Preparations comprising poorly water-soluble pharmaceutical agents and antimicrobial agents

Abstract

Compositions comprising a poorly water-soluble pharmaceutical agent, a carrier protein and an antimicrobial agent, wherein significant microbial growth is inhibited in the composition. The amount of the antimicrobial agent in the composition may be below the level that induces a toxicological effect, or at a level where a potential side effect can be controlled or tolerated. Compositions comprising a poorly water-soluble pharmaceutical agent, a carrier protein, a sugar and optionally an antimicrobial agent are further provided. Methods of using the compositions are further provided.

Description

TECHNICAL AREA The present invention relates to compositions comprising protein-associated, low water-soluble pharmaceutical agents for parenteral or other use and which further includes an antimicrobial agent. BACKGROUND OF THE INVENTION Many drugs for parenteral use and especially those administered intravenously, causing undesirable side effects. These drugs are frequently water- insoluble, and are thus formulated with solubilizing agents, surfactants, solvents and / or emulsifiers which can be irritating, allergic or toxic when they administered to patients (see, for example, Briggs et al., Anesthesis 37:1099 (1982), and Waugh et al., Am. J. Hosp. Pharmacists, 48:1520 (1991)). For example, is chemo- therapeutic drug paclitaxel active against carcinomas of the ovary, breast, lung, oesophagus and head and neck. However, paclitaxel has been shown to induce toxicities associated with with administration, as well as significant acute and cumulative toxicity as myelosuppression, neutropenic fever, anaphylactic reaction and peripheral neuropathy. Paclitaxel is very poorly water-soluble and as a result cannot be practically formulated with water for intravenous administration. Traditionally, paclitaxel is formulated for intravenous administration in a solution with polyoxyethylated castor oil (Cremophor) as the primary solvent and high concentrations of ethanol as a co-solvent Cremophor is associated with side effects that can be serious, including anaphylaxis and other hypersensitivity reactions requiring pretreatment with corticosteroids, antihistamines and H blockers (see for example Gelderblom et al., Eur. J. 2 of Cancer, 37:1590-1598, (2001)). Similarly, docetaxel is used in the treatment of anthracycline-resistant breast cancer, but has also been shown to induce side effects with hypersensitivity and fluid retention, which can be serious. To circumvent problems associated with administration-related side effects of drug formulations, alternative formulations have been developed. For example, TM Abraxane is a Cremophor-free, protein-stabilized formulation of paclitaxel that was developed to resolve or minimize the side effects caused by Cremophor EL / ethanol Similar protein-containing formulations have also been developed for other taxanes such as docetaxel and ortataxel, as well as other drugs. Because protein serves as a good substrate for microbial growth, a major challenge that must be considered when using these protein-containing formulations, a potential microbial contamination. To minimize the risk of microbial contamination, for example, the current intravenous formulation of Abraxane is stored in lyophilized form, and should be injected immediately (for example, within hours) after it is reconstituted in an aqueous medium. Bacterial growth may result from inadvertent contamination in a container containing a single dose. Bacterial contamination is even more of a problem when multiple doses are withdrawn from the containers as needed. Antibacterial agents such as EDTA, pentetate, or sulfite-containing agents are generally known and used in pharmaceutical preparations, see for example US 5,714,520, 5,731,355, 5,731,356, 6,028,108, 6,100,302, 6,147,122, 6,177,477, 6,399,087 and 6,469 069, WO 99 / 39696 and US Publ. No. 05 / 0004002. Many of the antibacterial agents are however, are significantly toxic. For example, the addition of sulfites to drug formulations potential adverse effects for the pediatric population and for those in the general population who are allergic to sulfur, see, for example, Baker et al., Anesthesiology, 103(4):1-17 (2005); Mirejovsky, Am. J. Health Syst. Pharm., 58:1047 (2001). The toxicities of these antibacterial agents are becoming a significant problem. in the formulation of protein-containing pharmaceutical drug mixtures which are frequently requires more antimicrobial agents than non-proteinaceous formulations do to be effective against significant microbial growth. Furthermore, many antimicrobial agents are known to interact with proteins and causes stability problems such as aggregation, see for example Lam et al., Pharm. Res. 14:725-729 (1997). The effect of antimicrobial agents on protein stability provides a difficult problem in formulating proteinaceous preparations of poorly water-soluble, pharmaceutical agents because suitable configuration of proteins is generally required for stabilization of poorly water-soluble pharmaceutical agents in the preparation. There is therefore a need to develop protein-containing formulations of low water-soluble pharmaceutical agents containing antimicrobial agents that provide a desired antimicrobial efficacy, but does not significantly affect protein stability and / or does not cause unacceptable toxicological effects upon administration. It is also a need to develop protein-containing formulations of poorly water-soluble, pharmaceuticals that can be more easily reconstituted. EP 1 348 430 A relates to an anti-tumor composition consisting of nanoparticles of paclitaxel and human serum albumin, with the addition of citric acid to an aqueous albumin solution. US 6,120,805 A discloses a composition comprising docetaxel and albumin in a phosphate buffer which is mixed and homogenized. The composition is added with mannitol and lyophilized. WO 00 / 06152 A discloses a paclitaxel composition comprising serum albumin in a citrate / phosphate buffer. The composition can be lyophilized and reconstituted in an aqueous sugar solution. The description in all publications, patents, patent applications and published patent applications mentioned herein are considered part of the present description. BRIEF SUMMARY OF THE INVENTION The present invention provides compositions (such as pharmaceutical preparations) comprising a poorly water-soluble pharmaceutical agent, a carrier protein (such as albumin), such as human serum albumin (HSA)), and an antimicrobial agent, wherein significant microbial growth is inhibited in the composition. In some embodiments, significant microbial growth in the preparations inhibited for a given period of time such as at least 4 hours (including, for example, at least about 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 or 120 hours). In some embodiments, the compositions are less prone to microbial contamination compared to preparations that do not contain any antimicrobial agent. In some embodiments, the compositions of the invention comprise a small water-soluble, pharmaceutical agent, a carrier protein (such as albumin, e.g. HSA), and an antimicrobial agent, wherein the antimicrobial agent is in an amount effective to inhibit significant microbial growth in the preparation or preparations. In certain embodiments, the poorly water-soluble pharmaceutical agent is a antineoplastic agent or a chemotherapeutic agent. In some embodiments, it is poorly water-soluble pharmaceutical agent any of (and in some embodiments selected from the group consisting of) paclitaxel, docetaxel, ortataxel or other taxanes, geldanamycin, 17-allylaminogeldanamycin, thiocolcicine and dimers thereof, rapamycin, cyclosporine, epothilone, radicicol and combretastatin. In some embodiments For example, there is provided a composition comprising a taxane or a derivative thereof (such as paclitaxel, docetaxel, or ortataxel), a carrier protein (such as albumin, for example HSA), and an antimicrobial agent where significant microbial growth is inhibited in In some embodiments, there is provided a composition comprising a taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel), a carrier protein (such as albumin, for example HSA), and an antimicrobial agent, wherein the antimicrobial agent is present in an amount effective to inhibit significant microbial growth in the preparation. In In some embodiments, the poorly water-soluble pharmaceutical agent is amorphous and / or non-crystalline taxane (such as paclitaxel). In some embodiments, the small water-soluble pharmaceutical agents used to prepare the preparation in a anhydrous form (as anhydrous docetaxel). In some embodiments, the antimicrobial The drug is not deferoxamine (i.e. different from deferoxamine). In some embodiments, there is provided a composition comprising a small water-soluble, pharmaceutical agent, a carrier protein (such as albumin, e.g. HSA), and an antimicrobial agent, wherein the antimicrobial agent is a gelling agent and wherein significant microbial growth is inhibited in the composition. In some embodiments there is provided a composition comprising a taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel), a carrier protein (such as albumin, for example HSA), and an antimicrobial agent, wherein the antimicrobial agent is a gelling agent and where significant microbial growth is inhibited in the preparation. In some In some embodiments, the antimicrobial agent is a polydentate gelling agent. In some In embodiments, the antimicrobial agent comprises one or more carboxylic acid groups. In some embodiments, the chelating agent is not deferoxamine (i.e., different from deferoxamine). In some embodiments, the chelating agent is any of (and in certain embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof, and mixtures thereof. In some embodiments, the the chelating agent citrate and EDTA. In some embodiments, there is provided a composition comprising a small water-soluble, pharmaceutical agent, a carrier protein (such as albumin, e.g. HSA), and an antimicrobial agent, wherein the antimicrobial agent is a non-gelating agent, and wherein significant microbial growth is inhibited in the composition. In some embodiments there is provided a composition comprising a taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel), a carrier protein (such as albumin, for example HSA), and an antimicrobial agent wherein the antimicrobial agent is a non-gelating agent agent and where significant microbial growth is inhibited in the preparation. In some In some embodiments, the non-gelling antimicrobial agent acts as a pro-oxidant. In In some embodiments, the non-gelling antimicrobial agent acts as antioxidant. In some embodiments, the non-gelling agent is any of (and in some embodiments selected from the group consisting of) sulfites, benzoic acid, benzyl alcohol, chlorobutanol, paraben and derivatives thereof. In some embodiments, the composition comprises a slightly water-soluble pharmaceutical agent, an albumin and an antimicrobial agent in which the weight ratio albumin:low water- soluble pharmaceutical agent in the composition is about 0.01:1 to about 100:1, and where significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises a small water-soluble pharmaceutical agent, an albumin and an antimicrobial agent wherein the weight ratio of albumin: poorly water-soluble pharmaceutical agent in the preparation is approximately 18:1 or less (including, for example, any of about 1:1 to about 18:1, about 2:1 to approx. 15:1, approx. 3:1 to approx. 12:1, approx. 4:1 to approx. 10:1, approx. 5:1 to approx. 9:1 ​​and approx. 9:1), and there significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises the preparation is a taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel), an albumin, and an antimicrobial agent in which the weight ratio of albumin:taxane or derivative thereof in the preparation is about 18:1 or less (including, for example, any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1 and about 9:1), and where significant microbial growth is inhibited in the preparation. In some embodiments, the poorly water-soluble pharmaceutical agent (such as a taxane or derivative thereof) coated with albumin. In some embodiments, the antimicrobial agent a chelating agent such as any of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives and mixtures thereof. In some embodiments, the gelling agent is not deferoxamine (i.e., are different from deferoxamine). In some embodiments, it is antimicrobial agent a non-gelling agent, such as any of (and in some embodiments selected from the group consisting of) sulfites, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof and mixtures thereof. In some embodiments the composition further comprises a sugar (such as the sugar described herein). In some embodiments, the composition comprises a protein-associated, low water- soluble, pharmaceutical agent and an antimicrobial agent, where significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises a protein- associated taxane or a derivative thereof (such as a protein-associated paclitaxel, protein- associated docetaxel or protein-associated ortataxel) and an antimicrobial agent where significant microbial growth is inhibited in the composition. In some embodiments, it is antimicrobial agent a chelating agent such as any of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. In some embodiments, the chelating agent is not deferoxamine (i.e. is different from deferoxamine). In some In some embodiments, the antimicrobial agent is a non-gelling agent such as any any of (and in some embodiments selected from the group consisting of) sulfites, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof and mixtures thereof. In some embodiments, the protein / pharmaceutical agent is in a particular form, which in various embodiments may have average diameters as described herein. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or essentially consisting of of) a poorly water-soluble pharmaceutical agent and a carrier protein; and (2) an anti- microbial agent, where significant microbial growth is inhibited in the preparation. In some In some embodiments, the poorly water-soluble agent is coated with the carrier protein. In some embodiments, the composition comprises particles (such as nanoparticles) comprising (in the form of) various embodiments consisting of or consisting essentially of) (1) taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel) and carrier protein; and (2) a antimicrobial agent, where significant microbial growth is inhibited in the preparation. In some In some embodiments, the taxane or a derivative thereof is coated with the carrier protein. In some In some embodiments, the antimicrobial agent is a gelling agent such as any preferably of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. In some embodiments, the chelating agent is not deferoxamine (i.e., is different from deferoxamine). In some embodiments, the antimicrobial agent is a non-gelating agent such as any of (and in some embodiments selected from the group consisting of) sulphites or derivatives thereof, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof, and mixtures thereof. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of, or consisting essentially of of) a slightly water-soluble pharmaceutical agent and albumin; and (2) an antimicrobial agent, in which the weight ratio albumin: poorly water-soluble, pharmaceutical agent in the preparation is about 0.01:1 to about 100:1, and where significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of, or consisting essentially of of) a slightly water-soluble pharmaceutical agent and albumin; and (2) an antimicrobial agent, in which the weight ratio albumin:slightly water-soluble, pharmaceutical agent in the preparation is about 18:1 or less (including, for example, any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1), and where significant microbial growth is inhibited in the preparation. In some embodiments include the composition (consisting of or consisting essentially of) particles (such as nanoparticles) comprising a taxane or a derivative thereof (such as paclitaxel, docetaxel or ortataxel) and albumin; and (2) an antimicrobial agent in which the weight ratio albumin:taxane or a derivative thereof in the preparation is approximately 18:1 or less (including for example any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1), and where significant microbial growth is inhibited in the composition. In some embodiments, it is poorly water soluble, pharmaceutical agent (such as a taxane or derivative thereof) coated with albumin. In some In some embodiments, the antimicrobial agent is a gelling agent such as any preferably of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. In some embodiments, the chelating agent is not deferoxamine (i.e., is different from deferoxamine). In some embodiments, the chelating agent is not citrate (i.e., is (different from citrate). In some embodiments, the antimicrobial agent is a non- chelating agent such as any of (and in some embodiments selected from the group consisting of) sulfites, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof and mixtures thereof. In some embodiments, the composition further comprises a sugar (such as the sugar described herein). In some embodiments, there is little water-soluble pharmaceutical agent docetaxel or its derivative. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or consisting essentially of of) paclitaxel and albumin; and (2) an antimicrobial agent, wherein the weight ratio of albumin: paclitaxel is about 0.01:1 to about 100:1, where significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or consisting essentially of of) paclitaxel and albumin; and (2) an antimicrobial agent, wherein the weight ratio of albumin: paclitaxel is about 18:1 or less (including, for example, any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and approx. 9:1), where significant microbial growth is inhibited in the preparation. In some embodiments, the albumin:paclitaxel weight ratio is any of 18:1 or smaller, 15:1 or smaller, 14:1 or smaller, 13:1 or smaller, 12:1 or smaller, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. In some embodiments, paclitaxel is coated with albumin. In some embodiments, the composition is substantially free (as free) of Cremophor. In some embodiments, the the preparation is a stable aqueous suspension of particles (such as nanoparticles) comprising paclitaxel and albumin (as particles of paclitaxel coated with albumin), where the preparation further comprises an antimicrobial agent, wherein the weight ratio of albumin:paclitaxel in the preparation is approximately 9:1 or less, and where significant microbial growth is inhibited in the composition. In some embodiments, the composition comprises a dry (such as lyophilized) composition which can be reconstituted (or resuspended or rehydrated) to generally provide a stable aqueous suspension of particles (such as nanoparticles) comprising paclitaxel and albumin (such as paclitaxel coated with albumin), where the preparation further comprises a antimicrobial agent, wherein the weight ratio of albumin:paclitaxel in the preparation is approximately 18:1 or less (including, for example, any of about 1:1 to about 18:1, about 2:1 to about 15:1, approx. 3:1 to approx. 12:1, approx. 4:1 to approx. 10:1, approx. 5:1 to approx. 9:1, and approx. 9:1), and there significant microbial growth is inhibited in the composition. In some embodiments, it is antimicrobial agent a chelating agent, such as any of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. In some embodiments, it is chelating agent is not deferoxamine (i.e. is different from deferoxamine). In some In some embodiments, the antimicrobial agent is a non-gelling agent such as a any of (and in some embodiments selected from the group consisting of) sulfites or derivatives thereof, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof and mixtures thereof. In some embodiments, the composition additionally comprises a sugar (such as sugar described here). In some embodiments, the particles (such as nanoparticles) as described herein have a average or mean diameter of not more than about one in 1,000, 900, 800, 700, 600, 500, 400, 300, 200 and 100 nm. In some embodiments, it is mean or average diameter of the particles not greater than about 200 nm. In some embodiments, the average or median diameter of the particles between about 20 nm to about 400 nm. In some embodiments, the mean or average diameter of the particles between about 40 nm to about 200 nm. In some In some embodiments, the particles are sterile filterable. In some embodiments, the composition comprises a poorly water-soluble pharmaceutical agent (such as a taxane or a derivative thereof), a carrier protein (such as albumin), and a antimicrobial agent in an amount effective to inhibit significant microbial growth in the composition. In some embodiments, the composition comprises a slightly water-soluble, pharmaceutical agent (such as a taxane or a derivative thereof), a carrier protein (such as albumin) in an amount effective to stabilize the poorly water-soluble, pharmaceutical agent in an aqueous medium, and an antimicrobial agent in an amount that is effective to inhibit significant microbial growth in the composition. In some embodiments the preparation comprises a poorly water-soluble pharmaceutical agent (such as a taxane or a derivative thereof), a carrier protein (such as albumin) in an amount effective to reduce one or more side effects upon administration of the poorly water-soluble pharmaceutical agent in a human, and an antimicrobial agent in an amount effective to inhibit significant microbial growth in the composition. In some embodiments, it is antimicrobial agent a chelating agent such as any of (and in some embodiments selected from the group consisting of) edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. In some embodiments, it is antimicrobial agent a non-gelling agent such as any of (and in some embodiments selected from the group consisting of) sulfites, benzoic acid, benzyl alcohol, chlorobutanol, paraben, derivatives thereof and mixtures thereof. The specific amounts of the antimicrobial agents are described in more detail below. The compositions as described herein may be a stable, aqueous suspension of the small water-soluble pharmaceutical agent, such as a stable aqueous suspension of the small water-soluble pharmaceutical agent at a concentration of any of about 0.1 mg / ml to approx. 100 mg / ml, approx. 0.1 mg / ml to approx. 50 mg / ml, approx. 0.1 mg / ml to approx. 20 mg / ml, approx. 1 mg / ml to approx. 10 mg / ml, approx. 2 mg / ml to approx. 8 mg / ml, approx. 4 mg / ml to approx. 6 mg / ml, and about 5 mg / ml. In some embodiments, the concentration of the low water- soluble pharmaceutical agent at least about any of 1.3 mg / ml, 1.5 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml, 8 mg / ml, 9 mg / ml, 10 mg / ml, 15 mg / ml, 20 mg / ml, 25 mg / ml, 30 mg / ml, 40 mg / ml and 50 mg / ml. In some embodiments, the composition is a dry (such as lyophilized) composition that can reconstituted, resuspended, or rehydrated to generally form a stable, aqueous suspension of the poorly water-soluble pharmaceutical agent. In some embodiments, the preparation is a liquid (such as aqueous) preparation obtained by reconstitution or resuspending a dry preparation. In some embodiments, the preparation is an intermediate (as aqueous) the preparation which can be dried (as lyophilized). In some embodiments, the composition is suitable for parenteral (such as intravenous) administration. administration. In some embodiments, the composition is suitable for multidose administration. In In some embodiments, the composition is sterile filterable. In some embodiments, the the preparation has no significant side effects in an individual (such as a human) when administration to the individual. In some embodiments, the compositions as described herein are substantially free (as free) of surfactants. In some embodiments, the compositions are described herein substantially free (as free) of Cremophor. The antimicrobial agent containing the compositions as described herein may further comprise a sugar or other lyophilization or reconstitution aids. In some embodiments, the amount of antimicrobial agent in the composition is below the level that induces a toxicological effect (i.e. above a clinically acceptable level for toxicity) or is at a level where a potential side effect can be controlled or tolerated when the composition is administered to the individual. In some embodiments, the antimicrobial agent present in an amount that does not adversely affect the stability or properties of the carrier protein in the preparation. In another aspect, there are provided compositions (such as lyophilized compositions or intermediate liquid preparations which can be lyophilized) comprising a slightly water-soluble, pharmaceutical agent, a carrier protein (such as albumin) and a sugar. In some embodiments- forms, the preparation comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or consisting essentially of) poorly water-soluble pharmaceutical agent (such as taxane or derivatives thereof) and an albumin; and (2) a sugar, wherein the weight ratio of albumin:slightly water-soluble pharmaceutical agent in the preparation is approximately. 0.01:1 to about 100:1. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or in the consisting essentially of) a poorly water-soluble pharmaceutical agent (such as a taxane or derivatives thereof) and an albumin; and (2) a sugar, in which the weight ratio of albumin:little water- soluble pharmaceutical agent in the preparation is about 18:1 or less (including for example any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1). In some embodiments, it is poorly water-soluble pharmaceutical agents coated with albumin. In some embodiments is the preparation a dry (such as lyophilized) preparation where the lyophilized preparation can reconstituted (or resuspended or rehydrated) to provide a generally stable aqueous suspension of the poorly water-soluble pharmaceutical agent, and where the time for reconstitution of the preparation in an aqueous solution is less than that of the preparation without sugar. In some embodiments, the concentration of sugar in the composition or a reconstituted suspension obtained from the preparation is greater than approximately 50 mg / ml. In some embodiments, the composition further comprises an antimicrobial agent such as antimicrobial agents as described herein. In some embodiments, it is poorly water-soluble, pharmaceutical agent docetaxel or a derivative thereof. In some embodiments, the invention provides a composition comprising paclitaxel, an albumin, and a sugar, where the weight ratio of albumin:paclitaxel is approximately 9:1 or less, and where the sugar in the preparation or a reconstituted suspension resulting from the composition is greater than about 50 mg / ml. In some embodiments, the composition comprises (1) particles (such as nanoparticles) comprising (in various embodiments consisting of or consisting essentially of) paclitaxel and albumin; and (2) a sugar, wherein the weight ratio of albumin:paclitaxel in the preparation is approximately 18:1 or less (including for example any of about 1:1 to about 18:1, about 2:1 to about 15:1, about 3:1 to about 12:1, approx. 4:1 to approx. 10:1, approx. 5:1 to approx. 9:1, and approx. 9:1), and there the sugar in the preparation or a reconstituted suspension resulting from the preparation, is greater than about 50 mg / ml. In some embodiments, the sugar is present in an amount effective to increase the stability of the poorly water-soluble pharmaceutical agent in the preparation compared with a preparation without the sugar. In some embodiments, the sugar is present in an amount which is effective in improving the filterability of the preparation compared to a preparation without sugar. In some embodiments, the sugar is present in an amount effective to reduce foaming during reconstitution of the lyophilized preparation compared to a preparation without the sugar. Further provided are unit dosage forms of compositions as described herein, articles of manufacture comprising the compositions or unit dosage forms of the invention in suitable packaging (such as vials or containers (including sealed vials or containers and sterile sealed vials or containers)), and set comprehensive preparations. The invention also provides methods for making and using these compositions as described here. It should be clear that one, some, or all of the properties of the different embodiments as described herein may be combined to form other embodiments of the invention. DETAILED DESCRIPTION OF THE INVENTION The present invention provides in one aspect compositions, including pharmaceutical preparations, comprising a poorly water-soluble pharmaceutical agent, a carrier protein and an antimicrobial agent. The carrier protein in the preparation generally does the poorly water-soluble, pharmaceutical agent more easily suspendable in an aqueous medium and / or supports maintenance of the suspension compared to preparations that does not include the carrier protein. The carrier protein is generally, but not necessarily, present in an amount sufficient to stabilize the poorly water-soluble pharmaceutical agent in an aqueous suspension and / or in an amount effective to reduce one or several side effects of administration of the poorly water-soluble pharmaceutical agent to an individual (such as a human being). The antimicrobial agent is generally present in an amount which is effective in inhibiting (such as delaying, reducing, slowing down and / or preventing) significantly microbial growth in the composition. Preferably, the amount of antimicrobial agent in the composition is below the level that induces a toxicological effect or at a level where a potential side effect can be controlled or tolerated. In another aspect, there are provided compositions (such as lyophilized compositions or an intermediate liquid preparation which can be lyophilized) comprising a slightly water-soluble, pharmaceutical agent, a carrier protein (such as albumin), and a sugar. General reference to "the preparation" or "preparations" includes and is applicable to on the compositions of the invention. The invention also provides pharmaceutical compositions comprising the components described herein. Reference to paclitaxel applies to paclitaxel or its derivatives and according to This means that the invention is intended to include both of these embodiments. Reference to "paclitaxel" is for convenience of description and is exemplary. Derivatives or analogs of paclitaxel includes, but is not limited to, compounds that are structurally similar paclitaxel and is in the same general chemical class as paclitaxel, for example docetaxel. In some embodiments, the derivative or analog of paclitaxel retains similar biological, pharmacological, chemical and / or physical properties (including (e.g. functionality) of paclitaxel. Examples of paclitaxel derivatives or analogues include docetaxel and ortataxel. The same principle of description applies also other agents provided herein which include, for example, antimicrobial agents and poorly water-soluble pharmaceutical agents (such as taxanes (including docetaxel, ortataxel or other taxanes), geldanamycin, 17-allyl-aminogeldanamycin, thiocolcicine and its dimers, rapamycin, cyclosporine, epothilone, radicicol and combretastatin). It should be clear that the aspect and embodiments of the invention as described herein includes "consisting of" and / or "essentially consisting of" aspects and embodiments. Antimicrobial agents The term "antimicrobial agent" as used herein refers to an agent which is in capable of inhibiting (such as delaying, reducing, slowing and / or preventing) the growth of one or several microorganisms. Significant microbial growth can be measured or indicated on a number of methods known in the art, such as one or more of the following: (1) microbial growth in a a preparation sufficient to cause one or more adverse effects in an individual when the preparation is administered to the individual; (2) more than approximately a 10-fold increase in microbial growth over a certain period of time (for example, over a 24-hour period) after extrinsic 3 contamination (as exposure to 10-10 colony forming units at a temperature of (range 20-25 °C). Other indications of significant microbial growth are described here. The antimicrobial agent described herein may be effective against the growth of a or more bacteria (including both gram positive and gram negative bacteria), fungi, or mold. For example, in some embodiments, the antimicrobial agent is effective against growth of any one or more gram positive cocci (such as Staphylococcus aureus and Staphylococcus epidermidis), fermentative gram-negative rods (such as Klebsiella pneumonidae, Enterobacter cloaceae, Escherichia Coli, Proteus species and Enterobacter gergoviae), non-fermentative gram negative rods (such as Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas fluorescens, Pseudomonas putida, Flavobacterium and Acinetobacter species), and spore-forming bacteria (such as Bacillus subtilis). In some embodiments, the antimicrobial agent is effective against the growth of a any one or more of yeasts (such as Candida albicans, Candida parapsilosis) and molds (such as Aspergillus niger and Penicillium notatum). Other bacteria whose growth can be inhibited include, for example, B. cereus, B. cohaerens, B. megatherium, B. plicatus, B. ubicuitarius, Corynebacterium nicotino- vorans, Enterobacter aerogenes, Lactobacillus arabinosus, L. asei, Ps. Effus and Ps. Ovalis. Other fungi whose growth may be inhibited include, for example, Candida krusei, C. pseudotropicalls, Hansenula anomala, Pichia membranaefaciens, S. anamensis, S. cerevisiae, S. ellipsoideus, S. spec, Torula lipolyticam, Willia anomala, and Z. nussbaumii. Other molds whose growth can be inhibited include, for example, Trichoderma lignorm, Fusarium spec, Gliocladium roseum, Mucor spec and Penicillium glausum. The effectiveness of antimicrobial agents against different microorganisms can measured in a manner known per se, such as by the USP / EP preservation methods efficacy tests or modifications thereof, see Sutton and Porter, PDA J. Pharm. Sci. Tech., 2002; 56:6, 300-311, see also US Pat. Publ. No. 2004 / 0009168. For example, The growth inhibition capacity of the antimicrobial agents in the final preparation is evaluated using of membrane filtration techniques and broth cultures. Around 50-200 colony-forming units (CFU) per mL four standard organisms recommended by the United States Pharmacopeia (USP) for preservative effectiveness tests can be inoculated into each formulation. These four organisms have been identified as: Staphylococci aureus (ATCC 6538), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027) and Candida albicans (ATCC 10231). In addition to these organisms, S. epidermidis (ATCC 12228) and S. aureus can (coagulase negative, ATCC 27734) are also tested. After inoculation of the test organisms, the test formulations are incubated at 30-35 °C. Count for the test organisms on selected time points (such as immediately after inoculation and after 24 hours of incubation at 30-35 °C) can be determined. In some embodiments, the antimicrobial agent is present in an amount that is effective in inhibiting significant microbial growth in at least any one of 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108 or 120 hours. The antimicrobial agent is considered effective, for example, if the agent is able to retard the growth of microorganisms in the preparation to no more than approx. 1 log increase (a factor of 10) within approximately 24 hours of extrinsic contamination. In some In embodiments, the antimicrobial agent is effective if it causes at least an approx. 1.0 log reduction from the original count at approximately 7 days, approximately one 3.0 log reduction at approximately 14 days and / or no increase at approximately day 28 in bacterial the samples. In some embodiments, the antimicrobial agent is effective if it causes at least about a 2.0 log reduction from the initial count at about 6 hours, about a 3.0 log reduction at approximately 24 hours and / or no recovery at approximately day 28 in the bacterial samples. In In some embodiments, the antimicrobial agent is effective if it causes an approx. 2.0 log reduction from initial count at approximately day 7 and / or no increase at approximately day 28 in yeast and mold samples. In some embodiments, the antimicrobial agent is effective if it causes at least about a 1.0 log reduction from the initial count at about 24 hours, about a 3.0 log reduction at approximately day 7 and no increase at approximately day 28 in the bacterial samples. In In some embodiments, the antimicrobial agent is effective if it causes about a 1.0 log reduction from initial count at approximately day 14 and no increase at approximately day 28 in the yeast and mold samples. In some embodiments, the amount of the antimicrobial agent in the composition is below the level that induces a toxicological effect (i.e. above a clinically acceptable toxicity level) or a level at which a potential side effect can be controlled or tolerated when the preparation is administered to an individual. Methods for determining toxicity or side effects for agents administered to an individual are generally known in the art and depends on the particular antimicrobial agent in the preparation. For example, many calcium-chelating antimicrobial agents (such as EDTA) can cause cardiac problems (such as cardiac arrhythmia) when administered to an individual at high levels. Indications for cardiac arrhythmia can thus be monitored to evaluate the toxicity effect of the calcium chelating agent. Other indications such as anemia (for ion chelators), weight loss and mortality, can also be evaluated in animal models to determine the optimal amount of the antimicrobial agent. In some embodiments, the antimicrobial agent is present in an amount that does not adversely affect the stability or properties of the carrier protein in the preparation. In some embodiments, the antimicrobial agent (such as EDTA and non-gelling, antimicrobial agents that are antioxidants) present in an amount effective to inhibit oxidation in the preparation. The specific amount of the antimicrobial agents in the preparation will vary depending on the particular antimicrobial agent or agents in the preparation and is described below in greater detail. Gelling agents In some embodiments, the antimicrobial agent is a chelating agent. Gelling agents act as antimicrobial agents primarily by removing significant metal ions (such as calcium, zinc, magnesium, etc.) and makes these unavailable to essential metabolic processes. The gelling agents are either specific to a especially metal ions (such as calcium, zinc, magnesium, etc) or show a broad spectrum metal ion specificity. In some embodiments, the chelating agent is a polydentate. In some In some embodiments, the chelating agent comprises one or more carboxylic acid groups. In some In some embodiments, the chelating agent is not deferoxamine. Suitable chelating agents includes, but is not limited to, edetate, citrate, pentetate, tromethamine, sorbate, ascorbate, derivatives thereof and mixtures thereof. An antimicrobial agent that is targeted here is an edetate, that is, ethylene- diaminetetraacetic acid (EDTA) and derivatives thereof. Suitable derivatives for use according to the invention includes disodium, trisodium, tetrasodium and disodium-calcium edetate. The nature of the edetate is not critical, provided that it fulfills the function of inhibition of significant growth of microorganisms for an extended period of time (such as at least about 24 hours). In some embodiments, the edetate is present in the compositions at a concentration of about 0.001 mg / ml to about 1 mg / ml, including, for example, any of 0.01 mg / ml to approx. 1 mg / ml, approx. 0.01 mg / ml to approx. 0.5 mg / ml, approx. 0.01 mg / ml to approx. 0.3 mg / ml, approx. 0.02 mg / ml to approx. 0.2 mg / ml, approx. 0.03 mg / ml to approx. 0.1 mg / ml, and approx. 0.05 mg / ml. IN In some embodiments, the concentration of edetate is less than about 1 mg / ml, for example less than about any one of 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.009, 0.008, 0.007, 0.006, 0.005, 0.004, 0.003, 0.002 or 0.001 mg / ml. In some embodiments, the weight ratio is edetate: slightly water-soluble pharmaceutical agent in the preparation about 0.002:1 to about 0.2:1, including, for example, 0.002:1 to about 0.1:1, about 0.002:1 to about 0.06:1, about 0.004:1 to about 0.04:1, about 0.006:1 to about 0.02:1, and about 0.01:1. In some embodiments, the weight ratio is edetate: slightly water-soluble pharmaceutical agent in the preparation less than about any any of 0.2:1, 1.5:1, 0.1:1, 0.05:1, 0.01:1 and 0.005:1. Another antimicrobial agent targeted here is a citrate such as sodium citrate. and citric acid. Suitable concentrations of citrate include, for example, about 0.1 mg / ml to approx. 200 mg / ml, approx. 0.2 mg / ml to approx. 100 mg / ml, approx. 0.3 mg / ml to approx. 50 mg / ml, approx. 0.5 mg / ml to about 10 mg / ml, and about 1 mg / ml to about 5 mg / ml. In some embodiments, the concentration of citrate less than about 200 mg / ml, which is less than about any preferably of 100, 50, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3 or 0.2 mg / ml. In some embodiments, the weight ratio of citrate:slightly water-soluble pharmaceutical agent about 0.02:1 to about 40:1, including for example about 0.04:1 to about 20:1, about 0.06:1 to about 10:1, about 0.1:1 to about 2:1, about 0.2:1 to about 1 mg / ml. In some embodiments, the weight ratio of citrate:slightly water-soluble pharmaceutical agent is less than about any of 40:1, 30:1, 20:1, 10:1, 5:1, 1:1, 0.5:1 and 0.1:1. In other embodiments, the antimicrobial agent is not citrate (i.e., is different from citrate). The antimicrobial agent may also be a pentetate (including calcium trisodium pentetate). In some embodiments, the amount of pentetate is less than about. 3 mg / ml (including, for example, less than about any of 2, 1.5, 1, 0.5, 0.3, 0.1, 0.09, 0.08, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 and 0.05 mg / ml). For example, the pentetate may be present in the range of any of about 0.005 to about 3 mg / ml, about 0.005 to about 0.1 mg / ml, or about 0.005 to about 0.05 mg / ml. In some embodiments, the weight ratio of pentetate:slightly water-soluble pharmaceutical agent about 0.001:1 to about 0.6:1, including, for example, about 0.001:1 to about 0.2:1, and about 0.01:1 to about 0.1:1. In some embodiments, the weight ratio of pentetate:low water-soluble pharmaceutical agent is less than about any of 0.6:1, 0.3:1, 0.1:1, 0.05:1 and 0.01:1. Another antimicrobial agent targeted here is tromethamine. Tromethamine as used herein refers to 2-amino-2-hydroxymethyl-1,3-propanediol, also known such as TRIS. In some embodiments, tromethamine is present in compositions in amounts of not more than about 2.5 mg / ml (including, for example, less than about any of 2.5, 2, 1.5 or 1 mg / ml). For example, tromethamine is present in the range of any any of about 1.5 to about 2.5 mg / ml, such as about 2 mg / ml. Another exemplary amount of tromethamine is about 2.4 mg / ml. In some embodiments, the weight ratio of tromethamine:lite water-soluble pharmaceutical agent about 0.1:1 to about 0.5:1 including, for example, about 0.2:1 to about 0.5:1 and about 0.2:1 to about 0.4:1. In some embodiments, the weight ratio is tromethamine:slightly water-soluble pharmaceutical agent in the preparation less than about one any of 0.5:1, 0.4:1, 0.3:1, 0.2:1 and 0.1:1. In some embodiments, the chelating antimicrobial agent is a sorbate (such as potassium sorbate). In some embodiments, the sorbate is present in the compositions in amounts of not more than about 2.5 mg / ml (including, for example, less than about any of 2.5, 2, 1.5 or 1 mg / ml). For example, the sorbate may be present in an amount of about 0.5 mg / ml. In some embodiments, the weight ratio of sorbate:water-soluble pharmaceutical agent in the composition less than about any of 0.5:1, 0.4:1, 0.2:1 or 0.1:1. In some embodiments, the chelating antimicrobial agent is an ascorbate. (as sodium ascorbate). In some embodiments, the ascorbate is present in the composition in amounts of no more than about 5 mg / ml (including, for example, less than about any any of 2.5, 2, 1.5 or 1 mg / ml). For example, the ascorbate may be present in a amount of 1 mg / ml. In some embodiments, the weight ratio of sorbate:slightly water-soluble pharmaceutical agent in the composition less than about any of 1:1, 0.5:1, 0.4:1, 0.2:1 or 0.1:1. Other suitable metal gelating, antimicrobial agents and their examples amounts include, but are not limited to, sodium formaldehyde sulfoxylate (0.1 mg / ml) and monothiolglycerol (5 mg / ml). Non-gelling agents In some embodiments, the antimicrobial agent is not a chelating agent. (ie is a non-gelating antimicrobial agent) which includes but is not limited to sulphites, benzoic acid, benzyl alcohol, chlorobutanol and derivatives thereof. These Non-gelling antimicrobial agents act via a number of mechanisms. In some In embodiments, the non-gelling antimicrobial agent acts as a pro-oxidant. In some embodiments, the non-gelling antimicrobial agent acts as a antioxidant. An antimicrobial agent in question here is a sulfite. The term "sulfites" refers to all pharmaceutically acceptable derivatives of sulfuric acid (orthosulfuric acid) and metasulphuric acid. Suitable sulfites include, but are not limited to, sodium sulfite and -bisulphite, potassium sulfite and bisulphite, sodium metabisulphite, potassium metabisulphite, or combinations thereof. In some embodiments, the sulfite is present from about 0.075 to about 6.6 mg / ml, including, for example, any of about 0.075 to about 1 mg / ml and about 0.25 mg / ml. In some embodiments, the sulfite is present in an amount less than about any of 5 mg / ml, 3 mg / ml and 1 mg / ml. In some embodiments, the weight ratio of sulfite:slightly water-soluble pharmaceutical agent about 0.01:1 to about 1.5:1, including, for example, 0.02:1 to about 1:1, and about 0.05:1 to about 0.5:1. In some embodiments, the weight ratio of sulfite:slightly water-soluble pharmaceutical agent is less than about any of 1.5:1, 1:1, 0.5:1 and 0.05:1. In some embodiments, the antimicrobial agent is a benzoic acid, benzyl- alcohol or derivatives thereof. In some embodiments, the antimicrobial agent selected is from the group consisting of benzyl alcohol, benzethonium chloride, sodium benzoate, potassium benzoate, benzyl benzoate, or various combinations thereof. In some embodiments, the amount of benzyl alcohol is in the range of about 0.175 to about 9 mg / ml, inclusive for example, any of about 0.7 to about 4.5 mg / ml, about 1.5 mg / ml and about 1 mg / ml. In some embodiments, the amount of benzyl alcohol is about 0.7 to about 9 mg / ml, optionally including an amount of EDTA of about 0.05 mg / ml. In some embodiments, the the composition a benzoic acid or a derivative thereof in the range of about 2 mg / ml to about 50 mg / ml, including, for example, any of about 1 mg / ml to about 20 mg / ml, about 2 mg / ml to about 10 mg / ml and about 5 mg / ml. In some embodiments, the composition comprises a benzyl benzoate or sodium benzoate in the range of 0.1 mg / ml to about 460 mg / ml, including, for example, 0.5 mg / ml to approx. 200 mg / ml, approx. 1 mg / ml to approx. 100 mg / ml, approx. 1 mg / ml to approx. 50 mg / ml and 1 mg / ml. In some embodiments, the composition comprises an amount of benzethonium chloride of about 0.1 mg / ml to about 1 mg / ml. In some embodiments, the weight ratio of benzoic acid or benzyl alcohol and the slightly water-soluble pharmaceutical agent in the preparation approximately 0.02:1 to about 150:1, including, for example, about 0.1:1 to about 40:1, about 0.2:1 to about 20:1, and about 0.2:1 to about 10:1. In some embodiments, the weight ratio of benzoic acid or benzyl alcohol:lite water-soluble agent in the composition less than about any of 150:1, 100:1, 50:1, 10:1, 5:1, 1:1, 0.5:1 and 0.1:1. In some embodiments, the antimicrobial agent is a chlorobutanol or derivatives thereof (such as chlorobutanol hemihydrate). Suitable amounts of chlorobutanol include for example about 2.5 mg / ml to about 50 mg / ml, about 5 mg / ml to about 20 mg / ml. In some In some embodiments, the antimicrobial agent is a phenol or a derivative thereof. Suitable amount of phenol (or a derivative thereof) includes, for example, about 0.7 mg / ml to about 25 mg / ml, about 1 mg / ml to about 20 mg / ml. In some embodiments, the antimicrobial agent a cresol (such as m-cresol) or a derivative thereof. Suitable amounts of cresol (or a derivative thereof) includes, for example, any of about 1.5 mg / ml to about 31 mg / ml and about 5 mg / ml to about 15 mg / ml. In some embodiments, the non-gelling agent is paraben which includes, but are not limited to, methyl, butyl and propyl paraben. A suitable amount of paraben (such as methylparaben) includes, for example, any of about 0.05 mg / ml to approx. 5 mg / ml, approx. 0.08 mg / ml to approx. 3 mg / ml, approx. 0.1 mg / ml to approx. 2 mg / ml, approx. 0.2 mg / ml to about 1.5 mg / ml and about 1 mg / ml. Other suitable antimicrobial agents include, but are not limited to, nitrates and nitrites (such as phenylmercuric nitrate), esters of p-hydroxybenzoic acid, propionic acid and propionates, sodium diacetates, sorbic acid and sorbates, sulfur dioxide, diethyl pyrocarbonate (DEPC), sodium hypochlorite, sodium iodide, thimerosals and the like. In some embodiments, the compositions described herein comprise at least two (including, for example, at least any one of 2, 3, 4, 5, 6, 7, 8, 9, or 10) different antimicrobial agents (such as at least two of the antimicrobial agents listed described here). These antimicrobial agents may be of the same type (different sulfite), or of different types (for example, a sulfite and a benzyl alcohol). For example, combinations of methylparaben and propylparaben (1-2 mg / ml) found to be particularly good against fungus. When multiple microbial agents are present in the preparation, the effective amount of each antimicrobial agent by the combined effects of the antimicrobial agents. If, for example, the antimicrobial agent works synergistically the effective amount of each antimicrobial agent may be much less than that required when the antimicrobial agent is present alone in a preparation. In some In some embodiments, the composition comprises both citrate and EDTA. Citrate and EDTA have been found to be particularly effective against E. coli. In some embodiments, the composition comprises 200 mM citrate and EDTA. In some embodiments, the composition comprises 200 mM citrate and any of 0.001%, 0.01%, 0.1% and 0.2% w / v EDTA. Slightly water-soluble, pharmaceutical agent The compositions described herein include poorly water-soluble, pharmaceutical agents. For example, the solubility in water for a poorly water-soluble agent may be about 20-25 °C be less than about 10 mg / ml, including for example less than about one any of 5, 2, 1, 0.5, 0.2, 0.1, 0.05, 0.02 or 0.01 mg / ml. A little water- Soluble pharmaceutical agents described herein may be, for example, anticancer and antineoplastic agents, antimicrotubule agents, immunosuppressive agents, anesthetics, hormones, agents for use in cardiovascular disorders, antiarrhythmics, antibiotics, antifungals, antihypertensives, antiasthmatics, anti-inflammatory agents, antiarthritic agents, vasoactive agents, analgesics / antipyretics, antidepressants, antidiabetics, antifungal agents, anti-inflammatories, anti-anxiety agents, immunosuppressives agents, antimigraine agents, sedatives, antianginal agents, antipsychotic agents, antimanic agents, antiarthritic agents, antigout agents, anticoagulants, thrombolytic agents, antifibrinolytic agents, hemorheological agents, antiplatelet agents, anticonvulsants, antiparkinsonian agents, antihistamines / antipruritics, agents useful for calcium regulation, antiviral agents, antimicrobial agents, anti-infectives, bronchodilators, hormones, hypoglycaemic agents, hypolipidemic agents, antiulcer / antireflux agents, antimalarials / antiemetics, and oil-soluble vitamins (e.g. vitamins A, D, E, K and similar). In some embodiments, the poorly water-soluble pharmaceutical agent is a antineoplastic agent. In some embodiments, it is a poorly water-soluble, pharma- A chemotherapeutic agent. Suitable poorly water-soluble pharmaceutical agents include, but are not limited to: limited to taxanes (such as paclitaxel, docetaxel, ortataxel and other taxanes), epothilones, camptothecins, colchicines, geldanamycins, amiodarones, thyroid hormones, amphotericin, corticosteroids, propofol, melatonin, cyclosporine, rapamycin (sirolimus) and derivatives, tacrolimus, mycophenolic acids, ifosfamide, vinorelbine, vancomycin, gemcita-bin, SU5416, thiotepa, bleomycin, diagnostic radiocontrast agents, and derivatives thereof. Others sparingly water-soluble pharmaceutical agents useful in the compositions of the invention are described for example in US 5,916,596, 6,096,331, 6,749,868 and 6,537,539. Further Examples of poorly water-soluble pharmaceutical agents include those compounds that are poorly water-soluble and which are summarized in "Therapeutic Category and Biological Activity Index" in The Merck Index (12th ed., 1996). In some embodiments, the poorly water-soluble pharmaceutical agent is a any of (and in some embodiments selected from the group consisting of) paclitaxel, docetaxel, ortataxel or another taxane or taxane analogue, 17-allyl- aminogeldanamycin (17-AAG), 18-derivatized geldanamycin, camptothecin, propofol, amiodarone, cyclosporine, epothilone, radicicol, combretastatin, rapamycin, amphotericin, liothyronine, epothilone, colchicine, thiocolchicine and its dimers, thyroid hormone, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, epothilones, radicicols, combretastatins, and analog or derivative thereof. In some embodiments, the poorly water-soluble pharmaceutical agent any of (and in some cases embodiments selected from the group consisting of) paclitaxel, docetaxel, ortataxel or other taxanes, geldanamycin, 17-allylaminogeldanamycin, thiocolcicine and its dimers, rapamycin, cyclosporine, epothilone, radicicol and combretastatin. In some embodiments, the poorly water-soluble pharmaceutical agent rapamycin. In some embodiments, it is poorly water-soluble pharmaceutical agent 17-AAG. In some embodiments, it is poorly water-soluble pharmaceutical agent a thiocolcicin dimer (such as IDN5404). In some embodiments, the poorly water-soluble pharmaceutical agent is a taxane or derivative thereof including, but not limited to, paclitaxel, docetaxel and IDN5109 (ortaxel), or a derivative thereof. In some embodiments the preparation comprises a non-crystalline and / or amorphous taxane (such as paclitaxel or a derivative thereof). In some embodiments, the composition is prepared using an anhydrous taxane (as anhydrous docetaxel or a derivative thereof). Anhydrous docetaxel has been shown to a more stable formulation than can be prepared with a hydrated docetaxel such as docetaxel trihydrate or hemihydrate. Carrier protein The compositions as described herein also include carrier proteins. The term "proteins" refers to polypeptides or polymers of amino acids with any any length (including full length or fragments), which may be straight or branched, include modified amino acids, and / or be interrupted by non-amino acids. The term also includes an amino acid polymer that is modified naturally or by intervention; for for example disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification. Also included within this term is, for example, polypeptides containing one or more analogues of a amino acid (including for example unnatural amino acids, etc.), as well as other modifications that are well known in the art. The proteins described herein may be naturally occurring, that is, obtained or derived from a natural source (such as blood), or synthesized (such as chemically synthesized or synthesized by recombinant DNA techniques). Examples of suitable carrier proteins include proteins commonly found in blood or plasma and which includes, but is not limited to, albumin, immunoglobulin including IgA, lipoproteins, apolipoprotein B, α-acid glycoprotein, β-2-macro-globulin, thyroglobulin, transferrin, fibronectin, factor VII, factor VIII, factor IX, factor X, and the like. In some embodiments, the carrier protein is a non-blood protein such as casein, α-lactalbumin and β-lactoglobulin. The carrier proteins can be either of natural origin or is synthetically produced. In some embodiments, the pharmaceutical comprises acceptable carriers albumin, such as HSA. HSA is a high-resolution globular protein with M r 65K and consists of 585 amino acids. HSA is the most abundant protein in plasma and accounts for 70-80% of the colloidal osmotic pressure in human plasma. The amino acid sequence of HSA contains a total of 17 disulfide bridges, a free thiol (Cys 34) and a single tryptophan (Trp 214). The intravenous use of HSA solution has been suggested for contraception and the treatment of hypovolemic shock (see, for example, Tullis, JAMA, 237, 355-360, 460-463, (1977)) and Houser et al., Surgery, Gynecology and Obstetrics, 150, 811-816 (1980)) and in connection with exchange transfusion in the treatment of neonatal hyperbilirubinemia (see, for example, Finlayson, Seminars in Thrombosis and Hemostasis, 6, 85-120, (1980)). Other albumins have also been contemplated such as bovine serum albumin. The use of such non-human albumins may be appropriate, for example by the use of these preparations in non-human animals such as veterinary animals (including pets and farm animals). Human serum albumin (HSA) has a number of hydrophobic binding sites (totaling eight for fatty acids, an endogenous ligand of HSA) and binds a varying set of drugs, especially neutral and negatively charged, hydrophobic compounds (Goodman et al., The Pharmacological Basis of Therapeutics, 9th ed., McGraw-Hill New York (1996)). Two high-affinity binding sites have been proposed in subdomains IIA and IIIA of HSA, which are greatly extended hydrophobic pockets with charged lysine and arginine residues near the surface which acts as an attachment point for polar ligand features (see, for example, Fehske et al., Biochem. Pharmacol., 30, 687-92 (1981), Vorum, Dan. Med. Bull., 46, 379-99 (1999), Kragh-Hansen, Dan. With. Bull., 1441, 131-40 (1990), Curry et al., Nat. Struct. Biol., 5, 827-35 (1998), Sugio et al., Protein. Eng., 12, 439-46 (1999), He et al., Nature, 358, 209-15 (1992), and Carter et al., Adv.Protein. Chem., 45, 153-203 (1994)). Paclitaxel and propofol has been shown to bind to HSA (see, for example, Paal et al., Eur. J. Biochem., 268(7), 2187-91 (2001), Purcell et al., Biochim. Biophys. Acta, 1478(1), 61-8 (2000), Altmayer et al., Arzneimittelforschung, 45, 1053-6 (1995), and Garrido et al., Rev. Esp. Anestestiol. Reanim., 41, 308-12 (1994)). In addition, docetaxel has been shown to bind to human plasma proteins (see, for example, Urien et al., Invest. New Drugs, 14(2), 147-51 (1996)). The carrier protein (such as albumin) in the preparation generally serves as a carrier for the poorly water-soluble pharmaceutical agents, that is, the carrier protein in the preparation makes the poorly water-soluble pharmaceutical agent more easily suspendable in an aqueous medium or supports the maintenance of the suspension compared to preparations that does not include a carrier protein. This can avoid the use of toxic solvents for solubilization of the poorly water-soluble pharmaceutical agent, which can thereby reduce one or more side effects of administering the poorly water-soluble, pharmaceutical agent to an individual (such as a human). Thus, in some embodiments, the preparation as described herein substantially free (as free) of Cremophor as ® Cremophor EL (BASF). In some embodiments, the composition is substantially free (as free) of surfactants. A composition is "substantially free of Cremophor" or "in essentially free of surfactant" if the amount of Cremophor or surfactant in the preparation is not sufficient to cause one or more adverse reactions in an individual when the preparation is administered to the individual. In some embodiments, the carrier protein is associated with the low water content. soluble pharmaceutical agents, that is, the preparation comprises a carrier protein- associated, poorly water-soluble, pharmaceutical agent. "Association" or "associated" used here in a general sense and refers to the carrier protein that influences a behavior and / or a property of the poorly water-soluble pharmaceutical agent in an aqueous medium preparation. For example, the carrier protein and the poorly water-soluble pharmaceutical agent as "associated" if the carrier protein makes the poorly water-soluble, pharmaceutical agent more easily suspended in an aqueous medium compared to a preparation without the carrier protein. As another example, the carrier protein and the poorly water-soluble, pharmaceutical agent associated if the carrier protein stabilizes the poorly water-soluble, pharmaceutical agent in an aqueous suspension. For example, the carrier protein and the small water-soluble pharmaceutical agents may be present in a particle or a nanoparticle which is further described here. A poorly water-soluble pharmaceutical agent is "stabilized" in an aqueous suspension if it remains suspended in an aqueous medium (as without visible precipitation or sedimentation) for an extended period of time such as at least approximately any of 0.1, 0.2, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24, 36, 48, 60 or 72 hours. The suspension is generally, but not necessarily, suitable for administration to an individual (like a human). Stability of the suspension is generally (but not necessarily) evaluated at a storage temperature (such as room temperature (such as 20-25 °C)) or below cooling conditions (such as 4 °C). For example, a suspension is stable at a storage temperature if it shows no flocculation or particle agglomeration which is visible to the naked eye or when viewed under the optical microscope at a magnification of 1,000 times, approximately 15 minutes after preparation of the suspension. Stability can also be evaluated under accelerated testing conditions such as at a temperature that is above approximately 40 °C. The carrier protein and the poorly water-soluble pharmaceutical agent in the preparation may be associated in various ways. In some embodiments, for example, the carrier protein in admixture with the poorly water-soluble pharmaceutical agent. In some embodiments, the carrier protein encapsulates or captures the poorly water-soluble, pharmaceutical agent. In some embodiments, the carrier protein is bound (e.g. non-covalently bound) to the poorly water-soluble pharmaceutical agent. In some In embodiments, the composition may exhibit one or more of the above aspects. In some embodiments, the composition comprises particles (such as nanoparticles) comprising (in various embodiments essentially consisting of) a small water-soluble, pharmaceutical agent and a carrier protein. When the poorly water-soluble, If the pharmaceutical agent is in liquid form, the particles or nanoparticles will also indicated as small droplets or nanodroplets. In some embodiments, there will be little water-soluble agent coated with the carrier protein. Particles (such as nanoparticles) of small Water-soluble pharmaceutical agents are described, for example, in US 5,916,596; 6,506,405; 6,537,579; and also in US pat. public No. 2005 / 0004002A1. In some embodiments, the composition comprises particles (such as nanoparticles) having a average or mean diameter of not more than about 1,000 nm, which is not more than approximately any of 900, 800, 700, 600, 500, 400, 300, 200 and 100 nm. In some embodiments, the average or median diameter of the particles is not greater than than about 200 nm. In some embodiments, the average or median diameter is for the particles between about 20 and about 400 nm. In some embodiments, it is average or mean diameter of the particles between about 40 and about 200 nm. In In some embodiments, the particles are sterile filterable. The particles (such as nanoparticles) as described here can be presented in a dry formulation (as a lyophilized preparation) or suspended in a biocompatible medium. Suitable biocompatible media include, but are not limited to, water, buffered aqueous medium, saline solution, buffered saline solution, possibly buffered solutions of amino acids, optionally buffered solutions of proteins, optionally buffered solutions of sugars, optionally buffered solutions of vitamins, optionally buffered solutions of synthetic polymers, lipid-containing emulsions, and the like. The amount of carrier protein in the preparation as described here will vary depending on the poorly water-soluble pharmaceutical agents and other components of the preparation. In some embodiments, the composition comprises a carrier protein in an amount sufficient to to stabilize the poorly water-soluble pharmaceutical agent in an aqueous suspension, for example in the form of a stable, colloidal suspension (such as a stable suspension of nanoparticles). In some embodiments, the carrier protein is in an amount that reduces the sedimentation rate of the poorly water-soluble pharmaceutical agent in an aqueous medium. For particulate preparations, the amount of carrier protein also depends on the size and density of the particles of the poorly water-soluble pharmaceutical agent. In some embodiments, the carrier protein is present in an amount that is sufficient to stabilize the poorly water-soluble pharmaceutical agent in an aqueous suspension at a suitable concentration. For example, the concentration of the small water-soluble pharmaceutical agents in the preparation about 0.1 mg / ml to about 100 mg / ml, including, for example, any of about 0.1 mg / ml to about 50 mg / ml, about 0.1 mg / ml to approx. 20 mg / ml, approx. 1 mg / ml to approx. 10 mg / ml, approx. 2 mg / ml to approx. 8 mg / ml, about 4 mg / ml to about 6 mg / ml, about 5 mg / ml. In some embodiments, the concentration of the poorly water-soluble pharmaceutical agent at least about any one of 1.3 mg / ml, 1.5 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml, 8 mg / ml, 9 mg / ml, 10 mg / ml, 15 mg / ml, 20 mg / ml, 25 mg / ml, 30 mg / ml, 40 mg / ml and 50 mg / ml. In some embodiments, the carrier protein is present in an amount that avoids the use of surfactants (such as Cremophor), so that the preparation is free of or in the substantially free of surfactant (such as Cremophor). In some embodiments, the composition comprises, in liquid form, from about 0.1% to about 50% w / v (for example approx. 0.5 w / v), approx. 5% w / v, approx. 10% weight / volume, approx. 15% weight / volume, approx. 20% (weight / volume), approx. 30% weight / volume, approx. 40% w / v, or about 50% w / v of carrier protein. In some embodiments For example, the composition in a liquid form comprises about 0.5% to about 5% weight / volume of carrier protein. In some embodiments, the weight ratio is carrier protein, e.g., albumin:lite water-soluble pharmaceutical agent so that a sufficient amount of poorly water-soluble pharmaceutical agent binds to, or is transported by the cell. While the weight ratio carrier protein: pharmaceutical agent will need to be optimized for different carrier protein and drug combinations are generally the weight ratio of carrier protein to albumin:pharmaceutical agent on a weight basis about 0.01: to about 100:1, about 0.02:1 to about 50:1, approx. 0.05:1 to approx. 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, approx. 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, or about 9:1. In some embodiments, the weight ratio of carrier protein:pharmaceutical agent is about any preferably of 18:1 or less, 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. In some embodiments, the carrier protein allows the composition to be administered to a individual (such as a human) without significant side effects. In some embodiments, the carrier protein (such as albumin) is present in an amount effective to reduce one or several side effects upon administration of the poorly water-soluble pharmaceutical agent to a human. The phrase "reduce one or more side effects by administering the small water-soluble pharmaceutical agent" refers to the reduction, alleviation, elimination or avoidance of one or more desired effects caused by the poorly water-soluble, pharmaceutical agents, as well as side effects caused by delivery vehicles (such as solvents that make the poorly water-soluble pharmaceuticals suitable for injection) used to deliver the poorly water-soluble pharmaceutical agent. Such side effects include, for example, myelosuppression, neurotoxicity, hypersensitivity, inflammation, venous irritation, phlebitis, pain, skin irritation, peripheral neuropathy, neutropenic fever, anaphylactic reaction, venous thrombosis, extravasation and combinations thereof. However, these side effects are only examples and others side effects, or combinations thereof, associated with various pharmaceuticals funds, can be reduced. In some embodiments, the composition comprises particles (such as nanoparticles) such as- comprising (in various embodiments consisting of, or essentially consisting of) a slightly water-soluble pharmaceutical agent and an albumin in which the weight ratio albumin:little water-soluble pharmaceutical agent is about 0.01:1 to about 100:1, about 0.02:1 to about 50:1, approx. 0.05:1 to approx. 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, approx. 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, or about 9:1. In some embodiments, the weight ratio of carrier protein:pharmaceutical agent is about any preferably of 18:1 or less, 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. In In some embodiments, the poorly water-soluble agent is a taxane or a derivative thereof. such as paclitaxel, docetaxel, ortataxel, or derivatives thereof. In some embodiments, the poorly water-soluble pharmaceutical agent is coated with albumin. In some embodiments, the particles (such as nanoparticles) comprise a small water-soluble, pharmaceutical agent and albumin suspended in an aqueous medium (as a aqueous medium containing the albumin). For example, the preparation may be a colloid suspension of the poorly water-soluble pharmaceutical agent particles (such as nanoparticles). In some embodiments, the composition is a dry (such as lyophilized) composition that can reconstituted or suspended into a stable suspension of particles as described herein. The concentration of the poorly water-soluble pharmaceutical agent in the liquid preparation or the reconstituted preparation may be diluted (0.1 mg / ml) or concentrated (100 mg / ml), including, for example, about 0.1 to about 50 mg / ml, about 0.1 to about 20 mg / ml, about 1 mg / ml to approx. 10 mg / ml, approx. 2 mg / ml to approx. 8 mg / ml, approx. 4 mg / ml to approx. 6 mg / ml, approx. 5 mg / ml. In some embodiments, the concentration of poorly water-soluble pharmaceutical means approximately any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45 or 50 mg / ml. In some embodiments, there is little water-soluble pharmaceutical agent a taxane or a derivative thereof, such as paclitaxel, docetaxel, ortataxel or derivatives thereof. In some embodiments, the composition comprises particles (such as nanoparticles) comprising paclitaxel, as particles with an average or median diameter of about 20 to about 400 nm, including, for example, about 40 to about 200 nm. In some embodiments- forms, the preparation comprises particles (such as nanoparticles) (in various embodiments consisting essentially of) paclitaxel and albumin. In some embodiments, paclitaxel coated with albumin. In some embodiments, the weight ratio is albumin:paclitaxel any of about 0.01:1 to about 100:1, about 0.02:1 to about 50:1, approx. 0.05:1 to approx. 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, about 3:1 to about 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1. In some embodiments, the albumin:paclitaxel weight ratio is less than any of 18:1 or less, 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. In some embodiments, the particles (such as nanoparticles) comprise paclitaxel. and albumin suspended in an aqueous medium (such as an aqueous medium containing the albumin). For example, the preparation may be a colloidal suspension of the paclitaxel-containing particles (such as nanoparticles). In some embodiments, the composition is a dry (as a lyophilized preparation) which can be reconstituted into an aqueous suspension of the paclitaxel-containing particles. In some embodiments, the concentration of paclitaxel in the composition between about 0.1 to about 100 mg / ml, including, for example, any of about 0.1 mg / ml to about 50 mg / ml, about 0.1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 10 mg / ml, about 2 mg / ml to about 8 mg / ml, about 4 mg / ml to about 6 mg / ml, and about 5 mg / ml. In some embodiments, the concentration of paclitaxel is at least about one of 1.3 mg / ml, 1.5 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml, 8 mg / ml, 9 mg / ml, 10 mg / ml, 15 mg / ml, 20 mg / ml, 25 mg / ml, 30 mg / ml, 40 mg / ml and 50 mg / ml. In some embodiments, the composition comprises an albumin-containing nanoparticle- formulation of paclitaxel (hereinafter referred to as Nab-paclitaxel). Nab-paclitaxel as TM TM TM Capxol (also known as Abraxane) is described in US 6,096,331. Capxol is a formulation of paclitaxel stabilized with human albumin USP and which can dispersed in a directly injectable physiological solution. When dispersed in a suitable aqueous TM medium such as 0.9% sodium chloride injection or 5% dextrose injection forms Capxol a stable colloidal suspension of paclitaxel. The size (i.e., average or average diameter) of the particles in the colloidal suspension can range from 20 nm to 8 microns with a preferred range of about 20-400 nm. Since HSA is free TM soluble in water, Capxol can be reconstituted in a wide range of concentrations from diluted (0.1 mg / ml paclitaxel) to concentrated (20 mg / ml paclitaxel), including for example about 2 mg / ml to about 8 mg / ml, about 5 mg / ml. In some embodiments, the paclitaxel concentration is about any one of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 mg / ml. Sugary preparations The present invention also provides compositions (such as pharmaceutical preparations) comprising a poorly water-soluble agent, a carrier protein (such as albumin) and a sugar. The composition may further comprise an antimicrobial agent as described herein. The preparation as described herein includes, for example, dry (such as lyophilized) preparations, liquid (such as aqueous) preparations obtained by reconstitution or resuspension of a dry preparation, or intermediate liquid (such as aqueous) preparations that can be dried (such as lyophilized). "Sugar" as used herein includes, but is not limited to, monosaccharide, disaccharide, polysaccharide and derivatives or modifications thereof. Suitable sugars for preparations as described herein include, for example, mannitol, sucrose, fructose, lactose, maltose, and trehalose. In some embodiments, sugar serves as a reconstitution enhancer that causes a lyophilized preparation to dissolve or suspended in water and / or aqueous solution more rapidly than the lyophilized preparation would dissolves without the sugar. For example, the preparation may be a dry (such as lyophilized) preparation in which the preparation can be reconstituted (or resuspended or rehydrated) into a stable aqueous suspension of the poorly water-soluble pharmaceutical agent, and wherein the time for reconstitution of the preparation in an aqueous solution is less than for the preparation without the sugar. In some embodiments, the preparation can be reconstituted (for example by mixing, tapping or vortexing) within at least about any of 8 minutes, 5 minutes or 2 minutes. In some embodiments, the sugar is present in an amount effective to increase the chemical stability of the poorly water-soluble pharmaceutical agent in the preparation. In In some embodiments, the sugar is present in an amount effective to improve the filterability of the composition. In some embodiments, the sugar is present in an amount which is effective in reducing foaming during reconstitution of the dry (as lyophilized) preparation. These improvements are compared to preparations without the sugar. In some embodiments, the concentration of sugar in a liquid suspension is (as the suspension before lyophilization or reconstituted suspension) greater than about one any of 50, 60, 70, 80, 90 or 100 mg / ml. In some embodiments, the sugar present in an amount of any of about 20 mg / ml to about 100 mg / ml, approx. 50 mg / ml to approx. 100 mg / ml, approx. 90 mg / ml. The weight ratio sugar:lite water-soluble pharmaceutical agent in the preparation may vary depending on the small water-soluble, pharmaceutical agent. Example ratio sugar:slightly water-soluble pharmaceutical agent (such as paclitaxel) includes, for example, about any of 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, or more. In certain embodiments, the composition comprises (1) particles (such as nanoparticles) comprising a poorly water-soluble pharmaceutical agent (such as taxane or derivatives thereof) and albumin; and (2) a sugar, wherein the weight ratio of albumin:pharmaceutical agent is about 0.01:1 to about 100:1, including for example about 0.02:1 to about 50:1, about 0.05:1 to about 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, approx. 3:1 to approx. 12:1, approx. 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1. In some embodiments, the weight ratio is albumin:pharmaceutical agent about 18:1 or less, including for example about any any of 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. The small Water-soluble pharmaceutical agents may be coated with albumin. In some embodiments, the invention provides a composition comprising paclitaxel, an albumin and a sugar, wherein the weight ratio of albumin:paclitaxel is about 0.01:1 to about 100:1, including for example about 0.02:1 to about 50:1, about 0.05:1 to about 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, approx. 3:1 to approx. 12:1, approx. 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1. In some embodiments, the weight ratio is albumin:paclitaxel about 18:1 or less, including, for example, any of 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. In some embodiments The composition comprises (1) particles (such as nanoparticles) comprising paclitaxel and albumin; and (2) a sugar, wherein the weight ratio of albumin:paclitaxel is about 0.01:1 to about 100:1, including, for example, any of about 0.02:1 to about 50:1, about 0.05:1 to about 20:1, approx. 0.1:1 to approx. 20:1, approx. 1:1 to approx. 18:1, approx. 2:1 to approx. 15:1, approx. 3:1 to approx. 12:1, about 4:1 to about 10:1, about 5:1 to about 9:1, and about 9:1. In some embodiments, the weight ratio of albumin:paclitaxel about 18:1 or less, including, for example, about one any of 15:1 or less, 14:1 or less, 13:1 or less, 12:1 or less, 11:1 or less, 10:1 or less, 9:1 or less, 8:1 or less, 7:1 or less, 6:1 or less, 5:1 or less, 4:1 or less and 3:1 or less. The paclitaxel may be coated with albumin. In some embodiments, the preparation is a dry (as lyophilized) preparation that can be reconstituted (or resuspended or rehydrated) to provide a generally stable aqueous suspension of the poorly water-soluble, pharmaceutical agent, and where the reconstitution time of the preparation in an aqueous solution is less than that of the composition in the absence of the sugar. In some embodiments, the concentration of sugar in the preparation or a reconstituted suspension resulting from result, greater than any of 50, 60, 70, 80, 90 or 100 mg / ml. In some In embodiments, the sugar is present at a concentration of any of about 20 mg / ml to approx. 100 mg / ml, approx. 50 mg / ml to approx. 100 mg / ml, or approx. 90 mg / ml. The sugar-containing preparations described herein may further comprise one or more antimicrobial agents such as the antimicrobial agents described herein. In addition to sugar, other reconstitution enhancers (such as those described in U.S. Publ. No. 2005 / 0152979) is added to the preparation. Other components of the preparations The compositions described herein may include other agents, excipients, or stabilizers to improve the properties of the preparation. For example, to increase stability by increasing the negative Ζ potential of nanoparticles, certain negatively charged components are added. Such negatively charged components include, but are not limited to limited to, bile salts, bile acids, glycocholic acid, cholic acid, chenodeoxycholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, lithocholic acid, urosedeoxycholic acid, dehydrocholic acid and others; phospholipids including lecithin (egg yolk) based phospholipids which include the following phosphatidylcholines: palmitoyloleoylphosphatidylcholine, palmitoyllinoleoylphosphatidylcholine, stearoyllinoleoyl- phosphatidylcholine, stearoyloleoylphosphatidylcholine, stearoylarachidoylphosphatidylcholine and dipalmitoylphosphatidylcholine. Other phospholipids include L-α-dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), and other related compounds. Negatively charged surfactants or emulsifiers are also suitable as additives, for example sodium cholesteryl sulfate and similar. In some embodiments, the composition is suitable for administration to a human. In In some embodiments, the composition is suitable for administration to a mammal, which, in a veterinary context, pets and farm animals. There is a wide spectrum of formulations of the composition of the invention (see, for example, US 5,916,596 and 6,096,331). The following formulations and methods should be considered as examples only and not in any way Formulations suitable for oral administration may include (a) liquid solutions as an effective amount of the compound dissolved in diluents, such as water, saline or orange juice, (b) capsules, sachets or tablets, each containing containing a predetermined amount of the active ingredient, as solids or granules, (c) suspensions in a suitable liquid, (d) suitable emulsions, and (e) powders. Tablet forms may include one or more of lactose, mannitol, corn starch, potato starch, microcrystalline cellulose, acacia, gelatin, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, stearic acid and other excipients, colorants, diluents, buffers, humectants, preservatives, flavorants and pharmacological compatible excipients. Lozenge forms may comprise the active ingredient in a flavoring substance, usually sucrose and acacia, or tragacanth, as well as lozenges comprising it active ingredient in an inert base such as gelatin and glycerin, or sucrose and acacia, emulsions, gels and the like, containing, in addition to the active ingredient, such excipients well known in the art. Formulations suitable for parenteral administration include aqueous and non-aqueous, isotonic, sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes that make the formulation compatible with the intended recipient's blood, and aqueous and non-aqueous, sterile suspensions which may include suspending agents, solubilizers, thickeners, stabilizers and preservatives. The formulations may be presented in unit dose or multidose sealed containers such as ampoules and vials and can be stored in a freeze-dried (lyophilized) state that only requires addition of the sterile, liquid excipient, such as water for injections, immediately before use. Extemporaneous injection solutions and suspensions may are prepared from sterile powders, granules and tablets of the type described previously. Injectable formulations are preferred. Formulations suitable for aerosol administration comprising the composition of the invention includes aqueous and non-aqueous, isotonic sterile solutions, which may contain antioxidants, buffers, bacteriostats and solutes, as well as as aqueous and non-aqueous, sterile suspensions which may include suspending agents, solubilizers, thickeners, stabilizers and preservatives, alone or in combination with other suitable components, which can be converted into aerosol- formulations for administration via inhalation. These aerosol formulations can be placed in pressurized, acceptable propellants, such as dichlorodifluoromethane, propane, nitrogen and the like. They can also be formulated as pharmaceutical agents for non-pressurized preparations, such as for for example a nebulizer or an atomizer. In some embodiments, the composition is formulated to have a pH range of about 4.5 to about 9.0, including, for example, pH ranges such as any of about 5.0 to about 8.0, about 6.5 to about 7.5 and about 6.5 to about 7.0. In some embodiments, the pH of the composition is formulated to not less than about 6, including for example not less than about any any of 6.5, 7 or 8 (as approx. 8). The preparation can also be made isotonic with the blood by adding a suitable tonicity modifier such as glycerol. Furthermore, articles of manufacture are provided comprising the preparations which described here in a suitable packaging. Suitable packaging for preparations as described here are well known in the art and include, for example, vials (such as sealed vials), containers, ampoules, flasks, bottles, flexible packages (for example, sealed Mylar or plastic bags), and the like. These production items can be further sterilized and / or Further provided are unit dosage forms comprising the compositions as described herein. These unit dosage forms may be stored in a suitable package in single or multiple unit doses and can also be further sterilized and sealed. The present invention also provides compositions comprising (or unit dosage forms) and / or articles of manufacture) as described herein and may further include instructions regarding methods of using the preparation, which they applications as further described herein. In some embodiments, the kit according to the invention comprises the invention a gasket as described above. In other embodiments, the kit comprises according to the invention packaging as described above and a second packaging comprising a buffer. In some embodiments, the invention provides a kit comprising (1) a composition comprising a poorly water-soluble pharmaceutical agent and a carrier protein; and (2) an antimicrobial agent, in which the poorly water-soluble pharmaceutical agent / protein preparation and the antimicrobial agent are present in separate packages, and there significant microbial growth in the preparation is inhibited by the addition of the antimicrobial agent to the poorly water-soluble pharmaceutical agent / protein preparation. In some In embodiments, the kit further comprises instructions for adding the antimicrobial agent to the pharmaceutical agent / protein preparation. The kit described herein can further include other materials that are desirable from a commercial or user point of view, including other buffers, diluents, filters, needles, syringes and packing inserts with instructions for performing all the methods described here. Kits can also be provided that contain sufficient doses of the small water-soluble pharmaceutical agents (such as paclitaxel) as described herein to provide effective treatment for an individual over an extended period of time, such as any one week, 2 weeks, 3, weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months or more. Sets can also include multiple unit doses of the poorly water-soluble pharmaceutical agent and pharmaceutical preparations and instructions for use and packaged in quantities sufficient for storage and use in pharmacies, such as hospital pharmacies and compounding pharmacies. Methods of preparation and use of the preparations Further provided are methods for making and using the compositions as described herein. For example, a method for preparing a composition is provided comprising a poorly water-soluble pharmaceutical agent (such as a taxane such as paclitaxel, docetaxel or ortataxel), a carrier protein (such as albumin), and an antimicrobial agent, where significant microbial growth is inhibited in the preparation, including combination (such as mixture) of a preparation containing a poorly water-soluble pharmaceutical agent and a carrier protein, with an antimicrobial agent. Methods for preparing preparations containing the carrier proteins and little water-soluble pharmaceutical agents are well known in the art. For example, nanoparticles containing poorly water-soluble pharmaceutical agents (such as paclitaxel) and carrier protein (such as albumin) is prepared under high shear conditions (for (e.g. sonication, high-pressure homogenization, or similar). These methods are described for example in US 5,916,596; 6,506,405; and 6,537,579 and also in US Publ. No. 2005 / 0004002A1. In short, the poorly water-soluble drug (such as docetaxel) is dissolved in a organic solvent and the solution can be added to a human serum albumin solution. The mixture is subjected to high-pressure homogenization. The organic The solvent can then be removed by evaporation. The resulting dispersion can be lyophilized. Suitable organic solvents are, for example, ketones, esters, ethers, chlorinated solvents and other solvents known per se. For example, the organic solvent be methylene chloride and chloroform:ethanol (for example, with a ratio of 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 or 9:1). The antimicrobial agent can either be mixed with the poorly water-soluble, pharmaceutical agent and / or the carrier protein, during the preparation of the preparation of the small water-soluble pharmaceutical agent / carrier protein, or added after the preparation of poorly water-soluble pharmaceutical agent / carrier protein is prepared. For example, it can antimicrobial agents are added together with an aqueous medium used to reconstitute / suspend the preparation of the poorly water-soluble pharmaceutical agent / carrier protein or added to an aqueous suspension of the carrier protein-associated, poorly water-soluble pharmaceutical agents. In some embodiments, the antimicrobial agent mixed with the preparation of a poorly water-soluble pharmaceutical agent and carrier protein before lyophilization. In some embodiments, the antimicrobial agent is added to the lyophilized pharmaceutical agent / carrier protein preparation. In some embodiments and when addition of the antimicrobial agent changes the pH value of the preparation, the pH value of the preparation is generally (but not necessarily) adjusted to a desired pH value. Examples of pH values ​​for the preparations include, for example range of about 5 to about 8.5. In some embodiments, the pH of the composition is adjusted to not less than about 6, including for example not less than any one of about 6.5, 7 or 8 (like about 8). Furthermore, methods for preparing pharmaceutical compositions are provided. comprehensive combination of any of the compositions described herein (including those above) with a pharmaceutically acceptable excipient. Methods of using the compositions of the invention are further provided. In In some embodiments, a method for treating a disease or condition is provided. condition that responds to a poorly water-soluble pharmaceutical agent, including administration of a composition comprising an effective amount of a poorly water-soluble, pharmaceutical agent, a carrier protein and an antimicrobial agent, where significant microbial growth is inhibited in the composition. In some embodiments, it is provided for example, a method for treating cancer in an individual (such as a human) comprising administering to the individual a composition comprising an effective amount of a poorly water-soluble antineoplastic agent (such as a taxane), a carrier protein, and a antimicrobial agent, where significant microbial growth is inhibited in the preparation. In some embodiments, the antimicrobial agent is in an amount sufficient to inhibit significant microbial growth in the composition. In some embodiments, it is antimicrobial agent present in the preparation in an amount such that it does not cause any toxicological effects when the preparation is administered to an individual (such as a human). The term "effective amount" as used herein refers to an amount of a compound or preparation sufficient to treat a specified disorder, condition or disease as improvement, alleviation, reduction and / or delay of one or more of its symptoms. Referring to cancer or other unwanted cell proliferation an effective amount includes an amount sufficient to cause a tumor to shrink and / or to reduce the rate of growth of the tumor (such as suppressing tumor growth). In In some embodiments, an effective amount is an amount sufficient to delay development. In some embodiments, an effective amount is an amount sufficient to prevent the appearance and / or recurrence. An effective amount can be administered by one or more administrations. Cancers to be treated with preparations as described here (for example, a preparation comprising an antineoplastic agent such as a taxane, rapamycin and 17-AAG) includes, but is not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. Examples of cancers that can be treated with the preparations described here includes, but is not limited to, squamous cell carcinoma, lung cancer (including small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous cell carcinoma of the lung), cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer (including gastrointestinal cancer), pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, melanoma, endometrial or uterine carcinoma, salivary gland carcinoma, renal or renal cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, head and neck cancer, colorectal cancer, rectal cancer, soft tissue sarcoma, Kaposi's sarcoma, B-cell lymphoma (including low-grade / follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-cleaved cell NHL, bulk disease NHL, mantle cell lymphoma, AIDS-related lymphoma, and Waldenstrom's macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), myeloma, hairy cell leukemia, chronic myelo-blastic leukemia and post- transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors) and Meigs syndrome. In some embodiments, a method is provided for the treatment of metastatic cancer (i.e. cancer that has metastasized from primary tumor). In some embodiments, a method is provided for reducing cell proliferation and / or cell migration. In some embodiments, a method of treating hyperplasia. In some embodiments, methods are provided for treating cancer by advanced steps. In some embodiments, methods are provided for processing breast cancer (which may be HER2 positive or HER2 negative), including for example advanced breast cancer, stage IV breast cancer, locally advanced breast cancer and metastatic breast cancer. In some embodiments, the cancer is lung cancer, including for example non-small cell lung cancer (NSCLC, such as advanced NSCLC), small cell lung cancer (SCLC, such as advanced SCLC), and advanced solid tumor malignancy of the lung. In some embodiments is the cancer ovarian cancer, head and neck cancer, gastric malignancies, melanoma (including metastatic melanoma), colorectal cancer, pancreatic cancer and solid tumors (such as advanced solid tumors). In some embodiments, the cancer is any of (and in some embodiments selected from the group consisting of) breast cancer, colorectal cancer, rectal cancer, non-small cell lung cancer, non-Hodgkin's lymphoma (NHL), renal cell cancer, prostate cancer, liver cancer, pancreatic cancer, soft tissue sarcoma, Kaposi's sarcoma, carcinoid carcinoma, head and neck cancer, melanoma, ovarian cancer, mesothelioma, glioma, glioblastoma, neuroblastoma and multiple myeloma. In some In embodiments, the cancer is a solid tumor. Individuals who are suitable for receiving these preparations depend on the nature of the little one water-soluble pharmaceutical agent, as well as the disease / condition / disorder that to be treated or prevented. Accordingly, the term individuals includes any vertebrate, mammal and human. In some embodiments, the individual is a mammal, including but not limited to, human, bovine, equine, feline, rabbit, rodent or primate. In some embodiments, the individual is a human. The preparations described here can be administered alone or in combination with other pharmaceutical agents including poorly water-soluble pharmaceutical agents. When for example the preparation contains a taxane (such as paclitaxel) it can be co-administered with one or more other chemotherapeutic agents including, but not limited to, ® carboplatin, navelbine (vinorelbine), anthracycline (Doxil), lapatinib (GW57016), herceptin, ® ® gemcitabine (Gemzar), capecitabine (Xeloda), alimta, cisplatin, 5-fluorouracil, epirubicin, ® cyclophosphamide, avastatin, velcade, etc. In some embodiments, the taxane preparation is co- administered with a chemotherapeutic agent selected from the group consisting of antimetabolites (including nucleoside analogues), platinum-based agents, alkylating agents, tyrosine kinase inhibitors, anthracycline antibiotics, vinca alkaloids, proteasome inhibitors, macrolides and topoisomerase inhibitors. These other pharmaceutical agents may be present in the same preparation as the drug (such as a taxane), or in a separate preparation which are administered simultaneously or sequentially with the drug (such as a taxane)-containing preparation. Combination therapy methods using nanoparticle formulations of taxane with other means (or therapeutic methods) are described in PCT / US2006 / 006167. The dose of the composition of the invention administered to an individual (as a human) will vary with the particular preparation, mode of administration and the particular disease being treated. The dose must be sufficient to produce a desired response such as a therapeutic or prophylactic response against a particular disease. For example, the dose may 2 of paclitaxel in the preparation is in the range of 100-400 mg / m, given over a 3-week schedule, or 2 50-250 mg / m given on a weekly schedule. In addition, and if given in a metronomic regimen (for example, daily, or a few times per week) the dose may be in the range of about 5- 2 75 mg / m. The compositions described herein can be administered to an individual (as a human) by various routes including, for example, intravenously, intraarterially, intrapulmonary, oral, inhalation, intravesicular, intramuscular, intratracheal, subcutaneous, intraocular, intrathecal, transmucosal and transdermal. For example, can The composition of the invention is administered by inhalation to treat respiratory conditions. The preparation can be used to treat respiratory conditions such as pulmonary fibrosis, bronchiolitis obliterans, lung cancer, bronchoalveolar carcinoma and the like. Furthermore, methods are provided for reducing the side effects associated with administration of a small, water-soluble pharmaceutical agent to a human, comprising administration to a human of a pharmaceutical composition comprising the poorly water-soluble pharmaceutical agents, a carrier protein and an antimicrobial agent, where significant microbial growth is inhibited in the preparation. For example, providing the present invention methods for reducing various side effects associated with the administration of the poorly water-soluble pharmaceutical agent including, but not limited to limited to, myelosuppression, neurotoxicity, hypersensitivity, inflammation, venous irritation, phlebitis, pain, skin irritation, peripheral neuropathy, neutropenic fever, anaphylactic reaction, hematological toxicity, and cerebral or neurological toxicity, and combinations thereof. In some embodiments, a method is provided for reduce hypersensitivity reactions associated with the administration of the small water-soluble pharmaceutical agents, including, for example, severe skin rashes, hives, flushing, dyspnea, tachycardia, and others. In some embodiments, there is antimicrobial agent present in an amount effective to inhibit the significant microbial growth in the pharmaceutical composition. In some embodiments, it is antimicrobial agent in the preparation is further present in an amount that does not cause any toxicological effects or at a level where a potential adverse effect can be controlled or tolerated when the preparation is administered to an individual. Additionally, a method for increasing the shelf life of a liquid is provided. composition comprising a poorly water-soluble pharmaceutical agent and a carrier protein. For For example, in certain embodiments, the invention provides a method for to hold a preparation (such as a pharmaceutical composition) comprising a small water-soluble, pharmaceutical agent and a carrier protein, preserved against microbial growth (the i.e. sterile, or essentially free from significant microbial growth) for at least 24 hours in a aqueous medium, comprising adding to the preparation an antimicrobial agent in a amount effective to inhibit significant microbial growth in the preparation. In some embodiments provide methods for inhibiting microbial growth in a composition (especially a pharmaceutical preparation) comprising a carrier protein and a slightly water-soluble, pharmaceutical agent, comprising adding to the preparation an antimicrobial agent in a amount effective to significantly inhibit microbial growth in the composition. The antimicrobial agent can either be mixed with the poorly water-soluble, pharmaceutical agent and / or the carrier protein during the preparation of the small water-soluble pharmaceutical agent / carrier protein preparation, or added with a aqueous medium used to reconstitute the pharmaceutical agent / carrier protein preparation. In some embodiments, methods are provided for maintaining a preparation preserved against microbial growth (i.e. sterile or essentially free from significant microbial growth) for at least any of 24, 36, 48, 60, 72, 84 or 96 hours. In a further aspect of the invention, the use of the compositions as described herein in the manufacture of a medicament. In particular, it is described the manufacture of a medicament for use in the therapy of conditions as described herein. Furthermore, the pharmaceutical composition thereof, described in various ways herein, is also intended for use in the manufacture of a medicament for use in the therapy of conditions and, in according to methods, as described here, unless otherwise stated. The following examples are intended to illustrate the invention without limiting it. EXAMPLE 1 This example provides formulations of paclitaxel: albumin and preservatives. The compositions are prepared essentially as described in US 5,439,686 and 5 916 596. In short, paclitaxel is dissolved in an organic solvent (such as methylene chloride or a chloroform:ethanol mixture) after which the solution is added to a human serum albumin solution. A suitable amount of an antimicrobial agent is then added to the mixture. The mixture is homogenized for 5 minutes at low speed to give a raw emulsion and then transferred to a high-pressure homogenizer. The emulsification is carried out at 9,000-40,000 psi while recirculating the emulsion for at least 5 cycles. It The resulting system is transferred to a rotary evaporator and the organic solvent is agent is removed rapidly at 40 °C, at reduced pressure (30 mm Hg) for 20-30 minutes. The dispersion is then further lyophilized for 48 hours. The resulting cake can be easily reconstituted to the original dispersion by adding sterile water or saline solution which may contain one or more additional antimicrobial agents. Examples of formulations of preparations that can be prepared are provided. below (only the concentrations of paclitaxel, human albumin and the antimicrobial the remedy is indicated): Formulation 1: 5 mg / ml paclitaxel; 56 mg / ml human albumin; 0.25 ml sodium metabisulfite Formulation 2: 5 mg / ml paclitaxel; 56 mg / ml human albumin; 0.05 mg / ml di- sodium edetate Formulation 3: 5 mg / ml paclitaxel; 56 mg / ml human albumin; 0.5 mg / ml potassium sorbate Formulation 4: 5 mg / ml paclitaxel; 56 mg / ml human albumin; 1 mg / ml sodium benzoate Formulation 5: 7 mg / ml paclitaxel; 56 mg / ml human albumin; 1 mg / ml sodium ascorbate Formulation 6: 7 mg / ml paclitaxel; 56 mg / ml human albumin; 1 mg / ml methylparaben Formulation 7: 7 mg / ml paclitaxel; 56 mg / ml human albumin; 1 mg / ml benzyl alcohol. EXAMPLE 2 This example shows how to determine the effectiveness of the antimicrobial agents in a composition as described in Example 1. The growth inhibition properties of the antimicrobial agents in the formulations that described in Example 1 is evaluated using membrane filtration techniques and broth cultures. Around 50-200 colony forming units (CFU) per ml of four standard organisms, recommended by the United States Pharmacopeia (USP) for preservation efficacy tests, are inoculated into each formulation. These four organisms have been identified as: Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), and Candida albicans (ATCC 10231). In addition to these organisms may also include S. epidermidis (ATCC 12228) and S. aureus (coagulase negative, ATCC 27734) are also tested. After inoculation of the test organisms, test formulations are incubated at 30- 35 °C. Counts of the test organism at selected time points (such as immediately after inoculation and after 24 hours of incubation at 30-35 °C) is determined. The antimicrobial agent in the formulation is considered effective if the anti- antimicrobial agent is capable of retarding the growth of microorganisms in the preparation of no more than 1 log increase (factor 10) within 24 hours of extrinsic contamination. EXAMPLE 3 This example shows improved reconstitution time in sugar-containing formulations of paclitaxel and albumin. The compositions were prepared essentially as described in US 5 439,686 and 5,916,596, in the presence or absence of sugar. In short, paclitaxel was dissolved in a chloroform:ethanol (1:1) mixture and the solution was added to a human serum albumin solution. The mixture was homogenized for 5 minutes at low rpm to give a crude emulsion and then transferred to a high-pressure homogenizer. The emulsification was carried out at 9,000-40,000 psi while recycling the emulsion in at least 5 cycles. The resulting system was transferred to a rotary evaporator and chloroform:ethanol was rapidly removed at 40 °C under a reduced pressure of 30 mm Hg for 20 30 minutes. The dispersion was then further lyophilized for 48 hours. The resulting cake was easily reconstituted to the original dispersion by addition of sterile water or saline solution which may contain one or more additional antimicrobial agents. Sugar was added either to the human serum albumin solution or added to the dispersion before lyophilization. Antimicrobial agents were not added in this particular experiment, but may be added. The following formulations were prepared: Formulation 1: The suspension before lyophilization contained 5 mg / ml paclitaxel; 56 mg / ml human albumin; 10 mg / ml mannitol. The suspension was filled into vials with 250 mg paclitaxel per vial. Formulation 2: The suspension before lyophilization contained 5 mg / ml paclitaxel; 56 mg / ml human albumin; 10 mg / ml sucrose. The suspension was filled into vials with 250 mg paclitaxel per vial. Formulation 3: The suspension before lyophilization contained 7 mg / ml paclitaxel; 56 mg / ml human albumin; 90 mg / ml sucrose. The suspension was filled into vials with 300 mg paclitaxel per vial. Formulation 4: The suspension before lyophilization contained 7 mg / ml paclitaxel; 56 mg / ml human albumin; 50 mg / ml mannitol. The suspension was filled into vials with 300 mg paclitaxel per vial. Formulation 5: The suspension before lyophilization contained 7 mg / ml paclitaxel; 56 mg / ml human albumin. The suspension was filled into vials with 300 mg paclitaxel per vial. Lyophilized products from formulations 3 and 4 were reconstituted during less than 2 minutes. The reconstitution times for lyophilized products of formulations 1, 2 and 5 were similar and between about 8-12 minutes. It was surprisingly found that 10 mg / ml sugar was not sufficient to significantly reduce reconstitution time for nab-paclitaxel. Around 50-90 mg / ml of sugar was required to reduce reconstitution time. EXAMPLE 4 This example shows further advantageous properties of sugary paclitaxel:albumin formulations. In an experiment, a preparation of paclitaxel and albumin (nab-paclitaxel) was prepared with and without the presence of sugars as described above. Lyophilized vials of albumin- Paclitaxel was prepared containing 300 mg per vial for both formulations. The The sugar-based formulation contained sucrose at a concentration of 90 mg / ml. The lyophilized products were subjected to accelerated stability conditions at 55 °C for up to 30 days. Percent impure 7-epitaxol was determined in each case and at time zero was approximately 0.1 %. After 15 days and 30 days at 55 °C, the impurity level for the sugar-free formulation was found to be 0.6%, 0.8% respectively and the level of impurity for the sugar-based formulation was found to be 0.4%, 0.6% respectively. Based on the surprisingly lower impurity generation in the sugar-based formulation should extend the shelf life be significantly longer than for the sugar-free formulation. In a further experiment, approximately 1,500 ml of the liquid suspension of each formulation containing approximately 7 mg / ml paclitaxel, 56 mg / ml human albumin and 90 mg / ml sucrose subjected to filtration through a series of filters with a 0.2 µm final filter 2 (200 cm EKV capsule). The filterability of each formulation was assessed based on the volume of nanoparticle suspension that could be filtered through the filter. For the sugar-free formulation, the maximum volume that could be filtered was 1,300 ml on which point filtration pressure increased to over 25 psi, indicating clogging or saturation of the filter membrane. For the sugar-based formulation, filterability was significantly increased noted without any pressure increase for 1,500 filtered ml. This surprisingly shows that the sugar-based nab-paclitaxel formulation is more easily filtered with minimal loss of potency compared to the sugar-free formulation. EXAMPLE 5 This example shows that the nab formulations can serve as growth media for microorganisms in terms of beneficial contamination. The formulations contained 5 mg / ml docetaxel, paclitaxel, 17-AAG respectively. Four strains of microorganisms were used in the experiment: E. coli (ATCC lot no. 97- 08 / lot no. 483284); S. aureus (ATCC lot no. 1836394 / lot no. 485823); C. albicans (ATCC lot no. 98-01A / lot no. 443131); P. aeruginosa (ATCC lot no. 378667 / lot no. 484882). 100-600 µl (around 100-200 CFU / ml) of each strain was inoculated into 2 ml test kit sample tubes (see Table 1, each sample was duplicated) and 2 ml TSB as control. Tryptic soy agar (TSA) plates were inoculated with 10% of the samples (20 drops of a 10 µl sterile disposable loop), duplicated for each sample. TSA plates were incubated aerobically at 25 °C ± 1 °C in the temperature-controlled incubator. The colony counts for test The organism and CFU / ml were determined at 0 hours, 24 hours and 48 hours after microbial inoculation. The formulation is indicated as "yes" (i.e. the formulation passed the test) if the formulation does not show more than a 10-fold increase in microbial growth over a 24-hour period period, or a 48 hour period. Table 1. Microbial growth 48 hours after inoculation Formulation E. coli P. aeruginosa S. aureus C. albicans Nab-docetaxel w / citrate NJJJ (200 mM citrate, 300 mM NaCl) Nab-docetaxel without citrate NNNN Abraxane NNNN Nab-17-AAG NNJN Rating = yes (Y) or no (N). Nab-paclitaxel (nanoparticle albumin formulation of paclitaxel) without antimicrobials agents (Abraxane), nab-docetaxel (nanoparticle albumin formulation of docetaxel) without antimicrobial agents and nab-17AAG (nanoparticle albumin formulation of 17-AAG) without antimicrobial agent all showed a significant bacterial growth (factor >10) over a period of time in either 24 or 48 hours for at least 3 of the 4 bacterial strains tested, see Table 1. This confirms that the contamination of a nab formulation without any growth inhibitor can result in a >10-fold increase in microorganism growth within 24 or 48 hours. Nab-docetaxel with 200 mM citrate, on the other hand, showed microbial suppression at 24 and 48 hours respectively, except in the case of E. coli. This was remedied by addition of EDTA. EDTA supplementation of nab-docetaxel with citrate at any Preferably, the concentrations 0.001%, 0.01%, 0.1% and 0.2% w / v suppressed E. coli growth completely. Although the invention has been described above in some detail by way of illustration and for example purposes for clarity and understanding it should be clear to the skilled person that less changes and modifications may be made. Therefore, the description and examples should not be construed as a limiting framework for the invention.

Claims

1. A composition comprising (a) nanoparticles comprising a low water-soluble, pharmaceutical agent and albumin, (b) an edetate, and (c) a sugar, where significant Microbial growth is inhibited in the preparation.

2. The composition of claim 1, wherein the poorly water-soluble pharmaceutical agent is coated. with albumin.

3. A composition according to claim 1 or 2, wherein the albumin is human serum albumin.

4. A composition according to any one of claims 1 to 3, wherein the weight ratio of the albumin to the poorly water-soluble pharmaceutical agent in the preparation is 18:1 or less.

5. A composition according to any one of claims 1 to 4, wherein the nanoparticles in the composition have an average diameter not greater than 200 nm.

6. A composition according to claim 5, wherein the composition is sterile filterable.

7. A composition according to any one of claims 1 to 6, wherein the composition is an aqueous suspension of the poorly water-soluble pharmaceutical agent at a concentration of 0.1 mg / ml to 20 mg / ml.

8. A composition according to any one of claims 1 to 7, wherein the composition is a lyophilized preparation that can be reconstituted into an aqueous suspension of the sparingly water-soluble, the pharmaceutical agent at a concentration of 0.1 mg / ml to 20 mg / ml.

9. A composition according to any one of claims 1 to 8, wherein the composition is suitable for parenteral administration.

10. A composition according to any one of claims 1 to 9, wherein the edetate is EDTA.

11. A composition according to any one of claims 1 to 10, wherein the poorly water-soluble, the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, ortataxel or other taxane, geldanamycin, 17-allylaminogeldanamycin, thiocolcicine dimer, rapamycin, cyclosporine, epothilone, radicicol and combretastatin.

12. The composition of claim 11, wherein the poorly water-soluble pharmaceutical agent is a taxane.

13. A composition according to claim 12, wherein the poorly water-soluble pharmaceutical agent is paclitaxel.

14. A composition according to any one of claims 1 to 13, wherein the sugar is sucrose, mannitol, fructose, lactose, maltose, or trehalose.

15. A composition according to any one of claims 1 to 13, wherein the pH of the composition is no less than 6.5, 7, or 8.

16. A composition according to any one of claims 1 to 15, wherein the antimicrobial agent is effective in an amount to result in no more than a 10-fold increase in microbial growth 3 over a 24-hour period after exposure to 10 to 10 colony-forming units at a temperature in the range of 20 °C to 25 °C.

17. A composition according to any one of claims 1 to 16 for use in a method for the treatment of cancer in an individual, where the poorly water-soluble pharmaceutical the agent is an antineoplastic agent.

18. A sealed vial comprising a composition according to any one of claims 1 to 17.

19. A method of preserving a composition comprising (a) a small amount of water soluble, pharmaceutical agent and albumin, and (b) a sugar against significant microbial growth comprising adding to the preparation an edetate in an amount effective to inhibit significant microbial load in the preparation.

20. The method of claim 19, wherein the sugar is sucrose, mannitol, fructose, lactose, maltose, or trehalose.