Anti-fatigue lead-free black plaster and preparation method thereof

Abstract

The invention provides an anti-fatigue lead-free black plaster and a preparation method thereof, and belongs to the field of traditional Chinese medicines. The preparation method comprises the following steps: adding tangerine leaves, rhodiola rosea, clove, cinnamon and croscarmellose sodium into vegetable oil, heating, frying, and filtering to obtain medicinal oil; heating the medicinal oil, adding ferric oxide, zinc oxide, magnesium oxide and activated carbon powder, continuously stirring until white bubbles are dispersed and black bubbles appear, and continuously heating and decocting the medicinal oil for 10-15 minutes; cooling to obtain hot paste; adding borneol into the hot paste, uniformly mixing, pouring into cold water, cooling, and soaking to obtain lead-free black paste; heating to remove moisture, cooling, and coating on a backing to obtain the anti-fatigue lead-free black plaster. The anti-fatigue lead-free black plaster has obvious fatigue relieving and refreshing effects, is prepared by using a lead-free process and is convenient to use, toxic components are reduced, and the plaster enables the medicine to be more easily absorbed by skin, so that multi-scene anti-fatigue application is realized.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and specifically relates to an anti-fatigue lead-free black plaster and its preparation method. Background Technology

[0002] Fatigue mainly manifests as decreased physical strength, mental fatigue, poor concentration, muscle soreness, and reduced work efficiency. Chronic fatigue not only severely impacts people's quality of life but can also induce various diseases; furthermore, fatigue among long-distance drivers and manual laborers often results in significant loss of life and property. Currently, there are various methods to combat fatigue, mainly including oral medications, health supplements, and physical therapy. Oral medications have drawbacks such as slow onset of action, gastrointestinal irritation, and the first-pass effect on the liver; physical therapy requires professional application and is inconvenient for daily use. External patches (such as black plasters), as a traditional Chinese medicine dosage form, have unique advantages such as direct action, convenient use, and avoidance of the first-pass effect on the liver and gastrointestinal irritation.

[0003] Black plasters, also known as lead oxide plasters, mainly consist of a matrix and a drug. The matrix forms the plaster's framework, primarily serving to adhere, shape, and act as a drug carrier. Currently, the most serious drawback of traditional black plasters is the risk of lead poisoning. This is because their matrix contains a large amount of lead oxide (lead tetroxide, Pb3O4), a key component in the formation of black plasters. Often called red lead or yellow lead, at high temperatures (around 300℃), lead oxide undergoes a saponification reaction with vegetable oil to produce fatty acid lead salts, transforming the oil from a liquid state into a thick, viscous black paste. With prolonged, large-area use, or when the skin is broken, the heavy metal lead in the matrix can be absorbed into the body through the skin, accumulating and leading to chronic lead poisoning, affecting the nervous system, hematopoietic system, and kidney function. During production, lead oxide is used extensively, posing a risk of long-term lead poisoning to workers and causing heavy metal environmental pollution. Summary of the Invention

[0004] Therefore, the present invention aims to provide an anti-fatigue lead-free black plaster and its preparation method, in order to solve at least one technical problem in the background art.

[0005] This invention is implemented as follows: The first aspect of this invention provides a method for preparing an anti-fatigue lead-free black plaster, wherein the lead-free black plaster comprises a drug and a lead-free matrix; the raw materials of the drug include orange leaves, rhodiola rosea, cloves, cinnamon and borneol; the raw materials of the lead-free matrix include vegetable oil, iron oxide, zinc oxide, magnesium oxide, croscarmellose sodium and activated carbon powder. The preparation method includes the following steps: Orange leaves, Rhodiola rosea, cloves, cinnamon, and croscarmellose sodium cellulose were added to vegetable oil, heated to the first temperature to fry the ingredients, and then filtered to obtain the medicinal oil. Heat the medicinal oil to the second temperature, add iron oxide, zinc oxide, magnesium oxide and activated charcoal powder, and stir continuously until the white bubbles disappear and black bubbles appear. Continue heating and simmering the oil for 10 to 15 minutes. After simmering, cool it to the third temperature to obtain the hot ointment. Add borneol to the hot paste and mix well. Then pour it into cold water to cool and soak, and you will get lead-free black paste. The lead-free black plaster is heated to the fourth temperature to remove moisture, cooled to the fifth temperature, and then applied to the backing to obtain the anti-fatigue lead-free black plaster.

[0006] Furthermore, the medicine comprises the following raw materials in parts by weight: 11 to 13 parts of orange leaves, 4 to 6 parts of Rhodiola rosea, 1 to 3 parts of cloves, 3 to 5 parts of cinnamon, and 2 to 4 parts of borneol.

[0007] Furthermore, the lead-free matrix comprises the following raw materials in parts by weight: 385 to 495 parts vegetable oil, 8 to 10 parts iron oxide, 18 to 22 parts zinc oxide, 7 to 9 parts magnesium oxide, 6 to 8 parts croscarmellose sodium, and 0.1 to 0.3 parts activated carbon powder.

[0008] Furthermore, the vegetable oil includes 350 to 450 parts soybean oil and 35 to 45 parts sesame oil.

[0009] Furthermore, the first temperature is 180℃~220℃, and the frying time is 10min~20min.

[0010] Furthermore, the second temperature is 260℃~300℃; the third temperature is 180℃~220℃.

[0011] Furthermore, the fourth temperature is 140℃~160℃; the fifth temperature is 60℃~80℃.

[0012] The second aspect of this invention provides an anti-fatigue lead-free black plaster prepared by the above-described preparation method.

[0013] Compared with the prior art, the present invention has the following beneficial effects: 1. The anti-fatigue lead-free black plaster of the present invention has obvious effects in relieving fatigue and refreshing the mind. It is prepared using a lead-free process, which makes it easy to use. At the same time, it reduces toxic components, making the medicine easier to be absorbed by the skin, thereby realizing anti-fatigue applications in multiple scenarios.

[0014] 2. The anti-fatigue lead-free black plaster of the present invention achieves a comprehensive effect of promoting local blood circulation, relieving muscle soreness and inflammation, improving tissue oxygen supply, clearing metabolic waste, and invigorating the spirit through a multi-target mechanism of action of promoting penetration (borneol, clove) + warming and unblocking (cinnamon) + invigorating qi and anti-oxidation (Rhodiola rosea) + regulating qi and refreshing the mind (orange leaf), thereby effectively combating physical and mental fatigue. Attached Figure Description

[0015] Figure 1 The total ion current chromatogram of the anti-fatigue lead-free black plaster prepared in Example 1 of this invention; Figure 2 The total ion current chromatogram of the anti-fatigue lead-free black plaster prepared in Comparative Example 1 of this invention; Figure 3 This is a comparison chart of the average speeds of mice in each group during the open field experiment of Example 2 of the present invention; Figure 4 This is a comparison chart of the resting time of mice in each group during the open field experiment of Example 2 of the present invention; Figure 5 This is a comparison chart of the movement distances of mice in each group during the open field experiment of Example 2 of the present invention; Figure 6 This is a comparison of the sleep latency of mice in each group during the sodium pentobarbital sleep induction experiment of Example 2 of the present invention; Figure 7 This is a comparison chart of sleep time in mice of different groups during the sodium pentobarbital sleep induction experiment of Example 2 of the present invention; Figure 8 This is a comparison chart of the swimming rest time of mice in each group during the forced swimming experiment of Example 2 of the present invention. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0017] An anti-fatigue lead-free black plaster includes a drug and a lead-free matrix; the raw materials of the drug include orange leaves, rhodiola rosea, cloves, cinnamon and borneol; wherein the orange leaves are 11 to 13 parts, the rhodiola rosea is 4 to 6 parts, the cloves are 1 to 3 parts, the cinnamon is 3 to 5 parts, and the borneol is 2 to 4 parts.

[0018] The raw materials for the lead-free matrix include vegetable oil, iron oxide, zinc oxide, magnesium oxide, croscarmellose sodium, and activated carbon powder; wherein the vegetable oil comprises 385-495 parts, iron oxide 8-10 parts, zinc oxide 18-22 parts, magnesium oxide 7-9 parts, croscarmellose sodium 6-8 parts, and activated carbon powder 0.1-0.3 parts. In a specific implementation, the vegetable oil is preferably a mixture of soybean oil and sesame oil, wherein the soybean oil comprises 350-450 parts and the sesame oil comprises 35-45 parts.

[0019] The preparation method of anti-fatigue lead-free black plaster includes the following steps: S1. Add orange leaves, rhodiola rosea, cloves, cinnamon and croscarmellose sodium to vegetable oil, heat to the first temperature (180℃~220℃) and fry for 10min~20min, then filter to obtain medicinal oil; S2. Heat the medicinal oil to the second temperature (260℃~300℃), add iron oxide, zinc oxide, magnesium oxide and activated carbon powder, and stir continuously until the white foam disappears and black foam appears. Continue heating and simmering the oil for 10min~15min. After simmering the oil, cool it to the third temperature (180℃~220℃) to obtain the hot ointment. S3. Add borneol to the hot paste and mix well. Then pour it into cold water to cool and soak, and you will get lead-free black paste. S4. Heat the lead-free black plaster to the fourth temperature (140℃~160℃) to remove moisture, cool it to the fifth temperature (60℃~80℃) and then apply it to the backing to obtain the anti-fatigue lead-free black plaster.

[0020] The pharmacological effects of tangerine leaves, rhodiola rosea, cloves, cinnamon, and borneol in anti-fatigue lead-free black plaster are as follows: Rhodiola rosea's core component, rhodioloside, can enhance cells' tolerance to hypoxia and improve energy metabolism; it can improve microcirculation and oxygen supply in local tissues; it also has strong antioxidant activity, which can eliminate excess free radicals generated after exercise, reduce oxidative stress damage to muscle cells, and thus accelerate physical recovery; Rhodiola rosea can also enhance immune function and improve the decline in immunity caused by fatigue.

[0021] Cinnamaldehyde, the main active ingredient in cinnamon, can cause vasodilation in the skin, significantly increasing blood flow and producing a strong warming sensation. This effectively dispels cold and relieves soreness and stiffness caused by poor blood circulation. Furthermore, it improves cold hands and feet and blood supply to local tissues by dilating peripheral blood vessels, thus accelerating the removal of metabolic waste.

[0022] Orange leaves are rich in volatile oils, which can be absorbed through the skin when applied externally. They have a mild stimulating effect and can promote local blood circulation. Orange leaf extract has a certain anti-inflammatory effect and can relieve mild muscle inflammation caused by fatigue. The aroma of orange leaves helps to refresh the mind and indirectly regulate the nervous system through the olfactory system, thus relieving mental stress.

[0023] Borneol has a strong transdermal penetration promoting effect, opening up skin channels with its super penetrating power; it can also relieve pain, and has a slight stimulating and anesthetic effect on nerve endings; it can also produce a cooling sensation, which complements the warming sensation of cinnamon and cloves, thus both clearing the meridians and preventing excessive heat.

[0024] Eugenol, the main component of cloves, is a natural transdermal absorption enhancer that can help the active ingredients of other drugs penetrate the skin barrier more effectively. Cloves produce a mild stimulation to the skin, causing capillary dilation and generating a warming sensation, thereby relieving fatigue and coldness caused by cold and dampness and poor blood circulation.

[0025] The roles of each component in the lead-free matrix of the anti-fatigue lead-free black plaster are as follows: The functions of cross-linked sodium carboxymethyl cellulose are: ① to increase drug dissolution during the extraction stage; ② to increase the amount of cross-linking of oils and fats during the molding stage, accelerate the saponification reaction, and make the plaster form well.

[0026] Function of activated charcoal powder: to adjust the texture of black plaster and increase its hardness.

[0027] The role of iron oxide, zinc oxide, and magnesium oxide: They replace the use of lead oxide / red lead oxide in traditional black plasters. The amount required is much lower than that of red lead oxide in traditional lead-containing black plasters, thereby reducing heavy metal pollution during production, avoiding contact between toxic heavy metals and skin, and preventing long-term accumulation of toxins in the body, thus increasing the safety of medication.

[0028] Example 1 A method for preparing an anti-fatigue lead-free black plaster, comprising the following steps: S1. Add 400g soybean oil, 40g sesame oil, 7g croscarmellose sodium, 12g orange leaves, 5g rhodiola rosea, 2g cloves and 4g cinnamon to a pot, heat to 180℃~220℃, fry the ingredients for 15 minutes, filter, and obtain medicinal oil.

[0029] S2. Heat the medicinal oil to 280℃, add 9g of iron oxide, 20g of zinc oxide, 8g of magnesium oxide and 0.2g of activated charcoal powder, and stir continuously until the white smoke dissipates, the white bubbles in the pot disappear and black bubbles begin to appear. Continue heating and simmering the oil for another 10 minutes. After stopping heating, let it cool to about 200℃ to obtain a hot ointment.

[0030] S3. Grind 3g of borneol into powder, add it to the hot paste and stir well. Then pour it into cold water to cool and soak for 24 hours to remove the fire toxicity, and obtain lead-free black paste.

[0031] S4. Place the lead-free black plaster in a pot and heat it at 150°C for 5 minutes to remove the moisture. Cool it to 70°C and apply it to the backing to obtain the anti-fatigue lead-free black plaster.

[0032] The anti-fatigue lead-free black plaster was sampled, dissolved, and injected into a GC-MS for analysis. The total ion chromatogram is shown below. Figure 1 As shown.

[0033] Comparative Example 1 The only difference between this comparative example and Example 1 is that cross-linked sodium carboxymethyl cellulose is not added in S1; the other conditions and reaction steps are the same as in Example 1.

[0034] The anti-fatigue lead-free black plaster prepared in this comparative example was sampled, dissolved, and injected into GC-MS for analysis and detection. The total ion chromatogram is shown below. Figure 2 As shown.

[0035] Depend on Figure 1 and Figure 2 The comparison shows that the drug component content of the anti-fatigue lead-free black plaster in Example 1 is significantly higher than that of the anti-fatigue lead-free black plaster in Comparative Example 1, indicating that the addition of cross-linked carboxymethyl cellulose sodium during frying extraction helps to dissolve the drug components and improve the quality of the plaster.

[0036] Comparative Example 2 The only difference between this comparative example and Example 1 is that the oil boiling time in S2 is adjusted to 20 minutes to prolong the reaction time of the plaster. Other conditions and reaction steps are the same as in Example 1.

[0037] Comparative Example 3 The only difference between this comparative example and Example 1 is that the oil boiling time in S2 is adjusted to 5 minutes to shorten the reaction time of the plaster. Other conditions and reaction steps are the same as in Example 1.

[0038] Comparative Example 4 The only difference between this comparative example and Example 1 is that activated carbon powder is not added in S2; the other conditions and reaction steps are the same as in Example 1.

[0039] Comparative Example 5 The only difference between this comparative example and Example 1 is that the amount of some components in the lead-free matrix in S2 is too low; the other conditions and reaction steps are the same as in Example 1.

[0040] Specifically, in this comparative example S2, the medicinal oil was heated to 280°C, and 4.5g of iron oxide, 10g of zinc oxide, 4g of magnesium oxide, and 0.2g of activated charcoal powder were added. The mixture was stirred continuously until the white smoke dissipated, the white bubbles in the pot disappeared, and black bubbles began to appear. The oil was then heated for another 10 minutes. After heating was stopped, the mixture was cooled to approximately 200°C to obtain a hot ointment.

[0041] Comparative Example 6 The only difference between this comparative example and Example 1 is that the amount of some components in the lead-free matrix in S2 is too high; the other conditions and reaction steps are the same as in Example 1.

[0042] Specifically, in this comparative example S2, the medicinal oil was heated to 280°C, and 15g of iron oxide, 30g of zinc oxide, 15g of magnesium oxide, and 0.2g of activated charcoal powder were added. The mixture was stirred continuously until the white smoke dissipated, the white bubbles in the pot disappeared, and black bubbles began to appear. The oil was then heated for another 10 minutes. After heating was stopped, the mixture was cooled to approximately 200°C to obtain a hot ointment.

[0043] The softening point is the temperature at which a plaster deforms and softens to a certain degree after being heated. The softening point is an important physical indicator of the heat resistance of black plasters. If the softening point is too low, the plaster will be too soft at room temperature or body temperature, easily slipping off the backing, staining clothing, and shifting during application. If the softening point is too high, the plaster will be too hard, failing to adhere tightly to the skin, affecting the transdermal absorption of active ingredients, and easily damaging the skin or causing severe pain when removed. Therefore, the softening point directly affects the clinical efficacy and user experience of black plasters. To ensure the adhesion and stability of black plasters to the human body, the softening point should be between 45℃ and 55℃. The softening points of the anti-fatigue lead-free black plasters prepared in Example 1 and Comparative Examples 1 to 6 were measured, and the results are shown in Table 1.

[0044] Table 1

[0045] The data in Table 1 show that: in Comparative Example 1, no cross-linked sodium carboxymethyl cellulose was added, resulting in insufficient oil reaction in the black plaster, a low softening point, and unsuitability for coating. Comparative Example 2 extended the reaction time of the plaster, resulting in the black plaster being over-cooked, having a higher softening point, and being unsuitable for coating use. Comparative Example 3 reduced the reaction time of the plaster, resulting in insufficient reaction of the black plaster, a lower softening point, and unsuitability for coating use; Comparative Example 4 did not add activated carbon powder, which resulted in a loose plaster structure and a low softening point, making it unsuitable for coating. Comparative Example 5 reduced the amount of iron oxide, zinc oxide, and magnesium oxide in the lead-free matrix, resulting in insufficient reaction of the black plaster, excessively low softening point, excessive stickiness, and unusability. Comparative Example 6 increased the amount of iron oxide, zinc oxide, and magnesium oxide in the lead-free matrix, resulting in excessive reaction of the black plaster, an excessively high softening point, and excessive hardness, rendering it unusable.

[0046] Comparative Example 7 This comparative example was used to evaluate the effects of iron oxide, zinc oxide, and magnesium oxide in the lead-free matrix on the quality of the finished product. Anti-fatigue lead-free black plaster was prepared according to the steps of Example 1, with the only difference being the adjustment of the amounts of iron oxide, zinc oxide, and magnesium oxide in step S2 (refer to groups 1-7 in Table 2). All other conditions and steps were the same as in Example 1. The experimental process was observed, the feel of the finished product was evaluated, and the softening point was tested. The results are shown in Table 2.

[0047] Table 2

[0048] Table 2 shows that the pastes made with iron oxide, magnesium oxide, and magnesium oxide + iron oxide as lead-free matrices failed to form a solid paste and could not be solidified. The pastes made with zinc oxide and iron oxide + zinc oxide as lead-free matrices had poor toughness and were prone to cracking. The paste made with zinc oxide + magnesium oxide as a lead-free matrices was too yellow, too soft, sticky, and had poor toughness. The paste made with a composite metal oxide of iron oxide + zinc oxide + magnesium oxide as a lead-free matrices had moderate hardness, good toughness, and a suitable softening point. This indicates that using a single metal oxide cannot meet the forming requirements of lead-free black plaster; using two metal oxides in combination improves the situation somewhat, but problems such as the paste being too yellow or too soft occur; using a composite metal oxide of three metal oxides improves all of the above problems.

[0049] Example 2 Animal experiments related to anti-fatigue were conducted using the black plasters prepared in Example 1 and Comparative Example 1.

[0050] 1. Open field experiment Experimental animals: Thirty-six healthy male Kunming mice of similar condition were randomly divided into 6 groups, with 6 mice in each group; the experimental groups are as follows: Control group (Group A): Blank plaster, administered to the neck; Positive drug group (Group B): Caffeine was administered by gavage at a dose of 57 mg / kg; Experimental groups (C1-C4): Group C1 used the non-crosslinked sodium carboxymethyl cellulose black plaster prepared in Comparative Example 1, with a plaster application amount of L*W*H=1.5cm*1.5cm*2mm; Groups C2-C4 used the black plaster prepared in Example 1, with application amounts of low dose (L*W*H=1.5cm*1.5cm*1.5mm), medium dose (L*W*H=1.5cm*1.5cm*2mm), and high dose (L*W*H=1.5cm*1.5cm*2.5mm), respectively, and were applied topically after shaving the neck.

[0051] Experimental Procedure: The positive control group received the medication via gavage once daily, while the experimental group received a new black plaster daily for three consecutive days. An open field test was conducted once daily. The group was allowed 3 minutes to familiarize themselves with the environment, and behavioral parameters were recorded over 5 minutes: total distance traveled (cm), average speed (cm / s), and rest time (s). The results are as follows: Figures 3 to 5 As shown, * indicates P < 0.05, and ** indicates P < 0.01.

[0052] Figures 3 to 5The results showed that on the first day of administration, compared with the control group (Group A), the average speed of the positive control group (Group B), the non-crosslinked sodium carboxymethyl cellulose black plaster test group (Group C1), and the low / medium / high dose black plaster test groups (Groups C2-C4) were significantly increased (P<0.05, P<0.01), the rest time was significantly reduced (P<0.05, P<0.01), and the movement distance was significantly increased (P<0.01). This indicates that the anti-fatigue lead-free black plaster can significantly improve the spontaneous activity ability of normal mice and has an invigorating effect. On the second day of administration, the experimental results were basically consistent with those of the first day. On the third day of administration, compared with the control group, the total movement distance of the mice in the positive control group was significantly increased (P<0.01), while the rest time and average speed were not significantly different; the average speed of the anti-fatigue lead-free black plaster groups C1-C4 was significantly increased (P<0.05, P<0.01), the rest time was significantly reduced (P<0.01), and the movement distance was significantly increased (P<0.01). This indicates that, compared to caffeine, the lead-free anti-fatigue black plaster in groups C1-C4 can exert a sustained effect in promoting spontaneous activity in mice. A comparison between groups C1 and C3 shows that, at the same dosage, the black plaster without cross-linked carboxymethyl cellulose sodium was less effective than the group containing cross-linked carboxymethyl cellulose sodium.

[0053] 2. Sodium amobarbital sleep induction experiment Another 36 male Kunming mice were randomly divided into 6 groups of 6 mice each. The experimental groups are as follows: Control group (Group A): Blank plaster, administered to the neck; Positive drug group (Group B): Caffeine was administered by gavage at a dose of 57 mg / kg; Experimental groups (C1-C4): Group C1 used the non-crosslinked sodium carboxymethyl cellulose black plaster prepared in Comparative Example 1, with a plaster application amount of L*W*H=1.5cm*1.5cm*2mm; Groups C2-C4 used the black plaster prepared in Example 1, with application amounts of low dose (L*W*H=1.5cm*1.5cm*1.5mm), medium dose (L*W*H=1.5cm*1.5cm*2mm), and high dose (L*W*H=1.5cm*1.5cm*2.5mm), respectively, and were applied topically after shaving the neck.

[0054] Experimental Procedure: After administration of the drug, the control and experimental groups rested for 15 minutes before undergoing an intraperitoneal injection of sodium amobarbital (137.5 mg / kg) to induce sleep. The positive control group received caffeine via gavage for 30 minutes before undergoing an intraperitoneal injection of sodium amobarbital (137.5 mg / kg) to induce sleep. Sleep latency and sleep duration were recorded for each group. The details for each group are as follows: Figure 6 and Figure 7 As shown.

[0055] Figure 6 and Figure 7 The results showed that, compared with the control group (Group A), the positive control group (Group B), the black plaster test group without cross-linked carboxymethyl cellulose sodium (Group C1), and the low / medium / high dose black plaster test groups (Groups C2-C4) had no significant effect on the sleep latency of mice (P>0.05), but the sleep time was significantly shortened (P<0.01), indicating that the anti-fatigue lead-free black plaster has a good wake-inducing effect. A comparison between Group C1 and Group C3 showed that, under the same dosage, the black plaster without cross-linked carboxymethyl cellulose sodium was less effective than the group with cross-linked carboxymethyl cellulose sodium.

[0056] 3. Forced swimming experiment Another 36 male Kunming mice were randomly divided into 6 groups of 6 mice each. The experimental groups are as follows: Control group (Group A): Blank plaster, administered to the neck; Positive drug group (Group B): Caffeine was administered by gavage at a dose of 57 mg / kg; Experimental groups (C1-C4): Group C1 used the non-crosslinked sodium carboxymethyl cellulose black plaster prepared in Comparative Example 1, with a plaster application amount of L*W*H=1.5cm*1.5cm*2mm; Groups C2-C4 used the black plaster prepared in Example 1, with application amounts of low dose (L*W*H=1.5cm*1.5cm*1.5mm), medium dose (L*W*H=1.5cm*1.5cm*2mm), and high dose (L*W*H=1.5cm*1.5cm*2.5mm), respectively, and were applied topically after shaving the neck.

[0057] Experimental Procedure: Both the control and experimental groups underwent a forced swimming test after a 15-minute rest period. The positive control group (caffeine) underwent the forced swimming test 30 minutes after gavage administration. Mice were allowed 2 minutes to familiarize themselves with the environment, and the cumulative swimming rest time was recorded over 8 minutes. A mouse was considered at rest when it floated on the surface and its hind legs remained stationary. The experiment lasted a total of 10 minutes, and the results are as follows: Figure 8 As shown.

[0058] Depend on Figure 8 It was found that, compared with the control group (Group A), the positive control group (Group B), the black plaster test group without cross-linked carboxymethyl cellulose sodium (Group C1), and the low / medium / high dose black plaster test groups (Groups C2-C4) significantly shortened the swimming rest time of mice (P<0.01), indicating that the anti-fatigue lead-free black plaster and caffeine can promote spontaneous activity and improve physical fatigue in mice. A comparison between Groups C1 and C3 showed that, under the same dosage, the black plaster without cross-linked carboxymethyl cellulose sodium was less effective than the group with cross-linked carboxymethyl cellulose sodium.

[0059] 4. Skin sensitization test Another 16 male Kunming mice were randomly divided into 4 groups of 4 mice each. The experimental groups are as follows: Control group (Group A): Blank plaster, neck hair shaved and medication applied topically; Positive drug group (Group B): Traditional lead-containing black plaster group, applied externally after shaving the neck hair; Experimental groups (C1 and C2): Group C1 used the non-crosslinked sodium carboxymethyl cellulose black plaster prepared in Comparative Example 1, and Group C2 used the black plaster prepared in Example 1. The dosage of both was the same, L*W*H=1.5cm*1.5cm*2mm, and the plaster was applied externally after shaving the neck.

[0060] The preparation method of the traditional lead-containing black plaster in the positive drug group (Group B) differs from that in Example 1 only in S2, which is as follows: heat the medicinal oil to 230°C, add 90g of red lead, stir continuously, wait for the white smoke to dissipate, continue heating to boil the oil for 5 minutes, stop heating and cool to about 200°C to obtain hot plaster; other conditions and reaction steps are the same as in Example 1, and the traditional lead-containing black plaster is obtained.

[0061] Experimental procedure: 24 hours before the experiment, long hair was clipped from both sides of the back of mice in each group, and then the hair was removed (approximately 3cm × 3cm). The drug was applied to the left side of the shaved area of ​​each group of mice, fixed with non-irritating rubber glue, and then housed separately. At 72 hours, the occurrence of skin erythema, edema, and systemic symptoms such as unsteady standing, difficulty breathing, and anaphylactic shock was observed and recorded.

[0062] Table 3

[0063] Based on the grading of erythema and edema in Table 3, the average score and sensitization rate of the sensitization reaction were calculated to determine the sensitization. The average score of the sensitization reaction was calculated as follows: (Total score for erythema formation + Total score for edema formation) / Total number of animals. The sensitization rate (%) was calculated as: (Number of animals exhibiting sensitization / Total number of test animals) × 100%.

[0064] 72 hours after sensitization, no severe systemic allergic reactions, such as death or shock, occurred in any of the groups of animals. In the experimental group (Group B), the traditional lead-containing black plaster group, one mouse showed mild erythema and mild edema, and one mouse showed moderate erythema and moderate edema. In the experimental group (C1), the anti-fatigue lead-free black plaster group, one mouse showed mild erythema and mild edema. No mice showed erythema or edema in the control group (Group A) and the experimental group (C2), the anti-fatigue lead-free black plaster group. The skin sensitization test symptom scores of the mice in each group are shown in Table 4.

[0065] Table 4

[0066] Table 4 shows that the anti-fatigue lead-free black plaster with added croscarmellose sodium did not cause any skin sensitization; the traditional lead-containing black plaster had moderate sensitization; and the anti-fatigue lead-free black plaster without added croscarmellose sodium had mild sensitization.

[0067] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for preparing an anti-fatigue lead-free black plaster, characterized in that, The lead-free black plaster includes a medicine and a lead-free base; the raw materials of the medicine include orange leaves, rhodiola rosea, cloves, cinnamon and borneol; the raw materials of the lead-free base include vegetable oil, iron oxide, zinc oxide, magnesium oxide, croscarmellose sodium and activated carbon powder. The preparation method includes the following steps: Orange leaves, Rhodiola rosea, cloves, cinnamon, and croscarmellose sodium cellulose were added to vegetable oil, heated to the first temperature to fry the ingredients, and then filtered to obtain the medicinal oil. Heat the medicinal oil to the second temperature, add iron oxide, zinc oxide, magnesium oxide and activated charcoal powder, and stir continuously until the white bubbles disappear and black bubbles appear. Continue heating and simmering the oil for 10 to 15 minutes. After simmering, cool it to the third temperature to obtain the hot ointment. Add borneol to the hot paste and mix well. Then pour it into cold water to cool and soak, and you will get lead-free black paste. The lead-free black plaster is heated to the fourth temperature to remove moisture, cooled to the fifth temperature, and then applied to the backing to obtain the anti-fatigue lead-free black plaster.

2. A process for the preparation of an anti-fatigue lead-free black plaster as claimed in claim 1, wherein, The medicine comprises the following raw materials in parts by weight: 11 to 13 parts of orange leaves, 4 to 6 parts of Rhodiola rosea, 1 to 3 parts of cloves, 3 to 5 parts of cinnamon, and 2 to 4 parts of borneol.

3. The preparation method of the anti-fatigue lead-free plaster according to claim 1 or 2, characterized in that, The lead-free matrix comprises the following raw materials in parts by weight: 385-495 parts vegetable oil, 8-10 parts iron oxide, 18-22 parts zinc oxide, 7-9 parts magnesium oxide, 6-8 parts croscarmellose sodium cellulose, and 0.1-0.3 parts activated carbon powder.

4. The preparation method of the anti-fatigue lead-free plaster according to claim 3, characterized in that, The vegetable oils include: 350 to 450 parts soybean oil and 35 to 45 parts sesame oil.

5. The method of claim 1, wherein the anti-fatigue lead-free plaster is prepared by mixing 1 part of the anti-fatigue lead-free plaster of claim 1 with 1 part of water. The first temperature is 180℃~220℃, and the frying time is 10min~20min.

6. The method for preparing an anti-fatigue lead-free black plaster according to claim 1, characterized in that, The second temperature is 260℃~300℃; the third temperature is 180℃~220℃.

7. The method for preparing an anti-fatigue lead-free black plaster according to claim 1, characterized in that, The fourth temperature is 140℃~160℃; the fifth temperature is 60℃~80℃.

8. The anti-fatigue lead-free black plaster prepared by the preparation method of any one of claims 1 to 7.

Images