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53-447: Depending on the ratio of lactide to glycolide used for the polymerization, different forms of PLGA can be obtained: these are usually identified in regard to the molar ratio of the monomers used (e.g. PLGA 75:25 identifies a copolymer whose composition is 75% lactic acid and 25% glycolic acid). The crystallinity of PLGAs will vary from fully amorphous to fully crystalline depending on block structure and molar ratio. PLGAs typically show

106-594: A depot injection formulation was introduced in 1989. On 24 March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Camcevi, intended for the treatment of the cancer of the prostate in adult men when the cancer is "hormone-dependent", which means that it responds to treatments that reduce

159-414: A glass transition temperature in the range of 40-60 °C. PLGA can be dissolved by a wide range of solvents , depending on composition. Higher lactide polymers can be dissolved using chlorinated solvents whereas higher glycolide materials will require the use of fluorinated solvents such as HFIP . PLGA degrades by hydrolysis of its ester linkages in the presence of water . It has been shown that

212-413: A dramatic reduction in estradiol and testosterone levels regardless of sex. Leuprorelin is available in the following forms, among others: The peptide sequence is Pyr-His-Trp-Ser-Tyr- D -Leu-Leu-Arg-Pro-NHEt (Pyr = L - pyroglutamyl ). Leuprorelin was discovered and first patented in 1973 and was introduced for medical use in 1985. It was initially marketed only for daily injection, but

265-399: A few nanometres to tens of micrometres thickness that are deposited onto a substrate. So-called structure zone models were developed to describe the microstructure of thin films as a function of the homologous temperature ( T h ), which is the ratio of deposition temperature to melting temperature. According to these models, a necessary condition for the occurrence of amorphous phases

318-410: A result, detailed analysis and complementary techniques are required to extract real space structural information from the diffraction patterns of amorphous materials. It is useful to obtain diffraction data from both X-ray and neutron sources as they have different scattering properties and provide complementary data. Pair distribution function analysis can be performed on diffraction data to determine

371-415: Is a solid that lacks the long-range order that is characteristic of a crystal . The terms " glass " and "glassy solid" are sometimes used synonymously with amorphous solid; however, these terms refer specifically to amorphous materials that undergo a glass transition . Examples of amorphous solids include glasses, metallic glasses , and certain types of plastics and polymers . The term comes from

424-555: Is a manufactured version of a hormone used to treat prostate cancer , breast cancer , endometriosis , uterine fibroids , for early puberty , or as part of transgender hormone therapy . It is given by injection into a muscle or under the skin . Leuprorelin is in the gonadotropin-releasing hormone (GnRH) analogue family of medications. It works by decreasing gonadotropins and therefore decreasing testosterone and estradiol . Common side effects include hot flashes , unstable mood, trouble sleeping , headaches , and pain at

477-456: Is acquired from the sample in question, and then used to reconstruct a 3D image. After image acquisition, a significant amount of processing must be done to correct for issues such as drift, noise, and scan distortion. High quality analysis and processing using atomic electron tomography results in a 3D reconstruction of an amorphous material detailing the atomic positions of the different species that are present. Fluctuation electron microscopy

530-499: Is an atomic scale probe making it useful for studying materials lacking in long range order. Spectra obtained using this method provide information on the oxidation state , coordination number , and species surrounding the atom in question as well as the distances at which they are found. The atomic electron tomography technique is performed in transmission electron microscopes capable of reaching sub-Angstrom resolution. A collection of 2D images taken at numerous different tilt angles

583-590: Is an important area of condensed matter physics aiming to understand these substances at high temperatures of glass transition and at low temperatures towards absolute zero . From 1970s, low-temperature properties of amorphous solids were studied experimentally in great detail. For all of these substances, specific heat has a (nearly) linear dependence as a function of temperature, and thermal conductivity has nearly quadratic temperature dependence. These properties are conventionally called anomalous being very different from properties of crystalline solids . On

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636-716: Is another transmission electron microscopy based technique that is sensitive to the medium range order of amorphous materials. Structural fluctuations arising from different forms of medium range order can be detected with this method. Fluctuation electron microscopy experiments can be done in conventional or scanning transmission electron microscope mode. Simulation and modeling techniques are often combined with experimental methods to characterize structures of amorphous materials. Commonly used computational techniques include density functional theory , molecular dynamics , and reverse Monte Carlo . Amorphous phases are important constituents of thin films . Thin films are solid layers of

689-523: Is by means of an enzyme known as esterase , which forms lactic acid and glycolic acid. These acids then undergo the Krebs Cycle to be degraded as carbon dioxide (CO 2 ) and water ( H 2 O ). These byproducts then get removed from the body through cellular respiration and through the digestive process. While the byproducts usually do not accumulate in the body, there are instances where these byproducts (lactic and glycolic acid) can be dangerous to

742-467: Is carried out into thin amorphous films as a gas separating membrane layer. The technologically most important thin amorphous film is probably represented by a few nm thin SiO 2 layers serving as isolator above the conducting channel of a metal-oxide semiconductor field-effect transistor (MOSFET). Also, hydrogenated amorphous silicon (Si:H) is of technical significance for thin-film solar cells . In

795-399: Is considered one of the very important and unsolved problems of physics . At very low temperatures (below 1-10 K), large family of amorphous solids have various similar low-temperature properties. Although there are various theoretical models, neither glass transition nor low-temperature properties of glassy solids are well understood on the fundamental physics level. Amorphous solids

848-456: Is implanted or placed in the body. There are different immune responses that the body could have depending on where the polymer is placed. For example, in drug delivery systems (DDS), PLGA and PLA implants with high surface area and low volume of injection can increase one's chance of immune response as the polymers degrade in the body. The biodegradation of PLGA makes it useful for plenty of medical practices. PLGA undergoes bulk degradation, which

901-399: Is its USAN Tooltip United States Adopted Name and USP Tooltip United States Pharmacopeia , leuprorelina is its DCIT Tooltip Denominazione Comune Italiana , and leuproréline is its DCF Tooltip Dénomination Commune Française . It is also known by its developmental code names A-43818, Abbott-43818, DC-2-269, and TAP-144. Leuprorelin is marketed by Bayer AG under

954-533: Is minimal systemic toxicity associated with using PLGA for biomaterial applications. However, it has been reported that the acidic degradation of PLGA reduces the local pH low enough to create an autocatalytic environment. It has been shown that the pH inside a microsphere can become as acidic as pH 1.5. Generally PLGA is considered to be quite biocompatible. Its high biocompatibility results from its composition due to lactic and glycolic acid fermentation from sugars, making them eco-friendly and less reactive in

1007-509: Is that ( T h ) has to be smaller than 0.3. The deposition temperature must be below 30% of the melting temperature. Regarding their applications, amorphous metallic layers played an important role in the discovery of superconductivity in amorphous metals made by Buckel and Hilsch. The superconductivity of amorphous metals, including amorphous metallic thin films, is now understood to be due to phonon -mediated Cooper pairing . The role of structural disorder can be rationalized based on

1060-730: Is used for suppressing estrogen production in transgender men . It is considered a possible treatment for paraphilias . Leuprorelin has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. Common side effects of leuprorelin injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, impotence, testicular shrinkage, constipation, stomach pain, breast swelling or tenderness, acne, joint/muscle aches or pain, trouble sleeping (insomnia), reduced sexual interest, vaginal discomfort/dryness/itching/discharge, vaginal bleeding, swelling of

1113-511: Is when a catalyst such as water inserts itself throughout the matrix of the polymer. A 75:25 lactide to glycolide PLGA ratio can be made as microspheres that degrade via bulk erosion. This allows degradation throughout the whole polymer to occur equally. Another injectable form of PLGA was developed to have eroding systems. This form can be used in Lupron Depot . To achieve this, PLGA is mixed with an organic water-miscible solvent approved by

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1166-501: The False Claims Act with claims filed by Douglas Durand, a former TAP vice president of sales, and Joseph Gerstein, a doctor at Tufts University 's HMO practice. Durand, Gerstein, and Tufts shared $ 95 million of the settlement. There have since been various suits concerning leuprorelin use, none successful. They either concern the oversubscription of the drug or undue warning about the side effects. Between 2010 and 2013,

1219-479: The Greek a ("without"), and morphé ("shape, form"). Amorphous materials have an internal structure of molecular-scale structural blocks that can be similar to the basic structural units in the crystalline phase of the same compound. Unlike in crystalline materials, however, no long-range regularity exists: amorphous materials cannot be described by the repetition of a finite unit cell. Statistical measures, such as

1272-450: The hypothalamic–pituitary–gonadal axis (HPG axis). However, normal functioning of this axis requires pulsatile release of GnRH from the hypothalamus. Continuous exposure to an agonist such as leuprorelin for several weeks causes pituitary GnRH receptors to become desensitised and no longer responsive. This desensitisation is the objective of leuprorelin therapy because it ultimately reduces LH and FSH secretion, leading to hypogonadism and

1325-653: The pharmaceutical industry , some amorphous drugs have been shown to offer higher bioavailability than their crystalline counterparts as a result of the higher solubility of the amorphous phase. However, certain compounds can undergo precipitation in their amorphous form in vivo , and can then decrease mutual bioavailability if administered together. Amorphous materials in soil strongly influence bulk density , aggregate stability , plasticity , and water holding capacity of soils. The low bulk density and high void ratios are mostly due to glass shards and other porous minerals not becoming compacted . Andisol soils contain

1378-460: The FDA has not established that these conditions were caused by leuprorelin. During the initial phase of luteinizing hormone-releasing hormone (LHRH) agonist therapy in individuals assigned male at birth , there is a notable phenomenon known as the "flare." This occurs when testosterone levels temporarily surge by approximately 50% within the first 1 to 2 weeks of therapy. This increase is a response to

1431-473: The FDA updated the Lupron drug label to include new safety information on the risk of thromboembolism, loss of bone density and convulsions. The FDA then asserted that the benefits of leuprorelin outweigh its risks when used according to its approved labeling. Since 2017, the FDA has been evaluating leuprorelin's connection to pain and discomfort in musculoskeletal and connective tissue. As of 2006 , leuprorelin

1484-707: The Food and Drug Administration (FDA). Once the PLGA is mixed into the solvent with the drug of choice to create a homogeneous solution or suspension. When this mixture is injected, the PLGA solidifies due to water insolubility and is replaced by the water. Slowly, the drug is delivered from the solution. A problem that may occur is during the initial injection, the drug may be released in a quick burst instead of gradually. Specific examples of PLGA's use include: Amorphous solid In condensed matter physics and materials science , an amorphous solid (or non-crystalline solid )

1537-474: The Lupron label advises against using the drug when one is considering pregnancy, due to a risk of birth defects. It may be used to reduce the risk of premature ovarian failure in women receiving cyclophosphamide for chemotherapy. Along with triptorelin and goserelin , it has been used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy . Researchers have recommended puberty blockers after age 12, when

1590-519: The amorphous phase only after the latter has exceeded a certain thickness, the precise value of which depends on deposition temperature, background pressure, and various other process parameters. The phenomenon has been interpreted in the framework of Ostwald's rule of stages that predicts the formation of phases to proceed with increasing condensation time towards increasing stability. Leuprorelin Leuprorelin , also known as leuprolide ,

1643-532: The ankles/feet, increased urination at night, dizziness, breakthrough bleeding in a female child during the first two months of leuprorelin treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicle pain, impotence, depression, or memory problems. The rates of gynecomastia with leuprorelin have been found to range from 3 to 16%. A cohort of women that were prescribed leuprorelin to delay precocious puberty as children has developed osteoporosis and brittle teeth at an unexpected rate; However,

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1696-507: The atomic density function and radial distribution function , are more useful in describing the structure of amorphous solids. Although amorphous materials lack long range order, they exhibit localized order on small length scales. By convention, short range order extends only to the nearest neighbor shell, typically only 1-2 atomic spacings. Medium range order may extend beyond the short range order by 1-2 nm. The freezing from liquid state to amorphous solid - glass transition -

1749-552: The atomic-length scale due to the nature of intermolecular chemical bonding . Furthermore, in very small crystals , short-range order encompasses a large fraction of the atoms ; nevertheless, relaxation at the surface, along with interfacial effects, distorts the atomic positions and decreases structural order. Even the most advanced structural characterization techniques, such as X-ray diffraction and transmission electron microscopy , can have difficulty distinguishing amorphous and crystalline structures at short size scales. Due to

1802-409: The body when accumulated in high local concentrations. There can also be small pieces of the polymers as the polymer degrades, causing an immune response by macrophages . These adverse effects can be reduced by using lower concentrations of the polymer, so that it gets naturally released throughout the body. Something else to consider regarding PLGA biocompatibility is the location at which the polymer

1855-414: The body. Lactic acid is metabolized in the tricarboxylic acid cycle and eliminated via carbon dioxide and water . Glycolic acid is metabolized in the same way, and also excreted through the kidney. The body also can metabolize the two monomers, which in the case of glycolic acid produces small amounts of the toxic oxalic acid , though the amounts produced from typical applications are minuscule and there

1908-414: The body. PLGA also degrades into non-toxic and non-reactive products that makes them quite useful for various medical and pharmaceutical applications. The biocompatibility of PLGA has been tested both in vivo and in vitro. The biocompatibility of this polymer is generally determined by the products that it degrades into, as well as the rate of degradation into degradation products. The way that PLGA degrades

1961-605: The brand name Viadur, by Tolmar under the brand names Eligard and Fensolvi, and by TAP Pharmaceuticals (1985–2008), by Varian Pharmed( Previously named Varian Darou Pajooh) under the brand name Leupromer and Abbott Laboratories (2008–present) under the brand name Lupron. In October 2001, the US Department of Justice, states attorneys general, and TAP Pharmaceutical Products, a subsidiary of Abbott Laboratories, settled criminal and civil charges against TAP related to federal and state medicare fraud and illegal marketing of

2014-513: The drug leuprorelin. TAP paid a total of $ 875 million, which was a record high at the time . The $ 875 million settlement broke down to $ 290 million for violating the Prescription Drug Marketing Act, $ 559.5 million to settle federal fraud charges for overcharging Medicare, and $ 25.5 million reimbursement to 50 states and Washington, D.C., for filing false claims with the states' Medicaid programs. The case arose under

2067-497: The free carboxylic acid ) demonstrate longer degradation half-lives. This flexibility in degradation has made it convenient for fabrication of many medical devices , such as, grafts , sutures , implants , prosthetic devices , surgical sealant films, micro and nanoparticles . PLGA undergoes hydrolysis in the body to produce the original monomers: lactic acid and glycolic acid. These two monomers under normal physiological conditions, are by-products of various metabolic pathways in

2120-528: The highest amounts of amorphous materials. The occurrence of amorphous phases turned out to be a phenomenon of particular interest for the studying of thin-film growth. The growth of polycrystalline films is often used and preceded by an initial amorphous layer, the thickness of which may amount to only a few nm. The most investigated example is represented by the unoriented molecules of thin polycrystalline silicon films. Wedge-shaped polycrystals were identified by transmission electron microscopy to grow out of

2173-521: The initial stimulation of luteinizing hormone (LH) by the LHRH agonist, leading to a rise in testosterone levels before they begin to decrease as intended. For individuals receiving LHRH agonists as part of gender-affirming care, this temporary increase in testosterone can be particularly distressing, exacerbating gender dysphoria and discomfort. To manage and mitigate these effects, healthcare providers often prescribe antiandrogens during this phase to help block

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2226-485: The lack of long-range order, standard crystallographic techniques are often inadequate in determining the structure of amorphous solids. A variety of electron, X-ray, and computation-based techniques have been used to characterize amorphous materials. Multi-modal analysis is very common for amorphous materials. Unlike crystalline materials which exhibit strong Bragg diffraction, the diffraction patterns of amorphous materials are characterized by broad and diffuse peaks. As

2279-597: The levels of the hormone testosterone. The applicant for this medicinal product is Accord Healthcare S.L.U. Leuprorelin was approved for medical use in the European Union in May 2022. Leuprorelin is the generic name of the drug and its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name , while leuprorelin acetate is its BANM Tooltip British Approved Name and JAN Tooltip Japanese Accepted Name , leuprolide acetate

2332-498: The person has developed to Tanner stages 2–3, and then cross-sex hormones treatment at age 16. This use of the drug is off-label, however, not having been approved by the Food and Drug Administration and without data on long-term effects of this use. They are also sometimes used as alternatives to antiandrogens like spironolactone and cyproterone acetate for suppressing testosterone production in transgender women . It also

2385-408: The phenomenological level, many of these properties were described by a collection of tunneling two-level systems. Nevertheless, the microscopic theory of these properties is still missing after more than 50 years of the research. Remarkably, a dimensionless quantity of internal friction is nearly universal in these materials. This quantity is a dimensionless ratio (up to a numerical constant) of

2438-470: The phonon wavelength to the phonon mean free path . Since the theory of tunneling two-level states (TLSs) does not address the origin of the density of TLSs, this theory cannot explain the universality of internal friction, which in turn is proportional to the density of scattering TLSs. The theoretical significance of this important and unsolved problem was highlighted by Anthony Leggett . Amorphous materials will have some degree of short-range order at

2491-441: The probability of finding a pair of atoms separated by a certain distance. Another type of analysis that is done with diffraction data of amorphous materials is radial distribution function analysis, which measures the number of atoms found at varying radial distances away from an arbitrary reference atom. From these techniques, the local order of an amorphous material can be elucidated. X-ray absorption fine-structure spectroscopy

2544-586: The site of injection. Other side effects may include high blood sugar , allergic reactions , and problems with the pituitary gland . Use during pregnancy may harm foetal development. Leuprorelin was patented in 1973 and approved for medical use in the United States in 1985. It is on the World Health Organization's List of Essential Medicines . It is sold under the brand name Lupron among others. Leuprorelin may be used in

2597-529: The strong-coupling Eliashberg theory of superconductivity. Amorphous solids typically exhibit higher localization of heat carriers compared to crystalline, giving rise to low thermal conductivity. Products for thermal protection, such as thermal barrier coatings and insulation, rely on materials with ultralow thermal conductivity. Today, optical coatings made from TiO 2 , SiO 2 , Ta 2 O 5 etc. (and combinations of these) in most cases consist of amorphous phases of these compounds. Much research

2650-427: The time required for degradation of PLGA is related to the monomers' ratio used in production: the higher the content of glycolide units, the lower the time required for degradation as compared to predominantly lactide materials. An exception to this rule is the copolymer with 50:50 monomers' ratio which exhibits the faster degradation (about two months). In addition, polymers that are end-capped with esters (as opposed to

2703-411: The treatment of hormone-responsive cancers such as prostate cancer and breast cancer . It may also be used for estrogen-dependent conditions such as endometriosis or uterine fibroids . It may be used for precocious puberty in both males and females, and to prevent premature ovulation in cycles of controlled ovarian stimulation for in vitro fertilization ( IVF ). This use is controversial since

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2756-420: The unwanted increase in testosterone and alleviate the associated distress. Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors . GnRH receptor agonists initially increase the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary and increased serum estradiol and testosterone levels via

2809-447: Was under investigation for possible use in the treatment of mild to moderate Alzheimer's disease . A by mouth formulation of leuprorelin is under development for the treatment of endometriosis . It was also under development for the treatment of precocious puberty , prostate cancer , and uterine fibroids , but development for these uses was discontinued. The formulation has the tentative brand name Ovarest. As of July 2018, it

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