A traditional Chinese medicine composition for internal disease treatment by external therapy and transdermal absorption, and a preparation method and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine health care, in particular to a traditional Chinese medicine composition for internal disease treated externally and transdermal absorption, a preparation method and application thereof, the traditional Chinese medicine composition comprises hawthorn kernel extract 40-60 parts, wind-preventing plant 6-10 parts, luffa fruit 6-10 parts, longleaf figwort 6-10 parts, Stachys geophilus 8-12 parts, Albizia julibrissin 6-10 parts and hooves 6-10 parts, the traditional Chinese medicine composition has the effect of internal disease treated externally and transdermal absorption, can be used with conditioning prescription, can promote the effective components of the prescription to penetrate the skin barrier and improve the transdermal efficiency, has the effect of promoting metabolism, the transdermal effect and the effect of promoting metabolism synergistically enhance the auxiliary conditioning effect of external treatment and internal regulation, is used on the skin through bath, leaching, fumigation or foot bath and the like, and is suitable for the auxiliary conditioning of chronic diseases.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine health care technology, and in particular to a traditional Chinese medicine composition for transdermal absorption that treats internal diseases externally, its preparation method and application. Background Technology

[0002] Treating internal diseases externally is an important part of the traditional Chinese medicine treatment system. Its core concept is to administer drugs through the skin, mucous membranes, or other external routes, allowing the active ingredients to be absorbed transdermally and enter the systemic circulation or act on target tissues, thereby achieving the purpose of regulating internal diseases or symptoms. Transdermal absorption has advantages such as avoiding the first-pass effect of the liver, reducing gastrointestinal irritation, and prolonging the duration of action, and is widely used in external dosage forms such as medicated baths, fumigation, and sitz baths.

[0003] However, the primary obstacle to transdermal absorption is the barrier function of the stratum corneum. The stratum corneum, composed of dense keratinocytes and intercellular lipids, significantly restricts the transdermal penetration of exogenous substances, making it difficult for most active ingredients in traditional Chinese medicine to penetrate efficiently. Especially for active ingredients that require systemic or local regulatory effects, overcoming the stratum corneum barrier and achieving adequate transdermal delivery has always been a core challenge in the development of topical traditional Chinese medicine formulations.

[0004] Currently, many topical Chinese medicine preparations still have significant shortcomings in terms of transdermal penetration enhancement. On the one hand, single penetration-enhancing components (such as certain volatile oils or chemical penetration enhancers) have a single mechanism of action, mainly acting on the lipid structure of the stratum corneum, making it difficult to simultaneously improve the solubility of active ingredients, transmembrane penetration, and local retention and transport after penetration. On the other hand, existing formulation designs often lack multi-target synergistic penetration-enhancing mechanisms. In addition, long-term use of some chemical penetration enhancers may pose skin irritation or safety risks, while topical products that rely solely on powdered or simply processed medicinal materials often fail to meet practical requirements in terms of effective ingredient dissolution rate and transdermal efficiency.

[0005] Therefore, there is an urgent need in this field for a traditional Chinese medicine composition that can be effectively absorbed through the skin and has multiple synergistic permeation-enhancing mechanisms. Summary of the Invention

[0006] The purpose of this invention is to provide a transdermal absorption traditional Chinese medicine composition for treating internal diseases externally, its preparation method and application, aiming to solve the problems of low transdermal absorption efficiency and lack of synergistic penetration-promoting mechanism in the prior art.

[0007] To achieve the above objectives, the present invention provides a transdermal traditional Chinese medicine composition for treating internal diseases externally, comprising the following raw materials in parts by weight: Hawthorn kernel extract 40-60 parts, Saposhnikovia divaricata 6-10 parts, Liquidambar formosana 6-10 parts, Cynanchum paniculatum 6-10 parts, Lycopodium clavatum 8-12 parts, Albizia julibrissin bark 6-10 parts, Achyranthes bidentata 6-10 parts; The hawthorn kernel extract was prepared by the following method: (1) After crushing and drying the hawthorn kernels, place them in a dry distillation apparatus and heat them to 280°C at a heating rate of 5-6°C / min. Collect the fraction at 100-280°C to obtain the hawthorn kernel dry distillate. (2) Place the hawthorn kernel dry distillation liquid into a distillation apparatus, heat it to 170°C at a heating rate of 5-6°C / min, keep it at the temperature for 8-12 min, and collect the distillate at the 100-170°C stage, which is recorded as distillate A. (3) Continue heating at a rate of 5-6℃ / min to 280℃, hold for 8-12 min, and collect the distillate from the 170-280℃ stage, which is recorded as distillate B; (4) Mix distillate A and distillate B to obtain hawthorn kernel extract.

[0008] In this invention, the drying method in step (1) is blower drying, the drying temperature is 55-65℃, and the time is 55-65min.

[0009] In this invention, the transdermal absorption traditional Chinese medicine composition for treating internal diseases externally preferably includes the following raw materials in parts by weight: 45-55 parts of hawthorn kernel extract, 7-9 parts of saposhnikovia root, 7-9 parts of luffa fruit, 7-9 parts of cynanchum paniculatum, 9-11 parts of lycopodium clavatum, 7-9 parts of albizia bark, and 7-9 parts of achyranthes bidentata.

[0010] In this invention, the transdermal absorption traditional Chinese medicine composition for treating internal diseases externally is further preferably composed of the following raw materials in parts by weight: 50 parts of hawthorn kernel extract, 8 parts of saposhnikovia root, 8 parts of luffa fruit, 8 parts of cynanchum paniculatum, 10 parts of lycopodium clavatum, 8 parts of albizia bark, and 8 parts of achyranthes bidentata.

[0011] This invention also provides a method for preparing the above-mentioned transdermal absorption traditional Chinese medicine composition for treating internal diseases externally, comprising the following steps: S1. After drying Saposhnikovia divaricata, Liquidambar formosana, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata, pulverize and sieve to obtain mixed medicinal powder; S2. Place the mixed powder in a distillation vessel, add water to soak it, then perform a first distillation, collect the first distillate, and separate the volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel for secondary distillation, and collect the secondary distillate and the residue. S4. Mix the dregs with water, decoct, filter, and concentrate to obtain a concentrated liquid; S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined and then subjected to coarse filtration and fine filtration to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0012] In this invention, the target moisture content of the drying process in S1 is <10%; the mesh size of the sieve is 50-100 mesh, specifically 80 mesh.

[0013] In this invention, the mass ratio of the mixed medicinal powder to water in S2 is 1:6-10, specifically 1:7-8, and the soaking time is 45-50h, specifically 47-48h; the temperature of the first distillation is 95-98℃, specifically 97℃; and the time is 2-3h, specifically 2.5h.

[0014] In this invention, the temperature of the secondary distillation in S3 is 95-98℃, specifically 97℃; and the time is 2-3h, specifically 2.5h.

[0015] In this invention, the mass ratio of the dregs to water in step S4 is 1:6-8, specifically 1:7; the decoction time is 1-2 hours, specifically 1.5 hours.

[0016] In this invention, the coarse filtration in S5 is performed by filtering through 80-100 mesh gauze; the fine filtration is performed by filtering through a 0.45μm microporous membrane.

[0017] The present invention also provides the application of the above-mentioned transdermal absorption traditional Chinese medicine composition for treating internal diseases externally in the preparation of medicated bath products that promote transdermal absorption.

[0018] In this invention, the medicated bath products that promote transdermal absorption include bath liquids, rinse liquids, fumigation liquids, fumigation liquids, or foot bath liquids.

[0019] The present invention also provides a medicinal solution for transdermal absorption, the medicinal solution being prepared by diluting the above-mentioned traditional Chinese medicine composition for transdermal absorption of internal diseases with water.

[0020] The medicinal solution provided by this invention has excellent transdermal penetration-enhancing effects and can be used as a penetration-enhancing matrix in combination with various traditional Chinese medicine formulas with different conditioning effects for the adjunctive treatment of chronic diseases, thus expanding the application field of the medicinal solution of this invention. The formulas include: conditioning formulas for hypertension, hyperlipidemia, hyperuricemia, or diabetes.

[0021] In this invention, the hypertension treatment formula includes: a formula for calming the liver and suppressing yang, a formula for promoting blood circulation and removing blood stasis, a formula for resolving phlegm and removing dampness, or a formula for nourishing the liver and kidneys.

[0022] In this invention, the high blood lipid conditioning formula includes: a formula for clearing the meridians and reducing lipids, a formula for treating obesity caused by phlegm and dampness, a formula for treating arteriosclerosis in middle-aged and elderly people, or a formula for treating high blood lipids due to liver and kidney deficiency.

[0023] In this invention, the high uric acid conditioning formula includes: a heat-clearing, dampness-removing, and turbidity-eliminating conditioning formula; a gout joint blockage conditioning formula; a spleen deficiency and dampness-heavy conditioning formula; or a damp-heat swelling and pain-relieving conditioning formula.

[0024] In this invention, the diabetes treatment formula includes: a blood-activating and meridian-clearing formula, a dryness-heat and yin deficiency formula, a phlegm-dampness obesity formula, or a numbness, soreness and distension relief formula.

[0025] In this invention, the formula for calming the liver and suppressing yang includes: 30 parts of Uncaria rhynchophylla, 20 parts of Prunella vulgaris, 15 parts of Chrysanthemum morifolium, 15 parts of Morus alba leaf, 20 parts of Achyranthes bidentata, and 25 parts of Haliotis diversicolor; the formula for promoting blood circulation and removing blood stasis includes: 20 parts of Salvia miltiorrhiza, 15 parts of Paeonia lactiflora, 12 parts of Ligusticum chuanxiong, 20 parts of Achyranthes bidentata, 20 parts of Leonurus japonicus, and 30 parts of Apocynum venetum leaf; the formula for resolving phlegm and removing dampness includes: 15 parts of Citrus reticulata peel, 20 parts of Poria cocos, 15 parts of Alisma plantago-aquatica, 25 parts of Cassia tora seed, 10 parts of Pinellia ternata, and 20 parts of Crataegus pinnatifida; the formula for nourishing the liver and kidneys includes: 15 parts of Lycium barbarum, 20 parts of Ligustrum lucidum, 25 parts of Taxillus chinensis, 15 parts of Chrysanthemum morifolium, 12 parts of Paeonia suffruticosa, and 20 parts of Paeonia lactiflora.

[0026] In this invention, the formula for regulating blood circulation and reducing fat includes: 30 parts of Salvia miltiorrhiza, 30 parts of hawthorn, 15 parts of Ligusticum chuanxiong, 20 parts of Achyranthes bidentata, 20 parts of lotus leaf, and 10 parts of safflower; the formula for regulating phlegm-dampness obesity and high fat includes: 30 parts of stir-fried hawthorn, 25 parts of Alisma plantago-aquatica, 20 parts of Poria cocos, 15 parts of tangerine peel, 25 parts of Cassia tora, and 12 parts of cinnamon twig; the formula for regulating arteriosclerosis in middle-aged and elderly people includes: 25 parts of Salvia miltiorrhiza, 20 parts of Paeonia lactiflora, 10 parts of Panax notoginseng, 20 parts of Lycopodium clavatum, 20 parts of Leonurus japonicus, and 15 parts of Apocynum venetum leaf; the formula for regulating liver and kidney deficiency and high fat includes: 25 parts of Taxillus chinensis, 15 parts of Polygonum multiflorum, 20 parts of Ligustrum lucidum, 12 parts of Paeonia suffruticosa, 20 parts of hawthorn, and 15 parts of Angelica sinensis.

[0027] In this invention, the heat-clearing, dampness-removing, and turbidity-eliminating formula includes: 30 parts of Smilax glabra, 25 parts of Dioscorea hypoglauca, 30 parts of Plantago asiatica, 20 parts of Lonicera japonica, 20 parts of Clematis chinensis, and 15 parts of Alisma plantago-aquatica; the gout joint congestion-regulating formula includes: 30 parts of Clematis chinensis, 20 parts of Clematis armandii, 20 parts of Lycopodium clavatum, 30 parts of Smilax glabra, 15 parts of Ligusticum chuanxiong, and 25 parts of Spatholobus suberectus; the spleen deficiency and dampness-heavy formula includes: 25 parts of Smilax glabra, 20 parts of Poria cocos, 30 parts of roasted Coix lacryma-jobi, 15 parts of Citrus reticulata peel, 20 parts of Plantago asiatica, and 20 parts of Trachelospermum jasminoides; the damp-heat swelling and pain-relieving formula includes: 30 parts of Lonicera japonica, 15 parts of Phellodendron chinense, 15 parts of Atractylodes lancea, 25 parts of Smilax glabra, 20 parts of Achyranthes bidentata, and 12 parts of Stephania tetrandra.

[0028] In this invention, the blood-activating and meridian-clearing formula includes: 25 parts of Salvia miltiorrhiza, 30 parts of Spatholobus suberectus, 20 parts of Achyranthes bidentata, 12 parts of Cinnamomum cassia, 15 parts of Ligusticum chuanxiong, and 20 parts of Clematis chinensis; the dryness-heat and yin deficiency formula includes: 20 parts of Rehmannia glutinosa, 15 parts of Ophiopogon japonicus, 25 parts of Lonicera japonica, 20 parts of Paeonia lactiflora, 12 parts of Paeonia suffruticosa, and 15 parts of Leonurus japonicus; the phlegm-dampness obesity formula includes: 20 parts of Poria cocos, 18 parts of Alisma plantago-aquatica, 20 parts of Nelumbo nucifera, 25 parts of Crataegus pinnatifida (fried), 20 parts of Trachelospermum jasminoides, and 15 parts of Citrus reticulata; the numbness, soreness, and distension relief formula includes: 20 parts of Clematis chinensis, 20 parts of Lycopodium clavatum, 15 parts of Angelica sinensis, 25 parts of Smilax glabra, 15 parts of Paeonia lactiflora, and 25 parts of Morus alba.

[0029] The above-mentioned treatment formula is only an example. Those skilled in the art can select the corresponding formula according to actual needs and use it in conjunction with the medicinal liquid of the present invention to achieve the health care effect of external treatment and internal regulation.

[0030] The medicinal liquid provided by this invention serves as a penetration-enhancing matrix. When used in combination with the above-mentioned conditioning formula, it can promote the transdermal absorption of the effective ingredients in the combined formula, enabling the active ingredients in the conditioning formula to penetrate the stratum corneum of the skin more efficiently and enter the systemic circulation. This synergistically enhances its conditioning and health-preserving effects, such as promoting blood circulation, removing blood stasis, eliminating dampness and turbidity, nourishing yin and calming the liver, thus achieving the health-preserving effect of external treatment and internal regulation.

[0031] The present invention has the following beneficial effects: This invention provides a transdermal absorption traditional Chinese medicine composition for treating internal diseases externally, comprising the following raw materials in parts by weight: 40-60 parts of hawthorn kernel extract, 6-10 parts of Saposhnikovia divaricata, 6-10 parts of Liquidambar formosana, 6-10 parts of Cynanchum paniculatum, 8-12 parts of Lycopodium clavatum, 6-10 parts of Albizia julibrissin bark, and 6-10 parts of Achyranthes bidentata; wherein the hawthorn kernel extract is prepared by the following method: (1) the hawthorn kernels are crushed, dried, and placed in a dry distillation apparatus, heated to 280°C at a heating rate of 5-6°C / min, and 100-20 parts are collected. (1) Distill at 80℃ to obtain hawthorn kernel dry distillate; (2) Put the hawthorn kernel dry distillate into a distillation apparatus and heat it to 170℃ at a heating rate of 5-6℃ / min, keep it at the temperature for 8-12min, and collect the distillate at the 100-170℃ stage, which is recorded as distillate A; (3) Continue to heat it to 280℃ at a heating rate of 5-6℃ / min, keep it at the temperature for 8-12min, and collect the distillate at the 170-280℃ stage, which is recorded as distillate B; (4) Mix distillate A and distillate B to obtain hawthorn kernel extract.

[0032] This invention uses a dry distillation-rectification method to obtain hawthorn kernel extract, which is enriched with a variety of natural active ingredients such as furfural, guaiacol, and small molecule organic acids.

[0033] Regarding transdermal absorption, furfural and guaiacol in hawthorn kernel extract are both small molecule compounds. Their suitable lipid solubility and physicochemical properties facilitate the dissolution and distribution of the active ingredients in the intercellular lipid channels of the stratum corneum. Phenolic components can interfere with the lipid arrangement of the stratum corneum and regulate its permeability, working synergistically with furfural to enhance the transdermal efficiency of the active ingredients. In terms of anti-inflammation, guaiacol in hawthorn kernel extract exhibits clear anti-inflammatory activity and can inhibit the synthesis of inflammatory mediators.

[0034] The hawthorn kernel extract can not only help improve the transdermal efficiency of the active ingredients in the formula, but also work synergistically with other ingredients in the formula to promote metabolism. The transdermal effect and the metabolism-promoting effect complement each other and synergistically enhance the auxiliary conditioning effect of the traditional Chinese medicine composition in external treatment and internal regulation.

[0035] The formula contains volatile oils from ingredients such as Saposhnikovia divaricata, Cynanchum paniculatum, Liquidambar formosana, and Lycopodium clavatum. These act as natural penetration enhancers, loosening the lipid arrangement between stratum corneum cells and reducing skin barrier resistance, creating favorable conditions for the subsequent penetration of active ingredients. Albizia julibrissin and Achyranthes bidentata saponins possess amphiphilic surface activity, emulsifying and dispersing the active ingredients in the medicinal solution into smaller particles, improving overall solubility and transmembrane permeability. Crataegus pinnatifida extract and Lycopodium clavatum promote local microcirculation, dilate capillaries, and accelerate blood flow, thereby accelerating the absorption and systemic transport of already penetrated ingredients. Achyranthes bidentata acts as a guide, directing the active ingredients of the formula to the site of action, increasing local concentration, and achieving precise targeting. This synergistic effect of multiple components and targets constructs a complete transdermal penetration enhancement chain: "loosening the barrier - improving solubility - promoting microcirculation - guiding targeting."

[0036] Furthermore, the composition of this invention possesses certain antibacterial and bactericidal effects. The fatty acid components in the hawthorn kernel extract can disrupt the lipid bilayer structure of microbial cell membranes and increase membrane permeability; paeonol in *Cynanchum paniculatum* can inhibit microbial cell wall synthesis; and the volatile oils and chromones in *Saposhnikovia divaricata* can interfere with the activity of key microbial enzymes. The synergistic effect of these multiple components inhibits common skin pathogens and fungi, reduces the microbial load on the skin surface, and helps maintain the skin's microecological balance.

[0037] Meanwhile, this traditional Chinese medicine composition itself has the effect of promoting metabolism. In the formula, Fangfeng, Xuchangqing, Lulutong, and Shenjincao dispel wind and dampness, promote qi circulation and unblock the meridians; Hehuanpi invigorates blood and reduces swelling; Huainiuxi invigorates blood and unblocks the meridians, guiding blood downward; and hawthorn kernel extract promotes digestion, eliminates food stagnation, and disperses blood stasis. The whole formula works together to dispel wind, invigorate blood, unblock the meridians and promote downward movement, so as to make the circulation of qi, blood and body fluids in the whole body smooth, thereby improving metabolism.

[0038] This invention also provides a method for preparing a transdermal Chinese medicine composition for treating internal diseases externally, comprising the following steps: S1, drying Saposhnikovia divaricata, Liquidambar formosana, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata, then pulverizing and sieving to obtain a mixed powder; S2, placing the mixed powder in a distillation vessel, adding water to soak it, and then performing a first distillation, collecting the first distillate, and separating the volatile oil and aqueous phase; S3, refluxing the aqueous phase back into the distillation vessel, performing a second distillation, and collecting the second distillate and the residue; S4, mixing the residue with water, decocting, filtering, and concentrating to obtain a concentrated liquid; S5, combining the volatile oil, the second distillate, the concentrated liquid, and hawthorn kernel extract, and then performing coarse and fine filtration to obtain the transdermal Chinese medicine composition for treating internal diseases externally.

[0039] This invention employs a combination of steam distillation and decoction to prepare a transdermal Chinese medicine composition for treating internal diseases externally. Firstly, it achieves the full extraction and efficient enrichment of volatile oil components from the medicinal materials. The formula contains volatile oil components from herbs such as Saposhnikovia divaricata, Cynanchum paniculatum, Liquidambar formosana, and Lycopodium clavatum, which are the core active substances responsible for promoting transdermal penetration. Through steam distillation, the volatile oils are evaporated with the steam and collected in the distillate, avoiding the loss of volatile components caused by direct powdering of the herbs. Furthermore, the entire process uses water as a medium, without introducing organic solvents, resulting in a safe and residue-free product. Compared to the potential solvent residue and skin irritation risks associated with organic solvent extraction methods, the product obtained using water as a medium contains no organic solvent residue. This makes it safer for use in scenarios requiring large-area and prolonged skin contact, such as medicated baths and fumigation, effectively reducing the potential risks of skin irritation and allergies, and suitable for long-term, repeated use. Simultaneously, the double distillation process further achieves the full recovery of trace amounts of volatile oils. After the aqueous phase is separated by the first distillation, the aqueous phase is refluxed to the distillation vessel for a second distillation. This process can fully distill off the trace amounts of volatile oil remaining in the medicinal material and dissolved in the aqueous phase, allowing the volatile oil components to be fully utilized and significantly increasing the concentration of effective components in the distillate.

[0040] In addition, water decoction extraction of the distilled residue can fully dissolve the active ingredients such as triterpenoid saponins, ecdysterone, and polysaccharides in herbs such as Albizia julibrissin bark and Achyranthes bidentata that are not distilled with water vapor. These active ingredients complement the aforementioned volatile oil components, achieving comprehensive retention of both volatile and water-soluble components. This avoids the loss of active ingredients caused by a single extraction process and improves the overall utilization rate of the herbs.

[0041] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0042] Figure 1 This is a comparison chart of the yolk sac area of ​​zebrafish in the 0.1% traditional Chinese medicine drainage solution group and the normal group according to the present invention; in, Figure 1In the diagram, A represents the yolk sac area of ​​zebrafish in the 0.1% traditional Chinese medicine drainage solution group and the normal group. Figure 1 B in the figure is a bar chart of the yolk sac area of ​​zebrafish in the 0.1% traditional Chinese medicine drainage solution group and the normal group; Figure 2 This is a statistical chart showing the sleep onset time and sleep duration before and after product use in the clinical trials of this invention; Figure 3 This is a comparison chart of the number of times the product was used before and after clinical trials of this invention, showing the frequency of drowsiness and frequent awakenings. Figure 4 This is a statistical chart showing the satisfaction with the product's effectiveness in clinical trials of this invention. Detailed Implementation

[0043] The present invention will be further described below with reference to the accompanying drawings and embodiments. Unless otherwise defined, the technical or scientific terms used in this invention should be understood in their ordinary sense by those skilled in the art. The features mentioned above or in the specific examples mentioned in this invention can be combined arbitrarily, and these specific embodiments are only used to illustrate the invention and are not intended to limit the scope of the invention.

[0044] The hawthorn kernel extract used in the following examples was prepared by the following method: (1) Crush the hawthorn kernels, dry them at 60℃ for 60 min using a blower, and then place them in a dry distillation apparatus and dry distill them at a rate of 6℃ / min. Collect the fractions at 100-280℃ to obtain hawthorn kernel dry distillate. (2) Place the hawthorn kernel dry distillate into a distillation apparatus, heat it to 170°C at a heating rate of 6°C / min, and keep it at that temperature for 10 min. Collect the distillate from the 100-170°C stage and record it as distillate A. (3) Then continue to heat up to 280℃ at a heating rate of 6℃ / min, hold for 10min, and collect the distillate from the 170-280℃ stage, which is recorded as distillate B; (4) Mix distillate A and distillate B to obtain hawthorn kernel extract.

[0045] Example 1 This embodiment provides a traditional Chinese medicine composition with transdermal penetration enhancement effect, which is composed of the following raw materials in parts by weight: 40 parts of hawthorn kernel extract, 6 parts of saposhnikovia root, 6 parts of luffa fruit, 6 parts of cynanchum paniculatum, 8 parts of lycopodium clavatum, 6 parts of albizia bark, and 6 parts of achyranthes bidentata.

[0046] The preparation process of the above-mentioned traditional Chinese medicine combination with transdermal penetration enhancement effect is as follows: S1. Dry the following herbs (Saposhnikovia divaricata, Luffa cylindrica, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata) to a moisture content of <10%, then pulverize them through a 50-mesh sieve to obtain a mixed powder. S2. Place the mixed powder in a distillation vessel, add 228 parts of water and soak for 45 hours. Then, perform a first distillation at 95°C. After 2 hours, condense and collect the first distillate. Let it stand to separate and obtain the volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel and carry out a second distillation at 95°C. After 2 hours, condense and collect the second distillate and the residue. S4. Mix the dregs of the medicine with water at a mass ratio of 1:6, decoct for 1 hour, filter, concentrate, and obtain a concentrated solution with a relative density of 1.05. S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined, coarsely filtered through 80-mesh gauze and then finely filtered through a 0.45μm microporous membrane to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0047] Example 2 This embodiment provides a traditional Chinese medicine composition with transdermal penetration enhancement effect, which is composed of the following raw materials in parts by weight: Hawthorn kernel extract 60 parts, Saposhnikovia divaricata 10 parts, Liquidambar formosana 10 parts, Cynanchum paniculatum 10 parts, Lycopodium clavatum 12 parts, Albizia julibrissin bark 10 parts, Achyranthes bidentata 10 parts.

[0048] The preparation process of the above-mentioned traditional Chinese medicine combination with transdermal penetration enhancement effect is as follows: S1. After drying Saposhnikovia divaricata, Liquidambar formosana, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata to a moisture content of <10%, pulverize them and pass them through a 100-mesh sieve to obtain a mixed powder. S2. Place the mixed powder in a distillation vessel, add 620 parts of water and soak for 50 hours, then distill once at 98°C. After 3 hours, condense and collect the first distillate, and let it stand to separate to obtain volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel and carry out a second distillation at 98°C. After 3 hours, condense and collect the second distillate and the residue. S4. Mix the dregs of the medicine with water at a mass ratio of 1:8, decoct for 2 hours, filter, concentrate, and obtain a concentrated solution with a relative density of 1.10. S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined, coarsely filtered through 100-mesh gauze and then finely filtered through a 0.45μm microporous membrane to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0049] Example 3 This embodiment provides a traditional Chinese medicine composition with transdermal penetration enhancement effect, which is composed of the following raw materials in parts by weight: 45 parts of hawthorn kernel extract, 7 parts of Saposhnikovia divaricata, 7 parts of Liquidambar formosana, 7 parts of Cynanchum paniculatum, 9 parts of Lycopodium clavatum, 7 parts of Albizia julibrissin bark, and 7 parts of Achyranthes bidentata.

[0050] The preparation process of the above-mentioned traditional Chinese medicine combination with transdermal penetration enhancement effect is as follows: S1. Dry the following herbs to a moisture content of <10% and then pulverize them through an 80-mesh sieve to obtain a mixed powder. S2. Place the mixed powder in a distillation vessel, add 352 parts of water and soak for 48 hours, then distill once at 97°C. After 2.5 hours, condense and collect the first distillate, and let it stand to separate to obtain volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel and carry out a second distillation at 97°C. After 2.5 hours, condense and collect the second distillate and the residue. S4. Mix the dregs of the medicine with water at a mass ratio of 1:7, decoct for 1.5 hours, filter, concentrate, and obtain a concentrated solution with a relative density of 1.05. S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined, coarsely filtered through 100-mesh gauze and then finely filtered through a 0.45μm microporous membrane to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0051] Example 4 This embodiment provides a traditional Chinese medicine combination with transdermal penetration enhancement effect, which consists of the following raw materials in parts by weight: 55 parts of hawthorn kernel extract, 9 parts of Saposhnikovia divaricata, 9 parts of Liquidambar formosana, 9 parts of Cynanchum paniculatum, 11 parts of Lycopodium clavatum, 9 parts of Albizia julibrissin bark, and 9 parts of Achyranthes bidentata.

[0052] The preparation process of the above-mentioned traditional Chinese medicine combination with transdermal penetration enhancement effect is as follows: S1. Dry the following herbs to a moisture content of <10% and then pulverize them through an 80-mesh sieve to obtain a mixed powder. S2. Place the mixed powder in a distillation vessel, add 392 parts of water and soak for 47 hours. Then, perform a first distillation at 97°C. After 2.5 hours, condense and collect the first distillate. Let it stand to separate and obtain volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel and carry out a second distillation at 97°C. After 2.5 hours, condense and collect the second distillate and the residue. S4. Mix the dregs of the medicine with water at a mass ratio of 1:7, decoct for 2 hours, filter, concentrate, and obtain a concentrated solution with a relative density of 1.05. S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined, coarsely filtered through 100-mesh gauze and then finely filtered through a 0.45μm microporous membrane to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0053] Example 5 This embodiment provides a traditional Chinese medicine combination with transdermal penetration enhancement effect, which consists of the following raw materials in parts by weight: 50 parts hawthorn kernel extract, 8 parts saposhnikovia root, 8 parts luffa fruit, 8 parts cynanchum paniculatum, 10 parts lycopodium clavatum, 8 parts albizia bark, and 8 parts achyranthes bidentata.

[0054] The preparation process of the above-mentioned traditional Chinese medicine combination with transdermal penetration enhancement effect is as follows: S1. After drying Saposhnikovia divaricata, Liquidambar formosana, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata to a moisture content of <10%, pulverize them and pass them through a 100-mesh sieve to obtain a mixed powder. S2. Place the mixed powder in a distillation vessel, add 400 parts of water and soak for 50 hours, then distill once at 97°C. After 3 hours, condense and collect the first distillate, and let it stand to separate to obtain volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel and carry out a second distillation at 97°C. After 2 hours, condense and collect the second distillate and the residue. S4. Mix the dregs of the medicine with water at a mass ratio of 1:7, decoct for 1 hour, filter, concentrate, and obtain a concentrated solution with a relative density of 1.02. S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined, coarsely filtered through 100-mesh gauze and then finely filtered through a 0.45μm microporous membrane to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

[0055] Animal experiments: Preparation of isolated mouse skin: Healthy male mice (22±5g) were acclimatized for 3 days. The fur on their backs was first clipped with scissors, then the remaining hair was carefully shaved off with an electric shaver, taking care to avoid damaging the skin surface. After euthanasia by cervical dislocation, the skin on the back was immediately peeled off, and subcutaneous fat and adhesions were carefully scraped away with a single-edged razor blade. The skin was then repeatedly rinsed with distilled water and physiological saline. A portion of the skin was taken and its thickness was measured using calipers (0.28±0.03 mm) for later use.

[0056] Preparation of the medicinal solution: Take 8 mL of the traditional Chinese medicine composition prepared in Example 1 and mix it with 30 mL of water. Stir the mixture to obtain a medicinal solution.

[0057] Franz diffusion cell transdermal assay: A vertical Franz diffusion cell was used (effective transdermal area 0.78 cm²). 2The receiving chamber had a volume of 6.5 mL. The prepared ex vivo skin was fixed between the supply and receiving chambers, with the stratum corneum (epidermis) facing the supply chamber and the dermis facing the receiving chamber. The receiving solution was a 20% (v / v) ethanol-physiological saline solution. An appropriate amount of the above solution was added to the skin surface in the supply chamber, and the mixture was stirred at 500 rpm using an electromagnetic stirrer. The receiving solution was collected after 1 hour. The solution and receiving solution were filtered through a 0.45 µm microporous membrane, and the total flavonoid content was determined by HPLC. Three groups were tested, and the average results were taken. The results are shown in Table 1.

[0058] Result calculation: Percentage of osmotic absorption = (c×V) / W×100%, where c is the mass concentration of the drug in the receiving solution, V is the volume of the receiving solution, and W is the dosage.

[0059] Table 1 Results of animal experiments

[0060] As shown in Table 1, the average transdermal absorption rate of the traditional Chinese medicine composition provided by the present invention reaches 89.17%, indicating that the active ingredients in the traditional Chinese medicine composition can efficiently penetrate the isolated mouse skin barrier and enter the receiving fluid, confirming that the traditional Chinese medicine composition provided by the present invention has a high transdermal absorption rate and a significant permeation-promoting effect.

[0061] Water quality - acute embryo toxicity of zebrafish (Danio rerio): Metabolism is a core process for maintaining energy balance and physiological function in the body, and its abnormalities are closely related to various metabolic diseases (such as obesity and diabetes). The yolk sac in the early developmental stage of zebrafish is a key organ for nutrient storage and energy metabolism; its size changes directly reflect the embryo's energy utilization efficiency and metabolic state. Rapid absorption of the yolk sac is significantly correlated with metabolic activities such as lipid breakdown and energy conversion. By detecting the absorption of yolk sacs in zebrafish, the metabolic-promoting effects of test substances can be evaluated.

[0062] Zebrafish strain: Wild-type AB strain zebrafish; Zebrafish age: 2 days post-fertilization (2 dpf); Culture conditions: Adult zebrafish were raised in a culture system with 10 hours of darkness, 14 hours of light, a water temperature of 28±0.5℃, and a pH of 7.0–7.5. They were fed twice a day with brine shrimp and once a day with compound feed. Embryos were raised in a 28±0.5℃ biochemical incubator (10 hours of darkness: 14 hours of light), with fresh E3 culture water changed every 24 hours.

[0063] Sample processing: Take 8 mL of the traditional Chinese medicine composition prepared in Example 1 into a beaker, add 2 L of boiling water and soak for 10 min to prepare the test solution.

[0064] Maximum tolerated concentration (MTC) determination: Two healthy, wild-type AB zebrafish embryos (dpf) were randomly selected and placed in 12-well cell culture plates (10 embryos per well). Traditional Chinese medicine (TCM) excretion solutions with volume concentrations of 0.05%, 0.1%, 0.2%, 0.4%, 0.8%, and 1.6% were prepared using E3 culture medium. The control group received E3 culture water, while the other groups received the corresponding concentrations of TCM excretion solutions. The plates were incubated at 28.5℃ for 3 days. The mean criterion (MTC) was determined based on the zebrafish malformation rate and mortality rate.

[0065] (1) Maximum Tolerable Concentration (MTC): After zebrafish were treated with 0.05%, 0.1%, 0.2%, 0.4%, 0.8%, and 1.6% of the herbal decoction of this invention, the mortality rates of each group were 0%, 0%, 0%, 0%, 0%, and 10%, respectively, and the deformity rates were 0%, 0%, 10%, 10%, 20%, and 20%, respectively. Therefore, the MTC of zebrafish treated with the herbal decoction of this invention is 0.1%.

[0066] Evaluation of its effect on promoting metabolism: (1) Experimental groups: Normal group and 0.1% volume concentration of traditional Chinese medicine excretion solution group.

[0067] (2) Intervention with the test substance: Two healthy wild-type zebrafish with a dpf (dextrose fraction) were randomly selected and placed in 6-well cell culture plates. The normal group was given E3 culture water, and the group given 0.1% traditional Chinese medicine excretion solution was given 0.1% traditional Chinese medicine excretion solution. The plates were incubated at 28.5℃ for several days for intervention.

[0068] (3) Detection of yolk sac area in zebrafish: After the intervention, the zebrafish were washed twice with E3 culture water. The zebrafish in each group were then observed and photographed under a stereomicroscope. The area of ​​the zebrafish yolk sac was analyzed using ImageJ software.

[0069] All data are expressed as mean ± sem. Data analysis was performed using GraphPad Prism software, and t-tests were used for analysis. Compared with the normal group, ** P <0.01 ( P The smaller the value, the more significant the difference.

[0070] The results of the zebrafish yolk sac area measurement are shown below. Figure 1 And Table 2.

[0071] Table 2 Results of zebrafish yolk sac area measurement

[0072] Depend on Figure 1As shown in Table 2, compared with the normal group, the yolk sac area of ​​zebrafish in the 0.1% traditional Chinese medicine drainage solution group was significantly reduced ( P <0.01), and the significant reduction in its area indicates accelerated yolk sac absorption, lipid decomposition, and energy conversion, confirming that the herbal composition of the present invention has a significant effect on promoting metabolism.

[0073] Application example: The traditional Chinese medicine composition obtained in Example 1 of this invention was prepared into a medicinal bath product—foot bath liquid. Subsequently, a targeted questionnaire survey was conducted among patients with sleep disorders. Through comparative data from a sample of 20 people, the product's effect on improving related symptoms was objectively evaluated.

[0074] Twenty participants aged 18-60 years with sleep disorders were selected, including 10 men and 10 women. All participants underwent rigorous screening before the experiment, and no one withdrew during the experiment. All participants had varying degrees of sleep quality problems before enrollment, such as difficulty falling asleep, insufficient sleep duration, daytime fatigue, or frequent awakenings.

[0075] Subjects completed a baseline sleep questionnaire upon enrollment and then used the foot bath solution for a foot bath every night before bed.

[0076] The method of use is as follows: Mix 8 mL of the traditional Chinese medicine composition prepared in Example 1 with 30 mL of water to obtain a medicinal solution. Place the medicinal solution in a foot bath basin, add an appropriate amount of water, ensuring the water level covers the ankles. Adjust the foot bath solution temperature to 39°C, then immerse both feet in the solution and soak for 10 minutes. Subsequently, increase the water temperature to 42°C and soak for 20 minutes. Use the treatment continuously for 3 weeks, and complete the questionnaire again after the trial period. Data are expressed as mean ± sem, and t-test analysis was performed using GraphPad Prism software (compared to before use: ** indicates...). P <0.01, *** indicates P <0.001).

[0077] Table 3 Mood Improvement Score

[0078] Note: 1 point = no improvement, 2 points = slight improvement, 3 points = significant improvement, 4 points = complete improvement.

[0079] As shown in Table 3, after three weeks of continuous use, the subjects experienced "complete improvement" in anxiety, irritability, and fatigue, and "significant improvement" in tension and morning mental state. This indicates that the active ingredients in the composition of this invention, after being absorbed through the skin, can act on the central nervous system via the meridians of the feet, exerting the effects of calming the mind, stabilizing the spirit, soothing the liver, and relieving depression, effectively improving the emotional problems associated with sleep disorders.

[0080] Table 4. Statistics on sleep latency and sleep duration before and after product use

[0081] From Table 4 and Figure 2 It can be seen that after three weeks of continuous use, the duration of sleep onset decreased from 1.4±0.9 h / day before the trial to 0.4±0.3 h / day, and the difference was highly significant (**). P <0.01). The significant reduction in sleep onset time indicates that the active ingredients in the herbal composition of this invention, after transdermal absorption, can effectively regulate the function of the central nervous system and shorten the transition time from wakefulness to sleep.

[0082] Table 5. Statistics on the frequency of drowsiness and frequent awakenings before and after product use.

[0083] From Table 5 and Figure 3 It can be seen that after 3 weeks of continuous use, the number of daytime naps decreased from 9±3 times / day before the trial to 4±1 times / day, and the difference was highly significant (***). P <0.001). The significant reduction in the number of daytime naps indicates that the improved nighttime sleep quality effectively restored the subjects' daytime alertness and cognitive function, indirectly confirming that the foot bath liquid of this invention has real physiological significance in improving core sleep indicators.

[0084] Table 6. User Satisfaction

[0085] From Table 6 and Figure 4 As can be seen, in the satisfaction evaluation, 17 people (85.0%) were very satisfied, and 3 people (15.0%) were satisfied, with an overall satisfaction rate of 100%. This result further confirms the efficacy of the foot bath liquid of this invention in improving sleep disorders from the perspective of subjective experience, indicating that the actual user experience of the product is highly consistent with the improvement of objective sleep indicators, demonstrating outstanding product competitiveness and broad market application prospects.

[0086] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A traditional Chinese medicine composition for transdermal absorption in the treatment of internal diseases, characterized in that, The raw materials include the following parts by weight: Hawthorn kernel extract 40-60 parts, Saposhnikovia divaricata 6-10 parts, Liquidambar formosana 6-10 parts, Cynanchum paniculatum 6-10 parts, Lycopodium clavatum 8-12 parts, Albizia julibrissin bark 6-10 parts, Achyranthes bidentata 6-10 parts; The hawthorn kernel extract was prepared by the following method: (1) After crushing and drying the hawthorn kernels, place them in a dry distillation apparatus and heat them to 280°C at a heating rate of 5-6°C / min. Collect the fraction at 100-280°C to obtain the hawthorn kernel dry distillate. (2) Place the hawthorn kernel dry distillation liquid into a distillation apparatus, heat it to 170°C at a heating rate of 5-6°C / min, keep it at the temperature for 8-12 min, and collect the distillate at the 100-170°C stage, which is recorded as distillate A. (3) Continue heating at a rate of 5-6℃ / min to 280℃, hold for 8-12 min, and collect the distillate from the 170-280℃ stage, which is recorded as distillate B; (4) Mix distillate A and distillate B to obtain hawthorn kernel extract.

2. The transdermal absorption traditional Chinese medicine composition for treating internal diseases externally according to claim 1, characterized in that, The raw materials include the following parts by weight: Hawthorn kernel extract 45-55 parts, Saposhnikovia divaricata 7-9 parts, Liquidambar formosana 7-9 parts, Cynanchum paniculatum 7-9 parts, Lycopodium clavatum 9-11 parts, Albizia julibrissin bark 7-9 parts, Achyranthes bidentata 7-9 parts.

3. A method for preparing a transdermal traditional Chinese medicine composition for treating internal diseases externally, as described in any one of claims 1-2, characterized in that, Includes the following steps: S1. After drying Saposhnikovia divaricata, Liquidambar formosana, Cynanchum paniculatum, Lycopodium clavatum, Albizia julibrissin bark, and Achyranthes bidentata, pulverize and sieve to obtain mixed medicinal powder; S2. Place the mixed powder in a distillation vessel, add water to soak it, then perform a first distillation, collect the first distillate, and separate the volatile oil and aqueous phase. S3. Reflux the aqueous phase into the distillation vessel for secondary distillation, and collect the secondary distillate and the residue. S4. Mix the dregs with water, decoct, filter, and concentrate to obtain a concentrated liquid; S5. The volatile oil, secondary distillate, concentrate and hawthorn kernel extract are combined and then subjected to coarse filtration and fine filtration to obtain a transdermal Chinese medicine composition for treating internal diseases externally.

4. The preparation method according to claim 3, characterized in that, The target moisture content of the drying process described in S1 is <10%; the mesh size of the sieve is 50-100 mesh.

5. The preparation method according to claim 3, characterized in that, The mass ratio of the mixed medicinal powder to water in S2 is 1:6-10, and the soaking time is 45-50 hours. The temperature for the first distillation described in S2 is 95-98℃, and the time is 2-3 hours.

6. The preparation method according to claim 3, characterized in that, The secondary distillation described in S3 is carried out at a temperature of 95-98℃ for 2-3 hours.

7. The preparation method according to claim 3, characterized in that, The mass ratio of the dregs to water in S4 is 1:6-8; the decoction time is 1-2 hours.

8. The preparation method according to claim 3, characterized in that, The coarse filtration described in S5 is filtration through 80-100 mesh gauze; The fine filtration is performed using a 0.45μm microporous membrane.

9. The use of the traditional Chinese medicine composition for treating internal diseases externally according to any one of claims 1-2, which is absorbed through the skin, in the preparation of a medicated bath product that promotes transdermal absorption.

10. The application according to claim 9, characterized in that, The medicated bath products that promote transdermal absorption include bath liquids, shower liquids, fumigation liquids, fumigation liquids, or foot bath liquids.

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