Synergistic treatment type multi-material sustained-release eye drop and preparation method

Abstract

The invention discloses a synergistic treatment type multi-material sustained-release eye drop and a preparation method. The preparation method comprises the following steps of: instantaneously forming chitosan aqueous solution which is blended with therapeutic materials into superfine gel particles under the action of direct current high voltage static; receiving the particles by using hyaluronic acid hydrosol or hyaluronic acid hydrogel; and coating the surface of chitosan particles with a hyaluronic acid gel crust layer to obtain a medicament sustained-release eye drop, wherein the size of the chitosan gel particles can be accurately controlled by controlling voltage, the concentration of the chitosan solution and the distance from a jet orifice to the liquid level of the hyaluronic acid hydrosol, and the flowability of the eye drop can be regulated by controlling the concentration of the hyaluronic acid, so that the adhesive capacity of the eye drop to the eye surface and a long-term treatment effect are improved. The preparation method has simple and practicable process, high repeatability, and clean and pollution-free whole preparation process flow; and as the provided multi-therapeutic material sustained-release eye drop for synergistic treatment on eye diseases does not need complicated process, and the proportion of each component and the release rate are convenient to control, so the preparation method has a good application prospect.

Description

technical field

[0001] The invention relates to biomedicine and biomaterial technology, in particular to a synergistic therapeutic multi-substance sustained-release eye drop and a preparation method. Background technique

[0002] High-voltage electrospinning technology is a new type of pollution-free preparation of nanofibers and porous films or foams that has rapidly emerged in recent years. The raw materials used in electrospinning have requirements for their spinnability. For example, pure chitosan solution is a polymer that is difficult to spin. It often forms gel particles under the action of high-voltage electrostatic field force, which is often regarded as as a worthless by-product. At the same time, high-voltage electrospinning also requires strict process parameters for the formation of nanofibers. For example, DC voltage, electric field strength, field distance, etc. need to be constantly explored to obtain limited optimization conditions before it is possible to ...

Examples

Embodiment 1

[0032] Weighing average molecular weight is 80000, and the degree of deacetylation 85% chitosan is dissolved in 3g / L acetic acid dilute solution and is mixed with 100 milliliters of chitosan solution of 20g / L, then adds cyclosporine A, cyclosporine A The mass ratio of the chitosan in the solution is 1:8, and it is uniformly mixed and loaded into the syringe of the electrospinning device;

[0033] Dissolve hyaluronic acid in water to prepare 100 ml of hyaluronic acid hydrosol with a concentration of 10g / L, then place it in a container and place it directly below the needle tip of a hollow metal needle of a syringe, and adjust the distance between the needle tip and the liquid level of hyaluronic acid hydrosol. The distance is 9cm, the solution is grounded with a wire, and continuously stirred at 120 rpm, the hollow metal needle is connected to a DC voltage of 10kV, and the chitosan solution in the syringe is pushed out at a speed of 0.20ml / hour for electrostatic spraying, with a...

Embodiment 2

[0035] With the preparation method of embodiment 1, the difference is: to the average molecular weight is 65000, in the chitosan solution of degree of deacetylation 88%, add 1: 1: 1 levofloxacin, natamycin and sodium cromoglycate, control levofloxacin, natamycin The ratio of the total mass of cromolyn sodium to the mass of chitosan in the solution is 1: 3, the DC voltage applied by the metal needle is changed to 18kV, and the distance between the needle tip and the grounded 12g / L hyaluronic acid hydrosol is changed to 18cm, the eye drops containing levofloxacin were prepared by high-voltage electrostatic spraying, and the eye drops attached to the eye drops were photographed by a digital camera. image 3 Shown, show that the eye drops prepared by this method are liquid preparations with good fluidity.

Embodiment 3

[0037] With the preparation method of Example 1, the difference is: the average molecular weight is 50000, and the degree of deacetylation is 82% chitosan solution, adding 1: 3 tobramycin and dexamethasone, and the concentration of the receiving solution is 6.0g / L. Hyaluronic acid hydrosol, the ratio of the total mass of tobramycin and dexamethasone to the mass of chitosan in the solution is controlled to be 1:2, and the gel state loaded with tobramycin and dexamethasone is prepared by 3kV high-voltage electrostatic spraying Eye drops, which are attached to the eye drops when photographed by a digital camera Figure 4 Shown, show that the eye drops prepared by this method are liquid preparations with good fluidity.

technical field

[0001] The invention relates to biomedicine and biomaterial technology, in particular to a synergistic therapeutic multi-substance sustained-release eye drop and a preparation method. Background technique

[0002] High-voltage electrospinning technology is a new type of pollution-free preparation of nanofibers and porous films or foams that has rapidly emerged in recent years. The raw materials used in electrospinning have requirements for their spinnability. For example, pure chitosan solution is a polymer that is difficult to spin. It often forms gel particles under the action of high-voltage electrostatic field force, which is often regarded as as a worthless by-product. At the same time, high-voltage electrospinning also requires strict process parameters for the formation of nanofibers. For example, DC voltage, electric field strength, field distance, etc. need to be constantly explored to obtain limited optimization conditions before it is possible to ...

Examples

Embodiment 1

[0032] Weighing average molecular weight is 80000, and the degree of deacetylation 85% chitosan is dissolved in 3g / L acetic acid dilute solution and is mixed with 100 milliliters of chitosan solution of 20g / L, then adds cyclosporine A, cyclosporine A The mass ratio of the chitosan in the solution is 1:8, and it is uniformly mixed and loaded into the syringe of the electrospinning device;

[0033] Dissolve hyaluronic acid in water to prepare 100 ml of hyaluronic acid hydrosol with a concentration of 10g / L, then place it in a container and place it directly below the needle tip of a hollow metal needle of a syringe, and adjust the distance between the needle tip and the liquid level of hyaluronic acid hydrosol. The distance is 9cm, the solution is grounded with a wire, and continuously stirred at 120 rpm, the hollow metal needle is connected to a DC voltage of 10kV, and the chitosan solution in the syringe is pushed out at a speed of 0.20ml / hour for electrostatic spraying, with a...

Embodiment 2

[0035] With the preparation method of embodiment 1, the difference is: to the average molecular weight is 65000, in the chitosan solution of degree of deacetylation 88%, add 1: 1: 1 levofloxacin, natamycin and sodium cromoglycate, control levofloxacin, natamycin The ratio of the total mass of cromolyn sodium to the mass of chitosan in the solution is 1: 3, the DC voltage applied by the metal needle is changed to 18kV, and the distance between the needle tip and the grounded 12g / L hyaluronic acid hydrosol is changed to 18cm, the eye drops containing levofloxacin were prepared by high-voltage electrostatic spraying, and the eye drops attached to the eye drops were photographed by a digital camera. image 3 Shown, show that the eye drops prepared by this method are liquid preparations with good fluidity.

Embodiment 3

[0037] With the preparation method of Example 1, the difference is: the average molecular weight is 50000, and the degree of deacetylation is 82% chitosan solution, adding 1: 3 tobramycin and dexamethasone, and the concentration of the receiving solution is 6.0g / L. Hyaluronic acid hydrosol, the ratio of the total mass of tobramycin and dexamethasone to the mass of chitosan in the solution is controlled to be 1:2, and the gel state loaded with tobramycin and dexamethasone is prepared by 3kV high-voltage electrostatic spraying Eye drops, which are attached to the eye drops when photographed by a digital camera Figure 4 Shown, show that the eye drops prepared by this method are liquid preparations with good fluidity.

Images