Pharmaceutical composition for treating or preventing skin itch as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a pharmaceutical composition for treating or preventing skin itch and a preparation method and application thereof. The medicine composition is prepared from the following raw materials in parts by weight: 50 to 200 parts of cortex moutan, 50 to 200 parts of radix paeoniae rubra, 50 to 200 parts of herba lobeliae chinensis, 50 to 200 parts of cortex pseudolaricis, 50 to 200 parts of liquorice root and 10 to 50 parts of borneol. The preparation method comprises the following steps: taking the raw materials in parts by weight; the cortex moutan, the radix paeoniae rubra, the Chinese lobelia, the cortex pseudolaricis and the liquorice are extracted according to a conventional extraction method, the borneol is added, and the mixture is mixed. The pharmaceutical composition for treating or preventing skin itch can be used for relieving itching and diminishing inflammation, and is low in cost, quick in effect, good in stability, free of irritation and small in side effect; aiming at the pathogenesis of dampness, heat and blood stasis, a simple and reasonable formula is used for obtaining a better effect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a pharmaceutical composition for treating or preventing skin pruritus and a preparation method and application thereof. BACKGROUND

[0002] Pruritus is a kind of skin disease with no obvious primary skin damage and with itching as the main symptom. It is a kind of neurofunctional disorder skin disease with itching as the main symptom and no primary lesion. According to different skin lesions and the site of the disease, different names are given to the symptoms of itching in the literature of traditional Chinese medicine in different dynasties, such as 'itching wind', 'yin itching', etc. It is now collectively referred to as wind itching. It is believed that the disease is mainly caused by wind evil, and all itching belongs to wind and deficiency. Blood deficiency causes wind, and wind is abundant, which causes itching. The treatment principle is to clear heat and remove dampness, cool blood and dispel wind, nourish blood and calm liver, and moisten dryness to stop itching. Clinical research believes that there are many causes of skin pruritus, among which the most common are dampness and heat, which cause skin itching, redness, heat and pain, and long-term consumption of blood and fire, which causes blood dryness, blood deficiency and secondary rash.

[0003] Most of the existing drugs for treating skin itching are western medicines, which have significant effects but can cause side effects such as dependence and drug resistance. Traditional Chinese medicine has the advantages of small side effects and long-lasting effects in the treatment of skin itching. However, the existing traditional Chinese medicine preparations for relieving itching have defects such as slow effect, complicated formula and preparation process, and high cost. For example, a patent document discloses a pharmaceutical composition for treating skin itching, which comprises peony, white bark, sophora flavescens, licorice, borneol and menthol. Different raw materials need to be extracted using different solvents and methods during preparation, which is very complicated and has high commercial cost. Therefore, it is of great clinical significance to develop a traditional Chinese medicine composition for treating skin itching with simple preparation method and significant effect. SUMMARY

[0004] Therefore, the purpose of the present application is to provide a pharmaceutical composition for treating or preventing skin itching and a preparation method and application thereof. The pharmaceutical composition for treating or preventing skin itching has a simple formula, low cost, fast effect after use and few side effects.

[0005] To this end, the present application provides the following technical solutions.

[0006] The present application provides a pharmaceutical composition for treating or preventing skin itching, which comprises the following raw materials in parts by weight: 50-200 parts of peony, 50-200 parts of red peony root, 50-200 parts of lobelia, 50-200 parts of vitex negundo var. cannabifolia, 50-200 parts of licorice, and 10-50 parts of borneol.

[0007] The application provides a preparation method of the medicine composition for treating or preventing skin itching, comprising the following steps: taking raw materials by weight; extracting cortex moutan, red peony root, lobelia, fructus chaenomelis and liquorice by a conventional extraction method, adding borneol, and mixing to obtain the medicine composition.

[0008] Typically, after the extraction, the method further comprises the step of concentrating the extract to obtain a clear paste, i.e. recovering the extraction solvent at low temperature and reduced pressure.

[0009] Optionally, the conventional extraction method comprises one or more of decocting extraction, soaking extraction, reflux extraction and ultrasonic extraction.

[0010] Optionally, the extraction solvent is at least one of ethanol and water; and optionally, the extraction solvent is an ethanol aqueous solution.

[0011] Optionally, the extraction is performed at least once.

[0012] Optionally, the extraction is performed for at least 24 hours; and optionally, the extraction is performed for 24-96 hours.

[0013] Optionally, the volume ratio of the extraction solvent to the raw medicine is greater than or equal to 5; and optionally, the volume ratio of the extraction solvent to the raw medicine is 5-10.

[0014] Optionally, before the extraction, the method further comprises the step of powdering cortex moutan, red peony root, lobelia, fructus chaenomelis and liquorice; and optionally, the method further comprises the step of passing the obtained mixed powder through an 80-mesh sieve and taking the undersize.

[0015] Optionally, before the mixing, the method further comprises the step of grinding borneol; and optionally, the borneol is ground into fine powder.

[0016] Optionally, before the mixing, the method further comprises the step of preparing borneol into a borneol diluent; optionally, the diluent is at least one of ethanol and water; optionally, the mass of the diluent is 4-6 times the mass of the borneol; and further optionally, the diluent is an ethanol aqueous solution.

[0017] Optionally, the volume fraction of ethanol in the ethanol aqueous solution is 50%-80%.

[0018] Optionally, the preparation method comprises the following steps: S1: taking raw materials according to weight parts; S2: powdering Radicis Moutan, Radicis Paeoniae Rubra, Lobelia Chinensis, Fructus Chaenomelis, and Glycyrrhiza Uralensis to obtain mixed powder, passing through an 80-mesh sieve, taking the sieve under the material, adding an ethanol aqueous solution, the ratio of the volume of the ethanol aqueous solution to the volume of the sieve under the material being 5-10, extracting for 24-96 hours, and solid-liquid separation to obtain a mixed extract; S3: grinding Borneol into fine powder, adding an ethanol aqueous solution to obtain a Borneol diluent, the mass of the ethanol aqueous solution being 4-6 times the mass of the Borneol; S4: mixing the mixed extract and the Borneol diluent to obtain the pharmaceutical composition for treating or preventing skin itching.

[0019] The application provides application of the above-mentioned pharmaceutical composition for treating or preventing skin itching or the pharmaceutical composition for treating or preventing skin itching prepared by the above-mentioned preparation method in the preparation of a medicine for treating or preventing skin itching.

[0020] Optionally, the medicine for treating or preventing skin itching further comprises a pharmaceutically acceptable adjuvant; optionally, the pharmaceutically acceptable adjuvant is at least one selected from a pharmaceutically acceptable solvent, a solubilizer, a cosolvent, an emulsifier, an osmotic pressure regulator, a stabilizer, a suspending agent, a coating material, an anti-adhesion agent, an integration agent, a penetration enhancer, a pH regulator, a buffer, a surfactant, an absorption agent, a diluent, a filtration aid, a controlled-release material.

[0021] Optionally, the dosage form of the medicine for treating or preventing skin itching comprises a skin administration preparation; optionally, the skin administration preparation is selected from an ointment, a cream, a gel, a lotion, a spray, a patch, a film, a cream, a solution, a powder or a plaster.

[0022] Optionally, the skin itching comprises at least one of exogenous cause-induced skin itching, endogenous cause-induced skin itching, and environment and physiological factor-induced skin itching; optionally, the exogenous cause-induced skin itching comprises mosquito bites, allergic dermatitis itching, contact dermatitis itching, and fungus infection-induced skin itching; optionally, the endogenous cause-induced skin itching comprises neurodermatitis itching, chronic disease secondary itching, damp-heat accumulation itching, blood stasis itching, and blood deficiency and dryness itching; optionally, the environment and physiological factor-induced skin itching comprises dampness accumulation itching, damp-heat stagnation itching, heat itching, and wind itching.

[0023] Typically, when the obtained skin administration preparation is a solution or a spray, the pharmaceutical composition for treating or preventing skin itching can be directly used after dilution with water in a volume ratio of 50:13, and when the obtained skin administration preparation is a gel, the pharmaceutical composition for treating or preventing skin itching can be concentrated to a relative density of 1.1-1.25, 0.5 parts of carbomer and glycerol are added, mixed, and then 0.5 parts of borax is added to obtain a gel.

[0024] In the present application, the relative density refers to the relative value of the density of a substance to the density of water at 4℃; grinding to fine powder refers to grinding to meet the fine powder in the Chinese Pharmacopoeia 2020 edition: fine powder to pass through a No. 5 sieve (180μm±7.6μm) and mixed with not less than 95% of powder passing through a No. 6 sieve (150μm±6.5μm).

[0025] The beneficial effects of the present application are:

[0026] The pharmaceutical composition for treating or preventing pruritus provided by this invention comprises the following raw materials in parts by weight: 50-200 parts of peony bark, 50-200 parts of red peony root, 50-200 parts of lobelia chinensis, 50-200 parts of sesame bark, 50-200 parts of licorice root, and 10-50 parts of borneol. It can be used to relieve itching and inflammation, is low in cost, fast-acting, stable, non-irritating, and has few side effects; targeting the causes of dampness, heat, and blood stasis, the simplified and rational formula achieves better results. Licorice root has the effects of clearing heat and detoxifying, relieving spasms and pain, and contains glycyrrhizic acid, glycyrrhetinic acid, glycyrrhizin, and glycyrrhizin glycosides, which can exert anti-inflammatory effects through multiple pathways, inhibit the synthesis of inflammatory mediators, regulate immune responses, inhibit oxidative stress, and have antiviral effects. For example, glycyrrhizic acid can inhibit the synthesis of inflammatory mediators such as prostaglandins (PGE2), tumor necrosis factor (TNF), and interleukins (ILS). Moutan bark has the effect of clearing heat and cooling blood, and paeonol in it has anti-inflammatory and antipyretic effects. Lobelia chinensis and Pseudolarix amabilis bark have detoxifying and antipruritic effects. Borneol can dispel wind and relieve itching, reduce inflammation and relieve pain, and has anti-inflammatory, antioxidant, antitumor, and antibacterial effects. Borneol can reduce inflammatory responses by inhibiting the activation of the NF-κB (nuclear factor-activated B cell κ-light chain enhancement) pathway, and has therapeutic or preventive effects on various inflammatory diseases. In this formula, Moutan bark and Paeonia lactiflora can clear heat and cool blood, promote blood circulation and remove blood stasis, and together they are the principal herbs. Moutan bark is good at clearing latent heat and stagnant heat in the blood, and has the effects of cooling blood and detoxifying, anti-inflammatory, antibacterial, and anti-allergic. Paeonia lactiflora can clear stagnant heat in the blood and remove blood stasis. Paeonia lactiflora has a wide range of pharmacological effects, including antithrombotic, antioxidant, hypoglycemic, antitumor, antidepressant, antiradiation, anti-inflammatory, antiviral, and immunomodulatory effects. The synergistic use of Moutan bark and Paeonia lactiflora enhances the effects of clearing heat and cooling blood, and anti-inflammatory and antipruritic effects. Lobelia chinensis and Pseudolarix amabilis bark are the assistant herbs. Lobelia chinensis assists the principal herb in enhancing its heat-clearing and detoxifying effects, while also promoting diuresis and reducing swelling, thus alleviating local redness and swelling in itchy areas. Pseudolarix amabilis bark, due to its significant hepatotoxicity when taken orally, is only used externally. It has the effects of removing dampness, killing insects, and relieving itching, assisting the principal herb in sterilizing and relieving itching. Licorice and borneol are the adjuvant herbs. Glycyrrhizic acid in licorice has hormone-like effects, which can both assist the principal herb in detoxifying and relieving itching and harmonize the properties of the herbs. Borneol can both clear heat and reduce swelling and promote transdermal absorption of the drug, improving local drug utilization. The entire formula can clear both excess and deficiency heat, and also promote diuresis, detoxify, disperse blood stasis, reduce inflammation, and kill insects and relieve itching. It can treat or prevent various types of pruritus caused by various reasons, including pruritus caused by insect bites, allergic dermatitis, neurodermatitis, and secondary pruritus caused by chronic diseases.

[0027] This invention provides a method for preparing the above-mentioned pharmaceutical composition for treating or preventing pruritus, comprising the following steps: taking raw materials according to the specified weight proportions; extracting peony bark, red peony root, lobelia bark, sesame bark, and licorice root using conventional extraction methods; adding borneol; and mixing to obtain the final product. This preparation method is simple, easy to operate, and convenient for large-scale production. Detailed Implementation

[0028] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0029] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0030] Experimental drugs:

[0031] Moutan Cortex: Hebei Guojin Taihang Traditional Chinese Medicine Co., Ltd., batch number 240405;

[0032] Red peony root: Hebei Guojin Taihang Traditional Chinese Medicine Co., Ltd., batch number 240107;

[0033] Lobelia chinensis: Hebei Guosongtang Pharmaceutical Co., Ltd., batch number: 318070001;

[0034] Pseudolarix amabilis bark: Hebei Kangbo Pharmaceutical Co., Ltd., batch number 224091101;

[0035] Licorice: Hebei Guoruitang Pharmaceutical Co., Ltd., batch number: 220101;

[0036] Borneol: Jiangsu Kangmei Pharmaceutical Co., Ltd., batch number: A230402;

[0037] 2,4-Dinitrochlorobenzene (DNCB); Beijing Chemical Reagent Factory;

[0038] Acetone: Chengdu Kelong Chemical Co., Ltd., batch number 201908140;

[0039] Soothing and antipruritic tincture: manufactured by Taikang Haien, used as a positive control.

[0040] Example 1

[0041] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0042] (1) Weigh out 100g of peony bark, 100g of red peony root, 100g of lobelia bark, 100g of sesame bark, 100g of licorice root, and 20g of borneol.

[0043] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder to obtain a mixed powder. Pass the mixed powder through an 80-mesh sieve, take the sieve material, add 75% vol ethanol at 5 times the volume of the sieve material, soak for 72 hours, filter, take the mixed filtrate, recover the ethanol under low temperature and reduced pressure, concentrate the mixed filtrate to a clear extract with a relative density of 1.05 (55℃), and set aside for later use.

[0044] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0045] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0046] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0047] Example 2

[0048] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0049] (1) Weigh out 50g of peony bark, 200g of red peony root, 50g of lobelia bark, 100g of sesame bark, 100g of licorice root, and 20g of borneol.

[0050] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder to obtain a mixed powder. Pass the mixed powder through an 80-mesh sieve, take the sieve material, add 75% vol ethanol at 8 times the volume of the sieve material, soak for 36 hours, filter, take the mixed filtrate, recover the ethanol under low temperature and reduced pressure, concentrate the mixed filtrate to a clear extract with a relative density of 1.02 (55℃), and set aside for later use.

[0051] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0052] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0053] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0054] Example 3

[0055] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0056] (1) Weigh out 200g of peony bark, 50g of red peony root, 100g of lobelia bark, 50g of sesame bark, 70g of licorice root, and 50g of borneol.

[0057] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder to obtain a mixed powder. Pass the mixed powder through an 80-mesh sieve, take the sieve material, add 7 times the volume of the sieve material to 80% vol ethanol, soak for 96 hours, filter, take the mixed filtrate, recover the ethanol under low temperature and reduced pressure, concentrate the mixed filtrate to a clear extract with a relative density of 1.03 (55℃), and set aside for later use.

[0058] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0059] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0060] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0061] Example 4

[0062] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0063] (1) Weigh out 100g of peony bark, 100g of red peony root, 200g of lobelia bark, 50g of sesame bark, 50g of licorice root, and 20g of borneol.

[0064] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder to obtain a mixed powder. Pass the mixed powder through an 80-mesh sieve, take the sieve material, add 60% vol ethanol at 5 times the volume of the sieve material, soak for 36 hours, filter, take the mixed filtrate, recover the ethanol under low temperature and reduced pressure, concentrate the mixed filtrate to a clear extract with a relative density of 1.03 (55℃), and set aside for later use.

[0065] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0066] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0067] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0068] Example 5

[0069] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0070] (1) Weigh out 100g of peony bark, 50g of red peony root, 60g of lobelia bark, 100g of sesame bark, 200g of licorice root, and 10g of borneol.

[0071] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice into powder to obtain a mixed powder. Add 60% vol ethanol, which is 5 times the volume of the mixed powder, and soak for 72 hours. Filter and recover the ethanol from the filtrate under low temperature and reduced pressure to obtain a clear extract with a relative density of 1.03 (55℃).

[0072] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0073] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0074] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0075] Example 6

[0076] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0077] (1) Weigh out 50g of peony bark, 100g of red peony root, 100g of lobelia bark, 200g of sesame bark, 50g of licorice root, and 20g of borneol.

[0078] (2) The peony bark, red peony root, half-lotus root, sesame bark, and licorice root are ground into powder to obtain a mixed powder. The mixed powder is passed through an 80-mesh sieve. The sieve material is taken and 75% vol ethanol with a volume of 6 times the volume of the sieve material is added. The mixture is soaked for 72 hours, filtered, and the ethanol is recovered from the filtrate under low temperature and reduced pressure to a clear extract with a relative density of 1.02 (55℃).

[0079] (3) Grind borneol into a fine powder, add 75% vol ethanol at 5 times the mass of borneol, stir well to obtain borneol dilution.

[0080] (4) Mix the mixed filtrate and the borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0081] (5) Concentrate the drug composition for treating or preventing skin itching to a relative density of 1.10 (55°C), add 10g carbomer and 45g glycerin, stir well, add 5g borax, and obtain a skin-administered gel.

[0082] Example 7

[0083] This embodiment provides a pharmaceutical composition for treating or preventing pruritus and a method for preparing the same, comprising the following steps:

[0084] (1) Weigh out 100g of peony bark, 50g of red peony root, 60g of lobelia bark, 200g of sesame bark, 100g of licorice root, and 10g of borneol.

[0085] (2) Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice into powder to obtain a mixed powder. Add 60% vol ethanol, which is 10 times the volume of the mixed powder, and soak for 24 hours. Filter and recover the ethanol from the filtrate under low temperature and reduced pressure to obtain a clear extract with a relative density of 1.03 (55℃).

[0086] (3) Grind borneol into a fine powder, add 50% vol ethanol at 6 times the mass of borneol, stir well to obtain borneol dilution.

[0087] (4) Mix the ointment and borneol dilution to obtain a pharmaceutical composition for treating or preventing skin itching.

[0088] (5) Add the drug composition for treating or preventing skin itching to a 2000 mL volumetric flask, add purified water to make up to volume, and obtain a skin administration solution.

[0089] Comparative Example 1

[0090] This comparative example provides a pharmaceutical composition for treating or preventing pruritus and its preparation method. The only difference from Example 2 is that the dosage of peony bark is adjusted to 20g and the dosage of red peony root is adjusted to 230g.

[0091] Comparative Example 2

[0092] This comparative example provides a pharmaceutical composition for treating or preventing pruritus and its preparation method. The only difference from Example 2 is that the dosage of Lobelia chinensis is adjusted to 130g and the dosage of Pseudolarix amabilis bark is adjusted to 20g.

[0093] Comparative Example 3

[0094] This comparative example provides a pharmaceutical composition for treating or preventing pruritus and its preparation method. The only difference from Example 2 is that it does not contain Paeonia lactiflora and the amount of Paeonia suffruticosa is adjusted to 250g.

[0095] Comparative Example 4

[0096] This comparative example provides a pharmaceutical composition for treating or preventing pruritus and its preparation method. The only difference from Example 2 is that it does not contain Lobelia chinensis and the amount of Pseudolarix amabilis bark is adjusted to 150g.

[0097] Experimental Example 1

[0098] The skin-administered formulations obtained in the embodiments of the present invention were subjected to clinical trials, and the specific cases are as follows:

[0099] Clinical Case 1:

[0100] The patient is a 33-year-old female, 5 months pregnant, with large red rashes on both armpits and abdomen, which are extremely itchy and affect her sleep.

[0101] The Western medical diagnosis was fungal infection, and ketoconazole cream was ineffective.

[0102] The TCM diagnosis is: headache, yellow urine, bad breath, and thick, greasy white tongue coating; it is a syndrome of damp-heat accumulation and itching.

[0103] The skin application solution obtained in Example 1 was used three times daily for 10 consecutive days. Second visit: Itching was reduced, with paroxysmal episodes of varying severity; sleep disturbances were lessened; the rash color was darker. The skin application solution obtained in Example 1 was continued three times daily for 7 consecutive days; itching completely subsided, and the rash disappeared.

[0104] Clinical Case 2:

[0105] The patient is a 16-year-old male who has been experiencing itchy skin and restless sleep for the past two months. He was previously diagnosed with chronic eczema and has used various topical medications, but they only provided temporary relief.

[0106] The TCM diagnosis is as follows: localized skin rash, symmetrically distributed on the chest, with scratch marks, hot flashes, dry stools, yellow urine, red tongue, and yellow greasy tongue coating; it is a heat-itching syndrome.

[0107] The skin medication solution obtained in Example 2 was applied three times daily for 7 consecutive days. Second visit: Skin itching was greatly reduced, sleep improved, nighttime sleep was sound, the rash significantly subsided, and other symptoms improved. The skin medication solution obtained in Example 2 was continued to be applied three times daily for one month; complete cure achieved.

[0108] Clinical Case 3:

[0109] The patient is a 54-year-old female who has experienced severe itching on her head and shins for the past week, which has affected her sleep.

[0110] The TCM diagnosis is: itching on the head and shins, accompanied by blisters, erosion, exudation, red rash, fatigue in the limbs, loss of appetite, white and greasy tongue coating, and slippery pulse; it is a syndrome of itching due to internal obstruction of dampness and turbidity.

[0111] The skin application solution obtained in Example 3 was used three times daily for two consecutive weeks. Second visit: The rash was lighter in color, itching was reduced and intermittent, and sleep was sound. The skin application solution obtained in Example 3 was continued three times daily for another two weeks; the itching resolved, and other symptoms disappeared.

[0112] Clinical Case 4:

[0113] The patient is a 59-year-old male who has been experiencing persistent itching and scratching in his right lower leg for two months.

[0114] The TCM diagnosis is: accompanied by erosion and redness, yellow urine, bad breath, and a thick, greasy white tongue coating; it is a syndrome of damp-heat stagnation and itching.

[0115] The skin application solution obtained in Example 4 was applied three times daily for two consecutive weeks. Second visit: scabs formed on the lower limbs, dark in color; other symptoms disappeared. The skin application solution obtained in Example 4 was continued three times daily for another two weeks; recovery was achieved.

[0116] Clinical Case 5:

[0117] The patient is a 43-year-old male who developed generalized itchy skin one year ago without any obvious cause. Applying moisturizing cream slightly relieved the symptoms. He had bowel movements once every 1-2 days, which were unformed. He occasionally got up at night. He slept well. His pulse was floating and slippery. His tongue tip was red with a yellow coating and teeth marks on the edges. There was extensive bruising in the veins under his tongue.

[0118] The diagnosis according to Traditional Chinese Medicine is: wind-heat syndrome with blood stasis and itching.

[0119] The skin application solution obtained in Example 5 was used: applied three times daily for two consecutive weeks until healed.

[0120] Clinical Case 6:

[0121] The patient is a 52-year-old male. Two months ago, he developed generalized itching without any obvious cause, mainly concentrated on the extensor surfaces of the limbs and back. The itching was intermittent, worsening at night, and moderate and tolerable, with no obvious rash. One week ago, the itching symptoms significantly worsened, spreading to the entire body, and red papules, scratch marks, and scabs appeared. The intense itching severely affected his sleep, prompting him to seek medical attention at our hospital.

[0122] The TCM diagnosis is: the patient has been ill for a long time and has blood deficiency, which has caused wind and dryness. The wind and dryness have invaded from the outside and the skin has been malnourished, resulting in blood deficiency and wind-dryness syndrome. The tongue is pale, the coating is thin, and the pulse is thready and rapid.

[0123] The skin medication solution obtained in Comparative Example 1 was applied three times daily for two consecutive weeks. Second visit: scabs formed on the lower limbs, dark in color, but the itching symptoms persisted. The skin medication solution obtained in Example 4 was then used, applied three times daily for another three days; the itching symptoms subsided.

[0124] Clinical Case 7:

[0125] The patient is a 35-year-old female with burning and itchy skin, which worsens in the afternoon and at night. After scratching, the skin becomes red, without exudation, and fine scales are visible. She also experiences irritability, night sweats, and weakness in the lower back and knees.

[0126] The diagnosis according to Traditional Chinese Medicine is: Yin deficiency with wind-heat syndrome.

[0127] The skin application solution obtained in Comparative Example 2 was applied three times daily for one week. There was no significant improvement in burning sensation and nighttime itching; scratching resulted in increased redness and scaling. The treatment was subsequently discontinued.

[0128] Clinical Case 8:

[0129] The patient is a 41-year-old male who presents with paroxysmal severe itching of the skin all over his body, which worsens with heat. After scratching, the skin bleeds, leaving red scratch marks and blood scabs. Some areas are mildly red and swollen, accompanied by irritability, thirst, scanty dark urine, dry stools, a red tongue with a thin yellow coating, and a floating and rapid pulse.

[0130] Traditional Chinese Medicine diagnosis: Wind-induced itching - Wind-heat and blood-heat syndrome.

[0131] The skin application solution obtained in Comparative Example 3 was applied three times daily for one week. The frequency and intensity of itching did not decrease; nighttime sleep was still disrupted by severe itching; the number of scratches and scabs did not decrease; and new scratches continued to cause symptoms such as irritability and constipation without improvement. The treatment was subsequently discontinued.

[0132] Clinical Case 9:

[0133] The patient is a 30-year-old female with dry, flaky skin, itching that worsens at night, scratch marks covering her lower back and limbs, pigmentation and lichenification, pale complexion, dizziness, fatigue, insomnia and forgetfulness, pale tongue with a thin white coating, and a thready pulse.

[0134] Traditional Chinese Medicine diagnosis: Wind-induced itching - Blood deficiency and wind-dryness syndrome.

[0135] The skin application solution obtained in Comparative Example 4 was applied three times daily for one week. Dry, flaky skin did not improve, itching remained the same as before treatment, pigmentation areas expanded, lichenification worsened, and insomnia and fatigue persisted. Subsequently, the drug solution from Example 1 was used three times daily. After two days, the symptoms improved.

[0136] Experiment Example 2

[0137] The skin-administered formulations obtained in the embodiments of the present invention were tested using an induced acute pruritus behavior experiment.

[0138] ICR mice with a body weight of 20±2g were used. During the experiment, the mice had free access to food and water. The ambient temperature was controlled at 18-22℃, the humidity at 50%-60%, and the light exposure was 12h-12h (light-dark).

[0139] 1. Preparation of contact dermatitis and pruritus models

[0140] Preparation of a mouse model of contact dermatitis: Forty ICR mice, half male and half female, were used. The abdominal hair of each mouse was shaved one day before the experiment, covering an area of ​​approximately 3cm × 3cm. On the day of the experiment, the mice were anesthetized by intraperitoneal injection of 5% chloral hydrate at 0.08ml / 10g. Then, 100ul of 5% DNFB (2,4-dinitrofluorobenzene)-acetone solution was applied to the shaved abdominal area to sensitize the mice. Another 100ul was applied the next day to reinforce sensitization. Five days later, 20ul each of 1% DNCB and 0.25% DNCB-acetone solution were evenly applied to both sides of the right ear to stimulate stimulation. Simultaneously, an equal dose of acetone was applied to the left ear for stimulation. Stimulation was repeated every 3 days for a total of 4 times (stimulation was performed on days 6, 9, 12, and 15), thus obtaining the mouse model of contact dermatitis.

[0141] Preparation of pruritus model mice: Forty ICR mice, half male and half female, were used. Hair was removed from the skin of the head, neck and behind the ears of the mice 1 day in advance. 0.2 ml of 0.025% dextran (solvent is physiological saline) was injected subcutaneously into the hair removal site to obtain pruritus model mice.

[0142] 2. Grouping and Dosing

[0143] Mice with contact dermatitis were randomly divided into four groups: a contact dermatitis model control group, a contact dermatitis positive drug group, a high-dose contact dermatitis test group, and a low-dose contact dermatitis test group, with 10 mice in each group. Ten unsensitized normal ICR mice were also used as a normal control group. The contact dermatitis model control group and the normal control group received 1 g / kg of physiological saline. The contact dermatitis positive drug group received 1 g / kg of soothing and antipruritic tincture. The high-dose contact dermatitis test group received 1 g / kg of the skin administration solution prepared in Example 1 of this application. The low-dose contact dermatitis test group received 0.5 g / kg of the skin administration solution prepared in Example 1 of this application. One hour after sensitization, the corresponding dose of the test solution was evenly applied to both sides of the right ear of each mouse. If a challenge date was approaching, the test solution was applied again 2 hours after each challenge. The treatment was continued for 15 days. Mice were sacrificed 24 hours after the last challenge, and relevant indicators were measured.

[0144] Mice with pruritus were randomly divided into a pruritus model control group, a pruritus-positive drug group, a high-dose pruritus test group, and a low-dose pruritus test group, with 10 mice in each group. Ten unsensitized common ICR mice were also used as a normal pruritus control group. The pruritus model control group and the normal pruritus control group received 1 g / kg of physiological saline. The pruritus-positive drug group received 1 g / kg of soothing and antipruritic tincture. The high-dose pruritus test group received 1 g / kg of the skin administration solution prepared in Example 1 of this application. The low-dose pruritus test group received 0.5 g / kg of the skin administration solution prepared in Example 1 of this application. After 3 days of continuous treatment, 1 hour after the last treatment, 0.2 ml of 0.025% dextran (solvent: physiological saline) was injected subcutaneously into the hair removal site in each group to induce the pruritus model.

[0145] 3. Testing

[0146] (1) Ear damage (contact dermatitis)

[0147] The damage to the right ear of mice in each group was observed 24 hours after each stimulation, and scores were calculated: 3 points were awarded for obvious redness, swelling, thickening, exudation, or obvious keratinization and crusting; 2 points were awarded for mild redness, swelling, and moderate exudation or moderate keratinization; 1 point was awarded for neither obvious redness nor exudation or mild keratinization; and 0 points were awarded for normal skin. The comprehensive scores of 10 mice in each group were calculated, and the results are shown in Table 1. It can be found that after desensitization and stimulation with DNCB, the auricle of the mice showed obvious swelling, and the degree of swelling increased significantly with the number of stimulations, the skin lesions gradually became more serious, and obvious crusting occurred; compared with the control group of the contact dermatitis model, the skin drug solution prepared in Example 1 of this invention can effectively alleviate the ear damage and crusting caused by DNCB sensitization.

[0148] Table 1

[0149]

[0150]

[0151] (2) Poor ear thickness (contact dermatitis)

[0152] The thickness of the middle part of the right ear was measured using a thickness gauge before induction and 24 hours after each stimulation. The difference in right ear thickness before and after stimulation was calculated. See Table 2, where n = 10. Statistical analysis is expressed as (X±s), * indicates P < 0.05, ** indicates P < 0.01, and the same applies below.

[0153] Table 2

[0154]

[0155] (3) Difference in ear weight (contact dermatitis)

[0156] After euthanizing the mice, ear pieces were drilled from the middle of both ears using an 8mm diameter punch, weighed, and the weight difference between the left and right ears was calculated. See Table 3, where n = 10.

[0157] Table 3

[0158]

[0159] The results in (2) and (3) show that, compared with the normal control group of contact dermatitis, the thickness of the right ear of mice in the contact dermatitis model control group was significantly increased after the first to fourth stimulations, and the final weight of the right ear and the weight difference between the right and left ears were also significantly increased. In the contact dermatitis positive drug group, the high-dose contact dermatitis test group, and the low-dose contact dermatitis test group, the thickness of the right ear of mice after the first to fourth stimulations was significantly lower than that of the contact dermatitis model control group, and the final weight of the right ear and the weight difference between the right and left ears were also significantly lower than those of the contact dermatitis model control group. This proves that the product prepared in this invention can improve the skin thickening symptoms caused by contact dermatitis in mice.

[0160] (4) Detection of serum IL-4 and IFN-γ (contact dermatitis)

[0161] Blood was collected in 1 ml samples from each eyeball of mice. The samples were centrifuged at 3000 rpm for 15 min. Serum samples were then collected and the levels of IL-4 and IFN-r were determined by ELISA according to the instructions of the IL-4 and IFN-r kits, respectively. See Table 4, where n = 8.

[0162] Table 4

[0163]

[0164] The results in (4) showed that, compared with the normal control group of contact dermatitis, the mice in the contact dermatitis model control group had significantly increased IL-4 and significantly decreased IFN-r. Compared with the contact dermatitis model control group, the mice in the positive drug group, high-dose group, and low-dose group of contact dermatitis test had significantly decreased IL-4 and significantly increased IFN-r, which proves from the perspective of serum factors that the product prepared in this invention can improve contact dermatitis in mice.

[0165] (5) Frequency of itching (itching)

[0166] Scratching of the head with forepaws, scratching of the trunk with hindaws, and biting of the whole body were used as indicators of itching in mice. The number of times the mice scratched within 15 minutes of the first scratch was recorded. See Table 5, where n=8.

[0167] Table 5

[0168] Group Scratch frequency (times / 15 min) Scratch normal control group 2.31±1.85 Scratch model control group 9.63±1.92 Scratch positive drug group 5.25±1.67** Scratch test high dose group 6.88±1.96 Scratch test low dose group 8.00±2.33

[0169] The results in (5) showed that the number of itching episodes in mice in the contact dermatitis model control group was significantly increased compared to the normal control group. In the contact dermatitis positive drug group and the high-dose contact dermatitis test group, the number of itching episodes in mice was significantly decreased compared to the contact dermatitis model control group; the number of itching episodes in the low-dose contact dermatitis test group was also somewhat decreased compared to the contact dermatitis model control group. This indicates that the product prepared in this invention does indeed have the effect of treating or preventing skin itching in mice.

[0170] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A pharmaceutical composition for treating or preventing pruritus, characterized in that, The ingredients include the following parts by weight: 50-200 parts of peony bark, 50-200 parts of red peony root, 50-200 parts of lobelia, 50-200 parts of sesame bark, 50-200 parts of licorice root, and 10-50 parts of borneol.

2. A method for preparing a pharmaceutical composition for treating or preventing pruritus as described in claim 1, characterized in that, Includes the following steps: Take the raw materials according to the weight proportions; extract the peony bark, red peony root, lobelia bark, sesame bark, and licorice root using conventional extraction methods, add borneol, and mix to obtain the final product.

3. The preparation method according to claim 2, characterized in that, The conventional extraction methods include one or more of the following: decoction extraction, maceration extraction, reflux extraction, and ultrasonic extraction; And / or, the extraction solvent is selected from at least one of ethanol and water; optionally, the extraction solvent is an aqueous ethanol solution; And / or, the number of extractions is at least 1; And / or, the extraction time is at least 24 hours; optionally, the extraction time is 24 to 96 hours. And / or, the ratio of the volume of the extraction solvent to the volume of the active pharmaceutical ingredient is ≥5; optionally, the ratio of the volume of the extraction solvent to the volume of the active pharmaceutical ingredient is 5 to 10.

4. The preparation method according to claim 2 or 3, characterized in that, Before the extraction operation, the process also includes the step of grinding peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder; optionally, it also includes the step of passing the obtained mixed powder through an 80-mesh sieve and removing the sieve material. And / or, prior to mixing, the step of grinding the borneol is also included; optionally, the borneol is ground into a fine powder; And / or, prior to mixing, the method further includes the step of preparing a borneol dilution; optionally, the diluent is selected from at least one of ethanol and water; optionally, the mass of the diluent is 4 to 6 times the mass of the borneol; further optionally, the diluent is an aqueous ethanol solution.

5. The preparation method according to claim 3 or 4, characterized in that, The volume fraction of ethanol in the ethanol-water solution is 50% to 80%.

6. The preparation method according to any one of claims 2 to 5, characterized in that, Includes the following steps: S1: Take the raw materials according to the weight proportions; S2: Grind peony bark, red peony root, lobelia bark, sesame bark, and licorice root into powder to obtain a mixed powder. Pass the powder through an 80-mesh sieve, take the sieve residue, add an ethanol aqueous solution, the volume ratio of the ethanol aqueous solution to the sieve residue is 5-10, extract for 24-96 hours, separate the solid and liquid to obtain a mixed extract. S3: Grind borneol into a fine powder, add an ethanol-water solution to obtain a diluted borneol solution, the mass of the ethanol-water solution being 4 to 6 times the mass of the borneol; S4: Mix the mixed extract and the borneol dilution to obtain the pharmaceutical composition for treating or preventing skin itching.

7. The use of a pharmaceutical composition for treating or preventing pruritus as described in claim 1, or a pharmaceutical composition for treating or preventing pruritus prepared by any one of claims 2 to 6, in the preparation of a medicament for treating or preventing pruritus.

8. The application according to claim 7, characterized in that, The medicament for treating or preventing pruritus also includes pharmaceutically acceptable excipients; optionally, the pharmaceutically acceptable excipients are selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, osmotic pressure regulators, stabilizers, suspending agents, coating materials, anti-adhesives, binding agents, penetration enhancers, pH adjusters, buffers, surfactants, absorbents, diluents, filter aids, and sustained-release materials.

9. The application according to claim 7 or 8, characterized in that, The dosage form of the medicine for treating or preventing skin itching includes a skin delivery preparation; optionally, the skin delivery preparation is selected from ointments, creams, gels, lotions, sprays, patches, films, creams, solutions, powders, or plasters.

10. The application according to any one of claims 7 to 9, characterized in that, The skin itching includes at least one of the following: skin itching caused by exogenous causes, skin itching caused by endogenous causes, and skin itching caused by environmental and physiological factors; optionally, the skin itching caused by exogenous causes includes skin itching caused by mosquito bites, allergic dermatitis, contact dermatitis, and fungal infection; optionally, the skin itching caused by endogenous causes includes neurodermatitis, secondary itching due to chronic diseases, damp-heat retention, blood stasis, and blood deficiency with wind-dryness; optionally, the skin itching caused by environmental and physiological factors includes damp-turbidity obstruction, damp-heat stagnation, heat-induced itching, and wind-induced itching.

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