CN1167412C - A kind of drug gel for percutaneous physiotherapy - Google Patents

Abstract

The present invention relates to a medical gel for percutaneous physical treatment, which is composed of a diclofenac sodium medicine comprising an absorbing agent, a hydrophilicity high molecular material, a compound permeation promoting agent, etc. The gel can reduce the change of a pH value before and after the action of an electric field, a pad does not need to be added when the gel is used, and the operation of the medical gel for percutaneous physical treatment is simple and convenient. The medical gel for percutaneous physical treatment enhances the operability of medical personnel and strengthens the elasticity of patients.

Description

A kind of drug gel for percutaneous physiotherapy

The invention relates to the field of pharmacy, and mainly relates to a drug gel for physiotherapy, which is suitable for clinical percutaneous physiotherapy.

At present, in clinical physiotherapy, iontophoresis is often used for two purposes: one is to use the dual therapeutic effects of current and drugs, and the other is to use the migration of drug ions under the action of electric field force to promote the passage of drugs through the skin. of transshipment. Iontophoresis is an effective means for diclofenac sodium, which produces a therapeutic effect mainly locally. At present, there are also methods such as vinegar iontophoresis to treat bone spurs, etc., but there is no convenient and ideal dosage form in the physical therapy process, and gauze or sponge is often used to absorb the drug solution, which is inconvenient to operate, and in order to avoid pH changes caused by electrolytic products. To the irritation of the skin, dozens of layers of gauze are often placed on the side of the lead plate near the skin, so the patient's compliance is poor and the operation is also inconvenient.

Diclofenac Sodium (Diclofenac Sodium, DS) is a potent anti-inflammatory, antipyretic, and analgesic drug. It is mainly used clinically to treat rheumatism and rheumatoid arthritis. Moderate pain, primary dysmenorrhea, fever, bursitis, and acute gout also have certain curative effects, and are currently widely used in more than 120 countries around the world. The dosage forms involved include tablets, suppositories, ointments, etc., and are administered orally It is the most widely used method clinically, but it is reported that about 12% of patients with oral administration of diclofenac sodium will have gastrointestinal side effects. When large doses and long-term administration are required, it may cause gastrointestinal bleeding, ulcers, etc., and 1 Because of this, 100% of the patients discontinued the drug, which limited its clinical application to some extent. Xie Xianyun (Patent Publication No. CN1174031A) uses diclofenac sodium as the main agent, mixes the hydrophilic pressure-sensitive adhesive matrix, the composite penetration enhancer, etc., coats it on the base paper, and then uses PVC or non-woven fabrics to make it. A diclofenac sodium transdermal controlled-release patch is mainly used for adhering to the skin for passive diffusion, not for clinical physical therapy. The method of transdermal administration can eliminate its stimulation to the gastrointestinal tract, produce a lasting and effective effect, and the administration can be interrupted at any time. However, transdermal administration is often limited by the barrier function of the stratum corneum of the skin, the passive diffusion rate of the drug is small, and it is difficult to achieve an effective concentration. It is often necessary to add a penetration enhancer or use physical penetration enhancement methods to improve the transdermal transport of the drug. There are also some reports at home and abroad using diclofenac sodium percutaneous administration.

The purpose of the present invention is to overcome some disadvantages such as single physiotherapy dosage form existing in the above-mentioned prior art, inconvenient use, etc., and provide a kind of drug gel for transdermal physiotherapy for clinical physiotherapy, and this gel can reduce the pH before the action of the electric field. The change of the value does not need to add pads when using, and the operation is simple, which not only improves the operability of medical staff, but also enhances the compliance of patients.

The present invention is realized through the following technical scheme: the drug gel is composed of diclofenac sodium drug containing ion exchange resin as absorbent, hydrophilic polymer material, composite penetration enhancer azone, propylene glycol, and glycerin.

The absorbent used is ion exchange resin, and its dosage is 0.1-1.0 g.

The pharmaceutical gel of the present invention is prepared by soaking two or more hydrophilic polymer materials in distilled water for a certain period of time to make them swell, heating and dissolving in a water bath, adding a composite penetration enhancer and an absorbent, and stirring evenly. Finally, diclofenac sodium was added, stirred evenly and poured into a petri dish, and dried.

The dosage of the used drug diclofenac sodium is 0.25-1.0 g. The hydrophilic macromolecular materials used include polyvinyl alcohol, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose and polyvinyl pyrrolidone, two or more of which are used, and the dosage is 0.2-8.0 g. The composite penetration enhancer includes azone and propylene glycol, and its dosage is 0.5-15ml.

The present invention has the following characteristics: (1) The present invention adopts polymer material to prepare diclofenac sodium percutaneous physiotherapy gel, which has a white and transparent appearance, good moisture retention and strength. (2) The gel of the present invention is easy to operate and has good operability in clinical application and patient compliance. (3) The gel of the present invention can increase the transdermal rate of diclofenac sodium, so that the pH value before and after the introduction of diclofenac sodium does not change significantly, so the use of liners can be avoided, and the practical application value of clinical physiotherapy can be enhanced. (4) The gel for transdermal physiotherapy of the present invention is suitable for transdermal introduction of non-steroidal anti-inflammatory drugs.

Figure 1 is the drug-time curve of diclofenac sodium gel percutaneous iontophoresis in rabbits (*: the electric field was removed after four hours).

The present invention is described further in conjunction with embodiment.

Embodiment 1: 6 gel prescriptions of the present invention:

Prescription Number 1 2 2 3 4 4 5 6

composition

Diclofenac sodium (g) 0.25 0.25 0.4 0.45 0.6 1.0

Polyvinyl alcohol (g) 5.0 5.0 3.0 8.0 3.0 8.0

Sodium carboxymethylcellulose (g) 1.5 0 1.0 1.5 3.0 0

Hydroxypropyl Methyl Cellulose (g) 2.0 1.0 1.0 0 3.0 1.5

Polyvinylpyrrolidone (g) 1.0 1.5 2.0 0.5 1.5 0

Glycerin (ml) 2.0 0 2.5 3.0 5.0 2.0

Azone (ml) 0.5 1.0 2.0 1.0 3.0 1.0

Propylene glycol (ml) 10.0 10.0 5.0 10.0 5.0 15.0

Exchange resin (g) 0.1 0.5 0.3 0.50 1.0 0

Distilled water (ml) 30.0 40.0 30.0 70.0 30.0 50.0

The pharmaceutical gel of the present invention is prepared by soaking two or more hydrophilic polymer materials in distilled water for a certain period of time to make them swell, heating and dissolving in a water bath, adding a composite penetration enhancer and an absorbent, and stirring evenly. Finally add diclofenac sodium, stir evenly and pour into glassware, dry.

Embodiment 2: use the drug gel that embodiment 1 provides, carry out in vitro test:

1. Preparation of Ex vivo Skin

Male SD rats with a weight of about 200 g were killed by neck dislocation, the abdominal skin hair was cut off, the skin was clipped, and the subcutaneous tissue was peeled off and soaked in normal saline for 30 minutes before use.

2. Experimental Apparatus and Methods

A modified Franz diffusion cell (with an area of 4.5cm ² and a volume of 14ml) was used, and the temperature of the water bath was controlled at 37±0.5°C, so that the dermis of the skin of the rat faced the receiving chamber. Paste the wet drug gel on the stratum corneum, press the lead plate, connect the negative pole of the regulated power supply, connect the Ag/AgCl electrode to the positive pole of the power supply, and insert it into the receiving chamber. The receiving solution is phosphate buffer solution with pH 7.4, and the current intensity is controlled. 0.2mA/cm ² , take samples at regular intervals, measure the absorbance at 276nm and 350nm according to the dual wavelength method, and calculate the cumulative penetration per unit area and skin penetration rate.

3. Comparison of pH value before and after in vitro iontophoresis of diclofenac sodium gel

Take a certain amount of diclofenac sodium gel before and after introduction respectively, put them in a small beaker, add 50ml of distilled water to dissolve, shake well and measure the pH value on the PHS-10B digital acidity meter.

The results of the in vitro test are shown in Table 1, Table 2, and Table 3

Table 1 Passive diffusion test results of diclofenac sodium gel prescription number 1 2 3 4 5 6 Transdermal rate (μg/h.cm ² ) 22.53±2.36 28.68±3.92 20.66±2.19 17.43±4.51 21.76±3.77 30.12±2.38

Table 2 Experimental results of diclofenac sodium gel percutaneous iontophoresis prescription number 1 2 3 4 5 6 Transdermal rate (μg/h.cm ² ) 35.21±2.98 61.40±2.11 41.75±7.63 25.66±5.34 37.24±3.16 48.95±4.33

Table 3 Comparison of pH before and after iontophoresis in different prescriptions of diclofenac sodium gel Gel No. pH value before import pH value after import ΔpH 1 7.28±0.07 7.86±0.10 0.58±0.14 2 7.36±0.12 7.83±0.11 0.47±0.15 3 7.30±0.08 7.98±0.16 0.68±0.37 4 7.29±0.06 8.01±0.25 0.72±0.29 5 7.37±0.18 7.95±0.23 0.58±0.13 6 7.39±0.13 9.03±0.17 1.64±0.25

Embodiment 3: in vivo test, select No. 2 prescription and prepare the same gel without exchange resin at the same time for in vivo test.

1. Passive Diffusion

Take healthy rabbits, weighing about 2.0±0.5kg. Fix the rabbit on the rabbit board, cut off a piece of hair about ^50cm2 on the abdomen of the rabbit, paste the gel on the cut skin, and take blood from the ear vein for measurement every half an hour.

2. Take a healthy rabbit with a body weight of about 2.0±0.5kg. Fix the rabbit on the rabbit board, take two pieces of about 50cm ² from the abdomen and cut the hair, paste gel on the cut skin, fix it with a lead plate (the area of the lead plate is 54cm ² ), and connect it to a regulated power supply Negative electrode, another piece of skin covered with water-soaked gauze, fixed with a lead plate, connected to the positive electrode of the regulated power supply. And make the distance between them 2cm. The current intensity was controlled at 0.3mA/cm ² , and blood was taken from the ear vein every half hour for measurement.

3. Take a certain amount of diclofenac sodium gel before and after introduction, put them in a small beaker, add 50ml of distilled water to dissolve, shake well and measure the pH value on a pHS-3C precision pH meter.

The results of the in vivo test are:

Passive diffusion in vivo cannot be detected because the drug concentration in the body is very low. The plasma concentration of diclofenac sodium after iontophoresis is shown in Figure 1, and the pH changes are shown in Table 4.

Table 4 Comparison of pH values before and after in vivo introduction of different prescriptions of diclofenac sodium gel pH value before import pH value after import ΔpH t P gel 1 7.37±0.03 9.20±0.04 1.83±0.05 23.96 P<0.01 gel 2 7.36±0.12 7.71±0.12 0.33±0.14

Note: Gel 1: without ion exchange resin Gel 2: with ion exchange resin

Claims (2)

1. a transdermal physiotherapeutic medicine gel mainly is made up of diclofenac sodium medicine, hydrophilic macromolecular material, compound penetrating agent azone and propylene glycol and glycerol, it is characterized in that: also comprise the ion exchange resin as absorbent.

2. the preparation method of transdermal physiotherapeutic medicine gel as claimed in claim 1, it is characterized in that: be to select for use two or more to be soaked in that certain hour makes it swelling in the distilled water hydrophilic macromolecular material, the heating in water bath dissolving, add compound penetrating agent and ion exchange resin, stir, add diclofenac sodium at last, stir and the impouring glass drying oven in, drying.