CN101829082B - Method for preparing veterinary injection of spectinomycin hydrochloride and lincomycin hydrochloride - Google Patents
Method for preparing veterinary injection of spectinomycin hydrochloride and lincomycin hydrochlorideDownload PDFInfo
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- CN101829082B CN101829082BCN 200910079592CN200910079592ACN101829082BCN 101829082 BCN101829082 BCN 101829082BCN 200910079592CN200910079592CN 200910079592CN 200910079592 ACN200910079592 ACN 200910079592ACN 101829082 BCN101829082 BCN 101829082B
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Abstract
Translated fromChineseDescription
Translated fromChinese技术领域technical field
本发明属于兽用抗生素领域，涉及一种盐酸大观霉素、盐酸林可霉素注射液的制备方法。The invention belongs to the field of veterinary antibiotics and relates to a preparation method of spectinomycin hydrochloride and lincomycin hydrochloride injection.
背景技术Background technique
大观霉素(spectinomycin)是由链霉菌所产生的一种氨基糖苷类抗生素，用于革兰氏阴性菌及支原体感染。大观霉素具有毒性低，在有效剂量范围内对哺乳动物的肝、肺、肾等毒副作用小等优点，正在成为兽药的首选品种之一。研究表明，大观霉素能有效治疗和预防由链球菌、丹毒丝状菌、金黄色葡萄球菌、巴氏杆菌、大肠杆菌、沙门氏菌及支原体引起的畜禽疾病，尤其对支原体和大肠杆菌混合感染效果显著。作为一种新型兽用抗生素，大观霉素的抗性菌株少。大观霉素肌肉注射吸收良好，约1h内血中浓度可达高峰，给药48h后几乎100％从尿中排除，残留量极低。Spectinomycin is an aminoglycoside antibiotic produced by Streptomyces, used for Gram-negative bacteria and mycoplasma infections. Spectinomycin has the advantages of low toxicity and less toxic and side effects on mammalian liver, lung, kidney, etc. within the effective dose range, and is becoming one of the preferred varieties of veterinary drugs. Studies have shown that Spectinomycin can effectively treat and prevent livestock and poultry diseases caused by Streptococcus, Erysipelas, Staphylococcus aureus, Pasteurella, Escherichia coli, Salmonella and Mycoplasma, especially for the mixed infection of Mycoplasma and Escherichia coli significantly. As a new veterinary antibiotic, spectinomycin has few resistant strains. Spectinomycin is well absorbed by intramuscular injection, and the blood concentration can reach a peak within about 1 hour. It is almost 100% excreted from urine after 48 hours of administration, and the residual amount is extremely low.
林可霉素(lincomycin)为一般糖类抗生素，用于革兰氏阳性菌和支原体感染。Lincomycin (lincomycin) is a general carbohydrate antibiotic for Gram-positive bacteria and mycoplasma infection.
大观霉素与林可霉素主要通过抑制细菌蛋白质的合成而达到抑杀病原微生物的作用，两者配伍应用具有协同作用，临床常用两者的盐酸盐。盐酸林可霉素和盐酸大观霉素配伍具有同时抗革兰氏阳性菌、革兰氏阴性菌和支原体的作用，其活性范围比单个的林可霉素或大观霉素要宽。Spectinomycin and lincomycin mainly inhibit and kill pathogenic microorganisms by inhibiting the synthesis of bacterial proteins. The combination of the two has a synergistic effect, and the hydrochloride of the two is commonly used in clinical practice. The combination of lincomycin hydrochloride and spectinomycin hydrochloride has the effect of resisting Gram-positive bacteria, Gram-negative bacteria and mycoplasma at the same time, and its activity range is wider than that of single lincomycin or spectinomycin.
目前市场上的兽用大观霉素、林可霉素的复方制剂主要为预混剂、可溶性粉等口服制剂，但两者的口服吸收都较差，而注射给药吸收则很好。将盐酸大观霉素和盐酸林可霉素制成注射剂可明显提高生物利用度和组织分布，起效更迅速。因此除肠道细菌感染外，对于其他组织及全身细菌感染或支原体感染性疾病的治疗，则更有必要使用盐酸大观霉素、盐酸林可霉素的注射剂，以达到理想的治疗效果。The compound preparations of veterinary spectinomycin and lincomycin currently on the market are mainly oral preparations such as premixes and soluble powders, but the oral absorption of both is relatively poor, while the absorption by injection is very good. Making spectinomycin hydrochloride and lincomycin hydrochloride into injections can significantly improve bioavailability and tissue distribution, and the onset of effect is more rapid. Therefore, in addition to intestinal bacterial infections, for the treatment of other tissue and systemic bacterial infections or mycoplasma infectious diseases, it is more necessary to use spectinomycin hydrochloride and lincomycin hydrochloride injections to achieve ideal therapeutic effects.
盐酸大观霉素不溶于乙醇、三氯甲烷、乙醚等有机溶剂，易溶于水，但其水溶液极不稳定，盐酸大观霉素在水溶液中效价、pH值均会快速下降，且颜色加深渐变为暗黄色。用常规的注射液的制备方法，虽然也加入了一些常用的抗氧化剂，但仍不能防止大观霉素的水解，不能得到稳定的盐酸大观霉素、盐酸林可霉素注射液，在加速试验条件下放置仅1个月即不符合质量标准的要求。因此如何解决盐酸大观霉素在水溶液中的稳定性是制备稳定的盐酸大观霉素、盐酸林可霉素注射液的关键。Spectinomycin hydrochloride is insoluble in organic solvents such as ethanol, chloroform, ether, etc., and is easily soluble in water, but its aqueous solution is extremely unstable. The titer and pH value of spectinomycin hydrochloride will decrease rapidly in aqueous solution, and the color will deepen and gradually change. It is dark yellow. With the preparation method of routine injection, though also added some anti-oxidants commonly used, still can't prevent the hydrolysis of spectinomycin, can not obtain stable spectinomycin hydrochloride, lincomycin hydrochloride injection, under accelerated test condition Putting it down for only 1 month does not meet the requirements of the quality standard. Therefore how to solve the stability of spectinomycin hydrochloride in aqueous solution is the key to preparing stable spectinomycin hydrochloride and lincomycin hydrochloride injection.
发明内容Contents of the invention
本发明的目的在于提供一种稳定的兽用盐酸大观霉素、盐酸林可霉素注射液的制备方法。本发明将盐酸大观霉素用环糊精进行包合，可以显著提高盐酸大观霉素在水溶液中的稳定性，从而保证了盐酸大观霉素、盐酸林可霉素注射液的稳定性和疗效。本发明突破了盐酸大观霉素、盐酸林可霉素复方注射液的关键技术难题，本发明的制备方法保证了该类产品良好的质量和药效，为兽医临床治疗畜禽细菌、支原体等感染，提供了质量稳定、疗效确切的药品。The object of the present invention is to provide a kind of preparation method of stable veterinary spectinomycin hydrochloride and lincomycin hydrochloride injection. In the present invention, inclusion inclusion of spectinomycin hydrochloride with cyclodextrin can significantly improve the stability of spectinomycin hydrochloride in aqueous solution, thereby ensuring the stability and curative effect of spectinomycin hydrochloride and lincomycin hydrochloride injection. The present invention breaks through the key technical problems of spectinomycin hydrochloride and lincomycin hydrochloride compound injection, and the preparation method of the present invention ensures the good quality and efficacy of such products, and is useful for veterinary clinical treatment of infections such as bacteria and mycoplasma in livestock and poultry , providing medicines with stable quality and definite curative effect.
本发明的目的是通过如下技术方案实现的：The purpose of the present invention is achieved through the following technical solutions:
本发明提供一种兽用盐酸大观霉素、盐酸林可霉素注射液的制备方法，其特征在于将盐酸大观霉素用环糊精进行包合，制成的盐酸大观霉素包合物再与盐酸林可霉素制备成复方注射液。The invention provides a preparation method of veterinary spectinomycin hydrochloride and lincomycin hydrochloride injection, which is characterized in that spectinomycin hydrochloride is clathrated with cyclodextrin, and the spectinomycin hydrochloride clathrate prepared is then Prepare compound injection with lincomycin hydrochloride.
其中，盐酸大观霉素与环糊精的重量配比优选为30∶1～1∶20。Wherein, the weight ratio of spectinomycin hydrochloride to cyclodextrin is preferably 30:1-1:20.
进一步，盐酸大观霉素与环糊精的重量配比优选为15∶1～1∶10。Furthermore, the weight ratio of spectinomycin hydrochloride to cyclodextrin is preferably 15:1-1:10.
本发明中所用的盐酸林可霉素与盐酸大观霉素的重量配比，可按常规重量配比加入即可，但为更好的发挥二者的协同增效作用，以达到较好的临床效果，盐酸大观霉素与盐酸林可霉素的重量配比可为20∶1～1∶10。The weight ratio of lincomycin hydrochloride and spectinomycin hydrochloride used in the present invention can be added according to the conventional weight ratio, but in order to better exert the synergistic effect of the two, to achieve better clinical effect, the weight ratio of spectinomycin hydrochloride to lincomycin hydrochloride can be 20:1-1:10.
进一步，盐酸大观霉素与盐酸林可霉素的重量配比优选范围为10∶1～1∶5。Further, the weight ratio of spectinomycin hydrochloride and lincomycin hydrochloride preferably ranges from 10:1 to 1:5.
更进一步，盐酸大观霉素与盐酸林可霉素的重量配比为2∶1。Furthermore, the weight ratio of spectinomycin hydrochloride to lincomycin hydrochloride is 2:1.
本发明所用的环糊精可以为α-环糊精、羟乙基-β-环糊精、羟丙基-β-环糊精、二甲基-β-环糊精、三甲基-β-环糊精、γ-环糊精中的任意一种。The cyclodextrin used in the present invention can be α-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin - any one of cyclodextrin and γ-cyclodextrin.
本发明的兽用盐酸大观霉素、盐酸林可霉素注射液的制备方法，其制备步骤如下：The preparation method of spectinomycin hydrochloride for animals of the present invention, lincomycin hydrochloride injection, its preparation steps are as follows:
(1)取适量注射用水，按重量配比加入环糊精溶解，加入盐酸大观霉素，40-60℃快速搅拌20-30分钟；(1) Take an appropriate amount of water for injection, add cyclodextrin according to the weight ratio to dissolve, add spectinomycin hydrochloride, and stir rapidly at 40-60°C for 20-30 minutes;
(2)加入盐酸林可霉素，搅拌溶解；(2) Add lincomycin hydrochloride, stir and dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌或钴60射线灭菌。(5) Filtration, potting, microporous membrane filtration sterilization or cobalt 60 ray sterilization.
本发明的兽用盐酸大观霉素、盐酸林可霉素注射液的制备方法，其制备也可以按如下步骤进行：The preparation method of spectinomycin hydrochloride for animals of the present invention, lincomycin hydrochloride injection, its preparation also can be carried out according to the following steps:
(1)将环糊精制成50℃的饱和水溶液，按重量配比加入盐酸大观霉素，搅拌至少30分钟，迅速降温至4℃以下，过滤，干燥，即得盐酸大观霉素的包合物；(1) Make the cyclodextrin into a saturated aqueous solution at 50°C, add spectinomycin hydrochloride according to the weight ratio, stir for at least 30 minutes, quickly cool down to below 4°C, filter, and dry to obtain the inclusion complex of spectinomycin hydrochloride thing;
(2)取适量注射用水，加入盐酸大观霉素包合物，搅拌溶解，加入盐酸林可霉素搅拌溶解；(2) Take an appropriate amount of water for injection, add spectinomycin hydrochloride inclusion compound, stir and dissolve, add lincomycin hydrochloride and stir to dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌或钴60射线灭菌。(5) Filtration, potting, microporous membrane filtration sterilization or cobalt 60 ray sterilization.
本发明不同于传统的复方注射液的制备方法，而是将盐酸大观霉素通过环糊精包合的处理，得到稳定的包合物，再将其与盐酸林可霉素制备成复方注射液。本发明的制备方法通过提高盐酸大观霉素在水溶液中的稳定性，从而保证了产品的质量与疗效。本发明的制备方法步骤简单，但突破了盐酸大观霉素、盐酸林可霉素复方注射液的关键技术难题，从而保证了该类产品良好的质量和药效，为兽医临床治疗畜禽细菌、支原体等感染，提供了质量稳定、疗效确切的药品。The present invention is different from the traditional preparation method of compound injection, but spectinomycin hydrochloride is subjected to cyclodextrin inclusion treatment to obtain a stable inclusion compound, and then it is prepared into compound injection with lincomycin hydrochloride . The preparation method of the invention ensures the quality and curative effect of the product by improving the stability of the spectinomycin hydrochloride in the aqueous solution. The preparation method of the present invention has simple steps, but breaks through the key technical problems of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Compound Injection, thereby ensuring the good quality and efficacy of these products, and providing a useful tool for veterinary clinical treatment of livestock and poultry bacteria, Mycoplasma and other infections, providing medicines with stable quality and definite curative effect.
通过下列实施例将更具体的说明本发明，但是应理解所述实施例仅是为了说明本发明，而不是以任何方式限制本发明的范围。The present invention will be described more specifically through the following examples, but it should be understood that the examples are only for illustrating the present invention, not limiting the scope of the present invention in any way.
具体实施方式Detailed ways
实施例1Example 1
处方：prescription:
盐酸大观霉素 10gSpectinomycin Hydrochloride 10g
盐酸林可霉素 5gLincomycin Hydrochloride 5g
羟丙基-β-环糊精 5gHydroxypropyl-β-cyclodextrin 5g
抗氧化剂 适量Antioxidant Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)取注射用水70mL，按重量配比加入羟丙基-β-环糊精，加入盐酸大观霉素，50℃快速搅拌30分钟；(1) Take 70mL of water for injection, add hydroxypropyl-β-cyclodextrin according to the weight ratio, add spectinomycin hydrochloride, and stir rapidly at 50°C for 30 minutes;
(2)加入盐酸林可霉素，搅拌溶解；(2) Add lincomycin hydrochloride, stir and dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌。(5) Filtration, potting, and microporous membrane filtration to sterilize.
实施例2Example 2
处方：prescription:
盐酸大观霉素 4gSpectinomycin Hydrochloride 4g
盐酸林可霉素 2gLincomycin Hydrochloride 2g
羟乙基-β-环糊精 40gHydroxyethyl-β-cyclodextrin 40g
抗氧化剂 适量Antioxidant Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)将羟乙基-β-环糊精环糊精制备成50℃饱和溶液，按重量配比加入盐酸大观霉素，搅拌30分钟，迅速降温至4℃以下，过滤，干燥，得盐酸大观霉素包合物；(1) Prepare hydroxyethyl-β-cyclodextrin cyclodextrin into a saturated solution at 50°C, add spectinomycin hydrochloride according to the weight ratio, stir for 30 minutes, rapidly cool down to below 4°C, filter, and dry to obtain hydrochloric acid Spectinomycin inclusion complex;
(2)取注射用水70mL，加入盐酸大观霉素包合物，搅拌溶解，加入盐酸林可霉素搅拌溶解；(2) Take 70 mL of water for injection, add spectinomycin hydrochloride inclusion compound, stir to dissolve, add lincomycin hydrochloride and stir to dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，钻60射线灭菌。(5) Filtration, potting, drilling 60 ray sterilization.
实施例3Example 3
处方：prescription:
盐酸大观霉素 30gSpectinomycin Hydrochloride 30g
盐酸林可霉素 15gLincomycin Hydrochloride 15g
γ-环糊精 1gγ-cyclodextrin 1g
抗氧化剂 适量Antioxidants Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)取注射用水70mL，按重量配比加入γ-环糊精，加入盐酸大观霉素，60℃快速搅拌30分钟；(1) Take 70mL of water for injection, add γ-cyclodextrin according to the weight ratio, add spectinomycin hydrochloride, and stir rapidly at 60°C for 30 minutes;
(2)加入盐酸林可霉素，搅拌溶解；(2) Add lincomycin hydrochloride, stir and dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌。(5) Filtration, potting, and microporous membrane filtration to sterilize.
实施例4Example 4
处方：prescription:
盐酸大观霉素 2gSpectinomycin Hydrochloride 2g
盐酸林可霉素 1gLincomycin Hydrochloride 1g
α-环糊精 40gα-cyclodextrin 40g
抗氧化剂 适量Antioxidant Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)将α-环糊精环糊精制备成50℃饱和溶液，按重量配比加入盐酸大观霉素，搅拌30分钟，迅速降温至4℃以下，过滤，干燥，得盐酸大观霉素包合物；(1) Prepare α-cyclodextrin cyclodextrin into a saturated solution at 50°C, add spectinomycin hydrochloride according to the weight ratio, stir for 30 minutes, rapidly cool down to below 4°C, filter, and dry to obtain spectinomycin hydrochloride package compound;
(2)取注射用水70mL，加入盐酸大观霉素包合物，搅拌溶解，加入盐酸林可霉素搅拌溶解；(2) Take 70 mL of water for injection, add spectinomycin hydrochloride inclusion compound, stir to dissolve, add lincomycin hydrochloride and stir to dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌。(5) Filtration, potting, and microporous membrane filtration to sterilize.
实施例5Example 5
处方：prescription:
盐酸大观霉素 15gSpectinomycin Hydrochloride 15g
盐酸林可霉素 7.5gLincomycin Hydrochloride 7.5g
二甲基-β-环糊精 1gDimethyl-β-cyclodextrin 1g
抗氧化剂 适量Antioxidant Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)取注射用水70mL，按重量配比加入二甲基-β-环糊精，加入盐酸大观霉素，40℃快速搅拌30分钟；(1) Take 70 mL of water for injection, add dimethyl-β-cyclodextrin according to the weight ratio, add spectinomycin hydrochloride, and stir rapidly at 40°C for 30 minutes;
(2)加入盐酸林可霉素，搅拌溶解；(2) Add lincomycin hydrochloride, stir and dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make up to volume with water for injection;
(5)过滤，灌封，钴60射线灭菌。(5) Filtration, potting, cobalt 60 ray sterilization.
实施例6Example 6
处方：prescription:
盐酸大观霉素 10gSpectinomycin Hydrochloride 10g
盐酸林可霉素 5gLincomycin Hydrochloride 5g
三甲基-β-环糊精 4gTrimethyl-β-cyclodextrin 4g
抗氧化剂 适量Antioxidant Appropriate amount
注射用水 加至100mLAdd water for injection to 100mL
制备方法：Preparation:
(1)取注射用水70mL，按重量配比加入三甲基-β-环糊精，加入盐酸大观霉素，50℃快速搅拌30分钟；(1) Take 70mL of water for injection, add trimethyl-β-cyclodextrin according to the weight ratio, add spectinomycin hydrochloride, and stir rapidly at 50°C for 30 minutes;
(2)加入盐酸林可霉素，搅拌溶解；(2) Add lincomycin hydrochloride, stir and dissolve;
(3)取少量注射用水，加入抗氧化剂，搅拌溶解；(3) Take a small amount of water for injection, add antioxidant, stir to dissolve;
(4)合并(2)、(3)液，用注射用水定容；(4) Merge (2), (3) liquid, make up to volume with water for injection;
(5)过滤，灌封，微孔滤膜过滤除菌。(5) Filtration, potting, and microporous membrane filtration to sterilize.
实验例1按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液的加速试验稳定性考察Experimental Example 1 According to the accelerated test stability investigation of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Injection prepared in Example 1
对照药物的制备：取注射用水70mL，加入盐酸大观霉素10g，搅拌溶解；加入盐酸林可霉素4g，搅拌溶解；加入用少量注射用水溶解的抗氧化剂；用注射用水定容；过滤，灌封，微孔滤膜过滤除菌。Preparation of the reference drug: Take 70mL of water for injection, add 10g of spectinomycin hydrochloride, stir and dissolve; add 4g of lincomycin hydrochloride, stir and dissolve; add a small amount of antioxidant dissolved in water for injection; dilute to volume with water for injection; Sealed and sterilized by microporous membrane filtration.
试验方法：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液，与对照药物比较在加速试验条件下的稳定性。在温度40±2℃，相对湿度75±5％的条件下放置六个月。在第1、2、3、6个月取样一次，分别按稳定性重点考察项目进行检测。Test method: Spectinomycin hydrochloride and lincomycin hydrochloride injection were prepared according to the method of Example 1, and the stability under accelerated test conditions was compared with the control drug. Place it under the conditions of temperature 40±2℃ and relative humidity 75±5% for six months. Samples are taken once in the first, second, third, and sixth months, and tested according to the key stability inspection items.
试验结果：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液与对照药物的稳定性的比较结果见表1Test result: according to the method for embodiment 1 preparation spectinomycin hydrochloride, the comparison result of the stability of lincomycin hydrochloride injection and control drug is shown in Table 1
表1加速试验结果Table 1 Accelerated test results
实验例2按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液的长期稳定性考察Experimental Example 2 According to the long-term stability investigation of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Injection prepared in Example 1
对照药物的制备：取注射用水70mL，加入盐酸大观霉素10g，搅拌溶解；加入盐酸林可霉素4g，搅拌溶解；加入用少量注射用水溶解的抗氧化剂；用注射用水定容；过滤，灌封，微孔滤膜过滤除菌。Preparation of the reference drug: Take 70mL of water for injection, add 10g of spectinomycin hydrochloride, stir and dissolve; add 4g of lincomycin hydrochloride, stir and dissolve; add a small amount of antioxidant dissolved in water for injection; dilute to volume with water for injection; Sealed and sterilized by microporous membrane filtration.
试验方法：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液，与对照药物比较在长期试验条件下的稳定性。在温度25±2℃，相对湿度60±5％的条件下放置12个月。在第3、6、9、12个月取样一次，分别按稳定性重点考察项目进行检测。Test method: Spectinomycin hydrochloride and lincomycin hydrochloride injection were prepared according to the method of Example 1, and the stability under long-term test conditions was compared with the control drug. Store for 12 months under the condition of temperature 25±2℃ and relative humidity 60±5%. Samples are taken once in the 3rd, 6th, 9th, and 12th months, and tested according to the key stability inspection items.
试验结果：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液与对照药物的稳定性的比较结果见表2Test result: according to the method for embodiment 1 preparation spectinomycin hydrochloride, the comparison result of the stability of lincomycin hydrochloride injection and contrast drug is shown in Table 2
表2长期试验结果Table 2 Long-term test results
实验例3按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液临床治疗呼吸道感染的药效考察Experimental Example 3 Investigation of Drug Effects of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Injection Prepared According to Example 1 in the Clinical Treatment of Respiratory Tract Infection
对照药物的制备：取注射用水70mL，加入盐酸大观霉素10g，搅拌溶解；加入盐酸林可霉素4g，搅拌溶解；加入用少量注射用水溶解的抗氧化剂；用注射用水定容至100mL；过滤，灌封，微孔滤膜过滤除菌。Preparation of the control drug: Take 70mL of water for injection, add 10g of spectinomycin hydrochloride, stir to dissolve; add 4g of lincomycin hydrochloride, stir to dissolve; add a small amount of antioxidant dissolved in water for injection; dilute to 100mL with water for injection; filter , potting, microporous membrane filtration sterilization.
试验方法：选取体重25±5kg，诊断为呼吸道感染的育肥猪90头，随机分为3组，即第I、II、III组，每组30头。第I组肌肉注射按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液，每公斤体重注射0.1mL，每天一次，连用三天；第II组肌肉注射对照药物，每公斤体重注射0.1mL，每天一次，连用三天。第III组为空白对照组，不给药。Test method: Select 90 fattening pigs with a body weight of 25±5kg and diagnosed as respiratory tract infection, and divide them into 3 groups at random, that is, groups I, II, and III, with 30 pigs in each group. Group I intramuscularly injected spectinomycin hydrochloride and lincomycin hydrochloride injection prepared according to Example 1, injected 0.1 mL per kilogram of body weight, once a day, for consecutive three days; 0.1mL, once a day, for three consecutive days. Group III was a blank control group without administration.
试验结果：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液与对照药物的临床试验结果见表3Test result: according to the method for embodiment 1 preparation spectinomycin hydrochloride, lincomycin hydrochloride injection and the clinical test result of control drug are shown in Table 3
表3治疗呼吸道感染的临床试验结果Table 3 Results of clinical trials for the treatment of respiratory tract infections
试验过程中第I组猪咳嗽、呼吸急促等呼吸道疾病症状明显减轻，精神状态明显好转，未发现任何药物不良反应。第II组猪呼吸道疾病症状减轻，精神状态好转，未发现明显药物不良反应。第III组猪呼吸道疾病症状未减轻，精神沉郁。During the test, the symptoms of respiratory diseases such as cough and shortness of breath of the pigs in group I were significantly alleviated, and the mental state was obviously improved, and no adverse drug reactions were found. The symptoms of pig respiratory disease in group II were alleviated, the mental state was improved, and no obvious adverse drug reactions were found. The symptoms of pig respiratory diseases in Group III were not alleviated, and the spirit was depressed.
实验例4按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液临床治疗仔猪腹泻的药效考察Experimental Example 4 Investigation of the efficacy of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Injection prepared according to Example 1 in the clinical treatment of piglet diarrhea
对照药物的制备：取注射用水70mL，加入盐酸大观霉素10g，搅拌溶解；加入盐酸林可霉素4g，搅拌溶解；加入用少量注射用水溶解的抗氧化剂；用注射用水定容至100mL；过滤，灌封，微孔滤膜过滤除菌。Preparation of the control drug: Take 70mL of water for injection, add 10g of spectinomycin hydrochloride, stir to dissolve; add 4g of lincomycin hydrochloride, stir to dissolve; add a small amount of antioxidant dissolved in water for injection; dilute to 100mL with water for injection; filter , potting, microporous membrane filtration sterilization.
试验方法：选取体重14±2kg，有腹泻症状的断奶仔猪90头，随机分为3组，即第I、II、III组，每组30头。第I组肌肉注射按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液，每公斤体重注射0.1mL，每天一次，连用三天；第II组肌肉注射对照药物，每公斤体重注射0.1mL，每天一次，连用三天；第III组为空白对照组，不给药。Test method: Select 90 weaned piglets with a body weight of 14±2kg and symptoms of diarrhea, and randomly divide them into 3 groups, namely groups I, II, and III, with 30 pigs in each group. Group I intramuscularly injected spectinomycin hydrochloride and lincomycin hydrochloride injection prepared according to Example 1, injected 0.1 mL per kilogram of body weight, once a day, for consecutive three days; 0.1 mL, once a day, for three consecutive days; Group III is the blank control group, without administration.
试验结果：按照实施例1的方法制备盐酸大观霉素、盐酸林可霉素注射液与对照药物的临床试验结果见表4Test result: according to the method for embodiment 1 preparation spectinomycin hydrochloride, lincomycin hydrochloride injection and the clinical test result of control drug are shown in Table 4
表4治疗仔猪腹泻的临床试验结果The clinical trial result of table 4 treatment piglet diarrhea
试验过程中第I组仔猪采食量明显增加、精神状态明显好转，未发现任何药物不良反应。第II组仔猪采食量增加、精神状态略有好转，未发现明显药物不良反应。第III组仔猪食欲、精神状态较差。During the experiment, the feed intake of piglets in group I increased significantly, and the mental state improved significantly, and no adverse drug reactions were found. Piglets in group II had increased feed intake and slightly improved mental status, and no obvious adverse drug reactions were found. Piglets in group III had poor appetite and mental state.
实验例5按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液临床治疗母猪产后三联症的药效考察Experimental Example 5 Investigation of the efficacy of Spectinomycin Hydrochloride and Lincomycin Hydrochloride Injection prepared according to Example 1 in the clinical treatment of postpartum triad of sows
对照药物的制备：取注射用水70mL，加入盐酸大观霉素10g，搅拌溶解；加入盐酸林可霉素4g，搅拌溶解；加入用少量注射用水溶解的抗氧化剂；用注射用水定容至100mL；过滤，灌封，微孔滤膜过滤除菌。Preparation of the control drug: Take 70mL of water for injection, add 10g of spectinomycin hydrochloride, stir to dissolve; add 4g of lincomycin hydrochloride, stir to dissolve; add a small amount of antioxidant dissolved in water for injection; dilute to 100mL with water for injection; filter , potting, microporous membrane filtration sterilization.
试验方法：选取体重200±10kg，诊断为产后三联症的母猪45头，随机分为3组，即第I、II、III组，每组15头。第I组肌肉注射按照实施例1制备的盐酸大观霉素、盐酸林可霉素注射液，每公斤体重注射0.1mL，每天一次，连用三天；第II组肌肉注射对照药物，每公斤体重注射0.1mL，每天一次，连用三天；第III组为空白对照组，不给药。Test method: Select 45 sows with a body weight of 200±10kg and diagnosed as postpartum triad, and divide them into 3 groups at random, namely, groups I, II, and III, with 15 sows in each group. Group I intramuscularly injected spectinomycin hydrochloride and lincomycin hydrochloride injection prepared according to Example 1, injected 0.1 mL per kilogram of body weight, once a day, for consecutive three days; 0.1 mL, once a day, for three consecutive days; Group III is the blank control group, without administration.
试验结果：按照实施例1的方法制备的盐酸大观霉素、盐酸林可霉素注射液与对照药物的临床试验结果见表5Test results: The clinical test results of Spectinomycin Hydrochloride, Lincomycin Hydrochloride Injection and control drugs prepared according to the method of Example 1 are shown in Table 5
表5治疗母猪产后三联症的临床试验结果Table 5 The results of clinical trials for the treatment of postpartum triad in sows
试验过程中第I组母猪食欲、精神状态明显好转，未发现任何药物不良反应。第II组母猪食欲、精神状态略有好转，未发现明显药物不良反应。第III组母猪食欲、精神状态较差。During the test, the appetite and mental state of group I sows improved significantly, and no adverse drug reactions were found. The appetite and mental state of sows in group II improved slightly, and no obvious adverse drug reactions were found. The appetite and mental state of sows in Group III were poor.
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| CN102793713A (en)* | 2011-07-07 | 2012-11-28 | 上海公谊兽药厂 | Lincomycin hydrochloride-spectinomycin sulfate injection and preparation method thereof |
| CN104473958A (en)* | 2014-12-15 | 2015-04-01 | 洛阳瑞华动物保健品有限公司 | Compound premix and preparation method and application thereof |
| CN106420635A (en)* | 2016-09-29 | 2017-02-22 | 乐山市瑞和祥生物制药有限公司 | Spectinomycin hydrochloride and lincomycin hydrochloride freeze-dried powder injection and preparation method of spectinomycin hydrochloride and lincomycin hydrochloride freeze-dried powder injection |
| CN111973613B (en)* | 2020-07-30 | 2022-04-08 | 瑞普（天津）生物药业有限公司 | Compound spectinomycin powder injection and preparation method thereof |
| CN113995722A (en)* | 2021-12-16 | 2022-02-01 | 四川欧邦生物科技有限公司 | Spectinomycin hydrochloride lincomycin hydrochloride soluble powder and preparation method thereof |
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