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CN-121971603-A - Medicine composition containing Vidixituzumab and preparation method and application thereof

CN121971603ACN 121971603 ACN121971603 ACN 121971603ACN-121971603-A

Abstract

The invention belongs to the field of medicines, and particularly relates to a medicine composition containing midecatuzumab and a preparation method and application thereof. The composition comprises the midecatuzumab, the Carilizumab, the trehalose, the L-, ornithine, a histidine buffer system and the polysorbate 80, and has the advantages of high stability, quick redissolution and low protein aggregate content after being prepared into freeze-dried powder. The invention also provides the application of the compound and the tegafur combined drug for treating the gastric cancer in the local progressive stage, and the combined use of the three drugs has obvious synergistic curative effect.

Inventors

  • CHAI JIE
  • WANG LONGGANG
  • LI RONG
  • SUN DONG

Assignees

  • 山东第一医科大学附属肿瘤医院(山东省肿瘤防治研究院、山东省肿瘤医院)

Dates

Publication Date
20260505
Application Date
20260407

Claims (10)

  1. 1. A pharmaceutical composition containing the Vidixituzumab and the Carlizumab is characterized by comprising the following components in parts by weight: 。
  2. 2. the pharmaceutical composition of claim 1, wherein the ratio of trehalose to ornithine is 18.55-28.45:37.10-56.90, and more preferably wherein the ratio of trehalose to ornithine is 1:2.
  3. 3. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises the following components in parts by weight: 。
  4. 4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a lyophilized powder.
  5. 5. A method for preparing the freeze-dried powder according to claim 4, which is characterized by comprising the following steps: 1) Weighing trehalose with a prescription amount, adding the trehalose into a pre-prepared histidine buffer system, adding a proper amount of water for injection, stirring until the trehalose is completely dissolved, and adjusting the pH of the system to 5.5-6.5 by using a proper regulator for later use; 2) Sequentially weighing the prescribed amounts of L-ornithine, polysorbate 80, midothiotal antibody and Caririzumab in the standby system, stirring and mixing uniformly after each feeding, adding water for injection to the prescribed total amount, and stirring uniformly to obtain semi-finished product liquid for standby; 3) Sampling to detect the pH value, the protein content and the appearance of the semi-finished product liquid, after the semi-finished product liquid is qualified, performing sterile filtration on the semi-finished product liquid by using a 0.22 mu m filter membrane, sampling again to detect the pH value, the protein content and the appearance after the filtration, and confirming the qualification; 4) And (3) detecting endotoxin in the filtered qualified filtrate, filling and half-plugging the qualified filtrate, and freeze-drying the qualified filtrate in a freeze dryer to obtain mixed freeze-dried powder of the Vidixituzumab and the Carrilizumab.
  6. 6. The method according to claim 5, wherein the preparation of the freeze-dried powder comprises the following steps: 1) Weighing trehalose with a prescription amount, adding the trehalose into a pre-prepared 15mM histidine buffer system, adding a proper amount of water for injection, stirring until the trehalose is completely dissolved, and adjusting the pH of the system to 6.0 by a proper regulator for later use; 2) Sequentially weighing the prescribed amounts of L-ornithine, polysorbate 80, midothiotal antibody and Caririzumab in the standby system, stirring and mixing for 15-20 min after each feeding until the mixture is uniform, adding water for injection to the prescribed total amount, and stirring the mixture uniformly to obtain a semi-finished product liquid for standby; 3) Sampling to detect the pH value, the protein content and the appearance of the semi-finished product liquid, after the semi-finished product liquid is qualified, performing sterile filtration on the semi-finished product liquid by using a 0.22 mu m filter membrane, sampling again to detect the pH value, the protein content and the appearance after the filtration, and confirming the qualification; 4) And (3) detecting endotoxin in the filtered qualified filtrate, filling and half-plugging the qualified filtrate, and freeze-drying the qualified filtrate in a freeze dryer to obtain the anti-freezing dry powder of the Vidixituzumab and the CarRui Li Zhushan.
  7. 7. The method according to claim 5, wherein the lyophilization process comprises three stages of pre-freezing, primary drying and secondary drying, and specifically comprises the steps of: (1) Pre-freezing, namely placing the penicillin bottle filled with the qualified filtrate on a baffle plate of a freeze dryer, pre-freezing at 5 ℃ for 15-60 min, then slowly cooling to-40 to-35 ℃ for 4-8 h, and finishing pre-freezing; (2) After the pre-freezing is finished, slowly heating the temperature of a separator system of the freeze dryer to-15 to-10 ℃ for 35-40 hours, then continuously heating to 0-5 ℃ for 10-12 hours, and finishing the primary drying; (3) And (3) secondary drying, namely after the primary drying is finished, heating the temperature of the separator system to 20-30 ℃, maintaining for 8-10 h for analytical drying, and pressing a plug and rolling a cover after the drying is finished, so that the whole freeze-drying process is finished.
  8. 8. The application of a combination drug of a tigogenin preparation, the vitamin E and the Carlizumab in preparing a drug for relieving or treating gastric cancer in a local advanced stage is disclosed, wherein the weight ratio of the tigogenin preparation to the vitamin E is 0.5:1.5-2.5:2-3, and more preferably 0.5:1.875:2.5.
  9. 9. The use according to claim 8, wherein the initial amounts of tig, vedio and carlizumab in the combination are 80mg, 150mg and 200mg, respectively, wherein tig is administered orally and vedio and carlizumab is administered by injection.
  10. 10. The use according to claim 9, wherein the tegafur preparation is a preparation prepared from tegafur, gimeracil, potassium octreotide and pharmaceutically acceptable excipients, further preferably a commercially available tegafur capsule, further preferably a vitamin Kang Da tegafur capsule.

Description

Medicine composition containing Vidixituzumab and preparation method and application thereof Technical Field The invention belongs to the field of medicines, and in particular relates to a medicine composition containing midecatuzumab and a preparation method and application thereof Background Gastric cancer is one of high-incidence malignant tumors in China, and patients with gastric cancer in local development stage have wide tumor infiltration range, low surgical excision rate, easy recurrence and metastasis and high clinical treatment difficulty. At present, single chemotherapy, targeted therapy or immunotherapy has limited curative effect, low objective remission rate, and a combined treatment scheme with better curative effect, better safety and more convenient administration is needed urgently. The midecarboxumab is an Antibody Drug Conjugate (ADC) targeting HER2, and has definite anti-tumor effect on HER2 positive gastric cancer. CarRui Li Zhushan is anti-PD & # x2011, 1 immune checkpoint inhibitor, and can activate body anti-tumor immunity. The combination of the two has potential synergistic effect. However, in clinic, the two drugs are mainly prepared and infused separately, and the problems of complicated operation, poor stability, poor patient compliance and the like exist. The antibody drug is sensitive to pH, temperature and ionic strength, and the liquid preparation is easy to cause protein aggregation, degradation and activity reduction. Therefore, developing a stable, well-reconstituted, compound lyophilized preparation of the Vidixizumab and the Carrilizumab, which is suitable for industrial production, has important clinical value. Disclosure of Invention Tigeolone is taken as a basic oral chemotherapeutic medicine for late gastric cancer, and can further improve the curative effect by being combined with targeted and immune medicines. At present, a fixed dose ratio and a compound preparation scheme of the tergeolone, the vecitumumab and the kari Li Zhushan anti-triple drug for treating the gastric cancer in the local progressive stage are still disclosed. The invention provides stable diabody freeze-dried powder by optimizing a prescription, a buffer system and a freeze-drying process, and the triple drug proportion is defined, so that the defects in the prior art are overcome. Specifically, the technical scheme of the invention is as follows: A pharmaceutical composition containing midecatuzumab and carlizumab, wherein the pharmaceutical composition comprises the following components in parts by weight: Specifically, the ratio of trehalose to ornithine is 18.55-28.45:37.10-56.90, and more preferably, the ratio of trehalose to ornithine is 1:2. Specifically, the pharmaceutical composition further comprises the following components in parts by weight: Specifically, the pharmaceutical composition is further freeze-dried powder. The second aim of the invention is to provide the preparation of the freeze-dried powder, which comprises the following steps: 1) Weighing trehalose with a prescription amount, adding the trehalose into a pre-prepared histidine buffer system, adding a proper amount of water for injection, stirring until the trehalose is completely dissolved, and adjusting the pH of the system to 5.5-6.5 by using a proper regulator for later use; 2) Sequentially weighing the prescribed amounts of L-ornithine, polysorbate 80, midothiotal antibody and Caririzumab in the standby system, stirring and mixing uniformly after each feeding, adding water for injection to the prescribed total amount, and stirring uniformly to obtain semi-finished product liquid for standby; 3) Sampling to detect the pH value, the protein content and the appearance of the semi-finished product liquid, after the semi-finished product liquid is qualified, performing sterile filtration on the semi-finished product liquid by using a 0.22 mu m filter membrane, sampling again to detect the pH value, the protein content and the appearance after the filtration, and confirming the qualification; 4) And (3) detecting endotoxin in the filtered qualified filtrate, filling and half-plugging the qualified filtrate, and freeze-drying the qualified filtrate in a freeze dryer to obtain mixed freeze-dried powder of the Vidixituzumab and the Carrilizumab. Specifically, the preparation of the freeze-dried powder further comprises the following steps: 1) Weighing trehalose with a prescription amount, adding the trehalose into a pre-prepared 15mM histidine buffer system, adding a proper amount of water for injection, stirring until the trehalose is completely dissolved, and adjusting the pH of the system to 6.0 by a proper regulator for later use; 2) Sequentially weighing the prescribed amounts of L-ornithine, polysorbate 80, midothiotal antibody and Caririzumab in the standby system, stirring and mixing for 15-20 min after each feeding until the mixture is uniform, adding water for injection to the prescribed total amount, and sti