A compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride and a preparation method thereof

Abstract

The application discloses a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride and a preparation method thereof. Compared with the prior art, the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride prepared by the application has high affinity to drugs, is safe to use, significantly improves the drug dissolution speed and stability of the drug after dissolution in water and oil environments, overcomes the problems of insufficient drug dissolution and irritation of the drug to a drug administration site, reduces the hemolytic side effect of the drug for animals and the nephrotoxicity, and can also reduce the drug resistance of the drug for animals by inhibiting the function of P-sugar protein. The compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride can expand the antibacterial spectrum and simultaneously prevent and treat various diseases by the synergistic effect of spectinomycin and lincomycin.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of antibacterial drugs, in particular to a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride and a preparation method thereof. BACKGROUND

[0002] Spectinomycin hydrochloride is mainly used for treating respiratory tract infection, digestive tract infection, skin infection caused by bacterial infection, treating or preventing urinary system infection, etc. in veterinary clinic. Lincomycin hydrochloride is a high-efficiency antibacterial drug against anaerobic bacteria, which is mainly used for treating infection of anaerobic bacteria and gram-positive bacteria in need of oxygen in veterinary clinic, and is also effective against anaerobic bacteria and facultative anaerobic bacteria in conditional and pathological anaerobic environment; it can be used for preventing and treating various infectious diseases of respiratory tract and digestive tract of animals, such as fowl plague, duck plague, pig reproduction disorder, respiratory syndrome, urogenital system infection, etc. of poultry, pigs, cattle and other animals.

[0003] In view of the limitations of single spectinomycin hydrochloride and lincomycin hydrochloride in antibacterial spectrum and antibacterial effect, in actual preparation research and production, spectinomycin hydrochloride and lincomycin hydrochloride are often used in combination to cope with mixed bacteria, improve the flexibility of the treatment scheme, reduce the resistance of bacteria to drugs, reduce the drug dosage of single drug and the drug burden of animals, and avoid or reduce possible side effects through reasonable combination. In the prior art, spectinomycin hydrochloride and lincomycin hydrochloride are scientifically compounded at a ratio of "2:1" to form a soluble powder, which is much more than single spectinomycin hydrochloride soluble powder; in the clinical treatment of poultry diseases, it is mainly used for the treatment of infectious synovitis, chronic respiratory disease, colibacillosis and other diseases.

[0004] CN114748495A discloses an oil-water double-soluble veterinary lincomycin-spectinomycin compound preparation, a preparation method and application thereof. The compound preparation comprises the following materials in parts by weight: polyethylene glycol 5-10 parts, cyclodextrin derivative 5-12 parts, poloxamer 2-4 parts, anhydrous sodium sulfite 2-7 parts, spectinomycin and / or salt form 60-100 parts, lincomycin and / or salt form 20-40 parts, and lactose 10-20 parts. The lincomycin-spectinomycin compound preparation prepared by the present application has a solubility of 370-390 g / L in aqueous vaccine and 80-120 g / L in oil vaccine, solving the problems of small solubility and unstable solution of spectinomycin and lincomycin in aqueous and oil vaccines. The present application reflects the solubility and dissolution rate in aqueous and oil vaccines, but does not reflect the stability problem of drug dissolution.

[0005] CN111297808A discloses a hydrochloric acid macrokaylin can be directly dissolved in oil sample soluble powder and its preparation method, which is composed of the following components: hydrochloric acid macrokaylin 40 parts, hydrochloric acid lincomycin 20 parts, oil / water type emulsifier 3-6 parts, water / oil type emulsifier 7-10 parts, immune polysaccharide 2-4 parts, auxiliary materials 20-28 parts; the soluble powder of the invention can be directly dissolved in oil sample without any oil sample diluent and is uniform, which ensures the quality and efficacy of such products, facilitates clinical operation and application of breeding, and reduces the use cost. The soluble powder of the invention mainly dissolves in oil sample, and does not show good stability in water. SUMMARY

[0006] In view of the above defects of the prior art, the technical problems to be solved by the present application are the drug dissolution rate and stability after dissolution of hydrochloric acid macrokaylin and hydrochloric acid lincomycin compound soluble powder in water and oil environment.

[0007] To achieve the above-mentioned purpose, the present application provides a compound soluble powder of hydrochloric acid macrokaylin and hydrochloric acid lincomycin and its preparation method.

[0008] A compound soluble powder of hydrochloric acid macrokaylin and hydrochloric acid lincomycin, comprising the following components: hydrochloric acid macrokaylin, hydrochloric acid lincomycin, glucose, pH regulator, sulfobutyl-beta-cyclodextrin sodium and surfactant.

[0009] Specifically, the compound soluble powder of hydrochloric acid macrokaylin and hydrochloric acid lincomycin consists of the following components by weight: hydrochloric acid macrokaylin 40-48 parts, hydrochloric acid lincomycin 18-20 parts, 5-10 parts of glucose, 3-5 parts of pH regulator, 4-6 parts of sulfobutyl-beta-cyclodextrin sodium and 4-6 parts of surfactant.

[0010] A preparation method of a compound soluble powder of hydrochloric acid macrokaylin and hydrochloric acid lincomycin, the preparation steps are as follows:

[0011] Weigh hydrochloric acid macrokaylin, hydrochloric acid lincomycin, glucose, pH regulator, sulfobutyl-beta-cyclodextrin sodium and surfactant, mix and crush and sieve, to obtain the compound soluble powder of hydrochloric acid macrokaylin and hydrochloric acid lincomycin.

[0012] The pH regulator is any one or more of sodium citrate, sodium carbonate, sodium bicarbonate and disodium hydrogen phosphate.

[0013] The sieving is 80-100 mesh sieving.

[0014] The surfactant is any one or more of vitamin E polyethylene glycol succinate, poloxamer, Tween-80 and polyethylene glycol; preferably vitamin E polyethylene glycol succinate.

[0015] Poloxamer and Tween-80 are non-ionic surfactants, which help drug emulsification and dispersion, make oily and aqueous ingredients mix evenly, also can promote the dispersion of solid particles, prevent its precipitation and agglomeration, improve the solubility and stability of the drug; polyethylene glycol non-ionic surfactant has good water solubility and biocompatibility, so that the drug can be dissolved in water, oil and other solvents, promote the drug to disperse uniformly in the solution, after covalent reaction with the drug, it can also improve the bioavailability and therapeutic effect of the drug, prolong the half-life of the drug, reduce the toxicity and side effects of the drug. Tween-80, vitamin E polyethylene glycol succinate can also reduce the drug resistance of animal drugs by inhibiting the function of P-glycoprotein, and vitamin E polyethylene glycol succinate has better inhibitory effect.

[0016] Vitamin E polyethylene glycol succinate is a water-soluble non-ionic surfactant, which has small irritation, low toxicity and good biocompatibility, and has good stability, solubility and release, and also has high surface activity and solubilizing properties, which plays the role of solubilizer and stabilizer in the application; vitamin E polyethylene glycol succinate contains hydrophilic end group polyethylene glycol chain and lipophilic group vitamin E at the same time, and the repulsive force generated by the steric hindrance makes the drug particles separate to produce a stable effect, prevents particle agglomeration, and has better stability; adding to the soluble powder can promote the drug to maintain high dissolution rate and stability in water or oil, thereby improving the efficacy and enhancing the bioavailability.

[0017] When the drug is dissolved, it will cause the oil vaccine to demulsify, so it is difficult for the drug to dissolve in the oil vaccine, the cyclodextrin derivative has a special cavity structure, and the inclusion compound is formed with the non-ionic surfactant, so that the polarity of the inner cavity of the cyclodextrin is reduced, the better the compatibility of the selected surfactant with the cyclodextrin cavity, the more stable the obtained inclusion compound, and the better the solubilization and emulsification effect compared with a single individual structure, which preferentially forms a stable emulsion when added to the oil vaccine, so that the drug dissolves faster in the oil vaccine. Sodium sulfobutyl-β-cyclodextrin is an anionic high water-soluble cyclodextrin derivative with high drug affinity and drug release property, which can form a non-covalent complex with the drug molecules when added to the veterinary medicine soluble powder, thereby improving the stability and safety of the drug; sodium sulfobutyl-β-cyclodextrin can also reduce the hemolytic side effects of the drug for animals, reduce the nephrotoxicity, and help to mask the bitter and smelly defects of lincomycin hydrochloride.

[0018] The present application finds that the high dissolution rate and stability of vitamin E polyethylene glycol succinate neutralize the emulsification and sustained-release property of sodium sulfobutyl-β-cyclodextrin, so that the drug dissolution rate curve is smooth, the irritation of the drug to the administration site is reduced, the drug quickly reaches the required blood concentration, and the action time of the drug is prolonged.

[0019] Advantages of the present application:

[0020] 1. Compared with the prior art, vitamin E polyethylene glycol succinate added in the present application plays the role of solubilizer and stabilizer, is added into the soluble powder to promote the high dissolution rate and stability of the drug in water or oil, prevent particle agglomeration, improve drug efficacy, and enhance bioavailability. Vitamin E polyethylene glycol succinate can also inhibit the function of P-glycoprotein to reduce drug resistance of the animal.

[0021] 2. Compared with the prior art, sulfobutyl-β-cyclodextrin sodium with drug sustained release property is added in the present application, which can also reduce the hemolytic side effect of the animal drug, reduce nephrotoxicity, help to cover up the shortcomings of bitter and smelly taste of lincomycin hydrochloride, and the cavity structure of sulfobutyl-β-cyclodextrin sodium forms an inclusion with nonionic surfactants to reduce the dissolution difficulty of the drug in oil.

[0022] 3. It is also found in the present application that the high dissolution rate and stability of vitamin E polyethylene glycol succinate neutralize the emulsification and sustained release property of sulfobutyl-β-cyclodextrin sodium to the drug, so as to make the drug dissolution rate curve smooth, reduce the irritation of the drug to the administration site, make the drug quickly reach the required blood drug concentration, and prolong the action time of the drug.

[0023] 4. The compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride prepared in the present application has high affinity to the drug, is safe to use, significantly improves the drug dissolution rate and stability after dissolution in water and oil environment, and overcomes the problems of insufficient drug dissolution amount and irritation of the drug to the administration site. The synergistic effect of spectinomycin and lincomycin can expand the antibacterial spectrum and prevent and treat multiple diseases at the same time. DETAILED DESCRIPTION

[0024] The parameters of the specific chemical substances used in the examples are as follows:

[0025] Spectinomycin hydrochloride: 2 million IU, spectinomycin hydrochloride, manufacturer: Shandong Lu Kang Pharmaceutical Co., Ltd., batch number H10930010.

[0026] Lincomycin hydrochloride: purity 98 wt.%, manufacturer: Shanghai Yuan Ye Biotechnology Co., Ltd., product number B33847.

[0027] Vitamin E polyethylene glycol succinate: effective ingredient content 99%, pharmaceutical grade, manufacturer: Wuhan Kaimi Lingke, product number 0327.

[0028] Polyethylene glycol: polyethylene glycol 6000, purity 99 wt.%, manufacturer: Guangzhou Zaidan Chemical Co., Ltd., model PEG6397P.

[0029] Example 1

[0030] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0031] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g sodium sulfobutyl-β-cyclodextrin, and 5g poloxamer. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0032] Example 2

[0033] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0034] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g sodium sulfobutyl-β-cyclodextrin, and 5g Tween-80, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0035] Example 3

[0036] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0037] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g sodium sulfobutyl-β-cyclodextrin, and 5g polyethylene glycol. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0038] Example 4

[0039] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0040] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g sodium sulfobutyl-β-cyclodextrin, and 5g vitamin E polyethylene glycol succinate. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0041] Comparative Example 1

[0042] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0043] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, and 10g poloxamer, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0044] Comparative Example 2

[0045] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0046] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, and 10g Tween-80, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0047] Comparative Example 3

[0048] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0049] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, and 10g polyethylene glycol. Mix them, pulverize them, and pass them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0050] Comparative Example 4

[0051] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0052] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, and 10g vitamin E polyethylene glycol succinate. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0053] Comparative Example 5

[0054] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0055] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, and 10g sodium sulfobutyl-β-cyclodextrin. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0056] Comparative Example 6

[0057] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0058] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g β-cyclodextrin, and 5g poloxamer, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0059] Comparative Example 7

[0060] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0061] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g β-cyclodextrin, and 5g Tween-80, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0062] Comparative Example 8

[0063] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0064] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g β-cyclodextrin, and 5g polyethylene glycol, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0065] Comparative Example 9

[0066] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0067] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g β-cyclodextrin, and 5g vitamin E polyethylene glycol succinate. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0068] Comparative Example 10

[0069] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0070] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g hydroxypropyl-β-cyclodextrin, and 5g poloxamer, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0071] Comparative Example 11

[0072] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0073] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g hydroxypropyl-β-cyclodextrin, and 5g Tween-80, mix them, and then pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0074] Comparative Example 12

[0075] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0076] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g hydroxypropyl-β-cyclodextrin, and 5g polyethylene glycol. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0077] Comparative Example 13

[0078] A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride is as follows:

[0079] Weigh out 42g spectinomycin hydrochloride, 20g lincomycin hydrochloride, 8g glucose, 4g sodium citrate, 5g hydroxypropyl-β-cyclodextrin, and 5g vitamin E polyethylene glycol succinate. Mix them and pulverize them through an 80-mesh sieve to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

[0080] Test Example 1

[0081] Solubility test

[0082] The compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride obtained from the preparation methods of Examples 1-4 and Comparative Examples 1-13 were injected into 20g of sterile water for injection at mass ratios of 10wt.%, 20wt.%, and 30wt.%, respectively, to obtain compound soluble powder-water solutions of spectinomycin hydrochloride and lincomycin hydrochloride. The solutions were shaken to dissolve and the dissolution time was recorded. Then, the solutions were injected into 250g of oilseed marrow at mass ratios of 0.2wt.%, 0.4wt.%, and 0.5wt.%, respectively, to obtain compound soluble powder-oilseed marrow solutions of spectinomycin hydrochloride and lincomycin hydrochloride. The solutions were tightly capped and shaken vigorously for 30s. After standing, the dissolution was observed, as well as the stability of the 0.3wt.% compound soluble powder-oilseed marrow solution of spectinomycin hydrochloride and lincomycin hydrochloride after 24 hours of dissolution. The water solubility test results are shown in Table 1, and the oilseed marrow solubility test results are shown in Table 2.

[0083] Table 1 Water solubility test

[0084]

[0085]

[0086] As shown in Table 1, the water solubility test results indicate that the compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride in Examples 1-4 and Comparative Examples 1-3 were completely dissolved in water at mass ratios of 10 wt.%, 20 wt.%, and 30 wt.%, respectively. The dissolution times of Examples 1-4 and Comparative Examples 6-13 were all less than 300 seconds. The comparison shows that the dissolution time of Examples 1-4 was shorter than that of Comparative Examples 6-13, indicating that the compatibility of nonionic surfactants with sodium sulfobutyl-β-cyclodextrin is higher than that of β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Among them, Example 4 showed the best water solubility and the shortest dissolution time.

[0087] Table 2 Oil Seed Dissolution Test

[0088]

[0089]

[0090] As shown in Table 2, the compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride from Examples 1-4 and Comparative Examples 1-13, when added to the oil-based vaccine at a mass ratio of 0.2 wt.%, were completely dissolved. However, when added at mass ratios of 0.3 wt.%, 0.4 wt.%, and 0.5 wt.%, incomplete dissolution or even complete dissolution occurred under the condition of shaking for only 30 seconds. Only Example 4, when added to the oil-based vaccine at mass ratios of 0.3 wt.%, 0.4 wt.%, and 0.5 wt.%, remained completely dissolved. When the compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride from Examples 1-4 and Comparative Examples 1-13 were added to the oil-based vaccine at 0.3 wt.%, slight stratification or layering was observed 24 hours after complete dissolution. Example 4 showed no stratification, thus demonstrating drug dissolution stability.

[0091] Test Example 2

[0092] 1. High-temperature stability test

[0093] The compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride obtained by the preparation methods of Examples 1-4 and Comparative Examples 1-13 were placed in an environment of 70°C, 60% relative humidity, unsealed and not protected from light for 14 days. Observations were made on days 5, 10, and 14 to check for clumping. The results of the high-temperature stability test are shown in Table 3.

[0094] Table 3 High Temperature Stability Test Results

[0095] Example Day 5 Day 10 Day 14 Example 1 No change No change Slight caking Example 2 No change No change Slight caking Example 3 No change No change Slight caking Example 4 No change No change No change Comparative Example 1 No change Slight caking Caked Comparative Example 2 No change Slight caking Caked Comparative Example 3 No change Slight caking Caked Comparative Example 4 No change Slight caking Caked Comparative Example 5 No change Slight caking Caked Comparative Example 6 No change No change Slight caking Comparative Example 7 No change Slight caking Slight caking Comparative Example 8 No change No change Slight caking Comparative Example 9 No change No change Slight caking Comparative Example 10 No change Slight caking Slight caking Comparative Example 11 No change Slight caking Slight caking Comparative Example 12 No change No change Slight caking Comparative Example 13 No change No change Slight caking

[0096] The high-temperature stability test of Example 2 shows that the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride in Example 4 is stable in physicochemical properties when placed in a high-temperature and high-humidity environment. After being stored at 70°C and 60% humidity for 14 days, it still looks normal and has no clumping.

[0097] 2. Accelerated stability test

[0098] Accelerated testing was conducted on the compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride obtained by the preparation methods of Examples 1-4 and Comparative Examples 1-13. The powders were placed at 40°C and 60% relative humidity for 6 months, and observations were made at months 0, 1, 2, 3, and 6 during the test period to check for clumping. The results of the high-temperature stability test are shown in Table 4.

[0099] Table 4. High Temperature Stability Test Results

[0100] Example Month 0 Month 1 Month 2 Month 3 Month 6 Example 1 No change No change No change No change Slight caking Example 2 No change No change No change No change Slight caking Example 3 No change No change No change No change Slight caking Example 4 No change No change No change No change No change Comparative Example 1 No change No change No change No change Slight caking Comparative Example 2 No change No change No change No change Slight caking Comparative Example 3 No change No change No change No change Slight caking Comparative Example 4 No change No change No change No change Slight caking Comparative Example 5 No change No change No change Slight caking Slight caking Comparative Example 6 No change No change No change No change Slight caking Comparative Example 7 No change No change No change No change Slight caking Comparative Example 8 No change No change No change No change Slight caking Comparative Example 9 No change No change No change No change Slight caking Comparative Example 10 No change No change No change No change Slight caking Comparative Example 11 No change No change No change No change Slight caking Comparative Example 12 No change No change No change No change Slight caking Comparative Example 13 No change No change No change No change Slight caking

[0101] The accelerated stability test comparison of Example 2 shows that the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride in Example 4 maintains stable physicochemical properties in the accelerated test. It can be stored for up to 6 months in an environment of 40°C and 60% relative humidity. It has no lumps and is in good condition. It does not need to be protected from light during storage.

[0102] Test Example 3

[0103] Toxicity testing

[0104] The compound soluble powders of spectinomycin hydrochloride and lincomycin hydrochloride prepared according to the methods of Examples 1-4 and Comparative Examples 1-5 were injected into 40g of sterile water for injection at a mass ratio of 25wt.% to obtain a compound soluble powder-water solution of spectinomycin hydrochloride and lincomycin hydrochloride. A total of ten groups were prepared. 54 experimental mice with a weight range of 18-22g were used, with half males and half females, and 6 mice in each group.

[0105] In nine groups of experiments, mice were subjected to subcutaneous and intraperitoneal administration to assess toxicity. Mice were injected intramuscularly with a compound soluble powder-water solution of spectinomycin hydrochloride and lincomycin hydrochloride at doses of 500, 250, and 100 mg / (kg·d) for 14 consecutive days, and intraperitoneally with doses of 500, 250, and 100 mg / (kg·d) for 14 consecutive days. Adverse reactions were observed.

[0106] The experimental results of Test Example 3 showed that no obvious toxic reactions were observed during the administration period. Mice in each dosage group of Examples 1-4 and Comparative Examples 1-5 showed no abnormalities; their mental and activity levels were good, their appetite and mental state were normal, and they exhibited no abnormalities. Therefore, the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride obtained according to the preparation methods of Examples 1-4 and Comparative Examples 1-5 can be considered safe and non-toxic.

Claims

1. A compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride, characterized in that, It consists of the following components by weight: 40-48 parts spectinomycin hydrochloride, 18-20 parts lincomycin hydrochloride, 5-10 parts glucose, 3-5 parts pH adjuster, 4-6 parts sodium sulfobutyl-β-cyclodextrin, and 4-6 parts surfactant. The surfactant is vitamin E polyethylene glycol succinate.

2. A method for preparing a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride as described in claim 1, characterized in that, The preparation steps are as follows: Weigh spectinomycin hydrochloride, lincomycin hydrochloride, glucose, pH adjuster, sodium sulfobutyl-β-cyclodextrin, and surfactant, mix them, pulverize and sieve them to obtain a compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride.

3. The method for preparing the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride as described in claim 2, characterized in that, The pH adjuster is any one or more of sodium citrate, sodium carbonate, sodium bicarbonate, and disodium hydrogen phosphate.

4. The method for preparing the compound soluble powder of spectinomycin hydrochloride and lincomycin hydrochloride as described in claim 2, characterized in that, The sieve used is an 80-100 mesh sieve.

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