KR20030023369A - Oily paclitaxel composition and formulation for chemoembolization and preparation method thereof - Google Patents

Abstract

PURPOSE: A process of preparing a paclitaxel oily composition for chemoembolization by adding paclitaxel to an oily contrast medium and then agitating is provided. The composition is easy to manufacture and sterilize and more physiochemically stable than conventional adriamycin/lipiodol preparation. CONSTITUTION: The paclitaxel oily composition is prepared by mixing 0.0001 to 10mg paclitaxel with 1ml oily contrast medium under sterilization conditions, agitating at room temperature and then sterilized by gamma ray. The oily contrast medium is iodized oil having an iodine content of 30 to 50% selected from iodized poppy seed oil, ethiodol and iodized soybean oil. The composition optionally contains 0.1 to 1ml animal oil such as squalane, vegetable oil such as soybean oil or a mixture thereof, based on 1ml oily contrast medium.

Description

PACLITAXEL COMPOSITION AND FORMULATION FOR CHEMOEMBOLIZATION AND PREPARATION METHOD THEREOF}

The present invention relates to a paclitaxel oil-based composition, a formulation thereof, and a method for preparing the same for solubilizing paclitaxel for use in arterial embolization.

Arterial embolization is a method of treating cancer by finding an artery that goes to the cancer site using a contrast agent and blocking nutrient supply to cancer tissues using anticancer agents and embolic materials.

Representative arterial embolization is hepatic artery embolization. This method involves dispersing various anticancer drugs such as doxorubicin (Adriamycin), cisplatin, and carboplatin in an oily contrast medium, and simultaneously administering embolization and contrast. .

Representative contrast agents used in such arterial embolizations are iodized oils such as lipiodol. However, the dispersion system in which the various anticancer agents are dispersed in Lipiodol has many limitations during the procedure because of physical instability. Anti-cancer agents widely used in the method of treating liver cancer in conventional diagnostic radiology include adriamycin and epirubicin. Since most of the anti-cancer drugs including adriamycin are water-soluble, they cannot be dissolved directly in Lipiodol. in the form of a suspension) was used. (Yoshihiro Katagiri et al., Cancer Chemother. Pharmacol 1989, 23, 238-242). However, in the case of the suspension made by this method, long-term storage is difficult because adriamycin particles are aggregated or precipitates are formed. Therefore, after dissolving an anticancer agent in an aqueous contrast agent, it was used to disperse it in Lipiodol, an oily contrast agent. That is, just before administration to the patient, the anticancer agent is dissolved in the aqueous contrast agent and mixed with the oily contrast agent by the pumping method. In this case, in order to maximize the stability of the emulsion, an aqueous contrast agent, Eurografin (1.328-1.332) or Iopamiro, having a specific gravity similar to that of Lipiodol (1.275-1.290), is used (Takashi Kanematsu Et al., Journal of surgical oncology 1984, 25, 218-226, Takafumi Ichida et al., Cancer Chemother.Pharmacol 1994, 33, 74-78).

However, by this method, only a temporary emulsion is formed, and the mixed state is unstable, so that the separation occurs again in a few minutes, and thus adriamycin precipitates, so that it is hardly absorbed by the body. Indeed, it can be observed that phase separation occurs even during infusion into the patient's blood vessels during the procedure. In addition, when the mixed solution is administered, adriamycin is absorbed at once, so antitumor effects cannot be expected continuously, and various side effects appear.

To date, the best known method for liver cancer treatment is a synthetic polymer called poly (styrene-co-maleic acid) -conjugated neocarzinostatin (SMANCS)], a poly (styrene-co-maleic acid) -conjugated neocarzinostatin. SMANCS has both hydrophilic and lipophilic properties and can be directly dissolved in Lipiodol (Konno, T. and Maeda, H., Targetting chemotherapy of hepatocellular carcinoma.Neoplasms of the liver, Eds) Okuda, K., and Ishak, KG, Springger-Verlag, Berlin, P343-352). Although the SMANCS / lipiodol formulation solves the problems of the adriamycin / lipiodol formulation, it is 10 times more expensive than the adriamycin / lipiodol formulation and is not generalized because the toxicity is also severe.

Meanwhile, paclitaxel, an anticancer agent, is known to exhibit significant cytotoxicity against various cancers such as ovarian cancer, breast cancer, esophageal cancer, melanoma, and leukemia. Taxol, which is mainly marketed by Bristol-Myers Squibb It is used as a brand injection.

Paclitaxel, a representative poorly soluble drug, has undergone simultaneous development of solubilization technology due to its low solubility. One such solubilization technique is the use of dissolution aids to use paclitaxel in systemic routes of administration, such as intravenous injection. Taxol mentioned above Injectables also use a dissolution aid called Cremophor EL (polyoxyethylene 35 castor oil). In other words, this formulation is spontaneously formed in microemulsion when dispersed in water as a pre-concentrate form of emulsion (see US Pat. No. 5438072). However, the use of such dissolution aids is known to cause further toxicity. Therefore, there is a need to develop a new formulation of paclitaxel excellent anti-cancer effect against various cancers.

To date, there has been no use of paclitaxel as an anticancer agent used in vascular embolization or contrast. Accordingly, the present invention intends to solubilize paclitaxel and use it for arterial embolization.

Accordingly, one object of the present invention is to provide a new composition of paclitaxel that can solubilize paclitaxel.

More specifically, an object of the present invention is to provide a preparation of oily paclitaxel for use in arterial embolization for the treatment of solid cancer.

That is, another object of the present invention is to provide an oil-based paclitaxel preparation that can stably maintain its original composition through an arterial embolization procedure of several hours.

Still another object of the present invention is to provide a method for preparing the paclitaxel composition.

1 is a CT photograph of one week after the paclitaxel / lipiodol formulation 0.3 CC of the present invention is selectively administered to liver cancer tissues of rabbits by hepatic artery embolization. The amount of paclitaxel administered corresponds to A) 1 mg, B) 3 mg and C) 0 mg.

Figure 2 is selectively administered paclitaxel / Lipiodol formulation of the present invention to liver cancer tissues of rabbits by hepatic artery embolization, and after one week, paclitaxel concentrations in liver cancer tissues and normal tissues are quantified and shown by HPLC. The amount of paclitaxel administered corresponds to A) 1 mg and B) 3 mg.

Figure 3 is a paclitaxel / Lipiodol formulation of the present invention 0.3 CC (1 mg group and 3 mg group) E is 0.4 CC (4 mg group) is selectively administered to liver liver tissue of rabbits by hepatic artery embolization 1 week after the total liver cancer tissue Shows the percentage of living cells among them. Only 0.3 cc of Lipiodol was administered to the control group.

In order to meet this need, the inventors of the present invention have studied paclitaxel formulations that can be used for arterial embolization as paclitaxel. While unexpectedly, paclitaxel is well soluble in oily contrast medium, resulting in a single phase viscosity range of 120 It was found to be a highly viscous oil of -180 cP (centipoises).

It has also been found that the paclitaxel / oil preparation composition is chemically and physically stable and can be preserved for a long time without a change in composition. Thus prepared paclitaxel / oily contrast agent composition shows a significantly improved physical properties compared to the conventional Lipiodol formulation using a water-soluble anticancer agent such as doxorubicin, it can be said that the formulation properties similar to SMANCS / Lipiodol formulation. In other words, the conventional SMANCS / Lipiodol formulation is expensive, and due to severe toxicity, it is not universalized, whereas the paclitaxel / oily contrast agent composition of the present invention is not only low production cost due to the low cost of the two materials as a raw material, the manufacturing process is very Simple and obtained formulations also have excellent stability and shelf life. That is, since the initial composition is stably maintained for several hours during arterial embolization, the anti-cancer agent is stably and prolonged when applied to arterial embolization, compared with conventional Lipiodol / Iopamiro / Adriamycin preparations that cause phase separation immediately after mixing. As well as the effect that can be delivered to the body, the formulation itself is stable, so the shelf life is also excellent. In addition, as described below, as a result of performing hepatic artery embolization using an animal model, it is expected to be widely used for arterial embolization because it shows excellent embolism effect and anticancer action.

Although arterial embolization is typical of hepatic artery embolization, it can be applied to various types of solid cancers in addition to hepatic artery embolization. For example, SMNACS / lipiodol formulations can be used to perform cancer therapy that targets only cancer cells, such as the treatment of rectal cell carcinoma through the renal artery (K. Tsuchiya, Tumor-targeted chemotherapy with SMANCS in lipiodol). for renal cell carcinoma: longer survival with larger size tumors.Urology. 2000 Apr; 55 (4): 495-500).

To date, there has been no use of paclitaxel as an anticancer agent used in vascular embolization or contrast. Accordingly, the present invention intends to dissolve paclitaxel in an oily contrast agent and use it for arterial embolization.

An example of an oily contrast agent that can be used in the paclitaxel / oil preparation composition of the present invention is iodide oil. Typical iodide oils include iodide poppy seed oil, i.e. Lipiodol Laboratoire Guerbet, France, ethiodol (Savage Laboratories, Melville, NY), and iodide soybean oil. Can be mentioned. For more information on iodide soybean oil, see Ma Tai. The effect of oral iodized oil on prevention and treatment of endemic goiter. Chienese Med. J. 61 (9): 533, 1981.

In the present invention, the iodine content of the iodide oil which can be used as an oily contrast agent is preferably 30 to 50% by weight. More preferably, the iodine content is 35 to 45% by weight. Most preferably, Lipiodol is preferably used as an oily contrast agent.

The amount of the oily contrast agent in the paclitaxel / oily contrast agent of the present invention is used in an amount of 0.0001 to 10 mg / 1 ml oily contrast agent. If the amount of paclitaxel exceeds 10 mg, it is not preferable because it is no longer dissolved in the oily contrast agent and precipitation occurs. Conversely, if the amount of paclitaxel is 0.0001 mg or less, the desired anticancer effect cannot be achieved.

In addition, the paclitaxel / oil-based contrast agent of the present invention may optionally additionally add an animal oil such as squalene or a vegetable oil such as soybean oil. That is, by replacing a part of the oily contrast agent with such animal oil, vegetable oil, or a mixture thereof, it is possible to reduce the manufacturing cost while maintaining biocompatibility as well as not lowering desired drug efficacy or stability. . The amount of such animal oil or vegetable oil is used in a ratio of oily contrast agent: animal oil and / or vegetable oil = 1: 0.1 to 1 by volume. Preferably the ratio is 1: 0.1 to 0.5.

The paclitaxel / oil-based contrast composition of the present invention can be prepared simply by first adding an appropriate amount of paclitaxel to the oil-based contrast agent so as to be in the above composition range, stirring and dissolving at room temperature. At this time, for rapid dissolution, it may be heated to a temperature of about 35 ~ 45 ℃ or sonication using a bath type sonicator (bath type sonicator). The paclitaxel / oil preparation composition thus prepared is stored after sterilization. Sterilization is performed under sterile conditions using sterilized raw materials from the beginning, or the oily contrast agent / paclitaxel composition is sterilized using a syringe filter (pore size 200 μm, PVDF sterile filter). Another sterilization method involves disinfecting iodized poppy seed oi and paclitaxel with gamma-ray or sterilization by EO gas sterilization and mixing, sterilizing the mixed composition by gamma ray or EO gas sterilization. It can also be disinfected.

Thus prepared paclitaxel / oily contrast agent composition of the present invention showed a stable storage stability at room temperature for more than 60 days.

In addition, the dosage and method of administration of the paclitaxel / oil-based contrast composition of the present invention may be varied at the discretion of the attending physician according to the patient's individual differences such as age, sex, weight, and severity of symptoms of the patient. The procedure can be repeated several times once a month. 2 ~ 15 ml is used at a time, and the artery that supplies blood to solid cancer, ie liver cancer, is injected along the hepatic artery.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the examples set forth below are provided to aid the understanding of the present invention, but the present invention is not limited to these examples.

Example 1 Preparation of Paclataxel / Lipiodol Composition

1 ml of Lipiodol (Lipiodol Ultra-fluid, Laboratoire Guerbet, France, 38% by weight of iodine) was added to 2,4,6,8,10,11 mg of paclitaxel (Samyang Corp.). Into a micro test tube, 1.5 ml polyethylene, Eppendorf AG, Germany) and dissolved by stirring at room temperature. For rapid dissolution, it may be heated to about 40 ° C. or sonicated in a bath sonicator. When the concentration of paclitaxel was 2 to 10 mg / 1 ml Lipiodol, paclitaxel was dissolved in Lipiodol because a single liquid phase was formed. However, if the paclitaxel concentration is 11 mg / 1 ml Lipiodol, paclitaxel initially dissolves in Lipiodol to form a single liquid phase, but when left for one day, the turbidity of the solution increases, and paclitaxel in the Lipiodol can be observed. It was confirmed that the solubility of about 10 mg / ml at room temperature (24 ~ 28 ℃). Viscosity was measured by adding 10 ml of paclitaxel / lipiodol obtained in a kinematic viscometer (Cannon-Fenske Type, Calibrated, Cat.No. 13-617E, Size 200, Fisher Scientific, Pittsburgh, PA) and measuring the drop time. The measured viscosity is 151 cP, indicating that the viscosity is much increased compared to 4.4 cP of Lipiodol at 25 degrees Celsius. When the viscosity is more than 45 cP embolism effect, the embolism effect of the prepared paclitaxel / Lipiodol composition seems to be large.

Example 2. Physical Stability of Paclitaxel / Lipiodol Composition

As an oily contrast agent, 10 mg of paclitaxel is added to 1 ml of Lipiodol (38% by weight of Lipoiodol Ultra-fluid, Laboratoire Guerbet, France, Iodine), and the solution is stirred at room temperature and dissolved. Warmed up to about 40 ° C to speed up the dissolution. It can be seen that after the preparation, a single liquid phase is formed and dissolved in paclitaxel Lipiodol. The prepared composition was sterilized through a syringe connected to a syringe filter (200 μm pore size, PVDF filter), and then stored at room temperature and 4 ° C. for 60 days, and physical stability and chemical degradation of paclitaxel were observed. Color change, odor, and phase separation of the liquid phase did not occur. Analysis of the components using HPLC showed that paclitaxel did not degrade at all. HPLC conditions were as follows.

SP8810 precision isocratic pump (Spectra-Physics Inc., San Jose, CA)

Column: Waters Bondpack C18 Column (3.9 mm x 300 mm, Waters Corp., Milford, MA)

Mobile phase: 50% (w / w) each of acetonitrile and water

Flow rate: 1 ml / min

Detector: Spectra 100 variable wavelength detector (Spectra-Physics)

Example 3. Preparation and Physical Stability of Ethiodol / Paclitaxel Compositions

Paclitaxel oil-based composition was prepared in the same manner as in Example 1 except that thiodol (Savage Laboratories, Melville, NY) was used instead of Lipiodol as an oily contrast agent. It can be seen that paclitaxel is well soluble in thiodol because the mixture forms a single liquid phase.

Physical stability of the prepared composition was tested in the same manner as in Example 2. After sterilization, stored at room temperature and 4 ° C. for 60 days, and physical stability and chemical degradation of paclitaxel were observed. Color change, odor, and phase separation of the liquid phase did not occur. Analysis of the components using HPLC showed that paclitaxel did not degrade at all.

Experimental Example 1. Manufacture of Liver Cancer Animal Model

10 ml of rabbit (VX-2 animal model of rabbit liver carcinoma) with a tumor with a diameter of 1-2 cm after implantation of VX2 carcinoma provided by Deutsches Krebsforschungszentrum Tumorbank in Germany into the femur of rabbit (Newzealand White) was about 2 weeks old Pentotal sodium solution (62.5mg / kg) is sacrificed by intravenous injection, the hairs around the tumor are removed, the skin is disinfected with iodine solution and alcohol, the skin is cut in the tumor site with a surgical knife and the tumor is removed. It peeled off and extracted. Excision of the tumor was removed to remove necrosis in the center, and a thin layer around the tumor was collected and mixed with calcium and magnesium-free Hank's balanced salt solution (Grand Island Biological Co., Grand Island, New York) to kill tumor tissue. Cut into fine pieces with scissors and surgical knives until 5ml RMPI-1640 (Rosewell Park Memorial Institute, Rosewell Park, New York) culture medium and mixed well and diluted to a concentration of 1x106 cells / mm3 tumor cells.

Intrahepatic Injection and Transplantation of Tumor Cell Solution: To anesthetize rabbits, intravenous injection of 23G needle into the vein of the ear to connect with 500ml saline solution to secure the vein, and then dilute 500mg of pentotal sodium in 40ml saline solution. (1.5 ml / kg) was injected into the ear vein at a rate of 1 ml per minute. The abdominal hair is then removed, sterilized with iodine solution and alcohol, punctured the left lobe of liver using 22G needle under ultrasound guidance, and 0.1ml of tumor tissue solution is injected into the parenchyma of liver with 1ml syringe with 22G needle. It was. Tumor tissue was injected into the front lobe of the five lobes of the liver, where ultrasound was most easily observed (FIG. 2). Antibiotics (PenbrexR, 250 mg) were injected intravenously to prevent secondary infection. Rabbits that had been injected with tumor tissue solutions were raised in normal feed in rabbits. Two weeks after tumor cell transplantation, tumors were detected by ultrasound and CT, and the growth curve was used to predict the future growth rate to some extent. Tumor location and size were tracked by ultrasound at 3 weeks interval and 2 weeks at 1 week after tumor cell transplantation.

Example 4 Carotid Artery Embolization in Liver Cancer Animal Model Using Paclitaxel / Lipiodol Composition

As an oily contrast agent, 10 mg or 3.33 mg of paclitaxel was added to 1 ml of Lipiodol, respectively, and placed in a test tube, followed by dissolution at room temperature. In order to accelerate the dissolution, it may be heated to about 40 ° C. or sonicated in a bath sonicator. It was found that paclitaxel was dissolved in Lipiodol because a uniform single liquid phase was formed after preparation. The prepared Lipiodol / Paclitaxel formulation was sterilized by passing a syringe connected to a syringe filter (200 μm pore size, PVDF filter). Carotid artery embolization was performed by selecting the artery supplying the tumor to the liver cancer animal model prepared in Experiment 1, using 0.3 ml of the paclitaxel / lipiodol formulation of the present invention using a microconduit. Thus, paclitaxel doses in each experimental group corresponded to 1 mg or 3 mg, respectively. At this time, only 0.3 cc of Lipiodol was injected into the liver cancer animal model as a control group. One week after the surgery, CT scans showed that Lipiodol was selectively detected only in the liver cancer tissues.

Example 5 Analysis of Paclitaxel Concentration in Liver Cancer Tissues after Carotid Embolization with Paclitaxel / Lipiodol Composition

Liver cancer animals embolized in Example 4 were sacrificed one week after the liver was removed. The liver tissues were divided into tissues identified with the naked eye of lipidodol, tissues not identified with the naked eye, and normal tissues located around liver cancer. The separated liver tissue was added to lysis buffer [62.5 mM Tris-HCl (pH 6.8), 2% sodium dodecyl sulfate, 5% b-mercaptoethanol, 10% glycerol] and then ground to destroy the tissue. This was centrifuged to determine the concentration of paclitaxel in the supernatant using HPLC. At this time, the conditions of HPLC are the same as in Example 2. As described in Example 4, quantitative results of paclitaxel in rabbits administered with 1 mg and 3 mg of paclitaxel are shown in FIGS. 2A and 2B, respectively. It was confirmed that the highest concentration of paclitaxel was found in liver cancer tissues in which Lipiodol was visible to the naked eye, and relatively high concentrations of paclitaxel were detected in liver cancer tissues in which Lipiodol was not visible. On the other hand, paclitaxel was selectively distributed only in liver cancer tissues even after one week of administration because paclitaxel concentration was hardly detected in normal liver tissues near liver cancer tissues.

Example 6 Liver Cancer Tissues after Carotid Artery Embolization with Lipiodol / Paclitaxel Composition

Necrosis rate measurement

As an oily contrast agent, 10 mg or 3.33 mg of paclitaxel was added to 1 ml of Lipiodol, respectively, and placed in a test tube, followed by dissolution at room temperature. Sonication was performed in a bath sonicator to speed up dissolution. It was found that paclitaxel was dissolved in Lipiodol because a uniform single liquid phase was formed after preparation. The prepared Lipiodol / Paclitaxel formulation was sterilized by passing a syringe connected to a syringe filter (200 μm pore size, PVDF filter). The liver cancer animal model prepared in Experiment 1 was supplied with tumors using microconduit with 0.3 ml (10 or 3.33 mg / ml formulation) or 0.4 ml (10 mg / ml concentration formulation) of the paclitaxel / lipiodol formulation of the present invention. Carotid artery embolization was performed. Thus, paclitaxel doses in each experimental group corresponded to 1 mg, 3 mg or 4 mg, respectively. At this time, only 0.3 cc of Lipiodol was injected into the liver cancer animal model as a control group. One week after the surgery, CT scans showed that Lipiodol was selectively detected only in the liver cancer tissues. Liver cancer animals that underwent embolization were sacrificed one week after the liver was removed. The size of the isolated liver cancer was about the same as that of the control group, which was 32 ± 5 mm in diameter, in the experimental group administered with the paclitaxel / lipiodol formulation. Pathological examination was performed to distinguish between necrotic and viable tumors in liver cancer tissues. The percentage of live tumors in all liver cancer tissues is shown in FIG. 3. More than 30% live tumors were identified in the control group treated with Lipiodol alone, but in the experimental group treated with paclitaxel / lipiodol formulation, the cancer cells were about 13.2%, 10.4% and 0.6% for the paclitaxel doses of 1mg, 3mg and 4mg, respectively. It can be seen that the decrease by more than 20%. These results show that paclitaxel in the paclitaxel / lipiodol formulation effectively kills cancer cells.

Example 7 Preparation of Lipiodol / Soybean Oil / Paclitaxel Compositions

10 mg of paclitaxel was added to 1 ml of Lipiodol and 0.2 ml of soybean oil, and the mixture was added to a test tube and stirred at room temperature to dissolve. Sonication was performed in a bath sonicator to speed up dissolution. Since the mixture forms a single liquid phase, it can be seen that paclitaxel is dissolved in Lipiodol / soybean oil, which is a mixed oil.

Example 8 Preparation of Lipiodol / Squalene / Paclitaxel Compositions

Lipiodol / squalene / paclitaxel composition was prepared in the same manner as in Example 6 except that squalane (squlane) instead of soybean oil and warmed at 40 ℃ to accelerate dissolution. Since the mixture forms a single liquid phase, it can be seen that paclitaxel is dissolved in Lipiodol / Squalene, the mixed oil.

The paclitaxel / oil-based contrast composition of the present invention is to propose a new dosage form in which the use of paclitaxel, which has been used only as an intravenous injection, as a homogeneous, highly viscous liquid, has been extended to be used for arterial embolization of solid cancer. The paclitaxel / oil-based contrast composition of the present invention is easy to manufacture and sterilize, and its components and composition are physicochemically stable than conventional adriamycin / lipiodol formulations, and thus, when used in arterial embolization for solid cancers, a stable composition is maintained until after surgery. Of course, it can maintain stability for at least 60 days at room temperature.

Claims (19)

A paclitaxel composition for chemical coloration, containing paclitaxel in a ratio of 0.0001 mg to 10 mg per 1 ml of an oily contrast agent. The chemical coloring preparation according to claim 1, wherein the oily contrast agent is an iodine content of 30 to 50% by weight of iodide oil selected from iodized poppy seed oil, ethiodol, and iodized soylbean oil. Composition. The chemical color composition according to claim 2, wherein the iodine content of the oily contrast agent is 35 to 48% by weight. The chemical color composition according to claim 2, wherein the oily contrast agent is iodide poppy seed oil having an iodine content of 35 to 48% by weight. The chemical color composition according to claim 1, which further contains animal oil or vegetable oil or a mixture thereof in a ratio of 0.1 to 1 ml with respect to 1 ml of the oily contrast agent. 6. The chemical color composition according to claim 5, wherein the animal oil is squalene and the vegetable oil is soybean oil. The composition for chemocoloring according to any one of claims 1 to 6, for the treatment of solid cancer. 8. The composition for chemical embolization for use in hepatic artery embolization according to claim 7, wherein the solid cancer is liver cancer. A single-phase, oil-based paclitaxel formulation containing paclitaxel in an amount of 0.0001 mg to 10 mg per 1 ml of an oily contrast agent and having a viscosity at room temperature of 120 to 180 cP. 10. The chemical coloring preparation according to claim 9, wherein the oily contrast agent is an iodine content of 30 to 50% by weight of iodine selected from iodized poppy seed oil, ethiodol, and iodized soylbean oil. Oily Paclitaxel Formulations. The oily paclitaxel preparation for chemical coloration according to claim 10, wherein the iodine content of the oily contrast agent is 35 to 48% by weight. The oily paclitaxel preparation for chemical coloration according to claim 10, wherein the oily contrast agent is iodide poppy seed oil having an iodine content of 35 to 48% by weight. 10. The oily paclitaxel preparation for chemical coloration according to claim 9, further comprising 0.1 to 1 ml of animal oil or vegetable oil or a mixture thereof with respect to 1 ml of the oily contrast agent. 14. The oily paclitaxel formulation for chemical coloration according to claim 13, wherein the animal oil is squalene and the vegetable oil is soybean oil. The oil-based paclitaxel formulation according to any one of claims 9 to 14, for treating solid cancer. The oil-based paclitaxel preparation for chemical embolization according to claim 15, wherein the solid cancer is liver cancer. A method of preparing an oil-based paclitaxel preparation for chemical coloration, comprising the steps of adding paclitaxel in an amount of 0.0001 mg to 10 mg with respect to 1 ml of an oily contrast agent and stirring and dissolving it at room temperature. 18. The method of claim 17 comprising mixing sterile oily contrast agent and paclitaxel under sterile conditions or subjecting to EO gas disinfection or gamma-ray disinfection. 19. The method for producing an oil-based composition according to claim 17 or 18, wherein the solution is heated or sonicated at a temperature of 35 to 45 ° C.