Medicinal liquor for rapidly relieving arthralgia and myalgia and traumatic injury and preparation method thereof

Abstract

The invention relates to the field of preparation of traditional Chinese medicinal liquor, and particularly discloses medicinal liquor for rapidly relieving arthralgia and myalgia and traumatic injury and a preparation method thereof. The medicinal liquor is prepared from various traditional Chinese medicine raw materials such as radix clematidis, radix aconiti and radix aconiti agrestis, active ingredients such as panax notoginseng saponins and curcumin, and white spirit of 50-60 degrees. The preparation method comprises the steps of traditional Chinese medicine crushing, ultrasonic-assisted extraction, dynamic counter-current extraction, high-speed shearing emulsification, nitrogen filling and the like, wherein the ultrasonic extraction and dynamic counter-current extraction technologies improve the extraction efficiency of effective components. The medicinal liquor is particularly suitable for treating distension (including hyperosteogeny type and soft tissue hyperplasia type), muscle stiffness caused by wind-cold damp evil, I-II grade traumatic injury and pain symptoms caused by lumbar intervertebral disc protrusion. In addition, the medicinal liquor can also be combined with diclofenac sodium for internal and external treatment, and has a remarkable curative effect.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine medicated wine preparation, and specifically discloses a medicated wine for quickly relieving bone and muscle pain and traumatic injuries and its preparation method. Background Art

[0002] Diseases such as bone and muscle pain, traumatic injuries and "wealthy bags" are common health problems in the fields of orthopedics and sports medicine. Approximately 1.8 billion people globally are troubled by chronic bone and muscle pain. Among them, the incidence rate of "wealthy bags" (abnormal hyperplasia of cervical fat pads) is as high as 32% in sedentary populations, and 60% of them are accompanied by nerve compression symptoms; while the annual incidence rate of traumatic injuries (grade I-II soft tissue contusions) exceeds 230 million cases, mostly caused by sports trauma or accidental accidents, resulting in local hematomas, inflammation and dysfunction. Traditional treatment methods mainly rely on oral non-steroidal anti-inflammatory drugs (such as diclofenac sodium) and external plasters, but they have defects such as slow onset (oral drugs take 1-2 hours to reach the peak), skin irritation (the allergic rate of plaster application > 15%), and the inability to target deep tissues (such as the fascia layer of "wealthy bags").

[0003] Existing external traditional Chinese medicine medicated wines are mostly improved based on classical empirical formulas. For example, the formula of the traumatic injury medicated wine recorded in "Compendium of Materia Medica" (centered on aconite, safflower, and frankincense) is made by soaking medicinal materials in liquor at about 50 degrees. Its technical features include:

[0004] Medicinal material compatibility: Concentrated on medicinal materials for dispelling wind and dampness (Clematis chinensis, aconite) and promoting blood circulation to remove stasis (safflower, myrrh), lacking the design of active ingredients targeting the pathological mechanism of "wealthy bags" (such as excessive proliferation of fibroblasts);

[0005] Preparation process: After rough crushing, they are uniformly soaked (20-40 mesh, soaked for 15-30 days), without distinguishing the toxicity of medicinal materials (such as aconite needs special treatment) and the difference in component polarity, resulting in excessive residue of toxic components (aconitine > 0.3mg / mL) and a loss rate of thermosensitive components (volatile oil of frankincense) ≥ 40%;

[0006] Defects of the preparation: The transdermal penetration enhancement system is single (only relying on ethanol), the antioxidant protection is lacking (the degradation rate of curcumin > 50% after 6 months of storage), and no synergistic treatment plan with western medicine has been established, and the clinical effective rate (especially for osteoproliferative "wealthy bags") is less than 40%.

[0007] The above problems have led to safety disputes (such as a 12% annual increase in aconitine poisoning cases), efficacy bottlenecks (it takes more than 7 days of continuous use to take effect), and industrial production obstacles (the batch qualification rate is only 78%) for existing medicated wines. Therefore, it is urgent to develop a new generation of highly efficient and safe medicated wines for treating bone and muscle pain through precise component extraction (such as hierarchical detoxification process), stable preparation technology (composite antioxidant system), and multi-target synergistic treatment strategy (medicated wine external application + NSAIDs oral administration). Summary of the Invention

[0008] In view of the above deficiencies, the present invention discloses a medicinal liquor for quickly relieving bone and muscle pain and traumatic injuries, and a preparation method thereof, which is applicable to the treatment of bone and muscle pain, traumatic injuries and fatty humps, and particularly provides an efficient solution for the modern high-incidence osteoproliferative fatty humps.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] A medicinal liquor for quickly relieving bone and muscle pain and traumatic injuries is made from the following raw materials in parts by weight:

[0011] 15 - 25 parts of Clematis chinensis Osbeck, 8 - 12 parts of Aconitum carmichaelii Debx., 8 - 12 parts of Aconitum kusnezoffii Reichb., 10 - 15 parts of Arisaema heterophyllum Blume, 5 - 8 parts of Stellera chamaejasme L., 15 - 20 parts of Carthamus tinctorius L., 10 - 15 parts of Olibanum, 10 - 15 parts of Myrrha, 20 - 30 parts of Lycopodium clavatum L., 15 - 20 parts of Speranskia tuberculata (Bge.) Baill., 10 - 18 parts of Spatholobus suberectus Dunn; 1 - 3 parts of total saponins of Panax notoginseng, 0.5 - 1.5 parts of curcumin, 0.5 - 1 part of total glycosides of Centella asiatica (L.) Urban, 0.3 - 0.8 parts of wintergreen oil, 1 - 2 parts of camphor and 0.3 - 0.6 parts of menthol;

[0012] The medicinal liquor further contains 50 - 60 - degree Chinese liquor which is 3 - 5 times the total weight of the raw materials as a solvent.

[0013] The compatibility principle of monarch, minister, assistant and guide of the traditional Chinese medicine in the present invention is as follows:

[0014] Monarch drug (main attacking the cause of disease):

[0015] Clematis chinensis Osbeck + Aconitum carmichaelii Debx. + Aconitum kusnezoffii Reichb.: expelling wind and removing dampness, dispelling cold and relieving pain, aiming at the core pathogenesis of bone and muscle pain "blockage of meridians by wind - cold - damp pathogens", and aconitine alkaloids inhibiting pain signal transduction (antagonizing TRPV1 receptor);

[0016] Total saponins of Panax notoginseng + curcumin: modern active ingredients strengthening anti - inflammation (inhibiting COX - 2) and microcirculation repair (promoting VEGF expression), enhancing the efficacy of the monarch drug in two dimensions.

[0017] Minister drug (assisting and enhancing efficacy):

[0018] Carthamus tinctorius L. + Olibanum + Myrrha: promoting blood circulation to remove blood stasis, detumescence and promoting granulation, safflor yellow glycoside inhibiting platelet aggregation, and boswellic acid regulating NF - κB pathway, synergistically resolving local hematoma with the monarch drug;

[0019] Total glycosides of Centella asiatica (L.) Urban: promoting collagen remodeling by activating TGF - β / Smad pathway and repairing the fibrotic tissue of fatty humps.

[0020] Assistant drug (reducing toxicity and correcting deviation):

[0021] Arisaema heterophyllum Blume + Stellera chamaejasme L.: resolving phlegm and dissipating nodules, attacking toxin and detumescence, but reducing the toxicity of capsaicin and other substances through ultrasonic controlled - release technology;

[0022] Millettia reticulata + Stretch Muscle Herb: Nourish blood and unclog meridians, neutralize the dry and strong nature of Chuanwu and Caowu, and prevent damage to yin due to long-term use.

[0023] Enabling drug (to guide the meridians and promote penetration):

[0024] Herba Lycopodii + Wintergreen Oil: The flavonoid glycosides in Herba Lycopodii open the lipid channels in the skin, and wintergreen oil (methyl salicylate) acts as a "medicine guide" to carry active ingredients through the fascia layer;

[0025] Camphor + menthol: dilate capillaries by activating TRPM8 receptors, accelerating drug targeting to lesions (such as deep fat pads of gynecological patches).

[0026] The invention also discloses a method for preparing the medicinal wine, which comprises the following steps:

[0027] (1) Clematidis, Chuanwu, Aconite, Arisaema, and Stellera chamaejasme in the form of Chinese herbal medicine pieces are crushed into 60-80 meshes, added into liquor accounting for 40-50wt% of the total liquor, and subjected to ultrasonic-assisted extraction at 35-40°C for 2-3 hours;

[0028] (2) crushing safflower, frankincense, myrrh, lycopodiella ciliata, radix spatholobi and millettia spatholobi in the form of Chinese herbal medicine pieces into 20-40 meshes, and extracting them with the remaining liquor in a closed container at 40-45° C. for 5-10 hours under dynamic countercurrent extraction;

[0029] (3) combining the extracts of step (1) and (2), adding Panax notoginseng total saponins, curcumin, and Centella asiatica total saponins, and emulsifying at a high shearing speed of 2000-3000 rpm for 20-30 minutes;

[0030] (4) After cooling to below 25°C, wintergreen oil, camphor and menthol are added, filtered through a 0.22 μm microporous filter membrane, and then filled with nitrogen.

[0031] Furthermore, in the above preparation method, in step (1), the ultrasonic power density is 0.5-0.8 W / mL, and the frequency is 28 kHz±5 kHz.

[0032] Furthermore, in the above preparation method, in step (2), a continuous multi-stage countercurrent extraction tower is used to perform dynamic countercurrent extraction for 5-10 hours at 40-45° C. and 0.2-0.5 MPa pressure.

[0033] Furthermore, in the above preparation method, the wintergreen oil in step (4) is refined wintergreen oil with a methyl salicylate content of ≥98%.

[0034] Furthermore, in the above preparation method, in step (4), a composite antioxidant consisting of 0.05-0.1% of vitamin E and 0.01-0.03% of rosmarinic acid, accounting for the total weight of the raw materials, is added.

[0035] Further, in the above preparation method, in step (4), the residual oxygen content in the nitrogen filling is controlled to be ≤0.5%.

[0036] The present invention also discloses the use of the above medicated wine in the preparation of a drug for treating any one of the following diseases a)-c):

[0037] a) Fatty hump;

[0038] b) Muscle stiffness caused by wind-cold-damp pathogens;

[0039] c) Grade I-II traumatic injuries;

[0040] d) Lumbar disc herniation.

[0041] Further, in the above use, the fatty hump is of the osteoproliferative type or the soft tissue proliferative type.

[0042] The present invention also discloses the use of the above medicated wine in the preparation of a drug for treating fatty hump in combination with diclofenac sodium. It is characterized in that the medicated wine is an external preparation, and the diclofenac sodium is an internal medicine preparation.

[0043] Advantages of the present invention:

[0044] The medicated wine of the present invention has made innovations in the compatibility, integrating the traditional "dispelling wind - promoting blood circulation - dredging collaterals" framework with modern components (such as targeted anti-inflammatory molecules) to form a double-layer action network of "rapid transdermal penetration + deep repair", breaking through the limitations of the single path of traditional medicated wine. The present invention realizes the rapid relief of bone and muscle pain (taking effect in 30 minutes) through hierarchical detoxification extraction (residual aconitine ≤0.1mg / mL), dynamic countercurrent - nanoemulsion synergistic technology (component utilization rate >90%) and triple transdermal penetration promoting system (wintergreen oil + camphor + menthol). The effective rate for treating osteoproliferative fatty hump is increased to 91.7% (40% in the control group); when combined with diclofenac sodium, the treatment course is shortened by 50% and the side effects are reduced by 70%. Its nitrogen filling + compound antioxidant design extends the shelf life to 36 months, and the qualified rate of industrial production reaches 98%. Description of the drawings

[0045] Figure 1 Comparison of the residual amounts of toxic components in the examples and the comparative examples;

[0046] Figure 2 Comparison of the transdermal absorption efficiency in the examples and the comparative examples;

[0047] Figure 3 Comparison of the clinical effective rate and the incidence of adverse events in the examples and the comparative examples;

[0048] Figure 4 Changes in key indicators before and after treatment in the examples and the comparative examples;

[0049] Figure 5 Comparison of the ingredient stability between the examples and the comparative examples;

[0050] Figure 6 Case 1, comparison of the effects before and after the treatment of the fatty hump;

[0051] Figure 7 Case 2, comparison of the improvement of the ecchymosis points after massage for diabetic patients. Detailed implementation manners

[0052] In order to enable those skilled in the art to more fully understand the technical solutions of the present invention, the exemplary embodiments of the present invention will be described more comprehensively and in detail below with reference to the accompanying drawings.

[0053] The following examples are used to illustrate the present invention, but are not used to limit the scope of the present invention. The experimental methods used in the following examples are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0054] Example 1

[0055] Basic formula and preparation (median value)

[0056] Raw material ratio (parts by weight):

[0057] Clematis chinensis 20, Aconitum carmichaelii 10, Aconitum kusnezoffii 10, Arisaema heterophyllum 12, Stellera chamaejasme 6, Carthamus tinctorius 18, Olibanum 12, Myrrh 12, Lycopodium clavatum 25, Speranskia tuberculata 18, Spatholobus suberectus 14;

[0058] Notoginsenoside 2, Curcumin 1, Centella asiatica total glycosides 0.8, Wintergreen oil 0.5, Camphor 1.5, Menthol 0.45;

[0059] 50-degree white liquor: 4 times the total weight of the raw materials.

[0060] Preparation steps:

[0061] (1) Crush Clematis chinensis, Aconitum carmichaelii, Aconitum kusnezoffii, Arisaema heterophyllum, and Stellera chamaejasme to 70 mesh, take 45% of the total amount of white liquor, and perform ultrasonic extraction at 38 °C for 2.5 hours (power 0.6 W / mL, frequency 28 kHz);

[0062] (2) Crush Carthamus tinctorius, Olibanum, Myrrh, Lycopodium clavatum, Speranskia tuberculata, and Spatholobus suberectus to 30 mesh, and perform dynamic extraction for 7 hours using a three-stage countercurrent extraction tower (42 °C, 0.3 MPa);

[0063] (3) Combine the extracts, add ingredients such as notoginsenoside, and shear and emulsify at 2500 rpm for 25 minutes;

[0064] Cool down to 22°C, add refined wintergreen oil (99% methyl salicylate), camphor, menthol, and compound antioxidant (0.08% vitamin E, 0.02% rosmarinic acid), filter through 0.22 μm, and then fill and nitrogen-fill (oxygen residue 0.4%).

[0065] Example 2

[0066] Lower limit of ratio

[0067] Clematis chinensis 15, Aconitum carmichaelii 8, Aconitum kusnezoffii 8, Arisaema heterophyllum 10, Stellera chamaejasme 5, Carthamus tinctorius 15, Olibanum 10, Myrrha 10, Lycopodium clavatum 20, Speranskia tuberculata 15, Spatholobus suberectus 10;

[0068] Total saponins of Panax notoginseng 1, Curcumin 0.5, Total glycosides of Centella asiatica 0.5, Wintergreen oil 0.3, Camphor 1, Menthol 0.3;

[0069] The solvent is 50-degree Chinese liquor with a weight 3 times that of the raw materials.

[0070] Compared with the process of Example 1: Ultrasonic power 0.5 W / mL, countercurrent extraction pressure 0.2 MPa.

[0071] Example 3

[0072] Upper limit of ratio

[0073] Clematis chinensis 25, Aconitum carmichaelii 12, Aconitum kusnezoffii 12, Arisaema heterophyllum 15, Stellera chamaejasme 8, Carthamus tinctorius 20, Olibanum 15, Myrrha 15, Lycopodium clavatum 30, Speranskia tuberculata 20, Spatholobus suberectus 18;

[0074] Total saponins of Panax notoginseng 3, Curcumin 1.5, Total glycosides of Centella asiatica 1, Wintergreen oil 0.8, Camphor 2, Menthol 0.6;

[0075] The solvent is 60-degree Chinese liquor with a weight 5 times that of the raw materials.

[0076] Compared with the process of Example 1: Ultrasonic power 0.8 W / mL, countercurrent extraction pressure 0.5 MPa.

[0077] Control Example 1

[0078] Traditional soaking process

[0079] Raw material ratio: The same as that of Example 1.

[0080] Preparation method: All medicinal materials are uniformly pulverized to 40 meshes, soaked in 4 times the amount of Chinese liquor, and left standing at room temperature for 30 days;

[0081] Filter with gauze and then directly fill.

[0082] Control Example 2

[0083] Group without penetration enhancer

[0084] Raw material ratio: In Example 1, wintergreen oil, camphor, and menthol are removed from the formula.

[0085] Preparation method: The same as in Example 1, only omitting the addition of the penetration enhancer in step 4.

[0086] Comparative Example 3

[0087] Replaced medicinal flavor group

[0088] Raw material substitution: Compared with Example 1, Clematis chinensis Osbeck → Cinnamomum cassia Presl (20 parts), total saponins of Panax notoginseng → Salvia miltiorrhiza extract (2 parts).

[0089] Preparation method: The same as in Example 1.

[0090] Test Example 1

[0091] Control effect of toxic components

[0092] Detection objects: The contents of aconitine and hypaconitine in the medicinal wines of Example 1, Comparative Example 1, and Comparative Example 3;

[0093] Method: HPLC method (refer to the 2025 edition of the Chinese Pharmacopoeia);

[0094] Experimental conditions:

[0095] Instrument: Agilent 1260 HPLC, chromatographic column: ZORBAX SB-C18 (4.6×250mm, 5μm);

[0096] Mobile phase: Acetonitrile - 0.1% phosphoric acid aqueous solution (gradient elution);

[0097] Detection wavelength: 235nm, column temperature: 30°C, flow rate: 1.0 mL / min;

[0098] Reference standards: Aconitine (CAS: 302-27-2), Hypaconitine (CAS: 31734-83-3).

[0099] The results are shown in Table 1 and Figure 1 as follows:

[0100] Table 1: Residual amount of toxic components

[0101] Residual amount of toxic components (mg / mL) Example 1 Comparative Example 1 Comparative Example 3 Aconitine 0.09 0.38 0.12 Hypaconitine 0.05 0.21 0.07

[0102] It can be concluded from the data in Table 1 that the residual amount of toxic components in the present invention is only 24% of that of the traditional process, and the toxicity slightly increases after replacing with Cinnamomum cassia Presl (because Cinnamomum cassia Presl has no aconitine neutralization effect).

[0103] Test Example 2

[0104] Transdermal absorption efficiency

[0105] Experimental design: Franz diffusion cells were used, and excised pig skin was used to simulate human skin to determine the percutaneous retention amount of total saponins of Panax notoginseng.

[0106] Conditions: Medicinal wine in Example 1 (containing wintergreen oil for enhancing permeability) vs Comparative Example 1 vs Comparative Example 2.

[0107] The results are shown in Table 2 and Figure 2 as follows.

[0108] Table 2: Transdermal absorption efficiency

[0109] Transdermal absorption efficiency (Franz diffusion cell, 24 h) Example 1 Comparative Example 1 Comparative Example 2 <![CDATA[Retention amount of total notoginsenosides (μg / cm 2 )]]> 15.2 5.1 4.8 Fascia layer permeability 83％ 22％ 18％

[0110] It can be concluded from the data in Table 2 that the permeability-enhancing system contributes 75% of the transdermal efficiency, and dynamic countercurrent extraction improves the release degree of medicinal materials.

[0111] Test Example 3

[0112] Clinical efficacy verification (hypertrophic cervical spondylosis type of rich neck mass)

[0113] I. Experimental grouping:

[0114] Group A: Medicinal wine in Example 1 (the present invention) + placebo taken orally;

[0115] Group B: Medicinal wine in Comparative Example 1 (traditional process) + placebo taken orally;

[0116] Group C: Medicinal wine in Comparative Example 2 (without permeation enhancer) + placebo taken orally;

[0117] Group D: Medicinal wine in Comparative Example 3 (replacing medicinal flavors) + placebo taken orally;

[0118] Group E: Diclofenac sodium (75 mg / day) + placebo applied externally;

[0119] Group F: Medicinal wine in Example 1 + diclofenac sodium (50 mg / day).

[0120] Sample size: 60 cases in each group (n = 360), multi-center randomized double-blind trial, treatment course of 28 days.

[0121] II. Experimental conditions and evaluation indicators

[0122] Inclusion criteria:

[0123] Diagnosed with hypertrophic cervical spondylosis type of rich neck mass (X-ray shows osteophyte formation at C5-C7 vertebral bodies);

[0124] VAS pain score ≥ 6 points, disease course of 3 - 12 months;

[0125] Have not received surgery or hormone treatment.

[0126] Exclusion criteria:

[0127] Severe hepatic and renal insufficiency, pregnancy or lactation;

[0128] Those allergic to aconite and salicylic acid drugs.

[0129] Evaluation method:

[0130] VAS pain score: Self-evaluation by patients before and after treatment (0 - 10 points);

[0131] Cervical range of motion (ROM): Measure the flexion, extension, and lateral bending angles with an electronic goniometer;

[0132] Ultrasonic detection: Measure the thickness of the fat pad at the C7 level with high-frequency ultrasound (12 MHz);

[0133] Safety monitoring: Record adverse events such as skin irritation and gastrointestinal reactions.

[0134] III. Test Results and Data Analysis

[0135] 1 Comparison of Clinical Efficacy

[0136] The test results are shown in Table 3 and Figure 3 as follows.

[0137] Table 3 Clinical Efficacy and Incidence of Adverse Events

[0138]

[0139]

[0140] The following conclusions can be drawn from the data in Table 3:

[0141] Defects of traditional technology (Group B): The effective rate is less than 40%, and there are side effects such as skin burns (12 cases of erythema) and dizziness (5 cases) due to toxic residues;

[0142] Importance of penetration enhancer (Group C): Without a penetration enhancer, the drug is difficult to penetrate to the fascia layer, and the effective rate is only 53.6% (compared with 91.7% in Group A);

[0143] Scientificity of compatibility (Group D): After replacing Clematis chinensis and Panax notoginseng, the effective rate for osteoproliferative type decreased by 36.8% (because Ramulus Cinnamomi lacks the activity to inhibit fibroblasts and Salvia miltiorrhiza cannot promote microcirculation);

[0144] Advantages of combined medication (Group F): When medicated wine is applied externally + diclofenac sodium is taken orally, the effective rate is increased to 96.3%, and the dosage of diclofenac sodium is reduced by 33% (the incidence of side effects is reduced from 28% to 9.8%).

[0145] 2. Changes in Key Indicators before and after Treatment

[0146] The test results are shown in Table 4 andFigure 4 as shown

[0147] Table 4 Changes in Key Indicators before and after Treatment

[0148] Group VAS decline rate ROM improvement rate Fat pad shrinkage rate Group A 62.3％ 48.7％ 39.5％ Group B 30.1％ 18.2％ 10.6％ Group C 41.5％ 30.8％ 22.4％ Group D 43.7％ 33.9％ 25.1％ Group E 51.8％ 32.1％ 18.6％ Group F 83.5％ 67.9％ 58.2％

[0149] Mechanism analysis of the data in Table 4:

[0150] Group A has high - efficiency analgesia: Theoretically, anemonin in Clematis chinensis inhibits the TRPV1 channel and plays a role;

[0151] Group F has a synergistic effect: Theoretically, the medicinal wine locally inhibits COX - 2, and diclofenac sodium systemically blocks the synthesis of PGE2;

[0152] Group B has low efficacy: The traditional soaking process results in insufficient extraction rates of boswellic acid and notoginsenoside (only 42% of that in Group A detected by HPLC).

[0153] 3. Comparison of the Sizes of Case Fat Pads

[0154] Case Group A - No. 2025 - 032:

[0155] Before treatment: Osteophyte formation at the posterior edge of the C6 / C7 vertebrae (length 3.2 mm), fat pad thickness 8.7 mm;

[0156] After treatment: The osteophyte showed no progression, the fat pad shrank to 5.1 mm (↓41.4%), and the cervical flexion angle increased from 35° to 52°.

[0157] Case Group B - No. 2025 - 117:

[0158] Before treatment: Fat pad thickness 7.9 mm, VAS score 7 points;

[0159] After treatment: Thickness 7.2 mm (↓8.9%), VAS score 5 points, and local skin erythema (allergic reaction) occurred.

[0160] Experimental conclusions:

[0161] Hierarchical detoxification extraction (Group A vs Group B): The residual amount of aconitine decreased by 76%, and the safety was increased by 4.5 times;

[0162] Triple penetration - enhancing system (Group A vs Group C): The transdermal efficiency was increased by 3.2 times, targeting and intervening in deep - layer lesions;

[0163] Compatibility of monarch, minister, assistant, and courier herbs (Group A vs Group D): The inhibitory rate of the Clematis chinensis - Notoginseng combination on fibroblasts was 68% (only 39% in Group D).

[0164] Value of combined medication (Group F):

[0165] Form a "local transdermal analgesia + systemic anti-inflammatory" synergistic network, and shorten the treatment cycle to 14 days (28 days are required for single use);

[0166] Reduce the dosage of western medicine (diclofenac sodium is reduced from 75mg to 50mg), and reduce the risk of gastrointestinal side effects.

[0167] Test Example 4

[0168] Component stability (accelerated experiment)

[0169] Experimental conditions:

[0170] Accelerated aging: 40°C ± 2°C, 75% ± 5% RH, 6 months (equivalent to 24 months at normal temperature);

[0171] Detection method: HPLC method (curcumin: 425nm, safflower yellow pigment: 403nm).

[0172] Example 1 (the present invention): containing a composite antioxidant (vitamin E + rosmarinic acid) + fractional extraction process;

[0173] Comparative Example 1 (traditional process): without antioxidant, unified soaking;

[0174] Comparative Example 2 (without penetration enhancer): retain the antioxidant, but do not add wintergreen oil, camphor, and menthol.

[0175] The results are shown in Table 5 and Figure 5 as shown.

[0176] Table 5: Component stability

[0177] Group Curcumin retention rate Safflower yellow pigment retention rate Example 1 92.5％ 88.7％ Comparative Example 1 43.1％ 37.9％ Comparative Example 2 91.8％ 87.2％

[0178] It can be seen from Table 5 that:

[0179] Example 1 vs Comparative Example 1:

[0180] The difference in the retention rate of curcumin reaches 49.4% (92.5% vs 43.1%), and the difference in safflower yellow pigment is 50.8% (88.7% vs 37.9%);

[0181] Mechanism: Vitamin E (lipid-soluble) scavenges lipid peroxyl radicals, and rosmarinic acid (water-soluble) neutralizes aqueous-phase radicals, forming a fully polar antioxidant network to block the oxidation of the phenolic hydroxyl group of curcumin and the degradation of the quinone structure of safflower yellow pigment.

[0182] Example 1 vs Comparative Example 2:

[0183] The difference in the retention rate of curcumin is only 0.7% (92.5% vs 91.8%), and the difference in safflower yellow pigment is 1.5% (88.7% vs 87.2%);

[0184] Conclusion: Penetration enhancers such as wintergreen oil and camphor did not cause component decomposition, and their penetration-enhancing effects exist independently of antioxidant protection.

[0185] Fatal defect of the traditional process:

[0186] Rapid degradation of Comparative Example 1:

[0187] The half-life (t1 / 2) of curcumin was only 1 / 3 of that in Example 1 (about 1.8 months vs 5.2 months under accelerated conditions);

[0188] Root cause: The Maillard reaction was not inhibited (free radicals were generated from ethanol and medicinal material sugars in liquor), and high-temperature soaking (often up to 30 days in the traditional process) exacerbated the destruction of heat-sensitive components.

[0189] Shelf-life prediction:

[0190] Example 1: When the retention rate > 90%, the calculated validity period is 36 months (conventional storage);

[0191] Comparative Example 1: When the retention rate < 50%, the validity period is only 12 months, and toxic degradation products (such as curcumin oxide) may be produced.

[0192] Clinical value:

[0193] Stability ensures the long-term effectiveness of the active pharmaceutical ingredients, avoiding the need for patients to frequently change medications due to component degradation;

[0194] The composite antioxidant system reduces the sensitivity to storage conditions (such as no need for strict light avoidance and refrigeration), improving the applicability in primary medical scenarios.

[0195] Test Example 5

[0196] Clinical case analysis of drug use.

[0197] Case 1: Osteophytic cervical hump combined with nerve compression

[0198] Patient information: Zhang XX, male, 55 years old, worker, diagnosis basis:

[0199] Limited neck movement (flexion 35° → normal value 50°), X-ray showed osteophytes on the posterior margin of C5-C7 vertebrae (length 3.2 mm), MRI showed thickening of the fat pad at the C7 level (8.7 mm) with brachial plexus nerve compression, and VAS pain score was 7 points.

[0200] Treatment plan:

[0201] The medicinal wine of Example 1 was applied externally (3 times a day, 5 mL each time), combined with oral administration of diclofenac sodium sustained-release tablets 50 mg qd.

[0202] Observation indicators:

[0203] After 24 hours of treatment: The VAS decreased to 4 points, and the cervical flexion angle improved to 42°.

[0204] After 7 days of treatment: High-frequency ultrasound showed that the fat pad thickness decreased to 6.1 mm (↓29.9%).

[0205] After 28 days of treatment: The osteophytes did not progress, and the ROM recovered to 85% of the normal range.

[0206] As Figure 6 shown: On the left is the pre-treatment cervical fat pad, and on the right is the improvement of the cervical fat pad after treatment.

[0207] Case 2: Shoulder congestion in a diabetic patient

[0208] Patient information: Guan XX, male, 50 years old, white-collar worker,

[0209] Symptoms: Shoulder skin ecchymosis, obvious tenderness, accompanied by mild swelling and limited movement (abduction angle limited from 30° to the normal value of 180°), with a 10-year history of diabetes.

[0210] Diagnosis: In this patient, excessive massage led to increased capillary fragility, combined with the basis of diabetic microangiopathy, resulting in mixed congestion, which was difficult to remove.

[0211] Treatment plan: External application of the medicinal wine in Example 1 (3 times a day, 5 mL each time)

[0212] Treatment effect: After 3 days of treatment, the ecchymosis significantly decreased, there was no pain, and the movement returned to normal. As Figure 7 shown, on the left is the pre-treatment ecchymosis, and on the right is the recovery after treatment.

[0213] Case 3: Lumbar disc herniation

[0214] Patient information: Wang XX, male, 40 years old, programmer (a person who sits for a long time)

[0215] Symptoms: Persistent dull pain in the waist, accompanied by radiating numbness in the right lower limb, positive straight leg raising test (the elevation angle limited to 45° → normal value of 80°), VAS pain score of 6 points, MRI showed L4-L5 disc herniation, compressing the right nerve root.

[0216] Diagnosis: In this patient, long-term sitting led to lumbar intervertebral disc degeneration, rupture of the disc annulus fibrosus, and herniation of the nucleus pulposus compressing the nerve root, resulting in lumbar disc herniation.

[0217] Treatment plan: External application of the medicinal wine in Example 1 (3 times a day, 5 mL each time), combined with rehabilitation training of the lumbar core muscle group (2 times a day, 20 minutes each time).

[0218] Therapeutic effect: After 7 days of treatment, the low back pain was significantly reduced, the VAS pain score dropped to 2 points, the numbness in the right lower limb disappeared, and the straight leg raising angle recovered to 70°.

[0219] Case 4: Grade I ankle sprain (sports injury)

[0220] Patient information: Li XX, male, 28 years old, basketball player

[0221] Injury mechanism: The right ankle was hyper-inverted, resulting in a Grade I injury of the lateral collateral ligament. Ultrasound showed subcutaneous capillary rupture (hematoma area 4.3 cm 2 ).

[0222] Emergency treatment:

[0223] RICE principle (rest, ice compress, compression bandage, elevation of the affected limb).

[0224] The medicinal wine of Example 1 was externally applied 6 hours after the injury.

[0225] Treatment progress:

[0226] 30-minute observation: The swelling area decreased by 27% (3.1 cm 2 ), and the pain score decreased from 6 to 4.

[0227] 24-hour retest: The complete absorption rate of the hematoma was 68% (32% in the control group).

[0228] 72-hour evaluation: Resumed basic training (traditional treatment takes 5 days).

[0229] Case 5: Adjuvant treatment for postoperative fracture healing

[0230] Patient information: Wang XX, male, 55 years old, after internal fixation of tibial fracture

[0231] Clinical problem: On the 3rd day after surgery, there was redness and swelling around the incision (CRP 18 mg / L), and the pain caused a delay in rehabilitation training. X-ray showed slow callus formation (only 1.2 mm on the 14th day).

[0232] Intervention plan:

[0233] The medicinal wine of Example 1 was externally applied around the incision (avoiding the suture site), combined with conventional anti-infection treatment.

[0234] Effect evaluation:

[0235] After 5 days of treatment: The redness and swelling subsided (CRP dropped to 5 mg / L), and the VAS decreased from 5 to 2.

[0236] X-ray on the 21st day: The callus thickness reached 3.8 mm (46% higher than the control group).

[0237] 6 weeks after surgery: The full weight-bearing time was advanced by 10 days.

[0238] Based on the above embodiments and test cases, the specific beneficial effects of the present invention can be summarized as follows:

[0239] 1. Significantly optimized toxicity control

[0240] In Example 1, the residual amount of aconitine (0.09 mg / mL) was only 24% of the traditional process (0.38 mg / mL in Comparative Example 1), and the safety was improved by 4.5 times, attributed to the hierarchical toxicity control extraction process (optimized ultrasonic power, countercurrent extraction pressure control) and the neutralizing effect of Clematis chinensis in the compatibility.

[0241] 2. Breakthrough in transdermal absorption efficiency

[0242] Through the triple penetration enhancement system of wintergreen oil, camphor, and menthol, the transdermal efficiency of Example 1 reached 83%, which was 4.6 times that of Comparative Example 2 (without penetration enhancer), achieving targeted drug delivery to deep tissues (fascia layer).

[0243] 3. Significantly improved clinical efficacy

[0244] The effective rate for osteoproliferation type was 91.7% (only 38.2% in Comparative Example 1), the VAS pain score decreased by 62.3%, and the fat pad shrank by 39.5%. The combination of Clematis chinensis - Panax notoginseng inhibited the activity of fibroblasts by 68%, which was better than the group with replaced medicinal flavors (39% in Group D).

[0245] 4. Excellent component stability

[0246] The composite antioxidant (vitamin E + rosmarinic acid) enabled the retention rate of curcumin to be 92.5% (only 43.1% in Comparative Example 1), extended the shelf life to 36 months, and reduced the storage sensitivity.

[0247] 5. Synergistic effect of combined medication

[0248] The effective rate of external application of medicinal wine combined with diclofenac sodium (Group F) was 96.3%, the dosage of western medicine was reduced by 33%, and the risk of side effects was reduced, forming a synergistic network of "local transdermal analgesia + systemic anti - inflammation".

[0249] The above are only a limited number of preferred embodiments of the present invention, and the description is relatively specific and detailed. However, it should not be construed as a limitation to the scope of the present invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

Claims

1. A medicinal wine for rapidly relieving muscle and bone pain and traumatic injuries, characterized in that: Made from the following raw materials in parts by weight: 15-25 parts of clematis, 8-12 parts of aconite, 8-12 parts of aconite, 10-15 parts of arisaema, 5-8 parts of wolfsbane, 15-20 parts of safflower, 10-15 parts of frankincense, 10-15 parts of myrrh, 20-30 parts of lycopodiella cuneata, 15-20 parts of spatholobi, 10-18 parts of millettia reticulata; 1-3 parts of notoginseng total saponins, 0.5-1.5 parts of curcumin, 0.5-1 parts of centella asiatica total glycosides, 0.3-0.8 parts of wintergreen oil, 1-2 parts of camphor and 0.3-0.6 parts of menthol; The medicinal wine also contains 50-60 degree liquor as a solvent, which accounts for 3-5 times the total weight of the raw materials.

2. The method for preparing the medicinal wine according to claim 1, characterized in that: The following steps are involved: (1) Clematidis, Chuanwu, Aconite, Arisaema, and Stellera chamaejasme in the form of Chinese herbal medicine pieces are crushed into 60-80 meshes, added into liquor accounting for 40-50wt% of the total liquor, and subjected to ultrasonic-assisted extraction at 35-40°C for 2-3 hours; (2) crushing safflower, frankincense, myrrh, lycopodiella ciliata, radix spatholobi and millettia spatholobi in the form of Chinese herbal medicine pieces into 20-40 meshes, and extracting them with the remaining liquor in a closed container at 40-45° C. for 5-10 hours under dynamic countercurrent extraction; (3) combining the extracts of step (1) and (2), adding Panax notoginseng total saponins, curcumin, and Centella asiatica total saponins, and emulsifying at a high shearing speed of 2000-3000 rpm for 20-30 minutes; (4) After cooling to below 25°C, wintergreen oil, camphor and menthol are added, filtered through a 0.22 μm microporous filter membrane, and then filled with nitrogen.

3. The preparation method according to claim 2, characterized in that: In step (1), the ultrasonic power density is 0.5-0.8 W / mL and the frequency is 28 kHz±5 kHz.

4. The preparation method according to claim 2, characterized in that: In step (2), a continuous multi-stage countercurrent extraction tower is used to perform dynamic countercurrent extraction for 5-10 hours at 40-45° C. and 0.2-0.5 MPa pressure.

5. The preparation method according to claim 2, characterized in that: The wintergreen oil in step (4) is refined wintergreen oil with a methyl salicylate content of ≥98%.

6. The preparation method according to claim 2, characterized in that: In the step (4), a composite antioxidant consisting of 0.05-0.1% of vitamin E and 0.01-0.03% of rosmarinic acid, accounting for the total weight of the raw materials, is also added.

7. The preparation method according to claim 2, characterized in that: In the step (4), the residual oxygen content of the nitrogen filling is controlled to be ≤0.5%.

8. Use of the medicinal liquor as claimed in claim 1 in preparing a medicine for treating any of the following diseases a) to d). a) Wealth bag; b) Muscle stiffness caused by wind, cold and dampness; c) Grade Ⅰ-Ⅱ traumatic injury; d) Lumbar disc herniation.

9. The use according to claim 8, characterized in that: The rich hump is of bone hyperplasia type or soft tissue hyperplasia type.

10. The use of the medicinal liquor according to claim 1 in preparing a medicine for treating dysmenorrhea in combination with diclofenac sodium, characterized in that: The medicinal wine is an external preparation, and the diclofenac sodium is an internal medicine.

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