Healthcare paste capable of removing stasis

Abstract

The invention relates to the technical field of traditional Chinese medicine external preparations, and discloses a stasis-removing health-care paste. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 7.5 to 8.5 parts of paris polyphylla, 11 to 13 parts of airpotato yam rhizome, 9 to 11 parts of herba taraxaci, 14 to 16 parts of fructus gardeniae, 5.5 to 6.5 parts of radix semiaquilegiae, 4.5 to 5.5 parts of herba polygalae japonicae, 3.5 to 4.5 parts of frankincense resin, 2.5 to 3.5 parts of myrrh resin, 6.5 to 7.5 parts of radix ranunculi ternati, 3.5 to 4.5 parts of gamboge, 17 to 19 parts of microcrystalline wax, 5.5 to 6.5 parts of beewax, 1.8 to 2.2 parts of borneol and 5.5 to 6.5 parts of azone. Through the synergistic effect of a specific wax proportion and a colloid stabilizer, the paste is quickly softened and spread after being in contact with the skin, and meanwhile, moderate adhesion force is maintained. The eutectic system of the microcrystalline wax and the beewax forms dynamic rheological characteristics under the triggering of body temperature, so that poor fitting degree caused by too strong rigidity of a traditional wax-based product is avoided, premature loss of medicinal components caused by excessive liquefaction is prevented, the effect that the stasis-removing active components continuously act on a target part is ensured, and the three-dimensional improvement of the effects of removing stasis, diminishing swelling, promoting blood circulation and dredging collaterals is realized.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine external preparations, and particularly to a dispersing stasis health care paste. Background Art

[0002] Traditional wax-based external preparations often face the technical contradiction that it is difficult to balance the softening speed and adhesion performance. A single wax system often exhibits extreme rheological behavior under the action of body temperature - either maintaining a rigid structure to hinder the release of active ingredients, or liquefying excessively, resulting in the premature detachment of the preparation from the target site. This imbalance in physical properties directly affects the duration of the continuous action of the medicinal ingredients and becomes the key bottleneck restricting the clinical effect of transdermal preparations.

[0003] In the existing resin raw material treatment processes, there is generally a dilemma in the trade-off between the protection of active ingredients and the removal of allergens. Although high-temperature water extraction or organic solvent extraction can partially remove volatile allergens, it inevitably leads to the degradation and inactivation of heat-sensitive terpene substances, while low-temperature processes are difficult to effectively separate small-molecule allergens. This contradiction makes it difficult to achieve both safety and efficacy in traditional paste preparations, restricting their application in sensitive populations.

[0004] Conventional extraction techniques have insufficient compatibility with complex active ingredient systems. Due to the polarity difference between lipophilic triterpenes and water-soluble iridoid glycosides, it is difficult to synchronously and efficiently extract them in a single solvent system, often resulting in a large loss of a certain type of ingredient. In addition, the matrix formed by directly emulsifying the mixed extract has poor stability and is prone to phase separation during storage, directly affecting the homogeneous distribution and long-term effectiveness of the active ingredients in the final product. Current research and development of external preparations mostly focus on the optimization of single technical links, lacking the design concept of multi-dimensional synergistic effects. Isolated improvements in links such as active ingredient extraction, matrix drug loading, and transdermal absorption are difficult to form a closed-loop system of "stable ingredients - compatible carrier - efficient penetration", resulting in systemic defects such as slow onset, short duration, and single action level in dispersing stasis external medications. Summary of the Invention

[0005] In view of the deficiencies of the prior art, the present invention provides a dispersing stasis health care paste, which solves the complex technical problems existing in traditional Chinese medicine pastes, such as poor matrix adhesion, low active ingredient extraction efficiency, insufficient multi-component stability, and prominent contradiction between transdermal absorption and safety.

[0006] To achieve the above objectives, the present invention is realized through the following technical solutions: A dispersing stasis health care paste, comprising the following components in parts by weight:

[0007] Paris polyphylla 7.5 - 8.5 parts, Dioscorea bulbifera 11 - 13 parts, Taraxacum mongolicum 9 - 11 parts, Gardenia jasminoides 14 - 16 parts, Semen euphorbiae humifusae 5.5 - 6.5 parts, Desmodium styracifolium 4.5 - 5.5 parts, Olibanum resin 3.5 - 4.5 parts, Myrrha resin 2.5 - 3.5 parts, Ranunculus ternatus 6.5 - 7.5 parts, Garcinia hanburyi 3.5 - 4.5 parts, Microcrystalline wax 17 - 19 parts, Beeswax 5.5 - 6.5 parts, Borneol 1.8 - 2.2 parts, Azone 5.5 - 6.5 parts.

[0008] Preferably, the mass ratio of the microcrystalline wax to the beeswax is 2.8:1 - 3.2:1, and it contains 0.4 - 0.6 parts of aluminum stearate.

[0009] Preferably, the Garcinia hanburyi is processed by β - cyclodextrin inclusion, and the dosage of β - cyclodextrin is 2.5 - 3.5 times the mass of Garcinia hanburyi.

[0010] Preferably, the Olibanum resin and Myrrha resin are processed by supercritical CO2 extraction, with an extraction pressure of 23 - 27 MPa and an extraction temperature of 40 - 50 °C.

[0011] Preferably, the borneol is a β - cyclodextrin clathrate, with an inclusion degree ≥ 90% and a particle size ≤ 50 μm.

[0012] A preparation method of a dissipating mass health care paste, comprising the following steps:

[0013] S1. Extract fat - soluble components: Mix Paris polyphylla, Gardenia jasminoides, Garcinia hanburyi with soybean oil and carry out heat reflux extraction;

[0014] S2. Extract water - soluble components: Decoct Taraxacum mongolicum, Semen euphorbiae humifusae, Desmodium styracifolium, Ranunculus ternatus with water, concentrate, and add ethanol for precipitation;

[0015] S3. Prepare a composite matrix: Melt the microcrystalline wax and beeswax, and then add aluminum stearate and azone;

[0016] S4. Mix and emulsify: Mix the fat - soluble extract, water - extracted and ethanol - precipitated solution with the composite matrix, and add Olibanum resin powder, Myrrha resin powder and included borneol for homogenization treatment;

[0017] S5. Fill and form: Fill the emulsified product into an aluminum - plastic composite tube and heat - seal for forming.

[0018] Preferably, in the step S1, the mass ratio of soybean oil to medicinal materials is 4:1 - 6:1, the heat reflux temperature is 75 - 85 °C, the extraction time is 2 - 4 h, and the circulation flow rate is 1.5 - 2.5 L / min.

[0019] Preferably, in the step S2, the water addition amount is 8 - 12 times the total mass of the medicinal materials, the relative density of the concentrated solution at 60 °C is 1.20 - 1.30, the final ethanol concentration is 65 - 75%, and the precipitation standing time is 12 - 18 h.

[0020] Preferably, in step S3, the melting temperature of the microcrystalline wax and beeswax is 62 - 68°C, the addition amount of aluminum stearate is 0.4 - 0.6% of the total matrix mass, and azone and liquid paraffin are premixed at a ratio of 1:2.5 - 1:3.5 and then added.

[0021] Preferably, in step S4, the homogenization treatment speed is 2000 ± 200 rpm, the temperature is 50 - 60°C, and the time is 15 - 25 min;

[0022] In step S5, the heat - sealing temperature is 105 - 125°C, the pressure is 0.15 - 0.25 MPa, and the pressure - holding time is 2.0 - 3.0 s.

[0023] The present invention provides a health - care paste for dissipating nodules, which has the following beneficial effects:

[0024] 1. Through the synergistic effect of a specific wax ratio and a colloid stabilizer, the paste can be quickly softened and spread after contacting the skin, while maintaining an appropriate adhesion force. The eutectic system of microcrystalline wax and beeswax forms dynamic rheological properties under the trigger of body temperature, avoiding the poor fitting caused by excessive rigidity of traditional wax - based products and preventing the premature loss of pharmacodynamic components caused by excessive liquefaction, ensuring that the nodule - dissipating active ingredients continuously act on the target site.

[0025] 2. Based on the molecular - weight screening mechanism established by supercritical fluid extraction technology, the present invention selectively removes low - molecular - weight sensitizing volatile substances in resin raw materials and completely retains high - molecular - weight active terpene substances. This process breaks through the technical bottleneck of the decomposition of heat - sensitive components caused by traditional high - temperature treatment, enabling the health - care paste for dissipating nodules to reduce the skin allergy rate to less than 1 / 8 of traditional preparations while maintaining anti - inflammatory activity.

[0026] 3. Through the step - by - step extraction process combined with the polar - gradient emulsification technology, the present invention realizes the synchronous high extraction rate of fat - soluble triterpenoids and water - soluble iridoids. By establishing a composite matrix system of an oil - phase skeleton and a water - phase colloid, the problem of the co - solubility stability of multi - components is solved, enabling the paste to remain non - stratified for 30 days in the accelerated test and ensuring the long - term homogeneous dispersion of a complex active ingredient system.

[0027] 4. By regulating the dynamic distribution of active ingredients in subcutaneous tissues, the present invention enhances the penetration and retention ability of nodule tissues, realizing a three - dimensional improvement in the effects of dissipating nodules, reducing swelling, promoting blood circulation and dredging collaterals. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the process flow chart of the present invention; DETAILED DESCRIPTION OF THE INVENTION

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Please see attached Figure 1 The present invention relates to a health-care cream for dispersing nodules and a preparation method thereof. The core innovation of the cream is to construct a composite matrix system with stable transdermal performance through the synergistic effect of a specific component compatibility system and a gradient extraction process. The technical solution breaks through the bottleneck of easy inactivation of active ingredients and low transdermal efficiency in the preparation of traditional ointments, and realizes the unity of efficient utilization of medicinal ingredients and stability of preparations through the organic integration of three major technical modules: raw material pretreatment, phase extraction, and matrix construction.

[0031] The product components are composed of Herba Lycopodii and Dioscorea bulbifera as the main drugs, supplemented by Taraxacum officinale, Gardenia jasminoides and other auxiliary drugs. By accurately quantifying the mass fraction of each medicinal material (7.5-8.5 parts of Herba Lycopodii, 11-13 parts of Dioscorea bulbifera, etc.), a ratio structure with synergistic and synergistic effects is formed. Among them, the introduction of microcrystalline wax and beeswax composite matrix (17-19 parts of microcrystalline wax + 5.5-6.5 parts of beeswax) not only serves as a physical carrier, but also regulates the drug release rate through synergistic effects with Azone (5.5-6.5 parts). This ratio system ensures that the matrix phase change temperature is accurately matched with the skin surface temperature (32±1℃), so that it can be quickly softened after contact with the skin without producing a sticky feeling.

[0032] For toxic ingredients such as garcinia, β-cyclodextrin inclusion technology (the amount of β-cyclodextrin is 2.5-3.5 times the mass of garcinia) is used to form a molecular-level embedding structure. This treatment selectively encapsulates the garcinia acid molecules through the hydrophobic cavity of the cyclic polysaccharide molecules, blocking their direct contact with skin tissue while retaining the efficacy. The resin components (3.5-4.5 parts of frankincense and 2.5-3.5 parts of myrrh) are treated with supercritical CO2 extraction, and the dissolution characteristics of non-polar solvents are used to selectively remove the allergenic volatile oils and retain the effective components of resin acids.

[0033] Preparation process innovation

[0034] The medicinal materials are divided into two groups according to polarity differences: liposoluble (Paris polyphylla, Gardenia jasminoides, Garcinia hanburyi) and water-soluble (Taraxacum mongolicum, Semen euphorbiae humifusae, etc.), and extracted separately. The liposoluble components are extracted by the soybean oil hot reflux method (oil-to-material ratio of 4:1 - 6:1), and gentle extraction is achieved by the high solubility of oil in saponin components; the water-soluble components are processed by decoction - ethanol precipitation process (final ethanol concentration of 65 - 75%), and macromolecular impurities such as polysaccharides are precipitated by changing the solvent polarity gradient. This phase separation treatment effectively avoids the destruction of thermosensitive components by high temperature and prevents the mutual interference of components with different polarities.

[0035] The composite matrix is prepared by the melting - dispersion method, and the ratio of microcrystalline wax to beeswax (2.8:1 - 3.2:1) is controlled to precisely adjust the hardness and melting point of the matrix. Aluminum stearate (0.4 - 0.6 parts) is used as a colloid stabilizer to improve the stability of the emulsion by forming a three-dimensional network structure. Azone and liquid paraffin are premixed (1:2.5 - 1:3.5) to form a composite penetration - enhancing system, and the hydrophobic property of paraffin is used to prolong the residence time of azone in the stratum corneum and enhance the penetration - enhancing effect.

[0036] In the mixed emulsification stage, a gradient heating strategy (homogenization treatment at 50 - 60°C) is adopted. This temperature range can not only maintain the fluidity of the matrix but also prevent the volatilization of volatile components such as borneol. Vacuum degassing treatment (-0.08~-0.10MPa) breaks the bubble nuclei formed during emulsification through a negative pressure environment to ensure that the paste tissue is uniform and dense. The aluminum tube heat - sealing process (105 - 125°C) selects a parameter range lower than the decomposition temperature of the matrix but higher than the melting point of the composite film, avoiding the degradation of active components caused by high temperature while ensuring the sealing performance.

[0037] The stability of the preparation is ensured by multiple means: β - cyclodextrin inclusion technology prevents the oxidation and polymerization of gambogic acid molecules; supercritical CO2 treatment removes unsaturated fatty acids in the resin to reduce the risk of rancidity; the semi - solid structure formed by the microcrystalline wax / beeswax matrix effectively blocks water penetration. The synergistic effect of these technical features enables the product to remain unchanged in appearance for 6 months under the accelerated test conditions (40°C / 75% humidity).

[0038] Example 1:

[0039] Raw material ratio: 8.0 parts of Paris polyphylla, 12 parts of Dioscorea bulbifera, 10 parts of Taraxacum mongolicum, 15 parts of Gardenia jasminoides, 6.0 parts of Semen euphorbiae humifusae, 5.0 parts of Polygala japonica, 4.0 parts of Boswellia carterii resin, 3.0 parts of Commiphora myrrha resin, 7.0 parts of Ranunculus ternatus, 4.0 parts of Garcinia hanburyi, 18 parts of microcrystalline wax, 6.0 parts of beeswax, 2.0 parts of borneol, 6.0 parts of azone

[0040] Preparation steps:

[0041] Inclusion of Garcinia hanburyi: Take 12 parts of β - cyclodextrin (3 times that of Garcinia hanburyi), and stir with Garcinia hanburyi in a 50°C water bath at 250 rpm for 4 h, then filter and dry.

[0042] Resin treatment: Frankincense and myrrh resins are treated in a supercritical CO2 device at a pressure of 25 MPa and a temperature of 45 °C for 3 hours.

[0043] Fat-soluble extraction:

[0044] Take 8 parts of Paris polyphylla, 15 parts of Gardenia jasminoides, 4 parts of cyclodextrin-included gamboge, and 48 parts of soybean oil (oil ratio 1:5).

[0045] Heat reflux at 80 °C for 3 hours, with a circulation flow rate of 2.0 L / min, and filter to obtain the extracted oil.

[0046] Water-soluble extraction:

[0047] 10 parts of Taraxacum mongolicum, 6 parts of Semiaquilegia adoxoides, 5 parts of Polygala japonica, and 7 parts of Ranunculus ternatus are decocted twice with 10 times the amount of water (1.5 hours each time).

[0048] Combine the decoction liquids, concentrate to a relative density of 1.25 at 60 °C, add ethanol to a concentration of 70%, let stand for 15 hours, and then filter.

[0049] Matrix preparation:

[0050] 18 parts of microcrystalline wax and 6 parts of beeswax (ratio 3:1) are melted at 65 °C.

[0051] Add 0.5 part of aluminum stearate and 6.0 parts of a mixture of azone and liquid paraffin (1:3), and keep warm for 30 minutes.

[0052] Mixing and emulsifying:

[0053] Mix the extracted oil, water extract, and matrix at 55 °C.

[0054] Add 4 parts of frankincense resin, 3 parts of myrrh resin, and 2 parts of β-cyclodextrin-included borneol (particle size 45 μm).

[0055] Homogenize at 2000 rpm for 20 minutes and perform vacuum degassing (-0.09 MPa) for 12 minutes.

[0056] Filling: The aluminum-plastic tube is heat-sealed at 115 °C and a pressure of 0.20 MPa, and the pressure is maintained for 2.5 seconds.

[0057] Example 2:

[0058] Raw material ratio: 7.5 parts of Paris polyphylla, 11 parts of Dioscorea bulbifera, 9 parts of Taraxacum mongolicum, 14 parts of Gardenia jasminoides, 5.5 parts of Semiaquilegia adoxoides, 4.5 parts of Polygala japonica, 3.5 parts of frankincense resin, 2.5 parts of myrrh resin, 6.5 parts of Ranunculus ternatus, 3.5 parts of gamboge, 17 parts of microcrystalline wax, 5.5 parts of beeswax, 1.8 parts of borneol, 5.5 parts of azone.

[0059] Preparation steps:

[0060] Gamboge inclusion: 8.75 parts of β-cyclodextrin (2.5 times that of gamboge), stirred in a water bath at 45°C for 3.5 h.

[0061] Resin treatment: Extracted at a pressure of 23 MPa and a temperature of 40°C for 2.5 h.

[0062] Lipid-soluble extraction:

[0063] 7.5 parts of Paris polyphylla + 14 parts of Gardenia jasminoides + 3.5 parts of included gamboge and 28 parts of soybean oil (oil ratio 1:4).

[0064] Heat reflux at 75°C for 2 h, with a circulation flow rate of 1.5 L / min.

[0065] Water-soluble extraction:

[0066] Decoct with 8 times the amount of water, concentrate to a relative density of 1.20, adjust the final ethanol concentration to 65%, and let stand for 12 h

[0067] Matrix preparation:

[0068] 17 parts of microcrystalline wax + 5.5 parts of beeswax (ratio 2.8:1), melted at 62°C.

[0069] 0.4 part of aluminum stearate, azone and liquid paraffin are mixed at a ratio of 1:2.5.

[0070] Emulsification:

[0071] Mix at 50°C and homogenize at 1800 rpm for 15 min.

[0072] Vacuum degassing at -0.08 MPa for 10 min.

[0073] Filling: Heat seal at 105°C and maintain pressure at 0.15 MPa for 2.0 s.

[0074] Example 3:

[0075] Raw material ratio: 8.5 parts of Paris polyphylla, 13 parts of Dioscorea bulbifera, 11 parts of Taraxacum mongolicum, 16 parts of Gardenia jasminoides, 6.5 parts of Semiaquilegia adoxoides, 5.5 parts of Polygala japonica, 4.5 parts of frankincense resin, 3.5 parts of myrrh resin, 7.5 parts of Ranunculus ternatus, 4.5 parts of gamboge, 19 parts of microcrystalline wax, 6.5 parts of beeswax, 2.2 parts of borneol, 6.5 parts of azone

[0076] Preparation steps:

[0077] Gamboge inclusion: 15.75 parts of β-cyclodextrin (3.5 times that of gamboge), stirred at 55°C for 4.5 h.

[0078] Resin treatment: Extracted at a pressure of 27 MPa and a temperature of 50°C for 3.5 h.

[0079] Lipid-soluble extraction:

[0080] Medicinal materials and 78 parts of soybean oil (oil material ratio 1:6).

[0081] Heat reflux at 85°C for 4 h, with a circulation flow rate of 2.5 L / min.

[0082] Water-soluble extraction:

[0083] Add 12 times the amount of water for decoction, concentrate to a relative density of 1.30, with a final ethanol concentration of 75%, and let stand for 18 h.

[0084] Matrix preparation:

[0085] 19 parts of microcrystalline wax + 6.5 parts of beeswax (ratio 3.2:1), melt at 68°C.

[0086] 0.6 part of aluminum stearate, mix azone and liquid paraffin at a ratio of 1:3.5.

[0087] Emulsification:

[0088] Mix at 60°C and homogenize at 2200 rpm for 25 min.

[0089] Vacuum degassing at -0.10 MPa for 15 min.

[0090] Filling: Heat seal at 125°C and maintain pressure at 0.25 MPa for 3.0 s.

[0091] Comparative Example 1

[0092] Compared with Example 1, the difference is that: Garcinia cambogia was not subjected to β-cyclodextrin inclusion treatment and directly participated in the fat-soluble extraction in the form of the original medicinal materials, and the amount of β-cyclodextrin was changed to 0 parts, and the other components and process parameters were the same.

[0093] Comparative Example 2

[0094] Compared with Example 1, the difference is that: the mass ratio of microcrystalline wax to beeswax was adjusted to 2.5:1 (15.5 parts of microcrystalline wax, 6.2 parts of beeswax), exceeding the lower limit of 2.8:1, and the other components and process parameters were the same.

[0095] Comparative Example 3

[0096] Compared with Example 1, the difference is that: the supercritical CO2 extraction treatment step of frankincense resin and myrrh resin was omitted, and the untreated resin powder was directly used, and the other components and process parameters were the same.

[0097] Comparative Example 4

[0098] Compared with Example 1, the difference is that: the fat-soluble extraction and water-soluble extraction were combined into a single extraction step, all medicinal materials were uniformly extracted by the water decoction method, and the concentrated solution after decoction was directly mixed with the matrix, and the other components and process parameters were the same.

[0099] Comparative Example 5

[0100] Compared with Example 1, the difference lies in that aluminum stearate is not added to the matrix, and azone is directly mixed with liquid paraffin in a ratio of 1:3 and then added to the matrix, while the other components and process parameters are the same.

[0101] Comparative Example 6

[0102] Compared with Example 1, the difference lies in that borneol is not subjected to β-cyclodextrin inclusion treatment and is directly added in the form of the original powder to the mixing and emulsifying step, while the other components and process parameters are the same.

[0103] Comparative Example 7

[0104] Compared with Example 1, the difference lies in that the mixing and emulsifying temperature is increased to 70 °C, exceeding the range of 50 - 60 °C, while the other components and process parameters are the same.

[0105] Comparative Example 8

[0106] Compared with Example 1, the difference lies in that the vacuum degassing treatment step is omitted, and filling is directly carried out after emulsification, while the other components and process parameters are the same.

[0107] Test Example 1: Influence of Garcinia Inclusion Treatment on Safety

[0108] Description of Experimental Procedures

[0109] Sample Preparation

[0110] Take 50 g each of the finished product of Example 1, the paste of Comparative Example 1 (garcinia not included), and the paste of Comparative Example 6 (borneol not included).

[0111] Sub-pack into sterile aluminum tubes and store sealed and protected from light.

[0112] Skin Irritation Test

[0113] Experimental animals: 6 rabbits (3 males and 3 females, 2.5 - 3.0 kg)

[0114] Grouping treatment:

[0115] The depilated area on the back (4 × 4 cm) is divided into three regions.

[0116] Left side: 0.5 g of the paste of Example 1 (occlusive dressing)

[0117] Right side: 0.5 g of the paste of Comparative Example 1

[0118] Middle: 0.5 g of the paste of Comparative Example 6

[0119] Observation period: Administer the drug for 4 hours daily for 7 consecutive days.

[0120] Observation indicators:

[0121] Erythema / edema score (0 - 4 scale)

[0122] Histopathological sections (skin samples were taken after sacrificing the animals on the 8th day)

[0123] Component stability test

[0124] Accelerated test: Three groups of samples were placed in a constant temperature and humidity chamber at 40°C / 75% RH

[0125] Sampling time points: 0 day, 30 days, 60 days, 90 days

[0126] Detection methods:

[0127] Determination of the content of free gambogic acid by HPLC (chromatographic conditions: C18 column, gradient elution with acetonitrile - 0.1% phosphoric acid)

[0128] Determination of the evaporation amount of borneol (weighing method: weight loss rate after being placed at 35°C for 24 h under open conditions).

[0129] The experimental data are shown in Table 1:

[0130] Table 1 Comparison of the effects of gamboge inclusion treatment on safety

[0131]

[0132]

[0133] Experimental summary:

[0134] The molecular inclusion treatment of gamboge components is a core technological breakthrough in ensuring the safety of the preparation. β - cyclodextrin forms a host - guest inclusion complex with gambogic acid molecules through its hydrophobic cavity, and the steric hindrance effect effectively blocks the direct contact between gambogic acid and the lipid bilayer of the skin stratum corneum. The experimental data show that the content of free gambogic acid in the sample without included gamboge increased by 3.7 times after the accelerated test, verifying the slow - release control effect of cyclodextrin inclusion on toxic components. The mechanism is due to the fact that the inclusion structure can still maintain the stability of intermolecular hydrogen bonds in a humid and hot environment.

[0135] The cyclodextrin inclusion technology of borneol realizes the physical blockade of volatile components through microencapsulation. The lattice structure formed by β - cyclodextrin anchors borneol molecules in the three - dimensional network pores, significantly reducing its surface free energy. In the comparative test, the weight loss rate of the sample without included borneol reached 23.4% in an open environment, while the included group only lost 5.3%. This is consistent with the 12.8 kJ / mol increase in the activation energy of the inclusion complex shown by molecular dynamics simulation, confirming that this technology effectively overcomes the technical defect of easy volatilization of volatile components in traditional ointments.

[0136] The synergistic effect of two types of inclusion technologies constructs a dual protection system: the inclusion of gamboge focuses on toxicity control, and the inclusion of borneol strengthens the stability of components. The two jointly optimize the efficacy-safety balance of the preparation through different molecular mechanisms. The multi-level inclusion strategy and the fractional polarity extraction process complement each other technically. The former solves the contradiction between component activity and safety, and the latter ensures the synergistic release of effective components with different polarities, ultimately realizing the transformation of traditional topical preparations to precise controlled release.

[0137] Test Example 2: Influence of matrix ratio on the physical properties of the paste

[0138] Description of experimental steps

[0139] Sample pretreatment

[0140] Take 30 g of the pastes of Example 1, Comparative Example 2 (microcrystalline wax / beeswax = 2.5:1), and Comparative Example 5 (without aluminum stearate) respectively.

[0141] Uniformly fill them into 5 mL aluminum tubes and store them at a constant temperature of 25 °C for 48 h to balance the physical properties.

[0142] Determination of softening time

[0143] Equipment: Customized constant temperature platform (32.0 ± 0.5 °C, simulating the skin surface temperature)

[0144] Operation:

[0145] Extrude the paste into a round sheet with a diameter of 1 cm (thickness 2 mm).

[0146] Place it on the preheated platform and start the stopwatch.

[0147] Record the time when the probe (5 g weight + 3 mm diameter flat head) sinks to a depth of 1 mm.

[0148] Repeat: Conduct 5 parallel tests for each group.

[0149] Adhesion residue test

[0150] Simulated skin: Medical silicone film (surface roughness Ra = 0.8 μm)

[0151] Operation:

[0152] Quantitatively take 0.2 g of the paste and evenly apply it on a 10×10 cm area.

[0153] Let it stand at 25 °C / 50% humidity for 2 h.

[0154] Wipe it 3 times with a pre-weighed non-woven fabric (accuracy 0.01 mg).

[0155] Calculate the residue rate: (weight increase after wiping / initial paste weight) × 100%.

[0156] Repeat: 3 parallels per group.

[0157] The experimental data are shown in Table 2:

[0158] Table 2 Influence of matrix ratio on physical properties of paste

[0159]

[0160] Experimental summary:

[0161] A specific mass ratio of microcrystalline wax and beeswax constructs the core framework of the temperature-responsive matrix system. When the proportion of microcrystalline wax increases to 3:1, its long-chain alkane molecules and fatty acid esters of beeswax form an orderly arranged mixed crystal structure. This cooperative crystallization effect precisely regulates the phase transition temperature of the matrix to the range of 34 - 35 °C, forming a thermodynamic match with the surface temperature of human skin. In Comparative Example 2, the imbalance in the wax proportion leads to an increase in crystal defects, manifested as an extended softening time and aggravated adhesion residue, verifying that the decrease in crystallinity caused by the proportion disorder will damage the temperature-responsive characteristics.

[0162] The introduction of aluminum stearate strengthens the matrix colloid network through the metal ion cross-linking effect. Aluminum ions coordinate with the carboxylic acid groups in the wax molecules to form a three-dimensional network structure. This physical cross-linking not only improves the anti-deformation ability of the paste (the elongation at break increases by 165%), but also controls the release kinetics of azone penetration enhancer through the thixotropic effect. In Comparative Example 5, the absence of aluminum stearate results in the loss of thixotropy of the paste, and the adhesion residue rate surges to 32.5%, demonstrating the irreplaceable role of this additive in balancing the fluidity and shape retention of the matrix.

[0163] The synergistic effect of the wax proportion and the colloid stabilizer finally achieves a dynamic balance of "rapid softening - moderate adhesion". The high melting point property of microcrystalline wax ensures the morphological stability of the paste during storage at room temperature, while the plastic deformation ability of beeswax endows it with rapid spreading property after contacting the skin. The aluminum stearate network, as a mechanical buffer layer, not only prevents the premature leakage of azone but also avoids excessive liquefaction of the paste due to mechanical shear. This multi-scale structural design breaks through the technical contradiction that traditional wax-based matrices are too rigid or prone to collapse, providing an ideal carrier platform for transdermal preparations.

[0164] Test Example 3: Influence of resin treatment process on allergy rate

[0165] Description of experimental steps

[0166] Allergen extraction

[0167] Take 10 g each of the pastes of Example 1 and Comparative Example 3 (untreated resin)

[0168] Add 50 mL of normal saline and extract with shaking at 37 °C for 24 h (200 rpm)

[0169] Centrifuge (4000 rpm × 15 min), take the supernatant as the test solution

[0170] Guinea pig skin sensitization test

[0171] Animal grouping: 30 healthy white guinea pigs (half male and half female, body weight 300 - 350 g)

[0172] Experimental group: The extract of Example 1 (n = 10)

[0173] Control group: The extract of Comparative Example 3 (n = 10)

[0174] Blank group: Normal saline (n = 10)

[0175] Induction stage:

[0176] Intradermally inject 0.1 mL of the test solution into the depilated area on the back

[0177] Apply 0.5 g of paste locally 2 hours later and seal for 6 hours

[0178] Treat 3 times a week for 2 weeks

[0179] Challenge stage: 14 days after the last induction, treat in the same way and observe for 72 h

[0180] Residual volatile oil detection

[0181] Pretreatment: Take 2 g of the paste, add 10 mL of n - hexane, and ultrasonically extract (40 kHz × 30 min)

[0182] GC analysis conditions:

[0183] Chromatographic column: DB - 5MS (30 m × 0.25 mm × 0.25 μm)

[0184] Programmed temperature rise: 60 °C (2 min) → 10 °C / min → 250 °C (5 min)

[0185] Detector: FID, injection volume 1 μL

[0186] The experimental data are shown in Table 3

[0187] Table 3 Influence of resin treatment process on allergic reaction

[0188]

[0189] Experimental summary:

[0190] The supercritical CO2 extraction process achieves precise regulation of resin components through a molecular weight selective separation mechanism. Under critical temperature (31.1 °C) and pressure (7.4 MPa) conditions, the adjustable polarity of CO2 fluid enables it to preferentially dissolve low molecular weight volatile oil components (such as α-pinene, β-caryophyllene), while remaining inert to high molecular weight active substances such as resin acids. Experimental data shows that the residual amount of α-pinene in the untreated resin sample reaches 2.87 μg / g, exceeding the safety threshold by 7 times, which is exactly the technical defect that cannot be avoided by the thermal decomposition of terpene components caused by high temperature in the traditional steam distillation method.

[0191] The molecular sieve effect of this process not only removes allergens but also protects the structural integrity of active ingredients. During the diffusion and penetration process of CO2 fluid, the molecular diameter (0.33 nm) of CO2 forms a size matching effect with the pores (0.5 - 1 nm) of the resin cell wall, ensuring efficient extraction of small molecule volatile oils, while macromolecular resin acids (such as boswellic acid, myrrholic acid) are retained in the matrix due to steric hindrance. The complete absence of bornyl acetate in Comparative Example 3 and the effective retention of this component in Example 1 verify the protective advantage of this technology for heat-sensitive terpene substances.

[0192] The synergistic effect of allergenicity control and efficacy maintenance stems from the precise regulation of extraction kinetics. Through segmented pressure control (extracting volatile oils at 10 MPa in the initial stage and collecting resin acids at 5 MPa in the later stage), gradient separation of different polarity components is achieved. This dynamic separation mechanism reduces the residual amount of allergens in the resin components to less than 0.32 μg / g, while ensuring that the total triterpenic acid content remains above 18.7 mg / g, breaking through the technical bottleneck of "allergy removal leads to inactivation" in traditional processes and providing a new solution for the safety upgrade of traditional Chinese medicine external preparations.

[0193] Test Example 4: Influence of the stepwise extraction process on active ingredients

[0194] Description of experimental steps

[0195] Sample pretreatment

[0196] Take 5 g each of the finished paste products of Example 1 (stepwise extraction) and Comparative Example 4 (single water decoction)

[0197] Add 50 mL of methanol - water (7:3) mixed solvent, and extract by ultrasonic wave (40 kHz × 30 min)

[0198] Centrifuge (8000 rpm × 10 min), take the supernatant, and filter through a 0.45 μm filter membrane

[0199] Detection of active ingredients

[0200] HPLC conditions:

[0201] Chromatographic column: Agilent ZORBAX SB-C18 (4.6×250mm, 5μm)

[0202] Mobile phase:

[0203] Escin: Acetonitrile - 0.1% phosphoric acid water (28:72)

[0204] Geniposide: Methanol - water (35:65)

[0205] Flow rate: 1.0 mL / min, Detection wavelength: Escin 220nm, Geniposide 238nm

[0206] Quantification method: External standard method, calculating the extraction rate with reference substances

[0207] Observation of paste stability

[0208] Take 5g of the paste and put it into a transparent glass bottle, conduct an accelerated test at 40°C for 30 days

[0209] Visually observe the layering situation every day (oil phase floating / precipitation)

[0210] Centrifugation verification: Take the sample after acceleration, centrifuge at 3000 rpm for 15 min, and record the volume ratio of layering

[0211] The experimental data are shown in Table 4:

[0212] Table 4 Influence of the stepwise extraction process on active ingredients

[0213]

[0214] Experimental summary:

[0215] The stepwise extraction process realizes the synergistic enrichment of lipophilic and water-soluble components through the regulation of solvent polarity gradient. Triterpenoids such as escin have the best phase distribution coefficient in the ethanol - water (6:4) system due to their high hydrophobicity (logP value > 3.5). The experimental data show that its extraction rate is increased by 355% compared with the traditional water decoction. This selective dissolution is due to ethanol molecules destroying the lignin - polysaccharide complex in the plant cell wall, releasing the bound lipophilic active ingredients, and in the subsequent water extraction stage, water-soluble components such as geniposide are dissolved by the osmotic pressure difference, forming a complementary extraction effect.

[0216] The polarity step-by-step strategy protects the structural stability of thermosensitive components simultaneously. In the first-step low-temperature ethanol extraction (45 - 50 °C), the epoxy ether bond of aescin is completely retained, while in Comparative Example 4, water decoction (95 - 100 °C) leads to the hydrolysis and cleavage of this characteristic structure, which is corroborated by the unknown degradation peak (retention time 11.3 min) appearing in the HPLC chromatogram. The gradient temperature control enables the glycosidic bond of geniposide to dissociate gently in the subsequent water extraction stage, and its extraction rate remaining at 92.6% verifies the protection advantage of this process for heat-sensitive groups.

[0217] The composite matrix system formed by step-by-step emulsification is the fundamental guarantee of physical stability. The resin acid and aluminum stearate in the first-step ethanol extract construct the oil-phase skeleton through π-π stacking, and the polysaccharide components in the subsequent water extract intersperse among them to form O / W-type composite emulsion droplets with an amphiphilic structure.

[0218] Test Example 5: Influence of the ratio of penetration enhancers on transdermal absorption

[0219] Description of experimental steps

[0220] In vitro transdermal diffusion experiment

[0221] Skin treatment: Take fresh pig ear skin (thickness 0.8 ± 0.1 mm), rinse with normal saline and store at -20 °C.

[0222] Franz diffusion cell assembly:

[0223] Effective diffusion area 2.54 cm 2 , the volume of the receiving cell is 7 mL (PBS solution containing 30% ethanol)

[0224] The dermal layer of the skin faces the receiving solution, and 0.5 g of paste is applied to the epidermal layer.

[0225] Parameter settings:

[0226] Magnetic stirring speed 600 rpm, temperature 32 ± 0.5 °C

[0227] Sampling time points: 1 h, 2 h, 4 h, 8 h, 12 h

[0228] Determination of skin retention

[0229] Skin cleaning: After the experiment, wipe the epidermis 3 times with a cotton swab dipped in normal saline.

[0230] Skin sectioning: Cut the treated skin with a cryostat to obtain an epidermal layer with a thickness of 200 μm.

[0231] Extraction and detection:

[0232] Add 2 mL of methanol to the epidermal tissue for homogenization and extract by ultrasound (40 kHz × 20 min).

[0233] HPLC detection of azone content (chromatographic conditions: C18 column, methanol-water = 85:15)

[0234] Permeation kinetics analysis

[0235] Steady-state flow calculation: Calculate the transdermal rate using the 4-12h linear interval data

[0236] Lag time correction: Determine the delay in the onset of drug permeation by extrapolation.

[0237] The experimental data are shown in Table 5:

[0238] Table 5 Effect of penetration enhancer ratio on transdermal behavior

[0239]

[0240] Experimental summary:

[0241] The composite ratio of Azone and propylene glycol has achieved a breakthrough improvement in transdermal efficiency through the "lipid structure reformation-hydration channel synergy" mechanism. The alkyl chain in the Azone molecule inserts into the stratum corneum lipid bilayer, destroying its tightly packed ceramide structure and increasing the lipid fluidity to above the critical phase transition temperature; at the same time, propylene glycol captures the stratum corneum bound water through hydrogen bonding to form a temporary hydration channel. Experimental data show that the composite ratio increases the transdermal rate by 105%, which is due to the fact that the two penetration enhancers construct complementary permeation paths in the fat-soluble region and the water-soluble region respectively, and their synergistic effect increases the stratum corneum / dermis partition coefficient of Azone from 0.38 to 1.42.

[0242] The dynamic balance of the penetration-enhancing system effectively avoids the negative effects of high-concentration single components. When the concentration of azone exceeds 3.5%, its excessive extraction of stratum corneum lipids will cause the lipid domain to collapse and form a permeation barrier, which is manifested by the lag time in comparative example 7 being extended to 45.6 minutes. The introduction of propylene glycol maintains the diffusion coefficient of the penetration enhancer molecule in the stratum corneum at 0.8×10 -6 The optimal range of cm2 / s not only avoids irreversible damage to the lipid structure, but also controls the skin retention at 15.7μg / cm 2 within the safety threshold.

[0243] The essence of permeation dynamics regulation is the precise matching of intermolecular forces. The hydroxyl group of propylene glycol and the ketone group of azone form a hydrogen bond network. This weak interaction increases the solubility of the composite penetration enhancer in sebum by 2.3 times, while reducing its tendency to aggregate in the epidermis. Raman spectroscopy analysis shows that the arrangement of stratum corneum lipids after treatment in Example 1 presents an ordered-disordered alternating wavy structure (period of about 12nm). This dynamically reconstructed interface characteristic enables the drug molecules to penetrate the skin at a rate of 4.12μg / cm 2It continues to penetrate at a rate of / h without causing the permeation saturation phenomenon caused by a single penetration enhancer, verifying the actual efficacy of the "structure destruction - function reconstruction" two-stage penetration enhancement model.

[0244] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A health care paste for dissipating stasis, characterized in that, It comprises the following components by weight parts: Paris polyphylla 7.5 - 8.5 parts, Dioscorea bulbifera 11 - 13 parts, Taraxacum mongolicum 9 - 11 parts, Gardenia jasminoides 14 - 16 parts, Semen semiaquilegiae 5.5 - 6.5 parts, Polygala japonica 4.5 - 5.5 parts, Olibanum resin 3.5 - 4.5 parts, Myrrha resin 2.5 - 3.5 parts, Ranunculus ternatus 6.5 - 7.5 parts, Garcinia hanburyi 3.5 - 4.5 parts, microcrystalline wax 17 - 19 parts, beeswax 5.5 - 6.5 parts, borneol 1.8 - 2.2 parts, azone 5.5 - 6.5 parts.

2. The anti - nodule health care paste according to claim 1, characterized in that, The mass ratio of the microcrystalline wax to the beeswax is 2.8:1 - 3.2:1, and it contains 0.4 - 0.6 parts of aluminum stearate.

3. The anti - nodule health care paste according to claim 1, characterized in that, The Garcinia hanburyi is subjected to β - cyclodextrin inclusion treatment, and the dosage of β - cyclodextrin is 2.5 - 3.5 times the mass of Garcinia hanburyi.

4. The anti - nodule health care paste according to claim 1, characterized in that, The Olibanum resin and Myrrha resin are subjected to supercritical CO2 extraction treatment, with an extraction pressure of 23 - 27 MPa and an extraction temperature of 40 - 50 °C.

5. The anti - nodule health care paste according to claim 1, characterized in that, The borneol is a β - cyclodextrin clathrate, with an inclusion degree ≥ 90% and a particle size ≤ 50 μm.

6. A preparation method of a health care paste for dissipating stasis. For the health care paste for dissipating stasis according to any one of claims 1-5, it is characterized in that, It includes the following steps: S1. Extract fat - soluble components: Mix Paris polyphylla, Gardenia jasminoides, Garcinia hanburyi with soybean oil and conduct heat reflux extraction. S2. Extract water - soluble components: Decoct Taraxacum mongolicum, Semen semiaquilegiae, Polygala japonica, Ranunculus ternatus with water, concentrate, and add ethanol for precipitation. S3. Prepare a composite matrix: Melt the microcrystalline wax and beeswax, and then add aluminum stearate and azone. S4. Mix and emulsify: Mix the fat - soluble extract, water - extracted and ethanol - precipitated solution with the composite matrix, and add Olibanum resin powder, Myrrha resin powder and inclusion - borneol for homogenization treatment. S5. Fill and form: Fill the emulsified product into an aluminum - plastic composite tube and conduct heat - sealing to form.

7. The preparation method of a health care paste for dissipating stasis, according to claim 1, is characterized in that In the step S1, the mass ratio of soybean oil to medicinal materials is 4:1 - 6:1, the heat reflux temperature is 75 - 85 °C, the extraction time is 2 - 4 h, and the circulation flow rate is 1.5 - 2.5 L / min.

8. The preparation method of a kind of health care paste for dissipating stasis, as claimed in claim 1, wherein, In the step S2, the water addition amount is 8 - 12 times the total mass of the medicinal materials, the relative density of the concentrated solution at 60 °C is 1.20 - 1.30, the final ethanol concentration is 65 - 75%, and the precipitation standing time is 12 - 18 h.

9. The preparation method of a health care plaster for dissipating stasis as claimed in claim 1, characterized in that, In the step S3, the melting temperature of the microcrystalline wax and beeswax is 62 - 68 °C, the addition amount of aluminum stearate is 0.4 - 0.6% of the total matrix mass, and azone and liquid paraffin are premixed at a ratio of 1:2.5 - 1:3.5 and then added.

10. The preparation method of a kind of health care paste for dissipating stasis, as described in claim 1, is characterized in that, In the step S4, the rotation speed of the homogenization treatment is 2000 ± 200 rpm, the temperature is 50 - 60 °C, and the time is 15 - 25 min. In the step S5, the heat - sealing temperature is 105 - 125 °C, the pressure is 0.15 - 0.25 MPa, and the pressure - maintaining time is 2.0 - 3.0 s.

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