CN101584689A - Compound ear drops containing antipyrine and lidocaine and preparation method thereof - Google Patents

Abstract

The invention discloses a compound ear drop containing antipyrine and lidocaine and a preparation method thereof. In total, it contains 1%-20% antipyrine and 0.5%-5% lidocaine or its salts. The compound ear drops containing antipyrine and lidocaine of the present invention has rapid action, significant curative effect and low cost, and has excellent antibacterial and anti-inflammatory effects for middle ear barotrauma and acute and chronic otitis media, especially for middle ear barotrauma The invention has good cure rate, obvious analgesic effect, reduces discomfort of patients such as otalgia and headache, and is convenient to use, low in price, simple in preparation and controllable in quality.

Description

Compound ear drops containing antipyrine and lidocaine and preparation method thereof

technical field

The invention relates to an ear drop, in particular to a compound ear drop containing antipyrine and lidocaine and a preparation method thereof.

Background technique

Acute and chronic otitis media are common and frequently-occurring diseases in clinical otology. Most of the pathogenic bacteria are Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic streptococcus, Proteus, etc. Some otitis media may be accompanied by anaerobic bacteria, etc. Symptoms include temporary hearing loss and pain in the affected ear, or accompanied by fever, examination shows sunken or bulging or perforated tympanic membrane, disappearance of tympanic membrane light cone, middle ear effusion or effusion, tympanic membrane hyperemia or hemorrhage, and even In the case of tympanic membrane perforation, exudate or pus can be seen, and there is tenderness in the external auditory canal, mastoid, etc., or palpable enlarged lymph nodes around the ear, or accompanied by tenderness.

Middle ear barotrauma is also called barotrauma otitis media. When the external air pressure changes, the pressure in the middle ear intratympanic chamber cannot reach the equilibrium with the external pressure instantaneously for some reason, resulting in corresponding pathological changes. Middle ear barotrauma is a common disease in aviation (especially when aircraft takes off and lands) and diving (mainly during diving). The symptoms of middle ear barotrauma are mainly severe pain, instantaneous hearing loss, unbearable pain, etc., which can lead to a reduction in working ability and even forced to stop working. Medical examination shows that the tympanic membrane of the affected ear is congested or sunken or perforated or bleeding, the light cone of the tympanic membrane disappears, and the middle ear chamber oozes and/or accumulates fluid. In the acute stage, there may be no symptoms such as tenderness, enlarged lymph nodes, and tenderness. The patient's otalgia persists, and the hearing impairment lasts for hours to days, usually conductive hearing impairment.

At present, the main components of ear drops clinically used for the treatment of the above-mentioned otitis media are antibiotics, antiseptics and/or glucocorticoids, etc., among which chloramphenicol (CN1247063A) and gentamicin are commonly used in antibiotics. phenol, kanamycin, neomycin, ciprofloxacin (CN 1126073A), metronidazole (CN 1137917A, CN 1260174A), norfloxacin (CN 1260174A), etc. phenol, boric acid, etc. are commonly used as disinfectant preservatives, Glucocorticoid drugs commonly used dexamethasone (CN 1247063A) and the like.

After many years of abuse of antibiotics, the drug resistance of pathogenic bacteria has become very serious, and the curative effect is limited. It is often necessary to conduct drug sensitivity tests of pathogenic bacteria before selecting sensitive antibiotics for treatment, and antibiotics can be passed The tympanic membrane enters the middle ear and produces toxicity, causing irreversible pathological damage, especially antibiotics such as gentamicin, neomycin, chloramphenicol, and kanamycin can cause permanent hearing loss and can cause vestibular dysfunction in the affected ear , causing sequelae such as tinnitus, deafness, and disability in the patient, and bringing great misery to the patient.

The use of disinfectant and preservatives has a certain effect, but the effect is limited, and can inhibit the normal function of cells to varying degrees, and easily damage the tympanic membrane and mucous membrane. Although the application of glucocorticoids can help the treatment of otitis media, long-term use will cause adverse consequences such as hormone drug dependence and systemic hormone reactions, and it is not suitable for sports athletes. After use, it may cause athletes Doping test was positive. The commonly used clinical treatment methods for otitis media are not effective in analgesia.

Contents of the invention

The object of the present invention is to provide a compound ear drop containing antipyrine and lidocaine and a preparation method thereof, so as to overcome the above-mentioned defects in the prior art.

The compound ear drops containing antipyrine and lidocaine of the present invention comprises antipyrine, lidocaine and pharmaceutically acceptable adjuvants, containing 1% to 20% by weight of the compound ear drops % antipyrine and 0.5% to 5% lidocaine or its salts, preferably, containing 4% antipyrine and 1% lidocaine hydrochloride;

Preferably, the weight percent components of the compound ear drops containing antipyrine and lidocaine include:

Antipyrine or its derivatives 1%～20%

Lidocaine or its salts 0.5% to 5%

Sodium Thiosulfate 0.1%～10%

Ethanol 10%～30%

Glycerin 50%～80%

The sum of the percentages of the above components is 100%;

The volume concentration of described ethanol is 75～95%;

Further preferably, the weight percent components of the compound ear drops containing antipyrine and lidocaine include:

Antipyrine or its derivatives 4～6%

Lidocaine or its salts 1-2%

Sodium thiosulfate 0.1%～1.0%

Ethanol 20～25%

Glycerin 68～74.5%

The sum of the percentages of the above components is 100%;

The antipyrine derivatives include antiisopropyl antipyrine, pyrenmethamine, antipyrine salicylate, antipyrine acetanilide or antipyrine acetanilide, etc., Among them, antipyrine is preferred;

The lidocaine salts include lidocaine hydrochloride or lidocaine glucose, preferably lidocaine hydrochloride.

Preferably, the compound ear drops containing antipyrine and lidocaine also includes more than one of isotonic agent, antioxidant, acidity regulator or preservative;

The isotonic agent can be selected from sorbitol, mannitol, glycerin, propylene glycol, glucose, sucrose, lactose, trehalose or fructose, and the consumption of the isotonic agent is the compound ear drops containing antipyrine and lidocaine. 60-95% of the total weight of the liquid;

The antioxidant can be selected from sodium sulfite, sodium bisulfite, sodium metabisulfite or vitamin C, and the dosage is 0-10% of the total weight of the compound ear drops containing antipyrine and lidocaine;

The acidity regulator or pH regulator can be selected from lactic acid, citric acid, acetic acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium acetate or sodium lactate, and the dosage is the compound ear drops containing antipyrine and lidocaine 0-0.5% of the total weight of the liquid;

The preservative can be selected from benzoic acid, benzoate, sorbic acid or sorbate, and the dosage is 0-0.5% of the total weight of the compound ear drops containing antipyrine and lidocaine.

The preparation method of the compound ear drops containing antipyrine and lidocaine of the present invention, comprises the steps:

Add antipyrine and lidocaine to ethanol, mix well, then add sodium thiosulfate to the above solution, mix well and dissolve, then add glycerin to the above solution, mix well and dissolve, and obtain the product;

Preferably, it also includes the step of adding one or more of isotonic agents, antioxidants, acidity regulators or preservatives.

Tests in vitro prove that the present invention adopts the drug combination of antipyretic, anti-inflammatory and analgesic drugs-antipyrine or its derivatives and local anesthetics-lidocaine or its salts, supplemented by sodium thiosulfate, ethanol, glycerol Inorganic and organic substances, such as liquid solution, are used to treat middle ear barotrauma and otitis media with good results.

On the one hand, the present invention takes antipyretic, anti-inflammatory and analgesic drugs-antipyrine or its derivatives and local anesthetic drug-lidocaine or its salts as the main pharmaceutical ingredients, with its characteristics of being easily soluble in water or aqueous solution, Play the role of anti-inflammatory analgesia and local anesthesia analgesia, play the effect of synergistic treatment of otitis media (especially middle ear barotrauma); Medium, increase the local absorption rate of the drug in the outer ear, and reduce the irritation of the drug to the external auditory canal, tympanic membrane and other parts.

The compound ear drops containing antipyrine and lidocaine according to the present invention can be applied to patients in need of treatment by dripping into the external auditory canal, and the recommended therapeutic dose is 4 drops each time, 2 to 3 times a day , can be used continuously for up to 10 days, which can be determined by a specialist according to the patient's condition.

The compound ear drops containing antipyrine and lidocaine in the present invention is weakly acidic, with a pH value of 4.5-7.0, adapts to the acid-base environment of the external auditory canal of the human body, reduces the possibility of bacterial infection, and is conducive to the exertion of antibacterial effects. It is especially suitable for occupations or positions with a high incidence of middle ear barotrauma, such as aviation and diving. It can treat occupational middle ear barotrauma, alleviate and reduce the complications and sequelae of middle ear barotrauma.

The compound ear drops containing antipyrine and lidocaine of the present invention has rapid action, significant curative effect and low cost, and has excellent antibacterial and anti-inflammatory effects for middle ear barotrauma and acute and chronic otitis media, especially for middle ear barotrauma The invention has good cure rate, obvious analgesic effect, reduces discomfort of patients such as otalgia and headache, and is convenient to use, low in price, simple in preparation and controllable in quality.

Detailed ways

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. For the experimental methods without specific conditions indicated in the following examples, the conventional conditions or the conditions suggested by the manufacturer are usually followed. Ratios and percentages are by weight unless otherwise indicated.

Example 1

Antipyrine 4g

Lidocaine Hydrochloride 1g

Sodium thiosulfate 0.1g

95 (volume)% ethanol 24g

Glycerin 70.9g

Dissolve antipyrine and lidocaine hydrochloride in ethanol solution to make a solution, then add sodium thiosulfate to the above solution, mix well, add glycerin, mix well and dissolve, and obtain ear drops.

The ear drops can be dripped into the external auditory canal for administration and treatment of the external auditory canal.

Example 2

Antipyrine 4g

Lidocaine Hydrochloride 1g

Sodium thiosulfate 0.5g

95 (volume)% ethanol 20g

Glycerin 74.5g

The preparation method is the same as in Example 1.

Example 3.

Antipyrine 4g

Lidocaine Hydrochloride 2g

Sodium thiosulfate 0.2g

75 (volume)% ethanol 25g

Glycerin 68.8g

The preparation method is the same as in Example 1.

Example 4. Compound ear drops containing antipyrine and lidocaine

Antipyrine 6g

Lidocaine Hydrochloride 2g

Sodium thiosulfate 0.1g

75 (volume)% ethanol 25g

Glycerin 66.9g

The preparation method is the same as in Example 1.

Example 5.

Antipyrine 6g

Lidocaine Hydrochloride 1g

Sodium thiosulfate 0.5g

95 (volume)% ethanol 20g

Glycerin 72.5g

The preparation method is the same as in Example 1.

Example 6.

Antipyrine 6g

Lidocaine Hydrochloride 1g

Sodium thiosulfate 0.1g

95 (volume)% ethanol 24g

Glycerin 68.9g

The preparation method is the same as in Example 1.

Embodiment 7, in vitro test

Pharmacological and Toxicological Experimental Research on Compound Ear Drops Containing Antipyrine and Lidocaine of the Present Invention

(1) In vitro antibacterial test: The in vitro antibacterial test adopts the paper disc method and the plate punching method, and compares it with the standard chloramphenicol. Results This product has inhibitory effect on Staphylococcus aureus and Pseudomonas aeruginosa, and is sensitive to common middle ear infection bacteria. The test results are shown in Table 1

Each embodiment of table 1 and chloramphenicol standard product in vitro bacteriostatic test bacteriostatic zone mean value

Unit: mm

Note: each experiment was repeated 3 times

(2) Toxicology experiment: in the acute toxicity experiment, the experimental mice were randomly divided into two groups, ie, the high-dose group and the low-dose group, which were administered orally respectively. The low-dose group was administered orally by 100 times of the transdermal absorption of the drug, and the high-dose group was orally administered by 1000 times of the transdermal absorption of the drug. The results showed that no mouse died after gavage, indicating that the drug is non-toxic, and it is a safe drug to use as ear drops. The test results are shown in Table 2

Each embodiment acute toxicity experiment of table 2

(3) Skin irritation test: the white rabbits were shaved off on both sides of the head 24 hours before administration, but the skin was not damaged. During the experiment, 2ml of ear drops of this product and 2ml of normal saline were dripped on sterilized filter paper, pasted on the left and right backs of rabbits, covered with one layer of oil paper and two layers of gauze, sealed with adhesive tape, and left for 30 minutes and 60 minutes respectively. Minutes, 24 hours and 48 hours to check the drug's skin irritation in rabbits. Results There was no erythema and edema on the skin of the rabbits, indicating that the drug has no irritation to the skin. The test results are shown in Table 3

Each embodiment skin irritation test of table 3

Note: "-" means negative symptoms, no erythema and edema

(4) Indications, usage and dosage

According to the effects of prescription drugs and pharmacological and toxicological experimental research, this product can be used to treat middle ear diseases such as middle ear barotrauma, acute and chronic otitis media, and catarrhal otitis media.

Before use, use 3% hydrogen peroxide to wash away the dirt in the external auditory canal, and then drip the medicinal liquid of this product, 4 drops each time, 2-3 times a day, stop the drug after the symptoms disappear, and use it continuously for up to 10 days.

The present inventor adopts the formula of embodiment 1 to treat 16 cases of middle ear barotrauma patients with otalgia and mild hearing impairment among divers, the total effective rate is 100%, and the cure rate is 93.75%. After 2-4 days of recovery, you can continue diving operations. The treatment results are shown in Table 4.

Table 4 embodiment 1 treats the curative effect statistics of middle ear barotrauma patient

Claims (9)

1. the compound recipe [that contains phenazone and lignocaine, it is characterized in that, comprise phenazone, lignocaine and pharmaceutically acceptable adjuvant,, contain the phenazone of 1%--20% and lignocaine or its esters of 0.5%--5% in compound recipe [gross weight.

2. the compound recipe [that contains phenazone and lignocaine according to claim 1 is characterized in that, contains 4% phenazone and 1% lignocaine or its esters.

3. the compound recipe [that contains phenazone and lignocaine according to claim 1 is characterized in that, the described percentage by weight component that contains the compound recipe [of phenazone and lignocaine comprises:

Phenazone or derivatives thereof 1%～20%

Lignocaine or its esters 0.5%～5%

Sodium thiosulfate 0.1%～10%

Ethanol 10%～30%

Glycerol 50%～80%

Described alcoholic acid volumetric concentration is 75～95%.

4. the compound recipe [that contains phenazone and lignocaine according to claim 1 is characterized in that, the described percentage by weight component that contains the compound recipe [of phenazone and lignocaine comprises:

Phenazone or derivatives thereof 4～6%

Lignocaine or its esters 1～2%

Sodium thiosulfate 0.1%～1.0%

Ethanol 20～25%

Glycerol 68～74.5%

5. according to each described compound recipe [that contains phenazone and lignocaine of claim 1～4, it is characterized in that, described phenazone derivant comprises that peace is for isopropylantipyrine, than woods methylamine methane, salipyrin, anilipyrine or anilipyrine.

6. according to each described compound recipe [that contains phenazone and lignocaine of claim 1～4, it is characterized in that described lignocaine salt comprises lidocaine hydrochloride or glucose lignocaine.

7. according to each described compound recipe [that contains phenazone and lignocaine of claim 1～4, it is characterized in that, in the described compound recipe [that contains phenazone and lignocaine, also comprise in isotonic agent, antioxidant, acidity regulator or the antiseptic one or more.

8. the compound recipe [that contains phenazone and lignocaine according to claim 7 is characterized in that described isotonic agent can be selected from sorbitol, mannitol, glycerol, propylene glycol, glucose, sucrose, lactose, trehalose or fructose;

Described antioxidant can be selected from sodium sulfite, sodium sulfite, sodium pyrosulfite or vitamin C;

Acidity regulator or pH regulator agent can be selected from lactic acid, citric acid, acetic acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium acetate or sodium lactate;

Described antiseptic can be selected from benzoic acid, benzoate, sorbic acid or sorbate.

9. prepare each described method that contains the compound recipe [of phenazone and lignocaine of claim 1～8, it is characterized in that, comprise the steps: phenazone, lignocaine are joined in the ethanol, mixing, then sodium thiosulfate is joined in the above-mentioned solution, the mixing dissolving joins glycerol in the above-mentioned solution then, the mixing dissolving promptly obtains product.