CN111759797A - Novel preparation of dithranol for treating psoriasis and preparation method thereof - Google Patents

Abstract

The invention discloses a novel preparation of dithranol for treating psoriasis and a preparation method thereof, belonging to the technical field of medical treatment. The invention comprises a mixed solution of nanoparticles and sodium alginate gel, wherein the nanoparticles comprise the following components: 5mg/mL dithranol original drug is dissolved in DMSO100uL, and DMSO is dimethyl sulfoxide; 3.5mL of 1mg/mL chitosan, and 0.5mL of 1mg/mL of TPP0.5mL.

Description

Novel preparation of dithranol for treating psoriasis and preparation method thereof

Technical Field

The invention relates to the technical field of medical treatment, in particular to a novel preparation for treating psoriasis by dithranol and a preparation method thereof.

Background

Psoriasis (PS) is induced by common genetic factors and environmental factors, is caused by immune-mediated chronic, recurrent, inflammatory and systemic diseases, and can be induced by various environmental factors such as trauma, infection, medicaments and the like to cause the disease of susceptible people, and the Psoriasis has typical clinical manifestations of squamous papule, plaque, limited or wide distribution, no infectivity, but difficult treatment and is often suffered for life. The pathogenesis of psoriasis involves various factors such as heredity, immunity and environment, and keratinocyte hyperproliferation or joint synoviocytes and chondrocyte inflammation is caused by immune reaction mainly mediated by T lymphocytes and jointly participated by various immune cells. The prevalence rate of psoriasis accounts for about 2-3% of the population worldwide, the life quality of patients is seriously affected, and the existing treatment measures are effective but cannot achieve long-term remission, so that the psoriasis has profound influence on the physical and mental health of human beings.

According to the latest guidelines, the classification of psoriasis mainly comprises spot psoriasis, plaque psoriasis, pustular psoriasis, erythrodermic psoriasis, arthropathic psoriasis, as well as specific parts including scalp psoriasis, nail psoriasis, reverse psoriasis, and psoriasis of specific groups including children psoriasis, psoriasis of pregnant and lactating women, psoriasis of the elderly. Despite the difficulties of radical treatment, topical treatments have been the first line of recommendation for psoriasis treatment, including glucocorticoids, vitamin D3 derivatives, vitamin a acid, dithranol preparations, tar preparations and calcineurin inhibitors, but the results have been far from satisfactory.

Disclosure of Invention

In order to overcome the defects, the invention provides a novel preparation for treating psoriasis by dithranol and a preparation method thereof.

A novel preparation of dithranol for treating psoriasis comprises a mixed solution of nanoparticles and sodium alginate gel, wherein the components of the nanoparticles are as follows:

5mg/mL dithranol original drug is dissolved in DMSO100uL,

3.5mL of 1mg/mL chitosan,

1mg/mL of mLTPP0.5 mL, TPP is sodium tripolyphosphate;

the sodium alginate gel comprises the following components:

1.5g of sodium alginate, and the sodium alginate,

1.0gβ-GP，

0.5g of sodium carboxymethylcellulose,

10mL 1％CaCl₂。

2. a method for preparing a novel formulation of dithranol for treating psoriasis is characterized in that:

firstly, preparing nanoparticles, wherein the preparation process comprises the following steps:

absorbing 3.5mL of chitosan solution prepared in advance by using a 5mL disposable plastic syringe, adding the chitosan solution into a 10mL glass bottle, adding a rotor into the bottle to be continuously stirred, absorbing 0.1mL of DIT solution with the concentration of 5mg/mL by using a 1mL disposable plastic syringe, slowly injecting the DIT solution into the chitosan solution, then absorbing 0.5mL of 1mg/mL of PP solution, dropwise adding the solution into the continuously stirred liquid at the speed of 60 drops/min, and then carrying out ultrasonic treatment by using a cell disruption instrument for 20min to obtain a DIT-CTS-NPs suspension;

and step two, preparing gel, wherein the preparation process comprises the following steps:

(1) dissolving 1.5g of sodium alginate in 30mL of water to swell for 24h to prepare A;

(2) adding 1.0g of beta-GP into the A, and uniformly crosslinking and stirring to prepare a B;

(3) accurately weighing 0.5g of sodium carboxymethylcellulose, and dissolving in 10mL of water to obtain a solution C;

(4) adding the liquid C into the liquid B, and fully stirring to obtain D;

(5) preparing 1% CaCl210mL with anhydrous calcium chloride to obtain solution E;

(6) adding the E into the D, and fully mixing to obtain sodium alginate gel;

and dialyzing the obtained DIT-CTS-NPs suspension with distilled water for 2 days, then freeze-drying to obtain pure DIT-CTS-NPs, diluting with a small amount of purified water, adding into the prepared gel, and uniformly stirring.

The invention has the beneficial effects that:

1. the dithranol chitosan nanoparticles with proper particle size and optimal dispersion coefficient are obtained by using an ion crosslinking method, and the preparation method and the process are simple. FT-IR, particle size measurement, PDI and zeta, and thermogravimetric analysis show that DIT-CS-NPs have high thermal stability and stable internal component structure.

2. In vitro cell experiments prove that the IC50 values of the DIT group and the DIT-CS-NPs group are both in the concentration range of 3.2-6.4 ug/mL. Compared with a control group, the action time of CAP alone is more than 300s, so that the growth of the HaCaT cells can be inhibited, and the growth of the HaCaT cells is optimally inhibited by the cooperation of the DIT-CS-NPs and the CAP. ROS results indicate that the generated reactive oxygen species can indirectly induce apoptosis. The action mechanisms of the two are related to oxidative stress, so the two ways of cooperation can greatly improve the curative effect. DIT is dithranol.

3. Animal experiments show that the DIT-CS-NPs gel can relieve epidermal proliferation, reduce erythema, scales and infiltration at skin lesions, reduce the level of cell factors, obviously relieve the irritation of dithranol to the skin lesions of mice, and simultaneously has the effects of enhancing water solubility and maintaining the release of dithranol. And the curative effect of the preparation on treating the plaque psoriasis by combining with CAP irradiation is proved, and the possibility of increasing the diversity of psoriasis treatment is provided.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

A novel preparation of dithranol for treating psoriasis comprises a mixed solution of nanoparticles and sodium alginate gel, wherein the components of the nanoparticles are as follows:

dissolving 5mg/mL dithranol raw drug in DMSO100 uL;

3.5mL of 1mg/mL chitosan,

1mg/mLTPP0.5 mL，

the sodium alginate gel comprises the following components:

1.5g of sodium alginate, and the sodium alginate,

1.0gβ-GP，

0.5g of sodium carboxymethylcellulose,

10mL 1％CaCl₂。

2. a method for preparing a novel formulation of dithranol for treating psoriasis is characterized in that:

firstly, preparing nanoparticles, wherein the preparation process comprises the following steps:

absorbing 3.5mL of chitosan solution prepared in advance by using a 5mL disposable plastic syringe, adding the chitosan solution into a 10mL glass bottle, adding a rotor into the bottle to be continuously stirred, absorbing 0.1mL of DIT solution with the concentration of 5mg/mL by using a 1mL disposable plastic syringe, slowly injecting the DIT solution into the chitosan solution, then absorbing 0.5mL of 1mg/mL of PP solution, dropwise adding the solution into the continuously stirred liquid at the speed of 60 drops/min, and then carrying out ultrasonic treatment by using a cell disruption instrument for 20min to obtain a DIT-CTS-NPs suspension;

and step two, preparing gel, wherein the preparation process comprises the following steps:

(1) dissolving 1.5g of sodium alginate in 30mL of water to swell for 24h to prepare A;

(2) adding 1.0g of beta-GP into the A, and uniformly crosslinking and stirring to prepare a B;

(3) accurately weighing 0.5g of sodium carboxymethylcellulose, and dissolving in 10mL of water to obtain a solution C;

(4) adding the liquid C into the liquid B, and fully stirring to obtain D;

(5) preparing 1% CaCl210mL with anhydrous calcium chloride to obtain solution E;

(6) adding the E into the D, and fully mixing to obtain sodium alginate gel;

and dialyzing the obtained DIT-CTS-NPs suspension with distilled water for 2 days, then freeze-drying to obtain pure DIT-CTS-NPs, diluting with a small amount of purified water, adding into the prepared gel, and uniformly stirring.

The IC50 values of the DIT group and the DIT-CS-NPs group are both in the concentration range of 3.2-6.4 ug/mL. Compared with a control group, the action time of CAP alone is more than 300s, so that the growth of the HaCaT cells can be inhibited, and the growth of the HaCaT cells is optimally inhibited by the cooperation of the DIT-CS-NPs and the CAP. ROS results indicate that the generated reactive oxygen species can indirectly induce apoptosis. The action mechanisms of the two are related to oxidative stress, so the two ways of cooperation can greatly improve the curative effect.

DIT is dithranol.

DIT-CS-NPs are chitosan nanoparticle gel loaded with dithranol.

CAP is an atmospheric pressure cold plasma.

HaCaT is a human immortalized keratinocyte.

ROS are reactive oxygen species.

TPP is sodium tripolyphosphate.

DMSO is dimethyl sulfoxide.

beta-GP is beta-disodium glycerophosphate hydrate.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (2)

1. A novel formulation of dithranol for the treatment of psoriasis, characterized in that: comprises mixed liquor of nanoparticles and sodium alginate gel, wherein the nanoparticles comprise the following components:

5mg/mL dithranol original drug is dissolved in DMSO100uL,

3.5mL of 1mg/mL chitosan,

1mg/mL TPP 0.5mL，

the sodium alginate gel comprises the following components:

1.5g of sodium alginate, and the sodium alginate,

1.0gβ-GP，

0.5g of sodium carboxymethylcellulose,

10mL 1％CaCl₂。

2. a method for preparing a novel formulation of dithranol for treating psoriasis is characterized in that:

firstly, preparing nanoparticles, wherein the preparation process comprises the following steps:

absorbing 3.5mL of chitosan solution prepared in advance by using a 5mL disposable plastic syringe, adding the chitosan solution into a 10mL glass bottle, adding a rotor into the bottle to be continuously stirred, absorbing 0.1mL of DIT solution with the concentration of 5mg/mL by using a 1mL disposable plastic syringe, slowly injecting the DIT solution into the chitosan solution, then absorbing 0.5mL of 1mg/mL TPP solution, dropwise adding the solution into the continuously stirred liquid at the speed of 60 drops/min, and then carrying out ultrasonic treatment by using a cell disruption instrument for 20min to obtain a DIT-CTS-NPs suspension;

and step two, preparing gel, wherein the preparation process comprises the following steps:

(1) dissolving 1.5g of sodium alginate in 30mL of water to swell for 24h to prepare A;

(2) adding 1.0g of beta-GP into the A, and uniformly crosslinking and stirring to prepare a B;

(3) accurately weighing 0.5g of sodium carboxymethylcellulose, and dissolving in 10mL of water to obtain a solution C;

(4) adding the liquid C into the liquid B, and fully stirring to obtain D;

(5) preparing 1% CaCl210mL with anhydrous calcium chloride to obtain solution E;

(6) adding the E into the D, and fully mixing to obtain sodium alginate gel;

and dialyzing the obtained DIT-CTS-NPs suspension with distilled water for 2 days, then freeze-drying to obtain pure DIT-CTS-NPs, diluting with a small amount of purified water, adding into the prepared gel, and uniformly stirring.