JP2005075783A - Composition for solubilizing or dispersing sparingly soluble compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a technique of solubilizing a sparingly soluble compound which can solubilize the compound at a sufficiently high concentration by utilizing a solubilizing composition at a comparatively low concentration. <P>SOLUTION: The composition for solubilizing or dispersing the sparingly soluble compound is used in preparing a lipid emulsifier or its freeze-dried preparation obtained by solubilizing or dispersing the sparingly soluble compound and comprises 0.1-30 wt.% oily ingredient, 0.01-6 wt.% emulsifier, and 0.01-50 wt.% cyclodextrin. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a composition for solubilizing or dispersing a hardly soluble compound, a method for preparing the composition, and a method for producing a fat emulsion by solubilizing or dispersing a hardly soluble compound using the composition. .

  A pharmaceutical product, particularly a pharmaceutical product administered intravascularly, must have an active ingredient compound (drug) solubilized (dispersed) and present in the pharmaceutical product to such an extent that the administration does not adversely affect the human body. is there. That is, it is important to prepare an aqueous solution form suitable for administration. However, conventionally, tacrolimus wettable powder as an immunosuppressant, cyclosporine, etc. Paclitaxel, and cytotoxins as heart disease treatment agents are particularly poorly soluble in water, and some solubilizers are essential for their formulation.

  Some of these poorly water-soluble compounds can be quite soluble in certain organic solvents, but the organic solvent itself has limited concentrations suitable for its administration. The concentration at which a hardly soluble compound can be dissolved is generally high, and administration at such a high concentration is problematic in terms of safety in that it causes cell damage, vascular degeneration, and the like. Therefore, it is necessary to dilute a highly concentrated organic solvent solution in which such a hardly soluble compound is dissolved to an appropriate concentration before the administration. According to such dilution, the hardly soluble compound is precipitated and administered. There are disadvantages that make it unsuitable.

  Conventionally, polyoxyethylene castor oil ("Cremophor-EL", BASF) is typically known as the solubilizer. However, even the solubilizer is known to contribute to side effects such as the appearance of anaphylactic shock, and also has a drawback associated with problems such as crystal precipitation in terms of formulation ( (See Patent Document 1 and Non-Patent Document 1).

  Other solubilizers include HP-β-CyD (2-hydroxypropyl-β-cyclodextrin), SBE-β-CyD (sulfobutyl ether-β-cyclodextrin), and certain fat emulsions. Yes. However, these solubilizers can only have a certain solubilizing effect only with respect to a specific poorly soluble compound. In addition, the solubilizing effect is still insufficient, and can only be obtained by blending in relatively large amounts to high concentrations, and administration of the resulting preparation means administration of these solubilizers at high concentrations. However, administration of such a solubilizing agent at a high concentration still has a safety problem.

As described above, conventionally, a small amount (low concentration) can be sufficiently used to solubilize poorly soluble compounds, and therefore, a safe solubilizer that does not cause the onset of diseases due to side effects, such as A solubilization technique for a hardly soluble compound using a solubilizer has not yet been developed.
Japanese National Publication No. 10-502921 Adam, JD, et al., (1993), "Journal of the national cancer institute monographs", No. 15, p.141-147

  It is an object of the present invention to provide an effective means for solubilizing a hardly soluble compound, particularly for solubilization that can solubilize the compound at a sufficiently high concentration by using a relatively low concentration with respect to the hardly soluble compound. It is an object of the present invention to provide a new safe solubilizing composition which is not itself accompanied by the appearance of side effects as seen in the prior art.

  As a result of intensive studies, the present inventors have found that an emulsified composition comprising a combination of a predetermined amount of an oil component, an emulsifier and cyclodextrins meets the above object. That is, the present inventors have found the fact that the composition can be safely administered by itself and can easily and sufficiently solubilize or disperse the hardly soluble compound. The present invention has been completed as a result of further research based on this knowledge. The gist of the present invention is as described in the following items 1-14.

  Item 1. A composition for preparing a fat emulsion obtained by solubilizing or dispersing a sparingly soluble compound or a freeze-dried preparation thereof, comprising 0.1-30% by weight of an oil component, 0.01-6% by weight of an emulsifier, and cyclodextrins A composition for solubilizing or dispersing a hardly soluble compound, characterized by containing 0.01 to 50% by weight.

  Item 2. The composition according to Item 1, wherein the oil component is contained in an amount of 0.5-50 times by weight with respect to the emulsifier and the cyclodextrin is contained in an amount of 1-3000 times in molar ratio with respect to the emulsifier.

  Item 3. The composition according to Item 1 or 2, comprising 0.2 to 20% by weight of an oily component, 0.02 to 3% by weight of an emulsifier, and 0.02 to 40% by weight of cyclodextrins.

  Item 4. The composition according to any one of Items 1-3, wherein the oil component is a natural and / or synthetic triglyceride and the emulsifier is a natural and / or synthetic phospholipid.

  Item 5. The composition according to Item 4, wherein the oily component is soybean oil and the emulsifier is egg yolk lecithin.

  Item 6. The composition according to any one of Items 1-5, wherein the cyclodextrins are 2-hydroxypropyl-β-cyclodextrin and / or sulfobutyl ether-β-cyclodextrin.

  Item 7. The composition according to any one of Items 1-6, wherein the hardly soluble compound is a taxin.

  Item 8. The composition according to item 7, wherein the hardly soluble compound is paclitaxel.

  Item 9. The composition according to any one of Items 1-8, which is a composition for preparing a fat emulsion obtained by solubilizing or dispersing 0.01-2% by weight of a hardly soluble compound.

  Item 10. The oil component is soybean oil, the emulsifier is egg yolk lecithin, the cyclodextrins are 2-hydroxypropyl-β-cyclodextrin and / or sulfobutyl ether-β-cyclodextrin, and solubilize or disperse paclitaxel Item 4. The composition according to any one of Items 1-3, which is a composition for preparing a fat emulsion containing 0.01-2% by weight of paclitaxel.

  Item 11. The method for producing a composition according to any one of Items 1 to 10, wherein an oily substance containing an oily component and an emulsifier is emulsified in water, and then a cyclodextrin is added to the obtained emulsion.

  Item 12. The composition according to any one of Items 1-10, wherein an oily substance containing an oily component and an emulsifier is prepared, and the preparation is emulsified in a solution in which cyclodextrins are dissolved in water. Manufacturing method.

  Item 13. A mixture of the composition according to any one of Items 1-10 and a solution in which a hardly soluble compound is dissolved in at least one solubilizing agent selected from the group consisting of ethyl alcohol, polyethylene glycol, and propylene glycol A method for producing a fat emulsion in which a hardly soluble compound is solubilized or dispersed.

  Item 14. The method for producing a fat emulsion containing the hardly soluble compound according to claim 13, wherein the hardly soluble compound is mixed with the composition according to any one of Items 1 to 10 at a concentration of 0.01 to 2% by weight. .

  As above-mentioned, this invention composition makes it an essential requirement to contain the predetermined amount of an oil-based component, an emulsifier, and cyclodextrins. In the composition of the present invention, the three components as the essential components act synergistically to exhibit the ability to sufficiently solubilize or disperse the hardly soluble compound. On the other hand, when any one of the three components is missing, the above-mentioned effects specific to the present invention cannot be achieved. The details of the excellent solubilization or dispersion effect (synergistic effect by the combined use of each component) of the hardly soluble compound found in the composition of the present invention are as shown in Examples below.

  Hereinafter, the composition of the present invention will be described in detail.

Slightly soluble compound In the present invention, the poorly soluble compound means a compound having a low solubility in water, which is conventionally known to be usable in the pharmaceutical field, in relation to its effective dose. Specifically, it refers to a compound in which the terms “hardly soluble”, “extremely difficult to dissolve”, and “almost insoluble” are used in the solubility described in the Japanese Pharmacopoeia, 14th Amendment. In other words, the amount of solvent required to dissolve 1 g or 1 mL of solute is 100 mL or more (concentration 1% or less), preferably 1000 mL or more (concentration 0.1% or less), more preferably 10000 mL or more (concentration 0.01% or less). Included in this.

  Specific examples of poorly soluble compounds include tacrolimus wettable powder as an immunosuppressant, cyclosporine, miconazole as an antifungal agent, sulfadimethoxine as a sulfa drug, roxithromycin and clarithromycin as antibiotics, Examples thereof include eninotabine and paclitaxel as malignant tumor drugs, and gitoxin as a therapeutic agent for heart diseases. Among these, paclitaxel and taxins containing the same are one of the most preferable hardly soluble compounds solubilized by the present invention. For example, the solubility of paclitaxel in water is 0.01% or less.

  The hardly soluble compound can be solubilized with the composition for solubilization of the present invention in the form of a bulk powder or an undiluted solution (oil) that is usually obtained. It is preferable to use the composition for solubilization of the present invention solubilized in a form dissolved in a medium, a diluent, etc.). Representative examples of the solubilizer include ethyl alcohol, polyethylene glycol and propylene glycol. The hardly soluble compound in a form dissolved in these solubilizers is generally at a concentration of about 0.1-50 w / v%, preferably about 0.2-30 w / v%.

Oily component and emulsifier In the composition of the present invention, vegetable oil can be usually used as the oily component (fat). Specific examples thereof include soybean oil, cottonseed oil, rapeseed oil, sesame oil, safflower oil, corn oil, peanut oil, olive oil, coconut oil, perilla oil, castor oil and the like. The oily component may be a chemically synthesized triglyceride such as 2-linoleoyl-1,3-dioctanoylglycerol and 2-linoleoyl-1,3-didecanoylglycerol. Further, it may be medium chain fatty acid triglyceride (MCT, triglyceride of fatty acid having 8 to 10 carbon atoms). Commercially available products based on the MCT include: “Coconard” (manufactured by Kao), “ODO” (manufactured by Nisshin Oil), “Miglyol” (SASOL), “Panasate” (Nippon Yushi Co., Ltd.) Etc.). The oily component in the present invention may be such a commercial product. Furthermore, the oil component may be animal oil, mineral oil, or the like. One of these can be used alone, or two or more can be used in combination. As a particularly preferred oily component, soybean oil can be exemplified.

  Typical examples of the emulsifier include natural yolk lecithin, soy lecithin, hydrogenated egg yolk lecithin obtained by hydrogenation thereof, and hydrogenated soy lecithin. The emulsifier may be a chemically synthesized phospholipid. The chemically synthesized phospholipids include phosphatidylcholine (dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, etc.), phosphatidylglycerol (dipalmitoylphosphatidylglycerol, dimyristoylphosphatidylglycerol, distearoylphosphatidylglycerol, Oil phosphatidylglycerol), phosphatidylethanolamine (dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine, dioleoylphosphatidylethanolamine, etc.). These emulsifiers are used alone or in combination of two or more. Preferred emulsifiers are egg yolk lecithin and soy lecithin.

The oily component and the emulsifier may be mixed in advance and emulsified in water in the form of a fat emulsion. The preparation method (emulsification dispersion method) of the fat emulsion is well known in the art. For example, a method of emulsifying (fine emulsification) the resulting crude emulsion using an appropriate high-pressure emulsifier after adding water for injection to the mixture of the two and roughly emulsifying the mixture. More specifically, the rough emulsification can be carried out using a homomixer such as TK homomixer manufactured by Tokushu Kika Kogyo Co., Ltd., usually at 5000 revolutions / minute or more for 5 minutes or more. The fine emulsification can be carried out using a high-pressure homogenizer such as a Menton gourin homogenizer (manufactured by Gourin) or an ultrasonic homogenizer. In the case of using a high-pressure homogenizer, it can be carried out by generally passing it under a pressure condition of about 200 kg / cm ² or more, about 2-50 times, preferably about 5-20 times. These mixing and emulsification operations may be performed at room temperature, or may be performed by employing a slight heating operation (usually about 55-80 ° C.).

  The blending ratio of the oil component and the emulsifier is not particularly limited as long as a fat emulsion is obtained. Usually, the oily component and the emulsifier are contained in the composition of the present invention obtained by using a fat emulsion prepared using them, and the oily component is 0.1 to 30% by weight, preferably about 0.2 to 20% by weight. A range of about 0.01 to 6% by weight, preferably about 0.02 to 3% by weight, is selected. Further, the ratio of the oil component and the emulsifier constituting the composition of the present invention is preferably selected from the ratio of the oil component to 0.5 to 50 times the weight of the emulsifier 1.

  The fat emulsion (emulsion) prepared above is not particularly necessary, but if necessary, it may be further added and mixed with appropriate amounts of various additives known to be added and blended in the seed fat emulsion. You can also. Examples of the additive include an antioxidant, an antibacterial agent, a pH adjuster, and an isotonic agent. Specific examples of the antioxidant include sodium metabisulfite, sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, and sodium thiosulfate. Examples of the antibacterial agent include sodium caprylate, methyl benzoate, disodium ethylenediaminetetraacetate (EDTA), and the like. As the pH regulator, hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, sodium hydroxide and the like can be used. As the tonicity agent, glycerin; sugars such as glucose, fructose and maltose; sugar alcohols such as sorbitol and xylitol can be used. Among these, the oil-soluble material can be used by being mixed in advance with an oil-based component constituting the emulsion. The water-soluble material can be mixed with water for injection or added and blended in the aqueous phase of the resulting emulsion. These addition amounts are obvious to those skilled in the art, and are not particularly different from those addition amounts conventionally known.

  The fat emulsion thus obtained can be adjusted to usually about pH 5.0-8.5, preferably about 5.5-8.0.

Cyclodextrins cyclodextrins include cyclodextrins, derivatives thereof and pharmacologically acceptable salts thereof. Here, cyclodextrin refers to a cyclic oligosaccharide composed of 6-12 glucose units. The derivative of cyclodextrin refers to a compound in which some or all of the hydroxyl groups at 2, 3, 6 positions of glucose constituting cyclodextrin are substituted with other functional groups. Specific examples of cyclodextrin and derivatives thereof include compounds represented by the following general formula (1).

(Wherein n is an integer of 6-12, R ¹¹ , R ¹² and R ¹³ are the same or different in each repeating unit, and each represents a hydrogen atom, an alkyl group, a monohydroxyalkyl group, a dihydroxyalkyl group, a sulfoalkyl group. Group, carboxyalkyl group or sugar residue.)
In the above, examples of the alkyl group include C _1-4 -alkyl groups such as methyl, ethyl, and propyl. Examples of the monohydroxyalkyl group include monohydroxy-C _1-4 -alkyl groups such as hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl and the like. Examples of the dihydroxyalkyl group include dihydroxy-C _1-4 -alkyl groups such as dihydroxymethyl, 2,2-dihydroxyethyl, and dihydroxypropyl. Examples of the sulfoalkyl group include sulfo-C _1-4 -alkyl groups such as sulfomethyl, 2-sulfoethyl and sulfobutyl. Examples of the carboxyalkyl group include carboxy-C _1-4 -alkyl groups such as carboxymethyl and 2-carboxyethyl. Moreover, as a sugar residue, a glucosyl group, a maltosyl group, panosyl group etc. can be illustrated, for example.

  Preferred cyclodextrins used in the present invention include α-cyclodextrin or a derivative thereof in which n = 6 in the general formula (1), β-cyclodextrin or a derivative thereof in which n = 7, and n = 8 Certain γ-cyclodextrins or derivatives thereof and δ-cyclodextrins or derivatives thereof where n = 9 are included. Specific examples of these preferable cyclodextrin derivatives include alkyl derivatives, hydroxyalkyl derivatives, sulfoalkyl ether derivatives or sugar-bonded derivatives of cyclodextrin. Examples of the alkyl derivatives of cyclodextrin include dimethyl-α-cyclodextrin, dimethyl-β-cyclodextrin, dimethyl-γ-cyclodextrin and the like. Hydroxyalkyl derivatives of cyclodextrin include 2-hydroxypropyl-α-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin and the like. Examples of the sulfoalkyl ether derivatives of cyclodextrin include sulfobutyl ether-α-cyclodextrin, sulfobutyl ether-β-cyclodextrin, sulfobutyl ether-γ-cyclodextrin and the like. The sugar-binding derivatives of cyclodextrin include glucosyl-α-cyclodextrin, glucosyl-β-cyclodextrin, glucosyl-γ-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, maltosyl-γ-cyclodextrin Etc. are included.

  Examples of pharmacologically acceptable salts of cyclodextrin and derivatives thereof include sodium salts, potassium salts, magnesium salts and the like.

  The compounding amount of cyclodextrins in the composition of the present invention can be appropriately selected from the range of about 0.01-50 wt%, preferably about 0.02-40 wt%. The effects of the present invention can be achieved by blending cyclodextrins within this range. The blending amount of the cyclodextrins is preferably selected so as to be in the range of about equimolar amount to about 3000 times molar amount with respect to the emulsifier component constituting the composition of the present invention.

Composition of the present invention The composition of the present invention is prepared by mixing predetermined amounts of the oil component, emulsifier and cyclodextrins. The mixing ratio of each component is 0.1-30 wt%, preferably 0.2-20 wt%, oil component 0.01-6 wt%, preferably 0.02-3 wt% and cyclodextrins 0.01-50 wt%, preferably 0.02 wt%. It should be selected from the range of -40% by weight.

  The mixing method of each component is not particularly limited as long as the mixture is in the form of an emulsion, and can be carried out according to a general method. For example, the desired composition of the present invention can be obtained by a method in which an oil component and an emulsifier are premixed, the mixture is emulsified in water, and cyclodextrin is added to the resulting fat emulsion. Further, for example, the desired composition of the present invention can also be obtained by a method in which an oily component and an emulsifier are mixed in advance and the mixture is emulsified in a solution in which cyclodextrin is dissolved in water.

Means for obtaining an emulsion that can be employed in each of the above methods (emulsification and dispersion methods) are well known in the art. For example, using a homomixer such as TK homomixer manufactured by Tokushu Kika Kogyo Co., Ltd., a rough emulsification means that usually requires 5 minutes or more at 5000 rpm or more, and a high-pressure homogenizer such as Manton Gourin homogenizer (Gourin) or ultrasonic Other fine emulsification means can be employed using a homogenizer. The fine emulsification using a high-pressure homogenizer is generally carried out by passing it about 2-50 times, preferably about 5-20 times under a pressure condition of about 200 kg / cm ² or more. Each emulsification operation may be performed at room temperature, or may be performed by employing a slight heating operation (usually about 55-80 ° C.).

Method for Solubilizing Slightly Soluble Compound Utilizing the Composition of the Present Invention The composition of the present invention can be easily solubilized (dispersed) in a form suitable for administration as a pharmaceutical using the composition of the present invention. .

  The solubilization can be basically carried out simply by mixing the composition of the present invention and a hardly soluble compound. Of course, a slight stirring operation or the like may be employed during the mixing.

  The mixing amount of the composition of the present invention and the hardly soluble compound is such that the hardly soluble compound is mixed in the composition of the present invention at a final concentration of 0.01-2.0% by weight, preferably 0.02-1.2% by weight. Is appropriate.

  In addition, it is preferable that the poorly soluble compound in the above mixing is used in a form dissolved in advance in an appropriate solubilizing agent such as ethyl alcohol, polyethylene glycol, propylene glycol or the like. The hardly soluble compound in a form dissolved in these solubilizers is generally at a concentration of about 0.1-50 w / v%, preferably about 0.2-30 w / v%.

  The object obtained by solubilizing the poorly soluble compound thus obtained can be filtered and sterilized into a product according to a conventional method. Filtration can be performed using a conventional membrane filter. Sterilization can be performed, for example, by high-pressure steam sterilization, hot water immersion sterilization, shower sterilization, or the like. The obtained product is useful as an application in which a poorly soluble compound incorporated therein is used, for example, an immunosuppressant, an antifungal agent, an antineoplastic agent and the like. In addition, the target product obtained by solubilizing the hardly soluble compound can be made into a freeze-dried preparation by a usual method.

Hereinafter, examples will be given to describe the present invention in more detail, but the present invention is not limited thereto.
Example 1-8
Compositions for solubilizing or dispersing the hardly soluble compound of the present invention comprising the respective components shown in Table 1 and Table 2 were prepared as follows.

  In addition, the following were used as each component in a table | surface.

Soybean oil (refined soybean oil, manufactured by Nisshin Oil Co., Ltd.)
Lecithin (purified egg yolk lecithin, manufactured by Kewpie Corporation)
HP-β-CyD (2-hydroxypropyl-β-cyclodextrin, “Cavitron82003”, manufactured by Cargill)
That is, after adding lecithin to soybean oil in the final concentrations shown in Table 1 and Table 2, add a solution in which glycerin is dissolved in water for injection to this, and use a Polytron homogenizer (manufactured by KINEMATICA) to add nitrogen. The crude emulsification was carried out at 25,000 rpm for 10 minutes under air flow and heating. Next, after adjusting the obtained crude emulsion to pH 8.2-8.3, using an APV gourin homogenizer (APV Gourin), an emulsification temperature of 40 under nitrogen flow until the average particle size becomes 0.3 μm or less. Fine emulsification was carried out at -80 ° C. and an emulsification pressure of 550 kg / cm ² to obtain an emulsion. To the obtained emulsion, HP-β-CyD was added in an amount to give the final concentrations shown in Table 1 and Table 2, and then stirred for 60 minutes to obtain the composition of the present invention.

  Next, 5 mL of the obtained composition of the present invention was added with the paclitaxel solubilizing agent solution (Example 1-6) or clarithromycin solubilizing agent solution (Example 7-8) described in Table 1 and Table 2. A predetermined amount was added, and the mixture was stirred for 60 minutes, and then filled with 10 mL of a 10 mL glass vial and sealed to obtain a hardly soluble compound solubilized emulsion sample to be tested.

  For this sample, the drug amount was measured by high performance liquid chromatography, and the drug amount per mL of the sample was calculated to obtain the formulation concentration.

The obtained sample was centrifuged at 13,000 g for 2 hours, the precipitate was dissolved in ethanol, the amount of drug was measured by high performance liquid chromatography, and the amount of drug precipitated per 1 mL of sample was calculated as the amount of precipitation. The value obtained by subtracting the amount of precipitation from the formulation concentration is the solubility (mg / mL), and the obtained results are also shown in Tables 1 and 2.
Comparative Example 1-6
Comparative samples shown as Comparative Examples 1 and 4 in Tables 1 and 2 were prepared in the same manner as in Example 1-8, except that HP-β-CyD was not added to the emulsion.

  Further, in Example 1-8, water for injection was used in place of the emulsion, and a solution obtained by dissolving HP-β-CyD in water for injection was used. Comparative samples shown as 3, 5, and 6 were prepared.

  The solubility results obtained for the obtained samples in the same manner as in Example 1-8 are also shown in Tables 1 and 2.

From the results shown in Tables 1 and 2, the following is clear. That is, the composition of the present invention is based on the combined use of a fat emulsion and cyclodextrins, and these act synergistically and are hardly soluble compared to the case where each of the fat emulsion and cyclodextrins is used alone. It can be seen that the compound can be solubilized or dispersed, and it is possible to formulate a hardly soluble compound, which was difficult in the prior art. In addition, according to the present invention, it is possible to prepare a relatively high concentration of the hardly soluble compound. Therefore, when the preparation is administered to the human body, the amount of liquid to be administered can be reduced, and it is effective in reducing the burden of administration. Furthermore, since the composition of the present invention does not use polyoxyethylene castor oil that has been used to solubilize poorly soluble compounds, it can be safely administered to the human body without the risk of anaphylactic shock caused by this. It is.

Claims (14)

A composition for preparing a fat emulsion obtained by solubilizing or dispersing a sparingly soluble compound or a lyophilized preparation thereof, comprising 0.1-30% by weight of an oil component, 0.01-6% by weight of an emulsifier and 0.01-50% of cyclodextrins A composition for solubilizing or dispersing a sparingly soluble compound, comprising: wt%. 2. The composition according to claim 1, wherein the oily component is contained in an amount of 0.5-50 times by weight with respect to the emulsifier, and the cyclodextrins are contained in an amount of 1-3000 times in molar ratio with respect to the emulsifier. The composition according to claim 1 or 2, comprising 0.2 to 20% by weight of an oily component, 0.02 to 3% by weight of an emulsifier and 0.02 to 40% by weight of cyclodextrins. The composition according to any one of claims 1 to 3, wherein the oil component is a natural and / or synthetic triglyceride and the emulsifier is a natural and / or synthetic phospholipid. 5. The composition according to claim 4, wherein the oil component is soybean oil and the emulsifier is egg yolk lecithin. 6. The composition according to claim 1, wherein the cyclodextrins are 2-hydroxypropyl-β-cyclodextrin and / or sulfobutyl ether-β-cyclodextrin. 7. The composition according to claim 1, wherein the hardly soluble compound is a taxin. 8. The composition according to claim 7, wherein the hardly soluble compound is paclitaxel. 9. The composition according to claim 1, which is a composition for preparing a fat emulsion obtained by solubilizing or dispersing 0.01-2% by weight of a hardly soluble compound. The oil component is soybean oil, the emulsifier is egg yolk lecithin, the cyclodextrins are 2-hydroxypropyl-β-cyclodextrin and / or sulfobutyl ether-β-cyclodextrin, and solubilized or dispersed paclitaxel The composition according to any one of claims 1-3, which is a composition for preparing a fat emulsion containing 0.01-2% by weight of paclitaxel. The method for producing a composition according to any one of claims 1 to 10, wherein a cyclodextrin is added to an emulsion obtained after emulsifying an oily substance containing an oily component and an emulsifier in water. The production of the composition according to any one of claims 1 to 10, wherein an oily substance containing an oily component and an emulsifier is prepared, and the preparation is emulsified in a liquid in which cyclodextrins are dissolved in water. Method. Mixing the composition according to any one of claims 1 to 10 with a solution obtained by dissolving a hardly soluble compound in at least one solubilizing agent selected from the group consisting of ethyl alcohol, polyethylene glycol and propylene glycol. A method for producing a fat emulsion in which a poorly soluble compound is solubilized or dispersed. 14. The method according to claim 13, wherein the hardly soluble compound is mixed with the composition according to any one of claims 1 to 10 at a concentration of 0.01 to 2% by weight.