Microcapsule containing oxaliplatin and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an oxaliplatin-containing microcapsule and a preparation method thereof. The microcapsules are prepared from the following components in parts by weight: 50 parts of oxaliplatin, 5 to 10 parts of meglumine, 1 to 5 parts of lacrotitol, 34.5 to 56.8 parts of Arabic gum, 15 to 33 parts of L-proline, 3.5 to 5.5 parts of polyethylene glycol 6000 and 4 to 8 parts of polyvinyl alcohol-polyethylene glycol grafted copolymer; the capsule material and the content of the capsule material are optimized, the encapsulation efficiency and the yield are remarkably improved, and the finally prepared preparation is relatively low in content of related substances, can be stored and applied for a long time and has a very good development value.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a microcapsule containing oxaliplatin and its preparation method. Background Technology

[0002] Oxaliplatin was developed by Debiopharm in Switzerland and manufactured and marketed by Sanofi in France. It was first launched in France in October 1996. Its structural formula is as follows:

[0003] Oxaliplatin is a platinum-based chemotherapy drug widely used to treat various cancers, especially colorectal cancer. It inhibits cancer cell proliferation by binding to DNA, forming cross-linked structures, and interfering with DNA replication and repair in cancer cells. Oxaliplatin is often used in combination with other chemotherapy drugs (such as fluorouracil and leucovorin) to enhance treatment efficacy. Oxaliplatin has better selectivity than other platinum-based drugs (such as cisplatin), especially effective against digestive system tumors such as colon cancer. However, it also has certain side effects, the most common being peripheral neuropathy (such as numbness and tingling in the hands and feet), as well as nausea, vomiting, and leukopenia. Due to its lower nephrotoxicity, oxaliplatin is more advantageous in treating patients with severe kidney damage caused by certain platinum-based drugs.

[0004] Oxaliplatin, also known as oxaliplatin or oxalate platinum, is a platinum-based derivative used clinically to treat patients with metastatic colorectal cancer who have failed fluorouracil therapy. It can be used alone or in combination with fluorouracil. It is a third-generation platinum-based antitumor compound following cisplatin and carboplatin, and is currently the only platinum-based drug with significant activity against colorectal cancer. Its mechanism of action involves producing alkylated conjugates that act on DNA, forming intra- and inter-strand cross-links to inhibit DNA synthesis and replication. It also has inhibitory effects on ovarian cancer and melanoma cell lines.

[0005] In August 2002, the U.S. Food and Drug Administration (FDA) approved Sanofi Chemicalbook's anticancer drug oxaliplatin (Eloxatin) for second-line treatment of metastatic colorectal cancer. In January 2004, the FDA officially approved injectable oxaliplatin (Eloxatin) in combination with 5-fluorouracil (5FU) and leucovorin (LV) (FOLFOX regimen) for first-line treatment of advanced colorectal cancer. The domestic market in China is currently dominated by three manufacturers: Sanofi-Aventis (Eloxatin); Jiangsu Hengrui Medicine Co., Ltd. (Aiheng); and Jiangsu Nanjing Pharmaceutical Factory (Eloxatin), who together hold over 85% of the domestic market share. Summary of the Invention

[0006] The invention provides microcapsules containing oxaliplatin, a formulation, and a method for preparing the same. The capsules prepared by the invention have a smoother dissolution curve. Through accelerated testing, the oxaliplatin-containing microcapsules prepared by the invention have a lower content of related substances (total impurities) and more stable active substances, thus solving the problem of high related substance content in oxaliplatin tablets in the prior art.

[0007] Specifically, the technical solution of the present invention is implemented as follows:

[0008] A microcapsule containing oxaliplatin, wherein the microcapsule comprises the following components by weight percentage: 50 parts by weight of oxaliplatin, 5-10 parts by weight of meglumine, 1-5 parts by weight of lactotol, 34.5-56.8 parts by weight of gum arabic, 15-33 parts by weight of L-proline, 3.5-5.5 parts by weight of polyethylene glycol 6000, and 4-8 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer.

[0009] Further, in a preferred embodiment of the invention, the microcapsule comprises the following components: 50 parts by weight of oxaliplatin, 7.5 parts by weight of meglumine, 3 parts by weight of lactotine, 45.5 parts by weight of gum arabic, 24 parts by weight of L-proline, 4.5 parts by weight of polyethylene glycol 6000, and 6 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer.

[0010] The present invention provides a method for preparing the microcapsules, comprising the following steps:

[0011] 1) Dissolve meglumine and lactotetrol in water, adjust the pH value, stir and add oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use;

[0012] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, stir to dissolve, prepare a wall material solution, cool to room temperature, and set aside.

[0013] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, spray dry, collect the microcapsules, cool, and obtain microcapsules.

[0014] Further, in a preferred embodiment of the invention, in step 1), meglumine and lactotol are dissolved in water at 45-55°C, citric acid is added to adjust the pH to 3-5, the temperature is maintained and oxaliplatin is added and stirred to dissolve, resulting in an aqueous solution containing the drug, which is then set aside.

[0015] Further, in a preferred embodiment of the invention, in step 2), gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer are added to purified water, heated and stirred at 50-60°C to dissolve, and a wall material solution with a mass fraction of 40-60% is prepared. The solution is then cooled to room temperature for later use.

[0016] Further, in a preferred embodiment of the invention, in step 3), the aqueous solution from step 1) is added to the wall material solution from step 2), homogenized and emulsified to obtain an emulsion, which is then spray-dried under conditions of an inlet air temperature of 170-180℃, a spray pressure of 0.35-0.40MPa, and a feed rate of 19.0-19.5mL / min. The microcapsules are collected, cooled, and then the microcapsules are obtained.

[0017] Furthermore, in a preferred embodiment of the invention, the method for preparing the microcapsules includes the following steps:

[0018] 1) Dissolve meglumine and lactidine in water at 50°C, add citric acid to adjust the pH to 4, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

[0019] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 55°C to dissolve, prepare a wall material solution with a mass fraction of 50%, cool to room temperature, and set aside.

[0020] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 175℃, spray pressure of 0.38MPa and feed rate of 19.25mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

[0021] This invention provides a formulation containing the microcapsules described herein, which can be any one of granules, tablets, capsules, or injections. More preferably, the formulation is a capsule.

[0022] Further, in a preferred embodiment of the invention, the preparation of the capsules includes the following components and steps: 50 parts by weight of oxaliplatin, 7.5 parts by weight of meglumine, 3 parts by weight of lactotine, 45.5 parts by weight of gum arabic, 24 parts by weight of L-proline, 4.5 parts by weight of polyethylene glycol 6000, and 6 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer.

[0023] 1) Dissolve meglumine and lactidine in water at 50°C, add citric acid to adjust the pH to 4, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

[0024] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 55°C to dissolve, prepare a wall material solution with a mass fraction of 50%, cool to room temperature, and set aside.

[0025] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 175℃, spray pressure of 0.38MPa and feed rate of 19.25mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

[0026] 4) Take the microcapsules from step 3), add an appropriate amount of lactose and micronized silica powder to obtain a mixture, fill the mixture, and polish it in a polishing machine to obtain the capsules.

[0027] Furthermore, the use of the oxaliplatin capsules prepared in this invention in the preparation of cancer drugs.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] This invention utilizes a superior encapsulation material, resulting in microcapsules with higher encapsulation efficiency and yield than conventional encapsulation materials, enabling mass production. Compared to ordinary capsules, the capsules prepared in this invention exhibit a sustained-release effect. After 6 months of storage under accelerated testing conditions (40±2℃, RH 75%±5), the microcapsules in Examples 5-7 showed no change in appearance or content, with lower levels of related substances. All microbiological indicators met requirements, demonstrating effective quality control exceeding that of general capsules. This ensures the reliability and consistency of the formulation during long-term storage and application, making it suitable for clinical use and possessing significant development potential. Attached Figure Description

[0030] Figure 1 The effects of different encapsulation materials on encapsulation efficiency and yield in different embodiments of the present invention.

[0031] Figure 2 Comparison of the dissolution (%) of the capsules prepared in this invention at different time points from 20 to 200 min.

[0032] Figure 3 Changes in the content of relevant substances in the embodiments of the present invention after being placed under accelerated test conditions (40±2℃, RH75%±5) for 6 months. Detailed Implementation

[0033] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0034] Example 1: A microcapsule containing oxaliplatin, prepared by the following method:

[0035] The preparation method includes the following steps

[0036] Dissolve meglumine and lactidine in water at 50°C, add citric acid to adjust the pH to 4, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

[0037] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 55°C to dissolve, prepare a wall material solution with a mass fraction of 50%, cool to room temperature, and set aside.

[0038] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 175℃, spray pressure of 0.38MPa and feed rate of 19.25mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

[0039] Example 2: A microcapsule containing oxaliplatin, prepared by the following method:

[0040] The preparation method includes the following steps

[0041] Dissolve meglumine and lactidine in water at 45°C, add citric acid to adjust the pH to 3, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

[0042] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 50°C to dissolve, prepare a wall material solution with a mass fraction of 40%, cool to room temperature, and set aside.

[0043] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 170℃, spray pressure of 0.35MPa and feed rate of 19.0mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

[0044] Example 3: A microcapsule containing oxaliplatin, prepared by the following method:

[0045] The preparation method includes the following steps

[0046] Dissolve meglumine and lactidine in water at 55°C, add citric acid to adjust the pH to 5, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

[0047] 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 60°C to dissolve, prepare a wall material solution with a mass fraction of 60%, cool to room temperature, and set aside.

[0048] 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 180℃, spray pressure of 0.40MPa and feed rate of 19.5mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

[0049] Example 4: A tablet containing oxaliplatin microcapsules, prepared as follows:

[0050] Take the microcapsules from Example 3, add 205g of microcrystalline cellulose, mix well and dry, pulverize and sieve, granulate, dry at low temperature, granulate, add 3g of magnesium stearate and 15g of sodium carboxymethyl starch, mix well, compress into tablets, and obtain the final product.

[0051] Example 5: A capsule containing oxaliplatin microcapsules, the preparation method of which is as follows:

[0052] Take the microcapsules from Example 1, take the microcapsules from step 3), add 200g of lactose and 43g of micronized silica gel to obtain a mixture, fill the mixture, and polish it in a grinder to obtain capsules containing oxaliplatin microcapsules.

[0053] Example 6: A capsule containing oxaliplatin microcapsules, the preparation method of which is as follows:

[0054] Take the microcapsules from Example 2, take the microcapsules from step 3), add 160g of lactose and 33.7g of micronized silica gel to obtain a mixture. Fill the mixture into containers and polish it in a polishing machine to obtain capsules containing oxaliplatin microcapsules.

[0055] Example 7: A capsule containing oxaliplatin microcapsules, the preparation method of which is as follows:

[0056] Take the microcapsules from Example 3, take the microcapsules from step 3), add 180g of lactose and 40g of micronized silica gel to obtain a mixture, fill the mixture, and polish it in a grinder to obtain capsules containing oxaliplatin microcapsules.

[0057] Comparative Example 1: A microcapsule containing oxaliplatin, prepared by the following method:

[0058] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0059] Comparative Example 2: A microcapsule containing oxaliplatin, prepared by the following method:

[0060] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0061] Comparative Example 3: A microcapsule containing oxaliplatin, prepared by the following method:

[0062] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0063] Comparative Example 4: A microcapsule containing oxaliplatin, prepared by the following method:

[0064] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0065] Comparative Example 5: A microcapsule containing oxaliplatin, prepared by the following method:

[0066] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0067] Comparative Example 6: A microcapsule containing oxaliplatin, prepared by the following method:

[0068] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0069] Comparative Example 7: A capsule containing oxaliplatin, prepared by the following method:

[0070] Add meglumine, lactotine, gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, stir at 60°C, add oxaliplatin to dissolve, cool to room temperature, add 180g of lactose and 40g of micronized silica powder, granulate, sieve, dry and fill into capsules to obtain the final product.

[0071] Comparative Example 8: A capsule containing oxaliplatin, prepared by the following method:

[0072] The oxaliplatin microcapsules were prepared according to the method described in Example 3; the capsules of the oxaliplatin microcapsules were prepared according to the method described in Example 7.

[0073] 1. Determination of Oxaliplatin Microencapsulation Efficiency

[0074] Encapsulation efficiency refers to the percentage of actual drug content in the microcapsules relative to the total drug content (i.e., drug loading) in the microcapsule sample; that is, the percentage of drug content in the prepared microcapsules relative to the total drug content of the system. A higher encapsulation efficiency indicates a better degree of drug encapsulation. The specific methods for determining the microcapsule encapsulation efficiency in each embodiment are as follows.

[0075] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; the mobile phase was phosphoric acid solution (0.6 mL of 10% phosphoric acid solution, diluted with water to 1000 mL, and the pH adjusted to 3.0 with sodium hydroxide solution or phosphoric acid) - acetonitrile (99:1); the detection wavelength was 210 nm. Approximately 10 mg of the sample was dissolved in 2 mL of hydrogen peroxide test solution, diluted with water to 10 mL, and shaken well. This solution was used as the system suitability test solution. Immediately 10 μL was injected into the liquid chromatograph, and the chromatogram was recorded. The peak elution order was: hydrogen peroxide solvent peak, impurity peak, and oxaliplatin peak. The resolution between the impurity peak and the oxaliplatin peak should be greater than 10.0.

[0076] Preparation of the reference solution: Accurately weigh an appropriate amount of oxaliplatin and add water to prepare a solution containing 0.05 mg per 1 mL.

[0077] Preparation of the test solution: Accurately weigh an appropriate amount of microcapsule samples from each embodiment and place them in a 100 mL volumetric flask. Dilute to 100 mL with 85% ethanol and shake well to ensure that all extracts from the outer surface of the microcapsules are completely dissolved in the ethanol solution. Accurately transfer 10 mL of the above solution to a 25 mL volumetric flask and dilute to the mark with 85% ethanol aqueous solution. Shake well and filter. Take 5 mL of the solution and place it in a 100 mL volumetric flask. Dissolve the sample in the phosphate solution-acetonitrile buffer solution and dilute to 100 mL. Shake well to ensure that all extracts from the outer surface of the microcapsules and the microcapsules are completely dissolved in the buffer solution. Repeat the above steps to obtain the test solution.

[0078] For the assay, 20 μl of standard solution and test solution were injected respectively. The amount of extract (m) on the outer surface of the microcapsules and the amount of total extract (M) of the microcapsules were calculated using the external standard two-point method.

[0079] Encapsulation efficiency = (Total drug amount M in the microcapsule sample - Drug amount m outside the microcapsule) × 100% / Total drug amount M in the microcapsule sample.

[0080] Depend on Figure 1 It can be seen that the encapsulation efficiency and yield of microcapsules vary with the selection of different encapsulation materials. Experimental results show that the optimal encapsulation efficiency and yield are achieved when the ratio of gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer is 45.5:24:4.5:6, significantly higher than other combinations and amounts of encapsulation materials. Microcapsules using gum arabic and conventional encapsulation materials, as described in existing patents and literature, exhibit poor encapsulation efficiency, making mass production difficult.

[0081] 2. In vitro cumulative dissolution test

[0082] The dissolution of microcapsules prepared in Example 3 and Comparative Examples 7-8 of this invention was compared. Dissolution time (min) was plotted on the x-axis to examine the cumulative dissolution percentage (%) of the above examples at 20, 40, 60, 80, 100, 120, 140, 160, 180, and 200 min. See Appendix. Figure 2 .

[0083] Figure 2 It can be seen that the cumulative dissolution percentage of the microcapsules in Example 7 was less than 60% within 60 minutes, and reached more than 90% dissolution within 140 minutes. It can be determined that, compared with the ordinary capsules in Comparative Example 7, the present invention has a certain sustained-release effect. Although Comparative Example 8 has a sustained-release effect, the overall dissolution effect is too slow and does not meet the release requirements.

[0084] 3. Determination of related substances

[0085] To verify the stability of the microcapsule formulations of Examples 5-7 of this invention, the inventors conducted accelerated stability tests on all microcapsules of the comparative examples. It should be noted that the samples selected for the microcapsule formulations of Examples 5-7 used in this experiment are samples obtained from representative formulations and preparation processes of this invention. Due to space limitations, the tests and results related to samples obtained from other formulations and preparation methods included in this invention are not exhaustively listed here.

[0086] Impurities in oxaliplatin were determined according to Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0087] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the packing material; the mobile phase was phosphoric acid solution (0.6 mL of 10% phosphoric acid solution was diluted with water to 1000 mL, and the pH was adjusted to 3.0 with sodium hydroxide solution or phosphoric acid) - acetonitrile (99:1); the detection wavelength was 210 nm.

[0088] Test solution: Take about 10 mg of microcapsules from Examples 5-7 and Comparative Examples 1-2, add 2 mL of hydrogen peroxide test solution to dissolve, dilute with water to 10 mL, shake well, and use as the system suitability solution. Immediately inject 10 μl into the liquid chromatograph and record the chromatogram. The peak order should be hydrogen peroxide solvent peak, impurity III peak, and oxaliplatin peak. The resolution between impurity III peak and oxaliplatin peak should be greater than 10.0.

[0089] For the assay, accurately weigh oxaliplatin and place it in a 100 mL volumetric flask. Dissolve and dilute to the mark with water, shake well, and use this as the test solution. Accurately inject 20 μL into the liquid chromatograph and record the chromatogram. Calculate the result by peak area using the external standard method.

[0090] Accelerated stability testing was conducted on two batches of samples of this invention (microcapsules of Examples 5-7 and microcapsules of Comparative Examples 1-2) in aluminum-plastic packaging (24 capsules / sample) using an accelerated stability test chamber (40±2℃, RH 75%±5) for 6 months, with samples taken at 0, 1, 2, 3, and 6 months respectively. The specific details are as follows: Figure 3 As shown.

[0091] Figure 3 After being placed under accelerated stability testing conditions (40±2℃, RH 75%±5) for 6 months, the microcapsules of Examples 5-7 showed no change in appearance or content, and the content of related substances was low. All microbiological indicators met the requirements. Based on the above accelerated stability test results, the microcapsule formulations of Examples 5-7 prepared by this invention exhibit good stability, and their quality is effectively controlled to a level higher than that of general capsules, ensuring the reliability and consistency of the formulations during long-term storage and application.

[0092] 4. Investigation of the physical stability of capsules in accelerated experiments

[0093] The capsules of Examples 5-7 and Comparative Examples 1-2 of this invention were subjected to accelerated stability testing under accelerated conditions (40±2℃, RH 75%±5) for 6 months. At the 6-month mark, their shape and microbial content were examined. The detection methods were based on the 2020 edition of the Chinese Pharmacopoeia, Part IV. The results are shown in Table 1.

[0094] Table 1. Physical properties of the capsules in Examples 5-7 and Comparative Examples 1-2

Claims

1. A microcapsule containing oxaliplatin, characterized in that, The microcapsules, by weight percentage, comprise the following components: 50 parts by weight of oxaliplatin, 5-10 parts by weight of meglumine, 1-5 parts by weight of lactotine, 34.5-56.8 parts by weight of gum arabic, 15-33 parts by weight of L-proline, 3.5-5.5 parts by weight of polyethylene glycol 6000, and 4-8 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer; the preparation method of the microcapsules includes the following steps. 1) Dissolve meglumine and lactotetrol in water, adjust the pH value, stir and add oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use; 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, stir to dissolve, prepare a wall material solution, cool to room temperature, and set aside. 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, spray dry, collect the microcapsules, cool, and obtain microcapsules.

2. The microcapsule as described in claim 1, characterized in that, The microcapsules comprise the following components: 50 parts by weight of oxaliplatin, 7.5 parts by weight of meglumine, 3 parts by weight of lactotine, 45.5 parts by weight of gum arabic, 24 parts by weight of L-proline, 4.5 parts by weight of polyethylene glycol 6000, and 6 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer.

3. The microcapsule as described in claim 1, characterized in that, The microcapsules include the following components: Step 1) Dissolve meglumine and lactidine in water at 45-55°C, add citric acid to adjust the pH to 3-5, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use.

4. The microcapsule as described in claim 1, characterized in that, The microcapsules include the following components: Step 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 50-60°C to dissolve, prepare a wall material solution with a mass fraction of 40-60%, cool to room temperature, and set aside.

5. The microcapsule as described in claim 1, characterized in that, The microcapsules comprise the following components: Step 3) The aqueous solution from Step 1) is added to the wall material solution from Step 2), homogenized and emulsified to obtain an emulsion, which is then spray-dried under conditions of an inlet air temperature of 170-180℃, a spray pressure of 0.35-0.40MPa, and a feed rate of 19.0-19.5mL / min. The microcapsules are collected, cooled, and then obtained.

6. The microcapsule as described in claim 1, characterized in that, The method for preparing the microcapsules includes the following steps: 1) Dissolve meglumine and lactidine in water at 50°C, add citric acid to adjust the pH to 4, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use. 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 55°C to dissolve, prepare a wall material solution with a mass fraction of 50%, cool to room temperature, and set aside. 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 175℃, spray pressure of 0.38MPa and feed rate of 19.25mL / min. Collect the microcapsules, cool them, and obtain microcapsules.

7. A formulation comprising the microcapsules according to any one of claims 1-6, characterized in that, The formulation may be any one of granules, tablets, capsules or injections.

8. The formulation as described in claim 7, characterized in that, Its features are, The preparation is a capsule.

9. The formulation as described in claim 8, characterized in that, The preparation of the capsules includes the following components and steps: 50 parts by weight of oxaliplatin, 7.5 parts by weight of meglumine, 3 parts by weight of lactotine, 45.5 parts by weight of gum arabic, 24 parts by weight of L-proline, 4.5 parts by weight of polyethylene glycol 6000, and 6 parts by weight of polyvinyl alcohol-polyethylene glycol graft copolymer. 1) Dissolve meglumine and lactidine in water at 50°C, add citric acid to adjust the pH to 4, maintain the temperature and stir while adding oxaliplatin to dissolve, and obtain an aqueous solution containing the drug for later use. 2) Add gum arabic, L-proline, polyethylene glycol 6000, and polyvinyl alcohol-polyethylene glycol graft copolymer to purified water, heat and stir at 55°C to dissolve, prepare a wall material solution with a mass fraction of 50%, cool to room temperature, and set aside. 3) Add the aqueous solution from step 1) to the wall material solution from step 2), homogenize and emulsify to obtain an emulsion, and spray dry it under the conditions of inlet air temperature of 175℃, spray pressure of 0.38MPa and feed rate of 19.25mL / min. Collect the microcapsules, cool them, and obtain microcapsules. 4) Take the microcapsules from step 3), add an appropriate amount of lactose and micronized silica powder to obtain a mixture, fill the mixture, and polish it in a polishing machine to obtain the capsules.

10. Use of the oxaliplatin formulation of claim 7 in the preparation of a cancer treatment drug.

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