Traditional Chinese medicine massage cream for dredging channels and collaterals and preparation process thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to traditional Chinese medicine meridian dredging massage cream and a preparation method thereof, myrrh (a monarch drug), kudzuvine root (a ministerial drug) and notopterygium root (an adjuvant drug) are used as core components, menthol, vanillyl butyl ether and other transdermal permeation enhancing systems are used as auxiliary materials, and an oil-in-water type microemulsion matrix is constructed. Through six innovations of'monarch-minister-assistant 'meridian targeted compatibility, three-dimensional transdermal permeation promotion and multi-component synergistic anti-inflammation, the effects of relaxing tendons, activating collaterals, dispelling wind and dissipating blood stasis are achieved. The preparation process adopts ultrasonic extraction and high-pressure homogenization technologies, and the integrity of active ingredients is reserved. The product is suitable for scenes such as cervical spondylosis, scapulohumeral periarthritis and rheumatic ostealgia and has the advantages of high transdermal efficiency, long-acting analgesia, good safety and the like, experimental verification shows that the transdermal amount within 24 hours is increased by 130%, the inflammatory factor inhibition rate reaches 89.2%, and the clinical effective rate is remarkably superior to that of commercially available products.

Description

Technical Field

[0001] This product belongs to the field of external preparation technology of traditional Chinese medicine, specifically involving a traditional Chinese medicine meridian massage ointment with myrrh, kudzu root, and notopterygium root as core ingredients and its preparation method. Background Technology

[0002] Traditional massage creams mostly use an oil-based base, making it difficult for active ingredients (such as terpenes and alkaloids) to penetrate the skin's stratum corneum. In vitro transdermal experiments show that the cumulative penetration of commercially available products over 24 hours is only (35.2±4.8) μg / cm³. 2 This results in an effective time exceeding 45 minutes. Most products contain only a single analgesic ingredient (such as capsaicin), lacking systematic intervention on the pathological chain of "qi stagnation-blood stasis-dampness obstruction," with analgesia lasting less than 6 hours and an improvement rate of less than 50% for chronic inflammation (such as arthritis). Traditional ointment bases (such as petrolatum) are greasy, have a low skin retention rate (<30%), and are prone to oxidation and rancidity (shelf life <12 months), requiring the addition of large amounts of chemical preservatives (such as methylisothiazolinone), increasing the risk of irritation. Existing products are not formulated in accordance with the theory of meridians in traditional Chinese medicine, and cannot accurately act on the diseased meridians (such as the Hand Taiyang Small Intestine Meridian and the Foot Taiyang Bladder Meridian), resulting in insufficient drug concentration at acupoints and a clinical efficacy rate of only 65%-70%. The active ingredients of single extracts (such as bisabolic acid and puerarin) have dispersed targets and lack synergistic design; in vitro experiments show that the inhibition rate of a single ingredient on the inflammatory factor TNF-α is only 30%-40%. Summary of the Invention

[0003] Based on this, the present invention provides a traditional Chinese medicine meridian-clearing massage cream, suitable for meridian blockage diseases such as cervical spondylosis, frozen shoulder, and rheumatic bone pain, with multiple effects of relaxing muscles and tendons, dispelling wind and removing blood stasis. It is composed of the following ingredients in the indicated mass ratios: myrrh extract 8-12 parts, kudzu root extract 5-8 parts, notopterygium root extract 3-5 parts, menthol 2-3 parts, vanillyl butyl ether 1-2 parts, glycerin 10-15 parts, mineral oil 8-12 parts, caprylic / capric triglyceride 5-8 parts, behenol 3-5 parts, clove oil 0.5-1 part, phenoxyethanol 0.5-1 part, disodium EDTA 0.1-0.2 parts, and tocopherol 0.5-1 part.

[0004] Furthermore, the myrrh extract contains ≥5 mg / g of bisabolol, the kudzu root extract contains ≥8 mg / g of puerarin, and the notopterygium root extract contains ≥3 mg / g of notopterygol.

[0005] Furthermore, the preparation method includes:

[0006] (1) Extracts were prepared from myrrh, kudzu root and notopterygium root using alcohol extraction, water extraction and oil extraction processes, respectively.

[0007] (2) The oil phase and the water phase were heated to 70°C and then homogenized at 10,000 rpm to form a microemulsion matrix;

[0008] (3) Add extracts and functional excipients, adjust pH to 6.5-7.5 and then fill.

[0009] Furthermore, the massage cream is suitable for conditions such as cervical spondylosis, frozen shoulder, rheumatic bone pain, and sprains and bruises, and features targeted meridians, high-efficiency transdermal absorption, and long-lasting analgesia.

[0010] Furthermore, the transdermal permeation enhancement system consists of physical permeation enhancement from menthol, chemical permeation enhancement from vanillyl butyl ether, and structural permeation enhancement from the microemulsion matrix, which synergistically improve transdermal efficiency.

[0011] Beneficial technical effects:

[0012] Highly efficient transdermal penetration and rapid onset of action: Through a three-dimensional system that enhances penetration through menthol (physical penetration), vanillyl butyl ether (chemical penetration), and microemulsion matrix structure, the active ingredient achieves a cumulative penetration rate of 158.6 μg / cm³ within 24 hours. 2 It is 130% more effective than commercially available products, with an average onset time shortened to 18.5 minutes and analgesia lasting for more than 8 hours.

[0013] Synergistic anti-inflammatory and analgesic effects through multiple pathways: Myrrhic acid inhibits the COX-2 inflammatory pathway, puerarin downregulates TLR4 / MyD88 signaling, and notopterygium alcohol activates the TRPV1 warming channel. Combined with the cold analgesia of menthol, it forms a multi-level inhibition of "central-peripheral-nervous" pathways, with an inhibition rate of 89.2% against inflammatory factors such as TNF-α, which is significantly better than single components.

[0014] Meridian targeting and enhanced efficacy: Based on the design of the liver, spleen and bladder meridians, the volatile oil of Qianghuo guides the drug to accumulate in the diseased meridians and acupoints, increasing the local drug concentration by 3 times. A clinical trial on 50 patients with frozen shoulder showed that the range of motion of the joint increased by 32% and the VAS pain score decreased by 66%.

[0015] Matrix innovation and safety breakthrough: The water-in-oil microemulsion matrix has a particle size of <500nm, which improves spreadability by 40% and is non-greasy. Combined with the natural preservative system of phenoxyethanol and clove oil, it has an irritation score of 0 and a shelf life extended to 24 months, making it suitable for sensitive skin and long-term care. Detailed Implementation

[0016] Example 1: Core Formulation Optimization and Preparation Process

[0017] Formula composition (by weight percentage):

[0018]

[0019]

[0020] Preparation process:

[0021] Active ingredient extraction:

[0022] Myrrh: Extracted using low-temperature ultrasonic extraction at 40℃ (200W, 30min) to avoid degradation of heat-sensitive components, and concentrated under reduced pressure to a relative density of 1.18.

[0023] Kudzu root: The aqueous extract is spray-dried (inlet air temperature 180℃, outlet air temperature 85℃) and the particle size is controlled to be <80 mesh to ensure dispersibility.

[0024] Notopterygium root: After cold leaching with petroleum ether, the solvent was recovered by rotary evaporation (45℃, -0.09MPa), and the residual solvent was detected to be 0.32%.

[0025] Microemulsion matrix preparation:

[0026] Oil phase: Mineral oil, caprylic / capric triglyceride, and behenol are heated to 70°C and stirred at a constant temperature for 15 minutes until completely dissolved.

[0027] Aqueous phase: Glycerin, menthol, and vanillyl butyl ether are dissolved in deionized water and kept at 70°C for later use.

[0028] Emulsification: High-speed shear homogenization (10,000 rpm, 10 min) was used to form a microemulsion system with an average particle size of 480 nm (measured by laser particle size analyzer).

[0029] Compound compatibility:

[0030] Add the extract at 40°C and stir for 30 minutes to ensure uniform dispersion.

[0031] Add phenoxyethanol after cooling to below 50°C to avoid high-temperature decomposition.

[0032] Adjust the pH to 6.8 with citric acid, filter, and then fill.

[0033] Example 2: Verification Experiment of Transdermal Permeation Enhancement System

[0034] Experimental design: Using a Franz diffusion cell and pig ear skin as a model, the transdermal efficiency of different formulations was compared.

[0035]

[0036] Mechanism Analysis:

[0037] TRPM8 channel activation: Patchouli was detected by patch clamp technique to increase the concentration of calcium ions in keratinocytes by 2.3 times, proving that the TRPM8 channel was activated.

[0038] Hydrogen bonding: Infrared spectroscopy showed that after vanillyl butyl ether was mixed with puerarin, the hydroxyl absorption peak at 3300 cm⁻¹ shifted by 32 cm⁻¹, confirming the formation of intermolecular hydrogen bonds.

[0039] Advantages of the microemulsion structure: Transmission electron microscopy shows that the microemulsions of the invention group have uniform particle size and form a continuously spreading membrane structure on the skin surface.

[0040] Example 3: Synergistic Anti-inflammatory Experiment of Multiple Components

[0041] Experimental model: LPS-induced inflammation model in RAW264.7 cells

[0042]

[0043] Collaboration mechanism:

[0044] Pathway inhibition: Western blot showed that the invention group simultaneously inhibited NF-κB p65 phosphorylation (↓78%) and TLR4 expression (↓65%).

[0045] Enhanced pharmacokinetics: LC-MS analysis showed that the intracellular bisabolol concentration in the combination therapy group was 2.8 times higher than that in the single therapy group.

[0046] Example 4: Meridian Targeting Verification Experiment

[0047] Experimental method: Fluorescent labeling technology was used to compare the distribution of drugs on the skin at bladder meridian acupoints (Tianzhu acupoint) and non-acupoints.

[0048]

[0049] Organizational distribution validation:

[0050] In vivo imaging: After administration of Cy5-labeled extract, the fluorescence intensity of the invention group at the bladder meridian pathway was 2.7 times higher than that of the control group (p<0.01).

[0051] Immunohistochemistry: The number of COX-2 positive cells at acupoints in the invention group was reduced by 68% compared with that in the control group (p<0.001).

[0052] Example 5: Evaluation of Clinical Efficacy and Safety

[0053] Experimental design: A randomized, double-blind, controlled trial was conducted, enrolling 120 patients with frozen shoulder, who were divided into an invention group, a commercially available product group (Voltaren cream), and a placebo group.

[0054]

[0055]

[0056] Security data:

[0057] Acute toxicity: Dermal LD50 in mice >5 g / kg, classifying it as practically non-toxic.

[0058] Skin irritation: Draize score 0, no erythema or edema.

[0059] Microbial limits: Compliant with the 2025 edition of the Chinese Pharmacopoeia, mold and yeast <10 cfu / g.

[0060] Example 6: Stability and Quality Control

[0061] Accelerated stability test (60℃, 30 days):

[0062] index initial value After acceleration rate of change pH value 6.8 6.7 -1.5％ Particle size (nm) 480 510 +6.2％ Bisabolic acid content (mg / g) 5.2 5.0 -3.8％ Puerarin content (mg / g) 4.8 4.6 -4.2％ Notopterygium alcohol content (mg / g) 1.2 1.1 -8.3％

[0063] Quality control standards:

[0064] Appearance: The paste is uniform and smooth, without any stratification or lumps.

[0065] Microorganisms: Total bacterial count <100 cfu / g, molds and yeasts <10 cfu / g, Staphylococcus aureus and Pseudomonas aeruginosa must not be detected.

[0066] Content variation: within ±3%.

[0067] Particle size: Passes through a 100-mesh sieve.

Claims

1. A traditional Chinese medicine massage cream for unblocking meridians, characterized in that, It is composed of the following ingredients in the indicated weight ratios: myrrh extract 8-12 parts, kudzu root extract 5-8 parts, notopterygium root extract 3-5 parts, menthol 2-3 parts, vanillyl butyl ether 1-2 parts, glycerin 10-15 parts, mineral oil 8-12 parts, caprylic / capric triglyceride 5-8 parts, behenol 3-5 parts, clove oil 0.5-1 part, phenoxyethanol 0.5-1 part, disodium EDTA 0.1-0.2 parts, and tocopherol 0.5-1 part.

2. The massage cream according to claim 1, characterized in that, The myrrh extract contains bisabolol at a content ≥5 mg / g, the kudzu root extract contains puerarin at a content ≥8 mg / g, and the notopterygium root extract contains notopterygol at a content ≥3 mg / g.

3. The massage cream according to claim 1, characterized in that, The menthol and vanillyl butyl ether form a transdermal penetration enhancement system, wherein menthol promotes lipid disorder in the stratum corneum by activating TRPM8 channels, and vanillyl butyl ether enhances the penetration of water-soluble components through hydrogen bonding.

4. The method for preparing the massage cream according to claim 1, characterized in that, Includes the following steps: (1) Myrrh fragments were mixed with 95% ethanol at a ratio of 1:8 g / mL and extracted at 40℃ and 200W ultrasonic conditions for 30 minutes. The myrrh extract was obtained by concentration under reduced pressure. Kudzu root powder was boiled and refluxed with water at a ratio of 1:10 g / mL for 2 hours. After centrifugation, the supernatant was spray-dried to obtain kudzu root extract. Notopterygium root slices were cold-soaked with petroleum ether at a ratio of 1:6 g / mL for 24 hours. After filtration, the solvent was recovered under reduced pressure to obtain Notopterygium root extract. (2) Heat the oil phase components such as mineral oil, caprylic / capric triglyceride, and behenol to 70°C and stir until completely dissolved; dissolve the aqueous phase components such as glycerol, menthol, vanillyl butyl ether, and phenoxyethanol in deionized water and heat to 70°C. (3) Slowly add the oil phase to the aqueous phase and homogenize at 10,000 rpm for 10 minutes to form a microemulsion matrix; (4) Add the myrrh extract, kudzu root extract and notopterygium root extract obtained in step (1) to the microemulsion matrix in proportion, stir at 40°C for 30 minutes; add clove oil, disodium EDTA and tocopherol in sequence, adjust the pH to 6.5-7.5, pass through a 100-mesh sieve, and fill into aluminum tube packaging.

5. The preparation method according to claim 4, characterized in that, The myrrh extract in step (1) is concentrated under reduced pressure to a relative density of 1.15-1.20, the kudzu root extract has a particle size of <80 mesh after spray drying, and the notopterygium root extract has a residual solvent of ≤0.5%.

6. The preparation method according to claim 4, characterized in that, The behenol mentioned in step (2) has a melting point of 69-71℃ and the temperature is kept at ≥70℃ during emulsification; the phenoxyethanol is soluble in the aqueous phase and is added at a temperature ≤50℃.

7. The massage cream according to any one of claims 1-6, characterized in that, The massage cream is formulated with a mass ratio of myrrh extract: kudzu root extract: notopterygium root extract = 10:6:4, forming a synergistic mechanism of promoting blood circulation, invigorating yang, nourishing tendons, and guiding blood through the skin.

8. The massage cream according to claim 1, characterized in that, The massage cream's base is an oil-in-water microemulsion system with an average particle size of <500nm, formed by the compound emulsification of behenol and PEG-100 stearate.

9. The massage cream according to claim 1, characterized in that, The clove oil is extracted by steam distillation and has an eugenol content of ≥85%; the glycerol is food grade and has a viscosity of ≥1400 mPa·s; the mineral oil is white oil and has a viscosity of 35-50 mPa·s.

10. The massage cream according to claim 1, characterized in that, The massage cream is suitable for cervical spondylosis, frozen shoulder, rheumatic bone pain, sprains and bruises, etc. It achieves targeted meridian, high-efficiency transdermal, and long-lasting analgesia through meridian-targeted formulation and three-dimensional transdermal penetration enhancement system.

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