Carrier paste as well as preparation method and application thereof

Abstract

The invention relates to carrier paste. The carrier paste comprises 50-90 parts by weight of traditional Chinese medicine superfine powder and 60-120 parts by weight of carrier glue, the carrier glue comprises 30-90 parts by weight of a glue body and 10-30 parts by weight of a silicon-based porous small molecule carrier; the traditional Chinese medicine superfine powder comprises peucedanum decursum superfine powder. The invention has the beneficial effects that the invention provides a personalized transdermal drug delivery product which is suitable for the clinical medication principle of one person for one prescription, is used for treating cough and has good biocompatibility.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine plasters, and particularly relates to a carrier plaster and a preparation method and application thereof. Background Art

[0002] TCM treatment emphasizes adapting the treatment to the individual, the place and the time. Adding or subtracting according to the symptoms and personalized diagnosis and treatment are the unique advantages of TCM. The TCM prescription of "differentiation and treatment, one prescription for one person" can not only be used for internal medicine, but also for external medicine that varies from person to person, which can better reflect the exquisiteness of TCM diagnosis and treatment. However, due to technical reasons such as preparation technology, process, equipment and carrier glue, traditional transdermal drug delivery products (external medicines) have problems such as poor quality, rough process technology, difficult quality control, and low level of large-scale production, which seriously limit the innovation of drug research and development, the controllability of product quality, and the intelligence of product production. Personalized transdermal drug delivery products refer to transdermal drug delivery products made according to the clinical medication principle of one disease and one prescription of traditional Chinese medicine, which are independently diagnosed by doctors, and selected and formulated according to the disease, person, time and place. The hospital preparation room selects raw materials and suitable matrices based on the above-mentioned prescriptions and uses one-person-one-prescription plaster equipment to make them. Transdermal component enrichment technology refers to the raw material preparation technology that effectively prevents the reduction of active ingredients in traditional Chinese medicine. It is one of the key technologies for personalized transdermal drug delivery products. Practice has shown that when a large number of decoctions (oral medicines) are prepared into traditional transdermal drug delivery products (external medicines), due to different preparation processes, the active ingredients of traditional Chinese medicines will be reduced and the biocompatibility is not ideal.

[0003] There have been many reports on patches for treating cough based on patch therapy, but there are few reports on the production of personalized transdermal drug delivery products for treating cough based on individual differences and syndrome differentiation. A major reason for this is that there have been no breakthroughs in transdermal component enrichment technology and biocompatibility technology.

[0004] In summary, it is necessary to invent a personalized transdermal drug delivery product for treating cough that is suitable for the clinical medication principle of one prescription for one person and has good biocompatibility. Summary of the invention

[0005] In view of the above technical problems, the first aspect of the present invention provides a carrier paste, the carrier paste comprises 50 to 90 parts by weight of superfine Chinese medicine powder and 60 to 120 parts by weight of carrier glue, preferably: the average particle size of the superfine Chinese medicine powder is 200 to 300 μm; wherein,

[0006] The carrier glue comprises: 30 to 90 parts by weight of colloid and 10 to 30 parts by weight of silicon-based porous small molecule carrier;

[0007] The Chinese medicine superfine powder includes: Peucedanum purpurogenum superfine powder.

[0008] A second aspect of the present invention provides a method for preparing a carrier paste.

[0009] The third aspect of the present invention provides a Chinese medicine composition, and the raw materials for preparing the Chinese medicine composition include purple flower peucedanum, mulberry leaves, honeysuckle, corydalis, coptis root, yellow vine, and liquorice. The prescription of the Chinese medicine composition is as follows: purple flower peucedanum has the effects of descending qi and resolving phlegm, dispersing wind and clearing heat, and is mainly used to treat cough symptoms such as phlegm-heat, wheezing, and yellow and thick sputum, so it is used as the main medicine here, targeting the main pathogenesis of cough. Mulberry leaves can evacuate wind-heat, clear the lungs and moisten dryness, and are often used to treat symptoms such as wind-heat colds and lung-heat dry coughs, and can assist peucedanum to enhance the effect of clearing heat and resolving phlegm; honeysuckle has the effect of clearing heat and detoxifying, and has a good alleviating effect on symptoms such as cough and sore throat caused by heat toxins, and mulberry leaves are used together to assist peucedanum as ministerial medicine. Yanhusuo has the effect of promoting blood circulation, promoting qi and relieving pain. In this compatibility, it can help relieve chest pain or discomfort caused by cough, and play the role of assisting the monarch and minister medicines; Coptis chinensis is bitter and cold, can clear away heat and dampness, purge fire and detoxify, and has a certain inhibitory effect on cough caused by lung heat or heat toxins, and can also reconcile the medicinal properties in the prescription; Phellodendron chinense can assist Phellodendron chinense to strengthen the effect of clearing heat and detoxifying, and also help to relieve cough symptoms; the above Yanhusuo is the monarch medicine, and Coptis chinensis and Phellodendron chinense are used as adjuvants. Licorice is used as a guiding medicine in this prescription, which can reconcile various medicines and alleviate the conflict between medicines. At the same time, licorice itself also has a certain expectorant and cough-relieving effect, which can enhance the overall efficacy of the prescription. The effects of this Chinese medicine composition are: promoting lung and resolving phlegm, relieving cough and relieving asthma; evacuating wind-heat, clearing heat and detoxifying; promoting blood circulation and removing blood stasis, promoting qi and relieving pain; reconciling various medicines and protecting the spleen and stomach.

[0010] A fourth aspect of the present invention provides a medicine patch, which is formed by compressing any of the aforementioned carrier pastes and coating materials.

[0011] The fifth aspect of the present invention provides the use of the aforementioned Chinese medicine composition, carrier ointment or plaster in a medicine for treating lung heat cough, exogenous wind-heat, heat toxicity congestion or qi stagnation and blood stasis; preferably: the symptoms of lung heat cough include cough with yellow sputum, chest tightness and shortness of breath; the symptoms of exogenous wind-heat include fever, headache, and sore throat; the symptoms of heat toxicity congestion include carbuncle, sore throat, and red and swollen eyes; the symptoms of qi stagnation and blood stasis include chest and flank pain, and abdominal pain.

[0012] The beneficial effect of the present invention is that it provides a personalized transdermal drug delivery product for treating cough which is suitable for the clinical medication principle of one prescription for one person and has good biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 :Actual picture of the medicine patch sample;

[0014] Figure 2 : TIC image of the patch sample in positive ion mode;

[0015] Figure 3 : TIC image of the patch sample in negative ion mode;

[0016] Figure 4 : TIC graph of blank sample of the patch sample in positive ion mode;

[0017] Figure 5 : TIC graph of blank sample of the patch sample in negative ion mode;

[0018] Figure 6 : FTIR spectrum of the patch sample;

[0019] Figure 7-1 : NMR spectrum of the patch sample (D2O);

[0020] Figure 7-2 : NMR spectrum of the dried patch sample (CDCI3);

[0021] Figure 8 : GC-MS spectrum of the sample;

[0022] Fig. 9 : XRF spectrum of the original sample. DETAILED DESCRIPTION

[0023] The following examples further illustrate the content of the present invention, but should not be construed as limiting the present invention. Without departing from the spirit and substance of the present invention, modifications or substitutions made to the methods, steps or conditions of the present invention all fall within the scope of the present invention.

[0024] TCM treatment emphasizes adapting the treatment to the individual, the place and the time. Adding or subtracting according to the symptoms and personalized diagnosis and treatment are the unique advantages of TCM. The TCM prescription of "differentiation and treatment, one prescription for one person" can not only be used for internal medicine, but also for external medicine that varies from person to person, which can better reflect the exquisiteness of TCM diagnosis and treatment. However, due to technical reasons such as preparation technology, process, equipment and carrier glue, traditional transdermal drug delivery products (external medicines) have problems such as poor quality, rough process technology, difficult quality control, and low level of large-scale production, which seriously limit the innovation of drug research and development, the controllability of product quality, and the intelligence of product production. Personalized transdermal drug delivery products refer to transdermal drug delivery products made according to the clinical medication principle of one disease and one prescription of traditional Chinese medicine, which are independently diagnosed by doctors, and selected and formulated according to the disease, person, time and place. The hospital preparation room selects raw materials and suitable matrices based on the above-mentioned prescriptions and uses one-person-one-prescription plaster equipment to make them. In recent years, according to the clinical medication principle of one prescription for one person of traditional Chinese medicine, many medical institutions have provided innovative transdermal dosage forms of plaster preparations (patch) services based on small-scale plaster production equipment, aiming to solve the pain point of making personalized transdermal products for different patients and based on syndrome differentiation, which has been difficult to achieve in TCM clinics for many years. Transdermal component enrichment technology refers to the preparation technology of raw materials that effectively prevents the reduction of active ingredients of traditional Chinese medicine. It is one of the key technologies for personalized transdermal products. Practice has shown that when a large number of decoctions (oral medicines) are prepared into traditional transdermal products (external medicines), due to different preparation processes, the active ingredients of traditional Chinese medicines will be reduced and the biocompatibility is not ideal.

[0025] Patching therapy is a treatment method that uses herbal medicine preparations (patches) to apply to the skin, orifices, acupoints and local lesions under the guidance of basic theories of traditional Chinese medicine. It belongs to the external treatment of traditional Chinese medicine. Common types of patch preparations include patches (including a backing layer, a drug reservoir, an adhesive layer and a protective layer that needs to be removed before use), plasters (a paste is applied to the backing material, including gel patches (formerly Babu plasters or gel plasters) and rubber patches (formerly rubber plasters)), plasters (including black plasters and white plasters), powders (directly applied to acupoints or mixed with water or other solvents to form a mass for application), pastes (applied to acupoints in a paste form), ointments (including hard plasters and ointments, spread on acupoints), pills (small pills are usually selected for pill application), cakes (flour is mixed with a paste and pressed into a cake shape and spread on acupoints), and tablets (the paste is made into tablets and then ground into a paste with water or vinegar and applied to acupoints). There have been many reports on the patch for treating cough based on patch therapy, but there are few reports on the realization of personalized transdermal drug delivery products for treating cough according to individual differences and syndrome differentiation. The main reason is that the transdermal component enrichment technology and biocompatibility technology have not made breakthroughs. CN105477293A discloses an external patch medicine for treating cough and asthma, which is to press the raw material powder of Chinese herbal medicine into a medicine cake in a sterile environment and place it in a non-woven fabric patch circle, which belongs to Chinese medicine patch. However, the medicine cake of the Chinese medicine patch only has honey as a blending agent, the medicine cake is easy to break, the experience is poor, the clothes are dirty, and it is inconvenient to carry; for people who are allergic to honey, the use of plasters containing honey may cause allergic reactions; and there is no small machine pressing equipment suitable for medical institutions to use in a sterile environment, and it is difficult to realize personalized transdermal drug delivery products according to individual differences and syndrome differentiation based on the Chinese medicine patch; similar Chinese medicine patches also have CN1891276A, which discloses a plaster for treating children's cough. CN103006986A discloses a method for preparing a traditional Chinese medicine for treating children's cough and an external patch thereof. The components are weighed according to weight percentage to prepare an extract including a distillate and an extractum, and then mixed with pharmaceutical excipients (sodium polyacrylate, a filler, a trivalent aluminum ion crosslinking agent, disodium ethylenediaminetetraacetate, glycerol, povidone, a paraben preservative, an organic acid and ethanol) to prepare an external patch, which belongs to a gel patch.However, the Chinese herbal medicine raw materials of the gel patch need to be made into extracts. If the Chinese herbal medicine raw material powder is directly mixed with pharmaceutical excipients to make an ointment, the content of the test compound in the medicinal material will be reduced, and then the bioavailability will be reduced. It is difficult to make personalized transdermal drug delivery products based on the Chinese medicine patch according to individual differences and syndrome differentiation. Similar gel patches include CN102210773A a Chinese medicine Babu plaster for treating pneumonia in children and its preparation method and its application, CN1899550A an external plaster for treating cold-type cough in children and its preparation method, CN 1899543A an external plaster for treating fever in children and its preparation method, CN1843452A an antiasthmatic and antitussive plaster and its preparation method, CN 118416029 A a gel plaster for treating variant asthma in children, CN112353862 A a Chinese medicine gel plaster for treating lung heat cough in children and its preparation method, CN 111467426 A A traditional Chinese medicine patch for moistening the lungs and relieving cough and its preparation method, CN 111265605A An acupoint patch for treating colds and coughs and its preparation method, CN 106236738 A A polymer hydrogel acupoint cough patch and its preparation method.

[0026] The mechanism of action of acupoint application is relatively complex, and is generally believed to be the stimulation and regulation of acupoints, the pharmacodynamic effect of drugs, and the superposition of the two. In order to stimulate the acupoints, the Chinese medicinal materials or concoctions used in the patch are generally irritating, so the adverse reactions of acupoint application are mainly manifested as redness, blistering, and ulceration at the application site. In addition, the view of the prior art is that: according to the meridian theory, the above phenomenon on the skin at the acupoint site is actually the response of the acupoint to drug stimulation.

[0027] In summary, it is necessary to invent a personalized transdermal drug delivery product for treating cough that is suitable for the clinical medication principle of one prescription for one person and has good biocompatibility.

[0028] Traditional transdermal drug delivery products

[0029] The traditional transdermal drug delivery products of the present invention include the above-mentioned patches such as traditional plasters, traditional Chinese medicine ointments, such as black plasters, Chinese medicine patches and rubber plasters. These traditional plasters all have various problems. Black plasters have technical problems such as high-temperature drug refining destroying active ingredients, excessive heavy metals, easy to produce allergic reactions, complicated processes, seasonal production, no specific standards, and serious environmental pollution. Chinese medicine patches have technical problems such as poor experience, dirty clothes, inconvenience in carrying, many allergies and adverse reactions, unreasonable penetrants, and poor efficacy. Rubber plasters have technical problems such as small drug loading and poor effect, one-time use, cannot be repeatedly peeled off, poor air permeability, easy to allergic, peeling pain, poor experience, residual skin, and dirty clothes.

[0030] Personalized transdermal drug delivery products

[0031] The personalized transdermal drug delivery product of the present invention refers to a transdermal drug delivery product prepared by a medical institution according to the Chinese medicine prescription (especially the traditional decoction prescription) that varies from person to person and is based on syndrome differentiation and treatment according to the clinical medication principle of Chinese medicine for one disease. The key features for realizing personalized transdermal drug delivery products include traditional decoctions with reliable efficacy, raw materials included in the "Chinese Pharmacopoeia", suitable matrices and one-person-one-prescription plaster equipment. Transdermal component enrichment technology refers to the raw material preparation technology that effectively prevents the reduction of active ingredients in traditional Chinese medicine. It is one of the key technologies for personalized transdermal drug delivery products. The transfer rate of active ingredients of raw materials to personalized transdermal drug delivery products should not be lower than the transfer rate of active ingredients of raw materials to decoctions.

[0032] One person one prescription plaster equipment

[0033] The plaster equipment of the present invention refers to a plaster equipment that can quickly prepare according to the prescription and ensure stable patch output and fast patch forming in order to realize the external treatment of traditional Chinese medicine for one person with one prescription. For example, CN 213048233 U discloses a small-scale patch and plaster production equipment.

[0034] Decoction

[0035] Decoction refers to a liquid dosage form made by boiling or soaking drugs and then removing the residue to obtain juice. Decoctions are in line with the principle of syndrome differentiation and treatment in traditional Chinese medicine, and the addition and subtraction of ingredients according to symptoms.

[0036] API

[0037] The raw materials of the present invention are all traditional Chinese medicines listed in the Chinese Pharmacopoeia.

[0038] Peucedanum decursivum is the dried root of the plant Peucedanum decursivum.(Miq.)Maxim. of the Umbelliferae family. It is dug up when the above-ground part withers in autumn and winter, the fibrous roots are removed, and it is sun-dried.

[0039] Mulberry leaves are the dried leaves of Morus alba L., a plant of the Moraceae family. They are harvested after the first frost, impurities are removed, and they are sun-dried.

[0040] Honeysuckle is the dried buds or flowers of Lonicera japonica Thunb. of the Caprifoliaceae family. It is harvested and dried before the flowers open in early summer.

[0041] Corydalis yanhusuo (Yuanhusuo) is the dried tuber of Corydalis yanhusuo WTW, a plant of the Poppy family. It is collected in early summer when the stems and leaves wither, the fibrous roots are removed, washed, and boiled in boiling water until there is no white core, then taken out and dried.

[0042] Coptis chinensis is the dried rhizome of Coptis chinensis Franch., Coptisdeltoidea CYCheng et Hsiao or Coptis teeta Wall. of the Ranunculaceae family. The above three are commonly known as "Wei Lian", "Ya Lian" and "Yun Lian" respectively. It is dug in autumn, the fibrous roots and mud are removed, dried, and the remaining fibrous roots are knocked off.

[0043] This product is the dried vine stem of Fibraurea recisa Pierre. It is harvested in autumn and winter, cut into sections and dried in the sun.

[0044] Licorice products are the dried roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. of the Leguminosae family. They are dug up in spring and autumn, the fibrous roots are removed, and the herbs are dried in the sun.

[0045] Add or subtract herbs

[0046] The added and subtracted medicinal materials of the present invention generally refer to the Chinese medicinal materials included in the Chinese Pharmacopoeia. The [nature and flavor and meridians], [function and indications], and [usage and dosage] of the Chinese medicinal materials (decoction pieces) included in the Chinese Pharmacopoeia are determined through traditional Chinese medicine theory and clinical practice. The Chinese medicine prescription of "differentiation and treatment, one prescription for one person" selects the Chinese medicinal materials included in the Chinese Pharmacopoeia as the added and subtracted medicinal materials, and its clinical effect is determined. Including but not limited to the following added and subtracted medicinal materials: frankincense, strychnos nux vomica, atractylodes macrocephala, evodia rutaecarpa, magnolia, dipsacus, asafoetida, poppy shell, summer no, hawthorn leaf, ligusticum chuanxiong, oriental rhizome, apocynum venetum leaf, celandine. Dried ginger, notopterygium, phellodendron, safflower, asarum, corydalis, myrrh, gentiana macrophylla, cyperus rotundus, clematis root, akebia.

[0047] Biocompatibility

[0048] Biocompatibility refers to the appropriate response caused by a material in a specific part of the body. The biocompatibility of a patch refers to the irritation reaction, skin sensitization reaction or cytotoxicity caused by the active components or matrix components of the patch in the skin. Common skin irritation reactions include itching, pain, blisters, skin ulcers, etc.

[0049] Some embodiments

[0050] Some embodiments of the present invention provide a carrier paste, wherein: the carrier paste comprises 50 to 90 parts by weight of superfine Chinese medicine powder and 60 to 120 parts by weight of carrier glue, preferably: the average particle size of the superfine Chinese medicine powder is 200 to 300 μm; wherein the carrier glue comprises: 30 to 90 parts by weight of colloid, 10 to 30 parts by weight of silicon-based porous small molecule carrier; the superfine Chinese medicine powder comprises: Peucedanum peucedanum superfine powder.

[0051] The preparation method of the Chinese medicine ultrafine powder of the present invention is to use a known ultrafine pulverizer to grind the Chinese medicine separately and then mix them. Any known ultrafine medicine powder equipment is within the selection range of the present invention, such as ZKY or JZL-100 ultrafine pulverizer.

[0052] In these embodiments of the present invention, "colloid" includes but is not limited to known hydrophilic matrix or rubber matrix suitable for preparing the plaster of "Chinese Pharmacopoeia", and the hydrophilic matrix includes sodium polyacrylate, sodium carboxymethylcellulose, gelatin, glycerol and micro-powder silica gel, etc. Rubber matrix includes rubber, thermoplastic rubber, rosin, rosin derivatives, vaseline, lanolin and zinc oxide, etc. "Silicon-based porous small molecule carrier" refers to a material with high specific surface area and pore structure prepared with silicon as the substrate, and their pore size can vary from nanometer to micrometer level.

[0053] The preparation method of the colloid, carrier glue or carrier paste of the present invention is to mix the raw materials using known heating equipment and mixing equipment. Any known heating equipment and mixing equipment are within the selection scope of the present invention, such as a conical or V-shaped mixer.

[0054] Some embodiments of the present invention provide a carrier paste, wherein the Chinese medicine superfine powder includes: 3 to 9 parts by weight of Peucedanum purpurogenum superfine powder, and any one of 5 to 10 parts by weight of mulberry leaf superfine powder or 6 to 15 parts by weight of honeysuckle superfine powder.

[0055] Some embodiments of the present invention provide a carrier paste, wherein: the Chinese medicine superfine powder also includes any one of: 3 to 10 parts by weight of Corydalis superfine powder, 2 to 5 parts by weight of Coptis chinensis superfine powder, 30 to 60 parts by weight of Phellodendron chinense superfine powder and 2 to 10 parts by weight of Licorice superfine powder.

[0056] Some embodiments of the present invention provide a carrier paste, wherein: the carrier paste comprises 66 parts by weight of superfine traditional Chinese medicine powder and 100 parts by weight of carrier glue.

[0057] Some embodiments of the present invention provide a carrier paste, wherein: the solid content of the carrier paste is 1-10%; preferably, the solid content of the carrier paste is 5%.

[0058] Some embodiments of the present invention provide a carrier paste, wherein: the colloid comprises: 10 to 30 parts by weight of mineral oil, 20 to 60 parts by weight of hydrogenated petroleum resin, 15 to 40 parts by weight of thermoplastic elastomer, and 0 to 5% by weight of antioxidant; the mineral oil is selected from liquid paraffin (molecular weight 23.9979, density 0.85 g / mL (20° C.)); the hydrogenated petroleum resin is selected from a polymer of hydrogenated C6-20-hydrocarbon (molecular formula C 45 H 78 )n, density 0.99g / mL (20°C)); the thermoplastic elastomer is selected from a polymer of styrene and isoprene (linear molecular formula [CH2CH(C6H5)] X [CH2CH=C(CH3)CH2] Y [CH2CH(C6H5)] Z , density 0.93g / mL (25℃), structural formula ); the antioxidant is selected from pentaerythritol tetrakis (3,5-di-tert-butyl-4-hydroxy) phenylpropionate (molecular formula C 73 H 108 O 12 , density 1.077 g / mL). The preferred colloid is medical hot melt adhesive, and the further preferred colloid is German Henkel hot melt adhesive. PS 8082.

[0059] Some embodiments of the present invention provide a carrier paste, wherein: the silicon-based porous small molecule carrier is a silica aerogel or a silica aerogel-chitosan composite material.

[0060] In these embodiments, the "silicon dioxide aerogel" of the present invention can be prepared by existing technologies. Preferably, the silica aerogel is prepared by using silane or silicone ester as raw materials, using a sol-gel method to prepare the gel, and using supercritical drying treatment to obtain the silica aerogel. More preferably, a silica aerogel material and a preparation method thereof are used according to Chinese patent CN103130231A.

[0061] Silica aerogel material example:

[0062] 1. According to the preparation method of Example 1 of Chinese Patent CN103130231A, a block of silica aerogel with a size of 400x400x20mm was prepared.

[0063] 2. Use pneumatic crushing equipment to crush the blocky silica aerogel to a particle size of less than 10 μm to obtain granular silica aerogel (i.e., silicon-based porous small molecule carrier).

[0064] In these embodiments, the "silica aerogel chitosan composite material" of the present invention can be prepared using existing technologies, such as "Preparation and Characterization of SiO2 Aerogel Chitosan Composite Drug Carrier Materials" (Liu Jingxiao et al., "Functional Materials", 2007, 38(9)).

[0065] Some embodiments of the present invention provide a carrier paste, wherein: the average particle size of the ultrafine Chinese medicine powder is 200-300 μm.

[0066] Some embodiments of the present invention provide a method for preparing a carrier paste, wherein the method comprises the following steps:

[0067] heating and dissolving the carrier adhesive to obtain a hot melt carrier adhesive;

[0068] The traditional Chinese medicine superfine powder is added into the hot-melt carrier glue and stirred to obtain the carrier paste.

[0069] Some embodiments of the present invention provide a medicine patch, wherein: the medicine patch is formed by pressing the aforementioned carrier paste and coating material.

[0070] The carrier ointment or medicated plaster of the present invention can be prepared by using known mixing equipment and plaster equipment, respectively, or can be prepared based on known one-person-one-prescription plaster equipment.

[0071] Some embodiments of the present invention provide a traditional Chinese medicine composition, wherein: the raw materials for preparing the traditional Chinese medicine composition include Peucedanum purpurogenum, mulberry leaves, honeysuckle, Corydalis yanhusuo, Coptis chinensis, Phellodendron chinense and liquorice.

[0072] Example 1

[0073] Prescription quantity (actual sampling is weighed in grams (g))

[0074] Chinese medicine ultrafine powder: 6 parts by weight of purple flower peucedanum ultrafine powder, 7 parts by weight of mulberry leaf ultrafine powder, 10 parts by weight of honeysuckle ultrafine powder, 6 parts by weight of Corydalis ultrafine powder, 2.5 parts by weight of Coptis chinensis ultrafine powder, 45 parts by weight of Phellodendron chinense ultrafine powder and 6 parts by weight of liquorice ultrafine powder.

[0075] Colloid: 20 parts by weight of liquid paraffin, 40 parts by weight of hydrogenated C6-20-hydrocarbon polymer, 22.5 parts by weight of styrene-isoprene polymer, 2.5% pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxy)phenylpropionate.

[0076] Carrier glue: 60 parts by weight of colloid, 15 parts by weight of granular silica aerogel;

[0077] Carrier paste: 66 parts by weight of traditional Chinese medicine superfine powder, 100 parts by weight of carrier glue.

[0078] Medicine patch: Specifications are 7cm*7cm; each medicine patch contains 0.8g of carrier paste.

[0079] Preparation method: Take samples according to the above prescription, and prepare Chinese medicine ultrafine powder, colloid, carrier glue, carrier paste and medicine patch in sequence according to the preparation method described in "Some Examples".

[0080] Example 2

[0081] Prescription quantity (actual sampling is weighed in grams (g))

[0082] Chinese medicine ultrafine powder: 3 parts by weight of Peucedanum peucedanum ultrafine powder, 5 parts by weight of mulberry leaf ultrafine powder, 6 parts by weight of honeysuckle ultrafine powder, 3 parts by weight of Corydalis ultrafine powder, 2 parts by weight of Coptis chinensis ultrafine powder, 30 parts by weight of Phellodendron chinense ultrafine powder and 2 parts by weight of liquorice ultrafine powder.

[0083] Colloid: 10 parts by weight of liquid paraffin, 20 parts by weight of hydrogenated C6-20-hydrocarbon polymer, 15 parts by weight of styrene-isoprene polymer, 1% pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxy)phenylpropionate.

[0084] Carrier glue: 30 parts by weight of colloid, 30 parts by weight of granular silica aerogel;

[0085] Carrier paste: 50 parts by weight of traditional Chinese medicine superfine powder, 60 parts by weight of carrier glue.

[0086] Medicine patch: Specifications are 7cm*7cm; each medicine patch contains 0.8g of carrier paste.

[0087] Preparation method: Take samples according to the above prescription, and prepare Chinese medicine ultrafine powder, colloid, carrier glue, carrier paste and medicine patch in sequence according to the preparation method described in "Some Examples".

[0088] Example 3

[0089] Prescription quantity (actual sampling is weighed in grams (g))

[0090] Chinese medicine ultrafine powder: 9 parts by weight of purple flower peucedanum ultrafine powder, 10 parts by weight of mulberry leaf ultrafine powder, 15 parts by weight of honeysuckle ultrafine powder, 10 parts by weight of Corydalis ultrafine powder, 5 parts by weight of Coptis chinensis ultrafine powder, 60 parts by weight of Phellodendron chinense ultrafine powder and 10 parts by weight of liquorice ultrafine powder.

[0091] Colloid: 30 parts by weight of liquid paraffin, 60 parts by weight of hydrogenated C6-20-hydrocarbon polymer, 40 parts by weight of styrene-isoprene polymer, 5% pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxy)phenylpropionate.

[0092] Carrier glue: 90 parts by weight of colloid, 10 parts by weight of granular silica aerogel;

[0093] Carrier paste: 90 parts by weight of traditional Chinese medicine superfine powder and 120 parts by weight of carrier glue.

[0094] Medicine patch: Specifications are 7cm*7cm; each medicine patch contains 0.8g of carrier paste.

[0095] Preparation method: Take samples according to the above prescription, and prepare Chinese medicine ultrafine powder, colloid, carrier glue, carrier paste and medicine patch in sequence according to the preparation method described in "Some Examples".

[0096] Example 4

[0097] Prescription quantity (actual sampling is weighed in grams (g))

[0098] Chinese medicine ultrafine powder: 6 parts by weight of Peucedanum peucedanum ultrafine powder, 7 parts by weight of mulberry leaf ultrafine powder, 10 parts by weight of honeysuckle ultrafine powder, 10 parts by weight of Corydalis ultrafine powder, 2 parts by weight of Coptis chinensis ultrafine powder, 30 parts by weight of Phellodendron chinense ultrafine powder and 10 parts by weight of liquorice ultrafine powder.

[0099] Colloid: German Henkel hot melt adhesive PS 8082.

[0100] Carrier glue: 60 parts by weight of colloid, 15 parts by weight of granular silica aerogel;

[0101] Carrier paste: 39.6 parts by weight of traditional Chinese medicine superfine powder, 60 parts by weight of carrier glue.

[0102] Medicine patch: Specifications: 10cm*12cm (such as Figure 1 Each patch contains 0.8 g of carrier paste.

[0103] Preparation method: Take samples according to the above prescription, and prepare Chinese medicine ultrafine powder, colloid, carrier glue, carrier paste and medicine patch in sequence according to the preparation method described in "Some Examples".

[0104] Embodiments 5 to 10

[0105] Examples 5 to 10 are substantially the same as Example 1, except for the differences shown in Table 1 below.

[0106] Table 1 Examples 5 to 10

[0107]

[0108]

[0109] Example 11 Decoction

[0110] The weight ratio of the Chinese medicinal materials in Example 11 is the same as that in Example 1, except that the decoction is prepared. The specific preparation method is: decoct each Chinese medicinal material twice with 7 times the amount of water, the first decoction is 2 hours, the second decoction is 1.5 hours, and the decoction is combined to obtain the decoction.

[0111] Positive control example 1:

[0112] The preparation method is based on the method of CN105477293A, and the medicinal materials are: Ganoderma lucidum, Scutellaria baicalensis, Ephedra sinica, Chan skin, Terminalia chebula, raw licorice, Leonurus chinensis, Schisandra chinensis, almond, Fritillaria cirrhosa, Plantago asiatica, and honey.

[0113] Positive control example 2:

[0114] The product is prepared by the method of CN1891276A, and the medicinal materials are: ephedra, asarum, white mustard seed, scutellaria baicalensis, sapodilla seed, fritillaria cirrhosa, light powder and honey.

[0115] Positive control example 3:

[0116] It is prepared by the method of CN111265605A, and the medicinal materials are: pinellia, saponin, platycodon, white mustard, asarum, momordica grosvenori, perilla seed, tangerine peel, green fruit, ginkgo, almond, licorice and emblica.

[0117] The technical effects of the present invention are further described below in conjunction with test examples.

[0118] Test Example 1

[0119] 1. Purpose of the experiment

[0120] The changes in the content of active ingredients of the Chinese medicine composition of the present invention when it is made into a decoction and a medicated plaster are tested.

[0121] Thermo QE plus liquid chromatography tandem high-resolution mass spectrometry and Compound discover data processing software were used to analyze the chemical components of traditional Chinese medicine samples.

[0122] 2. Sample information

[0123] 2.1 Decoction Take 200 mg of the sample of Example 11, add 10 mL of 50% methanol aqueous solution (v:v, methanol: water = 50:50), ultrasonicate for 30 min, take 1 mL of the supernatant and place it in a centrifuge tube, centrifuge at 14000 rpm for 5 min, take the supernatant and filter it through a 0.22 um microporous membrane, and place it in a sample injection bottle for UHPLC-MS / MS analysis. The blank sample was treated under the same conditions.

[0124] 2.2 Medicated patch

[0125] Sample pretreatment: Take the plaster parts of ten pieces of each patch of Examples 1 to 10, add 50% ethanol aqueous solution (v:v, ethanol:water=50:50), reflux to extract the Chinese medicine components, and concentrate the extract to obtain a preliminary extract.

[0126] Take 200 mg of concentrated extract sample, add 50% ethanol aqueous solution (v:v, ethanol: water = 50:50), ultrasonicate for 30 min, take 1 mL of supernatant and place it in a centrifuge tube, centrifuge at 14000 rpm for 5 min, take the supernatant and filter it through a 0.22 um microporous membrane, and place it in a sample injection bottle for UHPLC-MS / MS analysis. The blank sample was treated under the same conditions.

[0127] 3. Experimental instruments and reagents

[0128] 3.1 Experimental instruments and equipment

[0129] As shown in Table 2.

[0130] Table 2 Experimental instruments and equipment

[0131]

[0132] 3.2 Experimental reagents

[0133] Methanol and formic acid were purchased from Thermo Fisher; deionized water was prepared from a Milli Q Advantage A10 ultrapure water machine; 1.5 mL centrifuge tubes, 15 mL centrifuge tubes and injection vials were purchased from Axygen.

[0134] 4. Experimental Conditions

[0135] 4.1 Liquid phase conditions

[0136] Chromatographic column: ACQUITY UPLC HSS T3 column (2.1×100mm, 1.8um)

[0137] Column temperature: 35°C

[0138] Injection volume: 10uL

[0139] Flow rate: 0.3mL / min

[0140] Mobile phase: A (deionized water, containing 0.1% formic acid); B (acetonitrile, containing 0.1% formic acid), gradient elution. Specific gradient elution conditions are shown in Table 3:

[0141] Table 3 Gradient elution conditions

[0142] Time Flow Rate (mL / min) ％A ％B 0 0.3 100 0 10 0.3 70 30 25 0.3 60 40 30 0.3 50 50 40 0.3 30 70 45 0.3 0 100 60 0.3 0 100 60.5 0.3 100 0 70 0.3 100 0

[0143] 4.2 Mass spectrometry 3 conditions

[0144] The mass spectrometry data were collected using a Q Exactive Orbitrap high-resolution mass spectrometer, with the detection mode being Full MS-ddMS. 2 , positive and negative ion modes were scanned respectively, with a scanning range of m / z 100-1200, MS 1 The resolution is set to 70000, MS 2 The resolution was set to 17500, the ion source voltage was 3.2 kV, the capillary ion transfer tube temperature (Capillary temp) was 320 °C, the auxiliary gas heater temperature (Aux gas heater temp) was 350 °C, the sheath gas flowrate was 40 L / min, the auxiliary gas flow rate was 15 L / min, the AGC Target was set to 1e6, the TopN was set to 5, and the MS was triggered. 2 The collision energy was scanned with a stepwise fragmentation voltage NCE, which was set to 30, 40, and 50.

[0145] 5 Test results

[0146] The active ingredients of Chinese medicine in the patch (Examples 1 to 10) are higher than those in the decoction (Example 11). The comparison results of Example 1 and Example 11 are shown in Table 4. The experimental results show that the personalized transdermal drug delivery product (patch) of the present invention is suitable for the clinical medication principle of one person and one prescription. Even if the type and dosage of the medicinal materials of one person and one prescription are changed, the active ingredients of Chinese medicine are not reduced, and some active ingredients of Chinese medicine are even improved. In addition, for the active ingredients of Chinese medicine for which the detection method is provided in the Chinese Pharmacopoeia (2015), the test results using the pharmacopoeia method are consistent with the results of this test example.

[0147] Table 4 Active ingredient test results of decoction (Example 11) and medicated plaster (Example 1)

[0148]

[0149]

[0150] Test Example 2: Addition and subtraction of medicinal materials interference test

[0151] 1. Purpose of the experiment

[0152] To test the changes in the content of active ingredients of traditional Chinese medicine when the traditional Chinese medicine composition is made into decoction and medicine plaster after adding medicinal materials during dialectical treatment.

[0153] Thermo QE plus liquid chromatography tandem high-resolution mass spectrometry and Compound discover data processing software were used to analyze the chemical components of traditional Chinese medicine samples.

[0154] 2. Sample information

[0155] The decoction is prepared by the method of Example 11 with purple flowered peucedanum, mulberry leaves, honeysuckle, Corydalis, Coptis chinensis, Phellodendron chinense, licorice, frankincense, strychnos nux vomica, Atractylodes macrocephala, Evodia rutaecarpa, magnolia, Dipsacus asper, beet, Tinospora acuminata, Stephania macrocephala, Swertia japonica, Ferula asafoetida, poppy shell, summer nectar, poppy, hawthorn leaf, Ligusticum chuanxiong, Cinchona tree, costusroot, peucedanum, Chuanxiong, Alisma orientalis, Apocynum venetum leaf, celandine, honeysuckle, Albizzia julibrissin, etc.

[0156] Medicinal patch The above decoction was prepared into a medicinal patch by the method of Example 1.

[0157] 3. Experimental instruments and reagents

[0158] Same as Test Example 1.

[0159] 4. Experimental Conditions

[0160] Same as Test Example 1.

[0161] 5. Experimental Results

[0162] 5.1 TIC diagram

[0163] The TIC scans of the patch in positive ion mode and negative ion mode are shown in Figure 2. Figure 2 and Figure 3 The TIC diagram of the blank sample is shown in Figure 4 and Figure 5 shown.

[0164] 5.2 Analysis of components of traditional Chinese medicine

[0165] Based on the types of compounds detected, it is inferred that the samples may constitute Chinese medicine ingredients. The local self-built mzVault natural product database includes more than 1,200 compounds, all of which are summarized and annotated with the medicinal material sources of natural products according to the 2015 edition of the Chinese Pharmacopoeia. The online database contains more than 6,000 theoretical natural product mass spectrometry data (from Beijing Qingxi Technology Research Institute), which also annotates the medicinal material sources based on the 2015 edition of the Chinese Pharmacopoeia. The components of Chinese medicine are analyzed based on the integration of the two.

[0166] Analytical strategy: All-compound component assignment matching based on relative abundance.

[0167] All compounds with database matching scores > 70 were searched for medicinal material sources, and the abundance of compounds belonging to each medicinal material was summed up, the relative content percentage was calculated, and the ranking was performed. The results are shown in Tables 5 to 11, and the FTTR spectrum, NMR spectrum (D20), NMR spectrum (CDCI3), GC-MS spectrum, and XRF spectrum of the patch sample are shown in Tables 5 to 9.

[0168] Table 5 Matching results of Chinese medicine components

[0169] Name of medicinal material Peak area sum Relative content (%) Corydalis 31055217081.60 12.950 Peucedanum purpurogenum 20804988739.96 8.676 mastic 18021666313.34 7.515 Atractylodes macrocephala 13859023396.47 5.779 Yellow rattan 11218873883.59 4.678 Intermittent 10649158022.00 4.441 Strychnos nux vomica 9218111905.13 3.844 Coptis chinensis 8917170178.01 3.718 Magnolia 7404292358.22 3.088 Stephanotis 6515375786.06 2.717 beet 6032354127.02 2.515 Evodia rutaecarpa 6017402905.66 2.509 Green Bull Gallbladder 6002159378.01 2.503 Swertia japonica 5861871147.02 2.444 Asafoetida 5234475562.60 2.183 carbohydrate 4999525384.51 2.085 Poppy Shell 4747573156.36 1.980 Thistle Poppy 4396818817.45 1.833 Summer No 4238036219.65 1.767 Mulberry Leaves 4232620547.82 1.765 Licorice 4024548733.71 1.678 Hawthorn Leaves 3575623837.64 1.491 Gao Ben 3446101927.67 1.437 Woody 3444986383.78 1437 honeysuckle 2720565505.17 1.134 Peucedanum chinense 2280838703.99 0.951 Chuanxiong 2271518059.92 0.947 Alisma orientalis 2218542970.26 0.925 Apocynum venetum leaf 1965615238.52 0.820 Cinchona 1478671091.29 0.617 Celandine 1457477339.43 0.608 Albizia Julibrissin 1265613418.96 0.528

[0170] Table 6 Identification compound information

[0171]

[0172] Table 7 Identification compound information (continued)

[0173]

[0174] Table 8 Identification compound information (continued)

[0175]

[0176] Table 9 Identification compound information (continued)

[0177]

[0178] Table 10 Identification compound information (continued)

[0179]

[0180] Table 11 Identified compound information (continued)

[0181]

[0182] 5.3 Analysis of Results See Table 12 for the comparison results between the aforementioned medicated plaster and the corresponding decoction (charts and tables omitted).

[0183] Table 12 Comparison of active ingredient test results of decoction and plaster with the same formula

[0184]

[0185]

[0186]

[0187] The experimental results show that after adding medicinal materials such as purple flowered peucedanum, mulberry leaves, honeysuckle, Corydalis, Coptis, Phellodendron, licorice, frankincense, strychnos nux vomica, Atractylodes macrocephala, Evodia rutaecarpa, magnolia, Dipsacus asper, beet, Tinospora acuminata, Stephania macrocephala, Swertia japonica, Ferula asafoetida, poppy shell, summer clover, poppy, hawthorn leaf, Ligusticum chuanxiong, Cinchona, costusroot, peucedanum, Chuanxiong, Alisma orientalis, dogbane leaf, celandine, honeysuckle, and Albizzia julibrissin, the detection rate of the active ingredients in the plaster is still higher than that in the decoction without being affected by the addition of medicinal materials.

[0188] Test Example 3 Skin irritation test

[0189] 1. Purpose: To evaluate the potential irritation of samples to rabbits under test conditions through rabbit skin irritation test.

[0190] 2. Basis: GB / T 16886.10-2017 / ISO 10993-10:2010 Biological evaluation of medical devices Part 10: Irritation and skin sensitization tests

[0191] 3. Sample preparation:

[0192] The extraction of samples and blank controls (without sample extraction medium) must be carried out as described below. The extraction process is maintained with shaking (80r / min)

[0193] Table 13 Sample preparation

[0194]

[0195] 4. Animals

[0196] Animal species: Rabbit;

[0197] Animal strains: New Zealand White rabbit;

[0198] Animal source: Beijing Fangyuanyuan Farm;

[0199] Female, nulliparous and non-pregnant; 6 animals; randomly divided into groups.

[0200] 5. Methods

[0201] 4h-24h before the test, remove enough hair (about 10cm*15cm area) on both sides of the spine of the animal's back to use as the test and observation site. There must be sufficient distance between all application and observation sites on both sides of the spine. Apply gauze (2.5cm*2.5cm) containing about 0.5ml of polar extract to the test site on the back of 3 experimental animals, and the corresponding extraction medium without the test sample as a blank control is applied to the control part. Remove the application after 4 hours; observe the application site immediately, 1 hour, 24 hours, 48 ​​hours and 72 hours after the application is removed and record the observation results. Score the tissue reaction of erythema and edema in each part of each observation period according to the scoring system given in Table 1. The non-polar extract was operated on another 3 experimental animals in the same way. According to the observed results, the skin reaction of the test site did not exceed that of the control site.

[0202] Table 14 Skin reaction scoring system

[0203]

[0204] Note: Record and report any other abnormalities in the skin area

[0205] 6. Evaluation

[0206] Only observation data at (24±2)h, (48±2)h and (72±2)h are used for calculation. Recovery observation data before the test or after 72h are not used for calculation. After scoring at 72h, all erythema and edema scores caused by the test sample and blank at (24±2)h, (48±2)h and (72±2)h are added together for each animal, and then the sum of all scores is divided by 6 (two test / observation sites, 3 time points) to calculate the primary irritation index (PII) of a certain animal. The primary irritation index of the test sample is obtained by adding all primary irritation scores for each animal and then dividing by the total number of animals (usually 3). When a blank or negative control is used, the control primary irritation score is calculated and the primary irritation score of the test material is subtracted from this score to obtain the primary irritation score. The reaction type is determined by numbers (scores) and words (reaction type) according to Table 2.

[0207] Table 15 Rabbit primary irritation index type

[0208] Average score Reaction Type 0～0.4 Very slight 0.5～1.9 Mild 2～4.9 Moderate 5～8 Severe

[0209] 7. Test results

[0210] During the test, no abnormalities were observed in the clinical observation of all animals. The scores are shown in Table 3 Clinical Observation and Results. The difference in primary irritation index between the test group and the control group is summarized in Table 4.

[0211] Table 16 Clinical observations and results

[0212]

[0213]

[0214] Table 17 Results

[0215] Extract Experimental Group (PII) Control group (PII) Primary irritation score Polarity Group (SC) 0 0 0 Non-polar group (CSO) 0 0 0

[0216] 8 Conclusion

[0217] Under the test conditions, the primary irritation index of the test samples was 0 (polar extract group) and 0 (non-polar extract group). The rabbit irritation reaction of the test sample extracts was classified as very mild (polar extract group) and very mild (non-polar extract group).

[0218] Test Example 4 Skin sensitization test (Guinea pig maximum dose test)

[0219] 1. Purpose: To evaluate the potential of samples to induce skin sensitization in guinea pigs under test conditions through a maximum dose test in guinea pigs.

[0220] 2. Basis: GB / T 16886.10-2017 / ISO 10993-10:2010 Biological evaluation of medical devices Part 10: Irritation and skin sensitization tests

[0221] 3. Sample preparation: Same as skin irritation test.

[0222] 4. Animals

[0223] Guinea pigs, Hartley, ordinary grade, Beijing Fangyuanyuan breeding farm, 30, randomly divided into groups.

[0224] 5. Methods

[0225] 5.1 Before the start of the experiment, remove the hair from all test areas of the animals.

[0226] 5.2 Intradermal induction phase

[0227] Inject 0.1 mL in pairs at the medial part of the scapula of each animal after hair removal. Site A: Injection of a stable emulsion of Freund's complete adjuvant and a selected solvent in a 50:50 (volume ratio). For water-soluble materials, the solvent is physiological saline. Site B: Injection of the test sample (undiluted extract); the control group of animals is injected with only the corresponding solvent. Site C: The test sample (concentration used in site B) is mixed with an emulsion prepared with Freund's complete adjuvant and solvent (50%) in a 50:50 volume ratio and injected intradermally; the control group is injected with an emulsion prepared with blank solution and adjuvant.

[0228] 5.3 Local induction phase

[0229] Seven days after the intradermal induction phase, the concentration selected in Section B of the intradermal induction phase in 5.2 was used to treat an area of ​​approximately 8 cm 2 A patch (filter paper or absorbent gauze piece) is applied topically to the medial part of the shoulder blade of each animal, covering the induction injection site. No irritation reaction is produced according to the maximum concentration of the intradermal induction stage in 5.2. The test area should be pretreated with 10% sodium dodecyl sulfate (24±2)h before the local application of the patch, and massaged into the skin. Fix the patch with a closed bandage and remove the bandage and patch after (48±2)h. It is best to prepare the extract freshly. If the extract is stored for more than (24±2)h, the stability of the extract under storage conditions should be verified. The animals in the control group are operated in the same way using a blank solution.

[0230] 5.4 Excitation phase

[0231] 14 days after the local induction phase, stimulate all test animals and control animals with the test sample. Apply the same concentration of dilution to other untested sites as in 5.2 for the intradermal induction phase, such as the upper abdomen of each animal. Fix with a closed bandage and remove the bandage and patch after (24±2) hours.

[0232] 5.5 Animal Observation

[0233] Observe the skin condition of the stimulated area of ​​the animals in the test group and the control group (24±2)h and (48±2)h after removing the patch. It is particularly recommended to observe the skin reaction under natural light or light of the right spectrum. Describe and grade the skin erythema and edema reaction at each stimulated area and each observation time according to the Magnusson and Kligman grading standards given in Table 1. In order to minimize the deviation of the result evaluation, it is particularly recommended to read the data without knowing the experimental treatment information.

[0234] Table 18 Magnusson and Kligman classification

[0235]

[0236]

[0237] 6. Evaluation

[0238] According to the Magnusson and Kligman grading standard, when the grade of the control group animals is less than 1, and the grade of the test group is greater than or equal to 1, it generally indicates sensitization. If the grade of the control group animals is greater than or equal to 1, and the reaction of the test group animals exceeds the most severe reaction in the control group, it is considered sensitization.

[0239] 7. Test results

[0240] 7.1 Clinical Observation

[0241] No obvious abnormality was observed in the clinical observation of all animals during the observation period of this experiment. The clinical observation results are shown in Table 2.

[0242] 7.2 Skin Observation

[0243] No sensitization was shown. The skin reaction score results are shown in Table 2.

[0244] Table 19 Clinical observations and skin reactions

[0245]

[0246]

[0247] 8 Conclusion

[0248] Under the conditions of this test, no allergenic reaction was found in the sample extracts.

[0249] Test Example 5 In vitro cytotoxicity test (MTT method)

[0250] 1. Purpose: To evaluate the cytotoxicity of the test sample extracts.

[0251] 2. Basis: GB / T 16886.5-2017 / ISO 10993-5:2009 Biological evaluation of medical devices Part 5: In vitro cytotoxicity test

[0252] 3. Sample preparation:

[0253] The test sample and the test site are in contact with the skin. The test sample and the control sample are extracted with cell culture medium according to the following conditions. The extraction process is kept shaking (80r / min)

[0254] Table 20 Sample preparation

[0255]

[0256]

[0257] 4. Cell lines

[0258] Cell line: Mouse fibroblast L929 cells were obtained from the American Type Culture Collection (ATCC).

[0259] 5. Test Methods

[0260] Collect L929 cells with good growth status and adjust the density to 1*10 5 cells / mL. Inoculate 100 μL of the above cell suspension in each well of a 96-well cell culture plate, and culture in a cell culture incubator at 37°C and 5% CO2 for 48 hours to obtain a semi-confluent monolayer of cells. Observe under a microscope to ensure that the cell growth in each well of the 96-well cell culture plate is relatively equal. Aspirate the original culture medium, add 100 μL of test solution (100%, 75%, 50%, 25%), negative control solution, positive control solution and blank control solution to each well (add to the 2nd and 11th columns of the 96-well cell culture plate). The plates were placed in a 37°C, 5% CO2 cell culture incubator and cultured for 24 hours. The cell status of each well was observed under a microscope. The culture medium was carefully removed. 50 μL of MTT solution was added to each well. The plates were placed in a cell culture incubator and incubated for 2 hours. The MTT solution in the wells was discarded. 100 μL of isopropanol was added to each well. After shaking to dissolve, the absorbance was measured at 570 nm (reference wavelength 650 nm) on a microplate reader to calculate the survival rate.

[0261] 6. Evaluation and Data Analysis

[0262] The cell viability relative to the blank group was calculated using the following formula:

[0263] Survival rate % = (100*OD 570c ) / OD 570b

[0264] OD 570c : Average optical density of the experimental group, positive control group, and negative control group;

[0265] OD 570e : Mean optical density of the blank group;

[0266] Acceptance criteria: blank group OD 570 If the average value of the blank controls in the left and right columns is ≥0.2 and the difference between the average value of the blank controls in the left and right columns and the average value of all blank controls is not greater than 15%, the test meets the acceptance criteria.

[0267] If the survival rate drops to <70% of the blank group, it indicates potential cytotoxicity. The survival rate of the 50% test solution of the test sample should be the same as or higher than the survival rate of the 100% test solution, otherwise the test needs to be repeated.

[0268] 7. Test results

[0269] The average value of the blank controls in the left and right columns is 0.499, and the difference between the average value of the blank controls in the left and right columns and the average value of all controls is 1.85%. The test meets the acceptance criteria.

[0270] Microscopic observation after 24 hours of contact showed that most of the cells in the negative control group had normal morphology, and a small number of cells were rounded and loosely attached to the wall; the test results are shown in Table 1:

[0271] Table 21 Cytotoxicity test results

[0272]

[0273] Note: The OD values ​​in the table are the results after the sample extracts were in contact with the cells for 24 hours.

[0274] 8. Conclusion

[0275] Under the experimental conditions, the cell viability of the 100% extract of the patch was 74.16%>70%, showing no potential cytotoxicity. The results of the negative control, blank control and positive control were all in line with expectations.

[0276] Test Example 6 Biocompatibility Comparative Test

[0277] Taking positive control examples 1 to 3 and referring to the skin irritation reaction, skin sensitization reaction or cytotoxicity test methods of test examples 3 to 5, the results showed that the skin irritation was moderate to severe, and moderate to severe erythema, edema, skin ulceration and other allergic phenomena occurred, which were consistent with the performance of traditional acupoint application.

[0278] Test Example 7 Typical Case

[0279] According to the clinical medication principle of one prescription for one person, 100 patients with cough and asthma were counted, of which 97 were cured in 4 days, and 2 were transferred to other hospitals for treatment due to other reasons. Typical cases are as follows:

[0280] (1) Zhao, female, 4 years old. Visited the doctor on November 1, 2024. Main complaint: Cough for 2 weeks, the condition has been fluctuating, and has worsened in the past three days. Two weeks ago, she had a fever for 2 days due to mycoplasma infection. After the fever subsided, she began to cough. Oral antibiotics were ineffective and the condition worsened. The cough at night seriously affected her sleep, so she came to the outpatient clinic for diagnosis and treatment. Initial diagnosis, symptoms include cough, wheezing, shortness of breath, thick yellow sputum, uncomfortable coughing and spitting, red and swollen throat, accompanied by chest pain, and slight sweating. The tongue is red and a little prickly, with thick yellow fur, floating pulse, and purple fingerprints. Auscultation: rales in both lungs, Chinese medicine diagnosis: cough (phlegm-heat stagnation in the lungs type) Treatment: Use the external patch medicine of the present invention, apply it externally on the acupoints, after 2 patches, the cough and wheezing stop, and the symptoms completely disappear.

[0281] (2) Zheng, male, five years old. Visited the hospital on November 7, 2024, with the main complaint: fever, cough and asthma for 5 days, which worsened day by day, and the number of cough and asthma increased. Five days ago, he had fever, aversion to wind, cough, shortness of breath, sweating and thirst, thick sputum, redness, swelling and pain in the throat, and came to our specialist clinic for diagnosis and treatment. Initial diagnosis: symptoms include high fever, frequent cough, dry throat and sore throat, thick and yellow sputum, thirst and irritability, yellow tongue coating, red and dry, and slippery pulse. Chinese medicine diagnosis: cough and asthma (wind-heat invading the lungs). Treatment: Use the external patch medicine of the present invention, apply it on the acupoints, and after 2 patches, the fever subsides and the cough and asthma stop.

[0282] (3) He Moumou, female, 3 years old. Visited the doctor on October 18, 2024, with the main complaint: cough and asthma for a week, which has worsened in the past two days. A week ago, due to frequent cough and asthma, restlessness at night, and occasional night crying, she came to our clinic for treatment after taking Western medicine and Chinese patent medicine elsewhere without obvious effects. Initial diagnosis: coughing paroxysms, red face when coughing, dry throat and bitter mouth, red and dry lips, red edges and tips of the tongue with yellow fur; Chinese medicine diagnosis: cough and asthma (liver fire invading the lungs). Treatment: Use the external patch medicine of the present invention, apply it externally on the acupoints, the cough and asthma will stop after 2 patches, and the other symptoms will be alleviated. After 3 patches, all symptoms will completely disappear.

[0283] (4) Wang, male, 8 years old. Visited the doctor on December 9, 2024. Main complaint: fever and cough for 3 days. The child had cough and asthma for 3 days ago, followed by high fever. He had taken antipyretic, analgesic, antitussive and sedative drugs, but his illness did not subside, so he came to our clinic for treatment. Initial diagnosis: shortness of breath, sputum in the throat, chest tightness, cough, and thick sputum, which was yellow-green. Fever and red face, constipation and yellow urine, purple-red tongue, thick and greasy yellow fur, dilated sublingual veins, slippery and rapid pulse, Chinese medicine diagnosis: cough and asthma (heat toxicity carbuncle lung). Treatment: Use the external patch medicine of the present invention, apply it externally on the acupoints, after 3 patches, the fever subsided, the cough and asthma stopped, and the remaining symptoms completely disappeared, and then add another patch to consolidate the therapeutic effect.

[0284] Although the present invention has been described in detail above by general description, specific implementation methods and experiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A carrier paste, characterized in that: The carrier paste comprises 50-90 parts by weight of superfine Chinese medicine powder and 60-120 parts by weight of carrier glue, preferably: the average particle size of the superfine Chinese medicine powder is 200-300 μm; wherein, The carrier glue comprises: 30 to 90 parts by weight of colloid and 10 to 30 parts by weight of silicon-based porous small molecule carrier; The Chinese medicine superfine powder includes: Peucedanum purpurogenum superfine powder.

2. The carrier paste according to claim 1, characterized in that: The traditional Chinese medicine superfine powder comprises: 3 to 9 parts by weight of Peucedanum purpurogenum superfine powder, and any one of 5 to 10 parts by weight of mulberry leaf superfine powder or 6 to 15 parts by weight of honeysuckle superfine powder.

3. The carrier paste according to claim 2, characterized in that: The traditional Chinese medicine superfine powder also includes any one of: 3-10 weight parts of Corydalis superfine powder, 2-5 weight parts of Coptis chinensis superfine powder, 30-60 weight parts of Phellodendron chinense superfine powder and 2-10 weight parts of Licorice superfine powder.

4. The carrier paste according to any one of claims 1 to 3, characterized in that: The carrier paste comprises 66 parts by weight of traditional Chinese medicine superfine powder and 100 parts by weight of carrier glue.

5. The carrier paste according to any one of claims 1 to 3, characterized in that: The colloid comprises: 10-30 parts by weight of mineral oil, 20-60 parts by weight of hydrogenated petroleum resin, 15-40 parts by weight of thermoplastic elastomer, and 0-5% by weight of antioxidant; the mineral oil is selected from liquid paraffin; the hydrogenated petroleum resin is selected from hydrogenated C6-20-hydrocarbon polymer; the thermoplastic elastomer is selected from styrene and isoprene polymer; the antioxidant is selected from pentaerythritol tetra(3,5-di-tert-butyl-4-hydroxy)phenylpropionate; Preferably, the colloid is a medical hot melt adhesive; further preferably, the colloid is a German Henkel hot melt adhesive. PS 8082.

6. The carrier paste according to any one of claims 1 to 3, characterized in that: The silicon-based porous small molecule carrier is a silica aerogel or a silica aerogel chitosan composite material.

7. A method for preparing a carrier paste according to any one of claims 1 to 6, characterized in that: The method comprises the following steps: heating and dissolving the carrier adhesive to obtain a hot melt carrier adhesive; The traditional Chinese medicine superfine powder is added into the hot-melt carrier glue and stirred to obtain the carrier paste.

8. A medicated patch, characterized in that: The medicine patch is formed by compressing the carrier paste described in any one of claims 1 to 7 and a coating material.

9. A Chinese medicine composition, characterized in that: The raw materials for preparing the traditional Chinese medicine composition include peucedanum purpurogenum, mulberry leaves, honeysuckle, corydalis, coptis root, yellow vine and liquorice.

10. Use of a carrier ointment, a medicament patch or a Chinese medicine composition as claimed in any one of claims 1 to 9 in a medicine for treating lung-heat cough, exogenous wind-heat, heat-toxic congestion or qi stagnation and blood stasis; preferably: the symptoms of lung-heat cough include cough with yellow sputum and chest tightness and shortness of breath; the symptoms of exogenous wind-heat include fever, headache and sore throat; the symptoms of heat-toxic congestion include carbuncle, sore throat and red and swollen eyes; the symptoms of qi stagnation and blood stasis include chest and flank pain and abdominal pain.

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