Preparation method of high-stability antioxidant oxytetracycline hydrochloride

Abstract

The invention belongs to the field of chemical preparation, and particularly relates to a preparation method of high-stability antioxidant oxytetracycline hydrochloride, which comprises the following steps: (1) quantitatively adding methanol into a dissolving kettle through a high-position metering tank, adding anhydrous calcium chloride, and stirring until the calcium chloride is completely dissolved; (2) adding oxytetracycline until the oxytetracycline is stirred and dissolved to obtain an oxytetracycline solution; (3) feeding the oxytetracycline solution into a crystallization kettle by using nitrogen through a stainless steel press filter and a material filter to obtain a high-stability antioxidant oxytetracycline solution; and (4) adding a hydrogen chloride methanol solution into the high-stability antioxidant oxytetracycline solution, stirring and crystallizing to obtain oxytetracycline hydrochloride crystals. By controlling the proportion of methanol, anhydrous calcium chloride and oxytetracycline, it is guaranteed that the oxytetracycline hydrochloride crystal form is uniform in size; according to the stirring device, materials are stirred through overturning type stirring and inertia, so that the mixing uniformity of a solution is greatly improved.

Description

Technical Field

[0001] The invention belongs to the field of oxytetracycline preparation, and specifically relates to a method for preparing highly stable antioxidant oxytetracycline hydrochloride. Background Art

[0002] In the existing process, the production process of oxytetracycline hydrochloride is to use methanol as a solvent to dissolve the raw material oxytetracycline base; after standing for nearly 10 hours, cooling, crystallizing, and centrifuging, oxytetracycline hydrochloride is obtained. The existing process has the following problems: the oxytetracycline hydrochloride crystals obtained by the current process have small grains, and the raw material oxytetracycline base is not completely dissolved. Summary of the invention

[0003] In order to solve the above technical problems, the present invention provides a method for preparing highly stable antioxidant oxytetracycline hydrochloride, comprising: (1) quantitatively put methanol into a dissolving kettle through a high-level metering tank, add anhydrous calcium chloride, and stir until the calcium chloride is completely dissolved; (2) adding oxytetracycline until it is dissolved by stirring to obtain an oxytetracycline solution; (3) using nitrogen to pass the oxytetracycline solution through a stainless steel filter press and a material filter into a crystallization kettle to obtain a highly stable antioxidant oxytetracycline solution; (4) Adding the methanol solution of hydrogen chloride to the highly stable antioxidant oxytetracycline solution, stirring and crystallizing to obtain oxytetracycline hydrochloride crystals.

[0004] Furthermore, the mass ratio of the methanol, anhydrous calcium chloride and oxytetracycline is 50~60:3~4:15~20.

[0005] Furthermore, in step (1), the dissolving temperature is 27-31° C., and the stirring time is 30-35 minutes. In step (2), the stirring time is 40 to 45 minutes, and the stirring temperature is 26 to 30° C.; In step (4), the stirring time is 25 to 35 minutes, and the stirring temperature is less than or equal to 30°C.

[0006] The present invention also provides a preparation device for high-stability antioxidant oxytetracycline hydrochloride, wherein the dissolving kettle comprises: a rotating frame and a reaction kettle rotatably arranged on the rotating frame; The reactor comprises a support rotatably arranged on the rotating frame and a reaction cylinder slidably arranged on the support, wherein: The reaction cylinder is suitable for sliding along the length direction of the bracket.

[0007] Furthermore, the bracket is provided with a rotating cylinder, the rotating frame is provided with a hinged seat, and, The side wall of the reaction cylinder is provided with a waist-shaped hole, wherein: The rotating shaft passes through the hinge seat, the rotating cylinder and the waist-shaped hole in sequence to enter the reaction cylinder.

[0008] Furthermore, a stirring blade is provided at one end of the rotating shaft extending into the reaction cylinder.

[0009] Furthermore, one end of the rotating shaft away from the stirring blade is transmission-connected to the motor.

[0010] Furthermore, a guide groove is provided on the bracket, and a guide block adapted to the guide groove is provided on the outer wall of the reaction tube to limit the sliding stroke of the reaction tube.

[0011] Furthermore, a liquid inlet is provided at the top of the reaction cylinder, and a liquid discharge port is provided at the bottom of the reaction cylinder, wherein: The liquid discharge port is communicated with the valve.

[0012] Furthermore, the size of the reaction cylinder is adapted to the inner diameter of the bracket.

[0013] The beneficial effects of the present invention are that the present invention controls the ratio of methanol, anhydrous calcium chloride and oxytetracycline, thereby ensuring uniform size of oxytetracycline hydrochloride crystals; the present invention stirs the materials by flipping stirring and utilizing inertia to greatly improve the mixing uniformity of the solution.

[0014] Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practicing the present invention.

[0015] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, preferred embodiments are given below and described in detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0017] Figure 1 It is a schematic diagram of the overall structure of a preferred embodiment of the present invention; Figure 2 It is a schematic diagram of the reaction tube structure of a preferred embodiment of the present invention; Figure 3 It is a schematic diagram of the rotating drum structure of a preferred embodiment of the present invention.

[0018] In the figure: 100, bracket, 110, reaction tube, 120, rotating tube, 130, hinge seat, 140, waist-shaped hole, 150, rotating shaft, 160, valve. DETAILED DESCRIPTION

[0019] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0020] Example 1: A method for preparing a highly stable antioxidant oxytetracycline hydrochloride of this embodiment comprises the following steps: (1) quantitatively placing 1000 kg of methanol into a dissolving kettle through a high-level metering tank, adding 60 kg of anhydrous calcium chloride, controlling the dissolving temperature at 27° C. by using frozen brine or steam, and stirring and dissolving for 30 minutes until the calcium chloride is completely dissolved; (2) adding 300 kg of oxytetracycline, stirring and dissolving for 40 minutes, controlling the temperature at 26° C., and obtaining an oxytetracycline solution; (3) using nitrogen to pass the oxytetracycline solution through a stainless steel filter press and a material filter into a crystallization kettle to obtain a highly stable antioxidant oxytetracycline solution; (4) Adding the methanol solution of hydrogen chloride to the high-stability antioxidant oxytetracycline solution, stirring for 25 minutes, controlling the temperature at 26° C., and crystallizing to obtain oxytetracycline hydrochloride crystals.

[0021] Example 2: A method for preparing a highly stable antioxidant oxytetracycline hydrochloride according to the present embodiment comprises the following steps: (1) quantitatively placing 1100 kg of methanol into a dissolving kettle through a high-level metering tank, adding 70 kg of anhydrous calcium chloride, controlling the dissolving temperature at 29° C. by using chilled brine or steam, and stirring and dissolving for 32 minutes until the calcium chloride is completely dissolved; (2) adding 350 kg of oxytetracycline, stirring and dissolving for 42 minutes, controlling the temperature at 28° C., and obtaining an oxytetracycline solution; (3) using nitrogen to pass the oxytetracycline solution through a stainless steel filter press and a material filter into a crystallization kettle to obtain a highly stable antioxidant oxytetracycline solution; (4) Adding the methanol solution of hydrogen chloride to the high-stability antioxidant oxytetracycline solution, stirring for 30 minutes, controlling the temperature at 28° C., and crystallizing to obtain oxytetracycline hydrochloride crystals.

[0022] Example 3: A method for preparing a highly stable antioxidant oxytetracycline hydrochloride of this embodiment comprises the following steps: (1) quantitatively placing 1200 kg of methanol into a dissolving kettle through a high-level metering tank, adding 80 kg of anhydrous calcium chloride, controlling the dissolving temperature at 31° C. by using frozen brine or steam, and stirring and dissolving for 35 minutes until the calcium chloride is completely dissolved; (2) adding 400 kg of oxytetracycline, stirring and dissolving for 45 minutes, controlling the temperature at 30° C., to obtain an oxytetracycline solution; (3) using nitrogen to pass the oxytetracycline solution through a stainless steel filter press and a material filter into a crystallization kettle to obtain a highly stable antioxidant oxytetracycline solution; (4) Adding the methanol solution of hydrogen chloride to the highly stable antioxidant oxytetracycline solution, stirring for 35 minutes, controlling the temperature at 30° C., and crystallizing to obtain oxytetracycline hydrochloride crystals.

[0023] like Figures 1 to 3 As shown, the dissolving kettle comprises: a rotating frame and a reaction kettle rotatably arranged on the rotating frame; the reaction kettle comprises a bracket 100 rotatably arranged on the rotating frame and a reaction barrel 110 slidably arranged on the bracket 100, wherein the reaction barrel 110 is suitable for sliding along the length direction of the bracket 100. The existing stirring and mixing equipment can only put the liquid into the stirring barrel and mix it by rotating the blades. In the present application, the sliding of the reaction barrel 110 on the bracket 100 is used to utilize inertia to mix the liquid in the reaction barrel 110, which can improve the uniformity effect and prevent the occurrence of sediment.

[0024] The support 100 is provided with a rotating cylinder 120, the rotating frame is provided with an articulated seat 130, and the side wall of the reaction cylinder 110 is provided with a waist-shaped hole 140, wherein the rotating shaft 150 sequentially passes through the articulated seat 130, the rotating cylinder 120 and the waist-shaped hole 140 to enter the reaction cylinder 110. The diameter of the rotating cylinder 120 is larger than the length of the waist-shaped hole 140, and the waist-shaped hole 140 fits with one side of the rotating cylinder 120, thereby ensuring that the material will not fall from the waist-shaped hole 140; the width direction of the waist-shaped hole 140 is adapted to the diameter direction of the rotating shaft 150, so that the rotating shaft 150 can slide in the waist-shaped hole 140. The inner diameter of the rotating cylinder 120 is adapted to the rotating shaft 150, and the rotating shaft 150 passes through the rotating cylinder 120 and is fixedly connected to the rotating cylinder 120 without shaking; the hinge seat 130 is fixed on the rotating frame, and the rotating shaft 150 passes through the hinge seat 130, the rotating cylinder 120 and the waist-shaped hole 140 in sequence to the reaction cylinder 110. The end of the rotating shaft 150 extending into the reaction cylinder 110 is provided with a stirring blade, and the end of the rotating shaft 150 away from the stirring blade is connected to the motor transmission. The motor drives the rotating shaft 150 to rotate, the rotating shaft 150 drives the rotating cylinder 120 to rotate, and the rotating cylinder 120 drives the bracket 100 to rotate, so that the bracket 100 drives the reaction cylinder 110 to rotate.

[0025] Continue to see Figures 1 to 3 , the support 100 is provided with a guide groove, and the outer wall of the reaction cylinder 110 is provided with a guide block adapted to the guide groove to limit the sliding stroke of the reaction cylinder 110. In order to prevent the reaction cylinder 110 from sliding away from the support 100 along the length direction of the support 100, a guide block is provided on the outer wall of the reaction cylinder 110, and a guide groove is provided on the support 100, and the guide block is slidably arranged in the guide groove. In order to improve the sliding stability of the reaction cylinder 110, the size of the reaction cylinder 110 is adapted to the inner diameter of the support 100.

[0026] A liquid inlet is formed at the top of the reaction cylinder 110 , and a liquid discharge port is formed at the bottom of the reaction cylinder 110 , wherein the liquid discharge port is communicated with the valve 160 .

[0027] In the description of the embodiments of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0028] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0029] In the several embodiments provided in the present application, it should be understood that the disclosed systems, devices and methods can be implemented in other ways. The device embodiments described above are merely schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation. For example, multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some communication interfaces, and the indirect coupling or communication connection of devices or units can be electrical, mechanical or other forms.

[0030] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0031] In addition, each functional unit in each embodiment of the present invention may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit.

[0032] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A method for preparing highly stable antioxidant oxytetracycline hydrochloride, characterized in that: The following steps are involved: (1) quantitatively put methanol into a dissolving kettle through a high-level metering tank, add anhydrous calcium chloride, and stir until the calcium chloride is completely dissolved; (2) adding oxytetracycline until it is dissolved by stirring to obtain an oxytetracycline solution; (3) using nitrogen to pass the oxytetracycline solution through a stainless steel filter press and a material filter into a crystallization kettle to obtain a highly stable antioxidant oxytetracycline solution; (4) Adding the methanol solution of hydrogen chloride to the highly stable antioxidant oxytetracycline solution, stirring and crystallizing to obtain oxytetracycline hydrochloride crystals.

2. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 1, characterized in that: The mass ratio of the methanol, anhydrous calcium chloride and oxytetracycline is 50-60:3-4:15-20.

3. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 1, characterized in that: In step (1), the dissolving temperature is 27-31° C., and the stirring time is 30-35 minutes; In step (2), the stirring time is 40 to 45 minutes, and the stirring temperature is 26 to 30° C.; In step (4), the stirring time is 25 to 35 minutes, and the stirring temperature is less than or equal to 30°C.

4. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 1, characterized in that: The dissolving kettle comprises: A rotating frame and a reaction kettle rotatably arranged on the rotating frame; The reactor comprises a support rotatably arranged on the rotating frame and a reaction cylinder slidably arranged on the support, wherein: The reaction cylinder is suitable for sliding along the length direction of the bracket.

5. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 4, characterized in that: The support is provided with a rotating cylinder, the rotating frame is provided with a hinged seat, and, The side wall of the reaction cylinder is provided with a waist-shaped hole, wherein: The rotating shaft passes through the hinge seat, the rotating cylinder and the waist-shaped hole in sequence to enter the reaction cylinder.

6. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 5, characterized in that: A stirring blade is arranged at one end of the rotating shaft extending into the reaction cylinder.

7. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 6, characterized in that: One end of the rotating shaft away from the stirring blade is transmission-connected to the motor.

8. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 4, characterized in that: The bracket is provided with a guide groove, and the outer wall of the reaction tube is provided with a guide block adapted to the guide groove to limit the sliding stroke of the reaction tube.

9. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 4, characterized in that: The top of the reaction cylinder is provided with a liquid inlet, and the bottom of the reaction cylinder is provided with a liquid outlet, wherein: The liquid discharge port is communicated with the valve.

10. The method for preparing the highly stable antioxidant oxytetracycline hydrochloride according to claim 9, characterized in that: The size of the reaction cylinder is adapted to the inner diameter of the support.

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