Quick-acting cloprostenol sodium injection and preparation method thereof
By adding metal chelating agents and antioxidants to sodium cloprostenol injection and controlling the pH value, the problem of easy oxidation of sodium cloprostenol was solved, and a fast-acting sodium cloprostenol injection with high stability was prepared to meet the reproductive needs of female animals.
Patent Information
- Application Number
- CN202511712564.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-20
- Publication Date
- 2026-03-03
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Sodium cloprostol is easily oxidized and hydrolyzed, leading to drug degradation. Existing injection solutions lack stability and efficiency, making it difficult to meet the reproductive quality requirements of female animals.
The injection solution is prepared using 0.008-0.012% sodium cloprostenol, 0.002-0.003% metal chelating agent (such as disodium edetate), and 0.08-0.11% antioxidant (such as sodium thiosulfate). The solution is prepared through steps such as stirring, filtration, filling, and sealing, and the pH value is controlled at 6.5-7 to ensure drug stability.
The prepared fast-acting sodium cloprostenol injection effectively inhibits drug oxidative degradation, improves the reproductive quality of female animals, has good stability and induction effect, and is suitable for estrus synchronization and parturition induction in female animals.
Abstract
Description
Technical Field
[0001] This application relates to the field of veterinary drug technology, specifically to a fast-acting sodium cloprostenol injection and its preparation method. Background Technology
[0002] Under natural conditions, different female animals have different estrus cycles and farrowing times, which greatly increases the difficulty, workload, and cost of production management in large-scale farms. In actual production, drugs are often used to control and adjust the estrus process of a group of female animals, so that they come into estrus at a predetermined time, in order to carry out large-scale artificial insemination and embryo transfer, or to induce female animals to give birth at the same time to avoid nighttime births.
[0003] Cloprostol sodium is a synthetic PGF2a analog with biological effects similar to prostaglandins. It has a strong corpus luteum-dissolving effect, rapidly causing corpus luteum regression, inhibiting its secretion, reducing and stopping progesterone production, and promoting estrus. Simultaneously, cloprostol sodium also has a direct excitatory effect on uterine smooth muscle, causing contraction of uterine smooth muscle and mammary epithelial cells, cervical relaxation, and participating in parturition and lactation. Clinically, it can be used to treat anestrus in gilts and weaned sows, induce synchronous parturition in sows, and induce synchronous estrus in dairy cows. However, cloprostol sodium is sensitive to light, heat, and metal ions, and is easily oxidized and hydrolyzed, leading to degradation of the active ingredient. Therefore, there is a need for a cloprostol sodium injection solution that effectively improves the reproductive quality and stability of female animals. Summary of the Invention
[0004] To address the aforementioned issues, this application provides a fast-acting sodium cloprostenol injection solution and its preparation method for effectively improving the reproductive quality of female livestock.
[0005] To achieve the above objectives, this application provides a rapid-acting sodium cloprostenol injection, the injection comprising: 0.008-0.012% (W / V) sodium cloprostenol, 0.002-0.003% (W / V) metal chelating agent, 0.08-0.11% (W / V) antioxidant, and the balance being water for injection.
[0006] Furthermore, the metal chelating agent is disodium edetate or calcium sodium EDTA.
[0007] Furthermore, the antioxidant is sodium thiosulfate or vitamin C.
[0008] A method for preparing a rapid-acting sodium cloprostenol injection includes the following steps: S1. Add a metal chelating agent and an antioxidant to water for injection and stir. Add sodium cloprostenol and continue stirring. Add the remaining volume of water for injection and adjust the pH value to obtain the semi-finished sodium cloprostenol injection solution. S2. Filter, fill, seal and package the semi-finished sodium cloprostenol injection to obtain fast-acting sodium cloprostenol injection.
[0009] Furthermore, the stirring in step S1 is performed at a speed of 80-100 rpm for a time of 10-15 min.
[0010] Furthermore, the pH value is adjusted to 6.5-7 as described in step S1.
[0011] Furthermore, in step S2, the filtration process uses a filter membrane with a pore size of ≤0.22μm.
[0012] In summary, this application has the following beneficial effects: The fast-acting cloprostenol sodium injection prepared in this application uses disodium edetate to chelate metal ions, inhibiting the degradation of the drug catalyzed by metal ions, and sodium thiosulfate to remove free radicals in the drug solution, preventing the oxidative degradation of the active ingredient. Combined with appropriate pH adjustment and sterilization process, the antioxidant properties and safety of cloprostenol sodium injection can be ensured, meeting the needs of animal clinical drug use. Moreover, the preparation method of this application is simple, easy to operate, and applicable to industrial production. Detailed Implementation
[0013] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.
[0014] The raw materials used in the specific embodiments of this application are of analytical grade. Additionally: sodium chloroprostaglandin was purchased from Zouping Mingyuan Import & Export Trading Co., Ltd., item number P22954381; disodium edetate was purchased from Wuhan Xinxin Jiali Biotechnology Co., Ltd., item number 139333; and sodium thiosulfate was purchased from Jinan Century Tongda Chemical Co., Ltd., item number 23.
[0015] Example 1 A method for preparing a rapid-acting sodium cloprostenol injection includes the following steps: S1. Take 75ml of water for injection, then add 2mg of disodium edetate and 80mg of sodium thiosulfate and stir (80rpm, 10min). Then add 8mg of sodium cloprostenol and stir (80rpm, 10min). Then add water for injection to 100ml. Then adjust the pH to 6.5 with 0.1mol / L sodium hydroxide to obtain the semi-finished product sodium cloprostenol injection. S2. Filter the semi-finished sodium cloprostenol injection solution through a 0.22μm filter, fill, seal and package to obtain rapid-acting sodium cloprostenol injection solution.
[0016] Example 2 A method for preparing a rapid-acting sodium cloprostenol injection includes the following steps: S1. Take 75ml of water for injection, then add 2.5mg of disodium edetate and 100mg of sodium thiosulfate in sequence and stir (80rpm, 10min). Then add 10mg of sodium cloprostenol and stir (80rpm, 10min). Then add water for injection to 100ml. Then adjust the pH to 6.8 with 0.1mol / L sodium hydroxide to obtain the semi-finished product sodium cloprostenol injection. S2. Filter the semi-finished sodium cloprostenol injection solution through a 0.22μm filter, fill, seal and package to obtain rapid-acting sodium cloprostenol injection solution.
[0017] Example 3 A method for preparing a rapid-acting sodium cloprostenol injection includes the following steps: S1. Take 75ml of water for injection, then add 3.0mg of disodium edetate and 110mg of sodium thiosulfate and stir (80rpm, 10min). Then add 12mg of sodium cloprostenol and stir (80rpm, 10min). Then add water for injection to 100ml. Then adjust the pH to 7 with 0.1mol / L sodium hydroxide to obtain the semi-finished product sodium cloprostenol injection. S2. Filter the semi-finished sodium cloprostenol injection solution through a 0.22μm filter, fill, seal and package to obtain rapid-acting sodium cloprostenol injection solution.
[0018] Compare with Example 1 A method for preparing a rapid-acting sodium cloprostenol injection includes the following steps: S1. Take 75ml of water for injection, then add 3.0mg of disodium edetate and 110mg of sodium thiosulfate in sequence and stir (80rpm, 10min). Then add 12mg of sodium cloprostenol and stir (80rpm, 10min). Then add water for injection to 100ml. Then adjust the pH to 8 with 0.1mol / L sodium hydroxide to obtain the semi-finished product sodium cloprostenol injection. S2. Filter the semi-finished sodium cloprostenol injection solution through a 0.22μm filter, fill, seal and package to obtain rapid-acting sodium cloprostenol injection solution.
[0019] Performance testing Quality tests were conducted on Examples 1-3 and Control Example 1.
[0020] Experiment to induce estrus synchronization in cows: Experimental animals: Ayrshire cattle, 100 growing cows weighing over 350kg, free from reproductive system diseases and never bred.
[0021] Experimental Methods: Animals meeting the above experimental requirements were randomly divided into 5 groups without considering the estrous cycle: Group 1 (20 animals), Group 2 (20 animals), Group 3 (20 animals), Control Group 1 (20 animals), and a blank control group (20 animals). Groups 1, 2, 3, and Control Group 1 were injected with 2 ml of the corresponding prepared rapid-acting cloprostenol sodium injection, while the blank control group was injected with physiological saline. The injections were administered twice, 11 days apart, via intramuscular injection. Estrus was observed from day 3 to 5 post-injection, three times daily (morning, noon, and evening) by designated personnel, and verified through rectal examination. The estrus synchronization rate of the experimental dairy cows was statistically analyzed.
[0022] Stability test: The rapid-acting sodium cloprostenol injection solutions prepared in Examples 1-3 and Control Example 1 were placed at 40°C / 75%RH for 6 months, and the content of sodium cloprostenol after 6 months was detected by high performance liquid chromatography.
[0023] The results are shown in Table 1.
[0024] Table 1: Performance Test Results ; As shown in Table 1, the fast-acting cloprostenol sodium injection prepared in Examples 1-3 of this application has a good effect on inducing estrus synchronization in cows and good stability. According to the results in Table 1, it has a high estrus synchronization rate, especially Example 2, which has the best effect. Compared with Example 3, the pH value of the injection was increased in Control Example 1. The results showed that the estrus synchronization rate of Control Example 1 was not as high as that of Example 3, the effect of inducing estrus synchronization in cows was not as good as that of Example 3, and the stability was not as good as that of Example 3. After a 6-month stability test, the cloprostenol sodium content in the injection was much lower than that of Example 3, indicating that Control Example 1 was not as good as Example 3.
[0025] The above description is merely an example and illustration of the concept of this application. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the inventive concept or exceed the scope defined in the claims, they should all fall within the protection scope of this application.
Claims
1. A fast-acting sodium cloprostenol injection, characterized in that, The injection solution comprises: 0.008-0.012% (W / V) sodium cloprostenol, 0.002-0.003% (W / V) metal chelating agent, 0.08-0.11% (W / V) antioxidant, and the balance being water for injection.
2. The rapid-acting cloprostenol sodium injection according to claim 1, characterized in that, The metal chelating agent is disodium edetate or calcium sodium EDTA.
3. The rapid-acting cloprostenol sodium injection according to claim 1, characterized in that, The antioxidant is sodium thiosulfate or vitamin C.
4. A method for preparing the rapid-acting cloprostenol sodium injection as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Add a metal chelating agent and an antioxidant to water for injection and stir. Add sodium cloprostenol and continue stirring. Add the remaining volume of water for injection and adjust the pH value to obtain the semi-finished sodium cloprostenol injection solution. S2. Filter, fill, seal and package the semi-finished sodium cloprostenol injection to obtain fast-acting sodium cloprostenol injection.
5. The method for preparing a rapid-acting sodium cloprostenol injection according to claim 4, characterized in that, The stirring in step S1 is performed at a speed of 80-100 rpm for a time of 10-15 min.
6. The method for preparing a rapid-acting sodium cloprostenol injection according to claim 4, characterized in that, In step S1, the pH value is adjusted to 6.5-7.
7. The method for preparing a rapid-acting sodium cloprostenol injection according to claim 4, characterized in that, The filtration process described in step S2 uses a filter membrane with a pore size of ≤0.22μm.