A composition with cough-relieving and phlegm-removing effects and a preparation method thereof

Abstract

This invention provides a composition with antitussive and expectorant effects and its preparation method. The composition comprises raw materials such as Selaginella uncinata, Smilax glabra, Ficus microcarpa, Erythrina variegata, Basil, Cinnamomum cassia, Bambusa textilis, Rehmannia glutinosa, Prunus armeniaca, Pinellia ternata, Fritillaria thunbergii, and Magnolia officinalis. This invention uses a topical patch for administration through acupoint application, which can significantly prolong the cough latency period, reduce the frequency of coughs, and increase the amount of phenol red secreted from the trachea, exhibiting significant antitussive and expectorant effects. It addresses the root cause by tonifying Qi, resolving phlegm, relieving cough, and regulating Qi, and is suitable for coughs with excessive phlegm caused by spleen deficiency and internal dampness, and heat toxicity obstructing the lungs in the Lingnan region.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a composition having antitussive and expectorant effects and its preparation method. Background Technology

[0002] Coughing with excessive phlegm is a common respiratory symptom in clinical practice, which can be caused by various pathogenic mechanisms such as lung heat, phlegm-dampness, lung deficiency, and lung-kidney yin deficiency. The condition is prone to prolonged illness due to external pathogenic factors and weakened vital energy, making children and the elderly, whose vital energy is relatively weak, particularly susceptible. In the Lingnan region, due to its hot and humid climate, residents' coughs are often accompanied by unique pathogenic mechanisms such as spleen deficiency leading to internal phlegm-dampness, lung heat accumulating, and upward flow of qi, placing higher demands on the adaptability of cough-relieving and phlegm-reducing products to these mechanisms and their comprehensive efficacy. Herbal compositions, with their advantages of natural raw materials, low toxicity and side effects, and wide applicability, have become a major research direction in the field of cough-relieving and phlegm-reducing products. Among them, external patches, with their advantages of not requiring oral administration, avoiding gastrointestinal irritation, and convenient application, are particularly suitable for children, the elderly, and those with swallowing difficulties, demonstrating significant clinical demand.

[0003] Currently, existing herbal compositions and topical patches for relieving cough and expectoration still have many technical defects and are difficult to meet actual clinical needs: Existing herbal cough and phlegm-relieving products mostly adopt a formula approach that simply stops coughing and relieves asthma, only addressing local symptoms in the lungs. They neglect the overall conditioning approach of tonifying qi and strengthening the spleen, nourishing the kidneys and yin, and regulating qi and tonifying the body. They cannot replenish the body's vital energy at the root to resist external pathogens, nor do they intervene in advance for the pathogenesis of chronic cough that easily damages kidney yin, resulting in recurrent cough symptoms that are difficult to cure. At the same time, existing products do not take into account the climate and pathogenesis characteristics of the Lingnan region for targeted formulation, and their effect on improving coughs caused by spleen deficiency and phlegm dampness, or heat toxins obstructing the lungs is limited. Summary of the Invention

[0004] In view of this, the present invention proposes a composition with antitussive and expectorant effects and a method for preparing the same, thereby solving the above problems.

[0005] The technical solution of the present invention is implemented as follows: a composition having the effects of relieving cough and resolving phlegm, comprising the following raw materials in parts by weight: 10-30 parts of Selaginella uncinata, 30-70 parts of Smilax glabra, 15-25 parts of Ficus hirta, 2-8 parts of Erythrina variegata, 2-8 parts of dried basil, 5-15 parts of Ardisia crenata, 5-15 parts of Phyllostachys edulis, 10-20 parts of Rehmannia glutinosa, 5-15 parts of Prunus armeniaca, 5-15 parts of Pinellia ternata, 5-15 parts of Fritillaria thunbergii, and 5-15 parts of Magnolia officinalis.

[0006] Preferably, the composition comprises the following raw materials in parts by weight: 20 parts of Selaginella uncinata, 50 parts of Smilax glabra, 20 parts of Ficus microcarpa, 5 parts of Erythrina variegata, 5 parts of dried basil, 10 parts of Aralia elata, 10 parts of Phyllostachys nigra, 15 parts of Rehmannia glutinosa, 10 parts of Prunus armeniaca, 10 parts of Pinellia ternata, 10 parts of Fritillaria thunbergii, and 10 parts of Magnolia officinalis.

[0007] The composition of the present invention is preferably prepared as a topical patch, which is made from the extract of the composition and pharmaceutically acceptable excipients, including oils, honey and penetration enhancers. The excipients work synergistically with the extract to ensure the formability and stability of the patch, and to improve the dissolution and transdermal absorption efficiency of the active ingredients.

[0008] Preferably, the oil includes camellia oil, olive oil, sweet almond oil, or wheat germ oil. All of these oils are natural medicinal plant oils that are skin-friendly, non-irritating to the skin, and can effectively dissolve the fat-soluble active ingredients in the composition, thereby enhancing the skin penetration of the fat-soluble ingredients.

[0009] Preferably, the penetration enhancer is azone, propylene glycol, and carbomer gel matrix, with addition amounts of 0.5-1%, 3-5%, and 30-50% of the total weight of the composition, respectively. Azone is a highly effective transdermal penetration enhancer that can significantly improve the permeability of the stratum corneum and promote the transdermal absorption of active ingredients. Propylene glycol has both moisturizing and penetration-enhancing effects, synergistically enhancing the penetration-enhancing effect with azone while improving the moisturizing properties of the ointment and preventing it from drying out. The carbomer gel matrix, as a molding excipient, enables the ointment to form a stable gel, possessing good adherence and peelability, leaving no residue and not irritating the skin.

[0010] The present invention also provides a method for preparing the above composition, comprising the following steps: S1. Extract preparation: a. Crush the prescribed amount of medicinal materials, pass them through an 80-100 mesh sieve, add 90-95% v / v ethanol at a material-to-liquid ratio of 1:5-8 (g / ml), soak at room temperature for 20-30 hours, and then perform ultrasonic-assisted extraction for 1-3 hours. Filter the mixture, repeat the extraction 1-3 times with the residue, combine the filtrates, and concentrate under reduced pressure at 55-60℃ to recover the ethanol, obtaining alcohol extract A. Crushing the medicinal materials to 80-100 mesh increases the contact area between the medicinal materials and ethanol, improving extraction efficiency. 90-95% v / v ethanol is the optimal extraction solvent for fat-soluble components. Soaking at room temperature combined with ultrasonic-assisted extraction can fully extract fat-soluble antitussive and expectorant active ingredients under mild conditions, avoiding high temperature damage to component activity. Concentration under reduced pressure at 55-60℃ can quickly recover ethanol at low temperature, while ensuring that the active ingredients of alcohol extract A are not lost or destroyed.

[0011] b. Add water to the dregs after alcohol extraction at a ratio of 1:8-10 (g / ml), decoct for 1-2 hours, filter, and concentrate the filtrate to a relative density of 1.10-1.20 (60℃) to obtain water extract B. Water extraction of the dregs after alcohol extraction achieves comprehensive utilization of medicinal materials and avoids resource waste. The water decoction process can fully extract the water-soluble effective components in the medicinal materials and concentrate the water extract B to a relative density of 1.10-1.20, which not only ensures the concentration of water-soluble components but also allows for good integration with subsequent excipients.

[0012] Furthermore, in step S1, the ultrasonic frequency is 20-40kHz and the power is 200-500W. Limiting the ultrasonic frequency to 20-40kHz and the power to 200-500W ensures the cell wall breaking effect while avoiding degradation of effective components due to excessive power and frequency. The ultrasonic temperature of 30-45℃ balances extraction efficiency and component stability. S2. Matrix Preparation: Heat the oil to 60-70℃, add the alcohol extract A, and stir until dissolved to form the oil phase; separately, mix honey with the water extract B to form the aqueous phase. Heating the oil to 60-70℃ reduces its viscosity, allowing the alcohol extract A to dissolve quickly and completely, ensuring the homogeneity of the oil phase; honey, as a natural sweetener and solubilizer, can dissolve water-soluble active ingredients and improve the skin feel of the cream, reducing skin irritation.

[0013] Furthermore, in step S2, the mass ratio of the oil to extract A is 7-10:1, and the mass ratio of the honey to water-extracted extract B is 0.5-2:1. This ratio ensures the uniformity and stability of the oil phase and the water phase, laying the foundation for subsequent emulsification and molding.

[0014] S3. Emulsification and Forming: Slowly add the aqueous phase to the oil phase while simultaneously shearing and stirring at high speed. Add azone and propylene glycol, and continue stirring until homogeneous. Finally, add the carbomer gel matrix, adjust the pH to neutral, stir until homogeneous, and defoam to obtain the gel-type patch. Slowly adding the aqueous phase to the oil phase while simultaneously shearing and stirring at high speed ensures thorough emulsification of the oil and aqueous phases, forming a stable emulsion. Adjusting the pH to neutral ensures the skin compatibility of the patch and avoids acid and alkali irritation to the skin. The defoaming process removes air bubbles from the patch, ensuring its formability and adherence.

[0015] Furthermore, in step S3, the stirring speed is 1000-3000 rpm, which can achieve efficient emulsification of the oil phase and the water phase, ensuring the fineness and stability of the paste.

[0016] S4. Coating: The above-mentioned ointment is coated onto a non-woven fabric, covered with an anti-adhesive layer, and cut to obtain the external patch. The non-woven fabric serves as the base material for the patch, possessing good breathability and adhesion, making it suitable for skin application; the anti-adhesive layer protects the ointment and facilitates storage and use.

[0017] Furthermore, in step S4, the coating amount is 0.05-0.15 g / cm³. 2 This coating amount ensures the effective ingredient content of the patch while avoiding the problem of excess adhesive caused by excessive paste.

[0018] This invention also provides the application of the above-described composition or the composition prepared by the above-described method in the preparation of drugs or health products for relieving cough and expectoration. The composition is used to prepare a topical patch and applied to the bilateral Feishu (BL13), Guanyuan (CV4), and / or Yongquan (KI1) acupoints. Feishu (BL13) is the back-shu point of the lung; applying the patch here can directly act on the lungs, achieving the effect of clearing the lungs and relieving cough. Guanyuan (CV4) is a key acupoint for nourishing the original qi and strengthening the body; applying the patch here can replenish the body's vital energy. Yongquan (KI1) is the well point of the kidney meridian; applying the patch here can guide qi downwards, achieving the effect of relieving cough and reversing adverse flow. The combined application of these three acupoints, combined with the efficacy of the composition, achieves a dual effect of meridian drug delivery and transdermal drug delivery, significantly enhancing the effect of relieving cough and expectoration.

[0019] Compared with the prior art, the beneficial effects of the present invention are: The composition of this invention is scientifically formulated and treats both the symptoms and the root cause. It takes authentic Li ethnic medicinal materials as the core and combines them with classic antitussive and expectorant Chinese medicines. Based on the theory of traditional Chinese medicine, it regulates the pathogenesis of cough from multiple angles such as replenishing qi, clearing heat, drying dampness, lowering qi, and tonifying the kidney. It can not only quickly relieve the surface symptoms of cough and phlegm, but also replenish the body's vital energy from the root and cut off the pathogenesis, so as to avoid the cough from becoming prolonged and difficult to cure. It is also suitable for various cough symptoms caused by the hot and humid climate of Lingnan region. This formula follows the principles of traditional Chinese medicine's monarch-minister-assistant-guide herbal combinations. The principal herbs are *Achyranthes bidentata*, *Ficus hirta*, bitter almond, pinellia, and fritillaria thunbergii, primarily tonifying deficiency while resolving phlegm. Bitter almond, pinellia, and fritillaria thunbergii regulate qi and resolve phlegm, harmonizing cold and heat to treat the main symptoms of cough with excessive phlegm. This combination of cold and heat addresses the root cause of chronic cough damaging the lungs while quickly relieving the core symptoms of cough and excessive phlegm. The assistant herbs are *Magnolia officinalis*, *Selaginella tamariscina*, *Ardisia crenata*, and *Lonicera japonica*, primarily regulating qi, clearing heat, and promoting diuresis to address the symptoms of phlegm-dampness obstruction, qi stagnation, and heat transformation. Combined with the principal herbs, they form a formula that "tonifies deficiency without retaining pathogens and eliminates pathogens without harming the body's vital energy." The adjuvant herbs are *Salvia splendens* and dried basil, assisting in the treatment. The principal and assistant herbs clear heat and dampness, promote qi circulation and relieve pain. They also balance the warm and dry, cold and cool properties of the herbs in the formula. The adjuvant herbs use both warm and cold herbs, and the small doses enhance the efficacy and reduce toxicity. This approach takes into account both potential external pathogenic factors and protects the spleen and stomach functions. Rehmannia glutinosa is used as the guiding herb, which enters the kidney meridian. Prolonged cough damages the kidneys, and the adjuvant herbs that tonify the kidneys can guide the cough downwards, nourish the kidneys and replenish the marrow. This approach guides the other herbs to regulate the lungs and kidneys, interrupting the progression of the chronic cough. At the same time, its sweet and warm nature moderates the properties of the herbs in the formula, solving the common problem of "dryness and dampness damaging yin" in expectorant formulas. The herbs are clearly layered and work synergistically to achieve the effects of tonifying qi and strengthening the body, resolving phlegm and relieving cough, and clearing heat and removing dampness. This approach is suitable for the pathogenesis of cough with excessive phlegm in the Lingnan region.

[0020] The preparation method of the composition of the present invention adopts an extraction process that combines alcohol extraction and water extraction, which takes into account the full extraction of both fat-soluble and water-soluble effective components. The extraction efficiency is improved by ultrasound-assisted extraction. The process is simple, does not require expensive extraction equipment, and can be easily scaled up in factories, thus significantly reducing production costs. The topical patch prepared by this invention uses natural, skin-friendly excipients, resulting in a paste with good formability, excellent adherence, and no skin irritation. Furthermore, the addition of a compound penetration enhancer significantly improves the transdermal absorption efficiency of the active ingredients. The acupoint application method is convenient, eliminating the need for oral administration and avoiding gastrointestinal irritation, making it suitable for children, the elderly, and people of all ages. The raw materials for the composition of this invention are all natural herbal medicines, widely available and easily obtained, with high comprehensive utilization rate and no resource waste, aligning with the development concept of green pharmaceuticals. Simultaneously, it can be prepared as a drug or health product, with a wide range of applications and promising market prospects. Attached Figure Description

[0021] Figure 1 , Figure 2 These are the cough-relieving and expectorant external patches of the present invention. Detailed Implementation

[0022] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0023] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0024] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0025] The Chinese herbal medicines used in the embodiments of this invention are as follows: Cuiyuncao (a Li ethnic minority herbal medicine) medicinal properties: Sweet and bland in taste, cool in nature. It clears heat and promotes diuresis, stops bleeding, and relieves cough. It is mainly used to treat cough due to lung heat, hemoptysis, etc., and can also be used for damp-heat jaundice, dysentery, diarrhea, etc. Original texts state: *Bai Cao Jing* records that it "treats hematemesis, hemoptysis, hematochezia, hematuria, and metrorrhagia"; *National Compendium of Chinese Herbal Medicine* clarifies that it "clears heat and promotes diuresis, stops bleeding, and relieves cough. Used for acute jaundice-type infectious hepatitis, cholecystitis, enteritis, dysentery, nephritis edema, urinary tract infections, rheumatic joint pain, and hemoptysis due to pulmonary tuberculosis."

[0026] Niu Dali (a Li ethnic medicine) medicinal properties: Sweet in taste, neutral in nature. It nourishes the lungs and kidneys, benefits the liver and relaxes muscles and tendons, invigorates blood circulation and relieves pain. It has a certain therapeutic effect on coughs due to lung deficiency and difficulty expectorating phlegm, and can also alleviate chronic cough and wheezing caused by lung and kidney insufficiency. Original texts state: The *Lingnan Caiyao Lu* mentions "treating internal injury coughs, moistening the lungs and relieving coughs"; the *Commonly Used Chinese Herbal Medicine Handbook* of the Guangzhou Military Region records "strengthening muscles and tendons, invigorating blood circulation, nourishing deficiency and moistening the lungs. Treats lumbar muscle strain, rheumatoid arthritis, tuberculosis cough, and chronic hepatitis."

[0027] *Ficus lyrata* (a Li ethnic medicine), medicinal properties: sweet and slightly bitter in taste, warm in nature. It strengthens the spleen and lungs, promotes qi circulation and eliminates dampness, and relaxes muscles and tendons. It can improve coughs due to lung deficiency, excessive phlegm and wheezing, and is especially suitable for coughs caused by spleen deficiency and internal dampness. Original texts state: *Sheng Cao Yao Xing Bei Yao* states that it "stops coughs and resolves phlegm, moistens the lungs and generates fluids"; *Guangxi Ben Cao Xuan Bian* records that it "strengthens the spleen and eliminates dampness, promotes qi circulation and resolves phlegm, relaxes muscles and tendons. It treats coughs from pulmonary tuberculosis, chronic bronchitis, rheumatoid arthritis, lower back and leg pain, spleen deficiency edema, night sweats after illness, and leukorrhea."

[0028] Uttarakuru (a Li ethnic medicine), medicinal properties: bitter in taste and cold in nature. It clears heat and detoxifies, reduces swelling and relieves pain. It can be used for symptoms such as cough due to lung heat and sore throat, especially for cough and thick yellow phlegm caused by lung heat stagnation.

[0029] The original text states: "The National Compendium of Chinese Herbal Medicines records that it 'clears heat and detoxifies, reduces swelling and relieves pain. It is used for colds with fever, acute tonsillitis, pharyngitis, bronchitis, pneumonia, enteritis, dysentery, urinary tract infection, pelvic inflammatory disease, and carbuncles caused by heat toxins'; "Li Ethnic Medicine" includes it as a commonly used medicine of the Li ethnic group, used to treat pneumonia, cough, etc."

[0030] Basil (Li ethnic medicine), medicinal properties: pungent and sweet in taste, warm in nature. It dispels wind and releases the exterior, resolves dampness and harmonizes the middle jiao, promotes qi and blood circulation, detoxifies and reduces swelling. It has a certain therapeutic effect on cough and excessive phlegm caused by external wind-cold or internal dampness stagnation, and can also relieve abdominal distension caused by cough. Original text: The *Jiayou Materia Medica* records that it "regulates the middle jiao and aids digestion, removes foul odors, eliminates water retention, and is suitable for raw consumption. It also treats tooth root rot; its ash is very effective. For those suffering from vomiting, take half a *he* of the juice." The *Chinese Materia Medica Dictionary* states that it "dispels wind and releases the exterior, resolves dampness and harmonizes the middle jiao, promotes qi and blood circulation, detoxifies and reduces swelling. It treats colds with headache, fever and cough, heatstroke, indigestion, loss of appetite, abdominal distension and pain, vomiting and diarrhea, rheumatic pain, seminal emission, irregular menstruation, toothache and halitosis, pterygium covering the eyes, skin eczema, itchy rashes, traumatic injuries, and snake and insect bites."

[0031] Cinnabar root, medicinal properties: slightly bitter and pungent in taste, neutral in nature. It detoxifies and reduces swelling, invigorates blood circulation and relieves pain, dispels wind and dampness. It can be used for coughs due to lung heat and sore throats, especially those caused by the accumulation of heat toxins.

[0032] The original text states: "The Compendium of Materia Medica records that 'cinnabar root grows in deep mountains, and now only the people of Taihe Mountain collect it. The seedlings are about a foot tall, the leaves resemble holly leaves, but the back is very red. It grows luxuriantly in summer, and the roots are as large as chopsticks and red in color, which is similar to 'hundred-tael gold' (a type of medicinal herb)." The National Compendium of Chinese Herbal Medicine clearly states that it "detoxifies and reduces swelling, invigorates blood and relieves pain, dispels wind and eliminates dampness. It is used for sore throat, rheumatic pain, and traumatic injuries."

[0033] Water bamboo leaves, medicinal properties: sweet in taste and cold in nature. They clear heat, promote urination, reduce swelling, and detoxify. They can be used for symptoms such as cough with yellow phlegm due to lung heat, and can also relieve urinary difficulties caused by lung heat.

[0034] The original text states: "The Compendium of Materia Medica records that it "treats fever and chills, and is used to treat snake and insect stings; it is also used to treat sores on the head of children; it is used to treat sores on the head of children." The Quanzhou Materia Medica states that it "clears heat, promotes urination, reduces swelling, and detoxifies. It treats lung heat cough, bloody and white diarrhea, difficulty urinating, sore throat, carbuncles, boils, and carbuncles."

[0035] Rehmannia glutinosa (Shu Di Huang) has the following medicinal properties: It is sweet in taste and slightly warm in nature. It enters the liver and kidney meridians. It nourishes blood and yin, replenishes essence and marrow. It has a certain therapeutic effect on cough, dry cough with little phlegm, night sweats, and tidal fever caused by lung and kidney yin deficiency. It can nourish the yin of the lungs and kidneys and relieve cough symptoms. The original text states: The *Compendium of Materia Medica* records that it "fills bone marrow, grows muscles, generates essence and blood, replenishes deficiencies in the five internal organs, unblocks blood vessels, benefits the ears and eyes, blackens hair, treats five types of fatigue and seven types of injury in men, and treats uterine bleeding, irregular menstruation, and various pregnancy and childbirth diseases in women"; *Medicinal Properties Explained* states that "Rehmannia glutinosa, when steamed with wine, changes from cool to warm in nature, specifically entering the liver to replenish blood, also warming the gallbladder, benefiting heart blood, and further replenishing kidney water… filling bone marrow, it is a sacred medicine."

[0036] Bitter almonds, medicinal properties: bitter in taste, slightly warm in nature, and slightly toxic. They enter the lung and large intestine meridians. They lower qi, stop coughing, relieve asthma, and moisten the intestines to promote bowel movements. They are a commonly used medicine for treating coughs and asthma, effective for various types of coughs, including those caused by wind-cold, wind-heat, and lung-heat, especially suitable for coughs with excessive phlegm, chest tightness, and shortness of breath. Original texts state: The *Shennong Bencao Jing* records that it "treats coughs with shortness of breath, sore throat, lowers qi, treats postpartum hemorrhage, and cold-induced abdominal pain"; the *Bencao Gangmu* states that "almonds can disperse and lower, therefore they relieve muscle tension, dispel wind, lower qi, moisten dryness, and eliminate accumulations, and are used in medicines for treating injuries. They are used to treat sores and kill parasites, utilizing their toxicity. In medicines for treating wind-cold lung diseases, some use the whole almond, including the skin and tip, for its dispersing effect."

[0037] Pinellia ternata, medicinal properties: pungent, warm in nature, and toxic. It enters the spleen, stomach, and lung meridians. It dries dampness and resolves phlegm, relieves nausea and vomiting, and dissipates lumps and nodules. It is a key herb for drying dampness and resolving phlegm, and has significant effects on cough, copious clear phlegm, chest tightness, and epigastric fullness caused by damp phlegm or cold phlegm. It can also relieve vomiting caused by cough.

[0038] The original text states: The *Shennong Bencao Jing* records that it "treats typhoid fever with chills and fever, epigastric fullness, lowers qi, sore throat, dizziness, chest distension, cough, borborygmus, and stops sweating"; the *Bencao Gangmu* states that it "relieves abdominal distension, inability to close the eyes, leukorrhea, nocturnal emission, and vaginal discharge. Pinellia ternata can treat phlegm and abdominal distension because it is slippery and has a pungent and warm nature. Its slippery texture can moisten, and its pungent and warm nature can disperse and moisten. Therefore, it promotes the elimination of dampness and facilitates bowel movements, and opens the orifices and promotes urination. This is what is meant by 'pungent qi can resolve phlegm, and pungent nature can moisten.'"

[0039] Fritillaria thunbergii (Zhejiang fritillary bulb), medicinal properties: bitter in taste, cold in nature. It enters the lung and heart meridians. It clears heat, resolves phlegm, relieves cough, detoxifies, dissipates nodules, and reduces swelling. It is effective in treating wind-heat cough and phlegm-fire cough, and has a good effect on cough with yellow phlegm, sore throat, and throat inflammation. It can also dissipate scrofula and sores caused by phlegm-fire stagnation.

[0040] The original text states: "The Compendium of Materia Medica records that it is "very effective in treating lung abscess, lung weakness, cough, asthma, hemoptysis, epistaxis, and is most effective in reducing phlegm and qi, relieving stagnation, stopping pain, reducing bloating, clearing liver fire, improving hearing and vision, eliminating seasonal fever, jaundice, urinary retention, hematochezia, and hematuria; it also relieves heat toxins, kills various parasites, and treats sore throat, scrofula, mastitis, carbuncles, all kinds of carbuncles and boils, damp-heat sores, hemorrhoids, bleeding from metal wounds, and pain from fire sores"; "Supplement to the Compendium of Materia Medica" states that it "detoxifies and resolves phlegm, opens and promotes lung qi, and is suitable for all lung diseases with wind-heat and phlegm."

[0041] Magnolia officinalis, medicinal properties: bitter and pungent in taste, warm in nature. It enters the spleen, stomach, lung, and large intestine meridians. It dries dampness and eliminates phlegm, lowers qi and relieves fullness. It can be used for cough, excessive phlegm, chest tightness and shortness of breath caused by phlegm-dampness obstructing the lungs, and can also relieve abdominal distension caused by internal obstruction of phlegm-dampness.

[0042] The original text states: The Shennong's Classic of Materia Medica records that it "treats stroke, cold, headache, chills and fever, palpitations, qi and blood stagnation, dead tissue, and eliminates three types of parasites"; The Compendium of Materia Medica states that "Magnolia officinalis is warm and can dry dampness, pungent and can clear phlegm, and bitter and can lower qi. Therefore, when qi is stagnant in the middle and does not disperse, when food is stagnant in the stomach and does not move, or when dampness is stagnant and does not go away, or when damp phlegm is accumulating and not cleared, the warmth of Magnolia officinalis can dry dampness, the pungent can clear phlegm, and the bitter can lower qi."

[0043] Example 1 Prescription: 10g of Selaginella uncinata, 30g of Smilax glabra, 15g of Ficus hirta, 2g of Erythrina variegata, 2g of dried basil, 5g of Aralia elata root, 5g of Phyllostachys nigra leaf, 10g of Rehmannia glutinosa, 5g of Prunus armeniaca, 5g of Pinellia ternata, 5g of Fritillaria thunbergii, and 5g of Magnolia officinalis.

[0044] Example 2 Prescription: 30g of Selaginella uncinata, 70g of Smilax glabra, 25g of Ficus hirta, 8g of Erythrina variegata, 8g of dried basil, 15g of Cinnamomum cassia root, 15g of Phyllostachys nigra leaf, 20g of Rehmannia glutinosa, 15g of Prunus armeniaca, 15g of Pinellia ternata, 15g of Fritillaria thunbergii, and 15g of Magnolia officinalis.

[0045] Example 3 Prescription: 20g of Selaginella uncinata, 50g of Achyranthes bidentata, 20g of Ficus hirta, 5g of Erythrina variegata, 5g of dried basil, 10g of Cinnamomum cassia root, 10g of Phyllostachys nigra leaf, 15g of Rehmannia glutinosa, 10g of Prunus armeniaca, 10g of Pinellia ternata, 10g of Fritillaria thunbergii, and 10g of Magnolia officinalis. The method for preparing the compositions of Examples 1-3 above into a topical patch includes the following steps: S1. Extract preparation: a. Crush the prescribed amount of medicinal materials, pass them through a 90-mesh sieve, add 95% v / v ethanol at a material-to-liquid ratio of 1:6 (g / ml) and soak at room temperature for 24 hours. Then, use ultrasound-assisted extraction for 2 hours. The ultrasound process parameters are: ultrasound frequency 30kHz, ultrasound power 300W, and ultrasound temperature 35℃. Filter the mixture, repeat the extraction on the residue twice, combine the filtrates from the three extractions, and concentrate the extract under reduced pressure at 58℃ to recover the ethanol and obtain alcohol extract A. b. Add the residue after alcohol extraction to water at a ratio of 1:9 (g / ml), decoct for 1.5 hours, filter, and concentrate the filtrate to a relative density of 1.15 (60℃) to obtain water extract B.

[0046] S2. Matrix preparation: Heat camellia oil to 65℃, add alcohol extract A at a mass ratio of camellia oil: extract A = 8:1, stir to dissolve, and use as the oil phase; mix honey and water extract B at a mass ratio of honey: water extract B = 1:1 evenly, and use as the water phase. S3. Emulsification and molding: Slowly add the aqueous phase to the oil phase while shearing and stirring at a high speed of 2000 rpm. Add 0.8% azone and 4% propylene glycol by weight of the total composition, and continue stirring for 15 minutes. Finally, add 40% carbomer gel matrix by weight of the total composition, adjust the pH to 7.0 with triethanolamine, stir evenly, and degas under vacuum for 10 minutes to obtain the gel-type patch. S4. Coating: Apply the paste at a rate of 0.1 g / cm³. 2 The coating is applied to a nonwoven fabric, covered with a silicone paper release layer, and cut into 2cm×3cm patches to obtain the external patch.

[0047] Comparative Example 1 The difference between this comparative example and Example 3 is that *Smilax glabra* and *Ficus hirta* were removed; The prescription is as follows: 20g of Selaginella uncinata, 5g of Erythrina variegata, 5g of dried basil, 10g of Cinnamomum cassia root, 10g of Phyllostachys nigra leaf, 15g of Rehmannia glutinosa, 10g of Prunus armeniaca, 10g of Pinellia ternata, 10g of Fritillaria thunbergii, and 10g of Magnolia officinalis. The dosage, preparation method, and administration method of the remaining raw materials are exactly the same as those in Example 3 of this invention.

[0048] Comparative Example 2 The difference between this comparative example and Example 3 is that Magnolia officinalis, Selaginella tamariscina, Ardisia crenata root, and Bambusa textilis leaves were removed; The prescription is as follows: 50g of *Achyranthes bidentata*, 20g of *Ficus hirta*, 5g of *Sophora japonica*, 5g of dried basil, 15g of *Rehmannia glutinosa*, 10g of bitter almond, 10g of *Pinellia ternata*, and 10g of *Fritillaria thunbergii*. The dosage of the remaining raw materials, preparation method, and administration method are exactly the same as in Example 3 of this invention.

[0049] Experimental Example: Efficacy Test of Antitussive and Expectorant Pharmacognosy I. Experimental Materials (a) Laboratory animals SPF-grade Kunming mice, half male and half female, weighing 18-22g, totaling 150 mice, were randomly divided into an antitussive experimental group (75 mice) and an expectorant experimental group (75 mice). Both groups were provided by an institution with a laboratory animal production license. The animals were housed in a constant temperature of 22±2℃ and a constant humidity of 50±5%, with 12 hours of light and dark alternation. They had free access to food and water and were acclimatized for 3 days before the experiment was conducted.

[0050] (ii) Test Drugs 1. Test drug: The cough-relieving and expectorant composition for external use prepared in the best embodiment 3 of the present invention was cut into 0.5cm×1cm patches before use and applied to the acupoints of mice.

[0051] 2. Positive control drug: Commercially available conventional cough and phlegm-relieving external patches (Cough Patch from Sunflower Pharmaceutical), cut to the same specifications.

[0052] 3. Blank control: Blank gel patches without drug components (containing only camellia oil, honey, azone, carbomer gel matrix and other excipients), cut to the same size.

[0053] 4. Comparative Example Group: The cough-relieving and expectorant compositions prepared in Comparative Examples 1 and 2 of this invention were cut into 0.5cm×1cm patches before use.

[0054] (III) Test reagents Concentrated ammonia (analytical grade, concentration 25%-28%), phenol red reagent (analytical grade), 0.9% physiological saline, and 5% sodium bicarbonate solution are all commercially available qualified products. They should be prepared according to the test requirements before use.

[0055] (iv) Test instruments Ultrasonic nebulizer (nebulization rate 0.5 ml / min), mouse nebulized cough induction box (made of plexiglass, 10 cm × 20 cm × 15 cm), UV-Vis spectrophotometer, electronic analytical balance, surgical scissors, forceps, 1 ml syringe, centrifuge tubes, constant temperature water bath, etc.

[0056] II. Experimental Grouping The cough-suppressing and expectorant test groups were each divided into 3 subgroups, with 15 mice in each subgroup, half male and half female, as follows: 1. Blank control group: Blank control agent was applied to acupoints once a day for 12 hours each time; 2. Positive control group: Acupoint application of commercially available cough and phlegm-relieving external patches, once daily, for 12 hours each time; 3. Test drug group: The external patch of Example 3 of the present invention was applied to acupoints once a day for 12 hours each time.

[0057] Acupoints for application: Refer to the "Atlas of Acupoints for Mice" and select bilateral Feishu (BL13), Guanyuan (CV4), and Yongquan (KI1) acupoints on both sides of the mice (corresponding to acupoints for human application). Before application, gently wipe the skin of the acupoints on the mice with medical alcohol. After drying, apply the patch and fix it with medical breathable tape to prevent the mice from licking or biting it.

[0058] III. Test Methods (a) Cough suppression test 1. Mice in each group were administered the drug for 3 consecutive days according to the above grouping. A cough test was performed 1 hour after the last administration. 2. Place the mice individually in the nebulization cough induction chamber, turn on the ultrasonic nebulizer, and nebulize the ammonia nebulization solution prepared by mixing concentrated ammonia water and physiological saline at a volume ratio of 1:1. The nebulization time is 10s. After turning off the nebulizer, observe and record the latency (s) of the first cough of the mice and the number of coughs within 2 minutes after the end of nebulization. 3. Coughing criteria: A typical coughing action in mice, characterized by abdominal muscle contraction, wide-open mouth, head lifting and chest arching, is counted as one cough. Mild open-mouth breathing is not counted.

[0059] (ii) Expectorant test 1. Mice in each group were treated with the above-mentioned patch for 3 consecutive days. One hour after the last administration, the mice were injected intraperitoneally with 5 g / L phenol red saline solution at a dose of 0.2 ml / 10 g body weight. 2. Thirty minutes after intraperitoneal injection of phenol red, the mice were euthanized by cervical dislocation, and the trachea was quickly dissected and separated. The complete trachea was cut off from the upper end of the trachea to the bifurcation point, and the trachea was longitudinally cut open with surgical scissors. 3. Place the shredded tracheal tissue into a centrifuge tube containing 1 ml of 0.9% physiological saline, soak for 15 min, add 0.1 ml of 5% sodium bicarbonate solution (to eliminate the acidic interference of tracheal secretions and stabilize the phenol red color development), shake thoroughly, and then measure the absorbance (OD value) of the solution at a wavelength of 546 nm using a UV-Vis spectrophotometer. 4. Based on the phenol red standard curve, the amount of phenol red excreted in the trachea of ​​each group of mice (μg / ml) was calculated as an evaluation index of expectorant efficacy.

[0060] IV. Test Results (a) Effects on the latency period and frequency of coughing in ammonia-induced cough mice (antitussive effect) Compared with the blank control group, the cough latency of mice in both the positive control group and the test drug group was significantly prolonged, and the number of coughs within 2 minutes was significantly reduced; compared with the positive control group, the cough latency of mice in the test drug group was extremely prolonged, and the number of coughs within 2 minutes was extremely reduced. The results are shown in Table 1.

[0061] Table 1 Comparison of cough latency and number of coughs within 2 minutes in each group of mice (xˉ±s, n=15)

[0062] (II) Effect on phenol red secretion in mouse trachea (expectorant effect) Compared with the blank control group, the amount of phenol red secreted in the trachea of ​​mice in both the positive control group and the test drug group was significantly increased; compared with the positive control group, the amount of phenol red secreted in the trachea of ​​mice in the test drug group was extremely significantly increased. The results are shown in Table 2.

[0063] Table 2 Comparison of phenol red secretion in the trachea of ​​mice in each group (xˉ±s, n=15, μg / ml)

[0064] The results in Tables 1 and 2 above show that the external patch of the antitussive and expectorant composition prepared in this invention, after being applied to the bilateral Feishu (BL13), Guanyuan (CV4), and Yongquan (KI1) acupoints, significantly prolonged the cough latency period in ammonia-induced cough mice and dramatically reduced the number of coughs within 2 minutes, indicating that it has a significant antitussive pharmacological effect, and the antitussive effect is superior to commercially available conventional antitussive and expectorant external patches. Although the antitussive and expectorant effects of Comparative Example 1 were better than those of the blank control group, they were significantly weaker than those of the test drug group of this invention, and the antitussive effect was also worse than that of the positive control group. This proves that without the principal drug that tonifies Qi, strengthens the spleen, and benefits the lungs, the fundamental therapeutic effect of the composition is severely weakened, making it difficult to effectively improve the root pathogenesis of lung and spleen deficiency, resulting in a significant decrease in overall efficacy.

[0065] This topical patch significantly increased the amount of phenol red excreted from the trachea of ​​mice, indicating that it can effectively promote the expulsion of tracheal secretions in mice and has a significant expectorant pharmacological effect. Moreover, its expectorant effect is superior to that of commercially available conventional antitussive and expectorant topical patches. The expectorant effect of Comparative Example 2 was even slightly lower than that of Comparative Example 1, and significantly lower than that of the test drug group and the positive control group. Although the antitussive effect was slightly improved compared to Comparative Example 1, it was still far inferior to that of the test drug group. This proves that without the auxiliary herbs for clearing heat, promoting diuresis, and regulating qi, the composition's ability to expel pathogens is insufficient, especially its effect in resolving phlegm and dampness and clearing heat and toxins is significantly weakened. This verifies the indispensable synergistic effect of the auxiliary herbs in targeting symptoms such as "phlegm and dampness" and "heat and toxins."

[0066] This experiment confirms that the cough-relieving and expectorant composition of the present invention, applied topically through acupoints, has significant cough-relieving and expectorant effects, providing reliable animal experimental evidence for its clinical application in treating cough and excessive phlegm.

[0067] 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, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A composition having antitussive and expectorant effects, characterized in that, The ingredients include the following parts by weight: 10-30 parts of Selaginella uncinata, 30-70 parts of Smilax glabra, 15-25 parts of Ficus lyrata, 2-8 parts of Erythrina variegata, 2-8 parts of dried basil, 5-15 parts of Ardisia crenata, 5-15 parts of Phyllostachys edulis, 10-20 parts of Rehmannia glutinosa, 5-15 parts of Prunus armeniaca, 5-15 parts of Pinellia ternata, 5-15 parts of Fritillaria thunbergii, and 5-15 parts of Magnolia officinalis.

2. The composition according to claim 1, characterized in that, The ingredients include the following parts by weight: 20 parts of Selaginella uncinata, 50 parts of Smilax glabra, 20 parts of Ficus microcarpa, 5 parts of Erythrina variegata, 5 parts of dried basil, 10 parts of Aralia elata, 10 parts of Phyllostachys nigra, 15 parts of Rehmannia glutinosa, 10 parts of Prunus armeniaca, 10 parts of Pinellia ternata, 10 parts of Fritillaria thunbergii, and 10 parts of Magnolia officinalis.

3. The composition according to claim 1 or 2, characterized in that, The composition is a topical patch.

4. The composition according to claim 3, characterized in that, The topical patch is made from an extract of the composition and pharmaceutically acceptable excipients, including oils, honey, and penetration enhancers.

5. The composition according to claim 4, characterized in that, The oils include camellia oil, olive oil, sweet almond oil, or wheat germ oil.

6. The composition according to claim 4, characterized in that, The penetration enhancer is azone, propylene glycol, and carbomer gel matrix, and the addition amounts are 0.5-1%, 3-5%, and 30-50% of the total weight of the composition, respectively.

7. The method for preparing the composition according to any one of claims 1-6, characterized in that, Includes the following steps: S1. Extract preparation: a. Crush the prescribed amount of medicinal materials, pass them through an 80-100 mesh sieve, add 90-95% v / v ethanol solution at a material-to-liquid ratio of 1:5-8 (g / ml), soak at room temperature for 20-30 hours, extract with ultrasonic assistance for 1-3 hours, filter, repeat the extraction of the residue 1-3 times, combine the filtrates, concentrate under reduced pressure at 55-60℃ to recover the ethanol, and obtain alcohol extract A. b. Add water to the above-mentioned residue after alcohol extraction at a material-to-liquid ratio of 1:8-10 (g / ml), decoct for 1-2 hours, filter, and concentrate the filtrate to a relative density of 1.10-1.20 to obtain water extract B. S2. Matrix preparation: Heat the oil to 60-70℃, add alcohol extract A, stir to dissolve, and use as the oil phase; separately mix honey with water extract B evenly, and use as the water phase. S3. Emulsification and molding: Slowly add the aqueous phase to the oil phase while shearing and stirring at high speed. Add azone and propylene glycol, and continue stirring until homogeneous. Finally, add the carbomer gel matrix, adjust the pH to neutral, stir until homogeneous, and defoam to obtain the gel-type patch. S4. Coating: The above-mentioned paste is coated onto non-woven fabric, covered with an anti-stick layer, and cut to obtain the external patch.

8. The method for preparing the composition according to claim 7, characterized in that, In step S1, the ultrasonic frequency is 20-40kHz, the power is 200-500W, and the extraction temperature is 30-45℃; in step S2, the mass ratio of the oil to extract A is 7-10:1, and the mass ratio of the honey to water extract B is 0.5-2:

1.

9. The method for preparing the composition according to claim 7, characterized in that, In step S3, the stirring rate is 1000-3000 rpm; in step S4, the coating amount is 0.05-0.15 g / cm³. 2 .

10. The use of the composition according to any one of claims 1-6 or the composition prepared by the method according to any one of claims 7-9 in the preparation of a medicament or health product for relieving cough and expectoration, characterized in that, The composition is used to prepare a topical patch and is applied to the bilateral Feishu (BL13), Guanyuan (CV4), and / or Yongquan (KI1) acupoints.

Images