Composition containing glucosamine as well as preparation method and detection method thereof

Abstract

The invention relates to a composition containing glucosamine. The active ingredients of the composition are glucosamine or pharmaceutically acceptable salt thereof and lidocaine or pharmaceutically acceptable salt thereof, and the composition provided by the invention can be prepared into an injection, preferably a parenteral solution, more preferably a small-volume injection. The parenteral solution further comprises an antioxidant, a pH regulator and an alkaline solvent. The composition containing glucosamine provided by the invention can be used for overcoming the defects that freeze-drying preparation of glucosamine is long in freeze-drying time, high in energy consumption and not beneficial to production in the prior art and free-dying preparations in the same batch are different in the shape and solubility. Control on the stability of the parenteral solution and related substances is realized, and the side effect caused by degradation products is reduced, so that the safety and stability requirements of the parenteral solution are met. Therefore, the glucosamine parenteral solution provided by the invention can meet industrial production and can be safely and reliably applied to the field of medicine.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method and application of a composition containing glucosamine. Background technique

[0002] Amino dextran is a natural sugar derived from chitin, which is the main component of the cartilage matrix. By changing its side chain structure, it is easier to combine with water in the articular cartilage to maintain the lubrication of the joint cavity and buffer pressure. It has a certain protective effect on damaged chondrocytes and can be artificially synthesized. Currently, glucosamine, glucosamine hydrochloride, glucosamine sulfate sodium chloride double salt or potassium chloride double salt are commonly used. Glucosamine is one of the smallest units that make up polyglucosamine, and it forms polyglucosamine with uronic acid, including chondroitin sulfate, keratan sulfate, dermatan sulfate and hyaluronic acid.

[0003] Amino dextran is a natura...

Examples

Embodiment 1

[0050] Embodiment 1 Glucosamine sulfate injection (0.4g in terms of glucosamine sulfate)

[0051]

[0052] Preparation process: Take 80% of water to make 0.001mol / L hydrochloric acid solution, add glucosamine sulfate sodium chloride double salt and stir at 55°C to dissolve completely, then add 0.02% activated carbon, stir at 75°C for 20min, After decarbonization, add 0.01% activated carbon and lidocaine hydrochloride in the prescribed amount to the solution, stir at 45°C for 10 minutes, decarbonize, filter through 0.45 μm and 0.22 μm microporous membranes until clear, and the liquid is cooled Add water to a sufficient amount at 20°C, then adjust the pH value of the solution to 4.6, fill with 2ml, and finally sterilize at 121°C for 17 minutes.

[0053] Separately prepare a special solvent, as follows: 20g of diethanolamine plus 1000ml of water for injection to make 1000 vials. Preparation process: Weigh the above prescription amount of alkaline regulator diethanolamine, add...

Embodiment 2

[0054] Embodiment 2 Glucosamine sulfate injection (0.4g in terms of glucosamine sulfate)

[0055]

[0056] Preparation process: Take 80% water to prepare 0.001mol / L hydrochloric acid solution, add glucosamine sulfate sodium chloride double salt and stir to dissolve completely, then add 0.02% activated carbon, stir at room temperature for 20min, decarbonize, and then pour into the solution Add 0.01% activated carbon and lidocaine hydrochloride in the prescription amount, stir at room temperature for 10 minutes, decarbonize, filter through 0.45 μm, 0.22 μm microporous membranes until clarification, add water to a sufficient amount when the liquid is cooled to 20°C , and then adjust the pH value of the solution to 4.6, fill with 2ml, and finally sterilize at 121°C for 17min.

[0057] Special solvent is prepared with the method of embodiment 1.

experiment example 1

[0058] Experimental example 1: Due to the reaction process of 5-hydroxymethylfurfural, it is considered that this process is composed of a series of elementary reactions such as protonation, dehydration and deprotonation, among which protonation is relatively easy, and the energy barrier of deprotonation reaction is relatively low. High, is the rate-determining step of the conversion process. Therefore, changes in temperature have a greater effect on the decomposition of glucosamine than changes in pH. According to the preparation method of Example 4 in the CN201010270516 patent application, take 80% water to prepare hydrochloric acid solution, after the active ingredient is dissolved and add enough water, the pH reaches 5.5, 5.0, 4.7, 4.4, 4.2, 4.0, 3.5, 3.0 , 2.0, 1.0, and finally sterilized at 121°C for 17min. Simultaneously, the pH of Comparative Example 1 reached 5.5, 5.0, 4.7, 4.6, 4.4, 4.2, 4.0, and 3.5 before sterilization, and finally sterilized at 121° C. for 17 min...

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method and application of a composition containing glucosamine. Background technique

[0002] Amino dextran is a natural sugar derived from chitin, which is the main component of the cartilage matrix. By changing its side chain structure, it is easier to combine with water in the articular cartilage to maintain the lubrication of the joint cavity and buffer pressure. It has a certain protective effect on damaged chondrocytes and can be artificially synthesized. Currently, glucosamine, glucosamine hydrochloride, glucosamine sulfate sodium chloride double salt or potassium chloride double salt are commonly used. Glucosamine is one of the smallest units that make up polyglucosamine, and it forms polyglucosamine with uronic acid, including chondroitin sulfate, keratan sulfate, dermatan sulfate and hyaluronic acid.

[0003] Amino dextran is a natura...

Examples

Embodiment 1

[0050] Embodiment 1 Glucosamine sulfate injection (0.4g in terms of glucosamine sulfate)

[0051]

[0052] Preparation process: Take 80% of water to make 0.001mol / L hydrochloric acid solution, add glucosamine sulfate sodium chloride double salt and stir at 55°C to dissolve completely, then add 0.02% activated carbon, stir at 75°C for 20min, After decarbonization, add 0.01% activated carbon and lidocaine hydrochloride in the prescribed amount to the solution, stir at 45°C for 10 minutes, decarbonize, filter through 0.45 μm and 0.22 μm microporous membranes until clear, and the liquid is cooled Add water to a sufficient amount at 20°C, then adjust the pH value of the solution to 4.6, fill with 2ml, and finally sterilize at 121°C for 17 minutes.

[0053] Separately prepare a special solvent, as follows: 20g of diethanolamine plus 1000ml of water for injection to make 1000 vials. Preparation process: Weigh the above prescription amount of alkaline regulator diethanolamine, add...

Embodiment 2

[0054] Embodiment 2 Glucosamine sulfate injection (0.4g in terms of glucosamine sulfate)

[0055]

[0056] Preparation process: Take 80% water to prepare 0.001mol / L hydrochloric acid solution, add glucosamine sulfate sodium chloride double salt and stir to dissolve completely, then add 0.02% activated carbon, stir at room temperature for 20min, decarbonize, and then pour into the solution Add 0.01% activated carbon and lidocaine hydrochloride in the prescription amount, stir at room temperature for 10 minutes, decarbonize, filter through 0.45 μm, 0.22 μm microporous membranes until clarification, add water to a sufficient amount when the liquid is cooled to 20°C , and then adjust the pH value of the solution to 4.6, fill with 2ml, and finally sterilize at 121°C for 17min.

[0057] Special solvent is prepared with the method of embodiment 1.

experiment example 1

[0058] Experimental example 1: Due to the reaction process of 5-hydroxymethylfurfural, it is considered that this process is composed of a series of elementary reactions such as protonation, dehydration and deprotonation, among which protonation is relatively easy, and the energy barrier of deprotonation reaction is relatively low. High, is the rate-determining step of the conversion process. Therefore, changes in temperature have a greater effect on the decomposition of glucosamine than changes in pH. According to the preparation method of Example 4 in the CN201010270516 patent application, take 80% water to prepare hydrochloric acid solution, after the active ingredient is dissolved and add enough water, the pH reaches 5.5, 5.0, 4.7, 4.4, 4.2, 4.0, 3.5, 3.0 , 2.0, 1.0, and finally sterilized at 121°C for 17min. Simultaneously, the pH of Comparative Example 1 reached 5.5, 5.0, 4.7, 4.6, 4.4, 4.2, 4.0, and 3.5 before sterilization, and finally sterilized at 121° C. for 17 min...

Images