External acupoint sticking, preparation method and application thereof

Abstract

This invention relates to a topical acupoint patch, its preparation method, and its application, comprising the following raw materials in parts by weight: 45-55 parts of Cuscuta chinensis, 45-55 parts of Psoralea corylifolia, 45-55 parts of Loranthus parasiticus, 45-55 parts of Acanthopanax senticosus, 45-55 parts of Ligusticum chuanxiong, 45-55 parts of Lycopodium clavatum, and 15-25 parts of Zanthoxylum bungeanum. The topical acupoint patch of this invention has a therapeutic effect on knee osteoarthritis, especially on knee osteoarthritis of the kidney deficiency and blood stasis type.

Description

Technical Field

[0001] This invention relates to a topical acupoint patch, its preparation method, and its application, belonging to the field of traditional Chinese medicine preparation technology. Background Technology

[0002] In Traditional Chinese Medicine (TCM), knee osteoarthritis (KOA) falls under the categories of "knee pain" and "bone pain." Ancient physicians believed that the changes were related to the patient's age, constitution, and season. The etiology and pathogenesis include wind-cold-dampness, deficiency of the liver, spleen, and kidneys, stagnation of the meridians, and obstruction by phlegm and dampness. In clinical practice, kidney deficiency and blood stasis syndrome is one of the syndrome types of this disease. This is related to the deficiency of kidney essence in this population. Long-term deficiency of kidney essence often leads to blood stasis. The combination of deficiency and excess is the main pathogenesis of the disease, which is characterized by recurrent attacks and lingering symptoms.

[0003] Liver and kidney deficiency type and phlegm-blood stasis type are among the three major syndrome types in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," which conform to the common pathogenesis of KOA (Korean Osteopathy) with mixed deficiency and excess in clinical practice. The *Huangdi Neijing* states, "When Bi (a type of obstruction) is in the bones, it is heavy; when it is in the vessels, the blood congeals and does not flow." Its occurrence is due to original kidney deficiency and secondary blood stasis, with external pathogenic factors acting as a trigger. In the relationship between deficiency and excess, middle-aged and elderly patients suffer from malnourishment of the tendons and bones due to liver and kidney insufficiency. The disease initially affects the meridians, later penetrating deeper into the tendons and bones, resulting in insufficient Qi and blood, and impaired circulation.

[0004] Blood stasis, flowing to the joints, coupled with external pathogenic factors, easily leads to knee osteoarthritis, a common clinical manifestation of kidney deficiency and blood stasis type knee osteoarthritis. Clinical symptoms mainly include redness and swelling at the affected area, localized distending pain aggravated by pressure, fixed pain location, poor mobility, and difficulty in joint flexion and extension. It may also be accompanied by lower back and knee weakness, tinnitus, hearing loss, insomnia, forgetfulness, a purplish-dark tongue with ecchymosis, a thin white coating, and a wiry, thready, and hesitant pulse. Kidney deficiency and blood stasis syndrome is a complex condition involving both deficiency and excess. The fundamental treatment for this syndrome lies in tonifying the kidneys and replenishing essence, supplemented by promoting blood circulation and removing blood stasis. Sufficient essence nourishes the tendons and bones, and the removal of blood stasis ensures smooth blood flow.

[0005] The main symptoms of knee osteoarthritis include knee pain, swelling, stiffness, bony enlargement, and difficulty walking. This disease primarily affects middle-aged and elderly people, with the incidence increasing with age, and women having a higher prevalence than men. Western medicine treatment for knee osteoarthritis mainly involves nonsteroidal anti-inflammatory drugs (NSAIDs), chondroprotective agents, intra-articular injections of sodium hyaluronate, and surgery. To date, no medication can significantly reverse the pathological progression of osteoarthritis, and surgical treatment is expensive and carries a high risk of complications.

[0006] Acupoint application is an important external therapy in Traditional Chinese Medicine (TCM), belonging to the category of transdermal drug delivery. It integrates traditional acupuncture and drug therapy, essentially a treatment that combines medication, acupoints, and meridians. Meridians are the channels for the flow of Qi and blood in the body, connecting the upper and lower parts, communicating between the interior and exterior, and linking the internal organs and the body surface to form a unified whole, maintaining a relatively balanced and coordinated state of bodily functions. Acupoint application therapy involves applying a self-formulated drug to specific acupoints. Through the meridian effect and stimulation of active ingredients, it is absorbed through the skin to exert multiple effects.

[0007] Based on this, the present invention proposes a drug delivery method using acupoint application to treat knee osteoarthritis, especially the type of knee osteoarthritis caused by kidney deficiency and blood stasis. Summary of the Invention

[0008] This invention addresses the shortcomings of existing technologies by providing a topical acupoint patch, its preparation method, and its application. The specific technical solution is as follows:

[0009] A topical acupoint patch, comprising the following raw materials in parts by weight:

[0010] 45-55 parts by weight of Cuscuta chinensis, 45-55 parts by weight of Psoralea corylifolia, 45-55 parts by weight of Mistletoe, 45-55 parts by weight of Acanthopanax senticosus, 45-55 parts by weight of Ligusticum chuanxiong, 45-55 parts by weight of Lycopodium clavatum, and 15-25 parts by weight of Zanthoxylum bungeanum.

[0011] A further improvement is made to the external acupoint patch, which includes the following raw materials in parts by weight:

[0012] 50 parts by weight of Cuscuta chinensis, 50 parts by weight of Psoralea corylifolia, 50 parts by weight of Mistletoe, 50 parts by weight of Acanthopanax senticosus, 50 parts by weight of Ligusticum chuanxiong, 50 parts by weight of Lycopodium clavatum, and 20 parts by weight of Zanthoxylum bungeanum.

[0013] A further improvement is provided: a method for preparing an external acupoint patch, comprising the following steps:

[0014] The following ingredients are ground together and mixed evenly to obtain the medicinal powder: Cuscuta chinensis, Psoralea corylifolia, Loranthus parasiticus, Acanthopanax senticosus, Ligusticum chuanxiong, Lycopodium clavatum, and Zanthoxylum bungeanum.

[0015] Simply mix the powdered medicine with honey and water until it forms a paste.

[0016] Further improvements were made, with the mass ratio of medicinal powder, water, and honey being 100:(30-100):(10-50).

[0017] A further improvement is the application of a topical acupoint patch in the treatment of knee osteoarthritis.

[0018] A further improvement is made, the knee osteoarthritis described is a type of knee osteoarthritis caused by kidney deficiency and blood stasis.

[0019] A further improvement involves applying the external acupoint patch to the knee joint.

[0020] The beneficial effects of this invention are:

[0021] 1. The external acupoint patch described in this invention is made from natural medicinal raw materials. It is applied to the local area of ​​the knee joint and has a penetrating effect on local acupoints or skin. It has a therapeutic effect on knee osteoarthritis, especially for knee osteoarthritis of the kidney deficiency and blood stasis type.

[0022] 2. The external acupoint patch described in this invention has no iatrogenic infection, no toxic side effects, and is highly safe.

[0023] 3. The preparation and use of the external acupoint patch described in this invention are very convenient, and its application range is wide.

[0024] 4. The combination of dodder seed, psoralea corylifolia, mistletoe, eleutherococcus senticosus, chuanxiong rhizome, lycopodium clavatum, and Sichuan pepper has the effect of treating knee osteoarthritis. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0026] Example 1

[0027] A topical acupoint patch, the formula of which is as follows:

[0028] 50g of Cuscuta chinensis, 50g of Psoralea corylifolia, 50g of Loranthus parasiticus, 50g of Acanthopanax senticosus, 50g of Ligusticum chuanxiong, 50g of Lycopodium clavatum, and 20g of Zanthoxylum bungeanum.

[0029] Grind dodder seed, psoralea corylifolia, mistletoe, eleutherococcus senticosus, chuanxiong rhizome, lycopodium clavatum, and Sichuan pepper together into powder and mix evenly to obtain medicinal powder; add honey and water to the medicinal powder and mix into a paste to obtain the final product.

[0030] In some embodiments, the amount of honey and water used can be adjusted slightly according to the actual situation. For example, 100g of powder, 70g of water, and 30g of honey can be used.

[0031] When using, apply the paste directly to the knee joint. It can promote blood circulation, remove blood stasis, dispel wind and dampness, warm the meridians and promote blood flow, and relieve pain. It can effectively improve blood supply to organs and limbs, relieve inflammation and edema, and achieve the purpose of anti-inflammatory and analgesic effects.

[0032] Explanation: Psoralea corylifolia and Cuscuta chinensis are the principal herbs, which tonify the liver and kidneys, replenish essence and marrow; Loranthus parasiticus and Acanthopanax senticosus are the assistant herbs, which assist the principal herbs in tonifying the liver and kidneys; Ligusticum chuanxiong is added to invigorate blood circulation, remove blood stasis, regulate qi and relieve pain; Lycopodium clavatum is added to dispel wind and dampness, relax muscles and tendons; Zanthoxylum bungeanum is added as the guiding herb to open the pores, promote blood circulation and guide the medicine into the skin; In summary, this formula can not only treat meridian obstruction, but also supports the body's resistance without aiding the pathogenic factors, and replenishes essence and blood without being greasy.

[0033] Fang Zhong:

[0034] Psoralea corylifolia, entering the kidney and spleen meridians, is bitter, pungent, and warm in nature. It tonifies the kidneys and strengthens yang, as well as invigorates the spleen and stomach. It is an annual erect herb belonging to the legume family (Fabaceae). Isopsoralen is the main active ingredient in Psoralea corylifolia absorbed into the bloodstream. Its main function is to disrupt the dynamic balance of bone metabolism, stimulating the exosomes secreted by bone marrow mesenchymal stem cells to release circ-8604, which targets miR-26b-3p / ERα to regulate the proliferation and differentiation of osteoblasts MC3T3-E1, thereby promoting bone resorption and bone formation.

[0035] Cuscuta seed, entering the kidney, liver, and spleen meridians, is sweet and warm in nature. It is the dried, mature seed of *Cuscuta chinensis*, a plant in the Convolvulaceae family. Its main components are flavonoids, phenolic acids, polysaccharides, and lignins. It has the effects of nourishing the liver and kidneys, strengthening essence, reducing urination and diarrhea, calming the fetus, and improving eyesight. Cuscuta seed also has active compounds that induce hypoxia, endocrine resistance, and apoptosis signaling pathways, thus playing a role in treating PMOP (periosteal osteoporosis). Network pharmacology analysis suggests that Cuscuta seed mainly affects bone metabolism-related pathways and multiple metabolic pathways in vivo through multiple targets and systems, inhibiting osteoclast differentiation and biological activity, reducing bone loss, and promoting further differentiation and activity of osteoblasts.

[0036] Mistletoe dispels wind and dampness, nourishes the liver and kidneys, strengthens muscles and bones, and relieves pain. It is especially effective in treating pain caused by long-term liver and kidney deficiency in arthralgia.

[0037] Acanthopanax bark is pungent, sweet, and warm. It can dispel wind and dampness, and nourish the liver and kidneys. It is also suitable for the elderly, those who are weak, or those who have been ill for a long time.

[0038] Chuanxiong, a qi-regulating herb in the blood, is an important component of the famous traditional Chinese medicine formula Siwu Tang recorded in "Xian Shou Li Shang Xu Duan Mi Fang". It can not only promote blood circulation and remove blood stasis, but also has the effects of regulating qi, relieving stagnation and pain.

[0039] The herb *Shenjincao* is good at dispelling wind and dampness, and relaxing muscles and tendons. It can be taken internally or used as a decoction for external washing.

[0040] Sichuan pepper is pungent and warm, and its downward-moving properties are excellent for warming the waist and knees. It can open the pores, unblock joints, promote blood circulation, and relieve swelling and pain. Its pungent and warm nature makes it a representative of the "rich in flavor and aroma" described by Wu Shangxian, a famous physician of the Qing Dynasty, who considered it a culmination of external treatment methods in traditional Chinese medicine. Its main active ingredient, the volatile oil, contains a variety of compounds with clear anti-inflammatory and analgesic effects. Moreover, its anti-inflammatory and analgesic effects can be greatly enhanced after processing. At the same time, its pore-opening effect as an external medicine can promote the absorption of other external medicines, expel wind and cold, and enhance the wind-dispelling and dampness-removing effects when combined with *Lycopodium clavatum*.

[0041] Characterization Experiments

[0042] Thirty-six New Zealand white rabbits were randomly divided into four groups: a normal control group, a model group, an acupoint application group, and a Western medicine group, with nine rabbits in each group. Except for the normal control group, the other three groups underwent a kidney deficiency and blood stasis type KOA model: first, a kidney deficiency model was established, and after 8 weeks, a blood stasis model and an osteoarthritis model were simultaneously established. The specific steps are as follows:

[0043] ① The kidney deficiency model was modeled using the ovarian removal method. Ketamine (0.1g / kg) was administered via intraperitoneal injection for anesthesia. Under aseptic conditions, the ovaries were accessed via a midline approach along the lumbar side. The lumbar fascia was separated, the ovaries were exposed, the fallopian tubes and surrounding blood vessels were ligated, and both ovaries were removed. The patients were observed for 2 months.

[0044] ② The blood stasis model was established using a combination of adrenocortical hormones and epinephrine. Hydrocortisone 10 mg / kg was administered intramuscularly once daily, followed by a subcutaneous injection of epinephrine 0.36 mg / kg after 13 days of treatment.

[0045] ③ The osteoarthritis model uses the classic Hulth model, a classic surgical modeling method. The specific steps are as follows: After anesthetizing the animal, place it supine on the operating table. Under aseptic conditions, make a longitudinal incision of approximately 2 cm on the medial side of both knee joints to expose the knee joint. Then, sever the anterior and posterior cruciate ligaments and the medial collateral ligament, completely remove the medial meniscus, and preserve the articular cartilage surface. Postoperatively, the injured limb is not immobilized and is allowed free movement. Antibiotics may be administered appropriately to prevent infection. Seven days postoperatively, the animal is driven away twice daily for 30 minutes. A clear osteoarthritis model is obtained after 4 weeks.

[0046] After successful model establishment, the model group received no treatment, while the acupoint application group received the acupoint application of the drug described in Example 1, and the Western medicine group received topical diclofenac sodium. Treatment was administered three times per week for two weeks. The Lequesne MG behavioral score was used to assess the degree of knee joint damage in each group before and after the intervention. Serum prostaglandin E2 and interleukin-1β levels were detected by ELISA.

[0047] Table 1. Lequesne MG behavioral scores for each group of rabbits (points). )

[0048]

[0049] Note: Compared with the model group, ① P<0.05; compared with the Western medicine group, ② P<0.05.

[0050] Table 2. Expression of serum PGE-2 and IL-1β in rabbits of different groups after treatment.

[0051]

[0052] Note: Compared with the normal group, ① P<0.05; compared with the model group, ② P<0.05; compared with the Western medicine group, ③ P<0.05.

[0053] The Lequesne-MG score primarily assesses four aspects: local pain response, gait, range of motion, and joint swelling. Local pain response is assessed by pressing the affected area with fingers, graded on a scale of 0-3 (4 levels, 0-3 points), with higher scores indicating greater intensity. Gait is assessed by observing the gait of the affected limb during walking or running, graded on a scale of 0-3 (4 levels, 0-3 points), with higher scores indicating greater intensity. Range of motion is assessed by assessing the range of motion of the knee joint, graded on a scale of 0-3 (4 levels, 0-3 points), with higher scores indicating smaller range of motion. Joint swelling is assessed by observing the degree of swelling in the affected limb, graded on a scale of 0-2 (0-2 points), with higher scores indicating greater swelling.

[0054] PGE-2 originates from macrophages and is a non-protein, non-polymorphic substance produced by fatty acid metabolism. It belongs to the prostaglandin family and has important biological functions such as protecting the gastric mucosa, increasing renal blood flow, vasodilation, anticoagulation, and participation in inflammatory responses. Inflammation is one of the important pathological bases of KOA (knock-off osteoarthritis). Angiogenesis promotes excessive chondrocyte growth and intrachondral ossification, accelerating osteophyte formation. Data shows that PGE-2 receptors exist in the joint cavity of KOA patients. These receptors bind to PGE-2 and exert their effects. PGE-2, through the accumulation of cyclic adenosine monophosphate (cAMP) in the intercellular space, induces chondrocyte apoptosis and increases osteoclast formation.

[0055] IL-1β is a pro-inflammatory cytokine that is highly expressed in the joint cavity of patients with knee-arthritis (KOA) and can serve as a reference indicator for disease progression. IL-1β is a key factor in the physiological and pathological evolution of KOA and is one of the two subtypes of IL-1. It can be produced autocrinely or promoted by granulocyte-macrophage colony-stimulating factor (AMPF). IL-1β stimulates chondrocytes and synovium to produce PGE2 and cartilage matrix MMPs, which in turn promote chondrocyte apoptosis, inhibit cartilage matrix synthesis, and accelerate cartilage destruction.

[0056] Experimental results show that the acupoint application described in this embodiment can treat knee osteoarthritis, especially the kidney deficiency and blood stasis type of knee osteoarthritis. It can reduce the Lequesne-MG score, PGE-2 content, and IL-1β content in rabbits, and the efficacy is better than that of the Western medicine group (P<0.05).

[0057] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A topical acupoint patch, characterized in that, Made from the following parts by weight of raw materials: Cuscuta chinensis 45-55 parts by weight, Psoralea corylifolia 45-55 parts by weight, Loranthus parasiticus 45-55 parts by weight, Acanthopanax senticosus 45-55 parts by weight, Ligusticum chuanxiong 45-55 parts by weight, Lycopodium clavatum 45-55 parts by weight, Zanthoxylum bungeanum 15-25 parts by weight.

2. The external acupoint patch according to claim 1, characterized in that, Made from the following parts by weight of raw materials: 50 parts by weight of Cuscuta chinensis, 50 parts by weight of Psoralea corylifolia, 50 parts by weight of Mistletoe, 50 parts by weight of Acanthopanax senticosus, 50 parts by weight of Ligusticum chuanxiong, 50 parts by weight of Lycopodium clavatum, and 20 parts by weight of Zanthoxylum bungeanum.

3. The preparation method of an external acupoint patch according to claim 1, characterized in that... Includes the following steps: The following ingredients are ground together and mixed evenly to obtain the medicinal powder: Cuscuta chinensis, Psoralea corylifolia, Loranthus parasiticus, Acanthopanax senticosus, Ligusticum chuanxiong, Lycopodium clavatum, and Zanthoxylum bungeanum. Simply mix the powdered medicine with honey and water until it forms a paste.

4. The preparation method of an external acupoint patch according to claim 3, characterized in that: The mass ratio of the powder, water, and honey is 100:(30~100):(10~50).

5. The application of the external acupoint patch as described in claim 1 in the preparation of a drug for treating knee osteoarthritis.

6. The application of the external acupoint patch according to claim 5 in the preparation of a drug for treating knee osteoarthritis, characterized in that: The knee osteoarthritis described is a type of knee osteoarthritis caused by kidney deficiency and blood stasis.

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