Chuanhuning freeze-dried injection and preparation method thereof

Abstract

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a freeze-dried injection of guanin and a preparation method thereof. The preparation method of the freeze-dried injection of guanin is as follows: after the raw materials are uniformly mixed, the raw materials are filled into a Westlin bottle, and pre-freezing, primary drying and analytical drying are sequentially performed; wherein, the pre-freezing condition is to keep the temperature at-40 DEG C for 1.5-3 hours; the primary drying condition is performed according to the following procedure: gradient temperature rising in the range of-20 DEG C to 15 DEG C, and the time is 9-25.5 hours; the analytical drying condition is to keep the temperature at 45 DEG C for 3-7 hours. The freeze-dried injection of guanin prepared by the application has better appearance and color, meets the quality standard requirements of the product, and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to an injectable lyophilized form of Chuanhuning and its preparation method. Background Technology

[0002] Lyophilized injections are a type of pharmaceutical dosage form that removes moisture from drugs through low-temperature freezing to produce a dry powder or granular preparation. When needed, simply add an appropriate amount of solvent (such as water for injection) to quickly restore the drug to its original solution state, facilitating injection or infusion. The advantages of lyophilized injections include: good stability, convenient storage, rapid dissolution, and reduced injection pain.

[0003] Andrographolide for injection is an antiviral drug commonly used to treat viral pneumonia, viral upper respiratory tract infections, and other conditions. It is composed of sodium andrographolide monosuccinate half-ester, sodium bicarbonate, and sodium hydroxide, and has effects such as clearing heat and detoxifying, anti-inflammation, and antitussive properties. Andrographolide for injection has inhibitory effects on various viruses, such as influenza virus, respiratory syncytial virus, and adenovirus. Its mechanism of action is mainly through inhibiting viral replication and enhancing the function of the immune system. In addition, Andrographolide for injection can also reduce inflammatory responses, relieve symptoms such as cough, and has a certain therapeutic effect on some chronic inflammatory diseases such as chronic bronchitis.

[0004] Lyophilization is the core process for lyophilized injectables, affecting the product's appearance, internal quality, and stability. Different drugs require unique optimization of their lyophilization processes; otherwise, quality problems such as poor appearance and unacceptable solution color can easily occur. Current research lacks specific studies on the lyophilization process for injectable chuanhuning, and existing lyophilization processes cannot yield high-quality injectable chuanhuning lyophilized formulations. Therefore, there is an urgent need in this field to optimize the process for injectable chuanhuning lyophilized formulations. Summary of the Invention

[0005] To address the problems of existing technologies, this invention provides an injectable lyophilized form of chuanhuning and its preparation method.

[0006] A lyophilized injectable form of chuanhuning is made from the following raw materials in parts by weight:

[0007] Chuanhuning 16-24 parts

[0008] Sodium bicarbonate 2.4–3.6 parts,

[0009] 4-6 portions of glucose

[0010] Activated carbon 1.2–1.8 parts

[0011] 800-1200 parts water

[0012] The amount of sodium hydroxide used should be sufficient to adjust the pH to 6.5–7.2;

[0013] The preparation method is as follows: the raw materials are mixed, filled into vials, and then subjected to pre-freezing, primary drying, and analytical drying in sequence;

[0014] in,

[0015] Pre-freezing conditions include maintaining a constant temperature of -40 to -50°C for 1.5 to 3 hours;

[0016] The drying process is carried out under the following conditions: temperature gradient within the range of -20℃ to 15℃, for a time of 9 to 25.5 hours;

[0017] The drying conditions were constant temperature of -40 to -50℃ for 3 to 7 hours.

[0018] Preferably, the pre-freezing, primary drying, and desorption drying are performed in a freeze dryer.

[0019] Preferably, the drying conditions are performed according to the following procedure:

[0020] Maintain a constant temperature of -20℃ for 0.5 to 2 hours;

[0021] Keep at -10℃ for 2 to 4 hours;

[0022] Keep at -5℃ for 5 to 8 hours;

[0023] Maintain temperature at 0℃ for 1–10 minutes;

[0024] Keep at a constant temperature of 15℃ for 0.5 to 1.5 hours.

[0025] Preferably, during the primary drying process, the vacuum level is controlled at 10–20 Pa.

[0026] Preferably, the desorption and drying conditions are performed according to the following procedure:

[0027] The temperature was kept constant at 45℃ for 1 hour, and the vacuum degree was controlled at 10-20 Pa.

[0028] Maintain a constant temperature of 45℃ for 2–6 hours, with the front chamber controlled at 0–10 Pa.

[0029] The present invention also provides a method for preparing the above-mentioned injectable lyophilized cypermethrin, comprising the following steps: mixing the raw materials, filling them into vials, and sequentially performing pre-freezing, primary drying, and analytical drying;

[0030] in,

[0031] Pre-freezing conditions include maintaining a constant temperature of -40 to -50°C for 1.5 to 3 hours;

[0032] The drying process is carried out under the following conditions: temperature gradient within the range of -20℃ to 15℃, for a time of 9-25.5 hours;

[0033] The drying conditions are constant temperature of 40-50℃ for 3-7 hours.

[0034] Preferably, the pre-freezing, primary drying, and desorption drying are performed in a freeze dryer.

[0035] Preferably, the drying conditions are performed according to the following procedure:

[0036] Maintain a constant temperature of -20℃ for 0.5 to 2 hours;

[0037] Keep at -10℃ for 2 to 4 hours;

[0038] Keep at -5℃ for 5 to 8 hours;

[0039] Maintain temperature at 0℃ for 1–10 minutes;

[0040] Keep at a constant temperature of 15℃ for 0.5 to 1.5 hours.

[0041] Preferably, during the primary drying process, the vacuum level is controlled at 10–20 Pa.

[0042] Preferably, the desorption and drying conditions are performed according to the following procedure:

[0043] The temperature was kept constant at 45℃ for 1 hour, and the vacuum degree was controlled at 10-20 Pa.

[0044] Maintain a constant temperature of 45℃ for 2–6 hours, with the front chamber controlled at 0–10 Pa.

[0045] This invention optimizes the freeze-drying process for injectable cymenein lyophilized concentrate, solving the problem that existing freeze-drying processes fail to achieve satisfactory appearance or color. It improves the quality of injectable cymenein lyophilized concentrate, ensuring that its appearance and color meet standard requirements (appearance: white to slightly yellow freeze-dried lumps or powder; solution color: lighter than yellow or yellowish-green No. 4 standard colorimetric solution). Therefore, this invention has excellent application prospects.

[0046] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0047] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0048] In the following examples, reagents and raw materials not specifically described are all commercially available products.

[0049] Example 1: Lyophilized Chuanhuning for Injection

[0050] The raw materials used in this embodiment to prepare the injectable lyophilized Chuanhuning preparation are as follows:

[0051] Wearing Huning 20mg Sichuan Mianzhu Yonglong Biological Products Co., Ltd. Sodium bicarbonate 3mg Hebei Huachen Pharmaceutical Co., Ltd. glucose 5mg Tanfang Shengtai Pharmaceutical Co., Ltd. Activated charcoal (for injection use) 1.5mg Shanghai Activated Carbon Factory Co., Ltd. Sodium hydroxide Add an appropriate amount of pH adjuster to adjust the pH to 6.9. Hunan Ercon Pharmaceutical Co., Ltd. Water for Injection Add to 1ml self made

[0052] The preparation method is as follows: after the raw materials are mixed evenly, they are filled into vials and then subjected to pre-freezing, primary drying, and desorption drying in sequence. The three steps of pre-freezing, primary drying, and desorption drying are carried out in a freeze dryer.

[0053] The specific conditions for each step are as follows:

[0054] Pre-freezing: The temperature of the heat transfer oil is gradually reduced to -40℃ and kept at a constant temperature for 2 hours.

[0055] First drying:

[0056] The heat transfer oil temperature was raised to -20℃ and held at that temperature for 1 hour.

[0057] The heat transfer oil temperature was raised to -10℃ and held at that temperature for 3 hours.

[0058] The heat transfer oil temperature rises to -5℃ and remains constant for 7 hours;

[0059] The heat transfer oil temperature rises to 0℃ and remains at that temperature for 1 minute;

[0060] The heat transfer oil temperature is raised to 15℃ and kept at that temperature for 1 hour.

[0061] The vacuum level of the front chamber is controlled at 20Pa.

[0062] Analysis and drying:

[0063] The heat transfer oil temperature is raised to 45℃ and kept constant for 1 hour, while the vacuum degree of the front chamber is controlled at 20Pa.

[0064] The heat transfer oil temperature was maintained at 45℃ for 3 hours, and the front chamber was controlled at 2Pa.

[0065] The injectable lyophilized form of Chuanhuning prepared in this embodiment was tested, and its appearance and color are shown in the table below:

[0066] Properties Yellowish freeze-dried lumps or powder White to slightly yellow freeze-dried lumps or powder The color of the solution Lighter than yellow No. 4 Lighter than yellow or yellowish-green No. 4

[0067] The above results indicate that the injectable lyophilized cypermethrin prepared in this embodiment has excellent product quality.

[0068] Example 2

[0069] The raw materials used in this embodiment to prepare the injectable lyophilized Chuanhuning are as follows:

[0070] Wearing Huning 24mg Sichuan Mianzhu Yonglong Biological Products Co., Ltd. Sodium bicarbonate 2.4mg Hebei Huachen Pharmaceutical Co., Ltd. glucose 6mg Tanfang Shengtai Pharmaceutical Co., Ltd. Activated charcoal (for injection use) 1.2mg Shanghai Activated Carbon Factory Co., Ltd. Sodium hydroxide Add an appropriate amount of pH adjuster to adjust the pH to 6.5. Hunan Ercon Pharmaceutical Co., Ltd. Water for Injection Add to 1.2ml self made

[0071] The preparation method is as follows: after the raw materials are mixed evenly, they are filled into vials and then subjected to pre-freezing, primary drying, and desorption drying in sequence. The three steps of pre-freezing, primary drying, and desorption drying are carried out in a freeze dryer.

[0072] The specific conditions for each step are as follows:

[0073] Pre-freezing: The temperature of the heat transfer oil is gradually reduced to -50℃ and kept constant for 1.5 hours.

[0074] First drying:

[0075] The heat transfer oil temperature rises to -20℃ and remains at that temperature for 0.5 hours;

[0076] The heat transfer oil temperature was raised to -10℃ and held at that temperature for 4 hours.

[0077] The heat transfer oil temperature was raised to -5℃ and held at that temperature for 5 hours.

[0078] The heat transfer oil temperature rises to 0℃ and remains constant for 10 minutes;

[0079] The heat transfer oil temperature rises to 15℃ and is held at that temperature for 0.5 hours.

[0080] The vacuum level of the front chamber is controlled at 10 Pa.

[0081] Analysis and drying:

[0082] The heat transfer oil temperature is raised to 45℃ and kept constant for 1 hour, while the vacuum degree of the front chamber is controlled at 20Pa.

[0083] The heat transfer oil temperature was maintained at 45℃ for 7 hours, and the front chamber was controlled at 10Pa.

[0084] Example 3

[0085] The raw materials used in this embodiment to prepare the injectable lyophilized Chuanhuning are as follows:

[0086] Wearing Huning 16mg Sichuan Mianzhu Yonglong Biological Products Co., Ltd. Sodium bicarbonate 3.6mg Hebei Huachen Pharmaceutical Co., Ltd. glucose 4mg Tanfang Shengtai Pharmaceutical Co., Ltd. Activated charcoal (for injection use) 1.8mg Shanghai Activated Carbon Factory Co., Ltd. Sodium hydroxide Add an appropriate amount of pH adjuster to adjust the pH to 7.2. Hunan Ercon Pharmaceutical Co., Ltd. Water for Injection Add to 0.8ml self made

[0087] The preparation method is as follows: after the raw materials are mixed evenly, they are filled into vials and then subjected to pre-freezing, primary drying, and desorption drying in sequence. The three steps of pre-freezing, primary drying, and desorption drying are carried out in a freeze dryer.

[0088] The specific conditions for each step are as follows:

[0089] Pre-freezing: The temperature of the heat transfer oil is gradually reduced to -40℃ and kept constant for 2 hours.

[0090] First drying:

[0091] The heat transfer oil temperature was raised to -20℃ and held at that temperature for 2 hours.

[0092] The heat transfer oil temperature was raised to -10℃ and held at that temperature for 2 hours.

[0093] The heat transfer oil temperature was raised to -5℃ and held at that temperature for 5 hours.

[0094] The heat transfer oil temperature rises to 0℃ and remains constant for 10 minutes;

[0095] The heat transfer oil temperature rises to 15℃ and is kept constant for 1.5 hours.

[0096] The vacuum level of the front chamber is controlled at 20Pa.

[0097] Analysis and drying:

[0098] The heat transfer oil temperature is raised to 45℃ and kept constant for 1 hour, while the vacuum degree of the front chamber is controlled at 20Pa.

[0099] The heat transfer oil temperature was maintained at 45℃ for 3 hours, and the front chamber was controlled at 2Pa.

[0100] Comparative Example 1

[0101] This comparative example uses different conditions than Example 1 to prepare injectable lyophilized pendimethalin. The raw materials and preparation steps are the same as in Example 1.

[0102] The specific conditions for each step are as follows:

[0103] Pre-freezing: The temperature of the heat transfer oil is gradually reduced to -40℃ and kept constant for 2.5 hours.

[0104] First drying:

[0105] The heat transfer oil temperature was raised to -10℃ and held at that temperature for 9 hours.

[0106] The heat transfer oil temperature rises to 0℃ and remains at that temperature for 1 minute;

[0107] The heat transfer oil temperature is raised to 15℃ and kept at that temperature for 1 hour.

[0108] The vacuum level of the front chamber is controlled at 20Pa.

[0109] Analysis and drying:

[0110] The heat transfer oil temperature is raised to 50℃ and kept constant for 1 hour, while the vacuum degree of the front chamber is controlled at 20Pa.

[0111] The heat transfer oil temperature is maintained at 50℃ for 3 hours, and the front chamber is controlled under ultimate vacuum.

[0112] The injectable lyophilized form of chuanhuning prepared in this comparative example was tested, and its appearance and color are shown in the table below:

[0113] Properties Yellow freeze-dried lumps or powder White to slightly yellow freeze-dried lumps or powder The color of the solution Darker than yellow No. 4 Lighter than yellow or yellowish-green No. 4

[0114] It is evident that, without employing the process conditions of this invention, the quality of the injectable lyophilized cypermethrin in this comparative example does not meet the standards.

[0115] As can be seen from the above embodiments, the present invention optimizes the lyophilization process of injectable chuanhuning lyophilized agent. By optimizing the temperature control program, the appearance and color of the product are controlled, resulting in a higher quality injectable chuanhuning lyophilized agent. Therefore, the present invention has excellent application prospects.

Claims

1. A lyophilized preparation of chuanhuning for injection, characterized in that, It is made from the following raw materials in parts by weight: Chuanhuning 16-24 parts Sodium bicarbonate 2.4–3.6 parts, 4-6 portions of glucose Activated carbon 1.2–1.8 parts 800-1200 parts water The amount of sodium hydroxide used should be sufficient to adjust the pH to 6.5–7.2; The preparation method is as follows: the raw materials are mixed, filled into vials, and then subjected to pre-freezing, primary drying, and analytical drying in sequence; in, Pre-freezing conditions include maintaining a constant temperature of -40 to -50°C for 1.5 to 3 hours; The drying process is carried out under the following conditions: constant temperature at -20℃ for 0.5 to 2 hours; Keep at -10℃ for 2 to 4 hours; Keep at -5℃ for 5 to 8 hours; Maintain temperature at 0℃ for 1–10 minutes; Maintain a constant temperature of 15℃ for 0.5–1.5 hours; The drying conditions were determined according to the following procedure: The temperature was kept constant at 45℃ for 1 hour, and the vacuum degree was controlled at 10-20 Pa. Maintain a constant temperature of 45℃ for 2–6 hours, with the front chamber controlled at 0–10 Pa.

2. The injectable lyophilized cypermethrin according to claim 1, characterized in that: The pre-freezing, primary drying, and desorption drying are performed in a freeze dryer.

3. The injectable lyophilized cypermethrin according to claim 1, characterized in that: During the first drying process, the vacuum level is controlled at 10–20 Pa.

4. The method for preparing the injectable lyophilized cypermethrin according to claim 1, characterized in that, The process includes the following steps: mixing the raw materials, filling them into vials, and sequentially performing pre-freezing, primary drying, and analytical drying; in, Pre-freezing conditions include maintaining a constant temperature of -40 to -50°C for 1.5 to 3 hours; The drying process is carried out under the following conditions: constant temperature at -20℃ for 0.5 to 2 hours; Keep at -10℃ for 2 to 4 hours; Keep at -5℃ for 5 to 8 hours; Maintain temperature at 0℃ for 1–10 minutes; Maintain a constant temperature of 15℃ for 0.5–1.5 hours; The drying conditions were determined according to the following procedure: The temperature was kept constant at 45℃ for 1 hour, and the vacuum degree was controlled at 10-20 Pa. Maintain a constant temperature of 45℃ for 2–6 hours, with the front chamber controlled at 0–10 Pa.

5. The preparation method according to claim 4, characterized in that: The pre-freezing, primary drying, and desorption drying are performed in a freeze dryer.

6. The preparation method according to claim 4, characterized in that: During the first drying process, the vacuum level is controlled at 10–20 Pa.