CN112274498B - Compound lidocaine aerosol and preparation method thereof - Google Patents
Compound lidocaine aerosol and preparation method thereof Download PDFInfo
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- CN112274498B CN112274498B CN202011239201.9A CN202011239201A CN112274498B CN 112274498 B CN112274498 B CN 112274498B CN 202011239201 A CN202011239201 A CN 202011239201A CN 112274498 B CN112274498 B CN 112274498B
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Abstract
The invention discloses a compound lidocaine aerosol and a preparation method thereof, wherein the compound lidocaine aerosol comprises the following components in parts by weight: 0.2-3.5 parts of lidocaine, 0.2-3.5 parts of prilocaine, 1-3.5 parts of 0.1M sodium hydroxide, 2-35 parts of propellant, 1-17.6 parts of polyvinyl alcohol and 0.1-1.75 parts of rutin derivative; under the condition of not containing penetrating agent and surfactant, the invention releases lidocaine and prilocaine in basic form to subcutaneous layer, and uses polyvinyl alcohol to form film on skin surface, thus reducing the dosage of lidocaine and prilocaine and enhancing the safety of clinical use; the treatment of premature ejaculation of the male mainly inhibits the arteriole of the corpus cavernosum of the penis and the expansion of the anterior sphincter of capillary vessels to relax smooth muscles, thereby increasing the blood flow; the rutin derivative is added, so that the elasticity and permeability of the rutin derivative are increased by improving the function of capillary vessels, and adverse reactions such as vascular bleeding and the like caused by long-term use of the traditional lidocaine medicine are avoided.
Description
Technical Field
The invention belongs to the field of medicinal preparations, and particularly relates to a compound lidocaine aerosol and a preparation method thereof.
Background
At present, the most widely applied preparation form of the compound lidocaine clinically is cream or patch, and the compound lidocaine is mainly used for local surface anesthetics, treating male premature ejaculation, reducing the stinging caused by mosquito bites and the like.
Premature ejaculation in males is mainly caused by an excessively sensitive local nerve and an excessively low tolerance threshold to sexual stimulation; at present, the oral treatment medicine for treating the premature ejaculation of the male at home and abroad is dapoxetine, is mainly an antidepressant and is occasionally used for the premature ejaculation of the male; the oral treatment medicine also comprises sildenafil and apomorphine hydrochloride buccal tablets, and the two medicines have obvious side effects, such as headache, even syncope, dyspepsia and the like; the external medicine is mainly Bifal, but after the external medicine is used, the swelling and pain of the penis can be caused, and the burning sensation can be adjusted; the injection mainly uses phentolamine which is easy to cause pain at the injection part and persistent or abnormal erection, and side effects such as cavernous body fibrosis and the like can be caused after long-term use.
Therefore, the medicine for treating the premature ejaculation has the defects of more side effects, inconvenient use, long onset time and the like, and some side effects can cause irreversible damage, such as cavernous fibrosis; the oral medicine has long onset time, needs to be absorbed by different mucous membrane parts, and has relatively large administration dosage; the external medicine is mainly gel, needs to be smeared, and has the defects of slow effect, repeated smearing and strong irritation; the injection needs the assistance of specially-assigned people, is more inconvenient to use, and needs to puncture the skin, thereby bringing the risk of infection.
Disclosure of Invention
The invention aims to provide a compound lidocaine aerosol and a preparation method thereof, aiming at solving the technical problems of convenient carrying and use, improved curative effect, shortened onset time, reduced dosage and reduced adverse reaction; and how to prepare the aerosol.
In order to achieve the purpose, the invention adopts the following technical scheme;
the invention provides a compound lidocaine aerosol, which comprises the following components in parts by weight: 0.2-3.5 parts of lidocaine, 0.2-3.5 parts of prilocaine, 1-3.5 parts of 0.1M sodium hydroxide, 2-26 parts of propellant, 1-17.6 parts of polyvinyl alcohol and 0.1-1.75 parts of rutin derivative.
Polyvinyl alcohol is obtained by commercial procurement; the segments of the polyvinyl alcohol are usually linked in head-to-tail form, the polyvinyl alcohol may be completely hydrolyzed, and has repeating groups of-CH2-CH (OH), or partially hydrolyzed containing the repeating unit-CH2-ch (or), wherein R is hydrogen and acetyl or longer alkyl. But to ensure that the water solubility of the polyvinyl alcohol is not affected.
As a preferred scheme, the lidocaine, prilocaine and rutin derivative comprises the following components in percentage by weight: lidocaine: prilocaine: rutin derivatives are 1: 1: 0.5.
preferably, the rutin derivative is rutin sodium or rutin potassium.
Rutin sodium or rutin potassium belongs to rutin alkali metal salt, and the water solubility and the absorption effect of the rutin sodium or rutin potassium are higher than those of rutin; rutin has effects of improving blood vessel, maintaining normal resistance of capillary vessel, and preventing hemorrhage and edema caused by excessive fragility and permeability of capillary vessel; the composition also has the effects of restoring the elasticity of blood vessels, maintaining the normal resistance of capillary vessels, reducing the permeability of the blood vessels and restoring the normal elasticity of the capillary vessels bleeding due to increased fragility; also has antiinflammatory effect.
In addition, rutin alkali metal salt is added with propellant and other auxiliary materials.
Preferably, the propellant is propane butane or 1, 1, 1, 2-tetrafluoroethane or 1, 1, 1, 2, 3, 3, 3-heptafluoropropane and/or propane and/or isobutane.
International health stops have required decommissioning due to freon's destruction of the atmospheric ozone layer; the Vienna convention for the protection of the ozone layer stipulates that chlorofluorocarbons are eliminated before 2010; currently, Freon propellants are stopped to be used; 1, 1, 1, 2-tetrafluoroethane or 1, 1, 1, 2, 3, 3, 3-heptafluoropropane has begun to be used as a novel propellant in 1994, and has a shape and boiling point similar to freon.
Then, hydrocarbons are gradually produced, and the propellants mainly comprise propane, n-butane and isobutane, are stable in chemical property and low in toxicity, but cannot be used independently, and are generally used together with chlorofluorocarbon propellants.
And the propellant is a compressed gas propellant, which has stable chemical properties, but the pressure is easy to rapidly drop at normal temperature, and the effect of durable injection cannot be achieved.
The amount of propellant used in the present invention is selected based on the total amount of the components other than the propellant.
Preferably, the alcoholysis degree of the polyvinyl alcohol is 68-75%.
In addition, the invention also provides a preparation method of the compound lidocaine aerosol, which comprises the following specific steps.
a. Adding deionized water into polyvinyl alcohol, heating to 78-85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use;
b. preparation of rutin derivatives:
b1 adding 9-10 times of 68-72% ethanol aqueous solution into the sophora japonica rice, ultrasonically leaching in a water bath for 30-40 min, and carrying out solid-liquid separation to obtain a first crude extract;
b2, adding the filter residue in b1 into 68-72% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 8.5-9;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing a propellant to obtain the spray.
Preferably, the frequency of the ultrasonic leaching is 10 KHZ-30 KHZ.
Compared with the prior art, the invention has the following beneficial effects.
1, the lidocaine, prilocaine, 0.1M sodium hydroxide, the propellant, the rutin derivative and the polyvinyl alcohol are all the existing components, are nontoxic and stable in components, and have small irritation to the skin, particularly the skin on the surface of the male penis cavernous body.
2, the invention adopts the aerosol preparation, is convenient to carry and use, has improved curative effect compared with the common spray, and takes effect quickly.
3, the polyvinyl alcohol is a functional polymer material with excellent mechanical property, biocompatibility and biodegradability, and as a water-soluble polymer, the polyvinyl alcohol has good water solubility and can absorb a large amount of water to soften; the polyvinyl alcohol film can absorb water quickly, becomes a flexible film in the process of absorbing water, has improved flexibility and air permeability, has high adhesive force with other medicines, can be adsorbed on the surface of the skin quickly after the aerosol is sprayed, and can form a net-shaped or continuous film on the surface of the skin by adhering other components through the polyvinyl alcohol, thereby achieving good film forming effect and reducing the dosage.
4, the added rutin derivative, namely rutin sodium or rutin potassium, has the effects of improving blood vessels, keeping the normal resistance of capillary vessels, and preventing the arteriole of the corpus cavernosum of the penis and the expansion of the anterior sphincter of the capillary vessels due to the inhibition of an alpha receptor, so that smooth muscles are relaxed, the blood flow is increased, and adverse reactions such as vascular bleeding are generated; preventing bleeding and edema caused by hyperpermeability; also has anti-inflammatory effect, and can reduce irritation of medicine, reduce allergy probability of patients, and avoid irreversible injury.
6, the invention does not contain penetrant, surfactant and hormone components; in the compound lidocaine structure, the characteristic that the melting point is reduced when the lidocaine and the prilocaine are mixed according to the weight ratio of 1: 1 at normal temperature is utilized, and the compound lidocaine is mixed from a solid state to a liquid state at normal temperature; the ion flow required by blocking the generation and the conduction of nerve impulse is accumulated at the pain receptor and the nerve ending of the cortex to stabilize nerve cells, thereby achieving the anesthesia of the cortex, having no corrosion and stimulation to the skin and enhancing the safety of clinical use; in addition, due to the addition of rutin sodium or rutin potassium, the bleeding and edema of arterioles and capillaries of the corpus cavernosum penis caused by the permeability enhancement of the synergistic effect of lidocaine and prilocaine can be prevented in the process of using the invention.
In addition, the synergistic effect of lidocaine, prilocaine and sodium or potassium rutin can treat premature ejaculation of men, reduce pain of wounds, enhance elasticity of skin and blood vessels and help wound healing.
7, the aerosol preparation process is less, the time is short, and the labor cost of production is reduced to a certain extent.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The primary objects and other advantages of the invention may be realized and attained by the instrumentalities particularly pointed out in the specification.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
A first part: pharmaceutical formulation part
Example 1
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 0.2 part of lidocaine, 0.2 part of prilocaine, 1 part of 0.1M sodium hydroxide, 2 parts of propane and butane, 1 part of polyvinyl alcohol with 68 percent of alcoholysis degree and 0.1 part of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 78 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 9 times of 68% ethanol water solution into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 10KHZ for 30min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into a 68% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 8.5;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing a propellant to obtain the spray.
Example 2
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 3.5 parts of lidocaine, 3.5 parts of prilocaine, 3.5 parts of 0.1M sodium hydroxide, 15 parts of 1, 1, 1, 2-tetrafluoroethane, 11 parts of propane, 17.6 parts of polyvinyl alcohol with 75% of alcoholysis degree and 1.75 parts of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 9 times of 72% ethanol water solution into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 30KHZ for 40min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into a 68% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 9;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing a propellant to obtain the spray.
Example 3
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 2 parts of lidocaine, 2 parts of prilocaine, 2 parts of 0.1M sodium hydroxide, 10 parts of 1, 1, 1, 2, 3, 3, 3-heptafluoropropane, 8 parts of propane, 9.5 parts of polyvinyl alcohol with 75% of alcoholysis degree and 1 part of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 72% ethanol water solution 9.5 times the amount of flos Sophorae Immaturus into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 25KHZ for 36min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into 70% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 8.5;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing propellants 1, 1, 1, 2, 3, 3, 3-heptafluoropropane and propane to obtain the compound.
Example 4
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 2.4 parts of lidocaine, 2.4 parts of prilocaine, 2.3 parts of 0.1M sodium hydroxide, 13 parts of 1, 1, 1, 2, 3, 3, 3-heptafluoropropane, 8 parts of isobutane, 12.5 parts of polyvinyl alcohol with 75% alcoholysis degree and 1.2 parts of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 10 times of 72% ethanol water solution into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 18KHZ for 32min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into 71% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 9;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing propellants 1, 1, 1, 2, 3, 3, 3-heptafluoropropane and isobutane to obtain the compound pesticide.
Example 5
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 1.6 parts of lidocaine, 1.6 parts of prilocaine, 1.4 parts of 0.1M sodium hydroxide, 10 parts of 1, 1, 1, 2-tetrafluoroethane, 8 parts of isobutane, 9 parts of polyvinyl alcohol with 75% alcoholysis degree and 0.8 part of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 72% ethanol water solution 9.5 times the amount of flos Sophorae Immaturus into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 18KHZ for 32min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into 70% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 8.5;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing propellants of 1, 1, 1, 2-tetrafluoroethane and isobutane to obtain the product.
A second part: pharmacodynamic moiety
Control group 1
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 3.5 parts of lidocaine, 3.5 parts of prilocaine, 3.5 parts of 0.1M sodium hydroxide, 17.6 parts of polyvinyl alcohol with 68% of alcoholysis degree, 15 parts of 1, 1, 1, 2-tetrafluoroethane and 11 parts of propane.
A preparation method of compound lidocaine aerosol comprises the following steps: stirring lidocaine and prilocaine thoroughly, filtering, filling into spray aluminum can, sealing spray pump, and pressing into propellant 1, 1, 1, 2-tetrafluoroethane and propane.
Control group 2
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 3.5 parts of lidocaine, 3.5 parts of prilocaine, 3.5 parts of 0.1M sodium hydroxide and 17.6 parts of polyvinyl alcohol with 68% alcoholysis degree.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 78 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. And c, fully and uniformly stirring the product obtained in the step a, lidocaine and prilocaine, and filtering to obtain the compound.
Control group 3
The embodiment relates to a compound lidocaine aerosol, which consists of the following components in parts by weight: 3.5 parts of lidocaine, 3.5 parts of prilocaine, 3.5 parts of 0.1M sodium hydroxide, 17.6 parts of polyvinyl alcohol with 75% of alcoholysis degree and 1.75 parts of rutin sodium.
A preparation method of compound lidocaine aerosol comprises the following steps.
a. Adding deionized water into polyvinyl alcohol, heating to 85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use.
b. Preparation of rutin derivatives:
b1 adding 9 times of 72% ethanol water solution into flos Sophorae Immaturus, leaching in water bath with ultrasonic frequency of 30KHZ for 40min, and separating solid and liquid to obtain first crude extractive solution;
b2, adding the filter residue in b1 into a 68% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide or potassium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 9;
c. and c, fully and uniformly stirring the products obtained in the step a and the step b with lidocaine and prilocaine, and filtering to obtain the compound.
2.1 lidocaine spray on skin irritation test
2.1.1 test animals
20 rabbits with the weight of 3 kg-3.5 kg are taken, 10 rabbits are female and male respectively, the temperature in a laboratory is 25 +/-1 ℃, and the relative humidity is 65%.
2.1.2 test methods
Removing hair from two sides of spinal column of rabbit 24h before administration, wherein the area of each side hair removal is 15cm2After unhairing, checking whether the unhaired skin is scratched due to unhairing or not 24h, if the skin is injured, the rabbit is not suitable for performing an irritation experiment; the skin of the unhaired and sterilized rabbit is lacerated into a cross shape by using the needle tip of a sterilizing needle, and the size of the wound is not more than 10mm2The bleeding stopped, and the rabbits were used as a test for irritation of damaged skin.
In the test, the rabbits are divided into two groups, each group comprises 10 rabbits, and each group comprises five male rabbits and five female rabbits; adopting the same body to compare left and right, pressing the left hair removing area once, fixing a quantitative valve at 50 mu/press, coating a substrate on the right hair removing area as a contrast, fixing the control by gauze and adhesive tape, removing residual test object by warm water after giving the test object for 24 hours, and removing the test object for 1 hour, 24 hours and 48 hours for visual observation. The presence or absence of erythema and edema at the site of application was recorded.
Selecting the embodiment 2 with the largest weight part, wherein the comparison group 1 is formed by adding no rutin sodium on the basis of the embodiment 2, the comparison group 2 is formed by adding no rutin sodium and no propellant on the basis of the embodiment 2, the comparison group 3 is formed by adding no propellant on the basis of the embodiment 2, and the medicine use observation is carried out on two groups of rabbits; one group of the use examples 2 and the control group 3 were sprayed and smeared on the left and right sides of a rabbit hair-removed part, and the other group of the use control group 1 and the control group 2 were sprayed and smeared on the left and right sides of a rabbit hair-removed part; the test results are shown in Table 1.
TABLE 1 results of the skin irritation test with lidocaine spray
Therefore, the irritation of the aerosol spray to the skin and the wound is smaller than that of the smearing mode, and the irritation of the experimental group added with the rutin sodium is smaller than that of the experimental group not added with the rutin sodium.
2.2 drug efficacy test
2.2.1 test animals
20 male rabbits with the weight of 3 kg-3.5 kg, 20 female rabbits and 40 total rabbits are taken, wherein 20 female rabbits and 20 male rabbits are used for carrying out a skin injury recovery test, and the other 20 male rabbits are used for carrying out a male premature ejaculation treatment effectiveness test, and the temperature in a laboratory (25 +/-1) DEG C and the relative humidity are 65%.
2.2.2 establishment of skin Damage model and Damage treatment test
Removing hair from two sides of spinal column of rabbit 24h before administration, wherein the area of each side hair removal is 15cm2Checking whether the dehaired skin is scratched due to dehairing after 24h after dehairing, and if the skin is injured, the rabbit is not suitable for being subjected to a medicine effectiveness test; cutting the skin of unhaired and sterilized rabbit into cross with a sterilizing scalpel, with the wound size not more than 10mm2The depth is not more than 1cm, 2 pairs of injuries are respectively made on each rabbit, the damaged skin part of each rabbit is sprayed every 12 hours for 7 days, and the experimental conditions of the 1 st day, the 3 rd day and the 7 th day are recorded; the specific test results are shown in Table 2.
TABLE 2 test results on effectiveness of skin injury-treating drugs
It can be seen that the recovery of example 2 is the fastest compared with the three control groups, and the recovery of the control group 3 is faster than that of the control group 1 and the control group 2 and has small irritation to the skin because the medicinal components are the same as those of example 2 and rutin sodium is also added.
2.2.3 test results on effectiveness of treatment of premature ejaculation in males
20 male rabbits were sprayed on the genitals of the male rabbits according to examples 1 to 5 for three times, and sprayed once every 12 hours. The final test results are shown in table 3.
Table 3 male premature ejaculation treatment effectiveness test results:
therefore, the total onset rate of the components in the examples 3 and 4 is the highest, so the weight parts of the components in the examples 3 and 4 are the best onset groups, and the effect is the best; the overall onset of both example 2 and example 5 was slightly lower than that of example 3 and example 4, with the overall effectiveness of example 1 being the lowest.
In summary, the present invention is only a preferred embodiment, and not intended to limit the scope of the invention, and all equivalent changes and modifications in the shape, structure, characteristics and spirit of the present invention described in the claims should be included in the scope of the present invention.
Claims (3)
1. The compound lidocaine aerosol is characterized by comprising the following components in parts by weight: 0.2-3.5 parts of lidocaine, 0.2-3.5 parts of prilocaine, 1-3.5 parts of 0.1M sodium hydroxide, 2-26 parts of propellant, 1-17.6 parts of polyvinyl alcohol and 0.1-1.75 parts of rutin derivative;
wherein the lidocaine, prilocaine and rutin derivative comprise the following components in percentage by weight: lidocaine: prilocaine: rutin derivative = 1: 1: 0.5;
the rutin derivative is rutin sodium;
the propellant is propane butane or 1, 1, 1, 2-tetrafluoroethane or 1, 1, 1, 2, 3, 3, 3-heptafluoropropane and/or propane and/or isobutane;
the alcoholysis degree of the polyvinyl alcohol is 68-75%.
2. A method of preparing the compound lidocaine aerosol according to claim 1, comprising the steps of:
a. adding deionized water into polyvinyl alcohol, heating to 78-85 ℃, stirring until the polyvinyl alcohol is completely dissolved, and cooling to room temperature for later use;
b. preparation of rutin derivatives:
b1 adding 9-10 times of 68-72% ethanol aqueous solution into the sophora japonica rice, ultrasonically leaching in a water bath for 30-40 min, and carrying out solid-liquid separation to obtain a first crude extract;
b2, adding the filter residue in b1 into 68-72% ethanol water solution, carrying out ultrasonic extraction, and carrying out solid-liquid separation to obtain a second crude extract;
b3, combining the first crude extract and the second crude extract, and then carrying out reduced pressure distillation;
b4, adding 0.1M sodium hydroxide aqueous solution into the product of b3 for dissolving, and titrating until the pH value is 8.5-9;
c. and c, fully stirring and uniformly filtering the products obtained in the steps a and b, lidocaine and prilocaine, filling into a spray aluminum can, sealing a spray pump, and pressing a propellant of propane and butane or 1, 1, 1, 2-tetrafluoroethane or 1, 1, 1, 2, 3, 3, 3-heptafluoropropane to obtain the product.
3. The method for preparing the compound lidocaine aerosol according to claim 2, wherein the frequency of the ultrasonic leaching is 10KHZ to 30 KHZ.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179103A (en) * | 1995-03-17 | 1998-04-15 | 理查德·A·亨利 | Prilocaine and hydrofluorocarbon aerosol preparations |
| CN101785766A (en) * | 2010-01-26 | 2010-07-28 | 江苏天际药业有限公司 | Lidocaine and chlorhexidine aerosol |
| CN101816642A (en) * | 2010-05-21 | 2010-09-01 | 鲍亚华 | Compound lidocaine emulsifiable paste and preparation method thereof |
| CN111065415A (en) * | 2017-07-12 | 2020-04-24 | 詹姆斯·布兰查德 | Platform for local delivery of pharmaceutical agents and method of formulating same |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179103A (en) * | 1995-03-17 | 1998-04-15 | 理查德·A·亨利 | Prilocaine and hydrofluorocarbon aerosol preparations |
| CN101785766A (en) * | 2010-01-26 | 2010-07-28 | 江苏天际药业有限公司 | Lidocaine and chlorhexidine aerosol |
| CN101816642A (en) * | 2010-05-21 | 2010-09-01 | 鲍亚华 | Compound lidocaine emulsifiable paste and preparation method thereof |
| CN111065415A (en) * | 2017-07-12 | 2020-04-24 | 詹姆斯·布兰查德 | Platform for local delivery of pharmaceutical agents and method of formulating same |
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