Method for increasing the efficacy and solubility of taxanes
By adding solubilizers like PEG and Tween to taxanes, the method enhances their water solubility and efficacy, addressing the low solubility issue of taxanes and improving cancer treatment efficacy.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- INFLAMED PHARM GMBH
- Filing Date
- 2025-11-25
- Publication Date
- 2026-05-28
AI Technical Summary
Taxanes, such as paclitaxel, have low water solubility, which hinders their rapid and effective distribution throughout the body via the bloodstream.
A method involving the addition of solubilizers like polyethylene glycol (PEG) and Tween to taxanes, optionally with a water-miscible organic solvent, to enhance their water solubility, followed by drying to form a stable formulation.
The method significantly increases the water solubility of taxanes, maintaining or improving their efficacy against cancer and enhancing membrane penetration, while avoiding the drawbacks of existing formulations.
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Abstract
Description
Methods for increasing the efficacy and solubility of taxanes TECHNICAL AREA
[0001] The invention relates to a method for providing water-soluble taxane formulations. TECHNICAL BACKGROUND
[0002] Taxanes and paclitaxel (Taxol) have relatively low water solubility. However, sufficient water solubility is necessary, at least temporarily, to enable rapid and effective distribution throughout the patient's body via the bloodstream. Therefore, it is of interest to develop methods that increase the water solubility of taxanes, especially paclitaxel (Taxol) and paclitaxel derivatives. SUMMARY OF THE INVENTION
[0003] The invention relates to a method for providing water-soluble formulations of the taxanes comprising the steps I) a) Addition of at least one solubilizer (LV1) to the taxane while maintaining composition (A); optionally b) Addition of at least one further solubilizer (LV2) to composition (A) while maintaining composition (B); or II) Addition of the taxane to a mixture of at least one solubilizer (LV1) and at least one solubilizer (LV2) to obtain composition (A); wherein the taxane is optionally dissolved in a water-miscible organic solvent (OL1); optionally the solubilizer (LV1) or (LV2) may be dissolved in water.
[0004] Furthermore, the invention comprises a tax formulation, producible according to the inventive method, comprising, preferably consisting of: i) a taxane, preferably paclitaxel; and ii) polyethylene glycol, preferably polyethylene glycol (PEG), selected from , where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400.
[0005] The process according to the invention enables the conversion of medically relevant taxanes, particularly paclitaxel and paclitaxel derivatives, into significantly more water-soluble taxane formulations, as demonstrated in the examples. Furthermore, the taxane formulations according to the invention exhibit the same or improved efficacy against cancer as paclitaxel in vitro and increased octanol solubility as a model for membrane penetration. BRIEF DESCRIPTION OF THE FIGURES
[0006] Figure 1: Two cancer cell lines (A549 = lung cancer cell line; MCF7 = breast cancer cell line) were exposed to paclitaxel and to the TaxoCluster solid according to the invention, and the concentration at which cell death or impairment of metabolic activity occurred was determined. TaxoCluster solid corresponds to embodiment 1c in Table 2.
[0007] Figure 2: Two cancer cell lines (A549 = lung cancer cell line; MCF7 = breast cancer cell line) were exposed to paclitaxel and to TaxoCluster liquid I according to the invention, and the concentration at which cell death or impairment of metabolic activity occurs was determined. TaxoCluster liquid I corresponds to embodiment 1e in Table 2.
[0008] Figure 3: Two cancer cell lines (A549 = lung cancer cell line; MCF7 = breast cancer cell line) were exposed to paclitaxel and to the TaxoCluster liquid II according to the invention, and the concentration at which cell death or impairment of metabolic activity occurs was determined. TaxoCluster liquid II corresponds to embodiment 1d in Table 2.
[0009] Figure 4: Solubility in octanol was tested as a model for the membrane permeability of the Taxol formulations. A: Test of TaxoCluster liquid I and paclitaxel after 0.2 and 24 h; B: Test of solubility in octanol after 2 h of TaxoCluster liquid II, TaxoCluster solid, and paclitaxel; C: Test of solubility in octanol after 24 h of TaxoCluster liquid II, TaxoCluster solid, and paclitaxel.
[0010] Figure 5: Solubility of TaxoCluster liquid II, TaxoCluster solid, and paclitaxel in water.
[0011] Figure 6: A: Solubility of TaxoCluster solid over time in octanol. B: Solubility of Taxol over time in octanol. C: Solubility of TaxoCluster liquid II over time in octanol.
[0012] Figure 7: Solubility of TaxoCluster solid determined using crystal16 (The Crystal16 (Technobis HQ) is a system for characterizing solubility, dispersion stability and critical solution temperatures).
[0013] Figure 8: IR spectrum of the precipitate from the reaction mixture according to comparison example 1 from W02009 / 006799 A1.
[0014] Figure 9: IR spectrum paclitaxel (IR spectrum).
[0015] Figure 10: UV / VIS spectrum of the filtrate from comparison example 3.
[0016] Figure 11: UV / VIS spectrum of embodiment 1e. DETAILED DESCRIPTION OF THE INVENTION
[0017] The invention relates to a method for providing a water-soluble taxane formulation comprising the steps: I) a) Addition of at least one solubilizer (LV1) to the taxane while maintaining composition (A); optionally b) Addition of at least one further solubilizer (LV2) to composition (A) while maintaining composition (B); or II) a) Addition of the taxane to at least one solubilizer (LV1) while maintaining composition (A) and optionally to at least one further solubilizer (LV2) while maintaining composition (B); wherein in I) or II) the taxane is optionally dissolved in a water-miscible organic solvent (OL1); optionally the solubilizer (LV1) or (LV2) may be dissolved in water.
[0018] The taxane is preferably a taxole derivative according to formula (I): R 1is selected from the group consisting of H, -COPhenyl, -CO(Ci-C6)alkyl; R 2 to R 7 are independently selected from the group consisting of H, -CO(Ci-Ce)alkyl, -(Ci-C6)alkyl.
[0019] The term "alkyl" refers to a monoradical of a saturated straight or branched hydrocarbon. Preferably, the alkyl group comprises 1 to 6 carbon atoms, i.e., 1, 2, 3, 4, 5, 6, more preferably 1 to 4 carbon atoms. Exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,2-dimethylpropyl, isoamyl, n-hexyl, isohexyl, sec-hexyl, n- and the like.
[0020] Preferably, the taxol derivatives are selected from the group consisting of taxol (paclitaxel), docetaxel, and cabazitaxel, preferably taxol.
[0021] Step a) and / or b) can be carried out at a temperature of 40 to 90 °C.
[0022] In the context of this invention, "water-soluble" means that at least 34 to 100 g / l of the solid substance dissolves in water or that 1 ml of the liquid formulation dissolves in at least 1 ml of water.
[0023] The taxane formulation is preferably in the form of composition (A), (B), solution (A) or composition (D), more preferably in the form of composition (D).
[0024] Preferably, the taxane, taxol derivative, or taxol has a solubility in water of at most 10 to 33 g / l at 15 to 25 °C. More preferably, taxol and its derivatives have a solubility of 0.1 mg / l to 30 mg / l in water.
[0025] Table 1: The European Pharmacopoeia defines the following solubility categories at 15 °C to 25 °C in Water:
[0026] Preferably, the organic solvent (OL1) forms a common phase with the water after mixing;
[0027] Preferably the organic solvent (OL1) is selected from the group consisting of acetone, (Ci-Cs)alkyl-OH, DMSO, DMF, more preferably acetone, DMSO, DMF.
[0028] Preferably, the taxane formulation does not contain ethanol.
[0029] Preferably, one or more than one solubilizer (LV1) and / or (LV2) is selected from the group consisting of polyvinylpyrrolidone (PVP), Tween, polyethylene glycol (PEG).
[0030] Polyethylene glycol (PEG), selected from, is more preferred. where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400.
[0031] Preferably the polyethylene glycol (PEG) is selected from where n is an even number between 1000 and 35,000, preferably between 1000 and 3000.
[0032] “Tweens” are ethoxylated sorbitan fatty acid esters. Preferably, a tween comprises one or more compounds according to formula (I). Preferably, the sum of w+x+y+z is an even number between 15 and 30, more preferably 17 to 25, and particularly preferably 20. Preferably, the sum of w+x+y+z is an even number between 15 and 30, more preferably 17 to 25, most preferably 20. R is selected from -COCH2(CH2)nCH3, -COCH2(CH2)oCH2CH=CHCH2(CH2)pCH3. n is an even number between 5 and 20, preferably between 8 and 16, more preferably 9, 13, 15. o is an even number between 0 and 8, preferably 4 and 7, more preferably 5. p is an even number between 0 and 9, preferably 5 to 8, more preferably 6.
[0033] Preferably, the polyvinylpyrrolidone (PVP) is defined according to the following formula: The polyvinylpyrrolidone (PVP) preferably has an average Molecular weight from 10,000 to 40,000 g / mol, more preferably from 15,000 to 35,000 g / mol, even more preferably from 24,000 to 33,000 g / mol, particularly preferably from 17,000 g / mol to 32,000 g / mol. Where n is 90 to 360, preferably 135 to 315, more preferably 216 to 297, particularly preferably 153 to 288.
[0034] The process may optionally include a further step c) diluting the composition (A) or (B) with water, preferably with an isotonic solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, plasma, to obtain solution (A).
[0035] The process may optionally include a further step d), drying of the composition (A), (B) or the solution (A), while retaining the composition (D).
[0036] The drying in step d) can be carried out by any method known and suitable to a person skilled in the art, preferably in i) a drying oven or by ii) lyophilization.
[0037] For this purpose, the composition (A), (B) or the solution (A) is frozen at -100 to -20°C, more preferably at -90 to -30°C, even more preferably at -80 to -40°C, and most preferably at -70 to -50°C. The freezing can be carried out by the shell-freeze method.
[0038] For this purpose, the composition (A), (B) or the solution (A) is preferably frozen within 0.3 to 60 min, more preferably within 1 to 30 min, even more preferably within 1.1 to 10 min, and particularly preferably within 1.5 to 7 min. The vessel in which the solution is located during the freezing process is preferably rotated in the cooling medium at 10 to 1000 rpm, preferably at 50 to 600 rpm, more preferably at 100 to 400 rpm, and even more preferably at 100 to 250 rpm.
[0039] Lyophilization, also called freeze-drying, can be carried out as plate lyophilization (preferably piston lyophilization) or by spray freeze-drying. Preferably, the pressure during drying is 0.01 to 30 mbar, more preferably 0.02 to 20 mbar, more preferably 0.03 to 10 mbar, even more preferably 0.03 to 0.5 mbar, and most preferably 0.05 to 0.1 mbar. The endpoint of the drying process can be determined by a person skilled in the art from the temperature profile records. The drying processes preferably also remove volatile solvents with the same or lower boiling points than water.
[0040] Furthermore, the invention relates to the solution (A), which can be produced by the method as described above.
[0041] The invention also includes the composition (D), which can be produced by the method as described above.
[0042] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) dissolved in water to the taxane dissolved in (OL1), while retaining composition (A); d) drying composition (A), while retaining composition (D).
[0043] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) to the taxane dissolved in (OL1) to obtain composition (A); d) drying the composition (A) to obtain composition (D).
[0044] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) to the taxane dissolved in (OL1) to obtain composition (A); b) adding the at least one further solubilizer (LV2) dissolved in water to composition (A) to obtain composition (B); d) drying the solution () to obtain composition (D). The preferred taxane is paclitaxel (Taxol). Preferably (OL1) is ethanol. Preferably the taxane in composition (A) is dissolved in a concentration of 10 to 20 g / l, more preferably in a concentration of 15 to 17 g / l. Preferably, (LV1) is Tween. Preferably, the volume ratio of (LV1) and (OL1) in composition (A) is 0.5:1 to 1.5:1, more preferably 0.6:1 to 1.3:1. Preferably (LV2), PEG3000, is more preferably a 50% solution in water. Preferably the volume ratio of (LV2) and (OL1) in composition (B) is 3:1 to 6:1. Preferably, the composition (B) is diluted in step b) with water in the volume ratio, water: composition (B), 0.5 to 0.8, preferably 0.6 to 0.75.
[0045] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) to the taxane to obtain composition (A); b) adding the at least one further solubilizer (LV2) to composition (A) to obtain composition (B); optionally, step b) being carried out at a temperature of 40 to 90 °C; optionally c) diluting composition (B) with water, preferably with an isotonic solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, and plasma to obtain solution (A).
[0046] In one embodiment, the method for providing a water-soluble formulation comprises the following steps: a) Addition of the at least one solubilizer (LV1), preferably polyethylene glycol, more preferably PEG400, to the taxane, preferably Taxol, to obtain composition A; wherein step a) is carried out at a temperature of 40 to 90 °C; optionally c) dilution of composition (A) with water, preferably with an isotonic solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, plasma to obtain solution (A).
[0047] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding three solubilizers (LV1) previously mixed at a temperature of 40 to 90 °C to the taxane, wherein step a) is carried out at a temperature of 40 to 90 °C; optionally c) diluting the composition obtained from step a) with water, preferably with an isotonic solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, and plasma, to obtain solution (A).
[0042] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) to the taxane dissolved in (OL1), obtaining composition A;
[0043] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) Adding the at least one solubilizer (LV1) to the taxane, obtaining composition A; The preferred taxane is paclitaxel. Preferably the concentration of the taxane in composition A is 1 to 500 mg / ml, more preferably 7 to 11 mg / ml. Preferably, step a) is carried out at a temperature greater than 30 °C, more preferably at a temperature of 40 to 90 °C.
[0044] In one embodiment, the method for providing a water-soluble taxane formulation comprises the steps: a) adding the taxane to a mixture of at least one solubilizer (LV1) and at least one solubilizer (LV2) while maintaining the composition (A); The preferred taxane is paclitaxel. Preferably (LV1) is PEG, more preferably PEG400 Preferably (LV2) is Tween, preferably Tween 80. Preferably the mixture comprises 70 to 90 volume %, more preferably 80 volume % (LV1). Preferably the mixture comprises 10 to 30 volume %, more preferably 20 volume % (LV2). Preferably the concentration in composition (A) is 1 mg / ml to 500 mg / ml, more preferably 7.5 to 10 mg / ml. Preferably, step a) is carried out at a temperature greater than 30 °C, more preferably at a temperature of 40 to 90 °C.
[0045] In one embodiment, the method for providing a water-soluble formulation comprises the steps: a) adding the at least one solubilizer (LV1) dissolved in water to the taxane dissolved in (OL1), obtaining composition A; c) diluting composition A with water, preferably with isotonic NaCl solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, plasma, obtaining solution A.
[0046] A taxane formulation, producible according to the inventive process, comprising, preferably consisting of: i) a taxane, preferably paclitaxel (Taxol); and ii) polyethylene glycol, preferably polyethylene glycol (PEG), selected from where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400; optionally tween.
[0047] In one embodiment, this taxane formulation comprises i) 0.05 to 31 wt.%, preferably 0.1 to 10 wt.%, more preferably 0.42 to 1 wt.% taxane, preferably Taxol, based on the total mass of the taxane formulation; and / or ii) 69 to 99.95 wt.%, preferably 90 to 99.9 wt.%, polyethylene glycol, preferably selected from , where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400, based on the total mass of the taxane formulation; and / or iii) a water content higher than 1 wt.%, preferably not higher than 0.5 wt.% based on the total mass of the taxane formulation.
[0048] In one embodiment, the taxane formulation comprises i) 0.08 to 28.8 wt.% taxane, preferably taxol, based on the total mass of the taxane formulation; and / or ii) 18.8 to 99.6 wt.%, preferably 35 to 99.6 wt.%, more preferably 40 wt.% to 99.6 wt.% polyethylene glycol based on the total mass of the taxane formulation; and / or iii) 0.3 to 79 wt.%, preferably 35 to 64 wt.% tween, based on the total mass of the taxane formulation; and / or iv) the water content is not higher than 1 wt.%, preferably not higher than 0.5 wt.%, based on the total mass of the taxane formulation.
[0049] The taxane formulation can be used for the treatment of cancer, preferably breast cancer, lung cancer, stomach cancer, pancreatic adenocarcinoma, ovarian cancer, AIDS-associated Kaposi's sarcoma, prostate cancer, and non-small cell lung cancer.
[0050] The formulation is preferably administered orally, dermally, parenterally, nasally or by inhalation. EXAMPLES 1. Production of the formulations
[0051] Scheme 1 shows an overview of exemplary examples of possible embodiments. Scheme 1: Examples of methods according to the invention Tables 2, 3, and 4 show the implementation of individual embodiments of the inventive method. Table 2: Examples of different embodiments of the method according to the invention Table 3: Order of mixing components affects solubility Table 4: Improved solubility in water after application of the inventive procedure Drugbank (htps: / / qo.druqbank.com) 2. Pharmacodynamic and pharmacokinetic testing
[0052] 2.1 In-vitro / intravenous testing of Taxol vs. various TaxoClusters (water-soluble Taxol formulations) for their activity against two cancer cell lines Two cancer cell lines (A549 = lung cancer cell line; MCF7 = breast cancer cell line) were exposed to Taxol, as well as various Taxol formulations according to the invention, and the concentration at which cell death or impairment of metabolic activity occurs was determined (Fig. 1 to 3). Taxol was tested dissolved in DMSO. TaxoCluster solid corresponds to embodiment 1c in Table 2 TaxoCluster liquid I corresponds to embodiment 1e in Table 2. TaxoCluster liquid II corresponds to embodiment 1d in Table 2. The following could be shown. Table 5: Test results: It was shown that the Taxol formulations according to the invention are at least as effective as Taxol and, in the case of embodiments 1e and 1d, significantly more effective. 2.2 Membrane permeability
[0053] The solubility of the Taxol formulations in octanol was tested as a model for their membrane penetration. The results are shown in Figures 4 to 6. As shown in Figures 4 to 6, the solubility of the Taxol formulations according to the invention in octanol and water is significantly increased. Table 6: Comparison with commercially available Taxol formulations Paclitaxel contains polyoxyl castor oil (Cremophor), which can cause serious allergic reactions. Paclitaxel contains 393 mg of alcohol (ethanol) per ml, corresponding to 39.3% w / v. The amount in 52.5 ml of this medicine is equivalent to 515.8 ml of beer or 206.3 ml of wine. Therefore, the use of paclitaxel should be avoided in cases of liver problems, epilepsy, and alcohol dependence. In addition, co-medication with dexamethasone, diphenhydramine and cimetidine is required. The taxane formulations according to the invention do not have these disadvantages and, based on the in vitro results to date, it is expected that the dosage can be significantly lower than with paclitaxel. 3. Comparative example
[0053] In W02009 / 006799 A1 a comparative example was disclosed: Paclitaxel 30mg Polyethylene glycol 400 300mg Tween - 80 1400 Mannitol 400mg Water for injection 4ml Paclitaxel, polyethylene glycol 400, and Tween 80 were mixed and stirred. An aqueous mannitol solution was then added and mixed again. The solution was treated with 0.1% activated carbon and stirred for 20 minutes. After filtration through a 0.8 µl / µm coarse filter and subsequent sterilization through an O.22 µl / µm membrane, the solution was filled into vials. A portion was stored at room temperature, and the other portion was freeze-dried. After one hour at room temperature, the solution became cloudy. The freeze-dried samples were reconstituted with water for injection and were cloudy again after one hour. The example was reproduced. Neither before nor after the addition of the activated carbon was a clear solution obtained. Thus, the filtration step removes not only the activated carbon but also undissolved taxol. IR spectroscopy confirmed that the precipitate was undissolved paxlitaxel. Compare Figures 8 and 9. The filtrate was examined by UV / VIS spectroscopy. This revealed that it did not contain the full 30 mg used, but only a fraction of this amount (approximately 11%), see Figure 10. In embodiment 1e according to Table 2, the amount of paxlitaxel used in the corresponding aqueous solutions was detected by UV / VIS spectroscopy, see Figure 11. Furthermore, clear solutions were obtained in the concentrates prepared according to the inventive process with PEG400, which remained clear for at least 4 hours.
Claims
REQUIREMENTS 1. A method for providing a water-soluble formulation of the taxanes comprising the steps I) a) Addition of at least one solubilizer (LV1) to the taxane to obtain composition (A); optionally b) addition of at least one further solubilizer (LV2) to composition (A) to obtain composition (B); wherein optionally the solubilizer (LV1) or (LV2) may be dissolved in water; wherein the taxane is dissolved in a water-miscible organic solvent (OL1); wherein the at least one or more than one solubilizer (LV1) and / or (LV2) is selected from the group consisting of polyvinylpyrrolidone (PVP), tweens, polyethylene glycol (PEG); or II) a) addition of the taxane to at least one solubilizer (LV1) to obtain composition (A) and optionally at least one further solubilizer (LV2) to obtain composition (B); wherein step a) in II) is carried out at a temperature of 40 to 90 °C;wherein at least one or more than one solubilizer (LV1) and / or (LV2) is selected from the group consisting of polyvinylpyrrolidone (PVP), tweens, polyethylene glycol (PEG); 2. The method according to claim 1, wherein the method comprises a further step c): c) diluting the composition (A) or (B) with water, preferably with an isotonic solution, more preferably selected from the group consisting of isotonic NaCl solution, 5% galactose solution, Sterofundin, plasma, to obtain solution (A).
3. The method according to claim 1 or 2, wherein the method in claim 1 comprises a further step d), drying the composition (A), (B) or the solution (A) while retaining the composition (D).
4. The method according to claim 3, wherein the drying is carried out in i) a drying oven or by ii) lyophilization.
5. The method according to claims 1 to 3, wherein step a) and / or b) is carried out at a temperature of 40 to 90 °C.
6. The method according to claims 1 to 5, wherein the taxane is a taxane according to formula (I): R 1 is selected from the group consisting of H, -COPhenyl, -CO(Ci-Ce)alkyl; R 2 to R 7 are independently selected from the group consisting of H, -CO(Ci-Ce)alkyl, -(Ci-C6)alkyl; 7. The method according to claims 1 to 6, wherein the taxol derivative is selected from the group consisting of: docetaxel, cabazitaxel, 8. The method according to claims 1 to 7, wherein the organic solvent, i) (OL1) is water-soluble and / or forms a common phase with the water after mixing; and / or ii) (OL1) is selected from the group consisting of acetone, (Ci-Cs)alkyl-OH, DMSO, and DMF 9. The method according to claims 1 to 8, wherein i) one or more than one solubilizing agent (LV1) and / or (LV2) is selected from the group consisting of polyvinylpyrrolidone (PVP), tweens, polyethylene glycol (PEG) and / or ii) preferably the polyethylene glycol (PEG), selected from , where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400; iii) preferably the polyethylene glycol (PEG) is selected from , where n is an even number between 1000 and 35,000, preferably between 1000 and 3000.
10. The method according to claims 1 to 9, wherein i) the taxane is a taxol derivative, preferably taxol; and / or ii) the taxane has a solubility in water of at most 10 to 33 g / l at 15 to 25 °C, preferably taxol has a solubility of 0.1 mg / l to 30 mg / l in water.
11. The solution (A), producible by the method according to claims 2 to 10.
12. Composition (D), producible by the process according to claims 3 to 10.
13. A taxane formulation, producible according to the method of claims 1 to 10, comprising i) a taxane, preferably taxol; ii) polyethylene glycol, preferably polyethylene glycol (PEG), selected from , where n is an even number between 300 and 600, particularly preferably between 200 and 600, most preferably 400; iii) optionally Tween.
14. The taxane formulation according to claim 13, wherein the taxane formulation comprises i) 0.05 to 31 wt.% taxane, preferably taxol, based on the total mass of the taxane formulation; and / or ii) 69 to 99.95 wt.% polyethylene glycol based on the total mass of the taxane formulation; and / or the water content is not higher than 1 wt.%, preferably not higher than 0.5 wt.%, based on the total mass of the taxane formulation.
15. The taxane formulation according to claim 13, wherein the taxane formulation comprises i) 0.08 to 28.8 wt.% taxane, preferably taxol, based on the total mass of the taxane formulation; and / or ii) 18.8 to 99.6 wt.% polyethylene glycol based on the total mass of the taxane formulation; and / or iii) 0.3 to 79 wt.% tween based on the total mass of the taxane formulation; and / or iv) the water content is not higher than 1 wt.%, preferably not higher than 0.5 wt.%, based on the total mass of the taxane formulation.
16. The solution (A) according to claim 11, the composition (D) according to claim 12, and the taxane formulation according to claims 13 to 15 for use in the treatment of cancer, preferably breast cancer, lung cancer, adenocarcinoma of the pancreas, ovarian cancer, AIDS-associated Kaposi's sarcoma, prostate cancer, gastric cancer, non-small cell lung cancer.