Spectinomycin hydrochloride and lincomycin hydrochloride powder injection for injection and preparation method of spectinomycin hydrochloride and lincomycin hydrochloride powder injection

Abstract

The invention discloses spectinomycin hydrochloride and lincomycin hydrochloride powder injection for injection and a preparation method thereof, and belongs to the technical field of veterinary drug preparations. The spectinomycin hydrochloride and lincomycin hydrochloride powder injection for injection is prepared from the following components: spectinomycin hydrochloride, lincomycin hydrochloride, poloxamer 188, povidone K-17, anhydrous sodium citrate, anhydrous citric acid, L-leucine, anhydrous sodium sulfite, edetate disodium and mannitol. The powder can realize fault in the oil seedlings; the spectinomycin hydrochloride lincomycin hydrochloride powder injection can be quickly wetted within 30 seconds without demulsification within 24 hours, can also realize second-level redissolution in water for injection, is clear and transparent, and can be well suitable for spectinomycin hydrochloride lincomycin hydrochloride powder injection for injection which can be dissolved in water and also can be mixed and dissolved with vaccines.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of veterinary medicine preparation, and particularly relates to a powder injection of spectinomycin hydrochloride and lincomycin hydrochloride for injection and a preparation method. BACKGROUND

[0002] Spectinomycin hydrochloride belongs to aminoglycoside antibiotics and is mainly directed against gram-negative bacteria and mycoplasma; lincomycin hydrochloride belongs to lincomycin antibiotics and has strong antibacterial activity against most gram-positive bacteria and part of anaerobic bacteria. The combination of the two has a significant synergistic effect, can expand the antibacterial spectrum, and not only has a strong inhibitory effect on gram-positive bacteria, gram-negative bacteria and mycoplasma, but also can effectively delay the generation of bacterial drug resistance. Clinically, the compound preparation is widely used for preventing and treating chronic respiratory diseases of poultry, mycoplasma pneumonia of pigs, diarrhea of piglets and mixed infections caused by Escherichia coli, Salmonella and the like.

[0003] For example, the prior art Chinese patent CN202111547879.8 discloses a spectinomycin hydrochloride and lincomycin hydrochloride soluble powder and a preparation method thereof; and the prior art Chinese patent CN201410775259.3 discloses a compound premix, a preparation method and application thereof.

[0004] The soluble powder and the compound premix in the above technical solutions are oral preparations, which are convenient to administer, but have significant limitations. First, the oral bioavailability of lincomycin and spectinomycin is low, which cannot quickly reach an effective blood drug concentration in the acute infection period, and has a slow effect. Second, it is difficult to ensure that each diseased animal ingests an accurate drug dose through mixed drinking or mixed feeding, and the diseased animals often have anorexia, which leads to insufficient administration, affects the curative effect, and easily induces the generation of drug-resistant strains.

[0005] In order to solve the problems of slow effect and low bioavailability of oral preparations, an injection becomes a better choice.

[0006] For example, the prior art Chinese patent CN200910079592.X discloses a preparation method of a veterinary spectinomycin hydrochloride and lincomycin hydrochloride injection, which improves the stability of spectinomycin hydrochloride in an aqueous solution by preparing a clathrate of spectinomycin hydrochloride and cyclodextrin. Although this method improves the stability of the main drug to some extent, the cyclodextrin clathration process is complex, and the formation of the clathrate is affected by many factors, has large batch differences, and is difficult to realize large-scale industrial production. More importantly, this scheme only solves the hydrolysis problem of the drug itself, and does not solve the risk of oxidation discoloration in long-term storage of the injection, and as an aqueous injection, it still faces the potential threat of hydrolysis.

[0007] For example, Chinese patent CN201010606144.3 discloses a lincomycin and spectinomycin compound oil suspension injection, its preparation method, and its application. This method solves the hydrolysis problem by dispersing the drug in an oily medium to isolate it from moisture. However, oil suspension injections have high viscosity, poor needle penetration, and are difficult to inject; moreover, the oily medium is slowly absorbed in the body, easily causing drug residues and even granulomas at the injection site. Furthermore, the preparation process of this dosage form is complex, requiring specific gelation treatment, resulting in high production costs.

[0008] More importantly, with the development of large-scale farming, the need for combined use of vaccines and drugs is becoming increasingly urgent. Farmers hope to administer antibiotics simultaneously with vaccines, such as oil-adjuvanted inactivated avian influenza vaccines, to reduce the number of times chickens need to be handled and to reduce stress. However, none of the existing publicly available technologies can meet this need.

[0009] Therefore, it is particularly urgent to develop an injectable spectinomycin hydrochloride and lincomycin hydrochloride that is both water-soluble and miscible with vaccines, allowing the product to treat diseases alone and also to be used during immunization for preventative effects. Summary of the Invention

[0010] The first objective of this invention is to provide an injectable spectinomycin hydrochloride and lincomycin hydrochloride powder that is both water-soluble and miscible with vaccines.

[0011] The second objective of this invention is to provide an injectable spectinomycin hydrochloride and lincomycin hydrochloride powder for injection and its preparation method.

[0012] To solve the above-mentioned technical problems, the present invention discloses a spectinomycin hydrochloride and lincomycin hydrochloride powder for injection, comprising the following components: spectinomycin hydrochloride, lincomycin hydrochloride, poloxamer 188, povidone K-17, anhydrous sodium citrate, anhydrous citric acid, L-leucine, anhydrous sodium sulfite, disodium edetate, and mannitol.

[0013] A spectinomycin hydrochloride and lincomycin hydrochloride powder for injection, based on a total weight of 100g, comprises spectinomycin hydrochloride and lincomycin hydrochloride, accounting for 65.0%-75.0% of the total amount; The poloxamer 188 accounts for 4.0%-6.0% of the total; The povidone K-17 accounts for 8.0%-12.0% of the total; The anhydrous sodium citrate and anhydrous citric acid together account for 5.0%-8.0% of the total amount; The L-leucine accounts for 5.0%-7.0% of the total; The anhydrous sodium sulfite accounts for 0.3%-0.5% of the total. The sodium edetate comprises 0.01%-0.05% of the total amount; The mannitol is supplemented to 100 g.

[0014] The weight ratio of the spectinomycin hydrochloride to the lincomycin hydrochloride is 2:1 to 4:1.

[0015] The weight ratio of the anhydrous sodium citrate to the anhydrous citric acid is 6:1 to 8:1.

[0016] The weight ratio of the anhydrous sodium citrate to the anhydrous citric acid is 7:1. A preparation method of an injection of spectinomycin hydrochloride lincomycin hydrochloride powder includes the following steps: Step a: raw material processing: in a sterile environment, spectinomycin hydrochloride and lincomycin hydrochloride are respectively subjected to micronization treatment by means of an airflow pulverizer, and the particle size D90 is controlled to be less than 20 μm; Step b: the full amount of spectinomycin hydrochloride + the full amount of lincomycin hydrochloride + the full amount of poloxamer 188 + the full amount of L-leucine after micronization are put into a three-dimensional motion mixer; the rotation speed is set to be 12 rpm, and the mixing time is set to be 15-70 minutes; Step c: in the mixing tank of step b, the pretreated anhydrous sodium citrate, anhydrous citric acid, anhydrous sodium sulfite, disodium edetate are added, and the rotation speed is kept to be 12 rpm, and the mixing is kept for 15 minutes; Step d: in the mixing tank of step c, povidone K-17 and mannitol are added, and the rotation speed is increased to 20 rpm, and the mixing is kept for 15 minutes; Step e: under the operation of A-level laminar flow with relative humidity RH≤30%, the final mixed powder is divided into vials by means of a sterile screw rod dividing machine, a rubber stopper is half-pressed, and the vial is sent into a capping machine to be capped and sealed, and then subjected to lamp inspection, labeling and packaging.

[0017] Further, the mixing time of step b is 50 min.

[0018] The present application has the following beneficial effects: 1: The present application creatively adopts a binary interface modification system of poloxamer 188 + povidone K-17; wherein, micronized poloxamer 188 can significantly reduce the surface tension of the drug microparticles and the oil seed interface, and solve the problem of micro-powder wetting delay; and low molecular weight povidone K-17 forms a hydrophilic gel protective film on the drug surface in situ, effectively shielding the impact of high-concentration drug salt ions on the double electric layer of the oil seed; experiments prove that the synergistic effect of the two can not only realize rapid wetting of the powder in the oil seed within <30 seconds and 24-hour non-emulsion, but also realize second-level reconstitution in injection water and clear transparency, which can be well applied to injection of spectinomycin hydrochloride lincomycin hydrochloride powder that can be dissolved in water and mixed with vaccines.

[0019] 2、The application constructs a citric acid-sodium citrate organic buffer system, and locks a specific mass ratio, which can not only effectively inhibit the alkaline discoloration of spectinomycin and the acid degradation of lincomycin after reconstitution at a pH value of 3.8-4.2, but also minimally interferes with the Zeta potential of the oil slick, avoiding microemulsion breaking caused by electrolyte shock, 3、The preparation method of the application creatively prolongs the mixing time to a specific interval, utilizes the micro-heat generated by low-speed and long-time friction to make poloxamer 188 spread and smear on the surface of the micronized drug, so that the erosion of trace oxygen and moisture in the environment on the drug lattice is effectively blocked, the impurity growth rate is significantly lower than that of the conventional mixing process, and thermal damage deterioration caused by excessive mixing is avoided, and the optimal solution of chemical stability is achieved. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 It is the appearance diagram of the enlarged product of the injection spectinomycin hydrochloride lincomycin hydrochloride powder injection prepared in the embodiment 1 of the application. DETAILED DESCRIPTION

[0021] The application will be further described in detail below with reference to the embodiments, but is not limited to the application, and any equivalent replacement in the art according to the disclosure of the application belongs to the protection scope of the application. Unless otherwise defined, each technical and scientific term used herein has the same meaning as that generally understood by those skilled in the art to which the present application belongs.

[0022] In the present application, the terms "include", "contain" and "contain" and their equivalents should be understood as open, non-exclusive, i.e. "including but not limited to", which means that in addition to the listed elements, components and steps, other unspecified elements, components and steps can also be covered. In this text, unless the context clearly dictates otherwise, a singular term covers a plural reference, and vice versa.

[0023] In the present application, the excipients or reagents related to the injection liquid can come from commercial channels.

[0024] Each of the embodiments 1-6 contains specific ingredients as shown in Table 1: Table 1 An injection spectinomycin hydrochloride lincomycin hydrochloride powder injection is prepared by the following method, comprising the following steps: Step a: raw material treatment: in a sterile environment, spectinomycin hydrochloride and lincomycin hydrochloride are respectively micronized by an airflow pulverizer, and the particle size D90 is controlled to be less than 20 μm.

[0025] Step b: Put the micronized full amount of spectinomycin hydrochloride + full amount of lincomycin hydrochloride + full amount of poloxamer 188 + full amount of L-leucine into a three-dimensional motion mixer; set the rotation speed to 12 rpm and the mixing time to 15 minutes.

[0026] Step c: Add the pretreated anhydrous sodium citrate, anhydrous citric acid, anhydrous sodium sulfite, disodium edetate to the mixing tank of step b, and keep the rotation speed at 12 rpm and mix for 15 minutes.

[0027] Step d: Add povidone K-17 and mannitol to the mixing tank of step c, and increase the rotation speed to 20 rpm and mix for 15 minutes.

[0028] Step e: Under the operation of A-level laminar flow with relative humidity RH≤30%, the final mixed powder is packaged into a vial by a sterile screw packaging machine, the rubber plug is half-pressed, and the cap is sealed by a cap sealing machine. Then, the lamp inspection, labeling and packaging are performed.

[0029] Test example: The following tests are performed for the properties of the powder injection: Resting angle: The powder to be tested is allowed to flow naturally through a funnel of fixed height until the tip of the cone formed touches the outlet of the funnel, and the angle at the bottom of the cone is measured.

[0030] Wetting time (oily): 2.0 g of powder is poured onto the surface of 10 ml of oil adjuvant inactivated vaccine liquid preheated to 37°C at one time without shaking, and the time required for the powder to completely sink and disappear is recorded.

[0031] Sedimentation volume ratio (F): The wetted mixture is vigorously shaken for 30 seconds and then tightly sealed in a graduated cylinder. After 1 hour, the ratio of the height of the sediment (or cream layer) H to the initial height H0 is measured (F = H / H0). Microscopic demulsification detection: A smear of the standing mixture is taken and observed under a 400x optical microscope. If irregular water droplets or continuous water phase with a diameter > 50 μm appear in the field of view, it is determined to be demulsified.

[0032] Needle passability: After mixing 2 g of powder with 10 ml of oil vaccine, a 10 ml disposable syringe with a 7 gauge needle is used for extraction and injection, and the resistance is evaluated.

[0033] Zeta potential: The Zeta potential value of the reconstituted mixture is measured using a Zeta potential analyzer.

[0034] Reconstitution time and clarity (aqueous): 2.0 g of powder is added to 10 ml of water for injection, shaken gently, and the dissolution time is recorded. Visible foreign matter and turbidity are checked under an umbrella lamp.

[0035] Impurity detection: high performance liquid chromatography method is adopted, and the chromatographic conditions in the "spectinomycin hydrochloride" and "lincomycin hydrochloride" items in the Chinese Veterinary Drug Directory are determined, and the contents of impurities spectinomycin acid and impurities lincomycin B are focused on.

[0036] The performance test results of the powder injections of examples 1-6 are shown in table 2: Table 2 The beneficial effects of the present application are illustrated by the following sample examples.

[0037] According to the formulations shown in table 3, samples 1-8 are configured: Table 3 The preparation methods of samples 1-8 are consistent with example 1, and the difference lies in that the amount of the excipients is adjusted according to the above-mentioned formulations.

[0038] The performance test results of the powder injections of samples 1-8 are shown in table 4: Table 4 The test results show that: when only poloxamer 188 is used as in sample 2, although rapid wetting is achieved, but due to the lack of shielding of high-concentration drug ions, serious demulsification of oil droplets occurs within 1 hour, F=0.85; while only using povidone K-17 in sample 1, although the integrity of the interfacial film is maintained, the powder shows serious wetting delay, and the wetting time is more than 300s and the phenomenon of agglomeration and wall hanging.

[0039] In the oil adjuvant vaccine partner, this hydrophobic and charge-sensitive system, the conventional single means of the prior art cannot work; the experimental results confirm that only when poloxamer 188 and povidone K-17 are used in a specific ratio of 4.0%-6.0%:8.0%-12.0% can an unexpected synergistic effect be produced, the micronized poloxamer 188 can significantly reduce the surface tension of the drug microparticles and the oil droplet interface, solving the problem of micron wetting delay; and the low molecular weight povidone K-17 forms a hydrophilic gel protective film in situ on the drug surface, effectively shielding the impact of high-concentration drug salt ions on the double electric layer of the oil droplet; this is not a simple superposition of the functions of the two excipients, but a new oil / water interface steady state is constructed, thereby realizing the seemingly contradictory scheme of rapid wetting and long-term anti-demulsification According to the formulations shown in table 5, samples 9-12 are configured: Table 5 The preparation methods of samples 9-12 are consistent with those of Example 1, except that the amounts of the excipients are adjusted according to the above-mentioned formula.

[0040] The performance test results of the powder injections of samples 9-12 are shown in Table 6: Table 6 The above test data show that the introduction of inorganic strong electrolyte into the oil slick suspension system is the culprit that causes the system to be destroyed, even if sufficient amounts of protective agents and wetting agents are added to the formula, as shown in samples 9 (sodium bisulfate / sodium carbonate) and 10 (phosphate), the strong electrolyte shock of inorganic ions still causes the Zeta potential to drop sharply to -12 mV, triggering irreversible emulsion breaking or salting-out turbidity. This proves that the protective agent cannot resist the destruction of inorganic strong electrolyte.

[0041] In addition, the system shows extremely high sensitivity to pH, and a deviation of pH to below 3.5 (sample 11) causes lincomycin B to surge to 1.2% and serious emulsion breaking; a deviation of pH to above 4.5 (sample 12) causes spectinomycin to discolor (impurity 1.5%). Therefore, the anhydrous sodium citrate / citric acid and the 3.8-4.2 pH window formed thereby determined by the present application are not based on conventional process-wide screening, but are the creative selection of the inventors after excluding the interference of inorganic acids, under the conditions of drug stability and oil slick safety.

[0042] Samples 13-17 are prepared according to the formula shown in Table 7: Table 7 The preparation methods of samples 13-17 are consistent with those of Example 1, except that the amounts of the excipients are adjusted according to the above-mentioned formula.

[0043] The performance test results of the powder injections of samples 13-17 are shown in Table 8: Table 8 In solving the flowability and needle passability problems of micronized drugs, conventional techniques tend to use hydrophobic lubricants (such as magnesium stearate) or large specific surface area flow aids (such as micronized silica gel). However, the present applicant found in the research that these conventional powder engineering means completely fail in the special application scenario of the product, and the test data show that: Even if the formula contains sufficient amounts of wetting agents, sample 14 (magnesium stearate) still wraps the drug due to its extremely strong hydrophobic lotus effect, resulting in a wetting time > 600 s and being unable to be extracted; and sample 15 (micronized silica gel) introduces unacceptable turbidity and antigen adsorption risks.

[0044] The technical scheme of the present application breaks the routine and introduces L-leucine as a carrier. Data show that 5.0%-7.0% L-leucine not only significantly improves the rest angle from 48° to 28°, but more importantly, it ensures that the high-concentration suspension can smoothly pass through a 7-gauge needle without interfering with the wetting effect of poloxamer, overcoming the industry prejudice that the existing technology is prone to caking and difficult to inject.

[0045] Preparation method optimization: Preparation method 1: according to the formulation of Example 1, the specific preparation method comprises the following steps: Step a: raw material processing: in a sterile environment, the hydrochloric acid spectinomycin and the hydrochloric acid lincomycin are respectively subjected to micronization treatment by an airflow pulverizer, and the particle size D90 is controlled to be less than 20 μm.

[0046] Step b: the full amount of micronized hydrochloric acid spectinomycin + full amount of hydrochloric acid lincomycin + full amount of poloxamer 188 + full amount of L-leucine is put into a three-dimensional motion mixer. The rotation speed is set to 12 rpm, and the mixing time is set to 15 minutes.

[0047] Step c: to the mixing tank of step b, add the pretreated anhydrous sodium citrate, anhydrous citric acid, anhydrous sodium sulfite, disodium edetate, and keep the rotation speed at 12 rpm, mix for 15 minutes.

[0048] Step d: to the mixing tank of step c, add povidone K-17 and mannitol, and increase the rotation speed to 20 rpm, mix for 15 minutes.

[0049] Step e: under the operation of A-level laminar flow with relative humidity RH≤30%, the final mixed powder is packaged into a test tube by a sterile screw rod packaging machine, the rubber plug is half-pressed, and the cap is sealed by a cap rolling machine. Perform lamp inspection, labeling, and packaging.

[0050] Preparation method 2: the preparation method 2 is different from the preparation method 1 only in step b, and the rest of the preparation method is the same as the preparation method 1.

[0051] Step b of the preparation method 2: the full amount of micronized hydrochloric acid spectinomycin + full amount of hydrochloric acid lincomycin + full amount of poloxamer 188 + full amount of L-leucine is put into a three-dimensional motion mixer. The rotation speed is set to 12 rpm, and the mixing time is set to 30 minutes.

[0052] Preparation method 3: the preparation method 3 is different from the preparation method 1 only in step b, and the rest of the preparation method is the same as the preparation method 1.

[0053] Step b of Preparation Method 3: The micronized full amount of spectinomycin hydrochloride + full amount of lincomycin hydrochloride + full amount of poloxamer 188 + full amount of L-leucine were put into the three-dimensional motion mixer. The rotation speed was set to 12 rpm, and the mixing time was set to 50 minutes.

[0054] Preparation Method 4: The preparation method 4 is the same as the preparation method 1 except that step b is different from the preparation method 1.

[0055] Step b of Preparation Method 4: The micronized full amount of spectinomycin hydrochloride + full amount of lincomycin hydrochloride + full amount of poloxamer 188 + full amount of L-leucine were put into the three-dimensional motion mixer. The rotation speed was set to 12 rpm, and the mixing time was set to 70 minutes.

[0056] The products prepared by the preparation methods 1-4 were tested for initial impurities and impurity increase rate after being placed under accelerated conditions (40°C / 75%RH) for 3 months; Table 9 The applicant found that through the optimization of the preparation method, especially by controlling the mixing time and cooling rate in step b of the preparation method, the impurity reduction of the powder injection of the present application after long-term storage can be greatly enhanced, which is unexpected. By extending the mixing time to a certain interval, it is possible to use the micro-heat generated by low-speed and long-time friction to spread and smear the poloxamer 188 on the surface of the micronized drug; thus, the invasion of trace oxygen and moisture in the environment on the drug crystal lattice can be effectively blocked; the impurity increase rate is significantly lower than that of the conventional mixing process, and when the mixing time is further extended to 70 minutes (preparation method 4), the impurity increase rate rises to 0.65% instead. This may be because excessive mechanical shear force causes local thermal damage or amorphization of the drug crystal lattice. Therefore, the 30-50 minute mixing time locked by the present application can achieve the optimal solution of chemical stability, which constitutes a significant technical feature of the present application in the preparation process.

[0057] For purposes of description and disclosure, all patents, patent applications, and other publications are expressly incorporated herein by reference. Such publications are provided solely for their disclosure prior to the filing date of the present application. All statements as to the date or contents of these publications are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates or contents of these documents. Further, nothing herein is to be construed as an admission that these publications are part of the state of the art or are common general knowledge.

[0058] The above detailed description of the specific embodiments of the present application has been given to understand the purpose, technical solutions and beneficial effects of the present application. It should be understood that the above description is only a specific embodiment of the present application and is not used to limit the protection scope of the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A spectinomycin hydrochloride and lincomycin hydrochloride powder for injection, characterized in that, It contains: spectinomycin hydrochloride and lincomycin hydrochloride, accounting for 65.0%-75.0% of the total; Poloxamer 188 accounts for 4.0%-6.0% of the total; Povidone K-17 accounts for 8.0%-12.0% of the total; Anhydrous sodium citrate and anhydrous citric acid together account for 5.0%-8.0% of the total. L-Leucine accounts for 5.0%-7.0% of the total; Anhydrous sodium sulfite accounts for 0.3%-0.5% of the total. Disodium edetate accounts for 0.01%-0.05% of the total; Mannitol was replenished to 100%.

2. The spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 1, characterized in that, Based on a total weight of 100g, it contains: 46.6g spectinomycin hydrochloride, 23.4g lincomycin hydrochloride, 5.0g poloxamer 188, 10.0g povidone K-17, 5.7g anhydrous sodium citrate, 0.8g anhydrous citric acid, 6.0g L-leucine, 0.4g anhydrous sodium sulfite, 0.02g disodium edetate, and mannitol to bring the total weight to 100g.

3. The spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 1, characterized in that, The weight ratio of spectinomycin hydrochloride to lincomycin hydrochloride is 2:1 to 4:

1.

4. The spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 1, characterized in that, The weight ratio of anhydrous sodium citrate to anhydrous citric acid is 6:1 to 8:

1.

5. The spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 4, characterized in that, The weight ratio of anhydrous sodium citrate to anhydrous citric acid is 7:

1.

6. The spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 1, characterized in that, The pH value of the spectinomycin hydrochloride and lincomycin hydrochloride powder for injection after reconstitution is 3.8-4.

2.

7. A method for preparing spectinomycin hydrochloride and lincomycin hydrochloride powder for injection, characterized in that, The preparation method includes the following steps: Step a: Raw material processing: Under sterile conditions, spectinomycin hydrochloride and lincomycin hydrochloride were respectively micronized by air jet mill to control the particle size D90 < 20 μm; Step b: Add the micronized total amount of spectinomycin hydrochloride + total amount of lincomycin hydrochloride + total amount of poloxamer 188 + total amount of L-leucine into a three-dimensional motion mixer; set the speed to 12 rpm and the mixing time to 15-70 minutes; Step c: Add the pretreated anhydrous sodium citrate, anhydrous citric acid, anhydrous sodium sulfite, and disodium edetate to the mixing tank of step b, and mix for 15 minutes while maintaining a speed of 12 rpm. Step d: Add povidone K-17 and mannitol to the mixing tank from step c, increase the speed to 20 rpm, and mix for 15 minutes; Step e: Under Class A laminar flow conditions with relative humidity RH≤30%, the final mixed powder is dispensed into vials using a sterile screw dispenser, partially sealed with rubber stoppers, and then fed into a capping machine for sealing. The vials are then inspected by light, labeled, and packaged.

8. The method for preparing spectinomycin hydrochloride and lincomycin hydrochloride powder for injection according to claim 7, characterized in that, The mixing time in step b of the preparation method is 50 min.

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