阅读说明：本技术 一种表面麻醉膏及其制备方法 (Surface anesthesia cream and preparation method thereof ) 是由 赵志峰 何宗昊 靳岳 邬昊曦 于 2019-12-13 设计创作，主要内容包括：本发明公开了一种表面麻醉膏及其制备方法,将花椒浸膏5~15份,薄荷脑提取物10~20份,缓释剂5~10份,蜂蜡15~25份,基质150~250份混合后得到混合膏体,将膏体在氮气体系下分三次进行蒸馏,最终得到表面麻醉膏。采用本发明制得的表面麻醉膏中花椒麻味物质含量高达76.6%,将其涂抹在皮肤表面后静置10-15分钟,即可达到麻醉效果,再加上本发明独特的工艺提高了麻味物质的稳定性,能防止麻醉膏在使用过程中因长时间暴露在空气中氧化变性。在药物散失过程中,花椒浸膏还能作为渗透促进剂,此时薄荷油可以扩大角质细胞间的连接从而产生一个透皮渗透的快速通道,使真皮中的胶原纤维束在一定程度上松解,两者协同促进神经恢复与肌肉收缩,缓解麻醉皮肤的不适感。(The invention discloses a surface anesthesia cream and a preparation method thereof, wherein 5-15 parts of pepper extract, 10-20 parts of menthol extract, 5-10 parts of slow release agent, 15-25 parts of beeswax and 150-250 parts of matrix are mixed to obtain a mixed cream body, and the cream body is distilled for three times under a nitrogen system to finally obtain the surface anesthesia cream. The content of the pepper numb-flavor substance in the surface anesthesia cream prepared by the invention is as high as 76.6 percent, and the anesthesia effect can be achieved by applying the surface anesthesia cream on the skin surface and standing for 10 to 15 minutes. In the process of medicine dissipation, the pepper extract can also be used as a penetration enhancer, and the peppermint oil can expand the connection between corneocytes so as to generate a rapid transdermal penetration channel, so that collagen fiber bundles in dermis are loosened to a certain degree, and the peppermint oil and the collagen fiber bundles are cooperated to promote nerve recovery and muscle contraction and relieve the discomfort of anesthetized skin.)

1. The surface anesthesia cream is characterized by comprising the following raw materials in parts by weight:

5-15 parts of pepper extract, 10-20 parts of menthol extract, 5-10 parts of slow release agent, 15-25 parts of beeswax and 150-250 parts of matrix.

2. The anesthetic paste as claimed in claim 1, wherein the anesthetic paste is prepared from the following raw materials in parts by weight:

10 parts of pepper extract, 15 parts of menthol extract, 7.5 parts of slow release agent, 20 parts of beeswax and 200 parts of matrix.

3. A process for the preparation of a topical anesthetic paste according to claim 1 or 2, characterized in that the process comprises the steps of:

(1) adding fructus Zanthoxyli extract, Mentholum extract, sustained release agent, and Cera flava into matrix, and mixing to obtain mixed paste;

(2) introducing ethanol into the mixed paste, and heating in a nitrogen system to complete primary distillation to obtain a primary distilled paste;

(3) adding ethanol into the primary distilled paste body, and heating under a nitrogen system to finish secondary distillation to obtain a secondary finishing paste body;

(4) and adding n-butanol into the secondary distillation paste body, and heating under a nitrogen system to finish tertiary distillation to obtain the surface anesthesia paste.

4. The preparation method according to claim 3, wherein the pepper extract in the step (1) is prepared by the following method:

(1) crushing the pepper leaves, sieving the crushed pepper leaves with a 500-mesh sieve, adding 10-20 times of water by weight, mixing and stirring the mixture uniformly, and performing ultrasonic treatment for 1-2 hours to obtain a suspension A;

(2) distilling the suspension A in a steam distillation device at 100-150 ℃ for 3-5 h, separating the collected liquid to obtain pepper essential oil, and simultaneously pouring the separated water phase back into the suspension A to obtain suspension B;

(3) centrifuging or filtering the suspension B to obtain a pepper leaching solution C, adding water with the weight being 6-8 times that of pepper leaves into filter residues again, stirring and leaching for 1-2 hours, centrifuging or filtering to obtain a pepper leaching solution D, combining the pepper leaching solution C and the pepper leaching solution D, and concentrating in vacuum to the concentration of 20-40 Baume degrees to obtain a concentrated solution E;

(4) adding 2-4 times of the volume of the aqueous phase of the zanthoxylum bungeanum essential oil into the concentrated solution E, and preparing an emulsion of the concentrated solution wrapping the zanthoxylum bungeanum essential oil through high-strength mechanical emulsification, namely the zanthoxylum bungeanum extract.

5. The method according to claim 4, wherein the suspension B is filtered by 100 mesh filtration in step (3); the vacuum degree is 0.05-0.1 MPa.

6. The method according to claim 4, wherein the high-intensity emulsification in the step (4) is high-speed shearing at 10000rpm or more, or homogenization treatment at 10MPa or more, or colloid mill treatment.

7. The preparation method according to claim 3, wherein the ethanol used in the step (2) is 1% of the mixed paste, the heating temperature is 72-80 ℃, and the vacuum degree is 0.35-0.45 KPa.

8. The preparation method according to claim 3, wherein the ethanol used in the step (3) is 0.3% of the mixed paste, the heating temperature is 80-86 ℃, and the vacuum degree is 0.05-0.15 KPa.

9. The preparation method according to claim 3, wherein the n-butanol is used in an amount of 0.01% of the mixed paste in the step (4), the heating temperature is 76 to 84 ℃, and the vacuum degree is 0.005 to 0.001 KPa.

10. A topical anesthetic paste prepared according to any one of the preparation methods of claims 3 to 9.

Technical Field

The invention belongs to the technical field of anesthetic drugs, and particularly relates to a preparation method of a surface anesthetic paste and the surface anesthetic paste prepared by the method.

Background

Anesthesia, a reversible functional suppression of the central and peripheral nervous systems, produced by drugs or other means, is characterized primarily by a loss of sensation, particularly pain sensation, i.e., the meaning of anesthesia is that the patient is temporarily deprived of sensation, either globally or locally, using drugs or other means, for the purpose of painless surgical treatment.

With the development of society, people increasingly have more and more demands on minimally invasive surgery treatment and cosmetic surgery treatment, and meanwhile, the demand on painless treatment in the treatment process is more and more strong. The treatment processes are accompanied by pains of different degrees, the pains invisibly affect the psychology of patients, generate anxiety, and seriously affect the treatment effect.

The epidermal anesthesia is one of the commonly used auxiliary treatment means of minimally invasive surgery, cosmetic surgery and the like, and currently, western medicine anesthetics such as lidocaine with strong skin penetrating power are mainly adopted. The lidocaine has good local anesthetic effect and strong penetrating power, but has high toxicity, the general dosage is about 2-4%, the anesthetic effect is poor when the dosage is too small, and the duration is short. The amido bond of the lidocaine is stable, the lidocaine is not easy to hydrolyze in acid or alkaline solution, the speed of in vivo enzymolysis is slow, and most of the lidocaine is metabolized by the liver in vivo, so the lidocaine has great damage to the body. The dyclonine hydrochloride has the advantages of lasting effect, low toxicity and high irritation.

In dermatology and plastic surgery, when performing laser surgery or minor surgery on the superficial layer of the skin such as high-frequency electric burn, in order to reduce pain caused by the surgery, it is common to apply a skin anesthetic ointment to the site to be treated before the surgery to perform superficial anesthesia. The human skin is mainly composed of three parts, namely epidermis, dermis and subcutaneous tissue, wherein the outermost layer of the epidermis is covered by a horny layer, and the horny layer has hydrophobicity and negative charge and is the biggest barrier to the penetration of drugs into the skin. Due to this barrier property of the stratum corneum, it is difficult to achieve effective concentrations of anesthetic at doses that penetrate the skin. Therefore, in the method of using skin anesthetic ointment to reduce the pain of operation, a large amount of anesthetic ointment is usually applied to the operation site, and the patient needs to wait for the drug to act for a long time.

Clinically, in order to shorten the time for waiting for anesthesia to take effect, after the skin is generally coated with an anesthetic ointment, the part is further sealed by a preservative film to promote the absorption of the anesthetic, however, the mode of wrapping the anesthetic by the preservative film is not only troublesome, but also the waiting time for anesthesia to take effect is still too long, generally about one hour is needed, the anxiety of a surgical patient can be invisibly increased while the anesthetic is waited for taking effect for a long time, and bacteria are easily generated on the skin surface layer in the long-time waiting process. Or the pain of the patient is reduced by adopting a local anesthesia mode, but the dosage of the anesthetic of the local anesthesia is not easy to grasp, the sensitivity of each person to the anesthetic is different, and the recovery time of the anesthesia is different, so that the anesthesia part is still in an anesthesia state after the operation of the patient is completed for a long time, the muscle can not contract, the movement is inconvenient, and even the function of assisting the blood backflow is lost, so that the blood stasis in the vein is easily caused, and the thrombus is caused.

The Chinese prickly ash has been used as an important medicine-food dual-purpose material in China for over two thousand years, has unique spicy flavor, is widely used for cooking of Sichuan vegetables, chafing dishes and the like, and is known as one of eight major seasonings. The pepper numb taste substance is an unsaturated fatty acid amide substance represented by sanshool and homologues thereof, has strong irritation, is a substance basis for generating numb taste of pepper, and is one of important indexes for measuring the quality of pepper. In addition, the zanthoxylum bungeanum numb-taste substance also has the physiological activities of anesthesia, analgesia, cancer resistance, free radical resistance, serum cholesterol reduction and the like, thereby having wide market prospect.

However, the zanthoxylum bungeanum spicy substance has complex components and an unsaturated double bond structure which is extremely unstable, and the zanthoxylum bungeanum spicy substance is oxidized into yellow viscous substance within a few minutes after being exposed in the air, thereby becoming a technical bottleneck for restricting the large-scale preparation of the high-purity zanthoxylum bungeanum spicy substance. Therefore, no commercially available pepper numb taste substance standard substance is available, certain difficulty is brought to quantitative evaluation of numb taste substances in pepper and pepper products, and application of the pepper in the health food grade medicine field is limited.

The extraction and preparation methods of the pepper spicy substances are more, mainly comprise a water extraction method, a column chromatography method, a supercritical carbon dioxide method, a molecular imprinting technology and the like, but the methods have certain limitations in industrial application. For example, CN1305742A provides a method for preparing pepper spicy substances by boiling and extracting at high temperature and high pressure, but the spicy substances extracted by the method also contain alkaloid impurities such as skimmianine and green pepper alkali, have low purity and cannot be used as pepper spicy substance standards. CN102690208A provides a method for extracting hydroxy sanshool from zanthoxylum oil, and although the purity of the obtained zanthoxylum nummular substance is high, the requirement on equipment is high, the scale is small, the method is only limited in experimental research, and the large-scale production is difficult to realize. CN1488289A discloses a method for separating and purifying pepper numb-taste substances by adopting a supercritical carbon dioxide technology, which has high requirements on equipment and complex operation, and the obtained pepper numb-taste substances still cannot be used as standard products. CN106866455A discloses a preparation method of a high-purity fructus Zanthoxyli fructus-flavor substance, which avoids the traditional chromatographic column process, is not limited in preparation amount, facilitates large-scale production, and has high purity of the fructus Zanthoxyli fructus-flavor substance, but the fructus Zanthoxyli fructus-flavor substance has low stability, thus limiting the application of the fructus Zanthoxyli fructus-flavor substance in the field of medicine.

Based on the analysis, the epidermal anesthesia cream which can quickly permeate the skin before an operation to perform local effective anesthesia, simultaneously plays an antibacterial and disinfection role in the anesthesia process, can also promote blood flow of an anesthesia part after the operation, stimulates muscle contraction and relieves the anesthesia effect is urgently needed by the industry.

Disclosure of Invention

In view of the defects, the invention provides the epidermal anesthesia cream which can quickly permeate into the skin before an operation to carry out local effective anesthesia, simultaneously has the antibacterial and disinfection effects in the anesthesia process, and can promote the blood flow of the anesthesia part after the operation, stimulate the muscle contraction and relieve the anesthesia effect.

In order to solve the problems, the invention provides a surface anesthesia cream prepared by rich pepper spicy substances with high concentration, which can effectively reduce anxiety of preoperative patients, shorten the time for waiting anesthesia and accelerate the decomposition of postoperative anesthesia components, and is realized by the following means:

the surface anesthesia ointment is prepared from the following raw materials in parts by weight:

5-15 parts of pepper extract, 10-20 parts of menthol extract, 5-10 parts of slow release agent, 15-25 parts of beeswax and 150-250 parts of matrix.

Further, the anesthetic paste is prepared from the following raw materials in parts by weight:

10 parts of pepper extract, 15 parts of menthol extract, 7.5 parts of slow release agent, 20 parts of beeswax and 200 parts of matrix.

A preparation method of a topical anesthetic paste comprises the following steps:

(1) adding fructus Zanthoxyli extract, Mentholum extract, sustained release agent, and Cera flava into matrix, and mixing to obtain mixed paste;

(2) introducing ethanol into the mixed paste, and heating in a nitrogen system to complete primary distillation to obtain a primary distilled paste;

(3) adding ethanol into the primary distilled paste body, and heating under a nitrogen system to finish secondary distillation to obtain a secondary finishing paste body;

(4) and adding n-butanol into the secondary distillation paste body, and heating under a nitrogen system to finish tertiary distillation to obtain the surface anesthesia paste.

Further, the usage amount of the ethanol in the step (2) is 1% of the mixed paste, the heating temperature is 72-80 ℃, and the vacuum degree is 0.35-0.45 KPa.

Further, in the step (3), the using amount of the ethanol is 0.3% of the mixed paste, the heating temperature is 80-86 ℃, and the vacuum degree is 0.05-0.15 KPa.

Further, the usage amount of the n-butanol in the step (4) is 0.01% of the mixed paste, the heating temperature is 76-84 ℃, and the vacuum degree is 0.005-0.001 KPa.

Further, the pepper extract in the step (1) is prepared by the following method:

(1) crushing the pepper leaves, adding water with the weight being 10-20 times that of the pepper leaves, mixing and stirring uniformly, and performing ultrasonic treatment for 1-2 hours to obtain a suspension A;

(2) distilling the suspension A in a steam distillation device at 100-150 ℃ for 3-5 h, separating the collected liquid to obtain pepper essential oil, and simultaneously pouring the separated water phase back into the suspension A to obtain suspension B;

(3) centrifuging or filtering the suspension B to obtain a pepper leaching solution C, adding water with the weight being 6-8 times that of pepper leaves into filter residues again, stirring and leaching for 1-2 hours, centrifuging or filtering to obtain a pepper leaching solution D, combining the pepper leaching solution C and the pepper leaching solution D, and concentrating in vacuum to the concentration of 20-40 Baume degrees to obtain a concentrated solution E;

(4) adding 2-4 times of the volume of the aqueous phase of the zanthoxylum bungeanum essential oil into the concentrated solution E, and preparing an emulsion of the concentrated solution wrapping the zanthoxylum bungeanum essential oil through high-strength mechanical emulsification, namely the zanthoxylum bungeanum extract.

Further, the pepper leaves in the step (1) are crushed and then sieved by a 500-mesh sieve.

Further, filtering the suspension B obtained in the step (3) to pass through a 100-mesh sieve; the vacuum degree is 0.05-0.1 MPa.

Further, in the step (4), the high-strength emulsification is high-speed shearing of 10000rpm or more, or homogenization treatment or colloid mill treatment of 10MPa or more.

The invention has the beneficial effects that:

1. the surface anesthesia cream prepared by the invention can smoothly and quickly permeate and soak into the skin, quickens the reversible function inhibition of the nervous system and achieves the effect of quickly relieving pain.

2. The content of the pepper numb-flavor substances in the surface anesthesia cream prepared by the method and the process reaches 76 percent, the surface anesthesia cream is smeared on the surface of skin and then stands for 10 to 15 minutes, the effect of rapid anesthesia can be achieved, and the onset time is at least shortened by 15 to 20 minutes compared with the traditional anesthesia cream. In addition, the unique process of the invention improves the stability of the numb-flavor substance, can prevent the anesthetic paste from being oxidized and denatured due to long-time exposure in the air in the use process, improves the action time of the numb-flavor substance and leads the anesthetic effect to be more durable.

3. In the process of dissipating the surface anesthesia ointment prepared by adopting the process and the invention, the pepper extract not only has an anesthesia effect, but also can be used as a penetration enhancer, the transdermal absorption is promoted by changing the structure of the horny layer, at the moment, the peppermint oil can expand the connection among the horny cells so as to generate a rapid transdermal penetration channel, so that the collagen fiber bundles in the dermis are loosened to a certain degree, and the peppermint oil cooperate to promote the nerve recovery and the muscle contraction, thereby relieving the discomfort of the anesthesia skin.

4. The anesthetic paste provided by the invention adopts natural food to extract components, the burden of traditional western medicine anesthetic components on a human body is changed, and the natural pepper numb-flavor substance has a transdermal anesthetic effect, is harmless to the human body, and has an obvious effect and a long duration.

Detailed Description

The present invention is described in detail below with reference to specific examples, but the present invention should not be construed as being limited thereto. The test methods in the following examples, which are not specified in specific conditions, are generally conducted under conventional conditions, and the steps thereof will not be described in detail since they do not relate to the invention.