Yang-warming cold-eliminating pain-relieving patch based on nanometer and microcapsule transdermal absorption technology

Abstract

The invention discloses a yang-warming cold-eliminating pain-relieving plaster based on a nanometer and microcapsule transdermal absorption technology, and belongs to the technical field of medicines. The yang-warming cold-eliminating pain-relieving plaster comprises an active component and a matrix component, and the active component is wrapped in a microcapsule in a nano-particle form. According to the yang-warming cold-dispelling pain-relieving plaster based on the nanometer and microcapsule transdermal absorption technology, a yang-warming cold-dispelling medicine according to the traditional Chinese medicine theory is combined with the transdermal absorption technology, the dual effects of warming yang, dispelling cold and promoting blood circulation to remove blood stasis are achieved, the transdermal absorption efficiency of the medicine is remarkably improved, the duration time of the medicine effect is remarkably prolonged, and the plaster is not prone to being damaged when being used together with oral medicine. Not only can the pain relieving effect be enhanced, but also the dosage of oral medicines and related adverse reactions can be remarkably reduced.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a yang-warming, cold-dispelling and pain-relieving patch based on nano and microcapsule transdermal absorption technology. Background Art

[0002] Cancer pain is one of the most common and difficult-to-tolerate symptoms in patients with advanced cancer, which seriously affects the quality of life of patients. Especially for patients with constitutions such as spleen and kidney yang deficiency, cold coagulation and blood stasis, and qi stagnation and blood stasis, pain symptoms are often more stubborn and complicated. Clinically, existing treatment methods mainly rely on oral analgesics and topical patches. However, oral analgesics often bring about greater side effects during long-term use, such as constipation, addiction, digestive system damage, renal impairment and other adverse reactions. In addition, since cancer patients are often accompanied by physical weakness and spleen and kidney yang deficiency, simple analgesics are difficult to take into account the overall conditioning of the constitution, especially for pain caused by cold coagulation and blood stasis, qi stagnation and blood stasis, etc., the effect is limited.

[0003] Traditional Chinese medicine external ointment often takes a long time to produce therapeutic effects due to the large particle size of the ingredients and the low transdermal absorption rate, which makes it difficult to meet the needs of cancer pain patients for rapid pain relief. In recent years, with the development of modern medical technology, especially the application of nanotechnology and microcapsule technology, new breakthroughs have been brought to the external preparations of Chinese medicine. Nanotechnology can micronize drug particles to a range of 20-200 nanometers, so that the drug can penetrate the skin barrier faster and act directly on the lesion site, thereby accelerating the absorption of the drug and improving its bioavailability. Microcapsule technology can encapsulate the active ingredients of the drug, form a phased release mechanism, ensure that the drug is gradually released during the application process, prolong the drug effect time, and reduce the burden of frequent replacement of ointments for patients. However, how to combine these technologies with Chinese medicine ingredients to achieve efficient absorption of Chinese medicine ingredients and give full play to the efficacy of external ointments is a problem to be solved in this field. At the same time, most existing products for relieving cancer pain are still based on simple analgesia, lacking the overall conditioning function for patients with cold coagulation blood stasis, qi stagnation blood stasis and spleen and kidney yang deficiency constitution. Summary of the invention

[0004] The purpose of the present invention is to provide a warming yang and dispelling cold pain-relieving patch based on nano and microcapsule transdermal absorption technology to solve the problems existing in the above-mentioned prior art. The warming yang and dispelling cold pain-relieving patch based on nano and microcapsule transdermal absorption technology of the present invention combines the warming yang and dispelling cold medicine in traditional Chinese medicine theory with transdermal absorption technology, and has the dual effects of warming yang and dispelling cold, promoting blood circulation and removing blood stasis, and significantly improves the transdermal absorption efficiency of the medicine and the duration of the drug effect. When used in combination with oral drugs, it can not only enhance the analgesic effect, but also significantly reduce the dosage of oral drugs and related adverse reactions.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] The invention provides a warming yang, dispelling cold and relieving pain patch based on nano and microcapsule transdermal absorption technology. The patch comprises active ingredients and matrix ingredients. The active ingredients comprise the following raw materials in parts by weight: 10-12 parts of aconite root, 8-10 parts of frankincense, 10-15 parts of costusroot, 6-8 parts of asarum, 10-15 parts of wormwood leaf, 10-15 parts of radix rehmanniae, 10-12 parts of ligusticum chuanxiong, 10-12 parts of siler, 10-15 parts of julibrissin bark and 8-10 parts of myrrh; the matrix ingredients comprise the following raw materials: 8-10 parts of ginger oil, 5-8 parts of cassia twig oil, 20-30 parts of honey and 50-60 parts of vaseline; and the active ingredients are encapsulated in microcapsules in the form of nanoparticles.

[0007] Optionally, the active ingredient further comprises auxiliary ingredients, and the auxiliary ingredients account for 16-17 parts by weight.

[0008] Optionally, the auxiliary ingredients include one or more of methyl salicylate, capsaicin extract, chamomile extract and lavender extract.

[0009] Optionally, the particle size of the nanoparticles is 20-200 nm.

[0010] Optionally, the particle size of the microcapsule is 1-10 μm.

[0011] The present invention also provides a method for preparing the warming yang dispersing cold and relieving pain patch, comprising the following steps:

[0012] Firstly, aconite root, frankincense, costusroot, asarum, wormwood leaf, radix rehmanniae, rhizoma chuanxiong, saposhnikovia divaricata, bark of julibrissin and myrrh are ground to obtain fine Chinese medicine powder, and then the ground fine Chinese medicine powder is subjected to nano-grinding treatment to obtain nanoparticles;

[0013] The honey and vaseline are mixed and heated in a water bath until softened and mixed evenly to obtain a mixture, ginger oil and cassia oil are slowly added to the mixture, stirred evenly, and cooled to obtain a matrix component;

[0014] The active ingredients are prepared into microcapsules and then mixed with the matrix components, and then dried and formed into the warming yang, dispersing cold and relieving pain patch.

[0015] Optionally, the particle size of the traditional Chinese medicine fine powder is 120-300 mesh.

[0016] Optionally, the water bath heating temperature is 60-70°C.

[0017] The present invention also provides the use of the warming yang, dispersing cold and relieving pain patch in preparing a product for relieving cancer pain.

[0018] Optionally, the cancer pain is cancer pain caused by malignant tumors, including gastric cancer, liver cancer, pancreatic cancer, rectal cancer, bile duct cancer and breast cancer.

[0019] The present invention discloses the following technical effects:

[0020] The warming yang and dispelling cold pain-relieving patch based on nano- and microcapsule transdermal absorption technology of the present invention combines the warming yang and dispelling cold theory of traditional Chinese medicine with transdermal absorption technology. The nano-processing reduces the drug particle size to 20-200 nanometers, significantly improving its ability to penetrate the skin barrier; at the same time, the drug ingredients are encapsulated by microcapsule technology to achieve long-term sustained release. It not only has the dual effects of warming yang and dispelling cold, and promoting blood circulation and removing blood stasis, but also significantly improves the transdermal absorption efficiency of the drug and the duration of the drug effect.

[0021] The Yang-warming and cold-dispersing pain-relieving patch based on nano- and microcapsule transdermal absorption technology of the present invention is suitable for cancer pain patients and other chronic pain patients, especially patients with cold blood stasis, qi stagnation and blood stasis, spleen and kidney yang deficiency and other constitutions, and has the advantages of high efficiency, durability, mildness, etc. The present invention avoids the side effects of oral drugs through transdermal absorption technology, and can be used in combination with oral drugs to not only enhance the analgesic effect, but also significantly reduce the dosage of oral drugs and related adverse reactions. It is particularly suitable for patients who cannot tolerate or cannot use oral drugs for a long time, and improves the quality of life of patients. DETAILED DESCRIPTION

[0022] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0023] It should be understood that the terms described in the present invention are only for describing a particular embodiment and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. The intermediate value in any stated value or stated range, and each smaller range between any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0024] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0025] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0026] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0027] The raw material composition and dosage of the warming yang, dispersing cold and relieving pain patch based on nano and microcapsule transdermal absorption technology of the present invention are as follows, and the following raw materials are all in parts by weight:

[0028] 10-12 parts of aconite root, 8-10 parts of frankincense, 10-15 parts of costus root, 6-8 parts of asarum, 10-15 parts of wormwood leaf, 10-15 parts of raw rehmannia root, 10-12 parts of chuanxiong, 10-12 parts of siler, 10-15 parts of julibrissin bark, 8-10 parts of myrrh, 8-10 parts of ginger oil, 5-8 parts of cassia twig oil, 20-30 parts of honey and 50-60 parts of vaseline.

[0029] The warming yang and dispelling cold pain-relieving patch based on nano and microcapsule transdermal absorption technology of the present invention combines the warming yang and dispelling cold theory of traditional Chinese medicine with transdermal absorption technology, and has the dual effects of warming yang and dispelling cold and promoting blood circulation and removing blood stasis, and significantly improves the transdermal absorption efficiency of the drug and the duration of the drug effect.

[0030] Among the above raw materials, the principles of compatibility of monarch, minister, assistant and envoy in Chinese medicine formula are:

[0031] (1) Monarch Drug

[0032] Aconite: It is the core drug, which can warm and nourish the original Yang, warm the meridians and dispel cold, and has significant therapeutic effect on pain caused by yang deficiency and cold stagnation.

[0033] (2) Ministerial Drugs

[0034] Frankincense: It promotes blood circulation and qi, dissipates blood stasis and relieves pain. It assists aconite to further improve blood circulation and relieve pain caused by blood stasis.

[0035] Costus root: Mainly used for promoting qi and relieving pain.

[0036] Chuanxiong: Further enhances the effect of promoting blood circulation and removing blood stasis, especially for patients with cancer pain accompanied by local ischemia.

[0037] (3) Adjuvant

[0038] Asarum: dispels wind, relieves cold and relieves pain. It is effective in targeting pain caused by stasis caused by cold evil, and works together with Aconite to enhance the effect of dispelling cold and relieving pain.

[0039] Mugwort: Strengthens the effects of warming the meridians, relieving pain and regulating yang deficiency constitution, while improving patients' symptoms of cold stagnation.

[0040] Fangfeng: It has the effects of dispelling wind and cold, relieving spasms and relieving pain.

[0041] Myrrh: Works synergistically with frankincense to enhance the blood stasis-removing and analgesic functions, and improve the effect of relieving cancer pain.

[0042] (4) Adjuvant

[0043] Ginger oil: warms the middle and dispels cold, promotes transdermal absorption of drugs, is the key ingredient of this transdermal application, and also enhances the warming yang effect.

[0044] Cinnamon Twig Oil: warms the Yang and dredges the meridians, improving the overall drug penetration ability and ensuring that the drug reaches the affected area directly.

[0045] (5) Blending medicine

[0046] Shengdi: Nourishes yin and moistens dryness, alleviates the warming and drying properties of other medicines, prevents the imbalance of dryness and heat caused by yang deficiency constitution, and enhances the synergistic effect of medicines.

[0047] Albizia Julibrissin Bark: Soothes the mind and relieves depression. It targets common anxiety and insomnia symptoms in cancer patients, adds a mind-body regulating effect to the prescription, and optimizes the patient's overall condition.

[0048] The above formula uses aconite as the core monarch drug, warming yang and dispelling cold, supplemented by frankincense, costusroot and other ministerial drugs that promote blood circulation, qi and relieve pain, highlighting the overall regulatory effect of promoting qi, blood circulation and removing blood stasis; adjuvants such as asarum and wormwood further enhance the effect of dispelling cold and relieving pain; ginger oil and cassia oil are the guiding drugs, which enhance the penetration of the drug effect; raw rehmannia and julibrissin bark play a role in harmonizing yin and yang, and taking into account both body and mind, so that the whole formula achieves the effect of treating both the symptoms and the root cause, and harmonizing the inside and outside. The overall compatibility reflects the rigor and scientific nature of the monarch, minister, assistant and envoy of the Chinese medicine prescription, and has a clear targeted treatment feature.

[0049] In the present invention, aconite root, frankincense, costusroot, asarum, wormwood leaf, radix rehmanniae, rhizoma chuanxiong, saposhnikovia divaricata, bark of julibrissin and myrrh are active ingredients, which are first ground to make the particle size reach 120-300 meshes, and then the ground drugs are processed by nano-grinding equipment to control the particle size within the range of 20-200nm, which is more conducive to skin absorption.

[0050] In the present invention, honey, vaseline, ginger oil and cassia oil are used as raw materials for preparing the matrix. Honey provides natural moisturizing effect, enhances the adhesion of the matrix, and has a slight antibacterial effect; vaseline provides lubricity and sealing for the matrix, helps the drug to form a protective film on the skin surface, and prolongs the drug release time; ginger oil warms the middle and dispels cold, promotes transdermal absorption of the drug, and strengthens the overall warming effect; cassia oil warms the yang and dredges the meridians, enhances the permeability of the drug, and assists ginger oil in exerting its effect.

[0051] In some embodiments of the present invention, the raw material composition also includes auxiliary ingredients to enhance the analgesic effect or to achieve a calming and relaxing effect, such as one or more of methyl salicylate, capsaicin extract, chamomile extract and lavender extract.

[0052] In the present invention, the raw materials used to prepare the warming and cold-dispersing pain-relieving patch are all common raw materials in the field and can be obtained through conventional purchasing channels. In some embodiments of the present invention, chamomile extract was purchased from Hubei Wei's Chemical Reagent Co., Ltd., item number: HBWS2024; lavender extract was purchased from Zhenghe (Guangzhou) Biotechnology Co., Ltd., item number: L1-ZL1133; capsaicin extract was purchased from Jiangxi Baolin Natural Flavor Co., Ltd., item number: BL-LJ.

[0053] Examples 1-3 of the present invention are warming yang, dispelling cold and relieving pain patches based on nano and microcapsule transdermal absorption technology obtained with different raw material ratios and preparation parameters, and the preparation method comprises the following steps:

[0054] (1) Medicinal material processing

[0055] Grind aconite root, frankincense, costusroot, asarum, wormwood leaf, radix rehmanniae, rhizoma chuanxiong, saposhnikovia divaricata, bark of julibrissin and myrrh into fine powder with a particle size of 120-300 mesh.

[0056] (2) Nano-processing

[0057] The fine powder after grinding is subjected to nano-grinding treatment to make the particle size reach 20-200nm, so as to obtain traditional Chinese medicine nanoparticles.

[0058] (3) Matrix preparation

[0059] After mixing the honey and vaseline, place them in a water bath and control the temperature at 60-70°C. Heat until both are completely softened and mixed evenly. Stir continuously during the heating process to avoid partial overheating that may cause decomposition of the ingredients.

[0060] Slowly add ginger oil and cinnamon oil to the softened honey and vaseline mixture. Stir thoroughly after each addition to evenly disperse it in the matrix and ensure that the oil and matrix are fully integrated.

[0061] Remove the stirred mixture from the water bath and allow it to cool naturally to room temperature (about 20-25°C). Continue to stir gently during the cooling process to prevent stratification and eventually form a uniform and delicate matrix.

[0062] (4) Microcapsule preparation

[0063] The traditional Chinese medicine nanoparticles (including auxiliary components) obtained in step (2) are prepared into microcapsules with a particle size of 1-10 μm through microencapsulation technology.

[0064] (5) Drug mixing

[0065] The matrix obtained in step (3) and the microcapsules obtained in step (4) are mixed evenly.

[0066] (6) Molding and drying

[0067] The mixed medicine is evenly spread on the medical adhesive tape, and is formed after drying to obtain a warming yang, dispelling cold and relieving pain patch based on nano and microcapsule transdermal absorption technology.

[0068] The raw material ratios and process parameters of the warming yang dispersing cold and relieving pain patches prepared in Examples 1-3 are shown in Table 1.

[0069] Table 1 Raw material ratio and process parameters of Wenyang Sanhan Zhitong Patch

[0070]

[0071]

[0072] Effect verification

[0073] 1. General Information

[0074] Patients who visited the outpatient department of the Department of Oncology, West China Hospital, Sichuan University from April to July 2024 were selected. They were clinically or pathologically diagnosed with malignant tumors and accompanied by cancer pain, with an expected survival period of ≥3 months, ≤3 pain points, and TCM syndrome of yang deficiency and cold stagnation (the pain was severe when cold, relieved when warm, and the skin color was normal). A total of 77 patients were included and divided into an observation group and a control group according to the random number table method. The treatment group had 38 cases, including 21 males and 17 females; aged 30-75 (68.14±6.22) years old; 5 cases of gastric cancer, 15 cases of liver cancer, 7 cases of pancreatic cancer, 2 cases of rectal cancer, and 9 cases of bile duct cancer. The control group had 39 cases, including 20 males and 19 females; aged 27-75 (70.71±4.92) years old; 4 cases of gastric cancer, 14 cases of liver cancer, 10 cases of pancreatic cancer, 3 cases of rectal cancer, 6 cases of bile duct cancer, 1 case of breast cancer, and 1 case of rectal cancer. There was no significant difference in the general information (age, gender, disease type, pain location), pain severity, quality of life, etc. between the two groups of patients.

[0075] 2. Inclusion and Exclusion Criteria

[0076] Inclusion criteria:

[0077] (1) Patients aged ≥18 years diagnosed with malignant tumors by pathological examination; (2) Patients diagnosed with cancer pain, with the degree of pain complained of using the numerical rating scale (NRS) with scores of 1-3 for mild, 4-6 for moderate, and 7-10 for severe; (3) Patients with a survival period of >3 months; (4) Patients with no history of drug allergy; (5) Patients with a clear and fixed pain site, no skin ulceration, no local redness, swelling or fever, and TCM diagnosis of yang deficiency and cold stagnation syndrome; (6) Patients without severe liver, kidney, cardiovascular system, respiratory system, or hematopoietic system diseases; (7) The treatment plan was approved by the hospital ethics committee, and the patients voluntarily participated in this study and signed the informed consent form.

[0078] Among them, the key points of Yang deficiency and cold stagnation syndrome differentiation include the following aspects:

[0079] Pain: The pain is aggravated by cold and relieved by warmth. The pain is fixed and often feels like cold pain, stabbing pain or colic.

[0080] Fear of cold: cold limbs, especially hands and feet, which are difficult to warm up even in a warm environment.

[0081] Pale complexion: complexion White, plain, and listless.

[0082] Tongue and pulse: pale and fat tongue, white and smooth tongue coating, deep and slow or weak pulse.

[0083] The clinical manifestations are pain that worsens when exposed to cold and is relieved when exposed to warmth. The skin color is normal, and there is no obvious redness, swelling, heat or pain.

[0084] Exclusion criteria:

[0085] (1) Patients or their family members give up treatment for special reasons; (2) Patients with other serious systemic diseases; (3) Patients with pain caused by other reasons; (4) Patients with mental system diseases; (5) Patients who are allergic to opioids or antipyretic analgesics; (6) Patients with systemic pain or headache caused by brain metastasis; (7) Patients with unexplained rashes or local skin ulcers; (8) Patients who are allergic to topical drugs; (9) Patients who have received radiotherapy, chemotherapy, or targeted or immunotherapy within the past month.

[0086] 3. Treatment methods

[0087] All 77 patients were titrated with oral or intramuscular injection of immediate-release morphine according to the WHO three-step analgesia principle and the National Comprehensive Cancer Network (NCCN) adult cancer pain guidelines. After 24 hours, they were converted to sustained-release opioid preparations for oral administration, and immediate-release morphine titration was given when breakthrough pain occurred. On this basis, the treatment group was given the warming yang and cold-dispersing analgesic patch prepared in Example 2 for external use. Usage: Clean and wipe the local skin with warm water, apply the analgesic patch to the painful area (Ashi point), apply it to each area for 6 hours, once a day, and 7 days is a course of treatment. Closely observe the patient's reaction, whether pain, blisters, allergies, infections, etc. occur, and take corresponding measures.

[0088] 4. Observation indicators

[0089] (1) Main outcome measures: Numerical pain rating scale (NRS) was used for evaluation before and after treatment. 1-3 points: mild pain, tolerable; 4-6 points: pain that affects sleep, but still tolerable; 7-10 points: gradually intense pain, unbearable pain, affecting appetite and sleep. A reduction of 3 points in pain score was considered effective. (2) Secondary outcome measures: the number of breakthrough pains in the two groups during treatment; the equivalent morphine consumption on the first day and throughout the treatment. (3) Quality of life evaluation was based on the 2011 Quality of Life Scale (QOL) of the New Oncology Nursing, which included 12 aspects: appetite, spirit, sleep, fatigue, pain, family understanding and cooperation, colleagues’ understanding and cooperation, one’s own understanding of cancer, attitude towards treatment, daily life, adverse reactions to treatment, and facial expressions. The full score was 60 points, with poor quality of life being <20 points, poor being 20-30 points, average being 31-40 points, good being 41-50 points, and excellent being 51-60 points. (4) Adverse reactions: observe and record the common adverse reactions such as nausea, vomiting, constipation, and drowsiness in the two groups of patients after taking oral morphine hydrochloride sustained-release tablets; observe and record the adverse reactions of traditional Chinese medicine analgesic mud moxibustion and external application of Ashi acupoints.

[0090] 5. Statistical methods

[0091] SPSS23.0 statistical software was used for analysis. The measurement data were expressed as mean ± standard deviation (x ± s). Paired t-test was used to compare the measurement data before and after treatment. Two independent sample t-test was used to compare the groups. The rank sum test was used to compare the rank data. P < 0.05 was considered statistically significant.

[0092] 6. Results

[0093] (1) Pain score

[0094] Table 2 shows that there was no significant difference in NRS scores between the two groups before treatment (P>0.05). After treatment, the NRS score of the treatment group was lower than that of the control group (P<0.05), and the analgesic effect of the treatment group was better than that of the control group, indicating that the analgesic effect of the analgesic patch combined with morphine hydrochloride sustained-release tablets was better than that of morphine hydrochloride sustained-release tablets alone.

[0095] Table 2 NRS scores of the two groups of patients before and after treatment (points, x±s)

[0096]

[0097] (2) Quality of life evaluation

[0098] Table 3 shows that there was no significant difference in the quality of life (QOL) scores between the two groups before treatment (P>0.05). The quality of life scores of the treatment group were higher than those of the control group after treatment (P<0.05), indicating that the pain relief patch combined with morphine hydrochloride sustained-release tablets can improve the quality of life of patients with moderate to severe cancer pain.

[0099] Table 3 Evaluation of quality of life of patients in the two groups after the treatment (score, x±s)

[0100]

[0101] (3) Adverse reactions of morphine hydrochloride sustained-release tablets and pain-relieving patches

[0102] Table 4 shows that statistical analysis of nausea, vomiting, drowsiness and constipation caused by morphine hydrochloride sustained-release tablets showed no significant difference in the degree of nausea, vomiting and drowsiness between the treatment group and the control group (P>0.05). There was a significant difference in constipation symptoms between the two groups (P<0.05), and the degree of constipation in the treatment group was lighter than that in the control group. No adverse reactions occurred in the treatment group using the pain-relieving patch.

[0103] Table 4 Comparison of adverse reactions between the two groups (cases)

[0104]

[0105] (4) Comparison of weekly pain episodes, first-day and total morphine consumption

[0106] In terms of the number of weekly breakthrough pains, the number of weekly breakthrough pains in the treatment group with mild pain and moderate to severe pain was significantly different from that in the control group (P < 0.01). In terms of the first-day morphine consumption, there was no statistical difference between the treatment group with mild pain and moderate to severe pain and the control group (P > 0.05). In terms of the total morphine consumption, the difference between the treatment group with mild pain and moderate to severe pain and the control group was statistically significant (P < 0.01). See Table 5.

[0107] Table 5 Comparison of weekly breakthrough pain frequency, first day and total morphine consumption

[0108]

[0109]

[0110] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A warming yang, dispelling cold and relieving pain patch based on nano and microcapsule transdermal absorption technology, characterized in that: The invention comprises active ingredients and matrix ingredients. The active ingredients comprise the following raw materials in parts by weight: 10-12 parts of aconite root, 8-10 parts of frankincense, 10-15 parts of costusroot, 6-8 parts of asarum, 10-15 parts of wormwood leaf, 10-15 parts of radix rehmanniae, 10-12 parts of ligusticum chuanxiong, 10-12 parts of siler, 10-15 parts of bark of albizzia and 8-10 parts of myrrh; the matrix ingredients comprise the following raw materials: 8-10 parts of ginger oil, 5-8 parts of cassia twig oil, 20-30 parts of honey and 50-60 parts of vaseline; and the active ingredients are encapsulated in microcapsules in the form of nanoparticles.

2. The warming yang dispersing cold and relieving pain patch according to claim 1, characterized in that: The active ingredient also includes auxiliary ingredients, and the auxiliary ingredients account for 16-17 parts by weight.

3. The warming yang dispersing cold and relieving pain patch according to claim 2, characterized in that: The auxiliary ingredients include one or more of methyl salicylate, capsaicin extract, chamomile extract and lavender extract.

4. The warming yang dispersing cold and relieving pain patch according to claim 1, characterized in that: The particle size of the nanoparticles is 20-200 nm.

5. The warming yang dispersing cold and relieving pain patch according to claim 1, characterized in that: The particle size of the microcapsule is 1-10 μm.

6. A method for preparing the warming yang dispersing cold and relieving pain patch according to any one of claims 1 to 5, characterized in that: The steps include: The active ingredients of aconite, frankincense, costusroot, asarum, wormwood, radix rehmanniae, rhizoma chuanxiong, saposhnikovia divaricata, bark of julibrissin and myrrh are firstly ground to obtain fine Chinese medicine powder, and then the ground fine Chinese medicine powder is subjected to nano-grinding treatment to obtain nanoparticles; The honey and vaseline are mixed and heated in a water bath until softened and mixed evenly to obtain a mixture, ginger oil and cassia oil are slowly added to the mixture, stirred evenly, and cooled to obtain a matrix component; The active ingredients are prepared into microcapsules and then mixed with the matrix components, and then dried and formed into the warming yang, dispersing cold and relieving pain patch.

7. The preparation method according to claim 6, characterized in that: The particle size of the traditional Chinese medicine fine powder is 120-300 meshes.

8. The preparation method according to claim 6, characterized in that: The water bath heating temperature is 60-70°C.

9. Use of the warming yang dispersing cold and relieving pain patch according to any one of claims 1 to 5 in preparing a product for relieving cancer pain.

10. The use according to claim 9, characterized in that: The cancer pain is cancer pain caused by malignant tumors, including gastric cancer, liver cancer, pancreatic cancer, rectal cancer, bile duct cancer and breast cancer.

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