STABLE INJECTION OF SECUKINUMAB AND PREPARATION PROCEDURE THEREOF

Abstract

The present invention relates to a stable secukinumab injection, characterized in that it comprises 50-250 mg / ml of secukinumab, 5-50 mmol / l of histidine and histidine hydrochloride, 5-40 mmol / l of methionine, 150-370 mmol / l of low molecular weight sugar alcohol and polysorbate 80 at 0.01%-0.02% (v / v), in water for injection, pH 5.0-7.0, wherein the low molecular weight sugar alcohol is xylitol.

Description

STABLE INJECTION OF SECUKINUMAB AND PREPARATION PROCEDURE THEREOF CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority from Chinese Patent Application No. 201910412754.0, filed with the National Intellectual Property Administration of China on May 17, 2019, entitled: “STABLE INJECTION OF SECUKINUMAB AND PREPARATION PROCEDURE THEREOF”, and whose disclosures are incorporated herein by reference. FIELD This disclosure relates to the field of biopharmaceutical products and preparations, specifically to a stable secukinumab injection and the procedure for preparing it. BACKGROUND Psoriasis is a chronic immune-mediated skin disease, with approximately 125 million patients worldwide and 6.5 million psoriasis patients in China. Secukinumab is a fully humanized anti-IL-17A IgG1 monoclonal antibody. IL-17A is an inflammatory cytokine. By binding to IL-17A, the antibody directly blocks the interaction between IL-17A and its receptor, resulting in changes in immunity and inflammatory response, thus achieving the treatment target. Cosentyx® (active ingredient: secukinumab) is the world's first IL-17A-targeting biologic drug developed by Novartis, and its efficacy in treating psoriasis has been proven superior to traditional TNFα-targeting biologics such as Enbrel and Humira. However, it is not currently marketed in China, where there is a shortage of corresponding drug varieties. As a biologic antibody drug, the stability of an antibody preparation is a key factor in drug quality control. The present inventors found in their preliminary search that the original drug (CN201580076632.9) typically uses trehalose as a stabilizer. Since the use of other stabilizers is currently uncertain, there are very few domestic and international drug varieties available, leading to limited substitution options for this drug. In order to resolve the above technical problems, the present disclosure provides a stable secukinumab injection comprising 50-250 mg / ml of secukinumab, 5-50 mmol / l of histidine and histidine hydrochloride, 5-40 mmol / l of methionine, 150-370 mmol / l of low molecular weight sugar alcohol, and polysorbate 80 at 0.01%-0.02%, using water for injection as the remainder, pH 5.0-7.0. In this disclosure, the inventors have selected a class of low molecular weight sugar alcohols, preferably sorbitol or xylitol. In the field of injections, sorbitol is often used as a vehicle for sugar-free preparations and as a stabilizer for medications, with a commonly used concentration range of 10% to 25%. Xylitol, with a commonly used concentration range of 5% to 10%, is used as a sugar substitute for diabetic patients. There is no report on the application of sorbitol and xylitol in secukinumab injection. After a preliminary search of the literature and an experimental selection, the inventors found a new type of stabilizer, a class of low molecular weight sugar alcohols, especially sorbitol and xylitol.In the process of selecting the stabilizers, the inventors made a comparison between the injections added with the low molecular weight sugar alcohols and the injections of the preferred examples of the original drug, and performed stability tests, including physical stability (SEC-HPLC, polymeric protein SEC: General Requirements of the Chinese Pharmacopoeia 2015), visible particles (reference could be made to the General Requirements of the Chinese Pharmacopoeia 2015, 0904) and insoluble particles (reference could be made to the General Requirements of the Chinese Pharmacopoeia 2015, 0903) measured by the light-blocking procedure, as well as chemical stability (CEX-HPLC, lysine variant, reference could be made to the General Requirements of the Chinese Pharmacopoeia 2015, appendix IIIB) under long-term (4 °C), accelerated (25 °C) and high-temperature (40 °C) conditions.Stability results show that the stability of the secukinumab injection prepared by the present disclosure is superior to that of the secukinumab injection in the prior art (trehalose as a stabilizer, which is in the formulation of the original drug injection). Preferably, this disclosure provides a stable injection of secukinumab, comprising 100-250 mg / ml of secukinumab, 10-40 mmol / l of histidine and histidine hydrochloride, 5-40 mmol / l of methionine, 180-350 mmol / l of low molecular weight sugar alcohol and polysorbate 80 at 0.01%-0.02%, in water for injection, pH 5.5-6.5. Preferably, this disclosure provides a stable injection of secukinumab, comprising 140-200 mg / ml of secukinumab, 10-35 mmol / l of histidine and histidine hydrochloride, 5-30 mmol / l of methionine, 180-300 mmol / l of low molecular weight sugar alcohol and 0.02% polysorbate 80, in water for injection, pH 5.5-6.5. Preferably, this disclosure provides a stable injection of secukinumab, comprising 140-160 mg / ml of secukinumab, 10-30 mmol / l of histidine and histidine hydrochloride, 5-20 mmol / l of methionine, 210-280 mmol / l of low molecular weight sugar alcohol and 0.02% polysorbate 80, in water for injection, pH 5.5-6.5. Preferably, in the above-mentioned stable secukinumab injection, the low molecular weight sugar alcohol is sorbitol or xylitol. More preferably, the low molecular weight sugar alcohol is xylitol. More preferably, the pH of the injection is 5.8. This disclosure also provides a procedure for producing the above-mentioned stable secukinumab injection, comprising: 1) Buffer preparation Buffer A: Weigh histidine, methionine and low molecular weight sugar alcohol according to a formula, add water for injection until the concentrations of the formula are reached, shake and mix well; Buffer B: Weigh histidine hydrochloride, methionine and low molecular weight sugar alcohol according to a formula, add water for injection until the concentrations of the formula are reached, shake and mix well; Add buffer A to buffer B, adjusting to the final pH, which is a final buffer; and 2) preparation of a finished product a. concentrate secukinumab purified by ultrafiltration; b. Determine the concentration of the concentrated protein by extracting the concentrated protein, measuring the volume of the concentrated protein, determining the protein concentration, and starting buffer replacement when the protein concentration reaches 100-120 mg / ml; c. Replace the buffer by adding the final buffer in a volume equal to that of the concentrated protein in a sample beaker, mix well and repeat the replacement procedure several times, until the protein concentration is 100-120 mg / ml; and d. Concentrate the secukinumab by ultrafiltration after replacing the buffer, add polysorbate 80 and perform sterile filtration. Furthermore, the specific preparation procedure includes: 1) Buffer preparation: Buffer A: weighing 10-30 mmol / l of histidine, 5-20 mmol / l of methionine and 210-280 mmol / l of sorbitol according to a formula, add water for injection to reach a total volume of 7000 ml, shake and mix well; Buffer B: weighing 10-30 mmol / l of histidine hydrochloride, 5-20 mmol / l of methionine and 210-280 mmol / l of sorbitol according to a formula, add water for injection to reach a total volume of 7000 ml, shake and mix well; Add buffer A to buffer B, adjusting the pH to 5.5-6.5, which is a final buffer; 2) Preparation of a finished product: a. Transfer purified secukinumab to a sample vessel of the ultrafiltration system and start the ultrafiltration system, allowing a permeation rate of 2030 mL / min and a pressure no greater than 20 PSI (pounds per square inch) (137.895 kPa); b. Determine the concentration of the concentrated protein: extract the concentrated protein, measure the volume of the concentrated protein, determine the protein concentration using an ultra-micro spectrophotometer and begin replacing the buffer when the protein concentration reaches 100-120 mg / ml; c. Buffer replacement: Add the final buffer to an equal volume of the concentrated protein sample in a sample beaker, mix well and concentrate the protein until the protein concentration is 100-120 mg / ml and perform the replacement procedure 8 times; after each replacement, check the pH and conductivity of the final liquid from the permeate of the ultrafiltration system until they are identical or similar to those of the prepared buffer, indicating the end of the buffer replacement; d. Concentrate the secukinumab to 170-180 mg / ml by ultrafiltration after buffer replacement, collect the sample and record its volume, rinse the ultrafiltration system tubing with the buffer, collect the rinse solution and add it to the concentrated protein sample to make the protein concentration 140-160 mg / ml and the volume 1100 ml, and add polysorbate 80 to make the final polysorbate 80 concentration 0.02%. In a sterile environment, filter the resulting solution with a 0.22 µm filter membrane and then divide aliquots of the filtrate into 1 ml pre-filled syringes, a total of 1000 syringes, and label them. For the preparation process of the aforementioned secukinumab raw material, reference could be made to the original patent CN101001645A. The resulting secukinumab product has the same physical and chemical properties as the product manufactured by the original manufacturer. The purified secukinumab contains acetate buffer components and therefore has a pH of approximately 5, which does not favor the stability of the formulation. To ensure the stability of the formulation, the buffer must be replaced. This disclosure also provides for the use of stable secukinumab injection in the manufacture of a drug for the treatment of psoriasis. Through numerous selection experiments on surfactants, sugars or sugar alcohols, amino acids, excipients, etc., and on pH and buffer, respectively, the inventors selected low molecular weight sugar alcohols, such as sorbitol and xylitol, to formulate a secukinumab injection. Compared to the original drug, the stability of the secukinumab injection provided by this disclosure is significantly improved, overcoming the shortcomings of the prior art, enhancing the stability of secukinumab injections, and demonstrating outstanding industrial application. DETAILED DESCRIPTION This disclosure describes a stable injection of secukinumab and a procedure for preparing it, which those skilled in the art may achieve by appropriately improving the process parameters in light of this disclosure. It is understood that all such alternatives and modifications are obvious to those skilled in the art and are considered to be included in this disclosure. The procedure and application described herein have been described in accordance with preferred embodiments, and it is obvious that the procedure and application described herein may be changed, modified, or appropriately combined without departing from the content, spirit, and scope of this disclosure. All raw materials and reagents used in the stable secukinumab injection and the procedure for preparing them provided in this disclosure are commercially available. This disclosure will be explained in more detail below, along with examples. Experiment 1: Buffer Evaluation of the effect of different buffers (phosphate, histidine, citrate) in pre-filled syringes. Formula 1: 150 mg / ml secukinumab, 20 mmol / l sodium dihydrogen phosphate and disodium hydrogen phosphate, 5 mmol / l methionine, 200 mmol / l trehalose and 0.02% polysorbate 80, pH 5.8; Formula 2: 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 200 mmol / l trehalose and 0.02% polysorbate 80, pH 5.8; Fórmula 3: 150 mg / ml de secukinumab, 20 mmol / l de ácido cítrico y citrato de sodio, 5 mmol / l de metionina, 200 mmol / l de trehalosa y polisorbato 80 al 0.02%, pH 5.8. The three formulations were administered into pre-filled syringes, and stability tests were conducted under long-term (4°C), accelerated (25°C), and high-temperature (40°C) conditions to assess physical stability (SEC-HPLC, polymeric protein SEC: General Requirements of the Chinese Pharmacopoeia 2015), visible particles (reference to General Requirements of the Chinese Pharmacopoeia 2015, 0904), and insoluble particles (reference to General Requirements of the Chinese Pharmacopoeia 2015, 0903) measured by light-blocking, as well as chemical stability (CEX-HPLC, lysine variant; reference to General Requirements of the Chinese Pharmacopoeia 2015, Appendix IIIB). The results indicate that the histidine buffer and salt system exhibits superior stability. IVIA / a / 2U2 l / U IZO / Z Table 1. Results of the SEC-HPLC test (40 °C, 4 weeks) Sample Number Buffer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at Week 1 Main Peak Purity SEC (%) at Week 2 Main Peak Purity SEC (%) at Week 3 Main Peak Purity SEC (%) at Week 4 1 Phosphate 98.89 94.08 90.13 87.02 85.03 2 Histidine 98.87 96.34 94.71 92.04 90.57 3 Citrate 99.24 94.21 90.95 87.98 85.14 Table 2. Results of the CEX-HPLC test (40 °C, 4 weeks) Sample Number Buffer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at Week 1 Main Peak Purity CEX (%) at Week 2 Main Peak Purity CEX (%) at Week 3 Main Peak Purity CEX (%) at Week 4 1 Phosphate 84.26 74.60 71.56 64.27 55.46 2 Histidine 82.58 76.46 73.21 68.47 62.70 3 Citrate 84.81 76.25 72.60 67.05 57.89 Table 3. Results of the SEC-HPLC test (25 °C, 12 weeks) Sample Number Buffer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at Week 2 Main Peak Purity SEC (%) at Week 4 Main Peak Purity SEC (%) at Week 8 Main Peak Purity SEC (%) at Week 12 1 Phosphate 98.89 95.64 92.39 89.48 85.68 2 Histidine 98.76 96.11 94.76 93.20 91.80 3 Citrate 99.24 96.63 94.69 90.94 86.88 IVIA / a / ZUZ l / U IZO / Z Table 4. Results of the CEX-HPLC test (25 °C, 12 weeks) Sample Number Buffer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at Week 2 Main Peak Purity CEX (%) at Week 4 Main Peak Purity CEX (%) at Week 8 Main Peak Purity CEX (%) at Week 12 1 Phosphate 84.26 82.87 80.02 72.81 60.63 2 Histidine 82.58 83.30 81.88 78.27 65.99 3 Citrate 84.81 83.35 78.22 72.57 60.29 Table 5. Results of the SEC-HPLC test (4 °C, 16 weeks) Sample Number Buffer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at Week 4 Main Peak Purity SEC (%) at Week 8 Main Peak Purity SEC (%) at Week 12 Main Peak Purity SEC (%) at Week 16 1 Phosphate 98.89 95.88 92.90 89.96 86.39 2 Histidine 98.76 96.02 95.00 93.50 92.26 3 Citrate 99.24 96.02 93.05 90.16 87.49 Table 6. Results of the CEX-HPLC test (4 °C, 16 weeks) Sample Number Buffer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at Week 4 Main Peak Purity CEX (%) at Week 8 Main Peak Purity CEX (%) at Week 12 Main Peak Purity CEX (%) at Week 16 1 Phosphate 84.26 81.28 77.97 73.20 70.63 2 Histidine 84.58 82.29 80.35 79.33 77.86 3 Citrate 84.81 82.02 78.41 75.42 72.44 Experiment 2: pH Based on the formula of 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 200 mmol / l trehalose and polysorbate 80 al At 0.02% concentration, the pH was adjusted to 4.5, 5.0, 5.5, 5.8, 6.0, 6.5, and 7.0, respectively, to identify the effect of different pH levels on the stability of secukinumab. The samples were stored under high-temperature conditions for 4 weeks, and the stability of secukinumab was assessed by SEC-HPLC and CEX-HPLC. Based on the SEC-HPLC and CEX results HPLC determined that protein aggregation and hydrolysis were minimal at approximately pH 6.0. Experiment 3: Stabilizer For the development of preliminary injectable formulations, it is necessary to evaluate the effects of different stabilizers on the formation of soluble and insoluble aggregates of secukinumab (SEC-HPLC, DLS, visible particles and insoluble particles measured by the light-blocking procedure) and chemical stability (CEX-HPLC) during storage under long-term (4 °C), accelerated (25 °C), and high-temperature (40 °C) storage conditions. Sorbitol, xylitol, and trehalose were used as stabilizers, and the formulations are as follows: Formula 1: 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 239 mmol / l sorbitol and 0.02% polysorbate 80, pH 5.8; Formula 2: 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 241 mmol / l xylitol and 0.02% polysorbate 80, pH 5.8; Formula 3: 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 200 mmol / l trehalose and 0.02% polysorbate 80, pH 5.8. After the individual stability test in the initial stage, the concentrations of sorbitol and xylitol used in the above formula were the optimum concentration for stability. Based on the results, it can be seen that the formula with xylitol or sorbitol as a stabilizer has better stability than the formula with trehalose. According to the formulas in the original drug patent publication, the optimal formula of the original drug in CN201580076632.9 is Formula 3. Therefore, this disclosure overcomes existing technical problems and further improves the stability of the injection. Table 7. Results of the SEC-HPLC test (40 °C, 4 weeks) Sample Number Stabilizer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at Week 1 Main Peak Purity SEC (%) at Week 2 Main Peak Purity SEC (%) at Week 3 Main Peak Purity SEC (%) at Week 4 1 Sorbitol 98.73 97.57 96.31 96.02 95.86 2 Xylitol 98.61 97.45 96.97 96.37 96.06 3 Trehalose 98.72 96.08 94.52 93.04 91.44 Table 8. Results of the CEX-HPLC test (40 °C, 4 weeks) Sample Number Stabilizer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at Week 1 Main Peak Purity CEX (%) at Week 2 Main Peak Purity CEX (%) at Week 3 Main Peak Purity CEX (%) at Week 4 1 Sorbitol 82.77 75.14 71.99 69.83 66.02 2 Xylitol 82.67 79.92 76.80 73.43 69.02 3 Trehalose 82.77 72.05 69.84 64.14 61.07 Table 9. Results of the SEC-HPLC test (25 °C, 6 months) Sample Number Stabilizer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at 1M Main Peak Purity SEC (%) at 2M Main Peak Purity SEC (%) at 3M Main Peak Purity SEC (%) at 6M 1 Sorbitol 98.73 97.74 97.08 96.79 96.09 2 Xylitol 98.61 97.92 97.60 97.05 96.77 3 Trehalose 98.72 96.28 94.71 93.04 91.80 IVIA / a / ¿U¿ l / U IZD / Z Table 10. Results of the CEX-HPLC test (25 °C, 6 months) Sample Number Stabilizer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at 1M Main Peak Purity CEX (%) at 2M Main Peak Purity CEX (%) at 3M Main Peak Purity CEX (%) at 6M 1 Sorbitol 82.77 79.28 75.96 72.73 70.34 2 Xylitol 82.67 80.14 78.38 75.31 73.29 3 Trehalose 82.77 79.66 73.79 70.24 68.47 Table 11. Results of the SEC-HPLC test (4 °C, 6 months) Sample Number Stabilizer Main Peak Purity SEC (%) at Time Point 0 Main Peak Purity SEC (%) at 1M Main Peak Purity SEC (%) at 2M Main Peak Purity SEC (%) at 3M Main Peak Purity SEC (%) at 6M 1 Sorbitol 98.73 98.26 97.60 96.73 95.93 2 Xylitol 98.61 98.11 97.92 97.21 97.10 3 Trehalose 98.72 96.45 95.00 93.61 92.41 Table 12. Results of the CEX-HPLC test (4 °C, 6 months) Sample Number Stabilizer Main Peak Purity CEX (%) at Time Point 0 Main Peak Purity CEX (%) at 1M Main Peak Purity CEX (%) at 2M Main Peak Purity CEX (%) at 3M Main Peak Purity CEX (%) at 6M 1 Sorbitol 82.77 82.50 82.32 82.05 81.55 2 Xylitol 82.67 82.61 82.10 81.99 81.70 3 Trehalose 82.77 82.05 80.61 79.34 78.22 Example 1 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 239 mmol / l sorbitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 2 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 241 mmol / l xylitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 3 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 210 mmol / l sorbitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 4 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 280 mmol / l sorbitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 5 140 mg / ml secukinumab, 10 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 210 mmol / l sorbitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 6 160 mg / ml secukinumab, 30 mmol / l histidine and histidine hydrochloride, 20 mmol / l methionine, 280 mmol / l xylitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 7 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 210 mmol / l xylitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. Example 8 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 280 mmol / l xylitol and 0.02% polysorbate 80, in water for injection, pH 5.8. The preparation procedure is described in the Summary of this disclosure. The adjuvant materials for the previous examples and experiments are listed in Table 13. Table 13 Adjuvants Specification Manufacturer Quality Histidine 25 kg / barrel Shanghai Xiehe Amino Acid Co., Ltd. Pharmaceutical adjuvant Histidine Hydrochloride 25 kg / barrel Shanghai Xiehe Amino Acid Co., Ltd. Pharmaceutical adjuvant Methionine 100 g / bag Shanghai Wentai Biotechnology Co., Ltd. Pharmaceutical adjuvant, injectable grade Trehalose 5 kg / barrel Pfanstiehl Pharmaceutical adjuvant Polysorbate 80 100 ml / bottle Nanjing Well Pharmaceutical Co., Ltd. Pharmaceutical adjuvant, injectable grade Sorbitol 1000 g / bag Guangxi Nanning Chemical Pharmaceutical Co., Ltd. Pharmaceutical adjuvant Xylitol / Hunan Jiudian Pharmaceutical Co., Ltd. Pharmaceutical adjuvant Sodium Dihydrogen Phosphate 2000 g / bag Chengdu Huayi Pharmaceutical Excipient Manufacturing Co., Ltd. Pharmaceutical adjuvant Disodium Hydrogen Phosphate 2000 g / bag Chengdu Huayi Pharmaceutical Excipient Manufacturing Co., Ltd. Pharmaceutical Adjuvant Citric Acid 500g / bottle Hunan Er-Kang Pharmaceutical Co., Ltd.Pharmaceutical Adjuvant Sodium Citrate 500 g / bottle Hunan Er-Kang Pharmaceutical Co., Ltd. Pharmaceutical Adjuvant. The stable secukinumab injection and the preparation procedure provided herein have been described in detail above. The specific examples used herein are to illustrate the principles and embodiments of this disclosure, and the description of prior embodiments is only to aid in understanding the procedure and central idea of ​​this disclosure. It should be noted that those skilled in the art may make various improvements and modifications to this disclosure without departing from its principles, and such improvements and modifications are also included within the scope of protection of the claims herein.

Claims

1. A stable secukinumab injection comprising a stabilizer, wherein the stabilizer is a low molecular weight sugar alcohol.

2. The stable secukinumab injection according to claim 1, comprising 50-250 mg / ml secukinumab, 5-50 mmol / l histidine and histidine hydrochloride, 5-40 mmol / l methionine, 150-370 mmol / l low molecular weight sugar alcohol, and 0.01%-0.02% (v / v) polysorbate 80, in water for injection, pH 5.0-7.

0.

3. The stable secukinumab injection according to claim 1 or 2, comprising 100-250 mg / ml of secukinumab, 10-40 mmol / l of histidine and histidine hydrochloride, 5-40 mmol / l of methionine, 180-350 mmol / l of low molecular weight sugar alcohol and polysorbate 80 at 0.01%-0.02% (v / v), in water for injection, pH 5.5-6.

5. 4.The stable secukinumab injection according to claim 1 or 2, comprising 140-200 mg / ml of secukinumab, 10-35 mmol / l of histidine and histidine hydrochloride, 5-30 mmol / l of methionine, 180-300 mmol / l of low molecular weight sugar alcohol and 0.02% (v / v) polysorbate 80, in water for injection, pH 5.5-6.

5.

5. The stable secukinumab injection according to claim 1 or 2, comprising 140-160 mg / ml of secukinumab, 10-30 mmol / l of histidine and histidine hydrochloride, 5-20 mmol / l of methionine, 210-280 mmol / l of low molecular weight sugar alcohol and 0.02% (v / v) polysorbate 80, in water for injection, pH 5.5-6.

5.

6. The stable secukinumab injection according to claim 1 or 2, comprising 150 mg / ml secukinumab, 20 mmol / l histidine and histidine hydrochloride, 5 mmol / l methionine, 210-280 mmol / l low molecular weight sugar alcohol and 0.02% (v / v) polysorbate 80, in water for injection, pH 5.5-6.

5. 7.The stable injection of secukinumab according to any one of claims 1-6, wherein the low molecular weight sugar alcohol is sorbitol or xylitol.

8. The stable injection of secukinumab according to claim 7, wherein the low molecular weight sugar alcohol is xylitol.

9. The stable injection of secukinumab according to claim 7 or 8, wherein the pH of the injection is 5.

8. 10.A process for producing the stable secukinumab injection according to any one of claims 1-9, comprising 1) buffer preparation: buffer A: weighing histidine, methionine and the low molecular weight sugar alcohol according to a formula, adding water for injection to achieve the concentrations of the formula, shaking and mixing well; buffer B: weighing histidine hydrochloride, methionine and the low molecular weight sugar alcohol according to a formula, adding water for injection to achieve the concentrations of the formula, shaking and mixing well; adding buffer A to buffer B, adjusting to the final pH, which is a final buffer; and. 2) Preparation of a finished product: a. Concentrate purified secukinumab by ultrafiltration; b. Determine the concentration of the concentrated protein by extracting the concentrated protein, measuring the volume of the concentrated protein, determining the protein concentration, and beginning buffer replacement when the protein concentration reaches 100-120 mg / ml; c. Replace the buffer by adding the final buffer in a volume equal to that of the concentrated protein to a sample beaker, mixing thoroughly, and repeating the replacement procedure several times until the protein concentration is 100-120 mg / ml; and d. Concentrate the secukinumab by ultrafiltration after replacing the buffer, add polysorbate 80, and perform sterile filtration.

11. Use of the stable secukinumab injection according to any one of claims 1-9 in the manufacture of a medicament for the treatment of psoriasis.