External traditional Chinese medicine composition for dermatology department as well as preparation method and application of external traditional Chinese medicine composition

Abstract

The invention provides an external traditional Chinese medicine composition for the dermatology department and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The traditional Chinese medicine composition is prepared from fructus cnidii, rhizoma coptidis, cortex phellodendri, cortex dictamni, radix sophorae flavescentis, rhizoma polygoni cuspidati, herba violae, fructus kochiae, herba polygoni avicularis, herba artemisiae scopariae, rhizoma atractylodis, pericarpium zanthoxyli and borneol, the extraction process of the traditional Chinese medicine materials is adjusted in a targeted manner, the content of effective components in the extract is obviously increased, and particularly, the content of cnidium lactone and the content of volatile oil are obviously increased; the effects of dispelling wind, eliminating dampness, resisting inflammation, relieving itching and inhibiting bacteria in the traditional Chinese medicine composition are more effectively exerted; the proper oil-soluble matrix and water-soluble matrix are selected, and the mass ratio of the components is controlled, so that the water-soluble medicine component and the oil-soluble medicine component can be better mixed, and the stability of the composition can be obviously improved.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese medicine preparations, and in particular relates to a Chinese medicine composition for external use in dermatology, and a preparation method and application thereof. Background Art

[0002] The skin is a very important physiological organ of the body. It has a series of functions such as barrier, perception, temperature regulation, absorption, secretion, excretion, etc. It plays an irreplaceable role in maintaining the coordinated balance between the body and the surrounding environment and maintaining the normal physiological metabolism of the body. However, the occurrence of skin diseases seriously affects the health of the skin and hair. Infections of various bacteria and viruses and the inflammation caused by them are the main factors leading to skin and hair damage, dandruff, and skin itching.

[0003] The causes of pruritus are complex. The skin has itch receptors that transmit the sensation to the brain through nerve endings. The release of histamine in the affected area can promote the sensation of itch. Scratching can relieve itch due to tenderness, but it also promotes the release of more histamine, aggravating the itch, forming a vicious cycle of itch-scratching, leading to more serious skin damage and inflammation.

[0004] Skin allergy is the main cause of skin itching. There are many reasons for skin allergy, among which eczema is one of the most common allergic skin diseases. Its pathogenesis is: delayed hypersensitivity reaction caused by complex internal and external factors.

[0005] At present, the drugs for treating skin and hair damage are mainly western medicines such as antihistamines (such as loratadine, ebastine, cetirizine hydrochloride, etc.), antibiotics (terbinafine hydrochloride, itraconazole, terbinafine, fluconazole, etc.), hormones (such as desonide cream, mometasone furoate ointment, compound flumethasone ointment, etc.), vitamins and antiviral drugs (such as acyclovir, valacyclovir, penciclovir, recombinant human interferon), etc. These drugs, especially oral drugs, are very easy to produce drug resistance and drug tolerance, destroy the balance of the body's flora, and have serious side effects, even causing increased blood sugar, centripetal obesity, reduced immunity, stress ulcers, and aggravated gastric ulcers.

[0006] As the side effects of Western medicines become apparent, more and more studies are being conducted on Chinese medicine compositions for external use on the skin. For example, Chinese patent CN113398237A discloses an antibacterial, antipruritic and anti-dandruff Chinese medicine composition, which comprises the following raw materials in weight proportions: 60-100 parts of Artemisia argyi, 60-100 parts of ginger, 60-100 parts of processed Polygonum multiflorum, 60-100 parts of Alpinia officinalis, 60-100 parts of Rehmannia root, 60-100 parts of Zedoariae rhizome, The composition comprises 60-100 parts of radix spatholobi, 60-100 parts of eclipta prostrata, 60-100 parts of podifera, 60-100 parts of asarum, 60-100 parts of lotus leaf, 60-100 parts of walnut kernel, 60-100 parts of black mulberry, 60-100 parts of oriental arborvitae leaf, 60-100 parts of cnidium monnieri, 60-100 parts of zanthoxylum bungeanum, 60-100 parts of wax gourd peel, 60-100 parts of white mulberry bark and 60-100 parts of dandelion. The composition has the characteristics of mildness, long-lasting effect and non-irritation, and is widely used in external preparations for washing and protecting the skin and hair of people and animals, such as shampoo, hand sanitizer (cream or gel) and animal fur cleaner.

[0007] Another example is Chinese patent CN104147481A, which discloses an antipruritic external Chinese medicine composition and a preparation method thereof. The Chinese medicine composition is prepared from the following Chinese medicine raw materials: Stephania tetrandra, loofah, raw rehmannia, papaya, rush, liquorice, akebia, safflower, golden cherry, schisandra, asparagus, bamboo shavings, lycopodii bark, arctium, siler, immature bitter orange, cyperus, morinda officinalis, raspberry, plantain, thorny rose fruit, galangal, tangerine peel, purslane, fresh reed root, evodia, magnolia bark, eclipta, pollen, tribulus, golden buckwheat, snow lotus, burdock root. The Chinese medicine composition of the present invention, especially when prepared into an external preparation, can more effectively relieve skin allergies, eczema, or itching caused by mosquito bites and insect bites.

[0008] For example, Chinese patent CN100522206A discloses a non-hormonal anti-inflammatory external Chinese medicine ointment, and also provides a preparation process of the ointment. The ointment is mainly prepared from Cnidium monnieri, Coptis chinensis, Phellodendron chinense, Dictamni cortex, Sophora flavescens, Polygonum cuspidatum, Viola yedoensis, Kochia scoparia, Polygonum multiflorum, Artemisia capillaris, Atractylodes lancea, Zanthoxylum bungeanum and borneol. The Chinese medicine composition has the effects of clearing away heat and dampness, dispelling wind and relieving itching. It is clinically used to treat skin diseases such as eczema and atopic dermatitis, with significant effects, is non-irritating to the skin, non-allergic, non-toxic and side effects, and has a high degree of safety and effectiveness.

[0009] However, the effective ingredients of Chinese herbal medicines need to be extracted during use. At present, there are widespread problems of incomplete extraction of Chinese herbal medicines and serious loss of effective ingredients. The extraction process of effective ingredients in Chinese herbal compositions needs to be further optimized. Therefore, it is urgent to develop a Chinese herbal composition for external use in dermatology that has a high content of active ingredients and can effectively dehumidify and relieve itching. Summary of the invention

[0010] Based on the problems existing in the prior art, the present invention aims to provide a dermatological external Chinese medicine composition and a preparation method thereof. The present invention optimizes the extraction process of the Chinese medicine composition and uses the existing dermatological external Chinese medicine composition as a raw material to obtain a dermatological external Chinese medicine composition with a high content of active ingredients and significant anti-inflammatory and antipruritic effects.

[0011] During the implementation process, based on the fact that the Chinese medicinal materials used have anti-inflammatory and anti-allergic effects as well as antibacterial effects, different methods are used to extract the above-mentioned Chinese medicinal ingredients separately. The dermatological external preparation prepared from the extracts has good dehumidifying, antipruritic and anti-inflammatory effects.

[0012] In order to achieve the above object, the present invention adopts the following technical solutions:

[0013] The present invention provides a method for preparing a dermatological external Chinese medicine composition, comprising the following steps:

[0014] (1) adding 20-40 times the amount of water to the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum to distill and extract 2-3 times for 1-3 hours, collecting volatile oil, filtering the liquid to obtain extract 1 and residue;

[0015] (2) adding 8-12 times the amount of water to the formulated amount of coptis root, phellodendron, dactylum bark, sophora flavescens, polygonum cuspidatum, viola yedoensis, kochia scoparia, polygonum multiflorum, capillaris and the residue obtained in step (1), and boiling and extracting 1-2 times, the extraction time is 1 hour, and filtering the liquid to obtain extract 2;

[0016] (3) After extract 1 and extract 2 are mixed, they are concentrated to a relative density of 1.10-1.20 (60° C.), ethanol is added to make the alcohol content 60%-70%, stirred, allowed to stand, the supernatant is taken to recover ethanol, and concentrated to a relative density of 1.10-1.20 (60° C.), and then the pH value is adjusted to 5 with citric acid, and a penetration enhancer, a water-soluble matrix and a preservative are added respectively, heated to 70° C., and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase;

[0017] (4) mixing the oil-soluble matrix, heating to 70° C., and filtering to prepare an oil phase;

[0018] (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40° C., a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensation, and obtaining the Chinese medicine composition.

[0019] Preferably, the amount of water added in the above step (1) is 20-40 times, the number of extractions is 2 times, and the extraction time is 1-3 hours;

[0020] More preferably, the specific steps of the above step (1) are: distill and extract the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum in the formula amount twice, add 40 times the amount of water for the first time, and the extraction time is 3 hours, and add 20 times the amount of water for the second time, and the extraction time is 1 hour, collect volatile oil, and filter the liquid to obtain extract 1 and residue.

[0021] Preferably, the amount of water added in the above step (2) is 8-12 times the amount, and the decoction is performed twice, and the extraction time is 1 hour;

[0022] More preferably, the specific steps of the above step (2) are: add water to the formula amount of Coptis chinensis, Phellodendron chinense, Dictamni cortex, Sophora flavescens, Polygonum cuspidatum, Viola yedoensis, Kochia scoparia, Polygonum multiflorum, Capillaris capillaris and the residues obtained in step (1) and boil and extract twice, adding 12 times the amount of water for the first time and the extraction time is 1 hour, adding 8 times the amount of water for the second time and the extraction time is 1 hour, and filtering the medicinal liquid to obtain extract 2.

[0023] In the above step (5), the mass volume ratio of the volatile oil and borneol to the mass volume of ethanol is 0.5-2.0 g:15-20 mL.

[0024] The content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0025] 150-180 part of Fructus Cnidii, 30-50 part of Rhizoma Coptidis, 30-50 part of Cortex Phellodendri, 40-70 part of Cortex Dictamni, 40-70 part of Sophora Flavescentis, 60-90 part of Polygonum Cuspidati, 60-90 part of Viola Yenda, 80-110 part of Fructus Kochiae, 30-60 part of Polygonum Multiflorum, 30-60 part of Artemisia Capillaris, 20-40 part of Atractylodes, 15-35 part of Zanthoxylum bungeanum, and 10-25 part of Borneolum Syntheticum.

[0026] Preferably, the content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0027] Fructus Cnidium monnieri 167g, Rhizoma Coptidis 37g, Rhizoma Phellodendri 37g, Cortex Dictamni 56g, Sophora flavescens 56g, Polygonum cuspidatum 74g, Viola yedoensis 74g, Fructus Kochiae 93g, Polygonum multiflorum 56g, Artemisia capillaris 56g, Atractylodes lancea 37g, Zanthoxylum bungeanum 19g and Borneol 15g.

[0028] The penetration enhancer in the dermatological external Chinese medicine composition is dodecyltrimethylammonium bromide, and the water-soluble matrix is ​​a mixture of glycerol and sodium alginate, and the mass ratio of the two is 3-5:1, preferably 4:1.

[0029] The preservative is ethylparaben.

[0030] The oil-soluble matrix is ​​a mixture of vaseline, lanolin and glyceryl monostearate, with a mass ratio of the three being 5-8:1:2, preferably 6:1:2.

[0031] During the implementation of the present invention, it was found that the use of vaseline, lanolin and glyceryl monostearate as the oil-soluble matrix can better increase its hydrophilicity, thereby better mixing with the water-soluble matrix of the mixture of glycerol and sodium alginate, so that the active ingredients are more evenly dispersed.

[0032] As some preferred embodiments, the mass ratio of the oil-soluble matrix to the water-soluble matrix is ​​2-3.5:1, preferably 2.5-3:1.

[0033] The added amount of the penetration enhancer is 1-1.5% of the total amount of the traditional Chinese medicine ingredients.

[0034] The amount of the water-soluble matrix added is 15-25% of the total amount of the traditional Chinese medicine ingredients.

[0035] The amount of the solvent matrix added is 45-55% of the total amount of the traditional Chinese medicine ingredients.

[0036] The present invention also provides a dermatological external Chinese medicinal composition prepared by the preparation method.

[0037] The present invention also provides the use of the above-mentioned Chinese medicine composition for external use in dermatology in the preparation of a medicinal preparation for treating dehumidification and relieving itching.

[0038] The present invention also provides a dermatological external-use pharmaceutical preparation, comprising the dermatological external-use Chinese medicinal composition prepared by the above-mentioned preparation method.

[0039] The dosage form of the dermatological external preparation is lotion, ointment or gel.

[0040] The Chinese medicine used in the present invention and its effects are as follows:

[0041] Cnidium monnieri (L.) Cuss.: This product is the dried mature fruit of the plant Cnidium monnieri (L.) Cuss. of the Umbelliferae family. The fruit is harvested in summer and autumn when it is ripe, and then removed of impurities and dried in the sun. It has the effects of drying dampness and dispelling wind, killing insects and relieving itching, and warming the kidney and strengthening yang. It is mainly used to treat vaginal itching and leucorrhea, eczema itching, dampness and arthralgia, low back pain, kidney deficiency and impotence, and uterine coldness and infertility.

[0042] Coptis chinensis: This product is the dried rhizome of Coptis chinensis Franch., Coptisdeltoidea CYCheng et Hsiao or Coptis teeta Wall. of the Ranunculaceae family. It has the effects of clearing away heat and dampness, purging fire and detoxifying, and is mainly used to treat damp-heat fullness, vomiting and acid regurgitation, diarrhea, jaundice, high fever and coma, hyperactivity of heart fire, restlessness and insomnia, palpitations, vomiting and bleeding due to blood heat, red eyes, toothache, thirst, carbuncle, furuncle; externally, it can treat eczema, wet sores, and pus in the ear canal.

[0043] Phellodendron chinense Schneid.: This product is the dried bark of Phellodendron chinense Schneid., a plant of the Rutaceae family. It is commonly known as "Sichuan Phellodendron". After peeling the bark, remove the rough skin and dry it in the sun. It has the effects of clearing away heat and dampness, purging fire and removing steam, detoxifying and curing sores. It is mainly used to treat damp-heat diarrhea, jaundice and red urine, vaginal itching, hot stranguria, beriberi, bone steaming and fatigue fever, night sweats, spermatorrhea, sores, swelling and poison, eczema and wet sores.

[0044] Dictamnus dasycarpus Turcz.: This product is the dried root bark of Dictamnus dasycarpus Turcz. of the Rutaceae family. The roots are dug up in spring and autumn, the sand and rough bark are removed, the root bark is peeled off and dried. It has the effects of clearing away heat and dampness, dispelling wind and detoxifying. It is mainly used to treat damp-heat sores, yellow water dripping, eczema, rubella, scabies, sores, rheumatism, heat arthralgia, jaundice and red urine.

[0045] Sophora flavescens: This product is the dried root of Sophora flavescens Ait., a plant of the Leguminosae family. It is collected in spring and autumn, the root head and small branches are removed, washed and dried, or sliced ​​and dried while fresh. It has the effects of clearing away heat and dampness, killing insects, and diuresis. It is mainly used to treat heat dysentery, blood in stool, jaundice and urine retention, red and white vaginal discharge, vaginal swelling and itching, eczema, wet sores, skin itching, scabies and leprosy; it is also used externally to treat trichomonas vaginitis.

[0046] Polygonum cuspidatum: This product is the dried rhizome and root of Polygonum cuspidatum Sieb.et Zucc. of the Polygonaceae family. It is dug in spring and autumn, the fibrous roots are removed, washed, cut into short sections or thick slices while fresh, and dried in the sun. It has the effects of promoting dampness and relieving jaundice, clearing away heat and detoxifying, dispersing blood stasis and relieving pain, and relieving cough and reducing phlegm. It is mainly used to treat damp-heat jaundice, stranguria, leucorrhea, rheumatic pain, carbuncle, burns, amenorrhea, abdominal mass, traumatic injury, and cough due to lung heat.

[0047] Viola yedoensis: This product is the dried whole herb of Viola yedoensis Makino, a plant of the Violaceae family. It is harvested in spring and autumn, impurities are removed, and it is dried in the sun. It has the effects of clearing away heat and detoxifying, cooling blood and reducing swelling. It is mainly used to treat carbuncle, carbuncle, erysipelas, and snake bites.

[0048] Kochia scoparia: This product is the dried mature fruit of Kochia scoparia (L.) Schrad., a plant of the Chenopodiaceae family. The plant is harvested in autumn when the fruit is ripe, dried in the sun, the fruit is beaten, and impurities are removed. It has the effects of clearing away heat and dampness, dispelling wind and relieving itching. It is mainly used to treat painful urination, vaginal itching and leucorrhea, urticaria, eczema, and skin itching.

[0049] Polygonum aviculare L.: This product is the dried aerial part of Polygonum aviculare L., a plant of the Polygonaceae family. It is harvested in summer when the leaves are lush, the roots and impurities are removed, and it is dried in the sun. It has the effects of diuresis, stranguria, insecticide, and antipruritic. It is mainly used to treat hot stranguria, painful and astringent, short and red urine, abdominal pain caused by insect accumulation, skin eczema, and vaginal itching and leucorrhea.

[0050] Artemisia scoparia: This product is the dried aerial part of Artemisia scoparia Waldst.et Kit. or Artemisia capillaris Thunb. of Asteraceae. It is harvested in spring when the seedlings are 6-10cm high or harvested in autumn when the flower buds grow to the beginning of the flowers, remove impurities and old stems, and dry in the sun. The one harvested in spring is commonly known as "cotton artemisia", and the one harvested in autumn is called "flower artemisia". It has the effects of clearing dampness and heat, promoting bile and relieving jaundice. It is mainly used to treat jaundice, oliguria, damp-heat and summer-heat, and itching of wet sores.

[0051] Atractylodes: This product is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz. of the Asteraceae family. It is dug in spring and autumn, sand is removed, sun-dried, and the fibrous roots are knocked off. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, and improving eyesight. It is mainly used to treat dampness blocking the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatism, colds, night blindness, and blurred vision.

[0052] Zanthoxylum schinifolium Sieb.et Zucc. or Zanthoxylum bungeanum Maxim., a plant of the Rutaceae family, is a dried, mature fruit peel. The mature fruit is harvested in autumn, dried in the sun, and the seeds and impurities are removed. It has the effects of warming the middle and relieving pain, killing insects and relieving itching. It is mainly used to treat cold pain in the abdomen, vomiting, diarrhea, and abdominal pain caused by insect accumulation; it is also used externally to treat eczema and vaginal itching.

[0053] Borneol: This product is colorless, transparent or white, translucent, crispy crystals in the form of flakes; it has a light fragrance, a pungent and cool taste; it is volatile, produces thick smoke when ignited, and has a bright flame. It has the effects of awakening the mind, clearing away heat and relieving pain. It is mainly used to treat fever, coma, convulsions, stroke, phlegm, qi stagnation, coma, chest pain, red eyes, mouth sores, sore throat, and pus in the ear canal.

[0054] Compared with the prior art, the present invention has the following beneficial effects:

[0055] (1) The present invention adopts the traditional Chinese medicine composition of Cnidium monnieri, Coptis chinensis, Phellodendron chinense, Dictamni cortex, Sophora flavescens, Polygonum cuspidatum, Viola yedoensis, Kochia scoparia, Polygonum multiflorum, Artemisia capillaris, Atractylodes lancea, Zanthoxylum bungeanum and Borneol, and specifically adjusts the extraction process of the Chinese medicinal materials to more effectively exert the wind-dispelling and dampness-removing, anti-inflammatory, antipruritic and antibacterial effects of the Chinese medicine composition. The dermatological external ointment prepared by the dermatological external Chinese medicine composition obtained by the preparation method of the present invention has good anti-inflammatory and anti-allergic effects, and also has a certain antibacterial effect.

[0056] (2) The present invention significantly increases the content of effective ingredients in the extract by adjusting the material-liquid ratio and the extraction time during the extraction process, especially the content of osthole and volatile oil.

[0057] (3) The preparation method provided by the present invention can efficiently extract medicinal materials, and can significantly improve the therapeutic effect of the traditional Chinese medicine composition without the need to extract each medicinal material separately.

[0058] (4) The present invention selects appropriate oil-soluble matrix and water-soluble matrix and controls the mass ratio between the components, so that the water-soluble drug components and the oil-soluble drug components can be better mixed and the stability of the composition can be significantly improved. DETAILED DESCRIPTION

[0059] The following will be combined with the tables in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0060] Hereinafter, examples and comparative examples of the present invention will be shown to explain the composition of the present invention in more detail, but the present invention is not limited thereto.

[0061] Example 1 Preparation method of a dermatological external Chinese medicine composition

[0062] The following steps are involved:

[0063] (1) adding 40 times the amount of water to the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum used in the formula and distilling and extracting twice for 3 hours, collecting volatile oil, and filtering the liquid to obtain extract 1 and residue;

[0064] (2) boiling and extracting the dregs of the medicinal residues obtained in step (1) with water twice, adding 12 times the amount of water for the first time and 8 times the amount of water for the second time, the extraction time is 1 hour, and filtering the medicinal solution to obtain extract 2;

[0065] (3) After extract 1 and extract 2 are mixed, they are concentrated to 1.10-1.20 (60° C.), ethanol is added to make the alcohol content 60%, stirred, allowed to stand, the supernatant is taken to recover ethanol, and concentrated to a relative density of 1.10-1.20 (60° C.), and then the pH value is adjusted to 5 with citric acid, and dodecyltrimethylammonium bromide, glycerol, sodium alginate and ethylparaben are added respectively, heated to 70° C., and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase;

[0066] (4) Mix vaseline, lanolin and glyceryl monostearate, heat to 70° C., filter and prepare an oil phase;

[0067] (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40°C, a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensed, and preparing 1000 g, thereby obtaining the Chinese medicine composition.

[0068] The content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0069] Fructus Cnidium monnieri 167g, Rhizoma Coptidis 37g, Rhizoma Phellodendri 37g, Cortex Dictamni 56g, Sophora flavescens 56g, Polygonum cuspidatum 74g, Viola yedoensis 74g, Fructus Kochiae 93g, Polygonum multiflorum 56g, Artemisia capillaris 56g, Atractylodes lancea 37g, Zanthoxylum bungeanum 19g and Borneol 15g.

[0070] The content of dodecyltrimethylammonium bromide is 9.2g;

[0071] The total mass of the glycerol and sodium alginate is 120 g, and the mass ratio of the two is 3:1;

[0072] The total mass of the vaseline, lanolin and glyceryl monostearate is 372 g, and the mass ratio of the three is 5:1:2.

[0073] Example 2 Preparation method of a dermatological external Chinese medicine composition

[0074] The following steps are involved:

[0075] (1) Add water to the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum in the prescribed amount and distill and extract twice, adding 16 times the amount of water each time, the first distillation extraction is 3 hours, and the second distillation extraction is 1 hour, the volatile oil is collected, and the liquid is filtered to obtain an extract 1 and a residue;

[0076] (2) boiling and extracting the dregs of the medicinal residues obtained in step (1) with water twice, adding 12 times the amount of water for the first time and 8 times the amount of water for the second time, the extraction time is 1 hour, and filtering the medicinal solution to obtain extract 2;

[0077] (3) After extract 1 and extract 2 are mixed, they are concentrated to 1.10-1.20 (60° C.), ethanol is added to make the alcohol content 60%, stirred, allowed to stand, the supernatant is taken to recover ethanol, and concentrated to a relative density of 1.10-1.20 (60° C.), and then the pH value is adjusted to 5 with citric acid, and dodecyltrimethylammonium bromide, glycerol, sodium alginate and ethylparaben are added respectively, heated to 70° C., and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase;

[0078] (4) Mix vaseline, lanolin and glyceryl monostearate, heat to 70° C., filter and prepare an oil phase;

[0079] (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40°C, a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensed, and preparing 1000 g, thereby obtaining the Chinese medicine composition.

[0080] The content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0081] Fructus Cnidium monnieri 167g, Rhizoma Coptidis 37g, Rhizoma Phellodendri 37g, Cortex Dictamni 56g, Sophora flavescens 56g, Polygonum cuspidatum 74g, Viola yedoensis 74g, Fructus Kochiae 93g, Polygonum multiflorum 56g, Artemisia capillaris 56g, Atractylodes lancea 37g, Zanthoxylum bungeanum 19g and Borneol 15g.

[0082] The content of dodecyltrimethylammonium bromide is 11.5g;

[0083] The total mass of the glycerol and sodium alginate is 192 g, and the mass ratio between the two is 5:1;

[0084] The total mass of the vaseline, lanolin and glyceryl monostearate is 425 g, and the mass ratio of the three is 7:1:2.

[0085] Example 3 Preparation method of a dermatological external Chinese medicine composition

[0086] The following steps are involved:

[0087] (1) distilling and extracting the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum in the prescribed amount twice, adding 40 times the amount of water each time, distilling and extracting for 3 hours for the first time and 1 hour for the second time, collecting volatile oil, filtering the liquid to obtain extract 1 and residue;

[0088] (2) boiling and extracting the dregs of the medicinal residues obtained in step (1) with water twice, adding 12 times the amount of water for the first time and 8 times the amount of water for the second time, the extraction time is 1 hour, and filtering the medicinal solution to obtain extract 2;

[0089] (3) After extract 1 and extract 2 are mixed, they are concentrated to 1.10-1.20 (60° C.), ethanol is added to make the alcohol content 60%, stirred, allowed to stand, the supernatant is taken to recover ethanol, and concentrated to a relative density of 1.10-1.20 (60° C.), and then the pH value is adjusted to 5 with citric acid, and dodecyltrimethylammonium bromide, glycerol, sodium alginate and ethylparaben are added respectively, heated to 70° C., and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase;

[0090] (4) Mix vaseline, lanolin and glyceryl monostearate, heat to 70° C., filter and prepare an oil phase;

[0091] (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40°C, a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensed, and preparing 1000 g, thereby obtaining the Chinese medicine composition.

[0092] The content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0093] Fructus Cnidium monnieri 167g, Rhizoma Coptidis 37g, Rhizoma Phellodendri 37g, Cortex Dictamni 56g, Sophora flavescens 56g, Polygonum cuspidatum 74g, Viola yedoensis 74g, Fructus Kochiae 93g, Polygonum multiflorum 56g, Artemisia capillaris 56g, Atractylodes lancea 37g, Zanthoxylum bungeanum 19g and Borneol 15g.

[0094] The content of dodecyltrimethylammonium bromide is 10g;

[0095] The total mass of the glycerol and sodium alginate is 155 g, and the mass ratio of the two is 5:1;

[0096] The total mass of the vaseline, lanolin and glyceryl monostearate is 388.8 g, and the mass ratio of the three is 6:1:2.

[0097] Comparative Example 1

[0098] Prepared according to the method disclosed in the prior art CN100522206C, specifically:

[0099] The above thirteen herbs, except borneol, add 16 times the amount of water to Cnidium monnieri, Zanthoxylum bungeanum, and Atractylodes lancea, distill and extract for 6 hours, collect volatile oil, filter the liquid medicine, and set aside; the residue and the other nine herbs are decocted twice with water, each time for 1 hour, add 12 times the amount of water for the first time, and add 8 times the amount of water for the second time, filter, combine the filtrate with the distilled liquid medicine, concentrate to a relative density of 1.10-1.20 (60°C), adjust the pH value to 5 with citric acid, add appropriate amounts of sodium dodecyl sulfate, glycerol, and ethyl hydroxybenzoate respectively, heat to 70°C, stir for 30 minutes until the contents are fully mixed, and prepare the water phase. Take appropriate amounts of vaseline and hexadecanol, mix, heat to 70°C, filter, and prepare the oil phase. Slowly pour the water phase into the oil phase, stirring while adding, wait until the temperature drops to 38-40°C, dissolve the volatile oil and borneol in 20ml ethanol, add to the above mixture, stir until condensed, prepare 1000g, and pack.

[0100] Comparative Example 2

[0101] The difference from Example 3 is that the cream is prepared using the excipients disclosed in CN100522206C, specifically:

[0102] (1) distilling and extracting the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum in the prescribed amount twice, adding 40 times the amount of water each time, distilling and extracting for 3 hours for the first time and 1 hour for the second time, collecting volatile oil, filtering the liquid to obtain extract 1 and residue;

[0103] (2) boiling and extracting the dregs of the medicinal residues obtained in step (1) with water twice, adding 12 times the amount of water for the first time and 8 times the amount of water for the second time, the extraction time is 1 hour, and filtering the medicinal solution to obtain extract 2;

[0104] (3) After extract 1 and extract 2 are mixed, ethanol is added to make the alcohol content 60%, stirred, allowed to stand, the supernatant is taken to recover the ethanol, and concentrated to a relative density of 1.10-1.20 (60° C.), then the pH value is adjusted to 5 with citric acid, 10 g of sodium lauryl sulfate, 160 g of glycerol and 1.5 g of ethylparaben are added respectively, the mixture is heated to 70° C., and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase;

[0105] (4) Mix 245 g of vaseline and 160 g of hexadecanol, heat to 70° C., and filter to prepare an oil phase;

[0106] (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40°C, a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensed, and preparing 1000 g, thereby obtaining the Chinese medicine composition.

[0107] The content of the Chinese medicinal ingredients in the dermatological external Chinese medicinal composition is:

[0108] Fructus Cnidium monnieri 167g, Rhizoma Coptidis 37g, Rhizoma Phellodendri 37g, Cortex Dictamni 56g, Sophora flavescens 56g, Polygonum cuspidatum 74g, Viola yedoensis 74g, Fructus Kochiae 93g, Polygonum multiflorum 56g, Artemisia capillaris 56g, Atractylodes lancea 37g, Zanthoxylum bungeanum 19g and Borneol 15g.

[0109] Comparative Example 3

[0110] The difference from Example 3 is that the mass ratio of vaseline, lanolin and glyceryl monostearate is 4:2:3, and the rest is the same as Example 3.

[0111] Comparative Example 4

[0112] The difference from Example 3 is that the mass ratio of the oil-soluble matrix to the water-soluble matrix is ​​1.5:1, that is, the total mass of the glycerol and sodium alginate is 217.52 g, of which glycerol is 181.26 g and sodium alginate is 36.26 g;

[0113] The total mass of the vaseline, lanolin and glyceryl monostearate is 326.28 g, including 217.52 g of vaseline, 36.25 g of lanolin and 72.51 g of glyceryl monostearate.

[0114] Effect experiment:

[0115] 1. Detection of active ingredient content

[0116] Detection method:

[0117] [Content Determination] Determined by high performance liquid chromatography (General Rules 0512 of the Chinese Pharmacopoeia 2020 Edition).

[0118] The chromatographic conditions and system suitability test used octadecylsilane bonded silica gel as filler, methanol-0.1 mol / L ammonium sulfate solution (70:30) as mobile phase, and the detection wavelength was 322 nm. The theoretical plate number calculated based on the osthole peak should be no less than 3000.

[0119] Preparation of reference solution: Take an appropriate amount of osthole reference substance, weigh it accurately, and add methanol to prepare a solution containing 15 μg per 1 ml.

[0120] Preparation of test solution: Take about 2 g of the product, weigh it accurately, put it in a stoppered conical flask, add 50 ml of methanol accurately, stopper it, weigh it, treat it with ultrasound (300 W, 40 kHz) for 30 minutes, let it cool, weigh it again, make up the lost weight with methanol, shake it well, filter it, and take the filtrate to obtain the solution.

[0121] Determination method: Accurately pipette 10 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0122] Each 1g of this product contains osthole (C 15 H 16 O3), not less than 0.40 mg.

[0123] The test results are shown in Table 1 below.

[0124] Table 1

[0125] Osthole(mg / g) Volatile oil (mL) Example 1 0.72 2.5 Example 2 0.68 2.2 Example 3 0.75 2.8 Comparative Example 1 0.45 0.8

[0126] According to the test results in Table 1 above, the extraction method provided by the present invention significantly increases the content of effective ingredients in the extract by adjusting the material-liquid ratio and the extraction time during the extraction process, especially the content of osthole and the content of volatile oil are significantly increased, so that the content of osthole reaches more than 0.7 mg / g, and the content of volatile oil reaches more than 2.0 mL; while when the extraction method disclosed in the prior art is used, the content of osthole and the content of volatile oil are significantly reduced, resulting in a significant reduction in the utilization rate of traditional Chinese medicine.

[0127] 2. Transdermal test

[0128] Transdermal penetration test:

[0129] Referring to the master's thesis (Preparation and quality evaluation of TPGS-modified long-circulating liposomes of Sanguisorba officinalis saponin I, author: Song Tingting, Zunyi Medical University, 2021), the specific steps of the test are as follows:

[0130] (1) In this experiment, osthole was used as a test index, and the mass m of osthole in the sample of the pharmaceutical composition of the present invention was detected by HPLC.

[0131] (2) Healthy SD rats were killed by cervical dislocation, and the abdominal hair was removed with an electric razor. The abdominal skin was peeled off and processed. The processed abdominal skin was fixed between the sample pool and the receiving pool, and the sample of the pharmaceutical composition prepared by the present invention was applied to the stratum corneum of the mouse (the area of ​​the stratum corneum of the SD rat in contact with the drug-loading layer was 9 cm);

[0132] (3) The transdermal test was conducted on a TK6-500 transdermal diffusion tester. The tester was equipped with three diffusion cells. The cell structure was the same as the Franz cell, but the size was proportionally reduced. The cell opening area was about 9 cm 2 , the volume of each receiving pool is pre-calibrated, and the volume of each pool is in the range of 8-8.6mL;

[0133] (4) Prepare 0.9 wt % physiological saline as the receiving solution, fix the sample pool, keep the temperature at (32 ± 0.5) ° C, take samples at 1, 2, 4, 6, and 8 hours, 0.5 mL each time, and add an equal volume of receiving solution. The concentration of osthole in the receiving solution was detected by HPLC, and the cumulative permeability Q of osthole was calculated by formula 1. The test results are shown in Table 2.

[0134]

[0135] Where: V0 is the total volume of the sample, C i and C n is the drug mass concentration (mg / mL) measured at the i-th and n-th time points, V i is the sampling volume (mL), and m represents the total mass of total flavonoids in the sample.

[0136] Table 2

[0137] 8-hour cumulative transmittance Q / % Example 1 86.25 Example 2 88.42 Example 3 92.86 Comparative Example 2 80.13 Comparative Example 3 82.90 Comparative Example 4 78.56

[0138] According to the test results in Table 2 above, the transdermal permeation effect of the pharmaceutical compositions prepared in Examples 1-3 of the present invention is good, and the cumulative permeability in 8 hours can reach more than 85%, especially in Example 3, by controlling the type and ratio of the matrix components in the pharmaceutical composition, the transdermal permeation effect of the obtained pharmaceutical composition is the best, which can reach more than 90%; in Comparative Example 2, the transdermal effect of the pharmaceutical composition prepared using the matrix disclosed in the prior art is lower than that of the embodiment; in Comparative Example 3, changing the mass ratio of vaseline, lanolin and glyceryl monostearate will also affect the transdermal effect of the drug; in Comparative Example 4, changing the mass ratio of the oil-soluble matrix to the water-soluble matrix will significantly affect the mixing of the drug components, and thus have a significant effect on the transdermal effect.

[0139] 3. Stability

[0140] Centrifugation: Take an appropriate amount of sample into a centrifuge tube and centrifuge at 3500 rpm for 3 times, each time for 10 minutes. There should be no stratification or oil separation.

[0141] Freeze-thaw: Place the samples at a constant temperature of 55℃ for 6 hours and -15℃ for 24 hours for heat resistance and freezing tests, and restore them to room temperature for observation. No stratification or oil separation should occur.

[0142] The test results are shown in Table 3 below.

[0143] Table 3

[0144] name Centrifugation Heat resistant freezing Example 1 No stratification No stratification No stratification Example 2 No stratification No stratification No stratification Example 3 No stratification No stratification No stratification Comparative Example 2 Layering, a small amount of oil precipitation Layering, a small amount of oil precipitation No stratification Comparative Example 3 Layering, a small amount of oil precipitation Layering, more oil precipitation No stratification Comparative Example 4 Layering, more oil precipitation Layering, more oil precipitation No stratification

[0145] According to the test results in Table 3 above, the pharmaceutical composition provided by the present invention has better stability, and both heat resistance and cold resistance meet the requirements; the centrifugation and freeze-thaw test results in Comparative Examples 2-4 do not meet the requirements for the stability of the ointment, indicating that the selection of different excipients has a significant impact on its stability. In particular, the impact on heat resistance is greater; in particular, in Comparative Example 4, the mass ratio of the oil-soluble matrix to the water-soluble matrix is ​​changed to 1.5:1, and the stratification and oil separation amount after centrifugation and high temperature treatment are high, which does not meet the requirements for the stability of the ointment.

[0146] 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 in the protection scope of the present invention.

Claims

1. A method for preparing a dermatological external Chinese medicine composition, characterized in that: The following steps are involved: (1) adding 20-40 times the amount of water to the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum to distill and extract 2-3 times for 1-3 hours, collecting volatile oil, filtering the liquid to obtain extract 1 and residue; (2) adding 8-12 times the amount of water to the formulated amount of coptis root, phellodendron, dactylum bark, sophora flavescens, polygonum cuspidatum, viola yedoensis, kochia scoparia, polygonum multiflorum, capillaris and the residue obtained in step (1), and boiling and extracting 1-2 times, the extraction time is 1 hour, and filtering the liquid to obtain extract 2; (3) extract 1 and extract 2 are mixed and concentrated to 1.10-1.20, 60°C, ethanol is added to make the alcohol content 60%-70%, stirred, allowed to stand, the supernatant is taken to recover ethanol, and concentrated to a relative density of 1.10-1.20, 60°C, and then citric acid is used to adjust the pH value to 5, and a penetration enhancer, a water-soluble matrix and a preservative are added respectively, heated to 70°C, and stirred for 30 minutes until the contents are completely mixed to prepare an aqueous phase; (4) mixing the oil-soluble matrix, heating to 70° C., and filtering to prepare an oil phase; (5) slowly pouring the aqueous phase into the oil phase while stirring, and when the temperature drops to 38-40° C., a mixture is obtained; dissolving the volatile oil and borneol in ethanol to obtain a mixed solution; adding the mixed solution to the mixture, stirring until condensation, and obtaining the Chinese medicine composition.

2. The preparation method according to claim 1, characterized in that: The raw materials of the dermatological external Chinese medicine composition are composed of the following components in parts by weight: 150-180 part of Fructus Cnidii, 30-50 part of Rhizoma Coptidis, 30-50 part of Cortex Phellodendri, 40-70 part of Cortex Dictamni, 40-70 part of Sophora Flavescentis, 60-90 part of Polygonum Cuspidati, 60-90 part of Viola Yenda, 80-110 part of Fructus Kochiae, 30-60 part of Polygonum Multiflorum, 30-60 part of Artemisia Capillaris, 20-40 part of Atractylodes, 15-35 part of Zanthoxylum bungeanum, and 10-25 part of Borneolum Syntheticum.

3. The preparation method according to claim 1, characterized in that: The amount of water added in step (1) is 20-40 times, the number of extractions is 2 times, and the extraction time is 1-3 hours. The specific steps are: adding water to the Cnidium monnieri, Atractylodes lancea and Zanthoxylum bungeanum in the formula amount and distilling and extracting twice, adding 40 times the amount of water for the first time and extracting for 3 hours, adding 20 times the amount of water for the second time and extracting for 1 hour, collecting volatile oil, and filtering the liquid to obtain extract 1 and residues.

4. The preparation method according to claim 1, characterized in that: The amount of water added in step (2) is 8-12 times the amount, and the decoction is performed twice, and the extraction time is 1 hour.

5. The preparation method according to claim 1, characterized in that: The specific steps of step (2) are: adding water to the formula amount of coptis root, phellodendron, dactylum bark, sophora flavescens, polygonum cuspidatum, viola yedoensis, kochia fruit, polygonum multiflorum, capillaris and the residues obtained in step (1) and boiling and extracting twice, adding 12 times the amount of water for the first time, and the extraction time is 1 hour, and adding 8 times the amount of water for the second time, and the extraction time is 1 hour, and filtering the medicinal liquid to obtain extract 2.

6. The preparation method according to claim 1, characterized in that: The penetration enhancer is dodecyltrimethylammonium bromide, the water-soluble matrix is ​​a mixture of glycerol and sodium alginate, and the mass ratio of the two is 3-5:1; the oil-soluble matrix is ​​a mixture of vaseline, lanolin and glyceryl monostearate, and the mass ratio of the three is 5-8:1:

2.

7. The preparation method according to claim 1, characterized in that: The mass ratio of the oil-soluble matrix to the water-soluble matrix is ​​2-3.5:

1.

8. The preparation method according to claim 1, characterized in that: The amount of the penetration enhancer added is 1-1.5% of the total amount of the Chinese medicinal ingredients; the amount of the water-soluble matrix added is 15-25% of the total amount of the Chinese medicinal ingredients; and the amount of the solvent matrix added is 45-55% of the total amount of the Chinese medicinal ingredients.

9. A Chinese medicinal composition for external use in dermatology prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the dermatological external Chinese medicine composition according to claim 9 in the preparation of a dehumidifying and antipruritic drug preparation.

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