MX2008009920A - Polyalkylene glycols comprising a reduced amount of oligomers - Google Patents

Abstract

Polyalkylene glycol compositions having reduced low molecular weight oligomers are disclosed. Some compositions, particularly polyethylene glycol compositions have a number average molecular weight range from about 3000 to about 10,000 g/mol and have a total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g/mol and a a total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to 240 g/mol. Other polyalkylene compositions, particularly polyethylene glycol compositions, are characterized by a total oligomer concentration of less than about 90 ppm ofall oligomers having a molecular weight less than or equal to 460 g/mol and are obtained without further processing to remove oligomers having a molecular weight of less than about 460 g/mol. Methods for making such compositions are also disclosed.

Description

POLIALQUII_ENGLICOL.ES UNDERSTANDING A REDUCED AMOUNT OF OLIGOMERS PREVIOUS RELATED REQUESTS Not applicable.

DECLARATION OF FEDERALLY SPOED INVESTIGATION Not applicable.

REFERENCE TO MICROPHONE APPENDIX Not applicable.

FIELD OF THE INVENTION The invention relates generally to polyalkylene glycol compositions and methods for making such compositions. More particularly, the polyethylene glycol compositions described herein have a reduced concentration of low molecular weight oligomers.

BACKGROUND OF THE INVENTION Polyethylene glycol (PEG) is used in a wide variety of applications including, but not limited to, excipients, plasticizers, softeners, humectants, ointments, bitumens, paper coating, lubricants, cosmetics and pharmaceutical bases, solvents, binders, metal and rubber processing, and additives for food and animal feed. Some particular uses of PEG in pharmaceutical applications include, for example, formation of PEG-drug conjugates, treatment of neonatal respiratory distress syndrome, constipation treatment, treatment of encopresis in children and diagnosis and therapy of gastrointestinal diseases. Polyethylene glycol is usually produced by ring-opening polymerization catalyzed with ethylene oxide base. The reaction is initiated by adding ethylene oxide to a diol in the presence of a catalyst. This process results in a polydispersed mixture of polyethylene glycol polymers with a Poisson distribution centered on the target molecular weight. For example, PEG 400 has a number average molecular weight of about 400, but contains a distribution of ethylene glycol oligomers at much higher molecular weights; however, when these molecular weights are examined in aggregate, the number average molecular weight will be at or about 400. In general, it is expected that the number average molecular weight is within five percent of the nominal value labeled for polyethylene glycols with a labeled value of less than 1 000 g / mol, within 10% for labeled values between 1000 g / mol and 7000 g / mol and within 12.5% of labeled values greater than 7000 g / mol. Although most of the oligomers in a particular polyethylene glycol composition have a molecular weight close to the number average molecular weight, the compositions usually also contain significant concentrations of lower molecular weight species. And while high molecular weight polyethylene glycol molecules appear to be inert in the body, low molecular weight polyethylene glycol polymers can interact with the human body, especially the liver. Accordingly, the concentration of low molecular weight species such as ethylene glycol and diethylene glycol is specified in the US Pharmacopoeia at 0.25% (2, 500 ppm) or less with respect to polyethylene glycols having a molecular weight of 1000 g / mol or less for used in fields with application to a living body. Because these low molecular weight polyethylene glycol molecules can interact with the body, polyethylene glycols have low concentrations of low molecular weight species would be useful.

BRIEF DESCRIPTION OF THE INVENTION The embodiments of the invention described herein include methods for making a polyalkylene glycol composition having reduced low molecular weight oligomers. In some embodiments, the method includes providing a catalyst and an initiator; provide an alkylene oxide; and maintaining the reaction temperature and water concentration at a level sufficient to provide a polyalkylene glycol composition having a number average molecular weight range from about 3000 to about 1,000,000 g / mol, wherein the composition has a first concentration of total oligomer of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g / mol. In other modalities, the method includes providing a catalyst and an initiator, providing an alkylene oxide, and maintaining the concentration of water at a level sufficient to provide a polyalkylene glycol composition having a number average molecular weight range from about 3000 to about 1,000,000 g. / mol, and comprising a first total oligomer concentration of less than about 90 ppm of all oligomers having a molecular weight of less than or equal to 460 g / mol, wherein the composition is obtained without further processing to remove oligomers having a molecular weight of less than about 460 g / mol. Other embodiments of the invention are directed to polyethylene glycol compositions having reduced low molecular weight oligomer concentrations. In some embodiments, the compositions have a number average molecular weight range of from about 4000 to about 10,000 g / mol and comprise a first total oligomer concentration of about 400 ppm or less of all oligomers having a molecular weight of less than or equal to equal to 81 2 g / mol and a second total oligomer concentration of less than about 50 ppm of all oligomers having a weight molecular weight of less than or equal to 240 g / mol. Still in other embodiments of the invention, a polyethylene glycol composition with a bulk density of more than about 0.50 g / cm 3 having a number average molecular weight range from about 3000 to about 10,000 g / mol, in particular about 3000 g / mol. mole up to about 4000 g / mole, comprises a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g / mole and comprises a second total oligomer concentration of less than or equal to about 50 ppm of all oligomers having a molecular weight less than or equal to 240 g / mol. Some compositions described herein are polyethylene glycols having a number average molecular weight range from about 3000 to about 1,000,000 g / mol, wherein the composition has a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 81 2 g / mol and a second total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to 240 g / mol and comprising more than 0.1 g of water per 1.0 g of polyethylene glycol. In other embodiments, the polyalkylene glycol compositions herein have a number average molecular weight range from about 3000 to about 10,000 g / mol, in particular 4000 g / mol to 9000 g / mol and comprise a first concentration of total oligomer of less than about 90 ppm of all oligomers having a molecular weight less than or equal to 460 g / mol, wherein the composition is obtained without further processing to remove oligomers having a molecular weight of less than about 460 g / mol. In some of the methods and compositions described herein, the composition has a number average molecular weight ranging from about 3000 to about 4000 g / mol. In other embodiments, the number average molecular weight ranges from about 4000 to about 5000 g / mol. In still other embodiments, the number average molecular weight range is from about 5000 to about 7000 g / mol. In still other embodiments, the number average molecular weight range is from about 7000 to about 9000 g / mol. Some methods and compositions may also be characterized by one or more features described herein. For example, in some embodiments, the compositions produced by the methods described herein may comprise solid product, which has an average particle size of less than about 1 mm. Some modalities are characterized by the absence of or lack of need for an antioxidant. Some compositions provided herein are particularly suitable for use in pharmaceutical applications.

BRIEF DESCRIPTION OF THE DRAWINGS The embodiments of the invention can be understood from the following detailed description, when read with the accompanying figures. Reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which: FIGURE 1 compares a concentration profile of low molecular weight oligomer of polyethylene glycol with a molecular weight of about 33500 produced by conventional methods and that of a polyethylene glycol with a molecular weight of about 3350 of a composition of one embodiment of the invention. FIGURE 2 compares a larger portion of the low molecular weight oligomer concentration profile of polyethylene glycol with a molecular weight of about 3350 produced by conventional methods and that of a polyethylene glycol with a molecular weight of approximately 3350 of one embodiment of the invention.

DESCRI PTION OF I NVENTION MODALITIES Definitions In the following description, all figures described herein are approximate values, regardless of whether the word "around" or "approximate" is used in connection with them. They can vary by 1%, 2%, 5% and sometimes, from 1 to 20%. Whenever a numerical range with a lower limit, RL and an upper limit, Ru, is described, any figure that falls within the range is described in a specific way. In particular, the following figures within the range are described specifically: R = RL + k * (Ru-RL), where k is a variable that varies from 1% to 1 00% with an increase of 1%, is say, k is 1%, 2%, 3%, 4%, 5% 50%, 51%, 52%, ... 95%, 96%, 97%, 98%, 99% or 100%. Moreover, any numerical range defined by two R numbers as defined in the previous one is also described in a specific way. In one aspect, the invention provides polyethylene glycol compositions having low concentrations of polyethylene glycol low molecular weight oligomers. Low molecular weight oligomers of polyethylene glycol are molecules that are members of the polyethylene glycol family, but have a low molecular weight. For example, diethylene glycol and triethylene glycol are low molecular weight oligomers of polyethylene glycol which are sometimes referred to as 2-mer and 3-mer of polyethylene glycol, respectively. Oligomers are generally referred to herein by their characteristic molecular weight, for example, the pentamer and decamer can be identified as the oligomers of 238 g / mol and 458 g / mol, respectively. Where the term molecular weight is applied to compositions having a molecular weight distribution, it should be understood that the number average molecular weight is within less than 1,000 g / mol, within 10% of values reported between 1,000 and 7,000. g / mol and within 12.5% for reported values greater than 7000 g / mol. For example, a polymer composition described as having a number average molecular weight of 3350 g / mol should be interpreted to literally cover compositions with average number molecular weights ranging from 301 5 g / mol to about 3685 g / mol. In some embodiments, the invention provides a polyalkylene glycol composition, such as a polyethylene glycol, having a number average molecular weight range from about 3000 g / mol to about 10,000 g / mol, comprising a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g / mol. In some embodiments, the first total oligomer concentration is less than about 350 ppm, 275 ppm, 200 ppm or 1000 ppm. In other compositions, the first total concentration of oligomers may be even lower. Some compositions can also be characterized by a second concentration of total oligomer. In some compositions, there is less than about 50 ppm of all oligomers having a molecular weight of 240 g / mole or less. Other compositions have even lower concentrations of all those oligomers. For example, some compositions may have less than about 40 ppm, less than about 30 ppm, less than about 20 ppm, less than about 10 ppm, or less than about 5 ppm of all oligomers with a molecular weight of less than or equal to at 240 g / mol. The compositions can also be characterized by a third concentration of total oligomer. Thus, some compositions comprise less than about 1500 ppm of all oligomers with a molecular weight of 1472 g / mole or less. In some embodiments, the compositions comprise less than about 1400 ppm, less than about 1250 ppm, less than about 1000 ppm, less than about 750 ppm, less than about 500 ppm, or less than about 100 ppm of all those oligomers. The particular compositions comprise desirable combinations of the first, second or third total oligomer concentrations. For example, some compositions comprise a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of 812 g / molo less, a second total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of 240 g / mole or less, and a third total oligomer concentration of less than about 1500 ppm of all oligomers having a molecular weight of 1472 g / mole or less. Some compositions have a first total oligomer concentration of less than about 275 ppm of all oligomers having a molecular weight of 812 g / mole or less and a second total oligomer concentration of less than about 50 ppm of all oligomers having a weight molecular weight of 240 g / mol or less. In another aspect, some compositions provided herein are obtained without one or more processing or post-reaction steps designed to remove oligomers having a molecular weight of 460 g / mole or less. Thus, some polyethylene glycol compositions obtained without one or more such steps have the first total oligomer concentration of less than about 90 ppm of all those oligomers. Other compositions comprise less than about 85 ppm, less than about 80 ppm, less than about 75 ppm, less than about 70, less than about 60, less than about 50, less than about 40, less than about 30, less than about 20 , less than about 10 or less than about 5 ppm of all oligomers of 460 g / mol or less. Particular compositions that are obtained without further processing to remove low molecular weight oligomers comprise low concentrations of other oligomers as well. For example, some compositions obtained without further processing also comprise a second total oligomer concentration of less than about 50 ppm of all oligomers with a molecular weight of 240 g / mol or less. In some compositions, the total concentration of oligomers with a molecular weight of 240 g / mole or less can be less than about 40 ppm, less than about 30 ppm, less than about 20 ppm, less than about 10 ppm, or less than about 5 ppm. Other polyethylene glycol compositions obtained without further processing are characterized by low levels of oligomers with a molecular weight of 1472 g / mole or less. Thus, some compositions with a first total oligomer concentration of less than about 90 ppm of all oligomers with a molecular weight of 460 g / mole or less also have a third total concentration of oligomers of less than about 1500 ppm of all the oligomers with a molecular weight of 1472 g / mol or less. In some compositions, the total concentration of all oligomers having a molecular weight of less than or equal to 1472 g / mol is less than about 1400 ppm, less than about 1250 ppm, less than about 1000 ppm, or less than about 750 ppm In some embodiments , the total concentration of all oligomers having a molecular weight of less than or equal to 1472 g / mol is less than about 500 ppm, less than about 250 ppm, or less than about 100 ppm. Although the compositions herein may have any desirable molecular weight in the range of 3,000 to about 10,000 g / mol, the particular compositions described above have an average number-average molecular weight ranging from about 3000 g / mol to about 4000 g / mol , preferably about 3350 g / mol. Some compositions have a molecular weight ranging from 4000 g / mol to 7000 g / mol. In some embodiments, the compositions having the total oligomer concentrations described above also have a number average molecular weight ranging from about 4000 g / mol to about 5000 g / mol, more particularly 4000 g / mol to about 4400 g / mol. In other embodiments, the number average molecular weight ranges from about 5000 g / mol to about 7000 g / mol, in particular about 4750 g / mol to about 60,000 g / mol, more particularly about 4570 g / mol to about 5250 g / mol. mol, still more particularly about 5000 g / mol. In still other embodiments, the number average molecular weight of the composition ranges from about 7000 g / mol to about 9000 g / mol, in particular about 7500 g / mol to about 8500 g / mol. Some preferred compositions have a number average molecular weight of about 8000 g / mol. The average molecular weight of number and concentration of oligomer can be determined using the method described in the United States Phrmacopeia 28 / National Formulary 23, published by the United States Pharmacopeial Convention, Inc., for the measurement of average molecular weight of polyethylene glycol. The concentration of low molecular weight oligomers can be determined by analysis of 3,5-dinitrobenzoyl chloride derivatives of polyethylene glycol. The derived samples can be injected on an HPLC system (high performance liquid chromatography) for separation and subsequent detection by UV spectroscopy. The chromathographic response, molecular weight (s) and retention times of standards ethylene glycol, di (ethylene glycol), tri (ethylene glycol), tetra (ethylene glycol) and penta (ethylene glycol) are used to calculate the molar response factor for this analysis. Regardless of the molecular weight and total oligomer concentration, some polyethylene glycol compositions of the invention may comprise solid particles having an average particle size of less than about 1 mm. The lower limit on particle size in some embodiments may be about 1 miera, about 5 microns, about 20 microns, about 50 microns, 1 00 microns, 500 microns, or about 1,000 microns. In certain embodiments, the upper limit of the average particle size may have a value of approximately 1 00 microns, 200 microns, 500 microns or approximately 1,000 microns. Average particle sizes can be determined from commercially available laser diffraction devices, such as the Malvern S® particle size analyzer.

The particles can also be caracerized by their size distribution. As used herein, the terms "Di0", "D50" and "D90" indicate the respective percentiles of the normal logarithm of particle size distribution determined by the Mavern S® particle size analyzer used to analyze dry particles. Some compositions of the invention may comprise particles having a D50 value ranging from about 1 miera to about 1,000 microns, although in some embodiments the D50 value may fall outside this range. In some embodiments, D50 may be between about 50 microns to about 500 microns. In other embodiments, the D50 value may be about 1000 microns, approximately 200 microns, approximately 300 meters or approximately 400 microns. In still other embodiments, the D50 value may be about 10 microns, about 25 microns, about 50 microns or about 75 microns. The width and narrowness of a particle size distribution can be described by its stretch. The section is defined as (D9o-D1 0) / (D5o). Some compositions may comprise particles having a stretch from about 0.8 to about 3.0. In some embodiments, the length of the particles may be about 1.6, or about 1.8, about 2.0, about 2.2, or about 2.5. In still other embodiments, the particles may have a length of less than about 2.0, less than about 1.8, or less than about 1.6. Other compositions can be prepared where the particles have a length that is less than about 1.5, about 1.3 or about 1.1. The desirable stretch varies with apication. Alternatively or additionally, some solid compositions described herein have a desirable bulk density. The bulk density of some of the solid polyethylene glycol compositions described herein is greater than about 0.50, usually greater than 0.52, or 0.55 g / cm3. In other embodiments, the bulk density may be about 0.60, about 0.65, about 0.68, about 0.70, about 0.75, or about 0.80 g / cm3. Normally, bulk density does not need to exceed approximately 1.1 g / cm3. In some embodiments, the density is less than about 0.95 g / cm3, less than about 0.90 g / cm3, less than 0.85 g / cm3, less than 0.80 g / cm3, less than 0.75 g / cm3, less than 0.70 g / cm3 , or less than 0.65 g / cm3. Normally, bulk density ranges from about 0.50 to about 0.75 g / cm3. The bulk density of polyethylene glycol compositions can be measured according to the US Pharmacopoeia, Method 61 6 entitled "Bulk Density and Density in Pipe". Accordingly, if agglomerates are present in the material, the amount of material sufficient to complete the test should be passed through a 1.00 mm (No. 18) screen to break up the agglomerates that may have formed during storage. . The bulk density is determined by adding approximately 100 g of test material, M, with 0.1% of precision without compaction when emptying or transferring carefully using a spatula to a dry cylinder of 250 ml. For the compositions herein, normally about 80 to 0 grams is suitable for filling the cylinder. The dust should be carefully leveled without compacting, if necessary, and read the apparent unsettled volume, Vo, to the nearest graded unit. Calculate the density in bulk, in g for me, by the formula: (M) / (Vo). In general, determinations by replication and normal statistical methods are desirable for the determination of this propiedd. The compositions described herein can be made by any method. One such method comprises providing a catalyst and an initiator; providing an alkylene oxide, and maintaining the reaction temperature and water concentration at a level sufficient to provide a polyethylene glycol composition having a number average molecular weight range from about 3000 to about 10,000 g / mol, comprising a first concentration total oligomer of less than about 400 ppm of all oligomers having a molecular weight of 81 2 g / ml or less and a second total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to equal to 240 g / mol. In another embodiment, the method for making a polyalkylene glycol composition having low molecular weight oligomers comprises providing a catalyst and an initiator; provide an alkylene oxide; and maintaining the water concentration temperature at a level sufficient to provide a polyethylene glycol composition having a number average molecular weight range from about 3000 to about 10,000 g / mol, comprising a first total oligomer concentration of less than about 90 ppm. all oligomers having a molecular weight of less than or equal to 460 g / mol, wherein the method is free of post-reaction processing steps to remove the oligomers having a molecular weight of less than or equal to 460 g / mol.

Without wishing to support a particular theory, applicants believe that the presence of water in the reagents promotes the formation of low molecular weight oligomers. Water that is introduced into the initiator via the catalyst or some other form of contamination is ethoxylated to form low molecular weight oligomers. In particular, the presence of water in higher molecular weight initiators (or in the final stages of ethoxylation) is thought to have a significant impact on the distribution of low molecular weight oligomers. Surprisingly, the impact of water as an impurity in the diol initiator increases as the molecular weight of the initiator approaches the molecular weight of the final product. Thus, in embodiments of the methods herein, introducing water into the higher molecular weight initiators should be carefully controlled. In particular embodiments, water, such as water from the catalyst solution should be added when the initiator has a relatively low molecular weight. The relatively low molecular weight is determined with respect to the molecular weight of the final composition. In this way, the reaction points where the water should be controlled will be different when the molecular weight of the desired composition is, for example, 3350 g / mol, instead of 8000 g / mol. In addition to being provided with the catalyst, the water may also be present as an impurity in alkylene oxides, in particular ethylene oxide. As water introduced from the catalyst, the water present in the alkylene oxide results in low molecular weight oligomers in the latter stages of ethoxylation. Thus, in some embodiments, providing an alkylene oxide includes providing an alkylene oxide having less than about 100 ppm of water. In other embodiments, the alkylene oxide comprises less than about 50 ppm, particularly less than about 10 ppm of water. According to some embodiments of the invention, the water level is maintained below one or more of the levels indicated in Table 1. For example, at the time when the polyethylene glycol has a molecular weight of 1000 g / mol, the level of water in the reactor or reaction mixture is maintained below 0.14 percent by weight if the desired molecular weight of the final composition is 3350 g / mol. Likewise, if the desired molecular weight of the final composition is 8000 g / mol, the amount of water in the reactor or reaction mixture is maintained below 1.5 percent by weight at the time when the composition has a molecular weight of 1 000 g / mol.

Table 1 According to the values of Table 1, in some embodiments the concentration of water in the reactor is related to the molecular weight of an intermediate polyethylene glycol polymer, Mw'nt, in the reactor in one or more intermediate times, t, and the final desired molecular weight of the polyethylene glycol composition, Mw, follows the formula where a, are constants derived from empirical data reported in Table 1. The values for constants "a" "for cases where the intermediate composition has a molecular weight of less than 2000 g / mol and wherein the intermediate composition has a molecular weight of more than 2000 g / mol are recorded in Table 2. In some embodiments, lower water concentrations are desired. For example, the values calculated using the above equations serve to define an upper limit in water concentration for some modalities. In other embodiments, the concentration of water in the reactor at a given time may vary from 0 to 99 percent of the value given by the above formula. In particular embodiments, the concentration of water in the reactor at a given time may be 5, 10, 20, 30, 40, 50, 60, 70, 80 or 90 percent of the value produced by the formula. As long as the concentration of water and temperature are maintained in the desired range, polyethylene glycol can be made in conjunction with any additional process. For example, processes described in US Pat. Nos. 6372927, 6620976, 4721816, as well as application for publication of US patent no. 20021 61267 and published application WO2004081082, whose description of each of these references is incorporated herein by reference in its entirety.

Table 2: Constants for water concentration in reactor In some embodiments, a sufficiently low level of water in the reactor means that there is less than 1.5 percent by weight of water in the reactor when the molecular weight Mw of the polyethylene glycol in the reactor is 1000 g / mol less. In some embodiments, the concentration of water in the reactor ranges may be 1.0 percent by weight or less, 0.8 percent by weight or less, 0.7 percent by weight or less, 0.5 percent by weight or less, 0.3. percent by weight or less, or 0. 1 percent by weight or less, when the molecular weight Mw of polyethylene glycol in the reactor is 1000 g / mol or less. It should be recognized that polyethylene glycol having a molecular weight of 1000 g / mol does not need to be isolated or used as an initiator in the subsequent preparation of the desired composition. Instead of such embodiments, the water content of the composition when it has a molecular weight of 1000 g / mol is determinative. For example, it is envisioned that an initial polyethylene glycol having a molecular weight greater than or less than 1000 g / ml can be prepared and used further to prepare a composition of higher desired molecular weight. Regardless of the molecular weight of the initial polyethylene glycol, the water level can be determined when the composition achieves a molecular weight of 1000 g / mol, or as close as 1000 g / mol as is practically possible. Any suitable initiator for preparing polyalkylene glycols can be used. Particular novelties include poly (oxyethylene) compounds. Other suitable initiators include, diols having from 2 to 4 carbon atoms or active hydrogen initiators. In some embodiments, an initiator of diethylene glycol or ethylene glycol is particularly preferred. Providing the alkylene oxide can be done by any suitable means. The alkylene oxide can be any such compound. Normally, the alkylene oxide has from 2 to 10 carbon atoms, in particular ethylene oxide or propylene oxide. Of course, where a polyethylene glycol is desired, ethylene oxide should be used. Any catalyst now known or subsequently discovered can be used. Some suitable catalysts include potassium hydroxide, sodium hydroxide, ammonium hydroxide, metal oxide catalysts, alkaline earth oxides, antimony hexafluoride and antimony hexachloride. In particular embodiments, the catalyst includes sodium hydroxide, preferably as a 50% solution in water. However, care should be taken to minimize the presence of water in the reaction, especially in those embodiments where an initial portion of low molecular weight polyethylene glycol is formed and further reacted to provide a desired higher molecular weight polyethylene glycol composition. Other widely used catalysts include Na, K, NaH, KH, KOMe, KOEt, NaOMe, NaOEt and Na metal. Various catalysts for metal oxides, metal salts, phosphazene compounds, rare earths and double metal cyanide (DMC) have also been used as alkoxylation catalysts. Other catalysts described in US Pat. Nos. 6303832, 51 20697, 5104987, 5466523, 58441 1 5, 4727199, 4946984, 4721 81 6, 620794, 601 8017, 6429342, 6376721, 5023224, 5057628 and 51 02849 as well as in published applications WO200408102, WO2001014456 and in the Romanian patent R062314B, whose description of each of these references is incorporated herein by reference in its entirety. The components can be combined and allowed to react in any suitable reactor configuration or process. Preferably, after the catalyst is added to the diol initiator, eitlene oxide or other alkoxylate is added. These alkoxylates are added until the desired molecular weight is achieved. In some embodiments, the alkoxylates have water concentrations of less than about 50 ppm, less than about 25 ppm, or less than about 10 ppm of water. Normally, the alkoxylation reactions are carried out in batch form by heating the initiator in the presence of the catalyst to add the alkoxylate. Some suitable reactor designs and processes are described in US Pat. Nos. 6372927, 6620976, 4721 81 6, application for US publication no. 2002161267, and international application WO2004081082, each of which is incorporated herein by reference in its entirety. Some suitable reactor schemes include stirred tank reactors, plug flow reactors, fixed bed reactors or circuit reactors. In some modalities, a simple batch process is used. In some processes, two or more reactors are used. In those modalities where two or more reactors are used, the reactors can be connected in series. In other embodiments, the reactors may be isolated batch reactors. In other embodiments, the compositions can be made by forming a first polyethylene glycol composition of lower molecular weight. Subsequently, some or all of this lower molecular weight composition is further reacted to produce a higher molecular weight polyethylene glycol composition. Preferably, no additional catalyst is added to the reaction in embodiments where at least a portion of a first lower molecular weight polyethylene glycol composition is reacted to form the desired higher molecular weight composition, especially those where the catalyst used to form the the first low molecular weight portion includes water or reacts with the initiator to form water. Regardless of the particular design, the temperature of the reaction should be controlled carefully. In some embodiments, the method further includes maintaining the reaction at a temperature of less than about 165 ° C. Reaction temperatures of from about 1 20 ° C to about 160 ° C, from about 1 30 ° C to about 1 55 ° C, or 1 35 ° C to about 1 50 ° C are suitable for some embodiments. The methods of the invention may also include neutralizing the catalyst once the polyethylene glycol composition has been formed. Normally, the catalyst is neutralized with an acid, such as but not limited to mineral acids and organic acids. Phosphoric acid and acetic acid are particularly suitable for neutralizing basic catalysts, such as NaOH and KOH. Other suitable catalyst neutralizing methods are described in US Pat. 41 1 0268, 4430490, 4521568, 546839, 4426301 and 6191 31 5. The use of carbon dioxide is described in US Pat. Nos. 3833669, 41 29718 and 41 37398. The description of each of these references is incorporated by reference in its entirety and can be used according to some methods of the invention. The embodiments of the invention also further include removing all or some of the catalyst from the polyethylene glycol composition. Any suitable medium can be used so long as it does not detrimentally affect the composition, such as by increasing the concentration of low molecular weight oligomers of polyethylene glycol in the composition. Removing the catalyst using one or more acids is described in US Pat. Nos. 32991 51, 4306943, 4507475, 496701 7, 501 201 3, 5468840, 641 0676 and international applications WO2001 08801 5 and WO2204000914. The catalyst can also be removed by centrifugation, filtration or other chemical means as described in US Pat. Nos. 4254287, 4482750, 4528364, 4855509, 4877906, 4721 81 8, 4987271, 5344996, 581 1 566, European patent EP 1 370600 and Chinese patent CN 1 044472. Each of these descriptions is hereby incorporated by reference in its entirety . The polyethylene glycol compositions can also be treated by one or more of the following processes. In some modalities, the composition may be subjected to water extraction as described in U.S. Pat. 6504062 or ion exchange as described in U.S. Pat. 281 2360. In some embodiments, the reactive distillation can be used to treat the compositions as described in U.S. Pat. 526851 0 and European patent EP982341. If desired, the compositions can be passed through a membrane as described in U.S. Pat. 4946939 and 543431 5. In some embodiments, the process includes removing volatiles from the composition as described in U.S. Pat. 4443634. The removal of unsaturated components using ultrafiltration is described in U.S. Pat. 5767324 and by hydrogenation in Japanese patent JP53046907. In some embodiments, it may be desirable to remove unwanted color from the compositions by using a bleaching agent as described in U.S. Patent Application Publication no. 2000500965, by exchange of cations as described in J P1043629. In other embodiments, the compositions can be treated with silicate and aluminum oxide as described in JP 55108823. Hydrogen peroxide can also be used as described in R01 14124. In some embodiments, the color is removed by heating the composition in the presence of water and air as described in US4751 331. Each of these descriptions is incorporated herein by reference in its entirety. The polyethylene glycols described herein may be prepared for use in a variety of applications. Some compositions described herein are suitable for use as laxatives or washes. Some compositions can be used to treat chronic gastrointestinal disorder selected from the group consisting of ulcerative clitis, Crohn's disease and irritable bowel syndrome as described in U.S. Pat. 5443826 and WO2005007170. Some polyethylene glycol compositions described herein may be useful for treating or preventing intestinal gas, cramping or ano-rectal irritation. Some compositions are suitable for use as a suspending agent as described in U.S. Pat. 4942042. In particular embodiments, the compositions can be used as a laxative either alone or in conjunction with electrolytes as described in U.S. Pat. 6645481, WO2005049049, WO8700745. The use of polyethylene glycol and electrolyte compositions is also described in US Patents 5274001, 5124144, 5077048, U.S. Patent Application Publication no. 2030202957, WO2003037298, WO2004006833, German patent DE3807712 and Japanese patent JP041 981 26. Some compositions can be used for use as described in the publication of US patent application no. 2001 051659. Some compositions may be used as described in US Pat. Nos. 5074842, 57101 83, 3495010, 6444198 and Russian patents RU2144823 and RU21 1 1741. Each of these descriptions is incorporated herein by reference in its entirety. Some compositions have been shown to be useful as food additives, particularly in reduced calorie formulations as described in U.S. Pat. 695581 2. The polyethylene glycol compositions of some embodiments of the invention can be used as a softening agent, particularly in cosmetic formulations or as a carrier or filler in pharmaceutical applications. One skilled in the art will realize that compositions of technical grade, or compositions not prepared to meet pharmaceutical standards, will not be suitable for such uses.

EXAMPLES Comparative Example A First, a polyethylene glycol initiator with a molecular weight of 1000 is made by providing 44.2 grams of diethylene glycol initiator, 0.4 gram of a 50% solution of NaOH and 410 grams of ethylene oxide having less than about 1. 00 ppm of water. The reaction is performed at between 155 ° C and 170 ° C to produce a polyethylene glycol intermediate with a number average molecular weight of about 1000. A portion of 1 35 grams of the above material is reacted with 339 grams of ethylene oxide of high purity and 0.2 g of 50% solution of NaOH, while the temperature is maintained between 155 ° C and 1 70 ° C, followed by neutralization at a pH of 4.5-7.5, usually using phosphoric acid, acetic acid or a mix of them. The resulting polyethylene glycol has a molecular weight of about 3350 g / mol. Analysis of the low molecular weight oligomers shows that such a composition has a total concentration of 59 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 248 ppm of all oligomers with a molecular weight of less than or equal to 460 g / mol, 948 ppm of all oligomers with a molecular weight of less than or equal to 81 2 g / mol; and 3965 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Comparative Example B The procedure of Comparative Example A was repeated, except that an increased amount of catalyst, 1.0 grams of a 50% solution of NaOH, was used and the catalyzed diethylene glycol initiator was dried at < 0.4% by weight of water before the ethoxylation of the polyethylene glycol intermediate, which had a number average molecular weight of about 1000 g / mol and the subsequent ethoxylation at 3350 g / mol was not recatalized with NaOH. Analysis of the low molecular weight oligomers shows that such composition has a total concentration of 72 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 208 ppm of all oligomers with a molecular weight less than or equal to 460 g / mol, 644 ppm of all oligomers with a molecular weight of less than or equal to 81 2 g / mol, and 2313 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Comparative Example C The procedure of Comparative Example A was substantially repeated, except that the temperature was reduced from 155-170 ° C to 145-155 ° C. Analysis of the low molecular weight oligomers shows that such composition has a total concentration of 28 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 1 51 ppm of all oligomers with a molecular weight less than or equal to 460 g / mol, 668 ppm of all oligomers with a molecular weight of less than or equal to 812 g / mol; and 2994 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Comparative Example D Polyethylene glycol having a target molecular weight of 8000 g / mol is prepared by forming a polyethylene glycol initiator with a molecular weight of 1000 g / mol by providing 44.2 grams of diethylene glycol initiator, 0.4 gram of a 50% solution of NaOH and 410 grams of ethylene oxide having less than about 100 ppm of water. The reaction is carried out between 155 ° C and 170 ° C to provide a sample of relatively low molecular weight polyethylene glycol. A 44.3 gram portion of the above material is reacted with 41 3 grams of high purity ethylene oxide and 0.2 g of 50% solution of NaOH, while the temperature is maintained between 1 55 ° C and 170 ° C, followed by by neutralization at a pH of 4.5-7.5, usually using phosphoric acid, acetic acid or a mixture thereof. The resulting polyethylene glycol has a molecular weight of about 8000 g / mol. Analysis of the low molecular weight oligomers shows that such a composition has a total concentration of 74 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 235 ppm of all oligomers with a molecular weight of less than or equal to 460 g / mol, 679 ppm of all oligomers with a molecular weight of less than or equal to 81 2 g / mol; and 2693 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Example 1 Polyethylene glycol having a target molecular weight of 3350 g / mol is prepared by forming a polyethylene glycol initiator with a molecular weight of 1000 g / mol by providing 44.2 g of polyethylene glycol initiator and 1 gram of a 50% solution of NaOH . The catalyzed initiator solution is then dried to less than 0.4% by weight of water and 356 grams of ethylene oxide having less than about 100 ppm of water are added. The reaction is carried out between 155 ° C and 1 70 ° C to provide a polyethylene glycol having a molecular weight of about 1000 g / mol. A portion of 1 35 grams of the above material is reacted with 339 grams of high purity ethylene oxide and 0.0 g of 50% solution of NaOH, while the temperature is maintained between 145 ° C and 155 ° C, followed by neutralization at a pH of 4.5-7.5, usually using phosphoric acid, acetic acid or a mixture thereof. The resulting polyethylene glycol has a molecular weight of about 3350 g / mol. The loose bulk density for this material is 0.69 g / cm3. Analysis of the low molecular weight oligomers shows that such a composition has a total concentration of 25 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 75 ppm of all oligomers with a molecular weight of less than or equal to 460 g / mol, 246 ppm of all oligomers with a molecular weight of less than or equal to 812 g / mol; and 1009 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Example 2 Polyethylene glycol having a target molecular weight of 8000 g / mol is prepared by forming a polyethylene glycol initiator with a molecular weight of 1000 g / mol by providing 44.2 grams of diethylene glycol initiator and 1 gram of a 50% solution of NaOH . The catalyzed initiator solution is then dried to less than 0.4% by weight of water and 356 grams of ethylene oxide having less than about 1000 ppm of water are added. The reaction is carried out at between 1 55 ° C and 1 70 ° C to provide a polyethylene glycol having a molecular weight of about 1000 g / mol. A 50 gram portion of the above material is reacted with 370 grams of high purity ethylene oxide and 0.0 g of 50% NaOH solution, while the temperature is maintained between 135 ° C and 145 ° C followed by neutralization to a pH of 4.5-7.5, usually using phosphoric acid, acetic acid or a mixture thereof. The resulting polyethylene glycol has a molecular weight of about 8000 g / mol. The loose bulk density for this material is 0.61 g / cm3. Analysis of the low molecular weight oligomers shows that such a composition has a total concentration of 1 8 ppm of all oligos with a molecular weight of less than or equal to 240 g / mol, 64 ppm of all oligomers with a molecular weight less than or equal to 460 g / mol, 1 93 ppm of all oligomers with a molecular weight of less than or equal to 812 g / mol and 450 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol For comparison, these values are recorded in Table 3.

Example of a commercially available polyethylene glycol having a reported molecular weight of 3350 g / mol was obtained and its distribution of low molecular weight oligomers was measured. Analysis of the low molecular weight oligomers shows that this material has a total concentration of 69 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 204 ppm of all oligomers with a molecular weight of less than of or equal to 460 g / mol, 617 ppm of all oligomers with a molecular weight of less than equal to 812 g / mol; and 2014 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Comparative Example F Another commercially available polyethylene glycol having a reported molecular weight of 3350 g / mol was obtained and its distribution of low molecular weight oligomers was measured. Analysis of the low molecular weight oligomers shows that this material has a total concentration of 81 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 300 ppm of all oligomers with a molecular weight of less than or equal to 460 g / mol, 1076 ppm of all oligomers with a molecular weight of less than or equal to 812 g / mol; and 4590 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Comparative Example G A commercially available polyethylene glycol having a reported molecular weight of 8000 g / mol is analyzed. Analysis of the low molecular weight oligomers shows that this material has a total concentration of 70 ppm of all oligomers with a molecular weight of less than or equal to 240 g / mol, 21 8 ppm of all oligomers with a molecular weight less than or equal to 460 g / mol, 738 ppm of all oligomers with a molecular weight of less than or equal to 812 g / mol; and 371 9 ppm of all oligomers with a molecular weight of less than or equal to 1472 g / mol. For comparison, these values are recorded in Table 3.

Table 3 Although the invention has been described with a limited number of embodiments, these specific embodiments are not intended to limit the scope of the invention as described otherwise and are claimed herein. Moreover, variations and modifications exist for example, various additives, not listed herein, may also be used to further enhance one or more properties of the polyethylene glycol compositions described herein. For example, it may be desirable to add salts or other electrolytes to some compositions. In this way, mixing of the compositions described herein with salts, flavors, antioxidants or one or more other additives is envisaged. In other embodiments, the compositions do not include, or are essentially free of, any component not listed herein. As used herein, the term "essentially free of" means that such components are not present in more than trace amounts, such as about 5 or 10 ppm, or are not purposefully added to the composition. Removal of salts to a desirable level by filtration or other means may also be used in conjunction with some embodiments of the processes described herein to provide compositions having reduced salt content. In addition, compositions consisting of or consisting essentially of the components described should be considered as described herein. From the description provided herein, it will be recognized that the amount of water and thus the levels of oligomers of low molecular weight is affected by the amount of water in the reagents, in particular the initiator and the alkylene oxide. In this way, as reagents having reduced water content become available, the present disclosure can be used to provide compositions with even lower concentrations of low molecular weight oligomers. At least some embodiments of the methods described herein have the feature that they are capable of producing polymers having the low declared levels of low molecular weight oligomers without the need for extra process steps, such as but not limited to filtration techniques , designed to remove such low molecular weight oligomers. Likewise, the compositions described herein generally do not require purification steps to reduce the concentration of low molecular weight oligomers at the levels described. Such methods and compositions are provided by embodiments of the invention. Although the processes are described as comprising one or more steps, these steps may be combined or separated as may be convenient or otherwise desirable. Any step not specifically declared is not included. Finally, any figure described here should be interpreted as approximate, regardless of whether the word "around" or "approximately" is used to describe the figure. Finally in order but not in importance, the claimed compositions are not limited to the processes described herein. They can be prepared with any suitable process. The claimed appended claims cover all such variations and modifications as falling within the scope of the invention.

Claims (50)

1. REIVI NDICATIONS 1 . A method for making a polyalkylene glycol composition having reduced low molecular weight oligomers, which comprises: a) providing a catalyst and an initiator; b) provide an alkylene oxide; and c) maintaining the temperature and concentration of water to provide a polyalkylene glycol composition having a number average molecular weight range from about 3000 to about 1,000,000 g / mol, comprising a first concentration of total oligomer of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 81 2 g / mol.
2. 2. The method of claim 1, wherein the concentration of water in the reactor at one time or more, t, follows the inequality: where Mw'nt is the molecular weight of the composition at time t¡ and M i nt is less than or equal to 2000 g / mol; M fi n represents the final molecular weight desired composition; to! has a value of 1.92, a2 has a value of 3.8x1 0"4, a3 has a value of 260, a4 has a value of 0.0427, a5 has a value of 5590, a6 has a value of 1.54x10" 3, a7 has a value of 2.8x10"s, aa has a value of 2.25x105, a9 has a value of 98.8, a10 has a value of 1.86x107, a has a value of 5380, ai2 has a value of 5590 and a13 has a value 4.78x10"8.
3. 3. The method of claim 1, wherein the concentration of water in the reactor at one time or more, t, follows the inequality: wherein Mwmt is the molecular weight of the composition at time tj and Mwint is greater than or equal to 2000 g / mol; Mw "n represents the final desired molecular weight of the composition, a-? Has a value of 0.404, a2 has a value of 5.9x10" 5, a3 has a value of 1070, a has a value of 0.19, a5 has a value of 6040, a6 has a value of 2.6x10"4, a7 has a value of 1.49x10" 5, a8 has a value of 6.20x105, a9 has a value of 353, and each ai0-a13 has a value of 0.
4. 4 The method of any of the preceding claims, wherein the polyalkylene glycol is polyethylene glycol, which comprises a second total concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to 240 g / l. mol.
5. The method of any of the preceding claims, wherein the polyethylene glycol composition comprises a third total concentration of less than about 1500 ppm of all oligomers having a molecular weight of less than or equal to 1472 g / mol.
6. The method of any of the preceding claims, wherein the first total oligomer concentration of all oligomers having a molecular weight of less than or equal to 81 2 g / mol is less than about 275 ppm.
7. The method of any of the preceding claims, wherein the temperature is maintained at less than about 165 ° C.
8. The method of any of the preceding claims, wherein the temperature ranges from about 120 ° C to about 160 ° C.
9. The method of any of the preceding claims, wherein the temperature ranges from about 130 ° C to about 1,55 ° C.
10. The method of any of the preceding claims, wherein the temperature ranges from about 1 35 ° C to about 1 50 ° C. eleven .
11. The method of any of the preceding claims, wherein the initiator is a diol and the catalyst comprises an alkaline or alkaline-earth hydroxide and uses high purity ethylene oxide with less than about 1000 ppm of water.
12. The method of any of the preceding claims, wherein the catalyst is selected from the group consisting of potassium hydroxide, sodium hydroxide, ammonium hydroxide, metal oxide catalysts, alkali and alkaline earth metal hydroxides, antimony hexafluoride , antimony hexachloride, Na, K and alkaline and alkaline-earthy methoxides. 1 3.
13. The method of any of the preceding claims, wherein the catalyst is an alkaline or alkaline-earthy hydroxide.
14. The method of any of the preceding claims, wherein the initiator is chosen from water, ethylene glycol, diethylene glycol or any poly (oxyethylene) compound or other diol.
15. The method of any of the preceding claims, wherein the initiator is diethylene glycol.
16. 16. The method of any of the preceding claims, wherein the alkoxide is ethylene oxide having less than about 1000 ppm of water.
17. The method of any of the preceding claims, wherein the polyalkylene glycol is a polyethylene glycol and the concentration of water in the reactor is less than or equal to 1.5% at the time when the molecular weight, Mw, of the polyethylene glycol in the reactor is 1000 g / mol or less.
18. The method of any of the preceding claims, wherein the process first comprises forming a lower molecular weight polyethylene glycol composition, and subsequently forming the polyethylene glycol composition from at least a portion of the first lower molecular weight polyethylene glycol composition. .
19. The method of any of the preceding claims, wherein forming the polyethylene glycol composition is achieved in the absence of catalyst other than that provided to form the first lower molecular weight polyethylene glycol composition.
20. 20. A polyalkylene glycol composition having a number average molecular weight range of from about 4000 to about 1 000 g / mol, comprising a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g / mol and a second total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to 240 g / mol. twenty-one .
21. The composition of claim 20, wherein the polyalkylene glycol composition is a polyethylene glycol composition.
22. The composition of any of claims 20 to 21, having a third total oligomer concentration of less than about 1500 ppm of all oligomers having a molecular weight of less than or equal to 1472 g / mol.
23. The composition of any of claims 20 to 22, wherein the number average molecular weight range is from about 4000 to about 5000 g / mol.
24. The composition of any of claims 20 to 22, wherein the number average molecular weight range is from about 5000 to about 7000 g / mol.
25. The composition of any of claims 20 to 22, wherein the number average molecular weight range is from about 7000 to about 9000 g / mol.
26. 26. The composition of any of claims 20 to 25, wherein the first total oligomer concentration is less than about 275 ppm of all oligomers having a molecular weight less than or equal to 812 g / mol.
27. The composition of any of claims 20 to 26, having a third total oligomer concentration of less than about 1500 ppm of all oligomers having a molecular weight less than or equal to 1472 g / mol.
28. The composition of any of claims 20 to 26, wherein the number average molecular weight range is from about 4000 to about 7000 g / mol.
29. 29. The composition of any of claims 20 to 26, wherein the number average molecular weight range is from about 7000 to about 9000 g / mol.
30. 30. The composition of any of claims 20 to 26, wherein the composition has a solid product form and a bulk density of more than about 0.50 g / cm3.
31. 31 The composition of any of claims 20 to 26, wherein the composition has a solid product form and has an average particle size of less than about 1 mm.
32. 32. A solid polyethylene glycol composition having a bulk density of more than about 0.50 g / cm3 and less than 0.95 g / cm3 and a number average molecular weight range from about 3000 to about 10, 000 g / mol, comprising a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight of less than or equal to 812 g / mol and comprising a second total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight of less than or equal to 240 g / mol.
33. 33. The composition of claim 32, wherein the average particle size is less than 1 mm.
34. The composition of claim 32 or 33 having a third total oligomer concentration of less than about 1500 ppm of all oligomers having a molecular weight of less than or equal to 1472 g / mol.
35. 35. The composition of any of claims 31 to 34, wherein the number average molecular weight range is from about 3000 to about 4000 g / mol.
36. 36. The composition of any of claims 31 to 34, wherein the number average molecular weight range is from about 4000 to about 5000 g / mol.
37. 37. The composition of any of claims 31 to 34, wherein the number average molecular weight range is from about 5000 to about 7000 g / mol.
38. 38. The composition of any of claims 31 to 34, wherein the number average molecular weight range is from about 7000 to about 9000 g / mol.
39. 39. The composition of any of claims 20 to 38, wherein the composition is essentially free of antioxidants.
40. 40. A polyethylene glycol composition having a number average molecular weight range from about 3000 to about 10,000 g / mol, comprising a first total oligomer concentration of less than about 400 ppm of all oligomers having a molecular weight less than or equal to equal to 812 g / mol and a second total oligomer concentration less than about 50 ppm of all oligomers having a molecular weight less than or equal to 240 g / mol and comprising more than 0.1 g of water per 1.0 g of polyethylene glycol .
41. 41 A polyalkylene glycol composition having a number average molecular weight range of from about 3000 to about 10,000 g / mol, comprising a first total oligomer concentration of less than about 90 ppm of all oligomers having a molecular weight less than or equal to 460 g / mol, wherein the composition is obtained without additional processing to remove the oligomers having a molecular weight of less than about 460 g / mol.
42. 42. The composition of claim 41, wherein the first concentration of total oligomer is less than about 70 ppm of all oligomers having a molecular weight less than or equal to 460 g / mol.
43. 43. The composition of claim 41 or 42, having a second total oligomer concentration less than about 1500 ppm of all oligomers having a molecular weight less than or equal to 1472 g / mol.
44. 44. The composition of any of claims 41 to 43, wherein the polyalkylene glycol composition is a polyethylene glycol composition, wherein the number average molecular weight range is from about 3000 to about 4000 g / mol.
45. 45. The composition of any of claims 41 to 43, wherein the polyalkylene glycol composition is a polyethylene glycol composition, wherein the number average molecular weight range is from about 4000 to about 5000 g / mol.
46. 46. The composition of any of claims 41 to 43, wherein the polyalkylene glycol composition is a polyethylene glycol composition, wherein the number average molecular weight range is from about 5000 to about 7000 g / mol.
47. 47. The composition of any of claims 41 to 43, wherein the polyalkylene glycol composition is a polyethylene glycol composition, wherein the number average molecular weight range is from about 7000 to about 9000 g / mol.
48. 48. The composition of any of claims 41 to 47, wherein the composition has a solid product form and has a bulk density greater than about 0.50 g / cm3 to about 0.95 g / cm3.
49. 49. The composition of any of claims 41 to 48, wherein the composition has a solid product form and has an average particle size of less than about 1 mm.
50. 50. A method for making a polyethylene glycol composition having reduced molecular weight oligomers, comprising: a) providing a catalyst and an initiator; b) provide an alkylene oxide; and c) maintaining the temperature and concentration of water to provide a polyalkylene glycol composition having a number average molecular weight range from about 3000 to about 10,000 g / mol, comprising a first total oligomer concentration of less than about 400 ppm of all the oligomers having a molecular weight less than or equal to 812 g / mol; wherein the temperature is maintained at less than about 165 ° C; and wherein the concentration of water in the reactor is less than or equal to 1.5 percent by weight at a time when the molecular weight, Mw, of the polyethylene glycol in the reactor is 1000 g / mol or less. SUMMARY Polyalkylene glycol compositions are described having low molecular weight oligomers. Some compositions, in particular polyethylene glycol compositions have a number average molecular weight ratio from about 3000 to about 1,000,000 g / mol and have a total oligomer concentration less than about 400 ppm of all oligomers having a molecular weight less than or equal to 81 2 g / mol and a total oligomer concentration of less than about 50 ppm of all oligomers having a molecular weight less than or equal to 240 g / mol. Other polyalkylene glycol compositions, in particular polyethylene glycol compositions, are characterized by a total oligomer concentration of less than about 90 ppm of all oligomers having a molecular weight less than or equal to 460 g / mol and are obtained without further processing to remove the oligomers having a molecular weight less than about 460 g / mol. Methods for making such compositions are also described.