Equal-particle-number symmetric eutectic preparation process of medical-grade dextroborneol and levoborneol

Abstract

The invention relates to a medical-grade dextrorotatory borneol and levorotatory borneol equal-particle-number symmetric eutectic preparation process. The preparation process comprises the steps of raw material pretreatment, raw material weighing, vacuum premixing, low-temperature activation, gradient directional eutectic, low-temperature curing and sterile crushing. According to the invention, equal microscopic particle number is fundamentally ensured through the ratio of the amount of substance to the amount of substance of 1: 1, molecular-level physical coincidence is realized by combining gradient temperature control and directional crystallization, the prepared eutectic product has near-zero optical rotation, regular crystal form and high batch consistency, the problems of large curative effect difference and insufficient targeting property of the traditional mixing process are solved, and the application prospect is wide. And the process is safe and controllable, and is suitable for medical-grade large-scale production.

Description

Preparation process of medical-grade dextrorotatory borneol and levorotatory borneol iso-particle number-symmetric eutectic Technical Field

[0001] This invention relates to the technology of physical blending, directional crystallization and preparation of raw materials for precise diagnosis and treatment of medical hand-operated drugs, specifically to a process for preparing medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry eutectic. Background Technology

[0002] Dextrorotatory borneol and levorotatory borneol, as chiral enantiomers of natural borneol, are widely used in clinical fields such as psychiatric stimulation, anti-inflammatory and analgesic effects, drug penetration enhancement, and mucosal permeability improvement. Current technologies mostly employ mechanical mixing, melt blending, or grinding methods with a 1:1 mass ratio, achieving only macroscopic homogeneity and failing to ensure equal molecular or particle numbers at the microscopic level. The mixing process is random and disordered, easily leading to problems such as local chirality excess, crystal segregation, and optical rotation shift, directly resulting in inconsistent therapeutic effects, significant batch-to-batch differences, and unstable bioavailability. Currently, there is a lack of a purely physical process that can achieve precise particle number balance, molecular orientation, and ordered cocrystallization, failing to meet the needs of high-end medical precision diagnosis and treatment. Therefore, it is essential to design a process for preparing medical-grade dextrorotatory borneol and levorotatory borneol cocrystallization with symmetrical particle numbers. Summary of the Invention

[0003] This invention overcomes the shortcomings of existing mixing processes, such as unequal number of microparticles, disordered arrangement, and unstable therapeutic effects, and provides a process for preparing medical-grade borneol eutectic with equal particle number, symmetrical arrangement, and physical consistency.

[0004] To achieve the above objectives, the technical solution of this invention is: a process for preparing a symmetric eutectic of medical-grade dextrorotatory borneol and levorotatory borneol, comprising the following steps: S1, raw material pretreatment: vacuum drying of medical-grade dextrorotatory borneol and levorotatory borneol separately; S2, raw material weighing: weighing according to a molar ratio of 1:1 to ensure absolute equality of the number of microscopic particles; S3, vacuum premixing: adding the raw materials into a sealed vacuum vessel and premixing at low speed; S4, low-temperature activation: heating to 65±1℃ for molecular softening activation; S5, gradient oriented eutectic: segmented cooling at a rate of 0.5℃ / min to achieve mirror-image alignment of molecules; S6, low-temperature curing; S7, aseptic pulverization: pulverizing and passing through a 200-mesh sieve to obtain the symmetric eutectic product.

[0005] The drying conditions involved in step S1 are as follows: temperature is 55℃, pressure is -0.08MPa, and drying time is 120min.

[0006] The low-speed stirring premixing time in step S3 is 15 minutes.

[0007] The heating rate in step S4 is set to 1℃ / min, and the activation isothermal duration is 20min.

[0008] The gradient eutectic process involved in step S5 is divided into three stages: cooling from 65°C to 55°C and holding at that temperature for 10 minutes; cooling from 55°C to 40°C and holding at that temperature for 15 minutes; and finally cooling from 40°C to 25°C and holding at that temperature for 20 minutes.

[0009] The finished product has an optical rotation of -0.5° to +0.5°, with ordered molecular arrangement, no segregation, and no excess chirality.

[0010] By adopting the above technical solution, the beneficial effects of the present invention are: 1. The number of particles is completely equal, eliminating arrangement deviations from the root; 2. The molecular mirror image is completely consistent in physical structure, forming a regular racemic eutectic; 3. The diagnostic and therapeutic effects are highly stable, without chiral excess or crystal segregation problems; 4. It adopts a purely physical method, without solvent addition or chemical reaction, meeting medical-grade standards; 5. The process is feasible for industrialization, with strong batch-to-batch consistency. Attached Figure Description

[0011] Figure 1 is a schematic diagram of the steps of the present invention; Detailed Implementation

[0012] To further explain the technical solution of the present invention, the present invention will be described in detail below through specific embodiments.

[0013] As shown in Figure 1, the preparation process of this medical-grade dextrorotatory borneol and levorotatory borneol equivalent particle number symmetric eutectic includes the following steps: S1, raw material pretreatment: medical-grade dextrorotatory borneol and levorotatory borneol are vacuum dried separately; S2, raw material weighing: raw materials are weighed at a molar ratio of 1:1 to ensure that the number of microscopic particles is absolutely equal; S3, vacuum premixing: raw materials are put into a sealed vacuum vessel and premixed at low speed; S4, low-temperature activation: molecular softening activation is performed by heating to 65±1℃; S5, gradient oriented eutectic: segmented cooling is performed at a rate of 0.5℃ / min to achieve mirror alignment of molecules; S6, low-temperature curing; S7, aseptic pulverization: after pulverization, the product is passed through a 200-mesh sieve to obtain the symmetric eutectic finished product.

[0014] The drying conditions involved in step S1 are as follows: temperature is 55℃, pressure is -0.08MPa, and drying time is 120min.

[0015] The low-speed stirring premixing time in step S3 is 15 minutes.

[0016] The heating rate in step S4 is set to 1℃ / min, and the activation isothermal duration is 20min.

[0017] The gradient eutectic process involved in step S5 is divided into three stages: cooling from 65℃ to 55℃ and holding for 10 min; cooling from 55℃ to 40℃ and holding for 15 min; and finally cooling from 40℃ to 25℃ and holding for 20 min.

[0018] The finished product has an optical rotation of -0.5° to +0.5°, with ordered molecular arrangement, no segregation, and no excess chirality.

[0019] In practice, this also includes the finished product inspection and packaging in step S8. Example

[0020] Take 154.25 mg each of medical-grade dextrorotatory borneol and levorotatory borneol (molar ratio 1:1), vacuum dry at 55°C for 120 min, vacuum premix for 15 min, activate at 65°C for 20 min, gradient cooling eutectic, and low-temperature pulverize through a 200-mesh sieve to obtain a symmetrical eutectic product with 0° optical rotation. Example

[0021] Kilogram-level mass production: Mixed in a 1:1 ratio of substances, produced in a closed 100,000-level clean area, with an optical rotation of -0.3° to +0.3°, uniform crystal form, and a difference of <1% in treatment effect.

[0022] In summary, the obtained products have an equal number of microscopic particles, symmetrical arrangement, and highly uniform and stable therapeutic effects.

[0023] All of the above components are general standard parts or components known to those skilled in the art. Their structure and principles can be learned by those skilled in the art through technical manuals or conventional experimental methods.

[0024] The above embodiments and figures are not intended to limit the product form and style of the present invention. Any appropriate changes or modifications made by those skilled in the art should be considered as not departing from the patent scope of the present invention.

Claims

1. A process for preparing a medical-grade dextrorotatory borneol and levorotatory borneol equipment number-symmetric eutectic, characterized in that, Includes the following steps: S1. Raw material pretreatment: Medical-grade dextrorotatory borneol and levorotatory borneol are vacuum dried separately; S2. Raw material weighing: Weigh the raw materials according to a 1:1 molar ratio to ensure an absolute equality in the number of microscopic particles; S3. Vacuum premixing: Add the raw materials to a sealed vacuum reactor and stir at low speed for premixing; S4. Low-temperature activation: Heat to 65±1℃ for molecular softening and activation; S5. Gradient oriented eutectic: Cool in segments at a rate of 0.5℃ / min to achieve mirror-image alignment of molecules; S6. Low-temperature curing; S7. Aseptic pulverization: After pulverization, pass through a 200-mesh sieve to obtain a symmetrical eutectic product.

2. The preparation process of medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry according to claim 1, characterized in that, The drying conditions involved in step S1 are as follows: temperature is 55℃, pressure is -0.08MPa, and drying time is 120min.

3. The preparation process of medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry according to claim 1, characterized in that, The low-speed stirring premixing time in step S3 is 15 minutes.

4. The preparation process of medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry eutectic as described in claim 1, characterized in that, The heating rate in step S4 is set to 1℃ / min, and the activation isothermal duration is 20min.

5. The preparation process of medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry eutectic as described in claim 1, characterized in that, The gradient eutectic process involved in step S5 is divided into three stages: cooling from 65°C to 55°C and holding at that temperature for 10 minutes; cooling from 55°C to 40°C and holding at that temperature for 15 minutes; and finally cooling from 40°C to 25°C and holding at that temperature for 20 minutes.

6. The preparation process of medical-grade dextrorotatory borneol and levorotatory borneol with equal particle number symmetry eutectic as described in claim 1, characterized in that, The finished product has an optical rotation of -0.5° to +0.5°, with ordered molecular arrangement, no segregation, and no excess chirality.

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