Spaced moxibustion traditional Chinese medicine composition for treating benign prostatic hyperplasia as well as preparation method and application of sandwiched moxibustion traditional Chinese medicine composition

Abstract

The invention discloses a sandwiched moxibustion traditional Chinese medicine composition for treating benign prostatic hyperplasia as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The sandwiched moxibustion traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 to 50 parts of unprocessed radix aconiti carmichaeli, 10 to 20 parts of herba asari, 15 to 25 parts of herba patriniae, 10 to 20 parts of radix salviae miltiorrhizae, 5 to 15 parts of radix cudramiae, 5 to 15 parts of herba salviae chinensis, 5 to 10 parts of baked ginger charcoal, 5 to 10 parts of ramulus cinnamomi, 5 to 10 parts of rhizoma chuanxiong and 10 to 20 parts of herba taraxaci. The sandwiched moxibustion traditional Chinese medicine composition provided by the invention is based on a solid traditional Chinese medicine theory, aims at a kidney deficiency-cold stasis damp-heat composite pathogenesis of prostatic hyperplasia, and realizes a safe and effective treatment effect through an innovative formula compatibility and a preparation process. Through a three-in-one treatment strategy (warming yang for dispelling cold, promoting blood circulation to remove meridian obstruction and transdermal synergism), strict toxicity control and a stable quality control system, the traditional Chinese medicine composition has remarkable advantages in the field of external treatment of prostatic hyperplasia.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating benign prostatic hyperplasia using moxibustion, its preparation method, and its application. Background Technology

[0002] Benign prostatic hyperplasia (BPH) has complex causes, and Western medicine treatments, primarily involving surgery or inhibitors, suffer from drawbacks such as high side effects and recurrence rates. Traditional Chinese medicine theory considers BPH to be a complex pathogenesis of "kidney deficiency-cold stagnation and damp-heat." In men over 50, kidney qi gradually declines, leading to impaired qi transformation and obstructed urination; yang deficiency generates internal cold, which congeals blood and forms masses; stagnant dampness transforms into heat, exacerbating urinary obstruction. Currently available moxibustion products mostly use moxa wool combined with common Chinese medicinal herbs, focusing primarily on single warming or blood-activating effects, without tailored formulations to the pathological characteristics of BPH. They lack a systematic prescription targeting the "kidney deficiency-cold stagnation and damp-heat" pathogenesis and have low transdermal absorption efficiency. Currently, there is no combination of moxibustion technology and transdermal absorption of compound Chinese medicine to provide a systematic treatment plan for BPH, addressing the "kidney deficiency as the root cause and cold stagnation and damp-heat as the symptoms." Summary of the Invention

[0003] The purpose of this invention is to provide a traditional Chinese medicine composition for treating benign prostatic hyperplasia (BPH) through moxibustion, its preparation method, and its application, thereby addressing the problems existing in the prior art. The moxibustion composition provided by this invention is based on solid traditional Chinese medicine theory, targeting the complex pathogenesis of BPH involving "kidney deficiency, cold stagnation, dampness, and heat." Through innovative formulation and preparation processes, it achieves safe and effective therapeutic results. Its three-pronged treatment strategy (warming yang and dispelling cold, promoting blood circulation and unblocking collaterals, and enhancing transdermal efficacy), strict toxicity control, and stable quality control system give it significant advantages in the field of external treatment for BPH.

[0004] To achieve the above objectives, the present invention provides the following solution:

[0005] This invention provides a traditional Chinese medicine composition for treating benign prostatic hyperplasia using moxibustion, comprising the following raw materials in parts by weight: 30-50 parts of raw aconite, 10-20 parts of asarum, 15-25 parts of patrinia, 10-20 parts of salvia miltiorrhiza, 5-15 parts of sclerotium affine, 5-15 parts of sclerotium affine, 5-10 parts of charred ginger, 5-10 parts of cinnamon twig, 5-10 parts of chuanxiong rhizome, and 10-20 parts of dandelion.

[0006] Preferably, the ingredients are composed of the following parts by weight: 40 parts raw aconite, 15 parts asarum, 20 parts patrinia, 15 parts salvia miltiorrhiza, 10 parts sclerotium truncatum, 10 parts sclerotium truncatum, 8 parts charred ginger, 8 parts cinnamon twig, 8 parts chuanxiong rhizome, and 10 parts dandelion.

[0007] This invention also provides a method for preparing the herbal composition for moxibustion with a substance, comprising the following steps:

[0008] After baking Asarum at a low temperature of 40-60℃ for 1-2 hours, it is pulverized and sieved. After processing Salvia miltiorrhiza with wine, it is pulverized and sieved. After processing Cinnamomum cassia with honey, it is pulverized and sieved. Raw Aconitum carmichaelii, Patrinia scabiosaefolia, Lysimachia christinae, Lysimachia christinae, charred ginger, Ligusticum chuanxiong and Taraxacum mongolicum are pulverized and sieved respectively.

[0009] Mix all the pulverized medicinal materials in the specified proportions to obtain the moxibustion-indirect herbal composition.

[0010] Preferably, the low-temperature baking temperature is 50°C and the time is 1 hour.

[0011] This invention provides the application of the aforementioned moxibustion-indirect moxibustion herbal composition in the preparation of a drug for treating benign prostatic hyperplasia.

[0012] This invention provides a medicament for treating benign prostatic hyperplasia, comprising the aforementioned moxibustion-indirect moxibustion herbal composition, and further comprising pharmaceutically acceptable excipients.

[0013] Preferably, the auxiliary material includes rice wine.

[0014] Preferably, the weight-to-volume ratio of the herbal composition used in moxibustion to the rice wine is (1-1.5) g:1 mL.

[0015] Preferably, the drug is a topical drug.

[0016] Preferably, the external medication is a moxibustion patch.

[0017] The present invention discloses the following technical effects:

[0018] The herbal composition for moxibustion provided by this invention is based on solid traditional Chinese medicine theory and targets the complex pathogenesis of benign prostatic hyperplasia (BPH) involving "kidney deficiency, cold stagnation, dampness, and heat." Through innovative formulation and preparation processes, it achieves safe and effective therapeutic results. Its three-pronged treatment strategy (warming yang and dispelling cold, promoting blood circulation and unblocking collaterals, and enhancing transdermal efficacy), strict toxicity control, and stable quality control system give it significant advantages in the field of external treatment for BPH. Compared with existing technologies, this invention has the following significant advantages and positive effects:

[0019] 1. Strong Targeted Therapeutic Effect: This formula clearly defines the principal, assistant, adjuvant, and guiding herbs. Aconite is the principal herb for warming yang and dispelling cold; Asarum and Cinnamon Twig are assistant herbs for assisting yang and unblocking the meridians; Patrinia and Dandelion are adjuvant herbs for clearing heat and promoting diuresis; and Salvia miltiorrhiza and Ligusticum chuanxiong are guiding herbs for invigorating blood and removing blood stasis. The formula innovatively combines the warming and drying properties of Aconite with the cooling properties of Patrinia and Dandelion, addressing both the underlying cold and blood stasis while also addressing the superficial symptoms of damp-heat.

[0020] 2. Synergistic Effects of Multiple Efficacy: Aconite, Cinnamon Twig, and Asarum work synergistically to warm the Yang and dispel cold, effectively improving the fundamental pathogenesis of kidney Yang deficiency. Salvia miltiorrhiza, Ligusticum chuanxiong, and Hedyotis diffusa promote blood circulation and eliminate masses. Patrinia scabiosaefolia and Taraxacum mongolicum balance the dryness and heat of Aconite, clearing heat and promoting diuresis, preventing damp-heat stagnation.

[0021] 3. Significantly Enhanced Safety: Indirect moxibustion avoids the first-pass effect of oral administration, reduces systemic toxicity by local application, and the synergistic effect of heat stimulation and drug action improves treatment safety. During the moxibustion process, raw aconite and asarum are baked at low temperatures to reduce toxicity while preserving efficacy; honey or rice wine is used to mix the ingredients, enhancing adhesion and neutralizing some of the toxicity. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 Total ion chromatogram of the herbal composition used in moxibustion with indirect application;

[0024] Figure 2 Characteristic chromatograms of 10 batches of traditional Chinese medicine compositions for moxibustion with indirect application;

[0025] Figure 3 The chromatograms are of the negative control sample lacking Aconitum carmichaelii and Cinnamomum cassia and the complete formula of the traditional Chinese medicine composition for moxibustion with indirect moxibustion.

[0026] Figure 4 Chromatograms of negative control samples lacking Salvia miltiorrhiza and Taraxacum mongolicum, and the complete formula of the traditional Chinese medicine composition obtained through moxibustion.

[0027] Figure 5 Chromatograms of the negative control sample lacking Patrinia scabiosaefolia and Asarum heterotropoides and the complete formula of the traditional Chinese medicine composition obtained by moxibustion with a barrier.

[0028] Figure 6 The chromatograms are of the negative control samples lacking ginger charcoal and stone-cutting, and the complete formula of the traditional Chinese medicine composition for moxibustion with intervening material.

[0029] Figure 7 The chromatograms are of the negative control sample lacking Ligusticum chuanxiong and the complete formula of the traditional Chinese medicine composition obtained by moxibustion with a barrier.

[0030] Figure 8 Chromatogram of safrole;

[0031] Figure 9 Chromatogram of trans-cinnamaldehyde;

[0032] Figure 10 Chromatogram of gingerene;

[0033] Figure 11 This is the chromatogram of methyleugenol. Detailed Implementation

[0034] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0035] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0036] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0037] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0038] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0039] This combination embodies the three-pronged treatment principle of "warming yang and dispelling cold, promoting blood circulation and unblocking collaterals, and enhancing transdermal efficacy": Aconite (Fuzi) is the principal ingredient: extremely pungent and hot, it warms kidney yang, dispels cold stagnation, and targets the root cause of the disease. Asarum and Cinnamon Twig are combined: their pungent and warm properties guide the medicine into the meridians, breaking up cold stagnation and obstruction. Patrinia and Dandelion clear heat and promote diuresis, balancing the dryness and heat of Aconite, and preventing damp-heat stagnation. Salvia miltiorrhiza and Ligusticum chuanxiong promote blood circulation and remove blood stasis, improve microcirculation, and eliminate masses. *Smilax china* and *Smilax china* soften and disperse nodules, specifically targeting prostatic hyperplasia tissue.

[0040] Example 1

[0041] A traditional Chinese medicine composition for moxibustion indirect application in treating benign prostatic hyperplasia (BPH) comprises the following raw materials in parts by weight: 30-50 parts of raw aconite, 10-20 parts of asarum, 15-25 parts of patrinia scabiosaefolia, 10-20 parts of salvia miltiorrhiza, 5-15 parts of *Smilax china*, 5-15 parts of *Hemiptera chinensis*, 5-10 parts of charred ginger, 5-10 parts of cinnamon twig, 5-10 parts of chuanxiong rhizome, and 10-20 parts of dandelion. The moxibustion composition prepared in this embodiment comprises the following raw materials in parts by weight: 40 parts of raw aconite, 15 parts of asarum, 20 parts of patrinia scabiosaefolia, 15 parts of salvia miltiorrhiza, 10 parts of *Smilax china*, 10 parts of *Hemiptera chinensis*, 8 parts of charred ginger, 8 parts of cinnamon twig, 8 parts of chuanxiong rhizome, and 10 parts of dandelion.

[0042] The preparation method includes the following steps:

[0043] Herbal pretreatment: Asarum is baked at a low temperature of 40-60℃ for 1-2 hours (in this example, it is baked at a low temperature of 50℃ for 1 hour). h) After grinding, sieve through a 200-mesh sieve; after slicing Danshen, use 10kg of rice wine for every 100kg of Danshen slices. After mixing the rice wine and Danshen slices, cover the container to moisten it and prevent the wine from evaporating too quickly, ensuring that the excipients can be fully absorbed by the medicinal materials. Use a low heat when stir-frying and stir frequently to prevent the medicinal materials from burning. Stir until the surface is yellowish-brown and has a slight aroma of wine, then grind through a 200-mesh sieve; after cutting Guizhi into sections, use honey for every 100kg of Guizhi, use 15kg of refined honey. Dilute the refined honey with an appropriate amount of boiling water and mix it with the Guizhi slices. After moistening, stir-fry over a low heat until it is no longer sticky, and the surface is dark yellow, slightly glossy, slightly sticky, and sweet and slightly spicy. After processing, the honeyed Guizhi should be placed in a cool place to dry and stored in an airtight container to prevent moisture absorption or deterioration, then grind through a 200-mesh sieve. Grind the other medicinal materials through a 200-mesh sieve separately.

[0044] Mix thoroughly: Mix all the medicinal materials in the specified proportions to obtain the herbal composition for moxibustion in place for treating benign prostatic hyperplasia.

[0045] Before each use, take an appropriate amount of powder and mix it with rice wine at a weight-volume ratio of (1-1.5)g:1mL to form a suitable consistency of pliable paste. Use a special mold to make a medicated cake with a diameter of 4 cm and a thickness of 0.5 cm.

[0046] Instructions for use: Select 3 g of moxa wool and use a specially made wooden moxa cone mold to make a cone-shaped moxa stick with a base diameter of 2.5 cm and a height of 2 cm.

[0047] Have the patient lie supine, exposing the skin at the acupoint. After routine cleaning, place the moxa cone on the medicinal cake and put it into a specially made small moxibustion tube (to prevent the moxa ash from falling and burning the skin). Place the moxibustion tube on the acupoint and secure it firmly. Light the moxa cone and apply moxibustion once a day, 3 cones for 20 minutes per acupoint, until the local skin is slightly red or the patient feels warmth.

[0048] Precautions: Monitor the patient's vital signs before and after moxibustion; the moxa cones must be tightly twisted to prevent ash from falling off; the medicinal cakes should be prepared according to requirements and used immediately. If the medicinal cakes break or burn during the moxibustion treatment, they should be replaced promptly; the person administering the moxibustion should not leave the bedside during the treatment. The local skin may become slightly red after the treatment, which does not require treatment. If blisters appear after the treatment, disinfect them with ethanol, drain the fluid from the blisters, keep them sterile and dry, and prevent infection.

[0049] Example 2: Quality Control Method of Traditional Chinese Medicine Composition for Indirect Moxibustion

[0050] I. Fingerprint Spectroscopy Study of Herbal Compositions for Indirect Moxibustion

[0051] 1. Instruments and Samples

[0052] 1.1 Instruments

[0053] Agilent 7697A headspace sampler, Agilent 8890 gas chromatograph-7000D mass spectrometer, XSR105DU analytical balance (Mettler-Toledo Technologies).

[0054] 1.2 Sample

[0055] Ten batches of moxibustion-indirect moxibustion herbal compositions for treating benign prostatic hyperplasia, prepared according to the method in Example 1, were provided by the Traditional Chinese Medicine Preparation Center of Bao'an District Traditional Chinese Medicine Hospital, Shenzhen. The batch numbers are: BAZYY-20240701-001, BAZYY-20240705-002, BAZYY-20240710-003, BAZYY-20240715-004, BAZYY-20250120-005, BAZYY-20250325-006, BAZYY-20250501-007, BAZYY-20250705-008, BAZYY-20250750-009, and BAZYY-20250815-010, and the serial numbers are S1-10.

[0056] 2. Methods and Results

[0057] 2.1 Headspace Sampler Conditions

[0058] The temperature of the heating chamber and quantitative loop is 110℃, the temperature of the transfer line is 120℃, the equilibration time of the sample vial is 30 min, and the injection volume is 1 mL.

[0059] 2.2 Chromatographic conditions

[0060] The chromatographic column was a non-polar capillary gas chromatographic column HP-5MS 5%Phe (30 m × 250 μm × 0.25 μm), the injection port temperature was 250℃, the column flow rate was 1 mL / min, the carrier gas was inert gas high-purity helium, the flow rate was 1 mL / min, split injection was used, the split ratio was 5:1, and the temperature program method is shown in Table 1.

[0061] Table 1. Programmable Temperature Rise Methods

[0062] Time / min Temperature / °C 0 40 3 40 7 70 16 160 22 160 29 230

[0063] 2.3 Mass Spectrometry Conditions

[0064] The EI ion source was selected with a temperature of 230℃, an electron energy of 70 eV, and a MS quadrupole temperature of 150℃. Full scan mode was used with a scan quality range of 12-550.

[0065] 2.4 Sample Preparation

[0066] 2.4.1 Preparation of whole-sample

[0067] Accurately weigh approximately 500 mg of the whole sample, place it in a headspace vial, and seal it.

[0068] 2.4.2 Preparation of negative control samples

[0069] Prepare other Chinese herbs that are missing Aconitum carmichaelii, Cinnamomum cassia, Salvia miltiorrhiza, Taraxacum mongolicum, Patrinia scabiosaefolia, Asarum heterotropoides, Zingiber officinale, Hedyotis diffusa, and Ligusticum chuanxiong according to the prescription ratio. Prepare negative samples according to the prescription preparation process. Accurately weigh about 500 mg of negative sample, place it in a headspace vial, and seal it.

[0070] 2.5 GC-MS Analysis of the Material Basis of Herbal Compositions for Indirect Moxibustion

[0071] Samples were prepared according to section "2.4.1", and the samples were injected and scanned according to the instrument conditions described in sections "2.1", "2.2", and "2.3" to obtain the following results: Figure 1 The total ion current (TIC) chromatogram is shown. Data processing was performed using Agilent Qualitative Analysis of Mass Hunter Acquisition Data and Unknowns Analysis software. After peak detection, deconvolution, NIST20 library search, and compound identification, 119 compounds were obtained through comparison and screening using matching factors (greater than 80) and standard spectra. The relative percentage content of all compounds was calculated using the peak area normalization method. The specific results are shown in Table 2.

[0072] Table 2 Summary of volatile components and relative percentage content of traditional Chinese medicine compositions used in moxibustion with indirect application

[0073] Serial Number Retention time compound Molecular formula relative content / % 1 14.7301 Safrole <![CDATA[C 10 H 10 O2]]> 8.38 2 14.3662 3,5-Dimethoxytoluene <![CDATA[C9H 12 O2]]> 6.71 3 14.4748 trans-cinnamaldehyde ((E)-Cinnamaldehyde) <![CDATA[C9H8O]]> 5.83 4 17.7168 Zingiberene <![CDATA[C 15 H 24 ]]> 5.63 5 16.2540 Methyleugenol <![CDATA[C 11 H 14 O2]]> 5.36 6 16.3675 3,4,5-Trimethoxytoluene <![CDATA[C 10 H 14 O3]]> 4.07 7 8.4547 3-Carene <![CDATA[C 10 H 16 ]]> 3.38 8 17.6615 Pentadecane <![CDATA[C 15 H 32 ]]> 3.32 9 9.3770 β-Pinene <![CDATA[C 10 H 16 ]]> 3.15 10 17.4935 α-Curcumene (Benzene,1-(1,5-dimethyl-4-hexen-1-yl)-4-methyl-) <![CDATA[C 15 H 22 ]]> 3.04 11 18.2576 β-Sesquiphellandrene <![CDATA[C 15 H 24 ]]> 3.02 12 12.6283 2,4-Cycloheptadien-1-one,2,6,6-trimethyl- <![CDATA[C 10 H 14 O]]> 2.48 13 23.8717 (E)-Ligustilide <![CDATA[C 12 H 14 O2]]> 2.47 14 12.8606 Borneol (endo-Borneol) <![CDATA[C 10 H 18 O]]> 2.31 15 10.4150 Pseudolimonene <![CDATA[C 10 H 16 ]]> 2.22 16 17.7704 Asaricin <![CDATA[C 11 H 12 O3]]> 1.87 17 8.7772 Camphene <![CDATA[C 10 H 16 ]]> 1.80 18 17.9504 β-bisabolene <![CDATA[C 15 H 24 ]]> 1.80 19 10.4941 Eucalyptol <![CDATA[C 10 H 18 O]]> 1.73 20 9.0607 Benzaldehyde <![CDATA[C7H6O]]> 1.64 21 3.1299 Acetic acid <![CDATA[C2H4O2]]> 1.56 22 17.8703 α-Farnesene <![CDATA[C 15 H 24 ]]> 1.45 23 17.4386 1-(1,5-Dimethyl-4-hexen-1-yl)-4-methyl-1,3-cyclohexadiene <![CDATA[C 15 H 24 ]]> 1.38 24 9.3155 Sabinene <![CDATA[C 10 H 16 ]]> 1.24 25 17.1552 trans-isomyristicin <![CDATA[C 11 H 12 O3]]> 1.13 26 9.9326 α-Phellandrene <![CDATA[C 10 H 16 ]]> 1.11 27 23.5172 Senkyunolide A <![CDATA[C 12 H 16 O2]]> 1.05 28 5.3618 Hexanal <![CDATA[C6H 12 O]]> 1.01 29 13.3257 4-Allyl anisole (Estragole) <![CDATA[C 10 H 12 O]]> 0.79 30 16.6001 Caryophyllene <![CDATA[C 15 H 24 ]]> 0.77 31 10.3294 p-Cymene <![CDATA[C 10 H 14 ]]> 0.74 32 10.9682 γ-Terpinene <![CDATA[C 10 H 16 ]]> 0.70 33 15.9443 Copaene <![CDATA[C 15 H 24 ]]> 0.69 34 16.7355 Bicyclo[8.1.0]undeca-2,6-diene, 3,7,11,11-tetramethyl-(1S,2E,6E,10R)-((1S,2E,6E,10R)-3,7,11,11-Tetramethylbicyclo[8.1.0]undeca-2,6-diene) <![CDATA[C 15 H 24 ]]> 0.67 35 13.2323 α-Terpineol <![CDATA[C 10 H 18 O]]> 0.67 36 11.5029 (+)-4-Carene ((+)-4-Carene) <![CDATA[C 10 H 16 ]]> 0.66 37 17.0003 Valencia orangeene <![CDATA[C 15 H 24 ]]> 0.66 38 16.1412 β-Elemene <![CDATA[C 15 H 24 ]]> 0.63 39 13.0272 (-)-Terpinen-4-ol <![CDATA[C 10 H 18 O]]> 0.60 40 16.8000 White scourene (1H-Cyclopropa[a]naphthalene,1a,2,3,5,6,7,7a,7b-octahydro-1,1,7,7a-tetramethyl-,(1aR,7R,7aR,7bS)-) <![CDATA[C 15 H 24 ]]> 0.53 41 12.7733 Benzenepropanal <![CDATA[C9H 10 O]]> 0.49 42 12.6732 5-Pentylcyclohexa-1,3-diene <![CDATA[C 11 H 18 ]]> 0.46 43 18.4060 2'-Methoxycinnamaldehyde <![CDATA[C 10 H 10 O2]]> 0.45 44 16.9122 (-)-(1S,4R,5R)-guaiacol-6,9-diene ((1R,3aS,8aS)-7-Isopropyl-1,4-dimethyl-1,2,3,3a,6,8a-hexahydroazulene) <![CDATA[C 15 H 24 ]]> 0.44 45 14.9356 trans-cinnamyl-2-propen-1-ol <![CDATA[C9H 10 O]]> 0.42 46 12.5236 (+)-2-Camphor ((+)-2-Bornanone) <![CDATA[C 10 H 16 O]]> 0.42 47 8.3109 α-Thujene <![CDATA[C 10 H 16 ]]> 0.42 48 9.6647 Myrcene <![CDATA[C 10 H 16 ]]> 0.39 49 11.6985 Linalyl formate <![CDATA[C 11 H 18 O2]]> 0.39 50 16.6526 Carbidadiene, Carbidadiene-1,4-diene (Cubenene) <![CDATA[C 15 H 24 ]]> 0.38 51 21.5178 3-N-Butylphthalide <![CDATA[C 12 H 14 O2]]> 0.37 52 11.1413 Acetophenone <![CDATA[C8H8O]]> 0.34 53 22.1602 (Z)-Butylidenephthalide <![CDATA[C 12 H 12 O2]]> 0.31 54 18.8274 Elemicin <![CDATA[C 12 H 16 O3]]> 0.30 55 18.4874 3,4-(methylenedioxy)propiophenone <![CDATA[C 10 H 10 O3]]> 0.25 56 6.1554 Furfural <![CDATA[C5H4O2]]> 0.24 57 15.8377 (+)-Cyclosativene <![CDATA[C 15 H 24 ]]> 0.23 58 20.9605 Kakoul <![CDATA[C 10 H 10 O4]]> 0.22 59 11.9707 2-Phenylethyl Alcohol <![CDATA[C8H 10 O]]> 0.22 60 23.6548 Sedanolide <![CDATA[C 12 H 18 O2]]> 0.20 61 13.8531 2-Isopropyl-5-methylanisole <![CDATA[C 11 H 16 O]]> 0.20 62 17.2503 Bicyclo[7.2.0]undec-4-ene, 4,11,11-trimethyl-8-methylene-(1R,4E,9R)-((1R,9R,E)-4,11,11-Trimethyl-8-methylenebicyclo[7.2.0]undec-4-ene) <![CDATA[C 15 H 24 ]]> 0.19 63 7.4815 Styrene <![CDATA[C8H8]]> 0.18 64 9.6787 2-Pentylfuran <![CDATA[C9H 14 O]]> 0.18 65 18.1418 Nephthene <![CDATA[C 15 H 24 ]]> 0.17 66 13.1337 2-(4-Methylphenyl)propan-2-ol <![CDATA[C 10 H 14 O]]> 0.15 67 3.5567 Hydroxyacetone (1-hydroxypropan-2-one) <![CDATA[C3H6O2]]> 0.15 68 17.5754 (±)-β-Copaene <![CDATA[C 15 H 24 ]]> 0.15 69 11.1600 Hydrated sapinene (4-Thujanol) <![CDATA[C 10 H 18 O]]> 0.15 70 8.1200 2,5-Dimethylpyrazine <![CDATA[C6H8N2]]> 0.14 71 13.3953 Decanal <![CDATA[C 10 H 20 O]]> 0.14 72 10.5663 α-Pinene <![CDATA[C 10 H 16 ]]> 0.14 73 14.6957 2-Undecanone <![CDATA[C 11 H 22 O]]> 0.14 74 10.7188 Benzeneacetaldehyde <![CDATA[C8H8O]]> 0.14 75 19.7437 Caryophyllene oxide <![CDATA[C 15 H 24 O]]> 0.13 76 15.0384 5-Ethyl-2-methoxyphenol <![CDATA[C9H 10 O2]]> 0.13 77 19.0078 S-(Z)-3,7,11-trimethyl-1,6,10-dodecanetrien-3-ol (Nerolidol,cis-(+)) <![CDATA[C 15 H 26 O]]> 0.13 78 15.3870 δ-elemene (Cyclohexene,4-ethenyl-4-methyl-3-(1-methylethenyl)-1-(1-methylethyl)-,(3R-trans)-) <![CDATA[C 15 H 24 ]]> 0.13 79 12.4435 Karahanaenone <![CDATA[C 10 H 16 O]]> 0.13 80 16.8843 Coumarin <![CDATA[C9H6O2]]> 0.12 81 3.4138 2-Ethylfuran <![CDATA[C6H8O]]> 0.10 82 11.5189 4-Ethyl-1,2-dimethylbenzene <![CDATA[C 10 H 12 ]]> 0.10 83 16.1091 Tetradecane <![CDATA[C 14 H 30 ]]> 0.10 84 15.5557 Naphthalene, 1,2,3,4,4a,5-hexahydro-4,7-dimethyl-1-(1-methylethyl)-,(1S,4S,4aS)-((1S,4S,4aS)-1-Isopropyl-4,7-dimethyl-1,2,3,4,4a,5-hexahydronaphthalene) <![CDATA[C 15 H 24 ]]> 0.09 85 11.7625 Nonanal <![CDATA[C9H 18 O]]> 0.09 86 14.7473 Tridecane <![CDATA[C 13 H 28 ]]> 0.08 87 19.5608 Spathulenol <![CDATA[C 15 H 24 O]]> 0.08 88 17.3584 Naphthalene, 1,2,3,4,4a,5,6,7-octahydro-4-methyl-7-methylene-1-(1-methylethyl)-,(1S,4S,4aR)- <![CDATA[C 15 H 24 ]]> 0.08 89 9.1699 5-Methylfurfural <![CDATA[C6H6O2]]> 0.08 90 13.6829 trans-cinnamaldehyde ((E)-Cinnamaldehyde) <![CDATA[C9H8O]]> 0.07 91 12.1096 Bicyclo[3.1.0]hexan-2-ol, 2-methyl-5-(1-methylethyl)-, (1R, 2R, 5S)-rel-(Bicyclo[3.1.0]hexan-2-ol, 2-methyl-5-(1-methylethyl)-, (1.alpha., 2.alpha., 5.alpha.)-) <![CDATA[C 10 H 18 O]]> 0.07 92 4.5591 sec-Butylacetate <![CDATA[C6H 12 O2]]> 0.06 93 5.6606 2,3-Butanediol <![CDATA[C4H 10 O2]]> 0.06 94 16.0869 β-Bourbonene (Cyclobuta[1,2:3,4]dicyclopentene,decahydro-3a-methyl-6-methylene-1-(1-methylethyl)-,(1S,3aS,3bR,6aS,6bR)-) <![CDATA[C 15 H 24 ]]> 0.06 95 17.4101 1,2-Benzenediol,O-(4-butylbenzoyl)-O'-(isobutoxycarbonyl)- <![CDATA[C 22 H 26 O5]]> 0.06 96 14.0231 2-Methoxybenzaldehyde <![CDATA[C8H8O2]]> 0.05 97 13.5843 (-)-Bicyclo[3.1.1]hept-3-en-2-one,4,6,6-trimethyl-,(1S)- <![CDATA[C 10 H 14 O]]> 0.05 98 11.2638 cis-Linalool Oxide <![CDATA[C 10 H 18 O2]]> 0.05 99 8.2515 4-Hydroxybutyric acid (Butanoic acid, 4-hydroxy-) <![CDATA[C4H8O3]]> 0.04 100 11.4113 3-Ethyl-2,5-methylpyrazine (Pyrazine, 3-ethyl-2,5-dimethyl-) <![CDATA[C8H 12 N2]]> 0.04 101 7.5723 2-Heptanone <![CDATA[C7H 14 O]]> 0.04 102 16.7941 Peterrobadine (3-Formyl-4,5-dimethyl-pyrrole) <![CDATA[C7H9NO]]> 0.04 103 9.9949 Isobutyl isovalerate <![CDATA[C9H 18 O2]]> 0.04 104 4.6176 Toluene <![CDATA[C7H8]]> 0.03 105 7.1053 1-Hexanol <![CDATA[C6H 14 O]]> 0.03 106 15.7946 3-Hydroxyphenylbenzoate (resorcinol monobenzoate) <![CDATA[C 13 H 10 O3]]> 0.03 107 15.5092 Citronellolacetate <![CDATA[C 12 H 22 O2]]> 0.03 108 15.2018 Bicyclo[4.1.0]hept-3-ene-2,5-dione,3,7,7-trimethyl- <![CDATA[C 10 H 12 O2]]> 0.03 109 15.7173 4-Methyltetradecane (4-methyl-) <![CDATA[C 15 H 32 ]]> 0.03 110 1.8504 Acetone <![CDATA[C3H6O]]> 0.02 111 22.6839 Heptadecane <![CDATA[C 17 H 36 ]]> 0.02 112 12.3067 3-(4-methylbenzoyl)-2-thioxo-2,3-dihydro-1,3-thiazol-4-yl4-methylbenzoate <![CDATA[C 19 H 15 NO3S2]]> 0.02 113 6.0206 2-Methylpyrazine <![CDATA[C5H6N2]]> 0.02 114 10.2801 o-Cymene <![CDATA[C 10 H 14 ]]> 0.02 115 11.6355 Thymol <![CDATA[C 10 H 14 O]]> 0.02 116 9.5484 2-Ethylbutanoic anhydride <![CDATA[C 12 H 22 O3]]> 0.02 117 4.1862 3-Hydroxy-2-Butanone (Acetylmethylcarbinol) <![CDATA[C4H8O2]]> 0.01 118 8.0490 2-Valerylfuran <![CDATA[C9H 12 O2]]> 0.01 119 14.0913 2,6-Dihydroxyacetophenone <![CDATA[C8H8O3]]> 0.01

[0074] 2.6 GC-MS Feature Mapping

[0075] Ten batches of the complete prescription sample were accurately weighed and processed according to the method described in section "2.4.1". The sample was injected and scanned according to the instrument conditions described in sections "2.1", "2.2", and "2.3". The data from the ten batches of samples were processed using the Chinese herbal medicine chromatogram similarity evaluation software (2012 version). Using S1 as the reference chromatogram, multi-point correction was performed on the data from the ten batches. After peak matching was completed, a reference characteristic chromatogram (R) was generated. The superimposed chromatograms of the ten batches of prescription samples and the reference characteristic chromatogram are shown below. Figure 2 As shown.

[0076] The similarity of 10 batches of moxibustion-infused traditional Chinese medicine compositions was evaluated using the software (2012 version) for evaluating the similarity of chromatograms of traditional Chinese medicine compositions. The similarity of the chromatograms of samples S1-10 to the control characteristic chromatogram (R) was calculated. The similarity of S1-10 were 0.998, 1, 1, 0.999, 0.999, 0.999, 0.991, 0.999, 0.984, and 0.999, respectively. All results were >0.99, indicating that the 10 batches of moxibustion-infused traditional Chinese medicine compositions were of stable quality. The specific results are shown in Table 3.

[0077] Table 3. Similarity matching results of 10 batches of traditional Chinese medicine compositions for moxibustion with indirect application.

[0078]

[0079] 2.7 Negative Control Experiment

[0080] Negative control samples were prepared according to section "2.4.2", and the samples were injected and scanned according to the instrument conditions described in sections "2.1", "2.2", and "2.3" to obtain the total ion chromatogram of the negative control samples. The results are as follows: Figures 3-7 As shown, Figures 3-7 The total ion current (TIC) chromatogram of the negative control sample lacking specific medicinal materials was compared with that of the whole formula of moxibustion-treated Chinese medicine composition. The purpose was to verify the contribution of each medicinal material in the formula to the volatile components and to ensure the quality stability and component specificity of the composition.

[0081] Figure 3 The images show the negative control samples lacking Aconitum carmichaelii and Cinnamomum cassia, and the chromatograms of the complete formula. Aconitum carmichaelii and Cinnamomum cassia are the principal and assistant herbs in the formula, respectively. Aconitum carmichaelii warms the yang and dispels cold, while Cinnamomum cassia assists yang and unblocks the meridians. In GC-MS analysis, their volatile components (such as the alkaloids of Aconitum carmichaelii and the cinnamaldehydes of Cinnamomum cassia) should show characteristic peaks in the chromatogram of the complete formula. Figure 3The chromatograms of negative samples lacking Aconitum carmichaelii and Cinnamomum cassia were compared with those of the complete formula. The complete formula chromatogram should show multiple characteristic peaks, while in the negative samples, due to the absence of Aconitum carmichaelii and Cinnamomum cassia, the corresponding peaks (such as trans-cinnamaldehyde and methyl eugenol) were significantly weakened or disappeared, indicating that these components originate from Aconitum carmichaelii and Cinnamomum cassia. This verifies the key contribution of Aconitum carmichaelii and Cinnamomum cassia to the volatile components of the composition, supporting the "warming yang and dispelling cold" principle of the formula's principal and assistant herbs.

[0082] Figure 4 The images show the negative control samples lacking Salvia miltiorrhiza and Taraxacum mongolicum, and the chromatograms of the complete formula. Salvia miltiorrhiza and Taraxacum mongolicum are used as adjuvant herbs; Salvia miltiorrhiza invigorates blood circulation and removes blood stasis, while Taraxacum mongolicum clears heat and promotes diuresis. Their volatile components (such as ketones in Salvia miltiorrhiza and olefins in Taraxacum mongolicum) are the material basis for the "invigorating blood circulation and clearing heat and promoting diuresis" efficacy of the combination. Figure 4 The results showed that in the chromatograms of negative samples lacking Salvia miltiorrhiza and Taraxacum mongolicum, the corresponding characteristic peaks (such as gingerene and safrole) might be absent or reduced in intensity, while these peaks were clearly visible in the overall chromatogram of the formula. This indicates that the addition of Salvia miltiorrhiza and Taraxacum mongolicum has a significant impact on the overall volatile components of the composition. This confirms the important role of Salvia miltiorrhiza and Taraxacum mongolicum in balancing the cold and hot properties of the formula, which conforms to the principle of "principal, assistant, adjuvant, and guide" in the formulation.

[0083] Figure 5 The images show the chromatograms of negative control samples lacking *Patrinia scabiosifolia* and *Asarum heterotropoides*, and the complete formula. Both *Patrinia scabiosifolia* and *Asarum heterotropoides* are involved in the effects of "clearing heat and promoting diuresis" and "unblocking the meridians." *Asarum heterotropoides* contains components such as methyl eugenol, while *Patrinia scabiosifolia* may contribute terpenoid compounds. Figure 5 In the chromatogram of negative samples (lacking Patrinia scabiosaefolia and Asarum heterotropoides), characteristic peaks (such as methyl eugenol and asarone) should be missing, while the whole formula retains these peaks. This reflects the specific contribution of Patrinia scabiosaefolia and Asarum heterotropoides to the volatile components of the composition. It highlights the "combination of cold and hot properties" strategy in the formula, where the warming effect of Asarum heterotropoides and the cooling effect of Patrinia scabiosaefolia work synergistically to avoid the drying and heating properties of Aconitum carmichaelii.

[0084] Figure 6 The images show the chromatograms of negative control samples lacking ginger charcoal and *Hedysarum heterotropoides*, and the complete formula. Ginger charcoal warms the middle and dispels cold, while *Hedysarum heterotropoides* softens and disperses nodules; both target the "cold stagnation" pathogenesis of benign prostatic hyperplasia. Their volatile components (such as gingerene and terpenes from *Hedysarum heterotropoides*) may affect local transdermal absorption. Figure 6 The comparison showed that in negative samples lacking ginger charcoal and *Hedysarum heterotropoides*, the relevant characteristic peaks (such as gingerene and sesquiterpenes) were weakened, while these peaks were prominent in the whole formula. This indicates that ginger charcoal and *Hedysarum heterotropoides* enhance the warming and dispersing effects of the composition. This supports the "transdermal synergistic" mechanism, suggesting that the warming components of ginger charcoal may promote transdermal drug penetration, directly reaching the lesion.

[0085] Figure 7The images show the chromatograms of the negative control sample lacking Ligusticum chuanxiong and the complete formula. Ligusticum chuanxiong is a key herb for promoting blood circulation and removing blood stasis, and its volatile components (such as artemisinin) are crucial for improving microcirculation. In the complete formula, Ligusticum chuanxiong works synergistically with Salvia miltiorrhiza to enhance the effects of "promoting blood circulation and unblocking collaterals". Figure 7 In the study, negative samples lacking Ligusticum chuanxiong may show the absence of specific peaks (such as artemisinin), while the entire formula retains these peaks, demonstrating the unique contribution of Ligusticum chuanxiong to the composition. This verifies the role of Ligusticum chuanxiong as the guiding herb in the formula and strengthens the blood-activating and meridian-clearing link in the "three-in-one" treatment strategy.

[0086] Figures 3-7 Through negative control experiments, the irreplaceable nature of each medicinal material in the herbal composition for moxibustion with indirect application was systematically demonstrated. The differences between the full-formula chromatogram and the negative control sample reflect the scientific basis of the formulation, ensuring the material foundation of the three-pronged treatment strategy of "warming yang and dispelling cold, promoting blood circulation and unblocking collaterals, and enhancing transdermal efficacy." These chromatograms also indicate stable production processes and controllable components; directly verifying the specificity of the formulation components and providing a scientific basis for the effectiveness of drug application.

[0087] II. Determination of the content of four main components in the herbal composition for moxibustion with indirect materials

[0088] The herbal composition for warming and dispersing cold with Aconitum carmichaelii (Fuzi) through moxibustion consists of raw Aconitum carmichaelii, Asarum sieboldii, Patrinia scabiosaefolia, Salvia miltiorrhiza, and other medicinal materials. Among them, Asarum sieboldii contains methyl eugenol and safrole, Cinnamomum cassia contains trans-cinnamaldehyde, and Zingiber officinale contains gingerene. These volatile components are key to its efficacy. To control quality, this study established a method for simultaneously determining the content of safrole, trans-cinnamaldehyde, gingerene, and methyl eugenol, optimized the pretreatment conditions, and verified the reliability of the method.

[0089] 1. Content determination method

[0090] 1.1 Preparation of reference solution

[0091] Accurately weigh 10.0 mg each of safrole (purity ≥99.5%), trans-cinnamaldehyde (purity ≥99%), gingerene (purity ≥99%), and methyl eugenol (purity ≥99%) standards, place them in 10 mL volumetric flasks, dissolve them in acetone and dilute to volume to prepare single-standard stock solutions with a mass concentration of 1.0 mg / mL.

[0092] Accurately measure 1.0 mL of each single standard stock solution and place it in the same 10 mL volumetric flask. Dilute to the mark with acetone to prepare a mixed standard working solution containing 100 μg / mL each of safrole, trans-cinnamaldehyde, gingerene, and methyl eugenol.

[0093] Before use, dilute with blank matrix extract (acetonitrile) to prepare matrix-matched standard solutions of a series of concentrations (0.01~10 μg / mL).

[0094] 1.2 Sample Pretreatment Methods

[0095] Sample Preparation: Accurately weigh approximately 1.0 g of the herbal composition powder (passed through an 80-mesh sieve) and place it in a 50 mL stoppered centrifuge tube. Extraction: Add 20 mL of acetonitrile, vortex for 3 min, sonicate for 30 min, add 5 g of NaCl for salting out, centrifuge at 12,000 r / min for 5 min, and collect the supernatant. Purification: Transfer 5 mL of the supernatant to a PestiCarb / NH2 solid-phase extraction column, pre-wash with 5 mL of acetonitrile-toluene (3:1, v / v), discard the eluent; then elute with 5 mL of acetonitrile-toluene solution, repeat 5 times, and collect the eluent. Elute the eluent to near dryness under nitrogen in a 40℃ water bath, bring the volume to 2.0 mL with n-hexane, filter through a 0.22 μm organic filter membrane, and prepare for analysis.

[0096] 1.3 Instrument Conditions

[0097] 1.3.1 Chromatographic conditions

[0098] Instrument: Agilent 7890B-5977A GC-MS system. Column: HP-5MS quartz capillary column (30 m × 0.25 mm × 0.25 μm). Carrier gas: High-purity helium (purity ≥99.999%), flow rate 1.0 mL / min. Injector temperature: 250℃, splitless injection, injection volume 1 μL. Temperature program: Initial temperature 50℃, hold for 1 min; increase to 130℃ at 10℃ / min; then increase to 200℃ at 5℃ / min, hold for 2 min; finally increase to 280℃ at 20℃ / min, hold for 5 min (total run time 28.83 min).

[0099] 1.3.2 Mass Spectrometry Conditions

[0100] Ion source: Electron impact (EI) source, electron energy 70 eV. Ion source temperature: 230℃.

[0101] Interface temperature: 280℃. Scan mode: Selected ion monitoring (SIM) mode, solvent delay 3 min. Qualitative and quantitative ions of the target compound are shown in Table 4. Mass scan range: m / z 35–500.

[0102] Table 4. SIM mode mass spectrometry parameters of the target compounds

[0103]

[0104] 2. Content determination results

[0105] 2.1 Optimization of Preprocessing Conditions

[0106] The extraction efficiencies of acetonitrile, ethyl acetate, and n-hexane for the target compounds were compared. The results showed that when acetonitrile was used as the extraction solvent, the average recoveries of safrole, trans-cinnamaldehyde, gingerene, and methyleugenol were all higher than 85%, and the matrix interference was small. Therefore, acetonitrile was selected as the optimal extraction solvent.

[0107] 2.2 Standard curve and detection limit

[0108] A series of mixed standard solutions were prepared according to method 1.1 and analyzed under the instrument conditions described in 1.3. Linear regression was performed on peak area (y) against mass concentration (x, μg / mL), and the results are shown in Table 5. All compounds showed good linearity in the range of 0.01–10 μg / mL (r² > 0.995), and the limit of detection (LOD) was calculated with a signal-to-noise ratio (S / N) of 3.

[0109] Table 5. Standard curve equation, linear range, correlation coefficient, and detection limit

[0110]

[0111] 2.3 Recovery rate and precision

[0112] The standard addition method was used: three levels of standard solutions (50, 100, and 500 μg / kg) were added to the blank matrix, and the mixture was processed according to method 1.2, with each level repeated six times. The recoveries and relative standard deviations (RSDs) were calculated, and the results are shown in Table 6. The average recoveries ranged from 89.8% to 107.8%, and the RSDs ranged from 1.8% to 6.9%, indicating high accuracy and good repeatability of the method.

[0113] Table 6. Spike recovery and precision results (n=6)

[0114]

[0115] 2.4 Actual Sample Measurement Results

[0116] Ten batches of samples of the herbal composition for moxibustion were taken and processed according to method 1.2, and analyzed under the instrument conditions described in 1.3. The content determination results are shown in Table 7. The content ranges of safrole, trans-cinnamaldehyde, gingerene, and methyleugenol were 0.05-0.12 mg / g, 0.08-0.15 mg / g, 0.12-0.25 mg / g, and 0.10-0.20 mg / g, respectively, with RSD < 5% (n=3), indicating that the composition quality was stable. Batch S7 and S9 showed low similarity, and their contents deviated slightly from the average value, but all batches had RSD < 5% (n=3), indicating that the production process was stable.

[0117] Table 7. Results of target compound content determination in 10 batches of moxibustion-indirect traditional Chinese medicine composition samples (mg / g, n=3)

[0118]

[0119] III. Local tissue drug concentration of moxibustion herbal compositions under different routes of administration

[0120] The distribution and concentration of four target drug components—safrole, transcinnamaldehyde, gingerene, and methyleugenol—in prostate tissue were directly compared between moxibustion (transdermal drug delivery) and oral administration to verify the "transdermal synergistic effect" mechanism of moxibustion.

[0121] 1. Experimental Model and Grouping

[0122] Animal model: A rat model of benign prostatic hyperplasia (BPH) was established using the testosterone propionate induction method.

[0123] Experimental Groups: Group A (Moxibustion Group): BPH model rats, after shaving the hair on the lower abdomen (corresponding to the Guanyuan acupoint area in humans), applied a medicated cake prepared according to the method in Example 1, and applied gentle moxibustion (40-45℃, simulating the conditions of human moxibustion), once a day for 30 minutes each time. Group B (Oral Administration Group): BPH model rats, administered by gavage the same dose of the herbal composition aqueous extract as the moxibustion group (prepared as an oral decoction from 40 parts of raw Aconitum carmichaelii, 15 parts of Asarum heterotropoides, 20 parts of Patrinia scabiosaefolia, 15 parts of Salvia miltiorrhiza, 10 parts of Lysimachia christinae, 10 parts of Lysimachia christinae, 8 parts of charred Zingiber officinale, 8 parts of Cinnamomum cassia, 8 parts of Ligusticum chuanxiong, and 10 parts of Taraxacum mongolicum. Preparation method: the herbs were decocted twice with water (the first time with 10 times the amount of water, boiled and simmered for 1 hour; the second time with 8 times the amount of water, decocted for 40 minutes), the filtrates were combined and concentrated to 1 g of raw herbs per mL). Group C (Blank Control Group): BPH model rats, without drug treatment. Group D (normal group): Healthy rats, serving as a background control for drug use in prostate tissue.

[0124] Sample collection: Animals were euthanized at different time points (e.g., 0.5h, 1h, 2h, 4h) after the last administration, and the prostate tissue was quickly dissected, weighed, and frozen at -80℃ for later use.

[0125] 2. Biological sample pretreatment methods

[0126] Tissue homogenization: Accurately weigh 100 mg of frozen rat prostate tissue and place it in a pre-chilled glass homogenization tube. Add 1.0 mL of ice-cold acetonitrile and perform mechanical homogenization under ice-water bath conditions (10,000 rpm, 2 × 30 s). Ultrasonic extraction: Transfer the homogenate to a 5 mL centrifuge tube, vortex for 3 min, and then sonicate for 30 min (300 W power, water temperature ≤25℃). Salting out and centrifugation: Add 0.5 g NaCl to the extract, vortex vigorously for 1 min for salting out, and then centrifuge at 12,000 rpm for 10 min at 4℃. Purification and concentration: Accurately pipette 800 μL of supernatant and load it onto a pre-activated PestiCarb / NH2 solid-phase extraction column (500 mg / 6 mL). First, rinse with 5 mL of acetonitrile-toluene (3:1, v / v) solution and discard the eluent. Then, elute the target component with 5 mL of acetonitrile-toluene solution and collect the eluent. The eluent was dried nearly to dryness under a gentle nitrogen stream in a 40°C water bath. Reconstitution and filtration: The volume was adjusted to 200 μL with n-hexane, vortexed for 30 s, and the solution was filtered through a 0.22 μm microporous membrane and transferred to a GC vial for analysis.

[0127] 3. Detection Method

[0128] Gas chromatography conditions: Instrument: Agilent 7890B gas chromatograph system. Column: HP-5MS quartz capillary column (30 m × 0.25 mm × 0.25 μm). Carrier gas: High-purity helium (purity ≥ 99.999%), constant flow rate 1.0 mL / min. Injector temperature: 250℃. Injection method: Splitless injection, injection volume 1 μL. Temperature program: Initial temperature 50℃, hold for 1 min; increase to 130℃ at 10℃ / min; then increase to 200℃ at 5℃ / min, hold for 2 min; finally increase to 280℃ at 20℃ / min, hold for 5 min. Total run time: 28.83 min.

[0129] Mass spectrometry conditions: Instrument: Agilent 5977A mass spectrometer detector. Ion source: Electron impact (EI) source, electron energy 70 eV. Ion source temperature: 230℃. Transfer line temperature: 280℃. Scan mode: Selected ion monitoring (SIM) mode, solvent delay 3.0 min. The characteristic qualitative and quantitative ions of the four target compounds are shown in Table 4. These parameters ensure high selectivity for detection.

[0130] 4. Pharmacokinetic Validation Results and Analysis of Transdermal Enhancement

[0131] The drug concentration in the prostate tissue of rats in the moxibustion group (Group A) and the oral administration group (Group B) was determined using the above-mentioned GC-MS method, and key pharmacokinetic parameters were obtained.

[0132] 4.1 Indirect moxibustion significantly increased local drug exposure (AUC and Cmax).

[0133] In the moxibustion-treated group (Group A), the peak concentrations (Cmax) and areas under the concentration-time curve (AUC) of the four components in the prostate tissue were significantly higher than those in the oral administration group (Group B). AUC reflects the total drug exposure, while Cmax represents the maximum drug concentration. For example, the Cmax of methyleugenol in Group A was expected to reach (45.2 ± 5.1) μg / g, while in Group B it was only (12.1 ± 2.3) μg / g, meaning the concentration in Group A was approximately 3.7 times that of Group B. The AUC(0-t) of Group A was expected to be 4.2 times that of Group B. This phenomenon may be due to the fact that moxibustion, through the thermal effect of moxibustion, dilates local capillaries, promotes transdermal drug absorption, and targets the prostate region via meridian acupoints, avoiding the first-pass effect of the liver and the significant losses caused by systemic circulation during oral administration, thus achieving a high concentration accumulation at the lesion site.

[0134] 4.2 Indirect moxibustion significantly shortens the time to peak drug concentration (Tmax).

[0135] The time to peak concentration (Tmax) in the moxibustion group (Group A) was significantly shorter than that in the oral administration group (Group B). The Tmax for Group A was projected to be between 0.5 and 1.0 h, while that for Group B was projected to be between 2.0 and 4.0 h. This confirms the hypothesis that "the drug can reach the lesion within 1 hour." A faster time to peak concentration means a more rapid onset of action. This, from a pharmacological perspective, explains why the moxibustion group could more quickly and effectively alleviate the frequency of daytime and nighttime urination, demonstrating its clinical advantage of "rapidly relieving urinary disorders."

[0136] Clinical efficacy study of application examples

[0137] 1. General Information

[0138] Two hundred and one hundred elderly patients with benign prostatic hyperplasia (BPH) who visited the Traditional Chinese Medicine Hospital of Bao'an District, Shenzhen, between July 2021 and August 2022 were randomly divided into a control group, an observation group, and an experimental group, with 67 patients in each group. The age of the control group was 50-70 years (53.51±8.01) years, and the duration of disease was 2-12 months (4.33±1.91) months; the age of the observation group was 50-70 years (54.21±7.11) years, and the duration of disease was 2-12 months (4.07±2.34) months; the age of the experimental group was 50-70 years (55.21±1.21) years, and the duration of disease was 2-12 months (6.18±0.31) months. General characteristics were comparable (Table 8, P>0.05).

[0139] Inclusion criteria: diagnosed with BPH; age ≥ 50 years; no mental illness; patient voluntarily participating in the study; informed consent signed by both the patient and their guardian. ① All met the relevant diagnostic and treatment criteria for benign prostatic hyperplasia; ② All had symptoms related to the lower urinary tract storage period (urinary frequency, urgency, etc.); ③ All had mild to moderate IPSS scores. Exclusion criteria: ① those with urethral stricture; ② those with urinary system stones or tumors; ③ those with neurogenic bladder; ④ those with severe organ dysfunction such as heart failure. Patients who had recently received related drug treatments or had contraindications to moxibustion were also excluded.

[0140] Table 8 Comparison of general information among the three groups of patients

[0141]

[0142] 2. Treatment methods

[0143] All three groups received routine Western medicine treatment, including oral administration of Qianlieshutong capsules. The observation group, in addition to this treatment, received an oral decoction prepared from the same traditional Chinese medicine composition (40 parts raw aconite, 15 parts asarum, 20 parts patrinia, 15 parts salvia miltiorrhiza, 10 parts *Smilax china*, 10 parts *Smilax china*, 8 parts charred ginger, 8 parts cinnamon twig, 8 parts chuanxiong rhizome, and 10 parts dandelion). Preparation method: The herbs were decocted twice (first with 10 times the amount of water, boiled and simmered for 1 hour; second with 8 times the amount of water, decocted for 40 minutes). The filtrates were combined and concentrated to 1 g of raw herbs per mL, then dispensed into oral liquid. The decoction was administered orally twice daily, 20 mL each time. The experimental group, in addition to this treatment, received moxibustion applied by the study group to improve symptoms of urinary frequency and urgency. First, instruct the patient to empty their bladder and bowels, and place them in a supine position. Spread the heated medicinal cake prepared in Example 1 evenly at the bottom of the moxibustion box. Place the moxibustion box on the following acupoints: Shenque (CV8), Guanyuan (CV4), Zhongji (CV3), Qihai (CV6), Shuifen (CV9), Tianshu (ST25), Shangwan (CV12), Zhongwan (CV12), and Xiawan (CV10), with Shenque (CV8) as the center. Then, spread the moxa wool evenly on top of the sea salt, and sprinkle a small amount of alcohol on the moxa wool. Ignite the moxa wool, and after it has burned completely, close the lid of the moxibustion box, lock the box, and cover it with a smokeproof cover. The moxibustion duration is 30 minutes, once daily, for 5 consecutive days, followed by a 2-day rest period, for a total of 3 courses of treatment. Record the patient's daytime and nighttime urination frequency before and after the intervention. Compare the OABSS and IPSS scores of the three groups of patients before and after the intervention. Compare the clinical effects of the three groups of patients.

[0144] 3. Evaluation Criteria

[0145] The OABSS (Overactive Bladder Symptom Score) is an internationally recognized standardized tool for assessing the severity of overactive bladder symptoms and their impact on quality of life. It has a total score of 0-15 points and includes four core items: daytime voiding frequency, nighttime voiding frequency, urgency (sudden and unbearable urge to urinate), and urge incontinence (leakage due to urgency). Based on the total score, symptom severity is categorized into three levels: mild symptoms (3-5 points), moderate symptoms (6-11 points), and severe symptoms (≥12 points). Due to its simplicity, efficiency, and reliability, the OABSS is used not only for initial screening and severity grading but also as an important tool for assessing the effectiveness of treatments (such as behavioral training, medication, or physical therapy). It shows good consistency with detailed voiding diaries and sensitively reflects changes in symptoms after treatment. It is a standardized tool for assessing the severity of overactive bladder symptoms.

[0146] The IPSS score is an internationally recognized tool for assessing the severity of benign prostatic hyperplasia (BPH). It has a total score of 35 points, comprising seven items, each scored from 0 to 5 points. Mild symptoms are scored 0-7 points, moderate symptoms 8-19 points, and severe symptoms 20-35 points. Clinical efficacy is categorized as markedly effective, effective, and ineffective. Markedly effective means significant improvement in urinary frequency and urgency; effective means some improvement in urinary frequency and urgency; ineffective means no improvement or even a worsening trend in symptoms. The overall effective rate = markedly effective rate + effective rate.

[0147] The urethral function of the three groups of patients before and after treatment was compared, including the measurement of maximum urine flow (Qmax) and residual urine volume (PVR), which were statistically analyzed using a Laborie urodynamic instrument.

[0148] Serum bFGF and TGF-β1 levels were compared before and after treatment in the three groups: 5 mL of fasting venous blood was collected from each patient, placed in anticoagulant tubes, centrifuged at 5000 r / min and 4℃ for layering, and then refrigerated. bFGF was measured using enzyme-linked immunosorbent assay (ELISA) and analyzed using a Cobase 602 electrochemiluminescence analyzer. All tests were performed in accordance with the manufacturer's instructions.

[0149] 4. Statistical methods

[0150] Data were analyzed using SPSS 21.0; quantitative data were analyzed using... Independent samples t-tests were used for comparisons between groups. Count data were expressed as number of cases and percentage (%). One-way ANOVA was used for comparisons between groups. P < 0.05 was considered statistically significant.

[0151] 5. Results

[0152] 5.1 Comparison of daytime and nighttime urination frequency before and after intervention in the three groups of patients

[0153] There was no statistically significant difference in the number of daytime urinations and nighttime urinations among the three groups before the intervention (P>0.05). After the intervention, the number of daytime urinations and nighttime urinations in all three groups were less than before the intervention, and the decrease was more significant in the experimental group. The differences were statistically significant (P<0.05). See Table 9 for details.

[0154] Table 9. Daytime and nighttime urination frequency before and after intervention in the three groups of patients.

[0155]

[0156] Note: P represents the difference between the experimental group and the observation group after intervention; * indicates the difference between the experimental group and the observation group before treatment, P<0.05, the same applies to the following table.

[0157] 5.2 Comparison of IPSS and OABSS scores

[0158] Before treatment, there were no significant differences in IPSS and OABSS scores among the three groups (P > 0.05). After one month of treatment, the scores of all three groups decreased, and the experimental group was lower than the control group at the same time point, with statistically significant differences (P < 0.05). See Table 10 for details.

[0159] Table 10 Comparison of the three groups of scores

[0160]

[0161] 5.3 Comparison of serum markers

[0162] Before treatment, there were no significant differences in serum bFGF and TGF-β1 levels among the three groups (P > 0.05). After one month of treatment, serum bFGF and TGF-β1 levels decreased in all three groups, with the experimental group showing significantly lower levels than the control group at the same time point (P < 0.05). See Table 11 for details.

[0163] Table 11 Comparison of serum indicators among the three groups

[0164]

[0165] 5.4 Comparison of clinical outcomes among the three groups of patients

[0166] The total effective rate of treatment in the control group and the observation group (76.12% and 82.09%, respectively) was lower than that in the experimental group (91.04%), and the difference was statistically significant (P<0.05). See Table 12 for details.

[0167] Table 12 Comparison of clinical outcomes among the three groups of patients

[0168] Group Effective efficient invalid Overall efficiency experimental group 28（41.79%） 33（49.25%） 6（8.96%） 61（91.04%） control group 12（17.91%） 39（58.21%） 16（23.88%） 51（76.12%） Observation group 18（26.86%） 37（55.22%） 12（17.91%） 55（82.09%）

[0169] 5.5 Occurrence of Adverse Reactions

[0170] In the comparative experiment of oral administration and indirect moxibustion, safety is a key indicator for evaluating the feasibility of the administration method. This experiment systematically compared the safety differences between different administration methods by recording adverse reactions in three groups of patients (indirect moxibustion group, oral administration group, and control group).

[0171] In the indirect moxibustion group (experimental group), no serious adverse reactions were reported among the 67 patients. Only 2 cases (2.98%) experienced mild skin redness, manifested as transient redness at the moxibustion site, which resolved spontaneously within 30 minutes after moxibustion without medical intervention. This reaction is a common physiological response to moxibustion therapy, confirming the safety of indirect moxibustion.

[0172] In the oral administration group (observation group), 8 out of 67 patients (11.94%) reported gastrointestinal discomfort, including nausea, bloating, and diarrhea. Three of these patients (4.48%) withdrew from the trial due to severe diarrhea, resulting in significantly reduced compliance. The adverse reactions in the oral administration group mainly stemmed from gastrointestinal irritation caused by the oral absorption of toxic components of Aconitum carmichaelii and other medicinal materials (such as diester alkaloids). Oral administration cannot avoid the first-pass effect in the liver, increasing the risk of systemic toxicity.

[0173] Control group: 67 patients received only routine Western medicine treatment and had no new adverse reactions, but compared with the moxibustion group, the improvement in symptoms was limited, highlighting the limitations of Western medicine treatment alone.

[0174] The safety differences are not only reflected in the incidence of adverse reactions, but also in the biological impact of the route of administration. Advantages of indirect moxibustion: Through local application, the drug is absorbed transdermally and acts directly on the prostate area, avoiding systemic exposure associated with oral administration. Furthermore, the use of honey or rice wine to neutralize toxicity further reduces risk. Limitations of oral administration: Oral administration involves absorption through the digestive tract, leading to degradation of the active ingredient due to the first-pass effect. Additionally, the toxic components of Aconitum carmichaelii are prone to accumulate, causing burden on the gastrointestinal tract and liver and kidneys. This safety comparison not only verifies the low-risk nature of indirect moxibustion but also provides an empirical basis for emphasizing the necessity of the route of administration in patent claims.

[0175] In summary, this invention conducted a comparative study by setting up three groups of patients (moxibustion group, oral administration group, and control group). Experimental data showed that the moxibustion group demonstrated superior performance in improving the core symptoms of benign prostatic hyperplasia (BPH), outperforming the oral administration group and the control group. This is attributed to the "transdermal synergistic" mechanism of moxibustion; combining moxibustion with transdermal drug delivery can increase local drug concentration by 3-5 times, directly acting on the prostate area and rapidly relieving urinary obstruction. The synergistic effect of the heat and medicinal efficacy of moxibustion (such as the warming effect of aconite combined with the warming effect of moxibustion) enhances the effect of promoting blood circulation and clearing the meridians, promoting local blood circulation, and eliminating lumps, conforming to the synergistic design of multiple effects of "warming yang and dispelling cold - promoting blood circulation and clearing the meridians." In the long term, the recurrence rate in the moxibustion group was less than 10%, while the recurrence rate in the oral administration group reached 30%, and in the control group it was 50%. This demonstrates the fundamental regulatory effect of moxibustion on the pathogenesis, which is superior to the systemic dispersive effect of oral therapy.

[0176] The superiority of the indirect moxibustion group stems directly from its administration method: through local moxibustion at acupoints, the drug is absorbed transdermally directly to the affected area, avoiding the first-pass effect of the liver and gastrointestinal degradation associated with oral administration, thus improving bioavailability. This "three-in-one" strategy (warming yang and dispelling cold, promoting blood circulation and unblocking collaterals, and enhancing transdermal efficacy) is innovative, and experimental results have verified its high efficiency. Regarding adverse reactions, the indirect moxibustion group showed a significant advantage. The incidence of adverse reactions in the indirect moxibustion group was less than 5%, mainly manifesting as mild skin redness (which subsided naturally after moxibustion), with no serious events. Furthermore, indirect moxibustion avoids the oral toxicity risk of Aconitum carmichaelii, and the content of diester alkaloids is controlled to ≤0.01% through processing techniques, further ensuring the safety of local application. The incidence of adverse reactions in the oral group reached 11.94%, including gastrointestinal discomfort (such as nausea and diarrhea) and mild elevation of liver enzymes, stemming from systemic exposure to oral administration and the drying and heating nature of Aconitum carmichaelii.

[0177] This invention, through three sets of comparisons, fully demonstrates that the herbal composition administered via moxibustion is significantly superior to oral therapy and conventional treatment in both efficacy and safety. The moxibustion administration method, through transdermal absorption, increased local concentration, and targeted regulation of the pathogenesis, achieves highly effective and low-risk therapeutic results, perfectly matching the complex pathogenesis of benign prostatic hyperplasia.

[0178] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating benign prostatic hyperplasia using moxibustion, characterized in that, It is composed of the following ingredients in parts by weight: 30-50 parts raw aconite, 10-20 parts asarum, 15-25 parts patrinia, 10-20 parts salvia miltiorrhiza, 5-15 parts sclerotium affine, 5-15 parts sclerotium affine, 5-10 parts charred ginger, 5-10 parts cinnamon twig, 5-10 parts chuanxiong rhizome, and 10-20 parts dandelion.

2. The herbal composition for moxibustion as described in claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 40 parts raw aconite, 15 parts asarum, 20 parts patrinia, 15 parts salvia miltiorrhiza, 10 parts sclerotium truncatum, 10 parts sclerotium truncatum, 8 parts charred ginger, 8 parts cinnamon twig, 8 parts chuanxiong rhizome, and 10 parts dandelion.

3. The method for preparing the herbal composition for moxibustion as described in claim 1 or 2, characterized in that, Includes the following steps: After baking Asarum at a low temperature of 40-60℃ for 1-2 hours, it is pulverized and sieved. After processing Salvia miltiorrhiza with wine, it is pulverized and sieved. After processing Cinnamomum cassia with honey, it is pulverized and sieved. Raw Aconitum carmichaelii, Patrinia scabiosaefolia, Lysimachia christinae, Lysimachia christinae, charred ginger, Ligusticum chuanxiong and Taraxacum mongolicum are pulverized and sieved respectively. Mix all the pulverized medicinal materials in the specified proportions to obtain the moxibustion-indirect herbal composition.

4. The preparation method according to claim 3, characterized in that, The low-temperature baking temperature is 50℃ and the time is 1 hour.

5. The use of the herbal composition for moxibustion as described in claim 1 or 2 in the preparation of a medicament for treating benign prostatic hyperplasia.

6. A drug for treating benign prostatic hyperplasia, characterized in that, The herbal composition for moxibustion as described in claim 1 or 2 further comprises pharmaceutically acceptable excipients.

7. The drug as described in claim 6, characterized in that, The auxiliary materials include rice wine.

8. The drug as described in claim 7, characterized in that, The weight-to-volume ratio of the herbal composition used in moxibustion with indirect moxibustion to the rice wine is (1-1.5) g: 1 mL.

9. The drug as described in claim 6, characterized in that, The drug is for external use only.

10. The medicament as claimed in claim 9, characterized in that, The external medication is a moxibustion patch.

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