Dissolving method of sodium hyaluronate for solution preparation

Abstract

The invention relates to a dissolving method of hyaluronic acid for solution preparation. The method comprises the steps of: first adding a PBS solution into a solution preparation tank and starting stirring; adding sodium hyaluronate with a stirring rotating speed less than 150 round / min; closing a feed inlet after addition, filling inert gas in the solution preparation tank, controlling a pressure within a range of from 0 to 0.1MPa, stirring continuously, predissolving for 40-60 min, stopping stirring, carrying out limit swelling for 1-2 h and carrying out intermittent stirring; finally, finishing stirring, protecting the hyaluronic acid solution in inert gas and carrying out standing. The method for dissolving sodium hyaluronate can substantially increase soup dissolving homogeneity, avoid oxidation of product, enhance aseptic guarantee level during product production process and improve product quality; the standing process employs natural sedimentation to reduce bubble amount in an injection; beside, the method substantially shortens a dissolving time during solution preparation, reduces production cost and especially applies to industrialized production.

Description

Technical field: [0001] The invention relates to a dissolving method in the liquid preparation process of sodium hyaluronate. Background technique: [0002] Hyaluronic acid (HA for short) is composed of (1→3)-2-acetylamino-2-deoxy-β-D-glucose-(1→4)-O-β-D-glucuronic acid bis A linear polysaccharide composed of sugar repeating units with the molecular formula (C 14 h 21 NO 11 )n, the molecular weight range is 2×10 5 ~7×10 6 . [0003] [0004] Hyaluronic acid is generally in the form of sodium salt, white fibrous or powdery solid, has strong hygroscopicity, soluble in water, insoluble in organic solvents, and can be used as an auxiliary drug for ophthalmic surgery and deformed knee joint disease and shoulder periarthritis It also has important physiological functions in tissue generation, wound healing, tumor invasion and regulation of cell function. Sodium hyaluronate is mainly used as a raw material for medical sodium hyaluronate gel for ophthalmic surgery and sodi...

AI Technical Summary

Problems solved by technology

[0007] 1. The traditional vibration dissolution method takes a long time to dissolve and consumes a lot of energy, resulting in high production costs; it is not conducive to large-scale production operations

[0008] 2. Sodium hyaluronate is a high-molecular compound. It is easy to form a network structure when the temperature is low. Slow water absorption leads to slow diffusion. In addition, water molecules enter the network structure to form a non-flowing semi-solid gel. During the vibration process, the polymer Poor gel fluidity and poor solution uniformity

[0012] 1. Stirring and dissolving method: Due to the shear force generated by stirring, the molecular weight is broken, resulting in chain scission of the sodium hyaluronate polymer, and the average molecular weight drops significantly, which makes the product quality unstable and the quality index fluctuates, which is not conducive to large-scale production. operate

[0013] 2. Vigorous stirring produces stirring heat, which increases the temperature. Since sodium hyaluronate is a heat-labile product, the heat will cause the molecular degradation of sodium hyaluronate, the average molecular weight will decrease, and the product quality will be unstable.

[0014] 3. Stirring movement breaks the air bubbles into small bubbles, increases the contact surface and contact time between the gas and the liquid medicine, stirs to generate radial motion, forms a vortex, prolongs the residence time of the bubbles in the liquid medicine, and stirs to increase the bubbles of the liquid medicine significantly, and the bubbles Oxygen is the main factor for the oxidation of pharmaceutical preparations, and it is also an important factor for the reproduction of aerobic bacteria, which makes the product quality unstable

In addition, it is clinically required that the injection should not contain air bubbles. In the traditional dosing process, the air bubbles are mainly removed by vacuuming. The effect is obvious, and 70-80% of the air bubbles can be removed. However, because the vacuum degree of the vacuum pump cannot reach below -0.1MPa, the air bubbles cannot be pumped. Completely, resulting in a small number of small air bubbles remaining in the finished product, which brings difficulty to filling

[0015] 4. Stirring increases the foam. On the one hand, in order to prevent overflow, the liquid filling coefficient must be reduced, which reduces the production capacity. On the other hand, stirring makes the foam liquid level move up and down, and part of the liquid medicine adheres to the filling roof or the tank wall, even to the top. The shaft seal increases the chance of contact between the adhered liquid medicine and oxygen, increases the risk of bacterial contamination, and makes cleaning and sterilization difficult

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