupled with their high catalyst and volumetric productivities, renders them ideally suited for industrial biotransformations.
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Lymphocyte T-cell immunomodulator, or T-4 immune stimulating factor (TISF), is a single chain polypeptide that is a strongly cationic glycoprotein and is purified with cation exchange resin. Purification of protein from bovine-derived type II thymic epithelial cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose.
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In recent years, the cosmetic industry is mainly focused towards products made with natural ingredients and it is oriented to a sustainable consumption. Because of their natural origin, milk components correspond in many fields to the needs of cosmetology. Recent scientific study on a cream containing of lyophilized donkey milk showed different benefits for the skin. These results are related to the effectiveness of donkey milk components like proteins, minerals, vitamins, essential fatty acids, bioactive enzyme and coenzyme which allow the skin a balanced nourishment and a proper hydration.
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Botryosphaeran is produced under submerged fermentation conditions when Botryosphaeria rhodina MAMB-05 is grown on nutrient media containing glucose and mineral salts. Extracting the fermentation broth with alcohol causes the EPS (botryosphaeran) to precipitate from solution, and this can be separated by centrifugation or filtration. The precipitate recovered can be lyophilized to a white fibrous material that is sparingly soluble in water. Alternatively, the recovered precipitate is resolubilized in water (gentle heating with stirring) to form a viscous solution that forms a firm gel when cooled to 5°C.
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The liquid formulation was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change that was made to the formulation around April 2007 to include edetate disodium (EDTA). The upward trend in adverse reaction reporting rates had not been observed with the use of lyophilized sargramostim. The original liquid formulation without EDTA was returned to the market in the US in May 2008. In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area.
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The evofosfamide drug product formulation used until 2011 was a lyophilized powder. The current drug product formulation is a sterile liquid containing ethanol, dimethylacetamide and polysorbate 80. For intravenous infusion, the evofosfamide drug product is diluted in 5% dextrose in WFI.FDA Advisory Committee Briefing Materials Available for Public Release, TH-302: Pediatric oncology subcommittee of the oncologic drugs advisory committee (ODAC) meeting, December 4, 2012 Diluted evofosfamide formulation (100 mg/ml evofosfamide, 70% ethanol, 25% dimethylacetamide and 5% polysorbate 80; diluted to 4% v/v in 5% dextrose or 0.9% NaCl) can cause leaching of DEHP from infusion bags containing PVC plastic.
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Because ODTs are soft in nature, the ability to successfully package an ODT in a bottle is difficult. However, CIMA Labs markets their Durasolv ODT as being able to be placed into bottle for commercial sale, while CIMA's Orasolv is marketed for blisters only. Zydis ODT tablets manufactured by Catalent Pharma Solutions and Lyophilized Freeze drying tablets manufactured by Galien-LPS are delivered in a blister pack. The differences between the two CIMA products are proprietary, however, the primary difference is expected to be the use of microcrystalline cellulose (MCC), such as Avicel PH101, in the Durasolv product.
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Avonex was approved in the US in 1996, and in the European Union in 1997, and is registered in more than 80 countries worldwide. It is the leading MS therapy in the US, with around 40% of the overall market, and in the European Union, with around 30% of the overall market. It is produced by the Biogen biotechnology company, originally under competition protection in the US under the Orphan Drug Act. Avonex is sold in three formulations, a lyophilized powder requiring reconstitution, a pre-mixed liquid syringe kit, and a pen; it is administered via intramuscular injection.
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DraxImage MAA kits for preparing 99mTc-MAA are available in the United States from only a single manufacturer; Jubilant DraxImage Inc. The kits are delivered to nuclear pharmacies as lyophilized powders of non- radioactive ingredients sealed under nitrogen. A nuclear pharmacist adds anywhere from 50 - 100 mCi of Na[99mTcO4] to the reaction vial to make the final product, in the pH range of 3.8 to 8.0. After being allowed to react at room temperature for 15 minutes to ensure maximum labeling of the human albumin with 99mTc, the kit can then be diluted with sterile normal saline as needed.
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Shingrix is a suspension for intramuscular injection consisting of a lyophilized recombinant varicella zoster virus (VZV) glycoprotein E (gE) antigen that is reconstituted at the time of use with AS01B suspension as an immunological adjuvant. The antigen is a purified truncated form of the glycoprotein, expressed in Chinese hamster ovary cells. The AS01B adjuvant suspension is composed of 3-O-desacyl-4'- monophosphoryl lipid A (MPL) from Salmonella (Minnesota strain) and a saponin molecule (QS-21) purified from Quillaja saponaria (soap bark tree) extract, combined in a liposomal formulation consisting of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution.
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ErythroMer is a red blood substitute in development funded by the National Institutes of Health and U.S. Department of Defense. Similar to other HBOCs, the product is stable for several months even when freeze-dried, and can be reconstituted from its lyophilized state in emergency situations. This opens up the possibility of eventual stockpiling of ErythoMer making it easier to supply blood in large amounts to those who need it.. The development of this technology was done at Washington University at St. Louis and UIUC. Trials have been successful in rats, mice, and rabbits, and human trials are planned.
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Digifab is manufactured and distributed by BTG international Inc. under U.S. License No. 186. DigiFab is a sterile, lyophilized preparation of digoxin-immune ovine Fab (monovalent) immunoglobulin fragments. It is prepared by isolating the immunoglobulin fraction of the ovine serum, digesting it with papain and isolating the digoxin-specific Fab fragments by affinity chromatography. These antibody fragments have a molecular weight of approximately 46,000 Da. Each vial of DigiFab, which will bind approximately 0.5 mg digoxin, contains 40 mg of digoxin immune Fab, 75 mg (approx) of mannitol USP, and 2 mg (approx) sodium acetate USP as a buffering agent.
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The addition of NaCl reduces repulsive forces between like-charged DNA strands (negative) so that they pack densely on nanoparticle surfaces. A typical procedure for preparing polyvalent DNA gold nanoparticles is outlined briefly below:Hurst, S. J.; Lytton-Jean, A. K. R.; Mirkin, C. A. "Maximizing DNA Loading on a Range of Gold Nanoparticle Sizes," Analytical Chemistry, 2006, 78, 8313–8318. doi:10.1021/ac0613582. # Reduce dithiol moieties by adding 0.1 M dithiothreitol (DTT) in 0.18 M phosphate buffer (PB) (pH=8) to lyophilized thiolated DNA and letting the solution sit for at least 1 hour. # Purify the DNA using a NAP-5 column.
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To define the IU for a substance, an international collaborative study is organized by the WHO Expert Committee on Biological Standardization using various assay systems in several laboratories. The main goal of the study is to reach a consensus regarding methods of analysis and the approach to standardization so that results can be compared. The study is performed using highly purified preparations of the substance, typically in lyophilized form, called "international reference preparations" or IRPs. Each preparation is divided into precisely weighed samples, with each sample stored in its own ampoule labeled with a code corresponding to the source IRP.
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The serum concentration of prolactin can be given in mass concentration (µg/L or ng/mL), molar concentration (nmol/L or pmol/L) or in international units (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500. Reference ampoules of IS 84/500 contain 2.5 µg of lyophilized human prolactin and have been assigned an activity of .053 International Units. Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs; prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2.
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Imipenem/cilastatin is indicated for the treatment of severe or complicated skin, tissue, joint, respiratory tract, intra-abdominal, urinary tract and urogenital infections, but not meningitis (as it does not pass through the blood brain barrier), endocarditis, and sepsis due to susceptible organisms. Its use is generally restricted to severe infections largely in hospitalized patients. The recommended dosage is 250 mg to 1 gram given intravenously every 6 to 8 hours or in intramuscular doses of no more than 1.5 gm daily, usually for five to 14 days. It is commercially available as Primaxin as 250-mg or 500-mg infusion bottles for IV use or 500-mg or 750-mg vials of lyophilized powder for IM injection.
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The fluctuation method is comparable to the traditional pour plate method in terms of sensitivity and accuracy, however, it does have a number of advantages: it needs less test sample, it has a simple colorimetric endpoint, counting the number of positive wells out of possible 96 or 48 wells is much less time-consuming than counting individual colonies on an agar plate. Several commercial kits are available. Most kits have consumable components in a ready-to-use state, including lyophilized bacteria, and tests can be performed using multichannel pipettes. The fluctuation method also allows for testing higher volumes of aqueous samples (up to 75% v/v), increasing the sensitivity and extending its application to low-level environmental mutagens.
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In the United States, Infliximab is an expensive medication, costing about for a 100 mg dose, and is covered by almost every US medical insurance plan (though caps on many plans make it possible to be covered for only a subset of treatments in the course of a year). Infliximab is supplied as a sterile, white, lyophilized (freeze-dried) powder, so must be reconstituted and administered by a health care professional, usually in a hospital or office setting. For this reason, it is usually covered under major medical insurance rather than prescription drug coverage. The loading regimen for all approved indications occurs at weeks 0, 2, and 6 at the above dosages.
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He asked Wolfe to send him lyophilized cells of methanogens to analyse their cell walls. Carl Woese (left), Otto Kandler and Ralph Wolfe on their way to Mt. Hochiss in 1981 (photo by Gertraud Kandler) In January 1977, Kandler visited Woese for the first time. He was immediately convinced of Woese's new concept, for his cell wall analyses matched perfectly with Woese's 16S rRNA sequencing results. This was the beginning of a close and productive transatlantic complementary relationship and cooperation by the exchange of cultures, results and ideas. Kandler's group studied the cell wall composition and Woese's group the 16S rRNA gene sequences. In their fundamental frequently cited publication, Woese and Fox (November 1977) introduced the term "archaebacteria", at that time, comprising only methanogens.
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Even completely lyophilized human mandibles were used successfully in patients. In 1989, Sailer was the first to describe the use of dental implants simultaneously with the reconstruction of the atrophic maxilla.Sailer, H.F., A New Method of Inserting Endosseous Implants in Totally Atrophic Maxillae, in: J. Cran-Max-Fac Surgery Nr. 17, 1989, p. 299 Between 1992 and 2001 Sailer published several works on the production and application of bone-regenerating proteins (bone morphogenetic proteins) in collaboration with his colleagues Edit Kolb und Franz Weber. These proteins were designed to save the patient from undergoing an operative removal of the bone during reconstruction surgery in the region of the jaws and the faceSailer, H.F. & Weber F.E., Gewebsersatz durch die Anwendung von Bone morphogenetic proteins, in: Nova Acta Leopoldina Nr. 32, 2001, p.
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TLR signaling has been linked to accumulation and function of MDSC at the site of tumor and it also allows mesenchymal stromal cells to counter NK cell-mediated anti-tumor immunity. In HepG2 hepatoblastoma cells LPS increased TLR4 levels, cell proliferation and resistance to chemotherapy, and these phenomena could be reversed by TLR4 gene knockdown. Similarly, LPS stimulation of human liver cancer cell line H7402 resulted in TLR4 upregulation, NF-κB activation, TNF, IL-6 and IL-8 production and increased proliferation that could be reversed by signal transducer and STAT3 inhibition. Besides the successful usage of Bacillus Calmette–Guérin in the therapy of bladder cancer there are reports on the treatment of oral squamous cell carcinoma, gastric cancer and cervical cancer with lyophilized streptococcal preparation OK-432 and utilization of TLR4/TLR2 ligands – derivatives of muramyl dipeptide.
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1963 — Taiho Pharmaceutical Co., Ltd. established; Yukio Kobayashi appointed as president and representative director. Capital increased to ¥100 million A representative from each of the 49 distributors nationwide assumes the position of Board Member 1964 — In-house production plant established in Naruto, Tokushima Prefecture Nine new offices established throughout Japan, centered around the head office in Tokyo, as sales bases 1965 — Capital increased from ¥100 to ¥200 million 1969 — License with the Soviet Union to introduce Futraful in Japan 1971 — Lyophilized formulation plant (seventh plant) completed in the Imagire Industrial Park in Tokushima 1974 — Proprietary Medicine Division established 1975 — Advertising strategy (TV ads) started for Tiovita Drink 1976 — Business alliance formed with Nichiban Co., Ltd., with equity participation by Taiho Pharmaceutical 1977 — Employee welfare facility Otsuka Amagi Mountain Villa completed 1978 — Business alliance formed with Kotai Kasei Co., Ltd.
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